When should teriparatide (teriparatide) be initiated in an adult or postmenopausal/elderly patient with osteoporosis?

Indications for Starting Teriparatide

Teriparatide should be initiated exclusively in postmenopausal women or men with primary osteoporosis who are at very high risk for fracture, and it must be followed by bisphosphonate or denosumab therapy after completion of the 24-month treatment course. 1, 2

Defining Very High Fracture Risk

Teriparatide is reserved for patients meeting any of the following criteria:

• Recent osteoporotic fracture (within the past year) 2
• History of multiple clinical osteoporotic fractures 2
• Multiple concurrent risk factors for fracture combined with low bone mineral density 1, 2
• Failure of or contraindication to bisphosphonate therapy (fracture occurring while on bisphosphonates) 2
• T-score ≤ -3.5 in patients younger than 65 years 3

Treatment Hierarchy: When NOT to Use Teriparatide First

Bisphosphonates remain the first-line treatment for primary osteoporosis due to superior cost-effectiveness, high-certainty evidence for fracture reduction, and availability of generic formulations. 1

Teriparatide is explicitly a second-line or third-line agent, not initial therapy, unless the patient has already failed bisphosphonates or has contraindications to them. 1, 2

Choosing Between Teriparatide and Romosozumab

When a patient qualifies for anabolic therapy, the decision algorithm is:

• Choose romosozumab if:

  • No myocardial infarction or stroke within the past year 2
  • Cost is a significant concern (romosozumab costs approximately $5,574/year vs. teriparatide $22,156/year) 2
  • Patient prefers less frequent administration 2

• Choose teriparatide if:

  • Recent cardiovascular events (MI or stroke within past year), as romosozumab increases cardiovascular events (HR 1.9,95% CI 1.1-3.1) 2
  • Patient prefers self-administration at home via daily subcutaneous injection 2
  • History of malignancy prone to bone metastases (teriparatide may be cautiously considered in remote cancer history with severe osteoporosis) 2

Absolute Contraindications to Teriparatide

Do not initiate teriparatide in:

• Pediatric patients with open epiphyses (higher baseline osteosarcoma risk) 4
• Active malignancy prone to bone metastases or potential micrometastatic disease 2
• Pregnancy (discontinue when pregnancy is recognized) 4
• Breastfeeding women 4

Special Populations Requiring Caution

Patients on Digoxin

Monitor closely for digitalis toxicity, as teriparatide transiently increases serum calcium, which may predispose to digitalis toxicity. 4

Severe Renal Impairment (CrCl <30 mL/min)

Teriparatide AUC and half-life increase by 73% and 77% respectively in severe renal impairment, though maximum serum concentration remains unchanged. 4 The clinical significance is uncertain, but monitoring for hypercalcemia is prudent.

Glucocorticoid-Induced Osteoporosis

Teriparatide is indicated for patients requiring long-term glucocorticoid therapy who develop established osteoporosis. 3

Critical Treatment Parameters

Duration

Limit treatment to 24 months maximum due to osteosarcoma risk observed in rat models (though no human cases have been documented in postmarketing surveillance). 2, 4, 5

The full 24-month course provides superior fracture risk reduction compared to shorter durations, with nonvertebral fracture benefits becoming evident at 8-12 months. 5, 6

Sequential Therapy Requirement

Teriparatide MUST be followed immediately by antiresorptive therapy (bisphosphonates or denosumab) to prevent rapid bone loss and preserve gains in bone mineral density. 2, 7 Failure to initiate sequential therapy results in loss of therapeutic benefits.

Avoid Concurrent Bisphosphonates

Do not combine teriparatide with bisphosphonates during the treatment course, as bisphosphonates diminish the bone anabolic potential of teriparatide. 6 Previous bisphosphonate treatment may also reduce teriparatide efficacy. 6

Calcium and Vitamin D Management

Limit total daily calcium intake to ≤1500 mg (dietary plus supplements) with adequate vitamin D (≤1000 IU/day). 3 Excessive calcium increases hypercalcemia risk, which occurs 12.9 times more frequently with teriparatide than placebo. 7

Monitoring Requirements

• Measure serum calcium after 1 month of treatment 3
• If mild hypercalcemia occurs, withdraw calcium supplements, reduce teriparatide dosing frequency, or both 3
• Monitor for common adverse effects: nausea, dizziness, vomiting, leg cramps, headache, and palpitations (withdrawal due to adverse events occurs in 17 more per 1000 patients at 24 months) 7

Common Pitfalls to Avoid

1. Using teriparatide as first-line therapy instead of bisphosphonates in standard osteoporosis 1
2. Failing to initiate antiresorptive therapy after teriparatide completion, leading to rapid bone loss 2, 7
3. Combining with bisphosphonates during treatment, which blunts anabolic effects 6
4. Treating for less than 24 months when the full course is tolerated, as fracture benefits increase with duration 5
5. Excessive calcium supplementation (>1500 mg/day), increasing hypercalcemia risk 3