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BMC Endocrine Disorders
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Open Access 01-12-2024 | Research

Does higher serum 25-hydroxyvitamin D levels will harm bone mineral density?: a cross-sectional study

Authors: Bingcheng Xu, Qiai Li, Bo Luo, Hao Liu

Published in: BMC Endocrine Disorders | Issue 1/2024

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Abstract

Objective

Vitamin D plays a critical role in the prevention and management of osteoporosis. However, there is an ongoing debate regarding the most effective vitamin D supplementation strategies for maintaining optimal bone mineral density (BMD) levels in adults. This study sought to establish the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and total BMD in a substantial population sample.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) for the 2011–2018 cycles, encompassing 11,375 adult participants, were analyzed. The primary variables of interest were serum 25(OH)D levels and BMD. A multivariable logistic regression model was utilized to account for relevant variables associated with these correlations.

Results

A U-shaped relationship between serum 25(OH)D levels and BMD was observed. In males, a significant positive association was identified for 25(OH)D levels below 84.8 nmol/L (p < 0.0001), while levels above this threshold showed no significant correlation (p = 0.3377). In females, those with 25(OH)D levels below 31.4 nmol/L exhibited a significant positive association with BMD (p = 0.0010), but this association weakened and became marginally significant above this threshold (p = 0.0650).

