A 68-year-old woman presents to her primary care physician for her annual physical exam. Past medical history is significant for menopause at age 57. She does not take any medications. She does not smoke cigarettes or drink alcohol. , Lab work is all within normal limits. A bone mineral density test obtained prior to the appointment indicates a Z score of -2.6.
Which of the following describes the primary mechanism of action of the first-line agent to treat this patient’s osteoporosis?
B) Inhibition of osteoclast activity
This describes the mechanism of action of bisphosphonates such as alendronate, which decreases the rate of bone resorption. They are the preferred first line agent for the treatment of osteoporosis due to their efficacy, cost, and long-term safety data. Of note, they are not recommended for patients with esophageal disorders or chronic kidney disease.
Answer choice A: Antagonism of parathyroid hormone activity, is incorrect. This describes the primary mechanism of action of nasal calcitonin, which also directly inhibits osteoclastic bone resorption. It can be used to reduce pain from osteoporotic vertebral fractures and is indicated for osteoporosis only in patients who are more than 5 years post-menopause.
Answer choice C: Monoclonal antibody directed against RANKL, is incorrect. This describes the action of biologic agents such as denosumab. RANKL is a ligand secreted by osteoblasts that activates osteoclast precursors. Agents that target RANKL require close monitoring for hypocalcemia, particularly in patients with renal impairment.
Answer choice D: Parathyroid hormone receptor agonism, is incorrect. This describes the mechanism of teriparatide, a recombinant formulation of parathyroid hormone. Teriparatide promotes the physiologic activity of parathyroid hormone, including osteoblast stimulation, increased calcium absorption from the gastrointestinal tract, and increased calcium reabsorption from the renal tubules. Teriparatide and other ‘anabolic agents’ are sometimes preferred as initial pharmacotherapy for severe osteoporosis (Z score < -3 or < -2.5 with a fragility fracture).
Answer choice E: Selective estrogen receptor modulation, is incorrect. This describes the mechanism of action of raloxifene, which acts as an estrogen agonist in bone where it increases osteoblast activity and prevents bone loss. Raloxifene also antagonizes estrogen effects in breast and uterine tissues, thereby decreasing the risk of breast cancer. Selective estrogen receptor modulators (SERMs) are less effective than bisphosphonates in treating osteoporosis and are also accompanied by an increased risk of deep vein thrombosis.
Key Learning Point
Bisphosphonates are the preferred first-line agent for osteoporosis treatment and work via inhibition of osteoclast activity. They are not recommended in individuals with esophageal or kidney disease.
