Low serum levels of vitamins D and A predict hip fracture in the elderly. A multicenter case-cohort study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS)

Background: Norwegians have among the highest hip fracture rates worldwide. Vitamin D status is generally good and vitamin A intake is relatively high in Norway. Increased fracture risk at high intakes and serum levels of retinol have been observed in earlier epidemiologic studies. Objective: To study whether serum concentration of vitamins D and A in elderly Norwegians are related to risk of hip fracture, and whether high serum vitamin A (retinol) may counteract a possible protective effect of vitamin D. Methods: N=21,774 men and women aged 65-79 attended four community-based health studies during 1994- 2001. Subsequent hip fractures were retrieved from hospitals’ patient administrative systems, with maximum follow-up 10.7 years. 25(OH)D was determined by HPLC-APCI-MS and retinol by HPLC-UV in baseline serum samples in cases and weighted random samples of men and women. Adjusted Cox proportional hazards regression modified for the case-cohort design was performed using R. Results: During median follow-up 8.2 years, 340 men (3.4%) and 892 women (7.5%) suffered a hip fracture. We found an inverse association between 25(OH)D and hip fracture; HR 1.35 (95% CI 1.07-1.70) for 75 nmol/l. Compared with middle retinol levels (2-3 μmol/l), low levels (