Protective Effect of High Protein and Calcium Intake on the Risk of Hip Fracture in the Framingham Offspring Cohort

The effect of protein on bone is controversial, and calcium intake may modify protein's effect on bone. We evaluated associations of energy-adjusted tertiles of protein intake (ie, total, animal, plant, animal/plant ratio) with incident hip fracture and whether total calcium intake modified these associations in the Framingham Offspring Study. A total of 1752 men and 1972 women completed a baseline food frequency questionnaire (1991-1995 or 1995-1998) and were followed for hip fracture until 2005. Hazard ratios (HRs) were estimated using Cox proportional hazards regression adjusting for confounders. Baseline mean age was 55 years (SD 9.9 years, range 26 to 86 years). Forty-four hip fractures occurred over 12 years of follow-up. Owing to significant interaction between protein (total, animal, animal/plant ratio) and calcium intake (p interaction range = .03 to .04), stratified results are presented. Among those with calcium intakes less than 800 mg/day, the highest tertile (T3) of animal protein intake had 2.8 times the risk of hip fracture [HR = 2.84, 95% confidence interval (CI) 1.20-6.74, p = .02] versus the lowest tertile (T1, p trend = .02). In the 800 mg/day or more group, T3 of animal protein had an 85% reduced hip fracture risk (HR = 0.15, 95% CI 0.02-0.92, p = .04) versus T1 (p trend = .04). Total protein intake and the animal/plant ratio were not significantly associated with hip fracture (p range = .12 to .65). Our results from middle-aged men and women show that higher animal protein intake coupled with calcium intake of 800 mg/day or more may protect against hip fracture, whereas the effect appears reversed for those with lower calcium intake. Calcium intake modifies the association of protein intake and the risk of hip fracture in this cohort and may explain the lack of concordance seen in previous studies.