TY - JOUR
T1 - Protective Role of DHEAS in Age-related Changes in Bone Mass and Fracture Risk
AU - Yokomoto-Umakoshi, Maki
AU - Umakoshi, Hironobu
AU - Iwahashi, Norifusa
AU - Matsuda, Yayoi
AU - Kaneko, Hiroki
AU - Ogata, Masatoshi
AU - Fukumoto, Tazuru
AU - Terada, Eriko
AU - Nakano, Yui
AU - Sakamoto, Ryuichi
AU - Ogawa, Yoshihiro
N1 - Funding Information:
This work was supported in part by the JSPS KAKENHI (JP20K16525 and 21J40043 to M. Y-U., JP20K17514 to R.S., and JP20K17493 to H.U.), grant Daiwa Securities Health Foundation (to M. Y-U.), grant The JSBMR Rising Stars Grant (to M. Y-U.), grant JAPAN Osteoporosis Foundation (to M. Y-U.), grant Takeda Science Foundation (to H.U.), and grant Kaibara Morikazu Medical Science Promotion Foundation (to H.U.). M.Y-U. is grateful for JSPS Research Fellowship RPD (No. 202140043).
Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Purpose: Dehydroepiandrosterone sulfate (DHEAS) from the adrenal cortex substantially decreases with age, which may accelerate osteoporosis. However, the association of DHEAS with bone mineral density (BMD) and fracture is inconclusive. We conducted a Mendelian randomization (MR) analysis to investigate the role of DHEAS in age-related changes in BMD and fracture risk. Methods: Single nucleotide polymorphisms (SNPs) associated with serum DHEAS concentrations were used as instrumental variables (4 SNPs for main analysis; 4 SNPs for men and 5 SNPs for women in sex-related analysis). Summary statistics were obtained from relevant genome-wide association studies. Results: A log-transformed unit (μmol/L) increase in serum DHEAS concentrations was associated with an SD increase in estimated BMD at the heel (estimate, 0.120; 95% CI, 0.081-0.158; P = 9 × 10-10), and decreased fracture (odds ratio, 0.989; 95% CI, 0.981-0.996; P = 0.005), consistent with dual-energy X-ray absorptiometry-derived BMD at the femoral neck and lumbar spine. Their associations remained even after adjusting for height, body mass index, testosterone, estradiol, sex hormone-binding globulin, and insulin-like growth factor 1. The association of DHEAS with fracture remained after adjusting for falls, grip strength, and physical activity but was attenuated after adjusting for BMD. The MR-Bayesian model averaging analysis showed BMD was the top mediating factor for association of DHEAS with fracture. The association between DHEAS and BMD was observed in men but not in women. Conclusion: DHEAS was associated with increased BMD and decreased fracture. DHEAS may play a protective role in decreasing fracture risk, mainly by increasing bone mass.
AB - Purpose: Dehydroepiandrosterone sulfate (DHEAS) from the adrenal cortex substantially decreases with age, which may accelerate osteoporosis. However, the association of DHEAS with bone mineral density (BMD) and fracture is inconclusive. We conducted a Mendelian randomization (MR) analysis to investigate the role of DHEAS in age-related changes in BMD and fracture risk. Methods: Single nucleotide polymorphisms (SNPs) associated with serum DHEAS concentrations were used as instrumental variables (4 SNPs for main analysis; 4 SNPs for men and 5 SNPs for women in sex-related analysis). Summary statistics were obtained from relevant genome-wide association studies. Results: A log-transformed unit (μmol/L) increase in serum DHEAS concentrations was associated with an SD increase in estimated BMD at the heel (estimate, 0.120; 95% CI, 0.081-0.158; P = 9 × 10-10), and decreased fracture (odds ratio, 0.989; 95% CI, 0.981-0.996; P = 0.005), consistent with dual-energy X-ray absorptiometry-derived BMD at the femoral neck and lumbar spine. Their associations remained even after adjusting for height, body mass index, testosterone, estradiol, sex hormone-binding globulin, and insulin-like growth factor 1. The association of DHEAS with fracture remained after adjusting for falls, grip strength, and physical activity but was attenuated after adjusting for BMD. The MR-Bayesian model averaging analysis showed BMD was the top mediating factor for association of DHEAS with fracture. The association between DHEAS and BMD was observed in men but not in women. Conclusion: DHEAS was associated with increased BMD and decreased fracture. DHEAS may play a protective role in decreasing fracture risk, mainly by increasing bone mass.
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U2 - 10.1210/clinem/dgab459
DO - 10.1210/clinem/dgab459
M3 - Article
C2 - 34157116
AN - SCOPUS:85119480962
SN - 0021-972X
VL - 106
SP - E4580-E4592
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -
