AbstractObjectiveTo examine (i) the association of percentage of total energy intake from protein (protein intake %) with bone mineral density (BMD, g/cm²) and bone loss at the femoral neck, trochanter and lumbar spine (L2–L4) and (ii) Ca as an effect modifier.SettingThe Framingham Offspring Study.SubjectsMen (n 1280) and women (n 1639) completed an FFQ in 1992–1995 or 1995–1998 and underwent baseline BMD measurement by dual-energy X-ray absorptiometry in 1996–2000. Men (n 495) and women (n 680) had follow-up BMD measured in 2002–2005.DesignCohort study using multivariable regression to examine the association of protein intake % with each BMD, adjusting for covariates. Statistical interaction between protein intake % and Ca (total, dietary, supplemental) intake was examined.ResultsThe mean age at baseline was 61 (sd 9) years. In the cross-sectional analyses, protein intake % was positively associated with all BMD sites (P range: 0·02–0·04) in women but not in men. Significant interactions were observed with total Ca intake (<800 mg/d v. ≥800 mg/d) in women at all bone sites (P range: 0·002–0·02). Upon stratification, protein intake % was positively associated with all BMD sites (P range: 0·04–0·10) in women with low Ca intakes but not in those with high Ca intakes. In the longitudinal analyses, in men, higher protein intake % was associated with more bone loss at the trochanter (P = 0·01) while no associations were seen in women, regardless of Ca intake.ConclusionsThis suggests that greater protein intake benefits women especially those with lower Ca intakes. However, protein effects are not significant for short-term changes in bone density. Contrastingly, in men, higher protein intakes lead to greater bone loss at the trochanter. Longer follow-up is required to examine the impact of protein on bone loss.