Strontium Ranelate Prevents Structural Damage in Knee OA

Alice Goodman

November 13, 2012

WASHINGTON, DC — Three years of treatment with strontium ranelate prevents structural damage in patients with knee osteoarthritis (OA). Beneficial effects on structure were observed with both the 1-g and 2-g doses of strontium ranelate compared with placebo. These results of the Strontium Ranelate in Knee Osteoarthritis (SEKOIA) trial were presented here at ACR 2012.

The effects on structure also translated into less progression of knee OA to thresholds that lead to knee surgery, and doses of 2 g/day significantly improved symptoms and pain, researchers reported.

"Our study suggests that use of strontium ranelate could reduce the numbers of patients having knee surgery. Clinical improvement was seen at 18 months, and we found that the longer you treat [with this drug] the greater the difference is between treatment and placebo," said lead author Jean-Yves Reginster, MD, from the University of Liège in Belgium.

Strontium ranelate stimulates bone formation and decreases bone resorption. The drug is licensed and approved in more than 100 countries for treatment of postmenopausal osteoporosis and osteoporosis in men. It is not approved in the United States but is used off-label for osteoporosis.

SEKOIA was a 3-year, double-blind, placebo-controlled trial conducted at 98 centers in 18 countries. A total of 1683 patients with mild to moderate primary knee OA (based on American College of Rheumatology criteria) were randomly assigned to strontium ranelate at 1 g/day or 2 g/day or to placebo.

The primary endpoint for structure-modifying treatment was radiologic joint space narrowing (JSN) of the medial tibiofemoral compartment of the target joint evaluated on radiographs by 2 independent investigators.

Demographic and disease characteristics were similar between groups. Dr. Reginster said the patients were typical of those enrolled in clinical trials of knee OA: predominantly female, with an average body mass index of 30 kg/m2. Two thirds had mild knee OA and one third had moderate knee OA.

The dropout rate was 42%, which he said is similar to that in other OA placebo-controlled trials.

For the primary endpoint, significantly less JSN was observed in both active treatment groups vs placebo, and results were similar in the 1-g and 2-g groups. JSN was –0.23 in the 1-g group and –0.27 in the 2-g group vs –0.37 in the placebo group (P = .0018 for both comparisons with placebo).

Both doses of active drug were able to reduce radiologic cartilage loss of 5 mm or greater at 3 years compared with placebo; this threshold was reduced by 34% in the 1-g group vs placebo (P = .049) and 44% in the 2-g group vs placebo (P = .008).

"Patients with a radiological cartilage loss of 5 mm or more are 5 times more likely to get surgery over 10 years," he stated.

Significant improvements in the global Western Ontario and McMaster Universities (WOMAC) score and WOMAC Pain Score were achieved only with strontium ranelate, 2 g/day. Dr. Reginster pointed out that this is the approved dose for treatment of osteoporosis.

"All subscales of WOMAC showed significant benefit of strontium ranelate 2 g/day," he said.

The safety profile of strontium ranelate is well established, with more than 10 years of experience in the treatment of osteoporosis. The only contraindication to therapy is deep-vein thrombosis, he said.

Kathryn Dao, MD, director of Clinical Rheumatology at Baylor Research Institute in Dallas, Texas, said that these results are important "since we are so limited in therapeutic options for OA." She said further study is needed before strontium ranelate can be established as a treatment option for knee OA.

"Strontium ranelate seems to have a good side effect profile that is different from narcotics and NSAIDs [nonsteroidal antiinflammatory drugs], which are used to treat the pain of knee OA," she said.

The drug is not approved in the United States for osteoporosis because there are no fracture data, she continued, but it is used off-label at some centers.

Dr. Reginster disclosed financial ties with Servier, which makes strontium ranelate and with Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB, Merck Sharp and Dohme, Rottapharm, IBSA, Genevrier, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Novo-Nordisk, and Bristol-Myers Squibb. Dr. Dao's financial disclosures include research funding from Celgene, UCB, Amgen; National Advisory Board for UCB; and speaker for Lilly.

ACR 2012. Abstract 1596. Presented November 12, 2012.