Conclusions

For adult males, the optimal serum 25(OH)D level is 84.8 nmol/L, beyond which higher levels do not lead to increased BMD. A deficiency threshold for adult females should be above 31.4 nmol/L, as lower 25(OH)D levels are not conducive to BMD. These findings underscore the importance of maintaining appropriate vitamin D levels for bone health in both genders.
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Literature
1.
2.
Morin SN, Berger C, Papaioannou A, Cheung AM, Rahme E, Leslie WD, et al. Race/ethnic differences in the prevalence of osteoporosis, falls and fractures: a cross-sectional analysis of the Canadian longitudinal study on aging. Osteoporos Int. 2022;33:2637–48.PubMedCrossRef
3.
Bargagli M, Arena M, Naticchia A, Gambaro G, Mazzaferro S, Fuster D, et al. The role of Diet in Bone and Mineral metabolism and secondary hyperparathyroidism. Nutrients. 2021;13:2328.PubMedPubMedCentralCrossRef
4.
Shanshan Xue, Xue S, Oumer Kemal, Kemal O, Meihan Lu, Lu M, et al. Age at attainment of peak bone mineral density and its associated factors: the National Health and Nutrition Examination Survey 2005–2014. Bone. 2020;131:115163.CrossRef
5.
Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength: a Randomized Clinical Trial. JAMA. 2019;322:736–45.PubMedPubMedCentralCrossRef
6.
7.
Gordon CM, Zemel BS, Wren TAL, Leonard MB, Bachrach LK, Rauch F, et al. The determinants of peak bone Mass. J Pediatr. 2017;180:261–9.PubMedCrossRef
8.
Marwaha RK, Tandon N, Garg MK, Kanwar R, Narang A, Sastry A, et al. Bone health in healthy Indian population aged 50 years and above. Osteoporos Int. 2011;22:2829–36.PubMedCrossRef
9.
Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol. 2018;6:847–58.PubMedCrossRef
10.
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and Vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53–8.PubMedCrossRef
11.
Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2005;16:713–6.CrossRef
12.
Larsson SC, Melhus H, Michaëlsson K. Circulating serum 25-Hydroxyvitamin D levels and bone Mineral density: mendelian randomization study. J Bone Min Res. 2018;33:840–4.CrossRef
13.
Boyd SK, Burt LA, Sevick LK, Hanley DA. The relationship between serum 25(OH)D and bone density and microarchitecture as measured by HR-pQCT. Osteoporos Int. 2015;26:2375–80.PubMedCrossRef
14.
Anagnostis P, Bosdou JK, Kenanidis E, Potoupnis M, Tsiridis E, Goulis DG. Vitamin D supplementation and fracture risk: evidence for a U-shaped effect. Maturitas. 2020;141:63–70.PubMedCrossRef
15.
Grant WB, Karras SN, Bischoff-Ferrari HA, Annweiler C, Boucher BJ, Juzeniene A, et al. Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D–health outcome relationships reflect adverse effects? Dermatoendocrinol. 2016;8:e1187349.PubMedPubMedCentralCrossRef
16.
Taylor CL, Madans JH, Chapman NN, Woteki CE, Briefel RR, Dwyer JT, et al. Critical data at the crossroads: the National Health and Nutrition Examination Survey faces growing challenges. Am J Clin Nutr. 2023;117:847–58.PubMedPubMedCentralCrossRef
17.
Messina C, Albano D, Gitto S, Tofanelli L, Bazzocchi A, Ulivieri FM, et al. Body composition with dual energy X-ray absorptiometry: from basics to new tools. Quant Imaging Med Surg. 2020;10:1687–98.PubMedPubMedCentralCrossRef
18.
Yan Z, Xiong X, Tao J, Wang S. Association of bone mineral density with trichlorophenol: a population-based study. BMC Musculoskelet Disord. 2023;24:202.PubMedPubMedCentralCrossRef
19.
Marshall K, Teo L, Shanahan C, Legette L, Mitmesser SH. Inadequate calcium and vitamin D intake and osteoporosis risk in older americans living in poverty with food insecurities. PLoS ONE. 2020;15:e0235042.PubMedPubMedCentralCrossRef
20.
Crowe FL, Jolly K, MacArthur C, Manaseki-Holland S, Gittoes N, Hewison M, et al. Trends in the incidence of testing for vitamin D deficiency in primary care in the UK: a retrospective analysis of the Health Improvement Network (THIN), 2005–2015. BMJ Open. 2019;9:e028355.
21.
22.
Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, et al. Vitamin D-binding protein and vitamin D status of black americans and white americans. N Engl J Med. 2013;369:1991–2000.PubMedPubMedCentralCrossRef
23.
Walsh JS, Evans AL, Bowles S, Naylor KE, Jones KS, Schoenmakers I, et al. Free 25-hydroxyvitamin D is low in obesity, but there are no adverse associations with bone health. Am J Clin Nutr. 2016;103:1465–71.PubMedCrossRef
24.
