Teriparatide
Also known as: Forteo, Forsteo, PTH(1-34), rhPTH(1-34), recombinant human parathyroid hormone (1-34), Bonsity
FDA-approved (Forteo, 2002) for osteoporosis in high-fracture-risk postmenopausal women, men with primary/hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. EU-approved (Forsteo). Biosimilar/follow-on teriparatide products exist in several markets.
5 notable studies · 7 references
TLDR
Teriparatide (Forteo; PTH 1-34) is an FDA-approved bone-building osteoporosis drug that activates the parathyroid hormone receptor in daily pulses to stimulate new bone. Large randomized trials show it cuts vertebral fractures by roughly two-thirds versus placebo and outperforms risedronate and alendronate on vertebral fractures. A rat osteosarcoma signal led to an early boxed warning, which the FDA removed in 2020 after 15 years of human surveillance found no increased risk.
At a Glance
Classification: Recombinant 34-amino-acid N-terminal fragment of human parathyroid hormone; PTH1 receptor agonist; bone-forming (anabolic) osteoporosis drug
Teriparatide is the first 34 amino acids of human parathyroid hormone (PTH), the part of the hormone that carries its biological activity. It is an FDA-approved prescription drug, not an experimental research peptide. It was approved in the United States in 2002 (brand name Forteo, Eli Lilly; Forsteo in Europe). Other teriparatide products, including biosimilars and follow-on versions, have been approved in various markets since. Its claim to fame is that it builds bone. Most osteoporosis drugs (bisphosphonates such as alendronate and risedronate, and denosumab) mainly slow bone breakdown. Teriparatide stimulates new bone formation. FDA-approved uses include treatment of: • Postmenopausal women with osteoporosis at high risk of fracture • Men with primary or hypogonadal osteoporosis at high risk of fracture • Men and women with osteoporosis associated with long-term glucocorticoid (steroid) use at high risk of fracture. It has a large, high-quality evidence base, including the landmark 2001 NEJM fracture trial and a head-to-head fracture trial against risedronate. A famous safety story: in lifelong high-exposure rat studies, teriparatide caused osteosarcoma (bone cancer). The drug launched with a boxed warning and a two-year lifetime limit. After about 15 years of human surveillance found no increase in osteosarcoma, the FDA removed the boxed warning in 2020 and revised the two-year limit.
What Is Teriparatide?
Teriparatide = PTH(1-34), made by recombinant DNA technology. Full parathyroid hormone is 84 amino acids long. Its first 34 amino acids are enough to activate the PTH1 receptor (PTH1R). A key piece of physiology: PTH has opposite effects depending on exposure pattern. Continuously high PTH (as in hyperparathyroidism) → net bone loss Brief daily pulses of PTH → net bone formation. Teriparatide uses the second pattern. This is often called the "anabolic window."
What Are Researchers Studying?
Postmenopausal osteoporosis
The Fracture Prevention Trial (Neer et al., 2001) randomized 1,637 postmenopausal women with prior vertebral fractures. New vertebral fractures occurred in 14% on placebo versus 4–5% on teriparatide, and non-vertebral fragility fractures were roughly halved.
Head-to-head with bisphosphonates
In VERO, 1,360 postmenopausal women with severe osteoporosis were randomized to teriparatide or risedronate for 24 months. New vertebral fractures occurred in 5.4% versus 12.0%, and clinical fractures in 4.8% versus 9.8%. The difference in non-vertebral fractures was not statistically significant.
Glucocorticoid-induced osteoporosis
In 428 people on long-term steroids, teriparatide raised spine bone density more than alendronate over 18 months (7.2% vs. 3.4%) and was associated with fewer new vertebral fractures (0.6% vs. 6.1%).
Sequencing with other osteoporosis drugs
Studies such as DATA-Switch suggest that the order of treatments matters. Starting with an anabolic drug and then switching to an antiresorptive looks favorable, while switching from denosumab to teriparatide was associated with transient bone loss at some sites.
Osteosarcoma safety
Rats given high doses daily for most of their lifespan developed osteosarcoma at all tested doses. A 15-year U.S. surveillance study then found osteosarcoma in teriparatide-treated people at no more than the expected background rate. Combined with claims-database studies, this led to the 2020 label changes.
Fracture healing and other uses
Off-label research has examined fracture healing, spinal fusion and dental and periodontal applications. These are not approved indications, and the evidence is mixed.
How Does It Work?
Intermittent teriparatide exposure ↓ activates PTH1R on osteoblasts and osteocytes ↓ more osteoblast activity and survival, reduced sclerostin (an osteocyte brake on bone formation) ↓ bone formation outpaces bone resorption, at first ↓ thicker, better-connected trabecular bone and increased bone mineral density, especially at the spine ↓ fewer vertebral and non-vertebral fractures. Bone resorption markers also rise over time, so the anabolic effect is strongest in the first year or so. After a course of teriparatide, an antiresorptive drug is usually used to preserve the gains, because bone density otherwise tends to fall. Common side effects in trials included nausea, headache, dizziness, leg cramps and mildly raised blood calcium.
