VItamin D Effect on Osteoarthritis Study
Condition: Osteoarthritis, Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional
Phase: Phase 3

Summary: 
      Observational evidence suggests that vitamin D deficiency may have a role in the causes of
      osteoarthritis (OA) and there are biologically plausible mechanisms to explain this. There
      is, however, no evidence which shows that intervening with vitamin D supplementation can slow
      the progression of OA. This study is to determine if vitamin D supplementation can reduce
      knee pain and slow knee cartilage loss in OA patients comparing with a placebo. Use of MRI
      will provide sensitive measures of knee OA changes.
    

Detailed description: 
      Osteoarthritis (OA) is the most common joint disorder in the world. In 2004, OA was estimated
      to affect over 1.6 million Australians, with total costs of $1.4 billion. OA is the most
      frequent reason for joint replacement, at a cost of about $1 billion each year. Conventional
      treatment is palliative and costly, and currently there are no effective medical remedies for
      OA. These facts have led to 2000-2010 being labelled the Bone and Joint decade, and
      musculoskeletal disorders being recognised as a National Health Priority. The primary task
      for OA management should be to identify modifiable risk factors.

      Vitamin D deficiency is very common in older people and has been linked with osteoporosis and
      falls in both older women and men. Emerging data suggests that it also plays an important
      role in the pathogenesis of knee OA. Firstly, vitamin D may have direct effects on
      chondrocytes in osteoarthritic cartilage; secondly, chronic vitamin D inadequacy in adults
      has adverse effects on calcium metabolism, osteoblast activity, matrix ossification and bone
      density, and thus could impair the ability of bone to respond optimally to pathophysiological
      processes in OA; and thirdly, low vitamin D levels are associated with loss of muscle
      strength and muscle mass in older men and women, which may be associated with an increased
      risk of knee OA. Some observational studies have shown that vitamin D insufficiency is
      associated with the progression and development of radiographic knee or hip OA. Recently we
      have demonstrated that baseline serum levels of 25-hydroxy-vitamin D(25-(OH)D) predicts
      change in cartilage volume in older adults over 2 years, and increases in vitamin D levels
      are associated with a further protective association. This suggests that vitamin D
      supplementation may enhance cartilage and bone health, and thus prevent disease progression
      in patients with knee OA.

      The aim of this study is to compare the effects of vitamin D supplementation versus placebo
      on knee pain and knee structural changes in patients with symptomatic knee osteoarthritis
      over a 2- year period.

      The proposed study design is a randomised, placebo-controlled, double-blind clinical trial.
      We will recruit 400 subjects (50-79 years old, having relatively good health and serum
      vitamin D level of <60 and >12.5 nmol/L) with symptomatic knee OA for at least 6 months using
      a combined strategy in Southern Tasmania and Melbourne. Participants in the intervention arm
      (n=200) will receive 50,000 IU (1.25 mg) cholecalciferol tablets given once monthly, whilst
      those in the control arm (n=200) will receive an identical inert placebo. All participants
      will be provided recommended standard of care. Knee structural changes including knee
      cartilage volume, cartilage defects, tibial bone area, bone marrow lesions, and meniscal
      pathology (assessed by MRI), and knee pain at baseline and 2 years later will be determined
      as outcome measures. Other explanatory factors, such as serum vitamin D levels, height,
      weight, physical activity, and smoking will also be determined through study period.

      Significance:

      Observational evidence suggests that vitamin D deficiency may have a role in the progression
      of OA and there are biologically plausible mechanisms to explain this. However, randomized
      controlled trials using a sensitive method are required to determine whether intervening with
      vitamin D supplementation can in fact slow the progression of this disease. In this study,
      the randomized, placebo-controlled, double-blind design, and the use of MRI to provide
      sensitive and precise measures of knee structural change will ensure a rigorous evaluation of
      the impact of vitamin D supplementation on knee OA. It will be the first long term clinical
      trial to determine comprehensively the effects on knee structural changes (cartilage, bone)
      utilizing the pioneering MRI techniques and limb muscle strength assessment. This study
      builds upon previous clinical and epidemiological studies that supports the objectives of the
      Bone and Joint Decade organization and addresses a National Health Priority Area.
    

Intervention name(s): Vitamin D; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 50,000 IU (1.25 mg) cholecalciferol capsules once monthly for 2 years; Inert placebo capsules once monthly for 2 years.
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Vitamin D supplementation; Osteoarthritis; Knee; Randomised clinical trial (RCT); Cartilage; MRI