Vitamin D In Older Women - Fractures, Frailty and Mortality

Vitamin D (25OHD) is essential for maintaining calcium homeostasis and inadequate levels have been associated with negative musculoskeletal as well as extraskeletal effects. Individuals at especially high risk of developing hypovitaminosis D are the elderly. The aim of this thesis was to investigate the association between 25OHD insufficiency (25OHD <50 nmol/L) and fractures, frailty and mortality. Additionally, we described the normal distribution of parathyroid hormone (PTH) in older women in relation to 25OHD and kidney function (eGFR) and investigated whether PTH was an independent predictor of frailty and mortality. Data was obtained from women participating in the Malmö Osteoporotic Risk Assessment Cohort (OPRA). This cohort consists of 1044 community-dwelling women, aged 75 years, who were followed prospectively for more than 15 years with reevaluations at ages 80 and 85 years. Blood biochemistry including 25OHD, PTH and eGFR was available at all time points. Information on fractures and mortality was continuously registered and a frailty index was constructed. Women with 25OHD levels <50 nmol/L, sustained between ages 75 and 80 years, had a higher 10-year risk of suffering a major osteoporotic fracture compared to women who maintained 25OHD levels ≥50 nmol/L (HR=1.8 [1.2-2.8], p=0.008). Mortality risk within 10 years of follow-up was significantly higher in 25OHD insufficient women compared to those with 25OHD >75 nmol/L (75y: HR=1.4 [1.0-1.9], p=0.04 and 80y: HR=1.8, 95%CI=1.3-2.4, p<0.001). This increased risk remained after adjustment for smoking, diagnosis of osteoporosis and other comorbidities (at age 80).Between ages 75 and 80 years, PTH increased in 60% of all women (n=390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the normal reference range (NRR), accompanied by lower 25OHD (74 vs 83 nmol/L, p=0.001). Only when increases were >50% was PTH elevated beyond the NRR. Here, a pronounced decline in kidney eGFR (56 vs 61 mL/min/1.73 m2, p=0.002) was found, despite no further decline in 25OHD. At age 85 years, half of the women had stable or decreased PTH levels (51%; n=169). PTH levels above NRR were not independently associated with mortality. At both ages 75 and 80, women with 25OHD <50 nmol/L were more frail compared to 25OHD sufficient women (0.23 vs 0.18; p<0.001 and 0.32 vs 0.25; p=0.001). Accelerated progression of frailty was not associated with lower 25OHD. Variables within the frailty-index that were associated with 25OHD, were those related to muscle strength and function. PTH was not independently associated with frailty In conclusion, 25OHD levels <50 nmol/L were associated with significant impairments of the musculoskeletal system (fractures, frailty) and predicted all-cause mortality in independently living older women. Parathyroid hormone was inversely correlated to 25OHD and eGFR but was not an independent predictor of frailty or mortality.