An Expert Report on Risedronic Acid (DB00884)

I. Executive Summary

Risedronic acid is a potent, third-generation, nitrogen-containing bisphosphonate widely utilized in the management of metabolic bone diseases. It is classified as a small molecule antiresorptive agent, primarily indicated for the treatment and prevention of postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis, as well as for the treatment of Paget's disease of bone. The therapeutic effect of Risedronic acid is derived from its highly specific mechanism of action. It exhibits a strong affinity for bone mineral, concentrating at sites of active remodeling where it is internalized by osteoclasts. Within these cells, it potently inhibits farnesyl pyrophosphate synthase (FPPS), a critical enzyme in the mevalonate pathway. This inhibition disrupts essential cellular processes, leading to osteoclast inactivation and apoptosis, thereby significantly reducing the rate of bone resorption.

The clinical utility of Risedronic acid is, however, framed by a challenging pharmacokinetic profile. Its oral bioavailability is exceptionally low, averaging less than 1%, and is profoundly diminished by the presence of food and polyvalent cations. This necessitates a strict and often inconvenient administration protocol to ensure adequate absorption. Conversely, its long terminal half-life, a result of its persistence in bone tissue, provides the pharmacological rationale for less frequent dosing regimens, including weekly and monthly schedules, which have been developed to improve patient adherence.