Anabolic Agents for Osteoporosis
Direct Recommendation
For patients with very high fracture risk osteoporosis, initiate treatment with anabolic agents (teriparatide or abaloparatide) followed by sequential bisphosphonate therapy to prevent bone loss; for high fracture risk, anabolic agents or denosumab are preferred over bisphosphonates alone. 1
Patient Selection for Anabolic Therapy
Very High Fracture Risk Criteria (Strongest Indication)
Anabolic agents are conditionally recommended over anti-resorptive agents when patients meet any of the following 1:
- Prior osteoporotic fracture(s), particularly vertebral or hip fractures
- BMD T-score ≤ -3.5
- FRAX 10-year risk: Major osteoporotic fracture ≥30% OR hip fracture ≥4.5%
- Recent fracture (within past 12 months)
- Multiple clinical osteoporotic fractures
- Failure of other osteoporosis therapy
- High-dose glucocorticoids (≥30 mg/day for >30 days or cumulative ≥5 g/year) 1
High Fracture Risk Criteria
Anabolic agents or denosumab are conditionally recommended over bisphosphonates for 1:
- FRAX 10-year risk: Major osteoporotic fracture 10-30% OR hip fracture 1-4.5%
- BMD T-score between -2.5 and -3.5 with additional risk factors
Moderate Fracture Risk
For moderate risk patients, bisphosphonates, denosumab, or anabolic agents may be used in no preferred order, though bisphosphonates remain first-line due to cost-effectiveness 1
Available Anabolic Agents
Teriparatide (PTH 1-34)
- Dosing: 20 mcg subcutaneously once daily 2
- Efficacy: Reduces vertebral fractures (69 fewer events per 1000 patients) and any clinical fractures (27 fewer events per 1000 patients) compared to placebo 1
- Compared to bisphosphonates: Probably reduces radiographic vertebral fractures (66 fewer events per 1000 patients) and may reduce any clinical fracture 1
- In glucocorticoid-induced osteoporosis: Increased lumbar and hip BMD and decreased vertebral fractures at 36 months compared to alendronate 1
Abaloparatide (PTHrP analog)
- Dosing: 80 mcg subcutaneously once daily 3, 4
- Advantages over teriparatide: Greater BMD gains, superior efficacy for major osteoporotic fractures, and lower risk of hypercalcemia 3, 4
- Evidence in men: Based on BMD data, abaloparatide is considered appropriate first-line treatment for men with very high fracture risk 1
Romosozumab (Sclerostin Inhibitor)
- Dosing: 210 mg subcutaneously monthly 1, 3
- Dual mechanism: Stimulates bone formation AND suppresses bone resorption 3, 4
- Efficacy: Reduces vertebral fractures (13 fewer events per 1000 patients), clinical vertebral fractures (4 fewer events per 1000), and any clinical fractures (9 fewer events per 1000) at 12-36 months 1
- Critical caveat: Conditionally recommended only in patients intolerant of other agents due to uncertain cardiovascular harms (increased myocardial infarction, stroke, and death) 1
Treatment Duration and Sequential Therapy
Maximum Duration
- Limit anabolic therapy to 2 years maximum during a patient's lifetime unless they remain at or return to very high fracture risk 2
- Treatment beyond 2 years should only be considered after careful risk-benefit assessment 2
Mandatory Sequential Anti-Resorptive Therapy
This is critical: Discontinuation of anabolic agents results in rapid bone loss and increased fracture risk within 12-18 months 1
After teriparatide or abaloparatide:
- Start bisphosphonate immediately upon completion 1
- Alternative: Denosumab may be used, but must be followed by bisphosphonate when denosumab is discontinued 1
After romosozumab:
- Must be followed by bisphosphonate or denosumab 1
- If denosumab is used after romosozumab, it must then be followed by bisphosphonate 1
Important Contraindications and Precautions
Absolute Contraindications for Anabolic Agents 2
- Open epiphyses (pediatric patients with growth potential)
- Paget's disease of bone
- Bone metastases or skeletal malignancies
- Prior external beam or implant radiation therapy involving skeleton
- Hereditary disorders predisposing to osteosarcoma
- Hypersensitivity to the medication
Use with Caution 1, 2
- Active or recent urolithiasis (risk of exacerbation due to hypercalcemia)
- Underlying hypercalcemic disorders (avoid use)
- Worsening cutaneous calcification (discontinue if occurs)
- Young adults <40 years with open growth plates 1
- Patients of childbearing potential: Use caution; avoid pregnancy for 5 months after last dose of denosumab 1
Monitoring Requirements 2
- Administer initial doses under circumstances where patient can sit or lie down (risk of orthostatic hypotension)
- Measure serum calcium after 1 month of treatment 5
- Limit total daily calcium intake to 1500 mg from diet and supplements 5
- Ensure adequate vitamin D: Maintain serum 25(OH)D levels ≥30-50 ng/mL with 600-1000 IU daily 1, 5
Common Adverse Effects
Teriparatide 1, 2
- Withdrawal due to adverse effects: 17-127 more events per 1000 patients compared to placebo
- Most common: Nausea, dizziness, vomiting, headache, palpitations, leg cramps, arthralgia, pain
- Transient orthostatic hypotension may occur with initial doses
- Mild hypercalcemia: Manage by reducing calcium supplements or dosing frequency
Abaloparatide 3
- Lower risk of hypercalcemia compared to teriparatide
- Similar adverse effect profile otherwise
Romosozumab 1
- Cardiovascular concerns: Increased risk of myocardial infarction, stroke, and death (reason for conditional recommendation against use except in intolerant patients)
Drug Interactions
Digoxin 2
- Transient hypercalcemia from teriparatide may predispose to digitalis toxicity
- Monitor digoxin levels and cardiac status closely
Concurrent Bisphosphonate Therapy
- Avoid initiating PTH/PTHrP with bisphosphonates simultaneously 6, 5
- Prior bisphosphonate use blunts the anabolic response to PTH 1, 5
- Sequential therapy (anabolic first, then bisphosphonate) is superior to concurrent use 5
Special Populations
Men with Osteoporosis
- Same recommendations apply as for postmenopausal women 1
- Abaloparatide has strongest BMD data for men at very high fracture risk 1
- Assess serum testosterone as part of pre-treatment evaluation 1
Glucocorticoid-Induced Osteoporosis
- For very high fracture risk: PTH/PTHrP conditionally recommended over anti-resorptives 1
- For high fracture risk: PTH/PTHrP or denosumab conditionally recommended over bisphosphonates 1
- Teriparatide superior to alendronate for vertebral fracture reduction in this population 1
Pregnancy and Lactation 2
- Consider discontinuing when pregnancy is recognized
- Breastfeeding is not recommended
Cost Considerations
Teriparatide is significantly more expensive than bisphosphonates 1, 5. Generic bisphosphonates should be prescribed when appropriate rather than brand-name anabolic agents 1. However, for patients at very high fracture risk, the superior efficacy of anabolic agents justifies the cost 1.