What are the treatment options for osteoporosis?

Treatment Options for Osteoporosis

Bisphosphonates (alendronate, risedronate, or zoledronic acid) are the first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men, with strong evidence for reducing hip, vertebral, and nonvertebral fractures. 1, 2

First-Line Treatment: Oral Bisphosphonates

• Prescribe generic oral bisphosphonates (alendronate 70 mg once weekly or risedronate) as initial therapy for all patients with osteoporosis unless contraindications exist. 1, 2, 3
• Oral bisphosphonates reduce vertebral fractures by 52 per 1000 person-years, hip fractures by 6 per 1000 person-years, and significantly reduce nonvertebral fractures. 3
• Alendronate works by binding to bone hydroxyapatite and inhibiting osteoclast activity, reducing bone resorption without directly affecting bone formation. 4
• Generic formulations should always be prescribed over brand-name medications due to significantly lower cost with equivalent efficacy. 1, 2
• Once-weekly dosing (alendronate 70 mg) is therapeutically equivalent to daily dosing and improves adherence. 3, 5

Administration Requirements for Oral Bisphosphonates

• Must be taken in the fasting state with water at least 30 minutes before consuming any food or beverages. 5
• Patients should remain upright for at least 30 minutes after administration to prevent esophageal irritation. 4

Treatment Duration and Drug Holidays

• Treat with bisphosphonates for 5 years initially, then reassess fracture risk to determine whether to continue or take a drug holiday. 1, 2, 3
• After 5 years, if moderate-to-high fracture risk persists (T-score ≤-2.5, prior fracture, or high FRAX scores), continue treatment for 7-10 years total. 3
• Patients at lower risk after 5 years can discontinue treatment temporarily (drug holiday). 1, 3
• Do not perform bone density monitoring during the initial 5-year treatment period. 1, 2
• Increasing bisphosphonate duration beyond 5 years probably reduces vertebral fractures but not other fractures, with increased risk of long-term harms. 1

Second-Line Treatment: Denosumab

• Denosumab 60 mg subcutaneously every 6 months is recommended as second-line therapy for patients with contraindications to bisphosphonates or who experience adverse effects. 1, 2, 3
• Denosumab reduces vertebral and nonvertebral fractures with moderate-certainty evidence in women and low-certainty evidence in men. 1, 2
• Critical warning: Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures; patients MUST transition to bisphosphonate therapy after stopping denosumab. 2, 3, 6
• Do not stop, skip, or delay denosumab doses without first transitioning to another antiresorptive agent. 6

Denosumab Safety Concerns

• Serious infections (skin, abdomen, bladder, ear, endocarditis) may occur more frequently. 6
• Severe jaw bone problems (osteonecrosis) can develop; dental examination should be performed before starting treatment. 6
• Unusual thigh bone fractures may occur. 6
• Hypocalcemia risk—correct low calcium before initiating treatment. 6

Very High-Risk Patients: Anabolic Agents First

For patients at very high risk for fracture, initiate anabolic agents (teriparatide, abaloparatide, or romosozumab) BEFORE bisphosphonates, followed by mandatory transition to antiresorptive therapy. 2, 3

Defining Very High Risk

• Age >74 years 2, 3
• Recent fracture within 12 months 2, 3
• Multiple prior osteoporotic fractures 2, 3
• T-score ≤-3.0 2, 3
• Fractures despite ongoing bisphosphonate therapy 2, 3
• High FRAX scores (10-year risk of major osteoporotic fracture ≥20% or hip fracture ≥3%) 2

Anabolic Agent Options

• Teriparatide reduces vertebral fractures by 69 per 1000 patients and any clinical fractures by 27 per 1000 patients. 2, 3
• Teriparatide is indicated for postmenopausal women and men with osteoporosis at high risk for fracture who have failed or are intolerant to other therapies. 7
• Abaloparatide is supported by the strongest BMD data for men with osteoporosis at very high risk. 3
• Romosozumab is conditionally recommended for very high-risk postmenopausal women, limited to 12 monthly doses due to waning anabolic effect. 2, 3
• Anabolic agents must be limited to 2 years maximum, then MUST be followed by antiresorptive therapy (bisphosphonate or denosumab) to maintain bone gains. 1, 3
• Failure to transition to antiresorptive therapy after anabolic agents results in serious risk for rebound and multiple vertebral fractures. 1

Essential Adjunctive Measures for ALL Patients

Every patient with osteoporosis requires the following non-pharmacologic interventions regardless of medication choice: 2, 3

• Calcium 1000-1200 mg daily 2, 3
• Vitamin D 800-1000 IU daily (target serum level ≥20 ng/mL) 2, 3
• Weight-bearing and muscle resistance exercises 2, 3
• Balance exercises and fall prevention counseling 2, 3
• Smoking cessation 2, 3
• Alcohol reduction (avoid excessive intake) 2, 3

Glucocorticoid-Induced Osteoporosis

• For patients on ≥2.5 mg/day of glucocorticoids for >3 months, perform fracture risk assessment within 6 months of starting therapy. 3
• Oral bisphosphonates are strongly recommended for patients at high or very high fracture risk. 3
• Anabolic agents (teriparatide) are conditionally recommended over antiresorptive agents for very high fracture risk. 3
• Teriparatide is FDA-approved for men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture. 7

Common Adverse Effects and Monitoring

Bisphosphonates

• Mild upper GI symptoms (most common) 1
• Rare but serious: atypical subtrochanteric fractures, osteonecrosis of the jaw 1
• Asymptomatic reductions in serum calcium (approximately 2%) and phosphate (approximately 4-6%) 4
• Assess for medication side effects at each visit, including rare complications. 3

Monitoring Recommendations

• Biochemical markers of bone turnover are appropriate tools to assess adherence to anti-resorptive therapy. 3
• BMD testing should be performed every 1-2 years until stable, then every 2-3 years (except during initial 5-year bisphosphonate treatment). 3
• Reassess fracture risk at 5 years to determine continuation versus drug holiday. 2

Special Considerations for Men

• The same treatment algorithm applies to men as to postmenopausal women, with oral bisphosphonates as first-line and denosumab as second-line therapy. 1, 3
• Bisphosphonates are approved for men with primary osteoporosis based on improvement in bone mineral density. 1
• Denosumab is approved for men with secondary osteoporosis based on reduction in vertebral fractures. 1
• Assess serum total testosterone as part of pre-treatment evaluation. 3
• Consider appropriate hormone replacement therapy in men with low levels of total or free serum testosterone. 3

Treatments NOT Recommended

Do NOT use menopausal estrogen therapy, menopausal estrogen plus progestogen therapy, or raloxifene for the treatment of osteoporosis in women. 1

• Estrogen therapy is associated with increased risk for cerebrovascular accidents, venous thromboembolic events, and breast cancer. 1
• Raloxifene increases risk for cardiovascular events, thromboembolic events, pulmonary embolism, and cerebrovascular death. 1