A 66-year-old postmenopausal woman comes to the office to discuss her bone densitometry results. She has a history of hypertension and has smoked a pack of cigarettes daily for 30 years. BMI is 20.1 kg/m². Physical examination is unremarkable. Bone densitometry reveals low bone density consistent with osteoporosis. The patient is prescribed risedronate. Repeat bone densitometry 2 years later reveals no further loss of bone mineral density. Which of the following mechanisms most likely explains the drug's effect on bone mineral density?

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11ec160b_3c80_d480_9249_3b7aa9f7ba44_MD0001_00 Bisphosphonates (eg, alendronate, risedronate) treat osteoporosis by inhibiting osteoclast-mediated bone resorption. They have a chemical structure similar to that of pyrophosphate and attach to hydroxyapatite binding sites on bony surfaces. Osteoclasts that resorb the bone take up the bisphosphonate and are unable to adhere to the bony surface to continue resorption. Bisphosphonates also decrease osteoclast proton production, induce osteoclast apoptosis, and decrease development/recruitment of osteoclast precursor cells. The net result is to slow the rate of bone loss, and some patients may experience a small increase in bone mineral density. (Choice A) Sclerostin is a glycoprotein produced by osteocytes that inhibits osteoblast bone formation. Monoclonal antibody preparations (eg, romosozumab) that bind sclerostin reverse this effect and facilitate increased osteoblast activity. (Choice B) Denosumab is a monoclonal antibody that decreases bone resorption by binding to the receptor activator of nuclear factor kappa-B ligand (RANK-L) and blocking the interaction between RANK-L and RANK (a receptor located on osteoclast surfaces), which is required for preosteoclast maturation to osteoclasts. (Choices C, D, and F) Teriparatide is a recombinant formulation identical to the 34-amino-acid sequence at the N-terminal portion of endogenous parathyroid hormone (PTH). Similar to PTH, teriparatide stimulates maturation of preosteoblasts into bone-forming osteoblasts that lay down collagen and eventually mineralize the matrix. Teriparatide also increases gastrointestinal calcium absorption and renal tubular calcium reabsorption, which leads to decreased urinary calcium excretion. Educational objective: Bisphosphonates have a chemical structure similar to that of pyrophosphate and attach to hydroxyapatite binding sites on bony surfaces to inhibit bone resorption by osteoclasts.

A 66-Year-Old Postmenopausal Woman Comes to the Office to Discuss