Teriparatide

How Teriparatide works

Teriparatide is the biologically active N-terminal fragment of endogenous parathyroid hormone and acts at the PTH1 receptor. Intermittent once-daily exposure preferentially stimulates osteoblast activity over osteoclast activity, increasing bone formation and improving trabecular microarchitecture. Continuous rather than intermittent PTH exposure produces the opposite, resorptive effect.

What research has looked at

• Primary endpoint of the pivotal Fracture Prevention Trial (Neer 2001; 1,637 women randomized across placebo and two teriparatide dose arms, median follow-up about 21 months) in postmenopausal women with prior vertebral fracture: at the currently approved dose, new vertebral fractures occurred in 5 percent versus 14 percent with placebo, a 65 percent relative reduction (relative risk 0.35, 95 percent CI 0.22 to 0.55).
• Secondary endpoint of the same trial: new nonvertebral fragility fractures occurred in 3 percent versus 6 percent with placebo, a 53 percent relative reduction (relative risk 0.47, 95 percent CI 0.25 to 0.88). This was a secondary, not a primary, endpoint.
• Same trial: bone mineral density increased by roughly 9 percent at the lumbar spine and roughly 3 percent at the femoral neck relative to placebo.
• Labeled indications: treatment of postmenopausal women with osteoporosis at high fracture risk or who have failed or are intolerant to other available osteoporosis therapy; to increase bone mass in men with primary or hypogonadal osteoporosis meeting the same criteria; and treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy meeting the same criteria.
• The pivotal trial was stopped early after osteosarcoma was observed in rats and was not powered to demonstrate a reduction in hip fracture as a separate endpoint.

Evidence level: Approved labeling. Official prescribing information exists, based on clinical trials in people. These are areas studied or reported, not promised effects.

Reported side effects and risks

• Contraindicated in patients with hypersensitivity to teriparatide or to any of its excipients; reported hypersensitivity reactions have included angioedema and anaphylaxis.
• Osteosarcoma: an increase in the incidence of osteosarcoma was observed in male and female rats treated with teriparatide, and osteosarcoma has been reported in patients post-marketing, although an increased risk has not been observed in human observational studies. The label directs AVOIDING use in patients at increased baseline osteosarcoma risk: open epiphyses (pediatric and young adult patients; teriparatide is not approved in pediatric patients), metabolic bone diseases OTHER THAN osteoporosis including Paget's disease of the bone, bone metastases or a history of skeletal malignancies, prior external beam or implant radiation therapy involving the skeleton, and hereditary disorders predisposing to osteosarcoma. There are limited data assessing osteosarcoma risk beyond 2 years of use.
• Hypercalcemia: teriparatide may cause hypercalcemia and may exacerbate it in patients with pre-existing hypercalcemia, in whom it has not been studied. AVOID in patients known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism.
• Cutaneous calcification including calciphylaxis: serious reports of calciphylaxis and worsening of previously stable cutaneous calcification have occurred post-marketing. Risk factors include underlying autoimmune disease, kidney failure, and concomitant warfarin or systemic corticosteroid use. Discontinue in patients who develop calciphylaxis or worsening of previously stable cutaneous calcification.
• Risk of urolithiasis: not studied in patients with active urolithiasis. Consider the risks and benefits in patients with active or recent urolithiasis because of the potential to exacerbate the condition, and consider measuring urinary calcium excretion in patients with pre-existing hypercalciuria or suspected or known active urolithiasis.
• Orthostatic hypotension: transient symptomatic orthostatic hypotension was observed in 5 percent of healthy volunteers in short-term studies, typically beginning within 4 hours of dosing, occurring within the first several doses, and resolving without treatment. Administer initially under circumstances in which the patient can sit or lie down.
• Risk of digoxin toxicity: hypercalcemia predisposes patients to digitalis toxicity, so consider the potential onset of signs and symptoms of digitalis toxicity in patients receiving digoxin.
• Pregnancy and lactation: consider discontinuing when pregnancy is recognized; breastfeeding is not recommended.
• Most common adverse reactions per the label Highlights are arthralgia, pain and nausea. The current label carries no Boxed Warning; the osteosarcoma boxed warning was removed in November 2020 and the strict two-year lifetime limit was revised at the same time, but the label still states that use beyond 2 years cumulative should only be considered if the patient remains at, or has returned to, high fracture risk.

Sources

1. PubMed research on Teriparatide · NIH · National Library of Medicine
2. DrugBank record for Teriparatide · DrugBank
3. Active clinical trials for Teriparatide · U.S. National Library of Medicine

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Teriparatide FAQ