Objective: Osteoprotegerin (OPG) is an important regulator of bone turnover through its effects on osteoclastogenesis, yet findings from previous studies of circulating OPG and commonly measured bone indices in humans have been conflicting. We conducted a cross-sectional study to evaluate the association between plasma OPG and femoral neck bone density (FN BMD) and geometry in a large cohort of women and men.

Design: Participants included 1379 post-menopausal women and 1165 men, age 50–89 years (mean, 64 years), in the Framingham Offspring Study. Dual x-ray absorptiometry was used to evaluate FN BMD and geometry (bone width, section modulus, and cross-sectional area at the narrow neck region). Plasma OPG concentrations were measured by ELISA. Sex-specific analysis of covariance was used to calculate means and assess linear trend in BMD and geometry values across OPG quartiles, adjusted for confounders.

Results: OPG concentrations were greater in women than men, increased with age, and were greater in smokers and those with diabetes and heart disease. Multivariable-adjusted mean FN BMD in women increased from the lowest to the highest OPG quartile (trend, p<0.01). However, no linear trend between FN BMD and OPG was observed in men (trend, p=0.34). Section modulus and bone width increased with OPG in men (trend, p<0.01), whereas no association between hip geometry indices and OPG was observed in women.

Conclusion: Higher OPG concentration may indicate greater skeletal strength in women and men, possibly through reducing bone loss in women and through increasing periosteal apposition in men.