Abstract
Low bone health is associated with vitamin D deficiency in older individuals; however, this association is not well established in adults. The aim of the study was to analyze the association between serum concentrations of 25-hydroxyvitamin D and bone health in adults by systematic review and meta-analysis. The search was carried out in the LILACS, PubMed, Scopus, Web of Science, ScienceDirect databases from March 2017 to October 2018 with adult individuals (20-59 years). Bone health was evaluation performed through dual X-ray absorptiometry and serum concentrations of 25(OH)D. The random effect model was used to analyze data from bone mineral content and bone mineral. Random effects models were used and the sources of heterogeneity were explored by means of meta-regression. Thirty-five articles were selected. There was positive correlation between vitamin D and bone health in most of the evaluated sites. Correlation was observed in the analysis of subgroups for lumbar spine among men. When stratified, the studies presented high heterogeneity, which was explained by the sample size, mean serum vitamin D levels and risk of bias. Vitamin D is positively correlated to bone health in adult individuals.
Key words:
Mineral density; Vitamin D; Adults
Resumo
A baixa saúde óssea está associada à deficiência de vitamina D em indivíduos mais velhos; no entanto, isso não está bem estabelecido em adultos. O estudo objetivou-se analisar a associação entre concentrações séricas de 25-hidroxivitamina D e baixa saúde óssea em adultos por revisão sistemática e metanálise. A pesquisa foi realizada nas bases LILACS, PubMed, Scopus, Web of Science, ScienceDirect de março de 2017 a outubro de 2018 com indivíduos adultos (20-59 anos). A avaliação da saúde óssea foi realizada através da absorciometria dupla de raios X e concentrações séricas de 25(OH)D. O modelo de efeito aleatório foi utilizado para analisar dados do conteúdo mineral ósseo e densidade mineral óssea. Modelos de efeitos aleatórios foram utilizados e a heterogeneidade foi explorada por meio de meta-regressão. Trinta e cinco artigos foram selecionados. Houve correlação positiva entre a vitamina D e a saúde óssea na maioria dos locais avaliados. Observou-se correlação na análise de subgrupos da coluna lombar entre homens. Quando estratificados, os estudos apresentaram alta heterogeneidade, explicada pelo tamanho da amostra, pelos níveis séricos médios da vitamina e pelo risco de viés. A vitamina D está positivamente correlacionada com a saúde óssea em indivíduos adultos.
Palavras-chave:
Densidade mineral; Vitamina D; Adultos
Introduction
Over the last four decades there have been epidemiological and sociodemographic changes, with significant repercussions on living conditions and on the burden of chronic non-communicable diseases which constitute a global health problem11 Comissão Nacional sobre Determinantes Sociais da Saúde. As causas sociais das iniquidades em saúde no Brasil. Rio de Janeiro: Fiocruz; 2008.. Among the most common, the World Health Organization (WHO) has highlighted those related to complications arising from low bone mass, such as osteoporosis22 World Health Organization (WHO). WHO global report on falls prevention in older age. Geneva: WHO; 2010..
Osteoporosis is defined as a progressive, skeletal disease characterized by alterations in microarchitecture and consequent bone fragility22 World Health Organization (WHO). WHO global report on falls prevention in older age. Geneva: WHO; 2010.. This is an asymptomatic disease, usually identified when the individual presents a fracture, not only bringing damage in relation to the biological aspects, but also to the quality of life, as well as contributing to the increase in mortality and overloading the public health system due to the need for continued care22 World Health Organization (WHO). WHO global report on falls prevention in older age. Geneva: WHO; 2010.
3 Moraes LFS, Silva END, Silva DAS, Paula AP. Expenditures on the treatment of osteoporosis in the elderly in Brazil (2008-2010): analysis of associated factors. Rev Bras Epidemiol 2014; 17(3):719-734.-44 Arndt ÂBM, Telles JL, Kowalski SC. O custo direto da fratura de fêmur por quedas em pessoas idosas: análise no setor privado de saúde na cidade de Brasília. Rev Bras Geriatr Gerontol 2011; 14:221-231..
The evolution of osteoporosis and associated fractures are conditioned by some risk factors55 Yoo JE, Park HS. Prevalence and associated risk factors for osteoporosis in Korean men. Arch Osteoporos 2018; 13(1):88.
6 Kotwal N, Upreti V, Nachankar A, Hari Kumar KVS. A Prospective, Observational Study of Osteoporosis in Men. Indian J Endocrinol Metab 2018: 22(1):62-66.
7 Thorenson CK, Chung ST, Ricks M, Reynolds JC, Remaley AT, Periwal V, Li Y, Sumner AE. Biochemical and clinical deficiency is uncommon in African immigrants despite a high prevalence of low vitamin D: the Africans in America study. Osteoporos Int 2015; 26(11):2607-2615.
8 Camargo MBR, Kunii IS, Hayashi LF, Muszkat P, Anelli CG, Marin-Mio RV, Martini LA, França N, Lazaretti-Castro M. Modifiable factors of vitamin D status among a Brazilian osteoporotic population attended a public outpatient clinic. Arq Bras Endocrinol Metabol 2014; 58(5):572-582.
9 Shin HY, Kang HC, Lee K, Park SM. Association between the awareness of osteoporosis and the quality of care for bone health among Korean women with osteoporosis. BMC Musculoskelet Disord 2014; 15:334.-1010 Joo NS, Yang SW, Song BC, Yeum KJ. Vitamin A intake, serum vitamin D and bone mineral density: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2011). Nutrients 2015; 7(3):1716-1727., which lead to an osteometabolic imbalance caused by the deficiency of essential nutrients to maintain active bone metabolism, with the main nutrients being calcium and vitamin D77 Thorenson CK, Chung ST, Ricks M, Reynolds JC, Remaley AT, Periwal V, Li Y, Sumner AE. Biochemical and clinical deficiency is uncommon in African immigrants despite a high prevalence of low vitamin D: the Africans in America study. Osteoporos Int 2015; 26(11):2607-2615.,1111 Maeda SS, Borba VZC, Camargo MBR, Silva DMW, Borges JLC, Bandeira F, Lazaretti-Castro M, Brazilian Society of Endocrinology and Metabology (SBEM). Recommendations of the Brazilian Society of Endocrinology and Metabology (SBEM) for the diagnosis and treatment of hypovitaminosis D. Arq Bras Endocrinol Metab 2014; 58(5):411-433.,1212 Lips P. Vitamin D status and nutrition in Europe and Asia. J Steroid Biochem Mol Biol 2007; 103(3-5):620-625..
