Osteoporosis - ospemifene
Older women have a heightened risk of developing osteoporosis.
Older women have a heightened risk of developing osteoporosis.
With around a quarter of all women over 65 being affected, the clinical need for effective, side-effect free preventive treatments is enormous. After the menopause, plasma 17beta-oestrodiol levels drop to below 10% of those before the menopause, leading to a reduction in bone mineral density and all too often, ultimately, fractures. With the now-recognised side-effects of HRT precluding their routine use for osteoporosis prevention, the search is on for agents that are as good at cutting the risk of developing the condition, without the side-effects.
Numerous selective oestrogen receptor modulators have been developed, particularly for use in cancer patients. These include tamoxifen and raloxifene, both of which have a beneficial effect on bone density, but can have side-effects, and may exacerbate other symptoms of the menopause. A new SERM, ospemifene, has been developed by Orion, and is being developed with Hormos Medical.1 It has a similar affinity to a and b oestrogen receptors to tamoxifen, and was shown to prevent bone loss in animal models, without tamoxifen's hepatotoxicity.
In a randomised double blind placebo controlled Phase I study, 40 healthy postmenopausal women were given 25, 50, 100 or 200mg of ospemifene a day for 12 weeks.2
It was found to be safe, and generally well tolerated at all four doses, with the lowest incidence of minor side effects seen at the lower doses.
In a further randomised double blind trial, 160 healthy postmenopausal women were given 30, 60 or 90mg a day for three months.3 It had no effect on cardiovascular disease, and was found to be well tolerated.
A third randomised double blind study in 120 healthy postmenopausal women saw the subjects given 30, 60 or 90mg ospemifene or 60mg a day of raloxifene.4 The two higher doses of ospemifene had a similar effect on bone metabolism to raloxifene, and in addition all the patients given the new drug had improvements in their postmenopausal symptoms, compared with none of those given raloxifene. Ospemifene is now undergoing Phase II/III trials.