Yuan C, Wang J, Zhang W, Yi H, Shu B, Li C, et al. Effects of obesity with reduced 25(OH)D levels on bone health in elderly Chinese people: a nationwide cross-sectional study. Front Immunol. 2023;14:1162175.PubMedPubMedCentralCrossRef
25.
Godos J, Giampieri F, Chisari E, Micek A, Paladino N, Forbes-Hernández TY, et al. Alcohol consumption, bone Mineral Density, and risk of osteoporotic fractures: a dose-response Meta-analysis. Int J Environ Res Public Health. 2022;19:1515.PubMedPubMedCentralCrossRef
26.
27.
Hou W, Chen S, Zhu C, Gu Y, Zhu L, Zhou Z. Associations between smoke exposure and osteoporosis or osteopenia in a US NHANES population of elderly individuals. Front Endocrinol. 2023;14:1074574.CrossRef
28.
Merianos AL, Stone TM, Jandarov RA, Mahabee-Gittens EM, Choi K. Sources of Tobacco smoke exposure and their associations with serum cotinine levels among US children and adolescents. Nicotine Tob Res off J Soc Res Nicotine Tob. 2023;25:1004–13.CrossRef
29.
Cho Y, Choi S, Kim K, Lee G, Park SM. Association between alcohol consumption and bone mineral density in elderly Korean men and women. Arch Osteoporos. 2018;13:46.PubMedCrossRef
30.
Lai B, Jiang H, Gao R, Zhou X. Association between alcohol intake and bone mineral density: results from the NHANES 2005–2020 and two-sample mendelian randomization. Arch Osteoporos. 2024;19:21.PubMedCrossRef
31.
Lin Z, Shi G, Liao X, Huang J, Yu M, Liu W, et al. Correlation between sedentary activity, physical activity and bone mineral density and fat in America: National Health and Nutrition Examination Survey, 2011–2018. Sci Rep. 2023;13:10054.PubMedPubMedCentralCrossRef
32.
Kim YA, Lee Y, Lee JH, Seo JH. Effects of physical activity on bone mineral density in older adults: Korea National Health and Nutrition Examination Survey, 2008–2011. Arch Osteoporos. 2019;14:103.
33.
Brooke-Wavell K, Skelton DA, Barker KL, Clark EM, De Biase S, Arnold S, et al. Strong, steady and straight: UK consensus statement on physical activity and exercise for osteoporosis. Br J Sports Med. 2022;56:837–46.PubMedCrossRef
34.
Pinheiro MB, Oliveira J, Bauman A, Fairhall N, Kwok W, Sherrington C. Evidence on physical activity and osteoporosis prevention for people aged 65 + years: a systematic review to inform the WHO guidelines on physical activity and sedentary behaviour. Int J Behav Nutr Phys Act. 2020;17:150.PubMedPubMedCentralCrossRef
35.
Nilsson M, Ohlsson C, Mellström D, Lorentzon M. Previous sport activity during childhood and adolescence is associated with increased cortical bone size in young adult men. J Bone Min Res off J Am Soc Bone Min Res. 2009;24:125–33.CrossRef
36.
Leite NP, Alvarez TS, Fonseca FLA, Hix S, Sarni ROS. Vitamin D deficiency in bedridden elderly people at home. Rev Assoc Médica Bras. 2023;69:61–5.CrossRef
37.
Chen L, Cai M, Li H, Wang X, Tian F, Wu Y, et al. Risk/benefit tradeoff of habitual physical activity and air pollution on chronic pulmonary obstructive disease: findings from a large prospective cohort study. BMC Med. 2022;20:70.PubMedPubMedCentralCrossRef
38.
Cao C, Friedenreich CM, Yang L. Association of Daily Sitting Time and leisure-time physical activity with Survival among US Cancer survivors. JAMA Oncol. 2022;8:395–403.PubMedPubMedCentralCrossRef
39.
Wintermeyer E, Ihle C, Ehnert S, Stöckle U, Ochs G, de Zwart P, et al. Crucial role of vitamin D in the Musculoskeletal System. Nutrients. 2016;8:319.PubMedPubMedCentralCrossRef
40.
Thompson MJW, Aitken DA, Otahal P, Cicolini J, Winzenberg TM, Jones G. The relationship between cumulative lifetime ultraviolet radiation exposure, bone mineral density, falls risk and fractures in older adults. Osteoporos Int. 2017;28:2061–8.PubMedCrossRef
41.
42.
Nakamura K, Tsugawa N, Saito T, Ishikawa M, Tsuchiya Y, Hyodo K, et al. Vitamin D status, bone mass, and bone metabolism in home-dwelling postmenopausal Japanese women: Yokogoshi Study. Bone. 2008;42:271–7.PubMedCrossRef
43.
Swanson CM, Srikanth P, Lee CG, Cummings SR, Jans I, Cauley JA, et al. Associations of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D with bone Mineral Density, Bone Mineral Density Change, and Incident Nonvertebral fracture. J Bone Min Res. 2015;30:1403–13.CrossRef
44.
Hosseinpanah F, Rambod M, Hossein-nejad A, Larijani B, Azizi F. Association between vitamin D and bone mineral density in Iranian postmenopausal women. J Bone Min Metab. 2008;26:86–92.CrossRef
45.
Grimnes G, Joakimsen R, Figenschau Y, Torjesen PA, Almås B, Jorde R. The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal women with low bone mass—a randomized controlled 1-year trial. Osteoporos Int. 2012;23:201–11.PubMedCrossRef
