Osteoporosis - strontium ranelate

As many as 200 million women around the world are estimated to suffer from osteoporosis.

Bone remodelling is a normal process that takes place throughout life, but the skeletal disorder osteoporosis occurs when the rate of bone resorption exceeds the rate at which new bone is formed. It results in bones that are weakened and brittle, and as the condition of the bones deteriorates, so the frequency of fractures increases.

Drug therapy relies heavily on the bisphosphonate drugs like alendronate, but these can cause very severe gastrointestinal side effects. And with preventative hormone replacement therapy no longer being routinely prescribed to postmenopausal women, the need for effective drug treatments with reduced side effect profiles is now enormous.

As a consequence, Servier is developing strontium ranelate as a potential osteoporosis treatment.¹ Strontium is a familiar ingredient in toothpastes for sensitive teeth, and strontium ranelate has been found to decrease bone resorption and increase bone formation at the same time.

Its efficacy at preventing post-menopausal bone loss was investigated in a randomised, double blind, placebo controlled, dose ranging Phase II study in 160 healthy early post-menopausal women. The subjects were given 0.125, 0.5 or 1 g/day strontium ranelate orally, in combination with 500mg/day calcium supplements. Those given 1g strontium ranelate had significant increases in adjusted lumbar bone mineral density when compared with placebo, and they also experienced significant rises in serum bone alkaline phosphatase throughout treatment.

Another Phase II trial involved 353 osteoporotic postmenopausal women with at least one previous lumbar fracture being given 0.5, 1 or 2g strontium ranelate a day, alongside calcium and vitamin D supplements, for two years.²

Few adverse events were seen, and those given the active had increased bone mineral density and reduced incidence of vertebral fractures, with the best results seen in those given 2g doses.

Phase III trials are under way. In one, 1691 postmenopausal women with vertebral osteoporosis were given placebo or 2g of the active, plus supplements. Those given the active had a 41% lower relative risk of vertebral fractures.³ And in a larger trial, 5091 women were given 2g strontium ranelate and supplements a day for three years, with a 41% reduction in hip fractures seen in the treated group.⁴

Phase III studies continue and, if ultimately successful, strontium ranelate could become a much needed addition to the available treatments for osteoporosis.

1. J.Y. Reginster et al. Drugs Today 2003, 39, 89

2. P.J. Meunier et al. J. Clin. Endocrinol. Metab. 2002, 87, 2060

3. P. Marquis et al. Osteoporosis Int. 2002 13 (Suppl. 3) Abst O5

4. J.Y. Reginster et al. Osteoporosis Int. 2002 13 (Suppl. 3) Abst O14