The results demonstrate the presence of sex differences in OA prevalence and incidence, with females generally at a higher risk. Females also tend to have more severe knee OA, particularly after menopausal age. The site differences indicate the need for further studies to explore mechanisms underlying OA.

Our study demonstrated that osteoporosis-related fractures cause a substantial economic burden which will markedly increase over the coming decades. Consequently, healthcare resource planning must consider these increasing costs, and cost-effective screening and intervention policies must urgently be identified in an attempt to minimize the impact of fractures on the health of the burgeoning population as well as the healthcare budget.

ACTRN 12609000399291.

25OHD may be important for the maintenance of muscle function, and higher skeletal muscle mass and function as well as general PA levels may also be beneficial for 25OHD status, in community-dwelling older adults.

IMPORTANCE Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory.OBJECTIVE To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels. DESIGN, SETTING, AND PARTICIPANTSA multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013. INTERVENTIONS Participants were randomly assigned to receive monthly treatment with oral vitamin D 3 (50 000 IU; n = 209) or an identical placebo (n = 204) for 2 years. MAIN OUTCOMES AND MEASURES Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI).RESULTS Of 413 enrolled participants (mean age, 63.2 years; 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (Ն1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). End Point Change, Mean Difference (95% CI) P Value Vitamin D Placebo Tibial cartilage volume, %/y −3.4% −4.2% 0.8% (−0.2% to 1.8%) .13 WOMAC pain −49.9 −35.1 −14.8 (−32.5 to 2.9) .10 Tibiofemoral cartilage defects 0.3 0.5 −0.2 (−0.4 to 0.1) .21 Tibiofemoral bone marrow lesions −0.1 0.3 −0.5 (−0.9 to 0.0) .06CONCLUSIONS AND RELEVANCE Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis.