The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor kappaB legend with bone mineral density in older adults: the Rancho Bernardo study

OBJECTIVE: The role of osteoprotegerin (OPG) and its receptor activator of nuclear factor kappaB legend (RANKL) in the regulation of bone in humans remain unclear. We examined the sex-specific associations of serum OPG, RANKL, and their ratio with bone mineral density (BMD) in older adults. DESIGN: Participants were 681 community-dwelling adults, ages 45-90 years, who had serum OPG and RANKL measured and bone density scans in 1988-1991, with follow-up scans 5 and/or 10 years later. METHODS: Analyses were sex-specific; women using and not using estrogen were evaluated separately. Cross-sectional analyses used multivariable regression models; longitudinal analyses used repeated measures mixed effects models. RESULTS: In cross-sectional analyses, age- and weight-adjusted serum OPG levels were significantly positively associated with BMD at the lumbar spine in men, and at the femoral neck, total hip, and lumbar spine in women using estrogen, but not in non-users of estrogen. RANKL concentrations were significantly and inversely associated with BMD in men only, and at the total hip. Neither OPG nor RANKL was significantly associated with bone loss. Results for the RANKL/OPG ratio were the same as those for RANKL alone. CONCLUSIONS: These results suggest a modulatory effect of both endogenous and exogenous sex hormones on the biologic interaction of OPG, RANKL, and bone.