Will Your Patients With Knee OA Benefit from Vitamin D Supplementation?

Vitamin D supplementation did not reduce knee pain or volume of cartilage loss as measured by magnetic resonance imaging (MRI) in individuals with knee osteoarthritis (OA) and hypovitaminosis D, according to a study published in JAMA.¹

Knee OA is a musculoskeletal disorder that has significant impact on functional capacity.  There are no current disease-modifying agents for OA, so medication management has largely been directed towards analgesia.

Vitamin D3 (cholecalciferol) is synthesized in skin from 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 derived from the skin or diet must then undergo 25-hydroxylation in the liver, then 1-hydroxylation in the kidneys to yield its active form, 1,25-dihydroxycholecalciferol (calcitriol).²

Low levels of vitamin D can lead to the reduced intestinal absorption of calcium and phosphorus. Hypocalcemia can occur with longstanding vitamin D deficiency, causing secondary hyperparathyroidism and “bone cannibalism”, which may lead to bone demineralization.³ Some studies in the past have suggested that vitamin D supplementation may help decrease pain and swelling associated with knee OA⁴, but evidence has not been conclusive thus far.

To compare the effects of vitamin D supplementation on knee pain and knee cartilage volume in patients with hypovitaminosus D and symptomatic knee OA, Changhai Ding, MD, PhD, from the University of Tasmania, Melbourne, Australia, and colleagues designed a multi-center, randomized, double-blind, placebo-controlled trial that followed participants over 2 years.

Changes in MRI-measured tibial cartilage volumes and subjective measures of pain, as measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score, were chosen as primary outcome endpoints.  Changes in cartilage defects and bone marrow lesions on MRI were selected as secondary outcome endpoints.

413 study participants were randomly assigned to receive monthly oral doses of vitamin D3 (50 000 IU; n = 209) or placebo (n = 204), over the course of 2 years.

The researchers found that while vitamin D levels increased in the treatment group as compared to placebo group, there was no improvements in MRI-measured tibial cartilage volumes  (−3.4% in the vitamin D group vs −4.2% in the placebo group [between-group difference, 0.8% {95% CI, −0.2% to 1.8%}]; P = .13) or WOMAC pain scores (−49.9 in the vitamin D group vs −35.1 in the placebo group [between-group difference, −14.8 {95% CI, −32.5 to 2.9}]; P = .10).

There were also no differences in the change of tibiofemoral cartilage defects or bone marrow lesions between the vitamin D treatment group and the placebo group.¹

Summary and Clinical Applicability

Vitamin D supplementation for 2 years in study participants with symptomatic knee OA and low baseline levels of 25-hydroxyvitamin D did not result in decreased tibial cartilage loss or reduce knee pain when compared to placebo.¹

The authors conclude that, “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 OA”.

Reference

1. Jin X, Jones G, Cicuttini F, et al. Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis A Randomized Clinical Trial. JAMA. 2016;315(10):1005-1013. doi:10.1001/jama.2016.1961.

2. Deluca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004;80(6 Suppl):1689S-96S.

3. Lips P, Van schoor NM. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab. 2011;25(4):585-91.

4. Sanghi D, Mishra A, Sharma AC, et al. Does vitamin D improve osteoarthritis of the knee: a randomized controlled pilot trial. Clin Orthop Relat Res. 2013;471(11):3556-62.