What is the recommended treatment for severe osteoporosis using Teriparatide (recombinant human parathyroid hormone)

Teriparatide for Severe Osteoporosis

Teriparatide is reserved as a second-line or third-line anabolic therapy for patients with severe osteoporosis at very high fracture risk, particularly those who have failed or cannot tolerate bisphosphonates, or who have sustained fractures despite antiresorptive therapy. 1, 2

Patient Selection Criteria

Teriparatide should be considered specifically for:

• Postmenopausal women with severe osteoporosis who have documented vertebral or non-vertebral fractures, particularly those occurring despite adequate bisphosphonate therapy 1
• Patients at very high fracture risk defined by T-score ≤ -3.5, multiple prevalent fractures, or fractures on therapy 1, 2, 3
• Men with primary or hypogonadal osteoporosis at high fracture risk who have failed or are intolerant to other therapies 4, 5
• Glucocorticoid-induced osteoporosis in patients at high fracture risk or intolerant to bisphosphonates 1, 2, 4
• Patients undergoing spinal instrumentation surgery where teriparatide demonstrates superiority over bisphosphonates with reduced screw loosening (7% vs 13%) and improved fusion rates (82% vs 68%) 2

Treatment Protocol

Dosing and Administration

• 20 mcg subcutaneously once daily into the thigh or abdominal region 4, 5
• Maximum treatment duration: 2 years during a patient's lifetime, unless the patient remains at or returns to very high fracture risk 1, 4, 6
• Initial administration should occur under supervision where the patient can sit or lie down due to risk of orthostatic hypotension 4

Supplementation Requirements

• Calcium: 1,000-1,200 mg daily (combined dietary and supplemental intake, not exceeding 1,500 mg total) 1, 2, 6
• Vitamin D: 600-800 IU daily (up to 1,000 IU may be appropriate) 1, 2, 6

Sequential Therapy Strategy

• Following teriparatide discontinuation, transition to antiresorptive therapy (bisphosphonate or denosumab) to maintain bone gains 5, 7, 8
• Avoid concurrent bisphosphonate therapy as combination treatment is not more effective than teriparatide monotherapy and may blunt the anabolic response 6, 7, 8
• Prior bisphosphonate use may diminish teriparatide's anabolic potential, though it remains effective 8

Absolute Contraindications

Teriparatide must be avoided in patients with:

• Open epiphyses (children and adolescents with growing bones) 1, 4
• Paget's disease of bone or other metabolic bone diseases 1, 4
• Bone metastases or history of skeletal malignancies 1, 4
• Prior external beam or implant radiation therapy involving the skeleton 1, 4
• Hereditary disorders predisposing to osteosarcoma 4
• Hypersensitivity to teriparatide or its excipients 4

Important Warnings and Precautions

Osteosarcoma Risk

• Rat toxicology studies showed increased osteosarcoma, but a study of 200,000 patients demonstrated no significant difference in osteosarcoma incidence between treated patients and the general population 1, 4
• Avoid in patients with malignancies prone to bone metastases due to theoretical risk that increased bone turnover may promote micrometastatic propagation through liberation of bone-derived growth factors 1

Hypercalcemia

• Monitor serum calcium after 1 month of treatment 6
• Avoid in patients with underlying hypercalcemic disorders 4
• Discontinue if worsening cutaneous calcification develops 4
• Mild hypercalcemia can be managed by reducing calcium supplements or decreasing PTH dosing frequency 6

Urolithiasis

• Use with caution in patients with active or recent kidney stones due to risk of exacerbation 4

Orthostatic Hypotension

• Transient orthostatic hypotension may occur with initial doses, requiring patients to sit or lie down until symptoms resolve 4

Drug Interactions

• Digoxin toxicity risk: Transient hypercalcemia may predispose patients taking digoxin to toxicity 4

Clinical Efficacy

Teriparatide demonstrates:

• 65% reduction in new vertebral fractures in postmenopausal women 8
• 90% reduction in moderate-to-severe vertebral fractures 8
• 35% reduction in nonvertebral fractures by 21 months 8
• Significant improvements in bone mineral density at lumbar spine and femoral neck, predominantly affecting trabecular bone 5, 7, 3
• Fracture risk reduction becomes evident after 8-12 months of treatment 8

Special Populations

Pregnancy and Lactation

• Consider discontinuing when pregnancy is recognized 4
• Breastfeeding is not recommended during teriparatide therapy 4

Pediatric Use

• Safety and effectiveness not established in children 4
• Avoid use due to increased baseline risk of osteosarcoma in patients with open epiphyses 4

Cost Considerations

• Teriparatide is significantly more expensive than bisphosphonates, with cost-utility estimates suggesting it is best reserved for severe cases 5, 6, 7
• Generic bisphosphonates should be prescribed as first-line therapy when possible 1
• Cost-effectiveness improves in patients at very high fracture risk or those who have failed other therapies 7, 8