What is the role of teriparatide (recombinant parathyroid hormone) in fracture healing, particularly in older adults with osteoporosis and a history of fragility fractures?

Role of Teriparatide in Fracture Healing

Teriparatide is a second-line anabolic agent reserved exclusively for postmenopausal women and men with primary osteoporosis at very high fracture risk, and must be followed immediately by bisphosphonate or denosumab therapy to prevent rebound vertebral fractures. 1, 2

Patient Selection Criteria for Teriparatide

Teriparatide should only be considered when patients meet very high fracture risk criteria, defined as: 2, 3

• Recent osteoporotic fracture (particularly vertebral)
• History of multiple clinical osteoporotic fractures
• T-score ≤ -3.5 with multiple risk factors
• Fracture occurring despite adequate bisphosphonate therapy
• Failure or intolerance to first-line bisphosphonates 1, 3

Bisphosphonates remain first-line therapy for primary osteoporosis (strong recommendation, high-certainty evidence), and teriparatide should never be used when bisphosphonates are appropriate and tolerated. 1, 4

Fracture Prevention Efficacy

Vertebral Fractures

Teriparatide demonstrates high-certainty evidence for vertebral fracture reduction in postmenopausal women with osteoporosis: 2, 5

• Reduces any clinical fractures by 27 fewer events per 1,000 patients
• Reduces radiographic vertebral fractures by 69 fewer events per 1,000 patients
• Reduces new vertebral fractures from 14.3% (placebo) to 5.0% (65% relative risk reduction, p<0.001) 5

Nonvertebral Fractures

• Reduces overall nonvertebral fractures by 53% (from 5.5% to 2.6%, p<0.05) 5, 6
• Does not significantly reduce hip or wrist fractures (low-certainty evidence) 2, 6

Bone Mineral Density Effects

After median 19 months of treatment: 5

• Lumbar spine BMD increases 9.7% (vs 1.1% placebo, p<0.001)
• Femoral neck BMD increases 2.8% (vs -0.7% placebo, p<0.05)
• Total hip BMD increases 2.6% (vs -1.0% placebo, p<0.05)
• 96% of patients show increased lumbar spine BMD; 72% achieve ≥5% increase 5

Fracture Healing Enhancement

Clinical Evidence for Accelerated Healing

Teriparatide demonstrates specific benefits for fracture healing beyond fracture prevention: 7, 8

• Vertebral compression fractures: Achieves 89% union rate at 6 months versus 68% with bisphosphonates (p=0.026), with faster time-to-union (adjusted hazard ratio 1.86,95% CI 1.21-2.83) 8
• Distal radius fractures: Achieves earlier radiographic cortical bridging at 7.4 weeks versus 9.1 weeks with placebo 7
• Pelvic fractures: Accelerates healing to 7.8 weeks versus 12.6 weeks without treatment (p<0.001) 7

Surgical Applications

The Congress of Neurological Surgeons provides Grade B evidence that teriparatide should be considered preoperatively in osteoporotic patients undergoing spinal instrumentation: 3

• Reduces screw loosening (7% vs 13% with bisphosphonates)
• Improves fusion rates (82% vs 68%)
• Achieves earlier fusion (8 months vs 10 months)
• Demonstrates faster BMD recovery perioperatively 3

Specific Clinical Scenarios for Fracture Healing

Consider teriparatide in osteoporotic patients with: 7, 9

• Atypical femur fractures or open tibia fractures not expected to unite predictably
• Failed fracture healing (nonunion) requiring surgical intervention
• Complex fractures in severely osteoporotic bone at high risk for nonunion 7, 9

Do not use teriparatide when bisphosphonates are appropriate and fractures are expected to heal uneventfully, or in patients with metabolically normal bone. 7

Mandatory Sequential Therapy Protocol

Critical warning: Teriparatide must never be discontinued without immediately starting antiresorptive therapy—this causes rapid bone density loss and rebound vertebral fractures. 2, 4

• Transition immediately to bisphosphonates or denosumab after completing teriparatide 2, 4
• This sequential therapy is mandatory to preserve bone density gains 2, 4
• Failure to transition results in serious risk of multiple vertebral fractures 4

