Bisphosphonates and primary hyperparathyroidism.
Bisphosphonates (BP) are pyrophosphate analogs that include very potent inhibitors of bone resorption. BPs act directly on the osteoclast, suppressing isoprenylation by inhibiting farnesyl diphosphate synthase in the cholesterol pathway, which causes osteoclast inactivation. BPs should therefore reduce the bone loss produced by any cause, including hyperparathyroidism and hypercalcemia of malignancy (MIH), caused by parathyroid hormone (PTH) and PTH-related protein (PTHrP), respectively. BPs at higher doses than used in osteoporosis are indeed the treatment of choice for malignancy-induced hypercalcemia. Limited, but convincing, data show that BPs at doses effective in osteoporosis also reverse bone loss associated with mild primary hyperparathyroidism (PHPT).
Rodan
Gideon A
GA
Department of Bone Biology and Osteoporosis Research, Merck & Co., West Point, Pennsylvania 19846, USA.
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy*; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D051228:Geranyltranstransferase; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000209:etiology; D006961:Hyperparathyroidism / Q000150:complications / Q000188:drug therapy*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy; D010281:Parathyroid Hormone / Q000502:physiology; D044162:Parathyroid Hormone-Related Protein; D010282:Parathyroid Neoplasms / Q000188:drug therapy*; D036361:Peptide Hormones / Q000037:antagonists & inhibitors / Q000378:metabolism
D004164:Diphosphonates; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones; D019883:Alkyl and Aryl Transferases; D051228:Geranyltranstransferase