What Does the Research Show?
Human research
HIGH Large randomized controlled trials with fracture endpoints, head-to-head comparisons with bisphosphonates, and long-term post-marketing surveillance.
Animal research
HIGH Extensive preclinical work, including the two-year rat carcinogenicity studies that drove the original osteosarcoma warning.
In-vitro research
HIGH PTH1R signaling in bone cells is well characterized.
Notable Studies
Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis
humanJournal: New England Journal of Medicine. 1,637 postmenopausal women with prior vertebral fractures were randomized to one of two teriparatide doses or placebo (median follow-up 21 months). New vertebral fractures fell from 14% (placebo) to 5% and 4%, a relative risk of about 0.35 and 0.31. Non-vertebral fragility fractures fell from 6% to 3%. Spine bone density rose by 9–13 percentage points more than placebo.
Limitations: The trial was stopped early because of the rat osteosarcoma findings, which shortened follow-up. The higher dose added bone density but not more fracture reduction, and caused more side effects. Industry-sponsored.
View publication →Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety
animalJournal: Toxicologic Pathology. Fischer 344 rats received PTH(1-34) daily for 2 years at three dose levels. Bone mass rose markedly and marrow space shrank. Osteosarcoma developed in all treated groups, in a dose-dependent way. The authors argued that the near-lifelong exposure and the exaggerated rat skeletal response limit relevance to time-limited treatment in adult humans.
Limitations: Rat carcinogenicity study. It shows a hazard in rats but cannot by itself establish human risk.
View publication →Teriparatide or alendronate in glucocorticoid-induced osteoporosis
humanJournal: New England Journal of Medicine. 18-month double-blind trial in 428 women and men taking glucocorticoids long-term. Spine bone density increased more with teriparatide than alendronate (7.2% vs. 3.4%), and new vertebral fractures were fewer (0.6% vs. 6.1%). Non-vertebral fractures were similar. Raised serum calcium was more common with teriparatide.
Limitations: Bone density was the primary endpoint and fractures were secondary. Moderate size. Industry-sponsored.
View publication →Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial
humanJournal: Lancet. 1,360 postmenopausal women with severe vertebral osteoporosis were randomized to teriparatide or risedronate for 24 months. New vertebral fractures: 5.4% versus 12.0%. Clinical fractures: 4.8% versus 9.8% (hazard ratio 0.48). The reduction in non-vertebral fragility fractures (4.0% vs. 6.1%) was not statistically significant.
Limitations: Severe-osteoporosis population, so results may not generalize to milder disease. Industry-funded.
View publication →Teriparatide Did Not Increase Adult Osteosarcoma Incidence in a 15-Year US Postmarketing Surveillance Study
humanJournal: Journal of Bone and Mineral Research. U.S. cancer registries identified adult osteosarcoma cases diagnosed from 2003 to 2016, and patients were interviewed about prior medications. Three cases had prior teriparatide exposure versus 4.17 expected, a standardized incidence ratio of 0.72 (90% CI 0.20–1.86), consistent with background rates.
Limitations: Only 24% of cases were interviewed, and osteosarcoma is very rare, so precision is limited. Funded by the manufacturer.
View publication →What We Still Don't Know
• The best treatment sequence and duration across anabolic and antiresorptive drugs for different patients • How it compares on fracture outcomes with newer anabolic agents (abaloparatide, romosozumab) in large head-to-head trials • Very-long-term safety with repeated or extended courses beyond the studied durations • Its role in fracture healing, spinal fusion and other off-label uses • Effects in younger people, and why it is avoided where growth plates are open or bone cancer risk is elevated • Whether non-pharmaceutical "research" material labeled teriparatide has the identity, purity or potency of approved products.
Related Compounds
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Sources & References
- Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344(19):1434–1441.
- Vahle JL, Sato M, Long GG, et al. Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety. Toxicol Pathol. 2002;30(3):312–321.
- Saag KG, Shane E, Boonen S, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357(20):2028–2039.
- Leder BZ, Tsai JN, Uihlein AV, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015.
- Kendler DL, Marin F, Zerbini CAF, et al. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO). Lancet. 2018;391(10117):230–240.
- Gilsenan A, Midkiff K, Harris D, et al. Teriparatide did not increase adult osteosarcoma incidence in a 15-year US postmarketing surveillance study. J Bone Miner Res. 2021;36(2):244–251.
- Krege JH, Gilsenan AW, Komacko JL, Kellier-Steele N. Teriparatide and osteosarcoma risk: history, science, elimination of boxed warning, and other label updates. JBMR Plus. 2022.
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