Bisphosphonates

Bisphosphonates

1. Definition & overview

• Bisphosphonates (BPs / BPNs) are synthetic, non-hydrolysable analogues of inorganic pyrophosphate in which the central oxygen of the P–O–P backbone is replaced by a carbon atom, giving a metabolically stable P–C–P ("geminal" bisphosphonate) structure (G&G 14e Ch.52, p.1060; Golan 4e Ch.32, p.592).
• They are the most potent and most widely used antiresorptive drugs, acting selectively to inhibit osteoclast-mediated bone resorption (KDT 8e Ch.24, p.369; Golan 4e Ch.32, p.592).
• Core clinical role: first-line pharmacotherapy for osteoporosis (postmenopausal, male, glucocorticoid-induced), Paget disease of bone, hypercalcaemia of malignancy, and osteolytic skeletal metastases / multiple myeloma (G&G 14e Ch.52, pp.1060–1; KDT 8e Ch.24, pp.370–1).
• Consensus guideline opinion recommends bisphosphonates, in women without contraindications, as the primary intervention for reducing hip, vertebral and non-vertebral fractures (G&G 14e Ch.52, p.1061).
• Mechanistically they are anti-catabolic, not anabolic — they slow bone loss by suppressing resorption but, because bone remodeling is a coupled process, they do not produce large sustained gains in bone mineral density (BMD); BMD rises over the first ~12–18 months (filling/secondary mineralisation of the remodeling space) then plateaus (G&G 14e Ch.52, p.1064; Golan 4e Ch.32, p.590).
• Contrast with anabolic agents (teriparatide, abaloparatide, romosozumab) that build new bone — relevant when the patient has already lost a large amount of bone or has had fragility fractures (Golan 4e Ch.32, p.595; Katzung 16e Ch.42, p.819).