What is the treatment for osteoporosis?

Treatment of Osteoporosis

Bisphosphonates 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: Bisphosphonates

• Prescribe oral bisphosphonates (alendronate or risedronate) or intravenous zoledronic acid as initial therapy for all patients with osteoporosis, regardless of sex. 1, 2, 3
• Generic formulations should be prescribed whenever possible due to significantly lower cost with equivalent efficacy. 1, 2
• Bisphosphonates work by binding to bone hydroxyapatite and specifically inhibiting osteoclast activity, reducing bone resorption by approximately 50-70% within 3-6 months. 4
• Treat for 5 years initially, then reassess fracture risk to determine whether to continue or take a drug holiday. 1, 2
• The decision for bisphosphonate discontinuation should be based on baseline fracture risk, medication type and half-life in bone, and risk of fracture during the drug holiday. 1

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, 3
• Critical warning: Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures—patients MUST transition to bisphosphonate therapy after stopping denosumab. 2, 3

Very High-Risk Patients: Anabolic Agents First

For patients at very high risk for fracture, initiate anabolic agents before bisphosphonates, followed by mandatory transition to bisphosphonates or denosumab. 2, 3

Very High Risk Criteria (any of the following):

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

Anabolic Agent Options:

• Teriparatide (FDA-approved): Reduces vertebral fractures by 69 per 1000 patients and any clinical fractures by 27 per 1000 patients. 2, 5
  • Indicated for postmenopausal women and men with primary or hypogonadal osteoporosis at high risk for fracture. 5
  • Inject 20 mcg subcutaneously once daily in the thigh or abdomen. 5
  • Black box warning: Caused osteosarcoma in rat studies; use should not exceed 2 years lifetime. 5
• Romosozumab: Conditionally recommended for very high-risk postmenopausal women, limited to 12 monthly doses due to waning anabolic effect. 2

Critical Transition Requirement:

• After discontinuing any anabolic agent, immediately transition to an antiresorptive agent (bisphosphonate or denosumab) to preserve bone density gains and prevent serious rebound vertebral fractures. 1, 2

Essential Adjunctive Measures for ALL Patients

Every patient with osteoporosis requires the following non-pharmacologic interventions: 1, 2

• Calcium: 1000-1200 mg daily 2, 3
• Vitamin D: 800-1000 IU daily, targeting serum level ≥20 ng/mL 2, 3
• Weight-bearing and muscle resistance exercises 1, 2
• Balance exercises and fall prevention counseling 1, 2
• Smoking cessation 2, 3
• Alcohol reduction 2, 3

Treatment Indications

Initiate pharmacologic treatment for: 2

• T-score ≤-2.5 on DEXA scan 2
• T-score between -1.0 and -2.5 with 10-year FRAX risk of major osteoporotic fracture ≥20% or hip fracture ≥3% 2
• Low-trauma fracture, even if DEXA does not indicate osteoporosis 2

Monitoring Strategy

• Do not perform bone density monitoring during the 5-year pharmacologic treatment period. 2
• Reassess fracture risk at 5 years to determine continuation versus drug holiday. 2

Special Populations

• Older adults (>65 years): Individualize treatment selection based on fall risk, polypharmacy, drug interactions, and comorbidities that increase fracture risk. 1
• Males with primary osteoporosis: Use the same first-line (bisphosphonates) and second-line (denosumab) treatments as postmenopausal women, though evidence is extrapolated from female studies. 1, 3
• Glucocorticoid-induced osteoporosis: Treat men and women on sustained systemic glucocorticoid therapy (≥5 mg prednisone daily equivalent) who are at high risk for fracture. 5, 4

Common Pitfalls to Avoid

• Never transfer teriparatide from the delivery device to a syringe—this results in incorrect dosing. 5
• Never discontinue denosumab without immediately transitioning to bisphosphonates—this causes severe rebound fractures. 2, 3
• Do not continue bisphosphonates beyond 5 years without reassessing fracture risk—this increases long-term harm without additional benefit for most fractures. 1
• Monitor for bisphosphonate adverse effects including osteonecrosis of the jaw, atypical femoral fractures, and esophageal irritation. 3