Vitamin D plays a determining role in the initial stages of skeletal development1212 Lips P. Vitamin D status and nutrition in Europe and Asia. J Steroid Biochem Mol Biol 2007; 103(3-5):620-625.,1313 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357:266-281., constituting a factor for preventing rickets and osteomalacia1414 The Scientific Advisory Committee on Nutrition. Update on Vitamin D. London: The Stationery Office; 2007.. However, in adulthood there are still controversies regarding the relationship between this vitamin and low bone mineral density (BMD) and bone mineral content (BMC), which are biophysical parameters used to assess bone health1515 Pinto Neto AM, Soares A, Urbanetz A, Souza ACA, Ferrari AEM, Amaral B, Moreira C, Fernandes CE, Zerbini CAF, Baracat E, Freitas EC, Meirelles ES, Bandeira F, Gonçalves HT, Lemgruber I, Marques Neto JF, Borges JLC, Castro JAS, Fiat JC, Mendonça LMC, Oliveira L, Russo LAT, Gregório LH, Marone M, Castro ML, Haidar MA, Santos PRD, Plapler P, Carneiro R, Guarniero R, Machado RB, Pereira RMR, Lederman R, Radominski S, Eis SR, Pereira SRM, Szjenfeld V, Chahade W. Consenso Brasileiro de Osteoporose 2002. Rev Bras Reumatol 2002; 42(6):343-354.,1616 Brandão CMR, Ferre F, Machado GPDM, Guerra Jr AA, Andrade EIG, Cherchiglia ML, Acurcio FA. Public spending on drugs for the treatment of osteoporosis in post-menopause. Rev Saúde Publica 2013; 47(2):390-402.. Some studies report a positive association1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925., while others suggest that these are not correlated1919 Nguyen HT, Von Schoultz B, Nguyen TV, Dzung DN, Duc PTM, Thuy VT, Hirschberg AL. Vitamin D deficiency in northern Vietnam: prevalence, risk factors and associations with bone mineral density. Bone 2012; 51(6):1029-1034.,2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143..
Considering the controversial results of studies on the influence of serum vitamin D levels on bone metabolism in adults and that vitamin D deficiency has been presented as a global public health problem, it is necessary to summarize the available evidence on the subject. In addition, there are few systematic review studies with a meta-analysis employing this approach in adults2121 Man PW, van der Meer IM, Lips P, Middelkoop BJC. Vitamin D status and bone mineral density in the Chinese population: a review. Arch Osteoporos 2016; 11(1):14.,2222 Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet 2014; 383(9912):146-155.. Thus, the objective of this systematic review was to analyze the association between serum concentrations of 25-hydroxyvitamin D (25(OH)D) and BMC and BMD in adults.
Methods
This is a systematic review study with meta-analysis supported by the PRISMA rules (Preferred Reporting Items for Systematic reviews and Meta-Analyses)2323 Knobloch K, Yoon U, Vogt PM. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and publication bias. J Craniomaxilofac 2011; 39(2):91-92. on the relationship between vitamin D and BMD/BMC in adults. In this perspective, we sought to answer the following question: are serum concentrations of 25(OH)D associated with BMC and BMD in adults?
Search strategy
Two independent reviewers (KJ Segheto and M Pereira) conducted study searches in the LILACS, PubMed, Scopus, Web of Science and ScienceDirect electronic databases from March 2017 to October 2018, with the following descriptors/Mesh terms: “vitamin D”, “bone density”, “BMD”, “BMC”, “adult” and “observational study” and their respective corresponding terms in Portuguese and Spanish. The search strategy included truncating the terms to exclude texts which did not fit the objectives of this review, such that they were adjusted according to the search form of each database (Chart 1).
The search results were managed in the Mendeley® program to remove duplicates and apply the inclusion criteria. The manuscript titles were initially read and then the abstracts of those publications which fulfilled the inclusion criteria. Once the articles were selected, the reading was completed in full. The last selection stage was an analysis of the references of the original articles and the identified revisions, thus guaranteeing refinement in searching for relevant works for this review.
The whole selection and evaluation process of the articles was done in pairs. At the end of the review, disagreements on eligibility were resolved by consensus with a third reviewer (CJ Carvalho).
Eligibility criteria
The articles selected for this review had to meet the following eligibility criteria: original studies whose objective was to analyze the association between 25(OH)D and BMC and/or BMD, performed with adult individuals aged 20 to 59 years of age, having no association to diseases, with bone health evaluation performed through dual X-ray absorptiometry (DXA) and serum concentrations of 25(OH)D.
In this study, it was decided to evaluate the serum concentrations of 25(OH)D because they are the best indicator of this vitamin2424 Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society. Evaluation, treatment, and prevention of Vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Meta 2011; 96(7):1911-1930.. Thus, studies that included individuals with vitamin D supplementation were excluded. In addition, serum concentrations of 25(OH)D were converted when necessary using the following criteria: 1ng/ml=2.496 nmol/l (24). In this way, it was possible to guarantee standardization and comparison of the presented results.
Data extraction
Eligible articles were read in full and information on the year of study publication, sample size, type of study, vitamin D results, correlation coefficient and/or linear regression and fit variables used in the modeling were registered in specific form.
