What is the treatment for osteoporosis?

Treatment for Osteoporosis

Bisphosphonates (alendronate, risedronate, or zoledronic acid) are the first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men, with treatment duration of 5 years before reassessing fracture risk. 1, 2

First-Line Treatment: Bisphosphonates

• Prescribe oral bisphosphonates (alendronate or risedronate) or intravenous zoledronic acid as initial therapy for all patients with osteoporosis. 2
• Generic formulations should be prescribed whenever possible due to significantly lower cost with equivalent efficacy. 1, 2
• Bisphosphonates reduce hip, vertebral, and nonvertebral fractures with high-certainty evidence. 2
• Treat for exactly 5 years, then stop and reassess fracture risk to determine whether to continue or take a drug holiday. 1, 2

Administration Guidelines for Oral Bisphosphonates

• Take with a full glass of water (6-8 ounces), remain upright for at least 30 minutes, and avoid food/drink during this period to minimize esophageal risk. 3
• Ensure adequate calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) intake throughout treatment. 1, 2
• Correct vitamin D deficiency prior to bisphosphonate initiation, particularly for IV therapy. 4

Second-Line Treatment: Denosumab

• Use denosumab 60 mg subcutaneously every 6 months only as second-line therapy for patients with contraindications to bisphosphonates or who experience adverse effects. 1, 2
• This recommendation applies to both men (low-certainty evidence) and women (moderate-certainty evidence). 1, 2
• Critical warning: Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as rebound bone loss and multiple vertebral fractures will occur. 1, 2, 4

Very High-Risk Patients: Anabolic Agents First

For patients at very high fracture risk, initiate anabolic agents (teriparatide or romosozumab) before bisphosphonates, followed by mandatory transition to bisphosphonates or denosumab. 2

Defining Very High Risk

Very high risk includes patients with: 2

• Age >74 years
• Recent fracture within 12 months
• Multiple prior osteoporotic fractures
• T-score ≤-3.0
• Fractures occurring despite ongoing bisphosphonate therapy
• Significant bone loss (≥10% per year) despite bisphosphonate therapy

Anabolic Agent Options

• Teriparatide reduces vertebral fractures by 69 per 1000 patients and any clinical fractures by 27 per 1000 patients. 2
• Teriparatide is indicated for postmenopausal women and men with primary or hypogonadal osteoporosis at high risk for fracture. 5
• Inject 20 micrograms once daily subcutaneously in the thigh or abdomen for up to 2 years. 5
• Romosozumab is conditionally recommended for very high-risk postmenopausal women only, limited to 12 monthly doses due to waning anabolic effect. 2
• After discontinuing any anabolic agent, immediately transition to bisphosphonates or denosumab to preserve gains and prevent serious rebound vertebral fractures. 1, 2

Essential Adjunctive Measures for ALL Patients

Every patient requires the following non-pharmacologic interventions: 2

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

Treatment Duration and Drug Holidays

• Stop bisphosphonate treatment after 5 years unless the patient has strong indication for continuation (previous hip or vertebral fractures, multiple non-spine fractures, or hip BMD T-score ≤-2.5). 1, 2, 4
• Extending bisphosphonate therapy beyond 5 years reduces vertebral fractures but not other fractures, while increasing risk for long-term harms including osteonecrosis of the jaw (incidence <1 per 100,000 person-years) and atypical femoral fractures (3.0-9.8 per 100,000 person-years). 1, 4
• The decision for drug holiday should be individualized based on baseline fracture risk, medication type and half-life, and benefits versus harms. 1
• Do NOT perform routine BMD monitoring during the initial 5-year treatment period, as fracture reduction occurs even without BMD increases. 2, 4

Common Pitfalls to Avoid

• Never switch to denosumab after bisphosphonates unless the patient has contraindications or adverse effects from bisphosphonates. 1, 2
• Ensure all dental work is completed before initiating or continuing bisphosphonate therapy to reduce osteonecrosis of the jaw risk. 4
• Do not automatically continue bisphosphonates beyond 5 years without reassessing fracture risk. 1, 4
• Never discontinue denosumab without bridging to bisphosphonates within 6 months. 2, 4
• Do not use anabolic agents as first-line therapy except in very high-risk patients. 2

Special Populations

Men with Primary Osteoporosis

• The same first-line (bisphosphonates) and second-line (denosumab) treatments apply to men as to postmenopausal women, though evidence is extrapolated from female trials with downgraded certainty. 1

Glucocorticoid-Induced Osteoporosis

• Teriparatide is indicated for men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to ≥5 mg prednisone) at high risk for fracture. 5
• Bisphosphonates remain first-line unless very high risk criteria are met. 2