46.
Shin HR, Lee YJ, Ly SY. Optimal serum 25(OH)D levels and Vitamin D Intake Comparison of the effect of daily vitamin D2 and vitamin D3 supplementation on serum 25-Hydroxyvitamin D concentration. Nutrients. 2023;15:1856.PubMedPubMedCentralCrossRef
47.
Gong M, Wang K, Sun H, Wang K, Zhou Y, Cong Y, et al. Threshold of 25(OH)D and consequently adjusted parathyroid hormone reference intervals: data mining for relationship between vitamin D and parathyroid hormone. J Endocrinol Invest. 2023;46:2067–77.PubMedPubMedCentralCrossRef
48.
Chen X, Chu C, Doebis C, Xiong Y, Cao Y, Krämer BK, et al. Vitamin D status and its association with parathyroid hormone in 23,134 outpatients. J Steroid Biochem Mol Biol. 2022;220:106101.PubMedCrossRef
49.
Tsuprykov O, Chen X, Hocher C-F, Skoblo R. Lianghong Yin null, Hocher B. Why should we measure free 25(OH) vitamin D? J Steroid Biochem Mol Biol. 2018;180:87–104.PubMedCrossRef
50.
Mori T, Horibe K, Koide M, Uehara S, Yamamoto Y, Kato S, et al. The vitamin D receptor in Osteoblast-Lineage cells is essential for the Proresorptive activity of 1α,25(OH)2D3 in vivo. Endocrinology. 2020;161:bqaa178.PubMedPubMedCentralCrossRef
51.
Wierzbicka A, Oczkowicz M. Sex differences in vitamin D metabolism, serum levels and action. Br J Nutr. 2022;128:2115–30.PubMedCrossRef
52.
Dupuis ML, Pagano MT, Pierdominici M, Ortona E. The role of vitamin D in autoimmune diseases: could sex make the difference? Biol Sex Differ. 2021;12:12.PubMedPubMedCentralCrossRef
53.
54.
Kim H-N, Ponte F, Nookaew I, Ucer Ozgurel S, Marques-Carvalho A, Iyer S, et al. Estrogens decrease osteoclast number by attenuating mitochondria oxidative phosphorylation and ATP production in early osteoclast precursors. Sci Rep. 2020;10:11933.PubMedPubMedCentralCrossRef
55.
56.
Ferrari SL, Abrahamsen B, Napoli N, Akesson K, Chandran M, Eastell R, et al. Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int. 2018;29:2585–96.PubMedPubMedCentralCrossRef
57.
Seftel AD, Kathrins M, Niederberger C. Critical update of the 2010 Endocrine Society Clinical Practice Guidelines for male hypogonadism. Mayo Clin Proc. 2015;90:1104–15.
58.
Chen H-Y, Robinson JK, Jablonski NG. A cross-cultural exploration on the psychological aspects of skin color aesthetics: implications for sun-related behavior. Transl Behav Med. 2020;10:234–43.PubMed
59.
Aggarwal A, Pal R, Bhadada SK, Ram S, Garg A, Bhansali A, et al. Bone mineral density in healthy adult Indian population: the Chandigarh Urban Bone Epidemiological Study (CUBES). Arch Osteoporos. 2021;16:17.PubMedCrossRef
60.
Noel SE, Santos MP, Wright NC. Racial and ethnic disparities in Bone Health and outcomes in the United States. J Bone Min Res. 2021;36:1881–905.CrossRef
61.
Borba-Pinheiro CJ, Drigo AJ, de Alencar Carvalho MCG, da Silva NSL, Dantas EHM. Factors that contribute to Low Bone Density in Postmenopausal women in different amazonian communities. Ther Adv Musculoskelet Dis. 2011;3:81–90.PubMedPubMedCentralCrossRef
62.
Shen B, Mode NA, Noren Hooten N, Pacheco NL, Ezike N, Zonderman AB, et al. Association of Race and Poverty Status with DNA methylation-based age. JAMA Netw Open. 2023;6:e236340.PubMedPubMedCentralCrossRef
63.
Struffolino E, Van Winkle Z. Gender and race differences in pathways out of in-work poverty in the US. Soc Sci Res. 2021;99:102585.PubMedCrossRef
64.
Cashman KD, Dowling KG, Škrabáková Z, Gonzalez-Gross M, Valtueña J, De Henauw S, et al. Vitamin D deficiency in Europe: pandemic?12. Am J Clin Nutr. 2016;103:1033–44.PubMedPubMedCentralCrossRef
65.
Zhuang Y, Zhu Z, Chi P, Zhou H, Peng Z, Cheng H, et al. Efficacy of intermittent versus daily vitamin D supplementation on improving circulating 25(OH)D concentration: a bayesian network meta-analysis of randomized controlled trials. Front Nutr. 2023;10:1168115.PubMedPubMedCentralCrossRef
66.
Van Den EGhm H, Lips P, Schoonmade LJ, Lanham-New SA, Van Schoor NM. Comparison of the Effect of Daily Vitamin D2 and vitamin D3 supplementation on serum 25-Hydroxyvitamin D concentration (total 25(OH)D, 25(OH)D2, and 25(OH)D3) and importance of body Mass Index: a systematic review and Meta-analysis. Adv Nutr. 2024;15:100133.CrossRef
Metadata
Title
Does higher serum 25-hydroxyvitamin D levels will harm bone mineral density?: a cross-sectional study
Authors
Bingcheng Xu
Qiai Li
Bo Luo
Hao Liu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2024
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-024-01760-9

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