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Increased Plasma Osteoprotegerin Concentrations Are Associated with Indices of Bone Strength of the Hip

Institute for Aging Research (E.J.S., K.E.B., D.K., D.P.K.), Hebrew SeniorLife, Boston, Massachusetts 02131; Department of Medicine (E.J.S., D.K., D.P.K.), Harvard Medical School, and Cardiology Division (S.K.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Department of Biostatistics (S.D.), Boston University School of Public Health, Boston, Massachusetts 02215; Department of Radiology (T.J.B.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21224; and Program in Medical and Population Genetics (S.K.), Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02138

Address all correspondence and requests for reprints to: Elizabeth J. Samelson, Ph.D., Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, Massachusetts 02131. E-mail: samelson{at}hrca.harvard.edu.

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 (FN) bone density (BMD) and geometry in a large cohort of women and men.

Design: Participants included 1379 postmenopausal women and 1165 men, aged 50–89 yr (mean, 64 yr), 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 increasing periosteal apposition in men.