Treatment Duration and Limitations

• Maximum lifetime treatment duration: 24 months 2, 3
• Limited to 2 years unless patient remains at or returns to very high fracture risk 3
• Duration restriction based on osteosarcoma risk in animal models, though no cases linked to teriparatide in postmarketing surveillance 3, 4

Safety Profile and Adverse Effects

Common Adverse Effects

Teriparatide probably increases withdrawal due to adverse events, most commonly: 2

• Nausea, dizziness, vomiting
• Leg cramps and bone pain
• Arthralgia and injection site reactions 4

Metabolic Effects

• Causes hypercalcemia more frequently than other agents 2
• May cause hypercalciuria (measure urinary calcium if active urolithiasis suspected) 4
• Concerns for hyperuricemia in CKD patients 4

Absolute Contraindications

Teriparatide is contraindicated in: 3, 4

• Open epiphyses (pediatric patients)
• Paget's disease of bone
• Bone metastases or history of skeletal malignancies
• History of malignancy prone to metastasize to bone
• Prior external beam or implant radiation therapy involving skeleton 3, 4

Comparison with Alternative Anabolic Agents

Teriparatide vs Romosozumab

When choosing between anabolic agents for very high-risk patients: 2

Choose romosozumab when:

• No history of myocardial infarction or stroke within past year
• Cost is significant concern (romosozumab $5,574/year vs teriparatide $22,156/year average Medicare cost) 2

Choose teriparatide when:

• Recent cardiovascular events or significant cardiovascular disease (romosozumab increases CV events: HR 1.9,95% CI 1.1-3.1) 2
• Patient prefers self-administration at home 2

Teriparatide vs Bisphosphonates

Compared with bisphosphonates, teriparatide: 2

• Probably reduces radiographic vertebral fractures by 66 fewer events per 1,000 patients (moderate certainty)
• May reduce any clinical fracture by 46 fewer events per 1,000 patients (low certainty)
• However, bisphosphonates remain first-line due to more favorable balance of benefits, harms, patient preferences, and cost 2

Required Supplementation

All patients on teriparatide must receive: 3, 4, 5

• Calcium 1,000-1,200 mg daily
• Vitamin D 600-800 IU daily (optimize based on laboratory values) 3, 4, 5

Special Populations

Men with Osteoporosis

Teriparatide is indicated for men with primary or hypogonadal osteoporosis at high fracture risk, producing rapid and significant BMD improvements. 2, 4

Glucocorticoid-Induced Osteoporosis

The American College of Rheumatology conditionally recommends teriparatide over anti-resorptives only in patients at very high fracture risk with glucocorticoid-induced osteoporosis. 3

Chronic Kidney Disease

• Use in CKD G4-G5D is off-label 4
• Carries concerns for hypercalcemia and hyperuricemia in CKD patients 4

Cost Considerations

• Teriparatide is the most expensive osteoporosis treatment at $22,156 average annual cost per Medicare beneficiary 2
• Approximately 4-fold more expensive than romosozumab 2
• Significantly more expensive than generic bisphosphonates 4
• High cost mandates restriction to very high-risk patients who have failed or cannot tolerate first-line therapies 3, 4

Clinical Decision Algorithm

Step 1: Confirm very high fracture risk (recent fracture, multiple fractures, T-score ≤-3.5, or fracture on bisphosphonate therapy) 2, 3

Step 2: Verify bisphosphonates have failed, are contraindicated, or not tolerated 1, 3

Step 3: Screen for contraindications (malignancy history, Paget's disease, prior skeletal radiation, recent MI/stroke if considering romosozumab instead) 2, 3

Step 4: If considering for fracture healing specifically, confirm fracture is high-risk for nonunion or has already failed to heal 7, 9

Step 5: Ensure patient can commit to mandatory 24-month maximum treatment followed immediately by bisphosphonate/denosumab transition 2, 4

Step 6: Optimize calcium and vitamin D supplementation before initiating therapy 3, 4