Minodronate for the treatment of osteoporosis

Abstract

Minodronate is a third-generation bisphosphonate that was developed and approved for clinical use in osteoporosis therapy in Japan. The mechanism of action for suppressing bone resorption is the inhibition of farnesyl pyrophosphate synthase, a key enzyme in the mevalonic acid metabolic pathway of osteoclasts, to induce apoptosis of the cells. Minodronate is the strongest inhibitor of bone resorption among the currently available oral bisphosphonates. Large randomized, placebo-controlled, double-blind clinical trials have revealed an increase in bone mineral density of both the lumbar spine and femoral neck over 3 years of daily minodronate therapy and risk reduction in vertebral fractures over 2 years of therapy. The increase in bone mass and the prevention of vertebral fractures are similar to those with alendronate or risedronate. The incidence of adverse events, especially gastrointestinal disturbance, is the same as or less than that with weekly or daily alendronate or risedronate. The unique mechanism of action of minodronate via the inhibition of the P2X(2/3) receptor compared with other bisphosphonates may be an advantage in reducing low back pain in patients with osteoporosis. The monthly regimen of minodronate, introduced in 2011, is expected to have better patient adherence and longer persistence. In experimental animal models, minodronate preserved, or even ameliorated, bone microarchitectures, including microcracks and perforation of the trabeculae in the short term. The lowest incidence of bisphosphonate-related osteonecrosis of the jaw among all bisphosphonates and the lack of atypical femoral fractures attributed to its use to date, however, are partly because only a smaller population used minodronate than those using other bisphosphonates. To date, minodronate is available only in Japan. Hip fracture risk reduction has not been verified yet. More clinical studies on minodronate and its use in osteoporosis treatment, with a large number of subjects, should be conducted to verify hip fracture risk reduction and long-term results.

Keywords: bisphosphonate; bone marker; bone mineral density; bone quality; clinical trial; farnesyl pyrophosphate synthase; fracture; long-term therapy; minodronate; osteoporosis; pain reduction; zoledronate.