EULAR: Vitamin D supplementation fails to reduce knee OA pain

ROME – Vitamin D supplementation did not ease osteoarthritic knee pain measured using the Western Ontario and McMaster Universities Osteoarthritis Index in a 2-year, randomized, double-blind, placebo-controlled trial.

Results of the VIDEO (Vitamin D Effect on Osteoarthritis) study in patients with symptomatic knee osteoarthritis (OA) and low vitamin D levels also showed that replenishing vitamin D also had no effect on the loss of cartilage volume, although there might be a marginal benefit on bone marrow lesions (BMLs) and pain assessed using a visual analog scale (VAS).

“Vitamin D at 50,000 IU/month over 2 years did not meet the primary endpoint in this randomized, controlled trial,” said Jason Jin, a Ph.D. candidate at the Menzies Research Institute, University of Tasmania in Hobart, Australia, who presented the VIDEO study findings at the European Congress of Rheumatology.

He cited a recent commentary published in the Journal of the American Medical Association (JAMA 2015;313:1311-12) that looked at vitamin D research and clinical practice in which the authors said that “clinical enthusiasm for supplemental vitamin D has outpaced available evidence.” This seems to be true considering the results of this and other previous randomized trials, Mr. Jin observed.

“The background of this study is that, in the last decade, vitamin D has become a hot topic in osteoarthritis research and epidemiologic studies have found that vitamin D deficiency is very common in knee osteoarthritis patients,” he said. Low levels of vitamin D have been linked to increased knee pain, radiographic progression, and increased cartilage loss in OA.

Two prior randomized, controlled trials provided conflicting evidence, he highlighted, with one study showing that supplementation of 2,000 IU/day of vitamin D for 2 years had no effect on symptoms or knee structure (JAMA 2013;309:155-62) while another showed that a monthly dose of 60,000 IU for 1 year may be beneficial in terms of relieving pain and functional outcomes but longer follow-up was required (Clin. Orthop. Relat. Res. 2013;471:3556-62).

The VIDEO study was therefore designed to try to resolve some of the controversy and look at a larger group of patients for a longer period of time. The study’s hypothesis was that vitamin D might ease knee pain and perhaps have effect structural changes in patients with symptomatic knee OA who had low vitamin D levels. A low vitamin D level was defined as a serum measurement of 25(OH)D of 12.5-60 nmol/L (5-24 ng/mL) at baseline.

Of almost 600 patients screened, 413 were randomized, with 209 randomized to the oral vitamin D supplementation group and 204 to the matched placebo arm. Patients in each group had comparable characteristics at baseline, with a mean age of around 62 to ­63 years. Half the patients were female. Baseline serum vitamin D levels were about 43 nmol/L (17.2 ng/mL). Virtually all (96%) of patients had radiographic evidence of knee OA, 97% had cartilage defects, and 80% had bone marrow lesions.

While serum levels of 25(OH)D were successfully increased in the supplemented patients over the course of the study, this did not translate into an improvement in the coprimary endpoint of a change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain over 24 months. The difference in WOMAC pain between the vitamin D and placebo groups was a nonsignifcant –14.8 (–49.9 vs. –35.1; P = .102). Vitamin D–supplemented patients did, however, report marginally less VAS pain (–14.8 vs. –9.4; P = .038).

Total tibial cartilage volume loss, the second coprimary endpoint, was not significantly different between the vitamin D and placebo groups, at around 121 and 150 mm³ per annum, with 2-year changes of –3.44% vs. –4.23% per annum (P = .132). The secondary endpoints of changes in tibiofemoral cartilage defects (0.29 vs. 0.47; P = .159) and tibiofemoral BMLs (–0.59 vs. –0.21; P = .087) were also not significantly different, but patients randomized to vitamin D supplementation had fewer increases in BMLs (17% vs. 27%; P = .03).

There was no concern over the safety of vitamin D supplementation, although more general side effects were noted in the vitamin D vs. the placebo group.

Commenting on the strengths and weaknesses of the study, Mr. Jin noted it was a large, multicenter, randomized, double-blind, placebo-controlled trial with a reasonably long follow-up. The patient group studied has good generalizability to those seen in everyday practice, he suggested, noting that the main limitation was the number of patients lost to follow-up because of noncompliance: 21 patients in the vitamin D group vs. 8 patients in the placebo group.

