Does Vitamin D Improve Osteoarthritis of the Knee: A Randomized Controlled Pilot Trial
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Animal, epidemiologic, and human clinical studies suggest a putative role for vitamin D in osteoarthritis (OA). Inadequate sunlight exposure and lower serum levels of 25(OH)D appear in some reports to be associated with an increased risk for progression of knee OA.
We asked whether treatment with vitamin D would (1) reduce knee pain (WOMAC and VAS), (2) improve function (WOMAC), and (3) change levels of relevant biochemical markers in patients with knee OA with vitamin D insufficiency.
This randomized controlled pilot trial prospectively enrolled 107 patients with knee OA with vitamin D insufficiency (25(OH)D ≤ 50 nmol/L) to receive oral vitamin D or placebo. The primary outcome measures were pain and function, and the secondary were biochemical markers. At baseline, the two groups were comparable. The patients were followed for 1 year.
At 12 months, knee pain had decreased in the vitamin D group by mean −0.26 (95% CI, −2.82 to −1.43) on VAS and −0.55 (95% CI, −0.07 to 1.02) on the WOMAC, whereas in the placebo group, it increased by mean 0.13 (95% CI, −0.03 to 0.29) on the VAS and 1.16 (95% CI, 0.82 to 1.49) on the WOMAC (effect size = 0.37 and 0.78). Likewise knee function improved in the vitamin D group by mean −1.36 (95% CI, −1.87 to −0.85) over the placebo group which had a mean 0.69 (95% CI, −0.03 to 1.41; effect size = 0.06). There were significant biochemical changes in serum total calcium, 25(OH)D and alkaline phosphatase.
The results above suggest there is a small but statistically significant clinical benefit to vitamin D treatment in patients with knee OA, although we recommend a long-term study to determine whether these changes are clinically important and whether they will be sustained with time. Further studies with long-term radiologic evaluations are needed.
Level of Evidence
Level I, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.
- Akobeng AK. Understanding measures of treatment effect in clinical trials. Arch Dis Child. 2005;90:54–56. CrossRef
- Bellamy N. WOMAC Osteoarthritis Index: A Users Guide. London, Ontario, Canada: London Health Service Centre, McMaster University; 1996.
- Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833–1840.
- Bergink AP, Uitterlinden AG, Van Leeuwen JP, Buurman CJ, Hofman A, Verhaar JA, Pols HA. Vitamin D status, bone mineral density, and the development of radiographic osteoarthritis of the knee: The Rotterdam Study. J Clin Rheumatol. 2009;15:230–237. CrossRef
- Bijur PE, Silver W, Gallagher EJ. Reliability of the visual analog scale for measurement of acute pain. Acad Emerg Med. 2001;8:1153–1157. CrossRef
- Brandt KD, Dieppe P, Radin E. Etiopathogenesis of osteoarthritis. Med Clin North Am. 2009;93:1–24, xv.
- Chopra A, Patil J, Bilampelly V, Relwane J, Tandle HS; WHO-ILAR COPCORD Study. WHO International League of Associations from Rheumatology Community Oriented Program from Control of Rheumatic Diseases. Prevalence of rheumatic diseases in a rural population in western India: a WHO-ILAR COPCORD Study. J Assoc Physicians India. 2001;49:240–246.
- Demircioğlu DT, Paker N, Buğdayci DS. Relationship between the bone formation rate and functional status in symptomatic knee osteoarthritis. Turk J Rheumatol. 2011;26:316–320. Available at: http://romatizma.dergisi.org/text.php3?id=434. Accessed July 16, 2013.
