Bisphosphonates for the treatment of osteoporosis: insights for clinicians

Osteoporosis is a common skeletal disease characterized by a reduction in bone strength and increased risk of fractures. Osteoporotic fractures are associated with substantial morbidity, mortality, and high healthcare costs. Treatments for osteoporosis have been shown to increase bone strength and reduce fracture risk. The drugs most commonly used to treat osteoporosis are bisphosphonates: stable analogs of naturally occurring inorganic pyrophosphate. The bisphosphonates share a common chemical structure with side chain variations that convey differences in their pharmacological properties, such as affinity for bone mineral and inhibitory effect on osteoclastic bone resorption. The clinical profiles of bisphosphonates, such as time of onset and offset of effect, may differ according to these pharmacological properties. Bisphosphonates can be administered orally or intravenously with a wide range of doses and dosing intervals. Randomized placebo-controlled clinical trials have shown that bisphosphonates reduce fracture risk in postmenopausal women with osteoporosis and have a generally excellent safety record. Clinical challenges in using bisphosphonates to treat osteoporosis include appropriate selection of patients for initiating therapy, choosing which bisphosphonate to use, monitoring therapy to assure that medication is taken correctly and the desired effect is achieved, determining when drug discontinuation should be considered, and managing side effects, possible side effects, and fear of side effects. Strategies for treating patients with bisphosphonates should consider each of these issues.