TY - JOUR
T1 - Association of Genetic Variants Related to Serum Calcium Levels with Reduced Bone Mineral Density
AU - Li, Gloria Hoi Yee
AU - Robinson-Cohen, Cassianne
AU - Sahni, Shivani
AU - Au, Philip Chun Ming
AU - Tan, Kathryn Choon Beng
AU - Kung, Annie Wai Chee
AU - Cheung, Ching Lung
N1 - Publisher Copyright:
© 2019 Endocrine Society 2019.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Context: The role of serum calcium in bone metabolism is unknown, even though calcium/Vitamin D supplementations have been widely used and are expected to improve bone health. We aim to determine the independent role of serum calcium in bone mineral density (BMD). Design and setting: Two epidemiological analyses with 5478 and 5556 participants from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2006 and the Hong Kong Osteoporosis Study (HKOS) to evaluate the cross-sectional association of serum calcium with BMD. Two-sample Mendelian randomization (MR) studies using genetic variations as instrumental variables to infer causality. Summary statistics of genome-wide association study of serum calcium (N = 39 400) and lifelong whole-body BMD (N = 66 628) were used. Main outcome measure: BMD measured by dual-energy X-ray absorptiometry Results: In NHANES 2003-6 and HKOS, each standard deviation (SD) increase in serum calcium was significantly associated with 0.036-0.092 SD decrease in BMD at various sites (all P <. 05). In multivariable inverse-variance weighted MR analysis, genetic predisposition to higher serum calcium level was inversely associated with whole-body BMD after adjustment for serum parathyroid hormone, Vitamin D, and phosphate (-0.431 SD per SD increase in serum calcium; 95% CI: -0.773 to -0.089, P =. 014). Similar estimates were obtained in sensitivity analyses. Conclusions: Our study reveals that genetic predisposition to higher serum calcium level per se may have a negative impact on bone metabolism. Whether increased serum calcium caused by calcium/Vitamin D supplementations would have the same negative effect on bone remains unknown, which warrants further investigation. In addition to other adverse clinical outcomes, careful use of high-dose supplementations is required.
AB - Context: The role of serum calcium in bone metabolism is unknown, even though calcium/Vitamin D supplementations have been widely used and are expected to improve bone health. We aim to determine the independent role of serum calcium in bone mineral density (BMD). Design and setting: Two epidemiological analyses with 5478 and 5556 participants from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2006 and the Hong Kong Osteoporosis Study (HKOS) to evaluate the cross-sectional association of serum calcium with BMD. Two-sample Mendelian randomization (MR) studies using genetic variations as instrumental variables to infer causality. Summary statistics of genome-wide association study of serum calcium (N = 39 400) and lifelong whole-body BMD (N = 66 628) were used. Main outcome measure: BMD measured by dual-energy X-ray absorptiometry Results: In NHANES 2003-6 and HKOS, each standard deviation (SD) increase in serum calcium was significantly associated with 0.036-0.092 SD decrease in BMD at various sites (all P <. 05). In multivariable inverse-variance weighted MR analysis, genetic predisposition to higher serum calcium level was inversely associated with whole-body BMD after adjustment for serum parathyroid hormone, Vitamin D, and phosphate (-0.431 SD per SD increase in serum calcium; 95% CI: -0.773 to -0.089, P =. 014). Similar estimates were obtained in sensitivity analyses. Conclusions: Our study reveals that genetic predisposition to higher serum calcium level per se may have a negative impact on bone metabolism. Whether increased serum calcium caused by calcium/Vitamin D supplementations would have the same negative effect on bone remains unknown, which warrants further investigation. In addition to other adverse clinical outcomes, careful use of high-dose supplementations is required.
UR - http://www.scopus.com/inward/record.url?scp=85078685591&partnerID=8YFLogxK
U2 - 10.1210/clinem/dgz088
DO - 10.1210/clinem/dgz088
M3 - Journal article
C2 - 31650181
AN - SCOPUS:85078685591
SN - 0021-972X
VL - 105
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
M1 - dgz088
ER -