What is the recommended treatment regimen for anabolics therapy, such as teriparatide (parathyroid hormone), for patients with osteoporosis?

Anabolic Therapy for Osteoporosis: Treatment Regimen

For patients with very high fracture risk osteoporosis, initiate teriparatide 20 mcg subcutaneously once daily for up to 24 months, followed immediately by sequential bisphosphonate therapy to prevent rapid bone loss. 1, 2

Patient Selection: Who Should Receive Anabolic Therapy

Very High Fracture Risk Criteria (First-Line Anabolics)

Anabolic agents should be prioritized over antiresorptive therapy in patients meeting any of the following criteria:

• Recent fracture (within past 12 months) 3, 1
• Multiple clinical osteoporotic fractures 3, 1
• Prior vertebral or hip fracture 1
• BMD T-score ≤ -3.5 1
• FRAX 10-year risk: Major osteoporotic fracture ≥30% OR hip fracture ≥4.5% 1
• High-dose glucocorticoid use (≥30 mg/day for >30 days or cumulative ≥5 g/year) 1
• Failure of other osteoporosis therapy 3, 1
• Fracture probability above 1.2 times the age-specific intervention threshold 3

High Fracture Risk Criteria (Consider Anabolics or Denosumab)

For patients with FRAX 10-year risk of major osteoporotic fracture 10-30% or hip fracture 1-4.5%, or BMD T-score between -2.5 and -3.5 with additional risk factors, anabolic agents or denosumab are conditionally recommended over bisphosphonates. 1

Teriparatide Treatment Regimen

Dosing and Administration

• Standard dose: 20 mcg subcutaneously once daily 2
• Injection sites: Thigh or abdominal region 2
• Initial administration: Perform under circumstances where patient can sit or lie down due to risk of orthostatic hypotension 2
• Supplementation: Consider calcium and vitamin D based on individual needs; limit total daily calcium to 1500 mg from all sources 2

Treatment Duration

• Maximum duration: 24 months (2 years) 1, 2
• Lifetime use: Use for more than 2 years during a patient's lifetime should only be considered if the patient remains at or has returned to having high fracture risk 2
• Rationale: The anabolic effect declines with time, and there is poor response to repeated treatment 4

Monitoring

• Serum calcium: Measure after 1 month of treatment 5
• Mild hypercalcemia management: Withdraw dietary calcium supplements, reduce PTH dosing frequency, or both 5

Critical: Sequential Antiresorptive Therapy

Discontinuation of teriparatide results in rapid bone loss and increased fracture risk within 12-18 months, making sequential therapy mandatory. 3, 1

Sequential Therapy Protocol

• After teriparatide: Start bisphosphonate immediately upon completion 1
• Alternative: Denosumab may be used after teriparatide, but must be followed by bisphosphonate when denosumab is discontinued 1
• Evidence: Sequential therapy with romosozumab followed by alendronate reduces hip fractures (12 fewer events per 1000 patients), clinical vertebral fractures (13 fewer per 1000), and any clinical fracture (33 fewer per 1000) 3

Absolute Contraindications

Avoid teriparatide in the following situations due to increased osteosarcoma risk or other safety concerns:

• Open epiphyses (pediatric patients with growth potential) 1, 2
• Paget's disease of bone 6, 1, 2
• Bone metastases or history of skeletal malignancies 6, 1, 2
• Prior external beam or implant radiation therapy involving skeleton 6, 1, 2
• Metabolic bone diseases other than osteoporosis 2
• Hypersensitivity to teriparatide or excipients 2

Use with Caution

• Malignancies prone to bone metastases (breast, prostate, lung, kidney, thyroid cancer) 6
• Active or recent urolithiasis (risk of exacerbation) 2
• Underlying hypercalcemic disorders 2
• Young adults <40 years with open growth plates 1
• Patients of childbearing potential 1

Efficacy Data

Fracture Reduction

Teriparatide demonstrates superior efficacy compared to placebo and bisphosphonates:

• Vertebral fractures: 69 fewer events per 1000 patients vs. placebo; 66 fewer per 1000 vs. bisphosphonates 3, 1
• Any clinical fractures: 27 fewer events per 1000 patients vs. placebo 3, 1
• Clinical vertebral fractures: 45 fewer events per 1000 patients vs. placebo 3
• In glucocorticoid-induced osteoporosis: Increases lumbar and hip BMD and decreases vertebral fractures at 36 months compared to alendronate 1

BMD Improvements

• Lumbar spine: 10-13% increase at 24 months 1, 7
• Hip: 3-5% increase at 24 months 1, 7

Alternative Anabolic Agents

Abaloparatide (PTHrP analog)

• Considered appropriate first-line treatment for men with very high fracture risk 1
• Similar administration and sequential therapy requirements as teriparatide 1

Romosozumab (Sclerostin Inhibitor)

• Efficacy: Reduces vertebral fractures (13 fewer per 1000), clinical vertebral fractures (4 fewer per 1000), and any clinical fractures (9 fewer per 1000) at 12-36 months 3, 1
• Major limitation: Increased cardiovascular risk (hazard ratio 1.9 for cardiovascular events vs. alendronate) 3
• Recommendation: Conditionally recommended only in patients intolerant of other agents due to uncertain cardiovascular harms 1
• Sequential therapy: Must be followed by bisphosphonate or denosumab 1

Common Adverse Effects

Teriparatide

• Most common (>10%): Arthralgia, pain, nausea 2
• Other common effects: Dizziness, vomiting, headache, palpitations, leg cramps 3
• Withdrawal due to adverse effects: Increased risk compared to placebo (17-127 more events per 1000 patients) 3
• Serious adverse effects: No significant difference vs. placebo 3

Important Drug Interaction

• Digoxin: Transient hypercalcemia may predispose patients to digitalis toxicity; monitor closely 2

Special Populations

Men with Osteoporosis

The same recommendations apply to men with primary or hypogonadal osteoporosis at high risk for fracture. 1, 2

Glucocorticoid-Induced Osteoporosis

Teriparatide is indicated for men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture. 1, 2

Key Clinical Pitfalls to Avoid

• Never use teriparatide without planning sequential antiresorptive therapy – bone loss is rapid after discontinuation 3, 1
• Avoid concurrent bisphosphonate therapy – this blunts the anabolic effect of teriparatide 5
• Do not exceed 24 months of treatment unless patient returns to very high fracture risk 2
• Screen for contraindications carefully, particularly history of skeletal radiation or malignancies 6, 2
• Monitor for orthostatic hypotension with initial doses 2