What are the treatment options for osteoporosis?

Osteoporosis Treatment

First-Line Pharmacologic Treatment

For postmenopausal women with osteoporosis, clinicians should prescribe oral bisphosphonates (alendronate or risedronate) as initial therapy to reduce hip and vertebral fractures. 1 These agents have the strongest evidence for fracture reduction, favorable safety profiles, and are cost-effective compared to other options. 2

Bisphosphonate Specifics

• Alendronate, risedronate, and zoledronic acid all reduce vertebral, nonvertebral, and hip fractures in postmenopausal women with established osteoporosis. 1
• Weekly dosing (alendronate 70 mg once weekly) is as effective as daily dosing and improves adherence. 2, 3
• Intravenous zoledronic acid can be administered annually for patients unable to tolerate oral bisphosphonates. 1
• Bisphosphonates must be taken with specific instructions: on an empty stomach with plain water, remaining upright for at least 30 minutes, to minimize upper GI adverse effects. 4, 3

Treatment Duration

• Treat for 5 years initially, then reassess fracture risk to determine if continuation is warranted. 1
• Consider a drug holiday after 5 years for patients at lower fracture risk, as prolonged use (>5 years) increases risk of atypical femoral fractures and osteonecrosis of the jaw. 2, 5
• Patients at very high risk (prior hip or vertebral fracture, very low BMD) may benefit from continued therapy beyond 5 years. 1

Second-Line Treatment

Denosumab (60 mg subcutaneously every 6 months) should be used for patients with contraindications to or adverse effects from bisphosphonates. 1 Denosumab reduces vertebral, nonvertebral, and hip fractures. 1

Critical Denosumab Considerations

• Never discontinue denosumab without transitioning to another antiresorptive agent, as this causes rapid bone loss and dramatically increased risk of multiple vertebral fractures. 5, 6
• Denosumab increases infection risk, particularly skin infections and potentially endocarditis. 6
• Monitor for hypocalcemia, especially in patients with renal impairment or vitamin D deficiency. 6

Anabolic Agents for Severe Osteoporosis

Teriparatide or romosozumab should be considered first-line for patients at very high fracture risk (prior hip or vertebral fracture, multiple fractures, T-score <-3.0, or fracture on therapy). 1, 5

Anabolic Agent Protocol

• Teriparatide (20 mcg subcutaneously daily) reduces vertebral and nonvertebral fractures and is FDA-approved for high-risk postmenopausal women, men with osteoporosis, and glucocorticoid-induced osteoporosis. 7
• Limit anabolic therapy to 2 years maximum. 5
• Mandatory sequential therapy: After completing anabolic treatment, immediately transition to bisphosphonate or denosumab to maintain bone gains, as discontinuation without antiresorptive therapy results in rapid bone loss. 1, 5, 7

Treatment for Men

Bisphosphonates are first-line treatment for men with primary osteoporosis, with similar efficacy to women despite less robust trial data. 1

• Denosumab is second-line for men with contraindications to or intolerance of bisphosphonates. 1
• The same fracture risk thresholds and treatment algorithms apply to men as to postmenopausal women. 1

Glucocorticoid-Induced Osteoporosis

Oral bisphosphonates are first-line for patients on ≥2.5 mg/day prednisone (or equivalent) for ≥3 months who are at high fracture risk. 5

• Initiate fracture risk assessment within 6 months of starting glucocorticoid therapy. 5
• Teriparatide is FDA-approved for glucocorticoid-induced osteoporosis in high-risk patients. 7

Agents NOT Recommended

Do not use menopausal estrogen therapy, estrogen plus progestogen, or raloxifene for osteoporosis treatment due to unfavorable risk-benefit profiles. 1

• Estrogen therapy increases risk of stroke, venous thromboembolism, and breast cancer. 1
• Raloxifene increases cardiovascular events, thromboembolic events, pulmonary embolism, and cerebrovascular death. 1
• These agents may reduce vertebral fractures but lack hip fracture reduction data and carry significant harms. 1

Essential Adjunctive Measures

All patients require adequate calcium (1000-1200 mg daily) and vitamin D (600-800 IU daily, targeting serum level ≥20 ng/mL). 2, 5

• Weight-bearing exercise, muscle strengthening, and balance training reduce fracture risk. 2
• Fall prevention strategies including vision/hearing assessment, medication review for sedating drugs, and home safety evaluation are mandatory. 2
• Smoking cessation and limiting alcohol are strongly advised. 2

Monitoring Strategy

Do not monitor bone density during the initial 5-year treatment period, as BMD changes do not predict fracture reduction and frequent monitoring is not cost-effective. 1

• After 5 years, reassess fracture risk clinically (new fractures, height loss) to guide continuation decisions. 1
• Monitor for medication adherence and adverse effects at each visit. 5
• For patients on glucocorticoids or with cancer, consider BMD monitoring every 12-24 months. 2

Medication Selection Priorities

Prescribe generic bisphosphonates whenever possible to improve affordability and adherence. 1, 2

• Alendronate and risedronate are available as generics and equally effective. 2
• Brand-name medications should only be used when generic alternatives are contraindicated or not tolerated. 1

Common Pitfalls to Avoid

• Never stop bisphosphonates abruptly without reassessing fracture risk, as this increases vertebral fracture risk. 1
• Never discontinue denosumab without sequential antiresorptive therapy—this is the most critical error, causing rebound fractures. 5, 6
• Do not prescribe anabolic agents without planning sequential antiresorptive therapy. 1, 5
• Ensure patients understand proper bisphosphonate administration technique to minimize GI adverse effects. 4, 3
• Screen for and correct hypocalcemia and vitamin D deficiency before initiating denosumab or bisphosphonates. 6