Zhu, Kun; Lewis, Joshua R.; Sim, Marc; Prince, Richard L.
The vitamin D debate relates in part to ideal public health population levels of circulating 25-hydroxyvitamin D (25OHD) to maintain bone structure and reduce fracture. In a secondary analysis of 1,348 women aged 70-85 years at baseline (1998) from the Perth Longitudinal Study of Aging in Women (PLSAW, a five-year calcium supplementation trial followed by two five-year extensions), we examined the dose-response relations of baseline plasma 25OHD with hip DXA BMD at year 1, lumbar spine BMD and trabecular bone score (TBS) at year 5, and fracture-related hospitalizations over 14.5 years obtained by health record linkage. Mean baseline plasma 25OHD was 66.9±28.2 nmol/L and 28.5%, 36.4% and 35.1% of women had levels <50, 50-74.9 and ≥75 nmol/L, respectively. Generalized additive models showed that total hip and femoral neck BMD and TBS, but not spine BMD, were higher with increasing plasma 25OHD up to 100 nmol/L. Compared with those with 25OHD <50 nmol/L, women with 25OHD ≥75 nmol/L had significantly higher total hip and femoral neck BMD at year 1 (3.3-3.9%) and TBS at year 5 (2.0%), all P<0.05. During the follow-up 27.6% of women experienced any fracture-related, and 10.6% hip fracture-related hospitalization. Penalized spline regression models showed a decrease in risk with increased 25OHD levels up to 65 and 75 nmol/L for hip fracture and any fracture-related hospitalization, respectively. Cox regression grouped analyses showed that, compared with women with 25OHD <50 nmol/L, those with 25OHD levels 50-74.9 and ≥75 nmol/L had significantly lower risk for hip fracture (hazard ratio [95% CI]: 0.60 [0.40-0.91] and 0.61 [0.40-0.92], respectively), and any fracture-related hospitalization (hazard ratio [95% CI]: 0.77 [0.59-0.99] and 0.70 [0.54-0.91], respectively). In older Caucasian women 25OHD levels >50 nmol/L are a minimum public health target and 25OHD levels beyond 75 nmol/L may not have additional benefit to reduce fracture risk. This article is protected by copyright. All rights reserved.