What is the recommended use of Teriparatide (parathyroid hormone-related protein) for osteoporosis treatment?

Teriparatide for Osteoporosis Treatment

Teriparatide should be reserved exclusively for patients with severe osteoporosis at very high fracture risk who have failed or cannot tolerate bisphosphonates, administered as 20 mcg subcutaneously once daily for up to 24 months, followed by mandatory bisphosphonate therapy. 1, 2

Patient Selection Criteria

Very high-risk patients are defined by specific clinical characteristics that must be present before considering teriparatide:

• Age typically >74 years with documented osteoporosis 1
• Recent fracture within the past 12 months 1, 3
• History of multiple clinical osteoporotic fractures 1, 3
• T-score ≤-3.5 at any site 4, 5
• Fractures occurring despite adequate bisphosphonate therapy 4
• Documented failure or intolerance to bisphosphonates (first-line) or denosumab (second-line) 3, 2

The American College of Physicians provides a conditional recommendation for teriparatide use only in postmenopausal women meeting these criteria, with low-certainty evidence supporting this approach. 1 The evidence was insufficient to support a recommendation for men due to indirectness concerns. 1

Treatment Hierarchy and Positioning

Teriparatide is a third-line agent in the osteoporosis treatment algorithm:

• First-line: Oral bisphosphonates for all patients with osteoporosis 6, 4
• Second-line: Denosumab for patients with contraindications to bisphosphonates 6
• Third-line: Teriparatide for very high-risk patients who have failed or cannot tolerate first and second-line therapies 3, 2

This hierarchical approach is driven primarily by cost considerations, as teriparatide is significantly more expensive than generic bisphosphonates. 4, 5

Fracture Reduction Efficacy

Teriparatide demonstrates superior efficacy for vertebral fracture prevention compared to placebo:

• Reduces any clinical fractures by 27 fewer events per 1000 patients (high certainty) 1
• Reduces radiographic vertebral fractures by 69 fewer events per 1000 patients (high certainty) 1
• Reduces clinical vertebral fractures by 45 fewer events per 1000 patients (low certainty) 1
• Reduces moderate-to-severe vertebral fractures by 90% 7
• May show no difference in hip fracture risk (low certainty) 1

Compared to bisphosphonates, teriparatide shows modest advantages:

• Reduces radiographic vertebral fractures by 66 fewer events per 1000 patients (moderate certainty) 1
• May reduce any clinical fracture by 46 fewer events per 1000 patients (low certainty) 1

The fracture reduction benefit appears to increase with longer duration of therapy, with nonvertebral fracture reduction becoming evident after 8-12 months of treatment. 8, 7

Administration Protocol

Dosing and delivery specifications:

• Administer 20 mcg subcutaneously once daily 2
• Inject into the thigh or abdominal region 2
• Initial doses should be administered under circumstances where the patient can sit or lie down due to risk of orthostatic hypotension 2
• Each delivery device (pen) contains 28 daily doses and must be discarded after 28 days even if solution remains 2
• Do not transfer contents to a syringe 2

Treatment Duration and Sequential Therapy

The maximum lifetime treatment duration is 24 months, with mandatory follow-up therapy:

• Treatment should not exceed 24 months during a patient's lifetime unless the patient remains at or returns to very high fracture risk 1, 2
• Discontinuation of teriparatide without follow-up antiresorptive therapy results in rapid bone loss and increased fracture risk 1, 6
• Bisphosphonate therapy must be initiated immediately after teriparatide completion to maintain bone density gains 1, 6, 4
• Bone mineral density gradually decreases following teriparatide discontinuation but remains significantly higher than baseline for at least 30 months if followed by antiresorptive therapy 9

The 24-month limitation is based partly on osteosarcoma induction observed in rat carcinogenicity studies, though no increased risk has been demonstrated in humans. 2, 5

Absolute Contraindications

Do not use teriparatide in patients with:

• Open epiphyses (children and young adults with growing bones) 3, 2
• Paget's disease of bone 3, 2
• Bone metastases or history of skeletal malignancies 4, 3, 2
• Prior external beam or implant radiation therapy involving the skeleton 4, 2
• Hereditary disorders predisposing to osteosarcoma 2
• Known hypersensitivity to teriparatide or its excipients 2

Relative Contraindications and Cautions

Exercise caution or avoid use in:

• Patients with underlying hypercalcemic disorders 3, 2
• Active or recent urolithiasis (kidney stones) due to risk of exacerbation 2
• Patients taking digoxin, as transient hypercalcemia may predispose to digitalis toxicity 2
• Patients with worsening cutaneous calcification 2

Adverse Effects and Monitoring

Common adverse effects (>10% incidence):

• Arthralgia, pain, and nausea 2
• Dizziness, vomiting, headache, palpitations, and leg cramps 1, 3

Teriparatide increases withdrawal rates due to adverse events:

• 127 more withdrawals per 1000 patients at 36 months (moderate certainty) 1
• 17 more withdrawals per 1000 patients at 24 months (moderate certainty) 1

Monitoring requirements:

• Measure serum calcium after 1 month of treatment 5
• Mild hypercalcemia can be managed by withdrawing dietary calcium supplements, reducing PTH dosing frequency, or both 5
• Instruct patients to report persistent symptoms of hypercalcemia (nausea, vomiting, constipation, lethargy, muscle weakness) 2

Supplementation Requirements

Calcium and vitamin D supplementation must be optimized:

• Total daily calcium intake should be limited to 1500 mg from both supplements and dietary sources 5
• Vitamin D supplementation of 600-800 IU daily (up to 1000 IU/day acceptable) 4, 5
• Supplementation should be based on individual patient needs and laboratory values 6, 2

Drug Interactions and Concurrent Therapy

Avoid concurrent bisphosphonate therapy:

• Concurrent use with bisphosphonates should be avoided, as bisphosphonates diminish the bone anabolic potential of teriparatide 5, 7
• Previous bisphosphonate treatment may also reduce teriparatide efficacy 7
• Sequential therapy with bisphosphonates after teriparatide completion is appropriate and necessary 1, 6

Special Populations

Glucocorticoid-induced osteoporosis:

• Teriparatide is indicated for men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high fracture risk 2
• The American College of Rheumatology recommends teriparatide after oral bisphosphonates when they are not appropriate 4

Men with osteoporosis:

• Teriparatide is indicated for increasing bone mass in men with primary or hypogonadal osteoporosis at high fracture risk 2
• In men, teriparatide reduced moderate or severe vertebral fractures by 83% (p=0.01) 9

Pregnancy and lactation:

• Consider discontinuing when pregnancy is recognized 2
• Breastfeeding is not recommended during teriparatide therapy 2

Perioperative Considerations

For patients undergoing spinal instrumentation:

• Preoperative teriparatide decreases postoperative adverse events in osteoporotic patients 4
• Reduces screw loosening (7% vs 13% with bisphosphonates) 4
• Improves fusion rates (82% vs 68% with bisphosphonates) 4
• Achieves earlier fusion (8 months vs 10 months with bisphosphonates) 4

Critical Clinical Pitfalls

Common errors to avoid:

• Never use teriparatide as first-line therapy - it is reserved for very high-risk patients who have failed or cannot tolerate bisphosphonates 6, 3
• Never discontinue teriparatide without immediately starting bisphosphonate therapy - this results in rapid bone loss 1, 6
• Never exceed 24 months of treatment unless the patient remains at very high fracture risk 1, 2
• Never use in pediatric patients due to increased baseline risk of osteosarcoma 2
• Never combine with bisphosphonates concurrently - this reduces teriparatide efficacy 5, 7