Association of Genetic Variants Related to Serum Calcium Levels with Reduced Bone Mineral Density

Abstract

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