Risk of bias
The risk of bias of the studies was individually assessed through the Research Triangle Institute Item Bank (RTI-Item Bank) scale2525 Viswanathan M, Berkman ND. Development of the RTI item bank on risk of bias and precision of observational studies. J Clin Epidemiol 2012; 65(2):163-178.. This scale is composed of 29 questions, among which 7 items were selected to assess the risk of bias of the articles due to the methodological diversity of the designs of observational studies. After the analysis, the risk of bias was classified as: high risk of bias - a study with one or more negative answers to the items; moderate risk of bias - when one or more items were considered “partially” or “cannot be determined”; and low risk of bias - all items on the scale had a positive response2525 Viswanathan M, Berkman ND. Development of the RTI item bank on risk of bias and precision of observational studies. J Clin Epidemiol 2012; 65(2):163-178. (Chart 2).
Statistical analysis
Correlation coefficients and sample size were used to calculate the standard error to evaluate the correlation between 25(OH)D and bone health. The Z-test was used to analyze the data for the following bone sites: BMC, lumbar spine BMD (LS-BMD), hip (H-BMD), femoral neck (FN-BMD) and trochanter (T-BMD). The Cochran Q statistical test and the inconsistency test (I²)2525 Viswanathan M, Berkman ND. Development of the RTI item bank on risk of bias and precision of observational studies. J Clin Epidemiol 2012; 65(2):163-178. were used to evaluate the heterogeneity and consistency of the studies. When heterogeneity (I²>25%) was identified, the random effects model was used2626 Harris RJ, Deeks JJ, Altman DG, Bradburn MJ, Harbord RM, Sterne JAC. Metan: fixed-and random-effects meta-analysis. Stata J 2008; 8(1):3-28..
The publication bias was evaluated through the funnel plot symmetry2626 Harris RJ, Deeks JJ, Altman DG, Bradburn MJ, Harbord RM, Sterne JAC. Metan: fixed-and random-effects meta-analysis. Stata J 2008; 8(1):3-28.. The statistical evaluation of the effect of small studies was performed by the Egger test2727 Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315(7109):629-634.. The criterion for the application of these tests was the minimum number of eight studies. Gender-based subgroup analysis was also performed to identify possible sources of heterogeneity. The overall effect was derived from the DerSimonian and Laird method2626 Harris RJ, Deeks JJ, Altman DG, Bradburn MJ, Harbord RM, Sterne JAC. Metan: fixed-and random-effects meta-analysis. Stata J 2008; 8(1):3-28., using the random effects model, which takes into account the variation between the studies.
In addition to gender, meta-regressions were performed considering the following variables: age, group evaluated (1-men, 2-women, 3-men and women), sample size, mean concentration serum levels of vitamin D, latitude and longitude of the study site, and risk of bias score of each study. The results obtained from the correlation between vitamin D and bone health in adults are presented using a Forest Plot chart. A p-value less than 0.05 was considered significant in all analyzes. The STATA 14 program (Stata Corp, College Station) was used for data analysis.
Results
Characterization of the selected studies
A total of 2,562 articles were identified and 2,397 were excluded by reading the title and abstract, and thus 84 articles were selected for reading in full (Figure 1). In the end, 35 articles were included in the qualitative synthesis1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.
29 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.
30 Guzel R, Kozanoglu E, Guler-Uysal F, Soyupak S, Sarpel T. Vitamin D status and bone mineral density of veiled and unveiled Turkish women. J Womens Health Gend Based Med 2001; 10(8):765-770.
31 Lamberg-Allardt CJ, Outila TA, Kärkkäinen MU, Rita HJ, Valsta LM. Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Min Res 2001; 16(11):2066-2073.
32 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.
33 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.
34 Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B. Positive Association between 25-Hydroxy Vitamin D Levels and Bone Mineral Density: A Population-Based Study of Younger and Older Adults. Am J Med 2004; 116(9):634-639.
35 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.
36 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.
37 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.
38 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.
39 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.
40 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.
41 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.
42 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.
43 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.
44 Gutiérrez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011; 22(6):1745-1753.
45 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.
46 Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011; 26(7):1609-1616.
47 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.
48 Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int 2012; 23(2):675-686.
49 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.
50 Lim JS, Kim KM, Rhee Y, Lim SK. Gender-dependent skeletal effects of vitamin D deficiency in a younger generation. J Clin Endocrinol Metab 2012; 97(6):1995-2004.
51 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.
52 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.
53 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.
54 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.
55 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.
57 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.
58 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.-5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631., and those that presented a linear correlation coefficient as a measure of association were included in the meta-analysis, totaling 23 articles1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3333 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.
36 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.
37 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.
38 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.
39 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.
40 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.
41 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.
42 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.-4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5151 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.
52 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.-5353 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.,5555 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.
57 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.-5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966. (Figure 1). The main reasons for exclusion of the complete articles were the age group not corresponding to the studied age group (n=26), no evaluation of the influence of vitamin D concentration on BMC/BMD (n=9), participants in the study with associated diseases (n=6), review study (n=4), pregnancy (n=1), letter to the Editor (n=1), did not use the DXA to evaluate bone health (n=1), and did not evaluate 25(OH)D (n=1) (Figure 1, Chart 3).
Identification and selection flowchart for articles. BMC: Bone mineral content; BMD: bone mineral density; DXA: Double X-ray Absorptiometry; 25(OH)D: 25-Hydrovitamin D.
All the studies included in this review have a cross-sectional design. We included studies with year of publication from 1992 to 2017, most of which were published between 2011-2015 (37.1%)4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.
44 Gutiérrez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011; 22(6):1745-1753.
45 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.
46 Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011; 26(7):1609-1616.
47 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.
48 Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int 2012; 23(2):675-686.
49 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.