ROME – Vitamin D supplementation did not ease osteoarthritic knee pain measured using the Western Ontario and McMaster Universities Osteoarthritis Index in a 2-year, randomized, double-blind, placebo-controlled trial.

Results of the VIDEO (Vitamin D Effect on Osteoarthritis) study in patients with symptomatic knee osteoarthritis (OA) and low vitamin D levels also showed that replenishing vitamin D also had no effect on the loss of cartilage volume, although there might be a marginal benefit on bone marrow lesions (BMLs) and pain assessed using a visual analog scale (VAS).

“Vitamin D at 50,000 IU/month over 2 years did not meet the primary endpoint in this randomized, controlled trial,” said Jason Jin, a Ph.D. candidate at the Menzies Research Institute, University of Tasmania in Hobart, Australia, who presented the VIDEO study findings at the European Congress of Rheumatology.

He cited a recent commentary published in the Journal of the American Medical Association (JAMA 2015;313:1311-12) that looked at vitamin D research and clinical practice in which the authors said that “clinical enthusiasm for supplemental vitamin D has outpaced available evidence.” This seems to be true considering the results of this and other previous randomized trials, Mr. Jin observed.

“The background of this study is that, in the last decade, vitamin D has become a hot topic in osteoarthritis research and epidemiologic studies have found that vitamin D deficiency is very common in knee osteoarthritis patients,” he said. Low levels of vitamin D have been linked to increased knee pain, radiographic progression, and increased cartilage loss in OA.

Two prior randomized, controlled trials provided conflicting evidence, he highlighted, with one study showing that supplementation of 2,000 IU/day of vitamin D for 2 years had no effect on symptoms or knee structure (JAMA 2013;309:155-62) while another showed that a monthly dose of 60,000 IU for 1 year may be beneficial in terms of relieving pain and functional outcomes but longer follow-up was required (Clin. Orthop. Relat. Res. 2013;471:3556-62).

The VIDEO study was therefore designed to try to resolve some of the controversy and look at a larger group of patients for a longer period of time. The study’s hypothesis was that vitamin D might ease knee pain and perhaps have effect structural changes in patients with symptomatic knee OA who had low vitamin D levels. A low vitamin D level was defined as a serum measurement of 25(OH)D of 12.5-60 nmol/L (5-24 ng/mL) at baseline.

Of almost 600 patients screened, 413 were randomized, with 209 randomized to the oral vitamin D supplementation group and 204 to the matched placebo arm. Patients in each group had comparable characteristics at baseline, with a mean age of around 62 to ­63 years. Half the patients were female. Baseline serum vitamin D levels were about 43 nmol/L (17.2 ng/mL). Virtually all (96%) of patients had radiographic evidence of knee OA, 97% had cartilage defects, and 80% had bone marrow lesions.

While serum levels of 25(OH)D were successfully increased in the supplemented patients over the course of the study, this did not translate into an improvement in the coprimary endpoint of a change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain over 24 months. The difference in WOMAC pain between the vitamin D and placebo groups was a nonsignifcant –14.8 (–49.9 vs. –35.1; P = .102). Vitamin D–supplemented patients did, however, report marginally less VAS pain (–14.8 vs. –9.4; P = .038).

Total tibial cartilage volume loss, the second coprimary endpoint, was not significantly different between the vitamin D and placebo groups, at around 121 and 150 mm³ per annum, with 2-year changes of –3.44% vs. –4.23% per annum (P = .132). The secondary endpoints of changes in tibiofemoral cartilage defects (0.29 vs. 0.47; P = .159) and tibiofemoral BMLs (–0.59 vs. –0.21; P = .087) were also not significantly different, but patients randomized to vitamin D supplementation had fewer increases in BMLs (17% vs. 27%; P = .03).

There was no concern over the safety of vitamin D supplementation, although more general side effects were noted in the vitamin D vs. the placebo group.

Commenting on the strengths and weaknesses of the study, Mr. Jin noted it was a large, multicenter, randomized, double-blind, placebo-controlled trial with a reasonably long follow-up. The patient group studied has good generalizability to those seen in everyday practice, he suggested, noting that the main limitation was the number of patients lost to follow-up because of noncompliance: 21 patients in the vitamin D group vs. 8 patients in the placebo group.

