Pharmacotherapy Recommendations for Osteoporosis Prevention and Treatment

Key Takeaways

• Bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid), raloxifene, nasal calcitonin, and denosumab are approved for osteoporosis prevention in women, but no drugs are currently approved for prevention in men.
• Approved treatments for osteoporosis in men include 3 bisphosphonates (alendronate, risedronate, zoledronic acid), denosumab, and teriparatide.
• There are many considerations in choosing appropriate therapy. For a patient at very high risk of fracture, beginning with one of the anabolic agents, followed by an antiresorptive drug, may be ideal.

Maintaining healthy bones is a lifelong pursuit that requires attention to healthy lifestyle and good nutrition, especially adequate intake of calcium, vitamin D, and protein. For individuals at high risk of falls, interventions to reduce that risk should be implemented.

Pharmacologic therapy can be used prevent and treat osteoporosis, with the ultimate goal of preventing fractures. The decision to initiate pharmacologic therapy should be based on fracture risk assessment plus other factors, including patient preference, expected adherence to therapy, and cost. Fracture risk is estimated with consideration of bone mineral density, age, prior fracture, and other clinical risk factors, many of which are incorporated in the Fracture Risk Assessment Tool (FRAX).

Some postmenopausal women who do not have osteoporosis or high fracture risk (T-score >-2.5, no fracture, FRAX 10-year probability of major osteoporotic fracture <20%, and hip fracture <3%) are interested in prevention of osteoporosis before fracture risk becomes high. Drugs approved for prevention of postmenopausal osteoporosis are estrogen, raloxifene, estrogen/bazedoxifene, alendronate, risedronate, ibandronate, and zoledronic acid.

Other postmenopausal women prefer to manage with nonpharmacologic therapy until fracture risk is high according to a T-score ≤-2.5 or high fracture probability by FRAX, or a fracture has occurred. For these women, the approved drugs are the 4 bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid), raloxifene, nasal calcitonin (rarely used), and denosumab. The anabolic drugs (teriparatide, abaloparatide, romosozumab) are typically used when fracture risk is very high (eg, very low T-score; prior fracture, especially a recent one; multiple fractures).

For men with osteoporosis, there are 3 approved bisphosphonates (alendronate, risedronate, zoledronic acid), denosumab, and teriparatide. All of these are effective whether the man is eugonadal or hypogonadal. There are no approved drugs for prevention of osteoporosis in men.

Glucocorticoid-induced osteoporosis (GIO) is a special category of treatment that applies to women and men. Risedronate and zoledronic acid are approved for prevention and treatment of GIO, whereas alendronate, denosumab, and teriparatide are approved only for treatment of GIO.

Once it has been decided that pharmacologic treatment is indicated and the patient is willing to start treatment, the next decision is to select which of these many options is best. Patient comorbidities should be considered (eg, oral bisphosphonates should not be given to a patient with esophageal stricture, and teriparatide/abaloparatide should not be given when there is a history of radiation therapy to the skeleton). Past experience is important—with a history of a systemic adverse reaction to a bisphosphonate, a nonbisphosphonate such as denosumab might be a good choice. If cost is the main concern, a generic oral bisphosphonate such as alendronate might be used. For a patient at very high risk of fracture, beginning with one of the anabolic agents, to be followed by an antiresorptive drug, may be ideal.

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