A Comprehensive Monograph on Alendronic Acid (DB00630)

Executive Summary and Drug Identification

Executive Summary

Alendronic acid, a potent second-generation, nitrogen-containing bisphosphonate, represents a cornerstone in the management of metabolic bone diseases.[1] Marketed under brand names such as Fosamax® and Binosto®, it is established as a first-line therapeutic agent for the treatment and prevention of osteoporosis in postmenopausal women and men, glucocorticoid-induced osteoporosis, and for the management of Paget's disease of bone.[3] Its primary mechanism of action involves the specific inhibition of osteoclast-mediated bone resorption. It achieves this by targeting farnesyl pyrophosphate synthase, a critical enzyme in the mevalonate pathway, thereby disrupting essential cellular processes in osteoclasts and inducing their apoptosis.[1]

The clinical use of alendronic acid is defined by its unique and challenging pharmacokinetic profile, which includes extremely low oral bioavailability (less than 1%) and an exceptionally long terminal half-life in the skeleton, estimated to exceed 10 years.[6] This profile necessitates a strict and often inconvenient dosing regimen to ensure adequate absorption and minimize esophageal irritation, a primary adverse effect. While its efficacy in increasing bone mineral density and reducing fracture risk is well-documented in landmark clinical trials, its long-term use requires careful consideration.[8] The drug's prolonged skeletal residence time, while contributing to its sustained therapeutic effect, is also implicated in rare but serious adverse events, including osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). Consequently, the clinical management of alendronic acid therapy involves a continuous balance between its proven benefits in fracture prevention and the mitigation of risks associated with long-term administration, often leading to considerations of a "drug holida