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Abstract
Background Vitamin D may have a protective role for both symptoms and structures in osteoarthritis (OA).
Objectives The aim of this study was to evaluate the effects of vitamin D supplementation versus placebo on knee pain and structural changes in knee OA patients with low vitamin D.
Methods A multicentre, parallel randomized, placebo-controlled and double-blind clinical trial was performed in patients with symptomatic knee OA and a low 25-hydroxy vitamin D level (12.5 nmol/L to 60 nmol/L, mean 43.8±12.2 nmol/L at baseline) in Melbourne and Hobart, Australia. A central randomization centre used computer-generated random numbers to allocate treatments. 413 patients (mean age 63.2±7.0 years, 208 females) were randomized to either a single 50,000 IU monthly vitamin D3 capsule (n=209) or identical inert placebo (n=204) and followed for 2 years. The primary outcome measures were change in knee tibial cartilage volume by magnetic resonance imaging (MRI) and change in total knee pain assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary analyses included ≥20% and ≥50% improvement in total WOMAC knee pain, change in knee pain assessed by visual analogue scale (VAS), change in cartilage defects and change in bone marrow lesions (BMLs). Analyses were performed on an intention-to-treat basis using mixed models and multiple imputation by chained equations for missing data.
Results After 24 months, serum 25(OH)D level increased by a mean of 40.6 nmol/L in the vitamin D group compared to 6.7 nmol/L in the placebo group. There was no statistically significant difference in changes of total tibial cartilage volume (-3.44% p.a. versus -4.23% p.a., p=0.132) or total WOMAC pain score (-49.9 versus -35.1, p=0.102). In secondary analyses, knee pain decreased more in the vitamin D group than the placebo group for VAS pain over 2 years (mean difference -5.4, 95% CI -10.7 to -0.1, p=0.048). The vitamin D group was associated with a tendency to greater response for ≥20% improvement (64% versus 57%, p=0.164) and greater response for ≥50% improvement (50% versus 39%, p=0.036) in total WOMAC pain from baseline to month 24. There were no significant differences between two groups in changes of tibiofemoral cartilage defects (0.29 versus 0.47, p=0.159) and tibiofemoral BMLs (-0.59 versus -0.21, p=0.087); however, the vitamin D group had less increase in tibiofemoral BMLs (17% vs 27%, p=0.03). Adverse events were minor but were more common in the vitamin D group (42 versus 26). Severe adverse events were infrequent and similar (14 versus 12).
Conclusions In patients with symptomatic knee OA with vitamin D insufficiency, vitamin D supplementation over 2 years markedly increased serum levels but did not meet either primary endpoint. Secondary analyses suggest there may be modest benefits on knee pain and BMLs.
Acknowledgements We especially thank all participants who made this study possible. We acknowledge Jodi Barling, Kay Nguo, Judy Hankin and Alice Noon for coordinating this study, and Robert Warren for reading MRI images.
Disclosure of Interest None declared