50 Lim JS, Kim KM, Rhee Y, Lim SK. Gender-dependent skeletal effects of vitamin D deficiency in a younger generation. J Clin Endocrinol Metab 2012; 97(6):1995-2004.
51 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.
52 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.
53 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.
54 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.-5555 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.. Most of the studies were carried out in Asian countries (48.6%)1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3333 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,4242 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.,4545 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.,4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,4848 Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int 2012; 23(2):675-686.,5050 Lim JS, Kim KM, Rhee Y, Lim SK. Gender-dependent skeletal effects of vitamin D deficiency in a younger generation. J Clin Endocrinol Metab 2012; 97(6):1995-2004.
51 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.-5252 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.,5555 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.
57 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.-5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966. and with a sample consisting of up to 500 individuals (42.8%)1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.,3131 Lamberg-Allardt CJ, Outila TA, Kärkkäinen MU, Rita HJ, Valsta LM. Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Min Res 2001; 16(11):2066-2073.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,4242 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.,4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4545 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.,4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5353 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.
54 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.-5555 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.,5757 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.,5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631.. There was a predominance of studies with individuals of both genders (51.4%)2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.,3131 Lamberg-Allardt CJ, Outila TA, Kärkkäinen MU, Rita HJ, Valsta LM. Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Min Res 2001; 16(11):2066-2073.
32 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.
33 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.-3434 Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B. Positive Association between 25-Hydroxy Vitamin D Levels and Bone Mineral Density: A Population-Based Study of Younger and Older Adults. Am J Med 2004; 116(9):634-639.,4242 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.
43 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.-4444 Gutiérrez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011; 22(6):1745-1753.,4646 Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011; 26(7):1609-1616.,4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.
50 Lim JS, Kim KM, Rhee Y, Lim SK. Gender-dependent skeletal effects of vitamin D deficiency in a younger generation. J Clin Endocrinol Metab 2012; 97(6):1995-2004.
51 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.
52 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.-5353 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.,5555 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.-5757 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.. Articles that evaluated only women corresponded to 28.6% of the studies1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3030 Guzel R, Kozanoglu E, Guler-Uysal F, Soyupak S, Sarpel T. Vitamin D status and bone mineral density of veiled and unveiled Turkish women. J Womens Health Gend Based Med 2001; 10(8):765-770.,3636 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.,3838 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.,3939 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.,4545 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.,5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631. and only men at 20%3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.,3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,4141 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.,4848 Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int 2012; 23(2):675-686.,5454 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.,5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.. In addition to BMC (25.7%)1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.,4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4444 Gutiérrez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011; 22(6):1745-1753.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5353 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.,5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631., there was a predominance of studies which evaluated the following bone sites: LS-BMD (85.7%)1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.
29 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.-3030 Guzel R, Kozanoglu E, Guler-Uysal F, Soyupak S, Sarpel T. Vitamin D status and bone mineral density of veiled and unveiled Turkish women. J Womens Health Gend Based Med 2001; 10(8):765-770.,3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3333 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.
36 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.
37 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.
38 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.
39 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.
40 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.
41 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.
42 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.-4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4646 Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011; 26(7):1609-1616.
47 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.
48 Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int 2012; 23(2):675-686.
49 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.
50 Lim JS, Kim KM, Rhee Y, Lim SK. Gender-dependent skeletal effects of vitamin D deficiency in a younger generation. J Clin Endocrinol Metab 2012; 97(6):1995-2004.
51 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.-5252 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.,5454 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.
55 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.
57 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.
58 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.-5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631., FN-BMD (80%)1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.
29 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.-3030 Guzel R, Kozanoglu E, Guler-Uysal F, Soyupak S, Sarpel T. Vitamin D status and bone mineral density of veiled and unveiled Turkish women. J Womens Health Gend Based Med 2001; 10(8):765-770.,3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3333 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.,3636 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.
37 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.
38 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.
39 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.
40 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.
41 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.
42 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.-4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4545 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.,4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.
48 Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int 2012; 23(2):675-686.
49 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.
50 Lim JS, Kim KM, Rhee Y, Lim SK. Gender-dependent skeletal effects of vitamin D deficiency in a younger generation. J Clin Endocrinol Metab 2012; 97(6):1995-2004.
51 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.
52 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.
53 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.
54 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.
55 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.
57 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.
58 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.-5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631., H-BMD (65,7%)2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3434 Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B. Positive Association between 25-Hydroxy Vitamin D Levels and Bone Mineral Density: A Population-Based Study of Younger and Older Adults. Am J Med 2004; 116(9):634-639.
35 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.
36 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.
37 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.
38 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.
39 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.
40 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.
41 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.-4242 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.,4545 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.,4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5050 Lim JS, Kim KM, Rhee Y, Lim SK. Gender-dependent skeletal effects of vitamin D deficiency in a younger generation. J Clin Endocrinol Metab 2012; 97(6):1995-2004.
51 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.
52 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.-5353 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.,5656 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.
57 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.
58 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.-5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631. and T-BMD (42.8%)1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3333 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.,3636 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.,3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.,3939 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,4242 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.,4545 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.,4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.
50 Lim JS, Kim KM, Rhee Y, Lim SK. Gender-dependent skeletal effects of vitamin D deficiency in a younger generation. J Clin Endocrinol Metab 2012; 97(6):1995-2004.-5151 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.,5656 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.. Among the adjustment variables identified in articles using multiple linear regression, the most frequent were age (40%)2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3434 Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B. Positive Association between 25-Hydroxy Vitamin D Levels and Bone Mineral Density: A Population-Based Study of Younger and Older Adults. Am J Med 2004; 116(9):634-639.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.,3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.
38 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.
39 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.
40 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.-4141 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.,4444 Gutiérrez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011; 22(6):1745-1753.,4646 Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011; 26(7):1609-1616.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5252 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.,5555 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.,5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966., gender (25.7%)2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.,3131 Lamberg-Allardt CJ, Outila TA, Kärkkäinen MU, Rita HJ, Valsta LM. Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Min Res 2001; 16(11):2066-2073.,3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3434 Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B. Positive Association between 25-Hydroxy Vitamin D Levels and Bone Mineral Density: A Population-Based Study of Younger and Older Adults. Am J Med 2004; 116(9):634-639.,4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4444 Gutiérrez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011; 22(6):1745-1753.,4646 Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011; 26(7):1609-1616.,5151 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.,5757 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176., height (20%)2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.,3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,5252 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.,5757 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.,5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631. and total body mass (20%)1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.,3434 Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B. Positive Association between 25-Hydroxy Vitamin D Levels and Bone Mineral Density: A Population-Based Study of Younger and Older Adults. Am J Med 2004; 116(9):634-639.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,5252 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.,5757 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176. (Table 1).
Results of individual studies
Regarding the statistical test, it was observed that most of the articles evaluated the associations by linear correlation (n=27)2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.
29 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.-3030 Guzel R, Kozanoglu E, Guler-Uysal F, Soyupak S, Sarpel T. Vitamin D status and bone mineral density of veiled and unveiled Turkish women. J Womens Health Gend Based Med 2001; 10(8):765-770.,3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3333 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.,3636 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.,3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.,3939 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.
40 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.
41 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.
42 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.-4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4545 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.
46 Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011; 26(7):1609-1616.-4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.
50 Lim JS, Kim KM, Rhee Y, Lim SK. Gender-dependent skeletal effects of vitamin D deficiency in a younger generation. J Clin Endocrinol Metab 2012; 97(6):1995-2004.
51 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.
52 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.
53 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.
54 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.
55 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.
57 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.
58 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.-5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631.. The majority of studies identified a positive correlation between 25(OH)D and bone health for both men (n=5)3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.,4141 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.,4848 Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int 2012; 23(2):675-686.,5252 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.,5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966. and for women (n=8)1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3636 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.,3838 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.,3939 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.,4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,5656 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.. The bone site most frequently evaluated in men was LS-BMD (n=17)2020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.,5151 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.,5252 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.,5454 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.,5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966., while among women it was FN-BMD (n=12)2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.
29 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.-3030 Guzel R, Kozanoglu E, Guler-Uysal F, Soyupak S, Sarpel T. Vitamin D status and bone mineral density of veiled and unveiled Turkish women. J Womens Health Gend Based Med 2001; 10(8):765-770.,3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3636 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.,3939 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.,4242 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.,4545 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.,5555 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.-5757 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.,5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631..
Risk of Bias Results
We performed the risk assessment of individual bias of each study included in the review (Chart 2). We observed that 71.4% articles presented a high risk of bias1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.
29 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.
30 Guzel R, Kozanoglu E, Guler-Uysal F, Soyupak S, Sarpel T. Vitamin D status and bone mineral density of veiled and unveiled Turkish women. J Womens Health Gend Based Med 2001; 10(8):765-770.
31 Lamberg-Allardt CJ, Outila TA, Kärkkäinen MU, Rita HJ, Valsta LM. Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Min Res 2001; 16(11):2066-2073.-3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3434 Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B. Positive Association between 25-Hydroxy Vitamin D Levels and Bone Mineral Density: A Population-Based Study of Younger and Older Adults. Am J Med 2004; 116(9):634-639.
35 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.
36 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.-3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,4242 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.,4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4545 Harinarayan CV, Sachan A, Reddy PA, Satish KM, Prasad UV, Srivani P. Vitamin D Status and Bone Mineral Density in Women of Reproductive and Postmenopausal Age Groups: A Cross-Sectional Study from South India. J Assoc Physicians Indians 2011; 59:698-704.
46 Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011; 26(7):1609-1616.-4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,5353 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.,5454 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.,5757 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.
58 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.-5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631.. Only 25.7% were identified as having moderate risk of bias,41,44,48-52,55 and 2.8% with low risk of bias3333 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61..
The main aspects that contributed to the high risk of bias were: uniform inclusion and exclusion criteria; valid outcome evaluation, appropriate sample selection and general judgment of risk of bias, respectively (Figure 2).
Meta-analysis results
In the meta-analysis, only articles using Pearson’s linear correlation were included for the following bone sites: BMC - 7/91818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.,4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4747 Sadat-Ali M, Al Elq AH, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Influence of vitamin D on bone mineral density and osteoporosis. Ann Saudi Med 2011; 31(6):602-608.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5353 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.; LS-BMD - 11/302020 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, Al-Suhaili AI. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 2006; 39(5):1136-1143.,2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.,3838 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.,3939 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.,4141 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.,4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,5151 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.,5555 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.-5757 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.; H-BMD - 14/232929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.
36 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.-3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.,3838 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.,4141 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.,4242 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5151 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.
52 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.-5353 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.,5656 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.
57 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.-5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.; FN-BMD - 20/282828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3333 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.,3636 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.
37 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.
38 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.
39 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.
40 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.
41 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.
42 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.-4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5151 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.
52 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.
53 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.
54 Kassi EN, Stapvropoulos S, Kokkoris P, Galanos A, Moutsatsou P, Dimas C, Papatheodorou A, Zafeiris C, Lyritis G. Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males. Hormones 2015; 14(2):245-250.
55 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.
56 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458.
57 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.-5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.; and T-BMD - 10/152929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3333 Arya V, Bhambri R, Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians. Osteoporos Int 2004; 15(1):56-61.,3636 Güler T, Sivas F, Baskan BM, Günesen O, Alemdaroglu E, Ozoran K. The effect of outfitting style on bone mineral density. Rheumatol Int 2007; 27(8):723-727.,3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.,3939 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,4242 Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral density in resident doctors working at a teaching hospital. J Postgrad Med 2010; 56(2):65-70.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5151 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.,5656 Khashayar P, Meybodi HRA, Hemani MR, Keshtkar A, Dimai HP, Larijani B. Vitamin D status its relationship with bone mineral density in a healthy Iranian population. Rev Bras Ortop 2016; 51(4):454-458..
