Osteoporosis - minodronic acid
As we get older, bone density gradually decreases, leaving bones thinner and more susceptible to fractures. There are many reasons for this, but by far the most important is the age-related drop-off in levels of oestrogen in women and testosterone in men. The sudden fall in oestrogen levels leaves postmenopausal women particularly susceptible to osteoporosis, where bone density is reduced and the bones are increasingly likely to fracture.
As recently as 20 years ago, the only real treatments given to osteoporosis sufferers were vitamin and calcium supplements. Hormone replacement therapy has the benefit of reducing the loss in bone density. But there are now various bisphosphonate agents on the market, the first being etidronate, that prevent osteoclasts digesting the bone matrix.
Another bisphosphonate drug, minodronic acid, formerly referred to as YM529, is being developed by Japanese company Ono Pharmaceutical, which licensed the agent from Yamanouchi. In a Phase II open label multicentre study in patients with osteoporosis, female and male subjects were given 0.05, 0.5 or 1.5 mg of minodronic acid twice a day for 24 weeks, along with calcium lactate supplements. The three groups saw increased bone mineral density of 1.53, 3.76 and 7.82% respectively.1 Its efficacy and safety have been investigated in a multicentre randomised placebo-controlled trial in 352 postmenopausal women with osteoporosis. They were given 0.5, 1 or 1.5mg/day or placebo, plus calcium lactate supplements, for 36 weeks. Significant improvements in bone mineral density were substantially better in those given minodronic acid, and no serious adverse events were seen. Of particular note was the fact that the incidence of gastrointestinal problems were low, as ulceration is a common problem with bisphosphonate therapy.2 The compound is now undergoing Phase III testing in Japan. In addition, it is being evaluated for the treatment of bone metastasis resulting from breast and lung cancers, and for the treatment of multiple myeloma.