OTTAWA, Canada—Strontium ranelate reduces the risk of vertebral fractures in postmenopausal women with osteoporosis and increases bone mineral density (BMD) at all sites in postmenopausal women, whether or not they have osteoporosis, according to a Cochrane Review of clinical studies

The new oral agent also decreased the risk of nonvertebral fractures, including hip fractures, in a small number of studies, but this effect did not reach statistical significance.

Strontium ranelate (Protelos®, Servier) is a bone-seeking mineral that is thought to simultaneously decrease bone resorption and stimulate bone formation, although, the reviewers note, "[T]here is some controversy surrounding its mechanism of action."

The drug was approved for use in the European Union in 2004 and is currently available in 53 countries. It has not been released in the US or Canada, but approval is pending in Canada, said lead researcher Ann Cranney, MD, an associate professor of medicine at the university of Ottawa and the Ottawa Health Research Institute in Canada.

"Although the exact mechanism of action is not known, strontium ranelate may have a dual effect on both resorption and formation," Dr. Cranney  told CIAOMed. "So far, it looks promising as another option for people who cannot  take existing therapies."

The systematic review analyzed data from four randomized controlled trials of strontium ranelate for osteoporosis treatment or prevention. Three studies included postmenopausal women with osteoporosis, most of whom had already suffered at least one fracture. The fourth study enrolled postmenopausal women with osteopenia.

In the 2 treatment trials, women who took 2 g of strontium ranelate daily had a 37% reduction in vertebral fracture risk over a 3-year period compared with their counterparts who received a placebo. These two trials showed a 14% reduction in risk for osteoporosis-related fractures at other sites among participants taking the same dose of strontium ranelate compared with those who took placebo. The  studies were not powered to determine efficacy in prevention of hip fractures.

In all four trials, strontium ranelate increased bone density in both the spine and hip over a 2- to 3-year period. The greatest benefit in BMD was seen at the highest doses tested, 2 g/day in the treatment population and 1 g/day in the prevention population, but even the lowest dose tested produced some improvement.

The most common side effect was diarrhea, but this was not severe enough to cause withdrawal from the study. Strontium ranelate also carried a small absolute increase in the risk of blood clots. Two other therapies for osteoporosis, raloxifene (Evista®) and estrogen, pose a similar small increased  risk for these problems, the study authors point out.

[Strontium ranelate] is generally well-tolerated, although there are some initial concerns of a risk of blood clots," said Dr. Cranney.

New oral therapy reduces vertebral fractures

"The real objective of therapy is to reduce fractures, and it seems quite clear that strontium ranelate does have an effect on this end point," said Michael McClung, MD, director of the Oregon Osteoporosis Center in Portland, Oregon, in a written statement. "For vertebral fractures, it's in the same ballpark as we see with virtually every other drug that's been studied."

Dr. McClung said that the nonvertebral fracture risk reduction of about 14% doesn't compare very favorably with the 40% to 50% reduction in risk seen with the most commonly prescribed drugs for osteoporosis, alendronate (FosamaxR) and risedronate (ActonelR). He added, "These are the only two drugs that have shown a reduction in hip fracture risk in predesigned studies of people with osteoporosis."

Strontium ranelate is not available in the US. Dr. McClung said that supplements containing different forms of the mineral are available in health food stores but their efficacy is unknown.

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