Significant correlation of 25(OH)D was identified with: BMC (Fisher Z=0.31; 95%CI=0.18-0.44), H-BMD (Fisher Z=0.07; 95%CI=0.02-0.12), FN-BMD (Fisher Z=0.08; 95%CI=0.03-0.13) and T-BMD (Fisher Z=0.08; 95%CI=0.1-0.15). There was no statistically significant association between 25(OH)D and LS-BMD (Fisher Z=0.03; 95%CI=-0.01-0.08). In the subgroup analysis, a positive correlation was found between 25(OH)D and LS-BMD concentrations in men (Table 2). The evaluated studies presented high heterogeneity for all bone sites, with significant Q-test (p<0.05) and I² values above 70% (Figures 3 and 4).
Correlation between serum vitamin D concentrations and bone health in adults. Lumbar spine bone mineral density; Hip bone mineral density; Femoral neck bone mineral density; Trochanter bone mineral density.
It was possible to observe that there is no evidence of publication bias through the funnel graph (Figure 5). Considering the Egger’s test, the effect of small studies was only observed for the femoral neck (LS-BMD: p=0.083; H-BMD: p=0.088; FN-BMD: p=0.024; and T-BMD: p=0.074).
Funnel graph for studies on the association between serum vitamin D concentrations and bone health. Lumbar spine bone mineral density; Hip bone mineral density; Femoral neck bone mineral density; Trochanter bone mineral density.
Meta-regressions were performed to investigate possible sources of heterogeneity identified in the meta-analysis. We observed statistically significant sources of heterogeneity for: sample size for FN-BMD (p<0.01) and H-BMD (p=0.01); mean serum 25(OH)D concentrations of participants for H-BMD (p=0.03); and risk of bias for BMC (p=0.03). On the other hand, the mean age of the participants, the analyzed group (1-men, 2-women, 3-men and women), as well as the latitude and longitude did not significantly contribute to the occurrence of heterogeneity in the meta-analyzes (Table 3).
Discussion
We observed a significant positive correlation between serum 25(OH)D concentrations and bone health in adults in the evaluated bone sites. The studies selected for this review presented high heterogeneity and high coverage in relation to gender, ethnicity, study population, and countries, among other aspects. An effect of small studies were not observed except for the FN-BMD site (Chart 4).
The relationship between 25(OH)D and bone health in adults is biologically plausible, since deficiency of this vitamin has been considered an important determinant of several diseases, especially those related to bone health6060 Chen CH, Liu LK, Chen MJ, Lee WJ, Lin MH, Peng LN, Chen LK. Associations between vitamin D deficiency, musculoskeletal health, and cardiometabolic risk among community-living people in Taiwan: Age and sex-specific relationship. Medicine 2016; 97(52):e13866.
61 Levinger P, Begg R, Sanders KM, Nagano H, Downie C, Petersen A, Hayes A, Cicuttini F. The effect of vitamin D status on pain, lower limb strength and knee function during balance recovery in people with knee osteoarthritis: an exploratory study. Arch Osteoporos 2017; 12(1):83.
62 Feng Y, Cheng G, Wang H, Chen B. The associations between serum 25-hydroxyvitamin D level and the risk of total fracture and hip fracture. Osteoporos Int 2017; 28(5):1641-1652.-6363 Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, Liu S, Looker AC, Wallace TC, Wang DD. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int 2016; 27(1):367-376.. Vitamin D is important throughout development, as it allows a greater absorption of calcium in the intestine, which also positively contributes to bone health1313 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357:266-281.,2424 Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society. Evaluation, treatment, and prevention of Vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Meta 2011; 96(7):1911-1930.. Deficiency of vitamin D in the early stages of development may lead to developing weak, narrow and soft bones, providing a greater probability of fractures1313 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357:266-281.,2424 Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society. Evaluation, treatment, and prevention of Vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Meta 2011; 96(7):1911-1930.. In a systematic review, it was identified that low 25(OH)D in childhood increases the risk of fractures in this age group, requiring supplementation in these cases6464 Moon RJ, Harvey NC, Davies JH, Cooper C. Vitamin D and skeletal health in infancy and childhood. Osteoporos Int 2014; 25(12):2673-2684.. Although all the factors associated with the occurrence of osteoporosis have not yet been well established, it is known that peak bone mass during childhood and adolescence (the period for accumulating 50% of total bone mass) and the rate of bone loss during aging are determinants6565 Gordon CM, Zemel BS, Wren TA, Leonard MB, Bachrach LK, Rauch F, Gilsanz V, Rosen CJ, Winer KK. The determinants of peak bone mass. J Pediatr 2017; 180:261-269.. Thus, adequate concentrations of vitamin D during these development stages contribute to optimizing mineral gain, and consequently to better bone health in adulthood6565 Gordon CM, Zemel BS, Wren TA, Leonard MB, Bachrach LK, Rauch F, Gilsanz V, Rosen CJ, Winer KK. The determinants of peak bone mass. J Pediatr 2017; 180:261-269.. This may ease the process of loss at more advanced ages.
A meta-analysis conducted with randomized clinical trials aimed at assessing the relationship between calcium and vitamin D supplementation and fracture prevention in middle-aged and older adult individuals found that those who underwent vitamin D supplementation had a reduction in the risk of general fractures by 15% and of hip fractures by 30%6363 Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, Liu S, Looker AC, Wallace TC, Wang DD. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int 2016; 27(1):367-376.. Another meta-analysis identified similar results, noting an association between vitamin D insufficiency and hip fracture risk, with a 40% increase in risk of occurrence6262 Feng Y, Cheng G, Wang H, Chen B. The associations between serum 25-hydroxyvitamin D level and the risk of total fracture and hip fracture. Osteoporos Int 2017; 28(5):1641-1652.. Another study with predominantly white adults evaluating 2,294 individuals submitted to vitamin D supplementation found a positive association in six of the ten studies evaluated, four with beneficial effect on only one bone site and two on the hip, despite the heterogeneity between the trials6666 Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet 2014; 383(9912):146-155.. These authors emphasized that, although maintaining adequate serum levels of vitamin D is important, supplementation should be performed only in individuals identified with inadequate levels6666 Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet 2014; 383(9912):146-155..
