What is the treatment for severe osteoporosis?

Treatment of Severe Osteoporosis

For patients with severe osteoporosis at very high fracture risk, initiate treatment with anabolic agents (romosozumab or teriparatide) followed by mandatory transition to bisphosphonates or denosumab; for all other patients with severe osteoporosis, start with oral bisphosphonates as first-line therapy. 1, 2

Defining Very High Risk for Severe Osteoporosis

Very high-risk criteria that warrant anabolic therapy include 1, 2:

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

Treatment Algorithm for Severe Osteoporosis

Step 1: Risk Stratification

• If very high-risk criteria present: Proceed to anabolic therapy first 1, 2
• If very high-risk criteria absent: Proceed to bisphosphonate therapy 1, 2

Step 2A: Anabolic Therapy (Very High-Risk Patients)

First-line anabolic options 1, 2:

Teriparatide 20 mcg subcutaneously daily:

• Reduces vertebral fractures by 69 per 1000 patients 2
• Reduces any clinical fractures by 27 per 1000 patients 2
• Maximum duration: 24 months 2, 3
• FDA-approved for postmenopausal women and men with primary or hypogonadal osteoporosis at high fracture risk 3

Romosozumab:

• Conditionally recommended for very high-risk postmenopausal women 1, 2
• Limited to 12 monthly doses due to waning anabolic effect 2
• Increases BMD more profoundly and rapidly than alendronate 4

Critical warning: After completing anabolic therapy, patients must transition to bisphosphonate or denosumab to maintain bone density gains and prevent rapid bone loss (high-certainty evidence) 1, 2, 5

Step 2B: Bisphosphonate Therapy (Standard Severe Osteoporosis)

Preferred first-line agents (strong recommendation, high-certainty evidence) 6, 2:

Alendronate:

• 70 mg once weekly or 10 mg daily 2, 7
• Reduces hip, vertebral, and nonvertebral fractures 6, 2
• Generic formulation strongly recommended due to significantly lower cost 2

Risedronate:

• 35 mg once weekly, 5 mg daily, 75 mg on two consecutive days per month, or 150 mg monthly 2
• Reduces hip, vertebral, and nonvertebral fractures 6, 2

Zoledronic acid:

• 5 mg IV annually 2
• Reduces hip, vertebral, and nonvertebral fractures 6, 2
• Useful for patients with contraindications to oral bisphosphonates or adherence issues 2

Treatment duration: 5 years initially, then reassess fracture risk to determine continuation versus drug holiday 6, 2, 5

Step 3: Second-Line Therapy

Denosumab 60 mg subcutaneously every 6 months 6, 2, 5:

• Reserved for patients with contraindications to bisphosphonates or who experience adverse effects 6, 2
• Moderate-certainty evidence for postmenopausal women, low-certainty evidence for men 6, 2

Critical warning: Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures—patients must transition to bisphosphonate therapy after stopping denosumab 2, 5

Essential Adjunctive Measures for All Patients

Every patient requires (strong recommendation, high-certainty evidence) 1, 2, 5:

• Calcium: 1000-1200 mg daily 1, 2, 5
• Vitamin D: 800-1000 IU daily 1, 2, 5
• Weight-bearing and muscle resistance exercises 1
• Balance exercises and fall prevention counseling 1
• Smoking cessation 1
• Alcohol reduction 1

Monitoring During Treatment

• BMD testing every 1-2 years until stable, then every 2-3 years 5
• Evaluate for new fractures and medication compliance at each visit 5
• Assess for medication side effects, particularly upper GI symptoms with bisphosphonates 5, 7
• Do not perform routine BMD monitoring during the initial 5-year bisphosphonate treatment period (weak recommendation) 6

Critical Pitfalls to Avoid

Bisphosphonate administration errors 7:

• Must be taken in fasting state with plain water only
• Patient must remain upright for at least 30 minutes after administration
• No food, beverages, or other medications for at least 30 minutes

Sequential therapy failures 1, 2, 5:

• Never discontinue anabolic agents without transitioning to antiresorptive therapy
• Never discontinue denosumab without transitioning to bisphosphonate therapy
• Failure to transition causes rapid bone loss and multiple vertebral fractures

Rare but serious bisphosphonate complications (monitor after longer treatment duration) 6, 5:

• Osteonecrosis of the jaw
• Atypical femoral fractures

Agents NOT Recommended

Strong recommendation against (moderate-quality evidence) 6, 2:

• Estrogen therapy
• Estrogen plus progestogen
• Raloxifene

These agents carry unfavorable risk-benefit profiles including cardiovascular events, thromboembolic complications, stroke, and increased breast cancer risk 6, 2