A 46-year-old woman comes to the clinic to establish primary care as a new patient. She is a marathon runner but has been unable to train due to a vertebral stress fracture diagnosed via x-ray during a recent emergency department visit. She has a history of hypothyroidism for which she takes levothyroxine. The patient's last menstrual period was a year ago. Her diet consists mainly of vegetables and fruit, and she takes a daily multivitamin. Her mother died of breast cancer at age 52. The patient is concerned that her family history puts her at risk for breast cancer. X-ray absorptiometry studies demonstrate abnormally low bone density in the lumbar vertebrae. Which of the following drugs is the most appropriate option for decreasing the risk of both bone fractures and breast cancer in this patient?

Question

A 46-year-old woman comes to the clinic to establish primary care as a new patient.  She is a marathon runner but has been unable to train due to a vertebral stress fracture diagnosed via x-ray during a recent emergency department visit.  She has a history of hypothyroidism for which she takes levothyroxine.  The patient's last menstrual period was a year ago.  Her diet consists mainly of vegetables and fruit, and she takes a daily multivitamin.  Her mother died of breast cancer at age 52.  The patient is concerned that her family history puts her at risk for breast cancer.  X-ray absorptiometry studies demonstrate abnormally low bone density in the lumbar vertebrae.  Which of the following drugs is the most appropriate option for decreasing the risk of both bone fractures and breast cancer in this patient?

Quizplus · Accepted Answer

11ec160b_3c7f_9bfe_9249_bbe2cfef706d_MD0001_00 This patient has amenorrhea and low bone density, suggesting a low-estrogen state. This may be due to menopause, although her exercise history suggests possible hypothalamic amenorrhea (excessive exercise suppresses secretion of GnRH, leading to decreased release of FSH and low estrogen levels). Because estrogen decreases bone resorption, estrogen deficiency in women increases the risk for osteoporosis. Although estrogen replacement therapy (eg, ethinyl estradiol) can mitigate this risk, it can increase the risk of breast cancer and should be avoided in patients with a family history of breast cancer (Choice B). In addition, unopposed estrogen (ie, without concurrent progesterone) can cause endometrial proliferation resulting in endometrial hyperplasia and cancer. Selective estrogen receptor modulators (eg, raloxifene, tamoxifen) are nonsteroidal compounds that bind estrogen receptors and exhibit antagonist and agonist properties in a tissue-specific manner. Raloxifene has estrogen agonist activity on bone, which decreases bone resorption, improves bone density, and decreases the risk of vertebral fractures. In addition, raloxifene has an estrogen antagonist effect on breast tissue and can decrease the risk of breast cancer. It also acts as an estrogen antagonist in the uterus and does not increase the risk of endometrial cancer. Tamoxifen is a selective estrogen receptor modulator that has strong estrogen antagonist activity in the breast and is used in the treatment of estrogen receptor-positive breast cancer. It has estrogen-like effects on bone and can reduce the risk of osteoporosis in postmenopausal women. However, its agonist activity on the uterus increases the risk of endometrial hyperplasia/cancer and it is not appropriate for routine use in osteoporosis (Choice F). (Choice A) Bisphosphonates (eg, alendronate) inhibit osteoclast-mediated bone resorption. They have no estrogen agonist or antagonist activity and do not lower the risk of breast cancer. (Choice C) Leuprolide is a GnRH analog that stimulates FSH and LH release (and subsequent estrogen production) when administered in a pulsatile manner (eg, via a programmable pump for treatment of anovulation) but suppresses release when administered continuously (eg, for endometriosis). Continuous use may reduce breast cancer risk but is associated with accelerated bone loss. (Choice D) Medroxyprogesterone reduces the incidence of endometrial hyperplasia and endometrial carcinoma in postmenopausal women on estrogen replacement therapy, but otherwise has no benefit in management of osteoporosis. In addition, long-term use of medroxyprogesterone alone is associated with increased bone loss. Educational objective: Selective estrogen receptor modulators exhibit estrogen antagonist and agonist properties in a tissue-specific manner. Raloxifene has estrogen agonist activity on bone, which decreases bone resorption and improves bone density. Raloxifene has an estrogen antagonist effect on breast tissue and can decrease the risk of breast cancer; it also acts as an estrogen antagonist in the uterus, and does not increase the risk of endometrial cancer. __________ References: Selective estrogen receptor modulators: tissue specificity and clinical utility. (http://www.ncbi.nlm.nih.gov/pubmed/25210448)

A 46-Year-Old Woman Comes to the Clinic to Establish Primary