In our review, the most evaluated bone sites were LS-BMD, H-BMD and FN-BMD. These results are consistent with the recommendations for clinical practice, since they are anatomical regions where the initial process of bone loss (osteopenia) occurs1515 Pinto Neto AM, Soares A, Urbanetz A, Souza ACA, Ferrari AEM, Amaral B, Moreira C, Fernandes CE, Zerbini CAF, Baracat E, Freitas EC, Meirelles ES, Bandeira F, Gonçalves HT, Lemgruber I, Marques Neto JF, Borges JLC, Castro JAS, Fiat JC, Mendonça LMC, Oliveira L, Russo LAT, Gregório LH, Marone M, Castro ML, Haidar MA, Santos PRD, Plapler P, Carneiro R, Guarniero R, Machado RB, Pereira RMR, Lederman R, Radominski S, Eis SR, Pereira SRM, Szjenfeld V, Chahade W. Consenso Brasileiro de Osteoporose 2002. Rev Bras Reumatol 2002; 42(6):343-354.. However, recent studies have shown that evaluation of total bone health from BMC is also important1717 Islam MZ, Shaminn AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency a low bone status in adult female garment factory workers in Bangladesh. Br J Nutr 2008; 99(6):1322-1329.,1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.,4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4444 Gutiérrez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011; 22(6):1745-1753.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5353 George JA, Micklesfield LK, Norris SA, Crowther NJ. The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 2014; 99(6):2146-2154.,5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631., with the identification of mean bone mass values for the overall evaluation of the individual being necessary.
The relationship between vitamin D status and gender is still unclear. In this perspective, we identified a correlation between vitamin D and bone mineral density, regardless of gender. Thus, this variable does not appear to be an effect modifier on the relationship between vitamin D concentrations and total amount of bone mass of the individual. It should be considered that some evidence points to better bone health in men because higher concentrations of 25(OH)D have been identified6767 Hagenau T, Vest R, Gissel TN, Poulsen CS, Erlandsen M, Mosekilde L, Vestergaard P. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int 2009; 20(1):133-140.,6868 Prentice A. Vitamin D deficiency: a global perspective. Nutr Rev 2008; 66(10 Supl. 2)):S153-S164.. Another question concerns the relationship between 25(OH)D and different parathyroid hormones between genders, with a more pronounced influence in men than in women6969 Leung RY, Cheung BM, Nguyen US, Kung AW, Tan KC, Cheung CL. Optimal vitamin D status and its relationship with bone and mineral metabolism in Hong Kong Chinese. Bone 2017; 97:293-298.. Although the studies are not entirely conclusive, some authors claim that adequate vitamin D concentrations are also related to excess fat and hormones, especially estrogen7070 Ceglia L, Nelson J, Ware J, Alysandratos K-D, Bray GA, Garganta C, Nathan DM, Hu FB, Dawson-Hughes B, Pittas AG, Diabetes Prevention Program Research Group. Association between body weight and composition and plasma 25-hydroxyvitamin D level in the Diabetes Prevention Program. Eur J Nutr 2017; 56(1):161-170.,7171 Han SS, Kim M, Lee SM, Lee JP, Kim S, Joo KW, Lim CS, Kim YS, Kim DK. Association between body fat and vitamin D status in Korean adults. Asia Pac J Clin Nutr 2014; 23(1):65-75., and this may contribute to women having a higher prevalence of vitamin D deficiency, negatively influencing their bone health.
The risk of bias in the studies included in this review was mostly high, which may influence the results identified herein. There is considerable variation in the inclusion and exclusion criteria of the studies analyzed in this review, and consequently in the samples from the selected studies. In addition, according to the meta-regression results, sample size, mean serum vitamin D concentrations and risk of bias contributed significantly to the heterogeneity observed between the analyzed studies, suggesting that these variables should be considered in planning studies about this subject.
Most of the studies, as observed, used the correlation coefficient to evaluate the association between serum vitamin D concentrations and bone health, which is why the meta-analysis of this review was conducted using this measure of association as a reference. A very small number of studies used linear regression and presented results adjusted by confounding factors. The main variables used for adjustment in these models were age, gender, ethnicity, height and total body mass1818 Nakamura K, Nashimoto M, Matsuyama S, Yamamoto M. Low serum concentrations of 25-Hydroxyvitamin D in young adult japanese women: a cross sectional study. Nutrition 2001; 17(11-12):921-925.,2828 Sherman SS, Tobin JD, Hollis BW, Gundberg CM, Roy TA, Plato CC. Biocheminal parameters associated with low bone density in healthy men and women. J Bone Miner Res 1992; 7(10):1123-1130.,2929 Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 2009; 245(5):509-516.,3131 Lamberg-Allardt CJ, Outila TA, Kärkkäinen MU, Rita HJ, Valsta LM. Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Min Res 2001; 16(11):2066-2073.,3232 Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young indian adults with optimal vitamin D availability. Natl Med J India 2003; 16(6):298-302.,3434 Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B. Positive Association between 25-Hydroxy Vitamin D Levels and Bone Mineral Density: A Population-Based Study of Younger and Older Adults. Am J Med 2004; 116(9):634-639.,3535 Högström M, Nordström A, Nordström P. Relationship between vitamin D metabolites and bone mineral density in young males: a cross-sectional and longitudinal study. Calcif Tissue Int 2006; 79(2):95-101.,3737 Hannan MT, Litman HJ, Araujo AB, McLennan CE, McLean RR, McKinlay JB, Chen TC, Holick MF. Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men. J Clin Endocrinol Metab 2008; 93(1):40-46.
