Alendronate

Alendronate belongs to the bisphosphonate class of drugs, which are pyrophosphate analogs that bind strongly to hydroxyapatite in bone, particularly at sites of active remodeling. Nitrogen-containing bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) inhibit farnesyl pyrophosphate synthase in the mevalonate pathway within osteoclasts, impairing prenylation of small GTPases necessary for osteoclast cytoskeletal function and survival, ultimately causing osteoclast apoptosis and decreased bone resorption. This leads to increased bone mineral density, though the bone formed can be more brittle with long-term use due to suppressed remodeling.

Clinical indications include postmenopausal and glucocorticoid-induced osteoporosis, Paget's disease of bone, and osteogenesis imperfecta (adjunct). It is typically taken orally on an empty stomach with a full glass of water, and the patient must remain upright for at least 30 minutes afterward to prevent esophageal irritation.

Key adverse effects include esophagitis/esophageal ulcers (contraindicated in esophageal strictures, achalasia, or inability to sit upright), osteonecrosis of the jaw (especially with IV bisphosphonates or after dental extractions), atypical subtrochanteric femoral fractures with long-term use, and hypocalcemia (ensure adequate calcium/vitamin D supplementation before starting therapy). Renal impairment is a relative contraindication. Drug holidays are sometimes considered after 5 years of therapy to reduce the risk of atypical fractures while maintaining bone density benefits.

Monitoring includes DEXA scans to assess bone mineral density. Alendronate is often first-line therapy for osteoporosis prevention and treatment, especially in postmenopausal women and patients on long-term corticosteroids.