Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 54-year-old woman comes to the office for advice regarding maintaining bone health. She has no history of fracture. The patient recently had a lumpectomy and radiation therapy to treat breast cancer, is currently taking tamoxifen, and will begin taking an aromatase inhibitor in 2 months. She underwent menopause at age 52 years and has persistent hot flushes. Her risk factors for osteoporosis include a slim body habitus and a mother who had a hip fracture at age 67 years.

Physical examination findings, including vital signs, are normal. BMI is 20. Results of routine laboratory studies are normal.

A dual-energy x-ray absorptiometry scan shows T-scores of −2.1 in the lumbar spine, −2.3 in the femoral neck, and −1.9 in the total hip. Her Fracture Risk Assessment Tool (FRAX) score indicates a 22% risk of major osteoporotic fracture and a 2.4% risk of hip fracture over the next 10 years. Optimal calcium and vitamin D supplementation is recommended, and she is encouraged to begin weight-bearing exercise as tolerated.

Which of the following pharmacologic agents can be started in this patient?

A: Alendronate
B: Denosumab
C: Estrogen
D: Raloxifene
E: Teriparatide

MKSAP Answer and Critique

The correct answer is A: Alendronate.

The most appropriate medication for this patient is alendronate. She has osteopenia, and her major osteoporotic fracture risk by the Fracture Risk Assessment Tool (FRAX) is in a range for which the National Osteoporosis Foundation (NOF) guidelines favor treatment with antiosteoporotic therapy. The NOF recommends antiosteoporotic therapy for persons whose risk of major osteoporotic fracture over the next 10 years is 20% or greater or whose risk of hip fracture over the next 10 years is 3% or greater. Given her current FRAX score and the expectation that she will lose bone mass more rapidly after an aromatase inhibitor is started, it is reasonable to initiate therapy with alendronate now. Alendronate is approved for both osteoporosis prevention and treatment by the FDA.

Denosumab, a monoclonal antibody that inhibits osteoclast formation, is reserved for patients with a high risk of fracture, including those with multiple risk factors for fracture or a history of previous fractures. This patient does not fulfill these criteria.

Estrogen is contradicted in this patient with a new diagnosis of breast cancer.

Raloxifene, a selective estrogen receptor modulator, is also approved for osteoporosis prevention by the FDA. However, vasomotor symptoms are highly associated with its use, and it may not be well tolerated in a patient already experiencing significant hot flushes.

Teriparatide, or recombinant human parathyroid hormone (1-34), is an anabolic agent that increases bone density and decreases fracture risk. However, teriparatide carries a “black box” warning because of an increased risk of osteosarcoma and is contraindicated in this patient because of her history of radiation therapy, which increases the risk of osteosarcoma. Teriparatide is also contraindicated in persons with malignancy involving bone, Paget disease, or existing hyperparathyroidism or hypercalcemia.

Key Point

• In a patient with osteopenia and a history of radiation therapy, alendronate is the most appropriate drug to use for osteoporosis prevention.

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