How should teriparatide be administered in an adult with severe osteoporosis (e.g., postmenopausal woman or man over 50 on long‑term glucocorticoids) and what are its side effects and contraindications?

How to Use Teriparatide and Side Effects

Teriparatide is administered as a 20 mcg subcutaneous injection once daily into the thigh or abdomen, reserved exclusively for patients with severe osteoporosis at very high fracture risk who have failed or cannot tolerate bisphosphonates, and must be limited to a maximum of 2 years of treatment followed immediately by antiresorptive therapy. 1, 2, 3

Patient Selection and Indications

Teriparatide should only be used in the following high-risk populations 1, 2:

• Postmenopausal women with osteoporosis at very high fracture risk (T-score ≤ -3.5, history of vertebral or multiple fractures, or fractures occurring despite bisphosphonate therapy) 2, 3
• Men with primary or hypogonadal osteoporosis at high fracture risk 1, 2
• Glucocorticoid-induced osteoporosis in patients at high risk who cannot tolerate or have failed bisphosphonates 2, 1

Bisphosphonates remain first-line therapy—teriparatide is explicitly a second-line or third-line agent due to cost, limited treatment duration, and the need for sequential therapy 2, 4

Administration Protocol

Dosing and Technique 1

• Dose: 20 mcg subcutaneously once daily
• Injection sites: Rotate between thigh and abdominal region
• Initial administration: Give first doses under circumstances where patient can sit or lie down due to risk of orthostatic hypotension 1

Essential Supplementation 2

• Calcium: 1,000-1,200 mg daily from diet and supplements combined
• Vitamin D: 600-800 IU daily (maintain serum level ≥ 20 ng/mL)

Treatment Duration 1, 3

• Maximum lifetime use: 2 years total
• Extension beyond 2 years: Only if patient remains at or returns to very high fracture risk 1

Mandatory Sequential Therapy

Critical pitfall to avoid: Never discontinue teriparatide without immediately starting antiresorptive therapy 2, 5, 4

• Transition immediately to bisphosphonates or denosumab after completing teriparatide 2, 5
• Failure to transition causes rapid bone loss and rebound vertebral fractures 5, 4
• This sequential approach is non-negotiable for preserving bone density gains 2, 3

Side Effects and Adverse Events

Common Adverse Effects (>10%) 1, 2

• Arthralgia (joint pain)
• Generalized pain
• Nausea
• Headache
• Dizziness
• Leg cramps

Serious Adverse Events 2, 1

• Orthostatic hypotension: Transient episodes may occur with initial doses; administer first doses with patient able to sit/lie down 1
• Hypercalcemia: Monitor serum calcium after 1 month of treatment; manage by reducing calcium supplements or dosing frequency 1, 6
• Increased withdrawal rate: Teriparatide probably increases treatment discontinuation due to adverse effects (most commonly nausea, dizziness, vomiting, headache, palpitations) 2

Metabolic Effects 1, 6

• Hypercalciuria (increased urinary calcium)
• Risk of exacerbating urolithiasis in patients with active or recent kidney stones 1

Absolute Contraindications

Do not use teriparatide in 1, 3, 4:

• Hypersensitivity to teriparatide or excipients 1
• Open epiphyses (pediatric patients with open growth plates) 1, 3
• Paget's disease of bone or other metabolic bone diseases 1, 3
• Bone metastases or history of skeletal malignancies 3, 4
• Prior external beam or implant radiation involving the skeleton 3, 1
• Recent myocardial infarction or stroke (consider romosozumab contraindicated here, but teriparatide is preferred alternative) 4
• Underlying hypercalcemic disorders 1

Special Populations 1, 5

• Pregnancy: Discontinue when pregnancy is recognized 1
• Lactation: Breastfeeding not recommended 1
• Pediatric use: Contraindicated due to increased baseline osteosarcoma risk 1
• CKD G4-G5D: Use is off-label; concerns for hypercalcemia and hyperuricemia 5

Monitoring Requirements

Initial Monitoring 1, 6

• Serum calcium: Check after 1 month of treatment
• Urinary calcium: Consider measuring if patient has active urolithiasis or suspected hypercalciuria 5, 1

Management of Hypercalcemia 6

• Reduce or eliminate dietary calcium supplements
• Reduce teriparatide dosing frequency
• Discontinue if hypercalcemia persists

Drug Interactions

Digoxin 1: Transient hypercalcemia from teriparatide may predispose patients to digitalis toxicity; monitor digoxin levels and cardiac status closely

Clinical Efficacy Data

Fracture Reduction 2

• Vertebral fractures: 69 fewer radiographic vertebral fractures per 1,000 patients (high certainty)
• Any clinical fractures: 27 fewer events per 1,000 patients (high certainty)
• Hip fractures: May result in no significant difference (low certainty)

Comparison to Bisphosphonates 2

• Teriparatide probably reduces radiographic vertebral fractures by 66 fewer events per 1,000 patients compared to bisphosphonates (moderate certainty)
• May reduce any clinical fracture by 46 fewer events per 1,000 patients (low certainty)

Cost Considerations

Teriparatide is the most expensive osteoporosis treatment at approximately $22,156 average annual cost per Medicare beneficiary 4. This high acquisition cost mandates that it be reserved exclusively for patients at very high fracture risk or those who have failed/are intolerant to bisphosphonates 2, 3, 4.

Common Pitfalls to Avoid

• Never use as first-line therapy instead of bisphosphonates in standard osteoporosis 4
• Never discontinue without immediate antiresorptive transition—this causes rebound fractures 2, 5
• Never exceed 2 years lifetime use unless patient returns to very high fracture risk 1, 3
• Never use in patients with normal fracture risk—reserve for severe osteoporosis only 3, 7
• Never combine with bisphosphonates during active treatment—concurrent therapy is not more effective than monotherapy 6, 8