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 to maintain bone gains. 1
Defining Very High Risk for Severe Osteoporosis
Very high fracture risk includes patients meeting any of the following criteria: 1
- Age >74 years 1
- Multiple prior osteoporotic fractures 1
- T-score ≤-3.0 1
- High FRAX scores (≥20% for major osteoporotic fracture or ≥3% for hip fracture) 1
- Recent fracture within 12 months 2
- Fractures despite ongoing bisphosphonate therapy 2
First-Line Treatment Algorithm
For Very High-Risk Patients (Severe Osteoporosis)
Start with anabolic agents as initial therapy: 1
- Teriparatide 20 mcg subcutaneously daily for up to 24 months reduces vertebral fractures by 69 per 1000 patients and clinical fractures by 27 per 1000 patients 2, 3
- Romosozumab is conditionally recommended for very high-risk postmenopausal women (limited to 12 monthly doses due to waning anabolic effect) 1, 2
- Anabolic agents are superior to bisphosphonates in preventing vertebral and clinical fractures in patients with severe osteoporosis 4
Critical caveat: Teriparatide should be avoided in patients with open epiphyses, Paget's disease, bone metastases, history of skeletal malignancies, or prior skeletal radiation therapy due to theoretical osteosarcoma risk 3
For High-Risk Patients Not Meeting Very High-Risk Criteria
Bisphosphonates remain first-line therapy: 1, 2
- Alendronate 70 mg once weekly or 10 mg daily 2
- Risedronate 35 mg once weekly or 5 mg daily 2
- Zoledronic acid 5 mg IV annually 2
- Bisphosphonates reduce hip and vertebral fractures with high-certainty evidence 1, 2
- Generic formulations are strongly recommended due to significantly lower cost with equivalent efficacy 1, 2
Mandatory Sequential Therapy
After completing anabolic therapy (teriparatide or romosozumab), patients MUST transition to bisphosphonate or denosumab to maintain bone density gains and prevent rapid bone loss. 1, 2 This is non-negotiable—failure to transition results in loss of all therapeutic benefits. 2
Second-Line Treatment
Denosumab 60 mg subcutaneously every 6 months is reserved for: 1, 2
- Patients with contraindications to bisphosphonates 1, 2
- Patients who experience adverse effects from bisphosphonates 1, 2
- Evidence quality: moderate-certainty for postmenopausal women, low-certainty for 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
Treatment Duration
- Initial bisphosphonate treatment: 5 years, after which reassessment of fracture risk determines whether to continue or take a drug holiday 2
- Teriparatide: maximum 2 years during a patient's lifetime unless patient remains at or returns to very high fracture risk 3
- Romosozumab: maximum 12 monthly doses 2
Essential Adjunctive Measures for All Patients
Every patient with severe osteoporosis requires: 1, 2
- Calcium 1000-1200 mg daily 1, 2
- Vitamin D 800-1000 IU daily 1, 2
- Weight-bearing and muscle resistance exercises (squats, push-ups) 1, 5
- Balance exercises (heel raises, standing on one foot) 1, 5
- Fall prevention counseling 1
- Smoking cessation 1
- Alcohol reduction 1
Glucocorticoid-Induced Severe Osteoporosis
For patients on ≥2.5 mg/day prednisone for >3 months with very high fracture risk: 6