Clinical effects of bisphosphonates in involutional osteoporosis

The bisphosphonates are analogs of naturally occurring pyrophosphate. They appear to block bone resorption much more than mineralization. A series of compounds has been investigated. These have antiresorptive potencies ranging from 1 to 10,000. So far, structure-function relationships have eluded definition. These drugs increase the bone density in women with postmenopausal osteoporosis by about 5%-10% over 1 year. The bone density then appears to plateau, but most studies are of short duration. Improved bone density does not necessarily result in stronger bone, but no studies have had adequate power to assess fracture incidence. Bone formation rates decrease as measured histomorphometrically. This occurs while the bone density is improving, which implies an inhibition of bone resorption that is probably due to direct toxicity to the osteoclasts. Etidronate blocks mineralization as well as resorption and can cause osteomalacia, which is not seen with low-dose cyclical etidronate or with the second-generation compounds. The long-term effects of interfering with the remodeling cycle are still not known. Subtle side effects may be those on the bone itself. These might go undetected, since bone pain or fractures usually are attributable to the underlying disease.