A 60-year-old man comes to the office for follow-up after a recent emergency department visit due to cough. The patient was diagnosed with acute bronchitis and the symptoms resolved with symptomatic treatment. A chest x-ray obtained during that visit revealed no lung abnormalities, but the bones appeared osteopenic. The patient reports no bone pain and has had no fractures. He has a history of prostate cancer treated with radiation therapy and is taking leuprolide. The patient has no other medical problems and has no known drug allergies. He drinks a glass of wine daily and does not use tobacco or illicit drugs. He eats a balanced diet and exercises regularly. Blood pressure is 120/80 mm Hg and pulse is 80/min. Physical examination shows no abnormalities. A dual-energy x-ray absorptiometry (DXA) scan shows low bone mineral density. Which of the following is the most likely underlying mechanism of the observed finding in this patient?

Question

A 60-year-old man comes to the office for follow-up after a recent emergency department visit due to cough.  The patient was diagnosed with acute bronchitis and the symptoms resolved with symptomatic treatment.  A chest x-ray obtained during that visit revealed no lung abnormalities, but the bones appeared osteopenic.  The patient reports no bone pain and has had no fractures.  He has a history of prostate cancer treated with radiation therapy and is taking leuprolide.  The patient has no other medical problems and has no known drug allergies.  He drinks a glass of wine daily and does not use tobacco or illicit drugs.  He eats a balanced diet and exercises regularly.  Blood pressure is 120/80 mm Hg and pulse is 80/min.  Physical examination shows no abnormalities.  A dual-energy x-ray absorptiometry (DXA) scan shows low bone mineral density.  Which of the following is the most likely underlying mechanism of the observed finding in this patient?

Quizplus · Accepted Answer

11ec160b_3bc1_f20a_9249_4b933ddcdd5d_MD0001_00 Leuprolide is a GnRH analog used to suppress testosterone levels in the treatment of prostate cancer. When administered in a pulsatile fashion, leuprolide has agonist properties; however, long-term leuprolide use results in a continuous GnRH effect (also seen with GnRH infusion) that leads to the downregulation of GnRH receptors on gonadotropin cells in the pituitary gland. This suppresses pituitary LH release and leads to the reduced production of testosterone by Leydig cells. The lower levels of circulating testosterone produce a clinical effect similar to that of surgical orchiectomy. Hypogonadism can lead to accelerated bone loss and increased risk for osteoporosis. In male patients, androgens are aromatized to estrogens, which play a large role in bone homeostasis, largely by inhibiting osteoclast-driven cortical bone resorption. Androgens also act on osteoblasts and osteocytes in trabecular (sometimes called cancellous or spongy) bone to preserve bone density. (Choice B) Glucocorticoids (eg, prednisone) and proton pump inhibitors (eg, omeprazole) are associated with an increased risk of osteoporosis, at least partly due to the decreased intestinal absorption of calcium. GnRH analogs have little effect on intestinal calcium absorption. (Choices C and D) Elevated parathyroid hormone (PTH) levels stimulate osteoclast activity and release of calcium from bone, increasing the risk of osteoporosis. Similarly, low vitamin D concentrations lead to impaired calcium absorption with a compensatory increase in PTH. Conversion of 25-hydroxyvitamin D (ie, 25-hydroxycholecalciferol) to its active form, 1,25-dihydroxyvitamin D, by 1-alpha-hydroxylase (stimulated by PTH) occurs in the kidneys; this is one of the reasons that patients with chronic kidney disease are at increased risk of osteoporosis. However, this patient does not have a history of chronic kidney disease or hyperparathyroidism, and the vitamin D-PTH axis is not significantly influenced by leuprolide use. (Choice E) Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome due to release of PTH-related protein (PTHrP) by malignant cells. PTHrP is structurally similar to PTH and acts on the PTH-1 receptor. HHM is most commonly seen in squamous cell carcinoma (eg, lung), transitional cell carcinomas, and breast and ovarian cancers. It typically presents with severe, symptomatic hypercalcemia (eg, constipation, lethargy) rather than osteoporosis. Educational objective: Long-term use of GnRH agonists (eg, leuprolide) suppresses pituitary LH release and leads to the reduced production of testosterone. The lower levels of circulating testosterone produce a clinical effect similar to that of surgical orchiectomy and can lead to accelerated bone loss and increased risk for osteoporosis. __________ References: Bone health management in prostate cancer patients receiving androgen deprivation therapy. (http://www.ncbi.nlm.nih.gov/pubmed/21807761)

A 60-Year-Old Man Comes to the Office for Follow-Up After