Table.

Medications Licensed in the United States for Treatment of Osteoporosis

Drug Name (Class)	Route; Frequency	Types of Fractures Examined in Randomized Clinical Trials at Long-Term Follow-up (>36 mo)				Average Annual Medicare Spending Per Beneficiary in 2019	FDAWarning
		Hip	Clinical Vertebral	Any Clinical	Radiographic Vertebral
Antiresorptive drugs
Alendronate (bisphosphonate)*†‡	By mouth (tablet or solution); once a day (10 mg) or once a week (70 mg)§	Yes	No	Yes	Yes	$793-$1306 (brand-name); $39 (generic)	Upper gastrointestinal irritation; osteonecrosis of the jaw; atypical femur fractures; severe bone, joint, and muscle pain
Risedronate (bisphosphonate)*†‡	By mouth; once a day, once a week, or 2 dir a row once per month§	Yes	No	No	Yes	$2036-$2732 (brand-name); $604 (generic)	Upper gastrointestinal irritation; osteonecrosis of the jaw; atypical femur fractures; severe bone, joint, and muscle pain
Ibandronate (bisphosphonate)*‡	By mouth; once a month§	No	No	No	Yes	$1379 (brand-name); $220 (generic)	Upper gastrointestinal irritation; osteonecrosis of the jaw; atypical femur fractures; severe bone, joint, and muscle pain
Zoledronate (bisphosphonate)*†‡	Intravenous; once s year§	Yes	Yes	Yes	Yes	$855 (brand-name); $316-$987 (generic)	Osteonecrosisofthe jaw; atypical femur fractures; severe bone, joint, and muscle pain
Denosumab (RANK ligand inhibitor)†∥	By injection (subcutane-ous); every 6 mo¶	Yes	Yes	Yes	Yes	$1913-$12 241 (brand-name)	Dermatologic reactions and serious infection, including skin infections; suppression of bone turnover contributing to adverse outcomes, such as osteonecrosis ofthe jaw, atypical fractures, and delayed fracture healing
Anabolic drugs
Abaloparatide (parathyroid hormone-related protein)∥	By injection (subcutaneous); once a day	No	No	Yes**	Yes**	$9873 (brand-name)	Hereditary osteosarcoma disorders††
Teriparatide (recombinant human parathyroid hormone)∥‡‡	By injection (subcutaneous); once a day	Yes**	Yes**	Yes**	Yes**	$22 156 (brand-name)	Hereditary osteosarcoma disorders††
Romosozumab (sclerostin inhibitor)∥	By injection (subcutaneous); once a month for 12 mo§§	No	Yes**	Yes**	Yes**	$5574 (brand-name)	Cardiovascular risk Stroke history or risk∥∥
Estrogen agonist on bones
Raloxifene (selective estrogen receptor modulator)*‡	By mouth; once a day	Yes	Yes	Yes	Yes	$1730 (brand-name); $593 (generic)	Stroke history or risk Thromboembolism history or risk¶¶

FDA = U.S. Food and Drug Administration; RANK = receptor activator of nuclear factor κB.

^*Indicated for treatment of osteoporosis in postmenopausal females.

^†Indicated for males. Bisphosphonates have been approved for males with primary osteoporosis based on improvement in bone mineral density, and denosumab is approved for males with secondary osteoporosis based on a reduction in risk for vertebral fractures (19).

^‡Indicated for the prevention of osteoporosis in postmenopausal females with low bone mass.

^§All patients receiving bisphosphonate therapy should have the need for continued therapy reevaluated periodically. Patients at low risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. Patients who discontinue therapy should have their risk for fracture reevaluated periodically.

^ǁIndicated for postmenopausal females with osteoporosis who are at high risk for fracture, defined as a history of osteoporotic fracture or multiple risk factors for fracture or patients who have failed or are intolerant to other available osteoporosis therapy.

^¶Denosumab discontinuation is associated with multiple vertebral fractures in some patients (20).

^**Short-term follow-up (12 to 36 months).

^††Dose-dependent increase in incidence of osteosarcoma in preclinical studies.

^‡‡Indicated for males; increase in bone mass in males with primary or hypogonadal osteoporosis who are at high risk for fracture.

^§§Use of romosozumab should be limited to 12 monthly doses because the anabolic effect wanes after 12 monthly doses (21).

^ǁǁThe analysis of the FDA Adverse Event Reporting System suggested higher risk for major adverse cardiovascular events associated with romosozumab (22). The current FDA safety warnings recommend avoiding use of romosozumab in patients with high risk for major cardiovascular events (21).

^¶¶Higher risk for venous thromboembolism and fatal stroke in females who have documented coronary heart disease or are at increased risk for major coronary events (23).