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 (total, animal, plant, animal:plant ratio) with incident hip fracture and if total calcium intake modified these associations in the Framingham Offspring Study. 1,752 men and 1,972 women completed a baseline food frequency questionnaire (1991‐95 or 1995‐98) and were followed for hip fracture until 2005. Hazard ratios (HR) were estimated using Cox‐proportional hazards regression adjusting for confounders. Baseline mean age was 55 years (SD: 9.9, range: 26‐86 years). 44 hip fractures occurred over 12‐years of follow‐up. Due to significant interaction between protein (total, animal, animal:plant ratio) and calcium intake (P interaction range=0.03‐0.04), stratified results are presented. Among those with calcium intakes <800mg/d, the highest tertile (T3) of animal protein intake had 2.8 times risk of hip fracture (HR: 2.84, 95%CI: 1.20‐6.74, P=0.02) vs. the lowest tertile (T1, P‐trend=0.02). In the ≥800mg/d group, T3 of animal protein had an 85% reduced hip fracture risk (HR: 0.15, 95%CI: 0.02‐0.92, P=0.04) vs. T1 (P‐trend=0.04). Total protein intake and the animal:plant ratio were not significantly associated with hip fracture (P‐range=0.12‐0.65). Our results from middle‐aged men and women show that higher animal protein intake coupled with calcium intake ≥800mg/d may protect against hip fracture, while 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. © 2010 American Society for Bone and Mineral Research