ROME – Vitamin D supplementation did not ease osteoarthritic knee pain measured using the Western Ontario and McMaster Universities Osteoarthritis Index in a 2-year, randomized, double-blind, placebo-controlled trial.

Results of the VIDEO (Vitamin D Effect on Osteoarthritis) study in patients with symptomatic knee osteoarthritis (OA) and low vitamin D levels also showed that replenishing vitamin D also had no effect on the loss of cartilage volume, although there might be a marginal benefit on bone marrow lesions (BMLs) and pain assessed using a visual analog scale (VAS).

“Vitamin D at 50,000 IU/month over 2 years did not meet the primary endpoint in this randomized, controlled trial,” said Jason Jin, a Ph.D. candidate at the Menzies Research Institute, University of Tasmania in Hobart, Australia, who presented the VIDEO study findings at the European Congress of Rheumatology.

He cited a recent commentary published in the Journal of the American Medical Association (JAMA 2015;313:1311-12) that looked at vitamin D research and clinical practice in which the authors said that “clinical enthusiasm for supplemental vitamin D has outpaced available evidence.” This seems to be true considering the results of this and other previous randomized trials, Mr. Jin observed.

“The background of this study is that, in the last decade, vitamin D has become a hot topic in osteoarthritis research and epidemiologic studies have found that vitamin D deficiency is very common in knee osteoarthritis patients,” he said. Low levels of vitamin D have been linked to increased knee pain, radiographic progression, and increased cartilage loss in OA.

Two prior randomized, controlled trials provided conflicting evidence, he highlighted, with one study showing that supplementation of 2,000 IU/day of vitamin D for 2 years had no effect on symptoms or knee structure (JAMA 2013;309:155-62) while another showed that a monthly dose of 60,000 IU for 1 year may be beneficial in terms of relieving pain and functional outcomes but longer follow-up was required (Clin. Orthop. Relat. Res. 2013;471:3556-62).

The VIDEO study was therefore designed to try to resolve some of the controversy and look at a larger group of patients for a longer period of time. The study’s hypothesis was that vitamin D might ease knee pain and perhaps have effect structural changes in patients with symptomatic knee OA who had low vitamin D levels. A low vitamin D level was defined as a serum measurement of 25(OH)D of 12.5-60 nmol/L (5-24 ng/mL) at baseline.

Of almost 600 patients screened, 413 were randomized, with 209 randomized to the oral vitamin D supplementation group and 204 to the matched placebo arm. Patients in each group had comparable characteristics at baseline, with a mean age of around 62 to ­63 years. Half the patients were female. Baseline serum vitamin D levels were about 43 nmol/L (17.2 ng/mL). Virtually all (96%) of patients had radiographic evidence of knee OA, 97% had cartilage defects, and 80% had bone marrow lesions.

While serum levels of 25(OH)D were successfully increased in the supplemented patients over the course of the study, this did not translate into an improvement in the coprimary endpoint of a change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain over 24 months. The difference in WOMAC pain between the vitamin D and placebo groups was a nonsignifcant –14.8 (–49.9 vs. –35.1; P = .102). Vitamin D–supplemented patients did, however, report marginally less VAS pain (–14.8 vs. –9.4; P = .038).

Total tibial cartilage volume loss, the second coprimary endpoint, was not significantly different between the vitamin D and placebo groups, at around 121 and 150 mm³ per annum, with 2-year changes of –3.44% vs. –4.23% per annum (P = .132). The secondary endpoints of changes in tibiofemoral cartilage defects (0.29 vs. 0.47; P = .159) and tibiofemoral BMLs (–0.59 vs. –0.21; P = .087) were also not significantly different, but patients randomized to vitamin D supplementation had fewer increases in BMLs (17% vs. 27%; P = .03).

There was no concern over the safety of vitamin D supplementation, although more general side effects were noted in the vitamin D vs. the placebo group.

Commenting on the strengths and weaknesses of the study, Mr. Jin noted it was a large, multicenter, randomized, double-blind, placebo-controlled trial with a reasonably long follow-up. The patient group studied has good generalizability to those seen in everyday practice, he suggested, noting that the main limitation was the number of patients lost to follow-up because of noncompliance: 21 patients in the vitamin D group vs. 8 patients in the placebo group.