38 Adami S, Bertolgo F, Braga V, Fracassi E, Gatti D, Gandolini G, Minisola S, Rini GB. 25-Hydroxy Vitamin D levels in healthy premenopausal women: association with bone turnover markers and bone mineral density. Bone 2009; 45(3):423-426.
39 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.
40 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.-4141 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.,4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4444 Gutiérrez OM, Farwell WR, Kermah D, Taylor EN. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 2011; 22(6):1745-1753.,4646 Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, Wenger J, Karumanchi SA, Thadhani R, Bhan I. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 2011; 26(7):1609-1616.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5151 Shivane VK, Sarathi V, Lila AR, Bandgar T, Joshi SR, Menon PS, Shah NS. Peak bone mineral density and its determinants in an Asian indian population. J Clin Densitom 2012; 15(2):152-158.,5252 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.,5555 Wei QS, Chen ZQ, Tan X, Su HR, Chen XX, He W, Deng WM. Relation of age, sex and bone mineral density to serum 25-Hydroxivitamin D levels in Chinese women and men. Orthop Surg 2015; 7(4):343-349.,5757 Sayed-Hassan R, Abazid N, Alourfi Z. Relationship between 25-hydroxyvitamin D concentrations, serum calcium, and parathyroid hormone in apparently healthy Syrian people. Arch Osteoporos 2014; 9:176.,5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.. These are important factors which have an influence on bone health, but others are also relevant and should be considered in studies on the association between vitamin D and bone health. Genetics, behavior, sun exposure, dietary intake of calcium and foods reinforced with vitamin D, in addition to the vitamin supplementation itself, may have an impact on the status of 25(OH)D and consequently on bone health3434 Bischoff-Ferrari HA, Dietrich T, Orav J, Dawson-Hughes B. Positive Association between 25-Hydroxy Vitamin D Levels and Bone Mineral Density: A Population-Based Study of Younger and Older Adults. Am J Med 2004; 116(9):634-639.,3939 Allali F, Aichaoui SEL, Khazani H, Benyahia B, Saoud B, El Kabbaj S, Bahiri R, Abouqal R, Hajjaj-Hassouni N. High prevalence of Hypovitaminosis D in Morocco: relationship to lifestyle, physical performance, bone markers, and bone mineral density. Bone 2009; 38(6):444-451.,4040 Marwaha RK, Tandon N, Shivaprasad C, Kanwar R, Mani K, Aggarwal R, Bhadra K, Singh S, Sharma B, Tripathi RP. Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization. J Clin Densitom 2009; 12(3):314-321.,4141 Frost M, Abrahamsen B, Nielsen TL, Hagen C, Andersen M, Brixen K. Vitamin D status and PTH in young men: a cross-sectional study on associations with bone mineral density, body composition and glucose metabolism. Clin Endocrinol 2010; 73(5):573-580.,4343 Boot AM, Krenning EP, Keizer-Schrama SMPFM. The relation between 25-hydroxyvitamin D with peak bone mineral density and body composition in healthy young adults. J Pediatr Endocrinol Metab 2011; 24(5-6):355-360.,4949 Kull M, Kallikorm R, Lember M. Vitamin D as a possible independent predictor of bone mineral density in Estonian adults: a cross-sectional population-based study. Intern Med J 2012; 42(6):e89-e94.,5252 Joo N-S, Dawson-Hughes B, Yeum K-J. 25-Hydroxyvitamin D, calcium intake, and bone mineral content in adolescents and young adults: analysis of the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3, 2008-2009 and V-1, 2010). J Clin Endocrinol Metab 2013; 98(9):3627-3636.,5858 Zhang Q, Shi L, Peng N, Xu S, Zhang M, Zhang S, Li H, Zhuang H, Gong M, Wu D, Wang R. Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. Br J Nutr 2016; 115(6):960-966.,5959 Callegari ET, Garland SM, Gorelik A, Wark JD. Determinants of bone mineral density in young Australian women; results from the Safe-D study. Osteoporos Int 2017; 28(9):2619-2631.. It is therefore recommended that these issues be considered in future work, particularly through forward-looking approaches.
The present study has some limitations. The first one refers to the fact that all the selected studies have a cross-sectional design, and therefore by character these studies do not enable an establishment of a temporal relation between the studied variables. Another issue is the non-standardization of the evaluated bone sites, which makes it difficult to summarize the results. Finally, the comparison of vitamin D status may be hampered by a high variation of serum 25(OH)D measurement between different analytical methods.
As a positive, we highlight that this review includes an evaluation of the association between serum vitamin D concentrations in different bone sites in adults and the analysis of data exploring subgroups and heterogeneity sources. Moreover, the performance of all the review stages by independent authors is also worth mentioning, reducing the chance of selection bias of the studies.
In conclusion, we showed a positive association between serum concentrations of 25(OH)D and bone health from the results of this systematic review and meta-analysis. It should be noted that clinically healthy individuals without osteometabolic diseases were evaluated in this study. This is an important issue because given the positive association identified, there is need to maintain adequate vitamin D levels even in adults due to its biological importance.
It is therefore recommended that bone health evaluation be incorporated into clinical practice aimed at adults with vitamin D insufficiency or deficiency. It is known that osteoporosis is a silent disease and therefore requires preventive measures and early diagnosis in order to avoid critical illness or possible fractures.
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Publication Dates
- Publication in this collection
09 Aug 2021 - Date of issue
Aug 2021
History
- Received
26 Nov 2019 - Accepted
26 May 2020 - Published
28 May 2020
Source: Elaborated by the authors.
Source: Elaborated by the authors.
Source: Elaborated by the authors.
Source: Elaborated by the authors.
Source: Elaborated by the authors.