N K Arden1, S Cro2, S Sheard3, C J Doré4, A Bara5, S A Tebbs6, D J Hunter7, S James8, C Cooper9, T W O'Neill10, A Macgregor11, F Birrell12, R Keen13. 1. Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford OX3 7LD, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK; Arthritis Research UK Centre of Excellence for Sport, Injury, and Osteoarthritis, UK. Electronic address: Nigel.Arden@ndorms.ox.ac.uk. 2. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London WC2B 6NH, UK. Electronic address: s.cro@ucl.ac.uk. 3. Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford OX3 7LD, UK. Electronic address: sally.sheard@isis.ox.ac.uk. 4. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London WC2B 6NH, UK. Electronic address: caroline.dore@ucl.ac.uk. 5. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London WC2B 6NH, UK. Electronic address: a.bara@ucl.ac.uk. 6. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London WC2B 6NH, UK. Electronic address: susan.tebbs@ucl.ac.uk. 7. Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford OX3 7LD, UK; Chromatic Innovation Limited, Leamington Spa, UK. Electronic address: d.j.hunter@gmail.com. 8. St Richard's Hospital, Chichester, UK. Electronic address: samjames1@nhs.net. 9. Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford OX3 7LD, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. Electronic address: cc@mrc.soton.ac.uk. 10. Arthritis Research UK Centre for Epidemiology, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK; NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: terence.o'neill@manchester.ac.uk. 11. Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address: A.Macgregor@uea.ac.uk. 12. Institute of Cellular Medicine, Newcastle University, UK. Electronic address: fraser.birrell@newcastle.ac.uk. 13. Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK; Institute of Orthopaedics and Musculoskeletal Science, University College London, London, UK. Electronic address: Richard.Keen@rnoh.nhs.uk.
Abstract
OBJECTIVE: Epidemiological data suggest low serum 25-hydroxyvitamin D3 (25-OH-D3) levels are associated with radiological progression of knee osteoarthritis (OA). This study aimed to assess whether vitamin D supplementation can slow the rate of progression. METHOD: A 3-year, double-blind, randomised, placebo-controlled trial of 474 patients aged over 50 with radiographically evident knee OA comparing 800 IU cholecalciferol daily with placebo. Primary outcome was difference in rate of medial joint space narrowing (JSN). Secondary outcomes included lateral JSN, Kellgren & Lawrence grade, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, stiffness and the Get up and Go test. RESULTS: Vitamin D supplementation increased 25-OH-D3 from an average of 20.7 (standard deviation (SD) 8.9) μg/L to 30.4 (SD 7.7) μg/L, compared to 20.7 (SD 8.1) μg/L and 20.3 (SD 8.1) μg/L in the placebo group. There was no significant difference in the rate of JSN over 3 years in the medial compartment of the index knee between the treatment group (average -0.01 mm/year) and placebo group (-0.08 mm/year), average difference 0.08 mm/year (95% confidence interval (CI) [-0.14-0.29], P = 0.49). No significant interaction was found between baseline vitamin D levels and treatment effect. There were no significant differences for any of the secondary outcome measures. CONCLUSION: Vitamin D supplementation did not slow the rate of JSN or lead to reduced pain, stiffness or functional loss over a 3-year period. On the basis of these findings we consider that vitamin D supplementation has no role in the management of knee OA.
OBJECTIVE: Epidemiological data suggest low serum 25-hydroxyvitamin D3 (25-OH-D3) levels are associated with radiological progression of knee osteoarthritis (OA). This study aimed to assess whether vitamin D supplementation can slow the rate of progression. METHOD: A 3-year, double-blind, randomised, placebo-controlled trial of 474 patients aged over 50 with radiographically evident knee OA comparing 800 IU cholecalciferol daily with placebo. Primary outcome was difference in rate of medial joint space narrowing (JSN). Secondary outcomes included lateral JSN, Kellgren & Lawrence grade, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, stiffness and the Get up and Go test. RESULTS: Vitamin D supplementation increased 25-OH-D3 from an average of 20.7 (standard deviation (SD) 8.9) μg/L to 30.4 (SD 7.7) μg/L, compared to 20.7 (SD 8.1) μg/L and 20.3 (SD 8.1) μg/L in the placebo group. There was no significant difference in the rate of JSN over 3 years in the medial compartment of the index knee between the treatment group (average -0.01 mm/year) and placebo group (-0.08 mm/year), average difference 0.08 mm/year (95% confidence interval (CI) [-0.14-0.29], P = 0.49). No significant interaction was found between baseline vitamin D levels and treatment effect. There were no significant differences for any of the secondary outcome measures. CONCLUSION: Vitamin D supplementation did not slow the rate of JSN or lead to reduced pain, stiffness or functional loss over a 3-year period. On the basis of these findings we consider that vitamin D supplementation has no role in the management of knee OA.
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