Clinical use of bisphosphonates in the UK

Abstract

Bisphosphonates are synthetic analogues of naturally occurring pyrophosphate, but contain a P-C-P bond in the middle of the molecule instead of a P-O-P bond. The addition of different side chains allows many structural variations, producing bisphosphonates with a range of potencies and properties. Bisphosphonates are poorly absorbed from the bowel, but once absorbed they localise to the skeleton, where they inhibit the recruitment and function of osteoclasts. This provides a rationale for their use in the management of patients with bone diseases. Osteoporosis is characterised by a reduction in bone density, associated with skeletal fragility and an increased risk of fracture after minimal trauma. Bisphosphonates decrease bone resorption and formation, but because of the transient uncoupling of these processes, there is an increase in bone density of 5-10%. Cyclical etidronate, alendronate and risedronate decrease the incidence of further vertebral fractures, but only alendronate and risedronate have been shown to reduce the risk of hip and other non-vertebral fractures. Paget's disease is a focal disorder of bone remodelling, associated with bone pain, skeletal deformity and increased risk of fracture. Specific treatment is directed at suppressing the overactivity of osteoclasts, thereby decreasing bone turnover. Tiludronate, risedronate and iv pamidronate reduce the activity of Paget's more effectively than etidronate. Although bisphosphonates decrease bone pain and reduce the activity of Paget's disease, there is currently no evidence that any treatment will prevent skeletal deformity, fractures or other complications of the condition. The choice of bisphosphonate for the treatment of osteoporosis and Paget's disease will depend on the potential advantages and disadvantages in the individual patient.