- Ding C, Cicuttini F, Parameswaran V, Burgess J, Quinn S, Jones G. Serum levels of vitamin D, sunlight exposure, and knee cartilage loss in older adults. Arthritis Rheum. 2009;60:1381–1389. CrossRef
- Duncan R, Peat G, Thomas E, Hay E, McCall I, Croft P. Symptoms and radiographic osteoarthritis: not as discordant as they are made out to be? Ann Rheum Dis. 2007;66:86–91. CrossRef
- Felson DT, Niu J, Clancy M, Aliabadi P, Sack B, Guermazi A, Hunter DJ, Amin S, Rogers G, Booth SL. Low levels of vitamin D and worsening of knee osteoarthritis: results of two longitudinal studies. Arthritis Rheum. 2007;56:129–136. CrossRef
- Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000;133:635–646. CrossRef
- Glover TL, Goodin BR, Horgas Al, Kindler LL, King CD, Sibille KT, Peloquin CA, Riley JL 3rd, Staud R, Bradley LA, Fillingim RB. Vitamin D, race, and experimental pain sensitivity in older adults with knee osteoarthritis. Arthritis Rheum. 2012:64:3926–3935. CrossRef
- Griffith HW. Vitamins, Herbs, Minerals, & Supplements: The Complete Guide. MJF Books, New York, NY, USA; 1999.
- Haq I, Murphy E, Dacre J. Osteoarthritis. Postgrad Med J. 2003;79:377–383. CrossRef
- Heidari B, Heidari P, Hajian-Tilaki K. Association between serum vitamin D deficiency and knee osteoarthritis. Int Orthop. 2011;35:1627–1631. CrossRef
- Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281. CrossRef
- Hunter DJ, Hart D, Snieder H, Bettica P, Swaminathan R, Spector TD. Evidence of altered bone turnover, vitamin D and calcium regulation with knee osteoarthritis in female twins. Rheumatology (Oxford). 2003;42:1311–1316. CrossRef
- Kellgren JH, Lawrence JS. The Epidemiology of Chronic Rheumatism. Vol II. Atlas of Standard Radiographs of Arthritis. In: Kellgren JH, ed. Oxford, UK: Blackwell Scientific; 1963.
- Lane NE, Gore LR, Cummings SR, Hochberg MC, Scott JC, Williams EN, Nevitt MC. Serum vitamin D levels and incident changes of radiographic hip osteoarthritis: a longitudinal study. Study of Osteoporotic Fractures Research Group. Arthritis Rheum. 1999;42:854–860. CrossRef
- Laslett LL, Quinn S, Burgess JR, Parameswaran V, Winzenberg TM, Jones G, Ding C. Moderate vitamin D deficiency is associated with changes in knee and hip pain in older adults: a 5-year longitudinal study. Ann Rheum Dis. 2013 Apr 17 [Epub ahead of print].
- McAlindon T, LaValley M, Schneider E, Nuite M, Lee JY, Price LL, Lo G, Dawson-Hughes B. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial. JAMA. 2013;309:155–162. CrossRef
- McAlindon TE, Felson DT, Zhang Y, Hannan MT, Aliabadi P, Weissman B, Rush D, Wilson PW, Jacques P. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med. 1996;125:353–359. CrossRef
- Muraki S, Dennison E, Jameson K, Boucher BJ, Akune T, Yoshimura N, Judge A, Arden NK, Javaid K, Cooper C. Association of vitamin D status with knee pain and radiographic knee osteoarthritis. Osteoarthritis Cartilage. 2011;19:1301–1306. CrossRef
- Pham T, Van Der Heijde D, Lassere M, Altman RD, Anderson JJ, Bellamy N, Hochberg M, Simon L, Strand V, Woodworth T, Dougados M; OMERACT-OARSI. Outcome variables for osteoarthritis clinical trials: the OMERACT-OARSI set of responder criteria. J Rheumatol. 2003;30:1648–1654.
- Valdes AM, Spector TD. Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol. 2011;7:23–32. CrossRef
- Vupputuri MR, Goswami R, Gupta N, Ray D, Tandon N, Kumar N. Prevalence and functional significance of 25-hydroxyvitamin D deficiency and vitamin D receptor gene polymorphisms in Asian Indians. Am J Clin Nutr. 2006;83:1411–1419.
- Does Vitamin D Improve Osteoarthritis of the Knee: A Randomized Controlled Pilot Trial
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- 1. Department of Orthopaedic Surgery, King George’s Medical University, Nabiullah Road, near Daliganj Chauraha, Lucknow, India
- 2. Department of Pathology, KG Medical University, Lucknow, India
- 3. Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India