Teriparatide

Recombinant human parathyroid hormone fragment PTH(1-34), an FDA-approved bone-anabolic injection (Forteo, 2002) that stimulates new bone formation and reduces fracture risk in high-risk osteoporosis.

Also referenced as: Forteo, Bonsity, PTH(1-34), PTH 1-34, rhPTH(1-34), recombinant human parathyroid hormone (1-34), teriparatide acetate, LY333334, Teribone

Also appears in: Longevity

What is Teriparatide?

Teriparatide is a 34-amino-acid peptide identical to the N-terminal fragment of human parathyroid hormone, PTH(1-34), produced by recombinant DNA technology in E. coli (molecular weight 4117.8 Da). It was the first bone-anabolic drug approved in the United States: Forteo received FDA approval on November 26, 2002, and has since been joined by a 505(b)(2) follow-on (Bonsity, approved October 4, 2019) and ANDA generics (from November 2023 onward). The same PTH(1-34) sequence circulates in the research-peptide market as lyophilized “PTH 1-34,” where it is marketed around bone-density and fracture-healing interest.

How it works

Teriparatide activates the PTH/PTHrP type 1 receptor (PTH1R) on osteoblast-lineage cells. The direction of the effect depends entirely on exposure pattern: intermittent, once-daily pulses are anabolic, while sustained elevation (as in hyperparathyroidism) is catabolic.

• Osteoblast survival and recruitment — intermittent PTH extends the lifespan of mature osteoblasts by suppressing apoptosis and promotes exit of progenitors from the cell cycle into bone-forming cells, increasing osteoblast number at bone surfaces (Jilka, Bone, 2007;40(6):1434–1446; Jilka et al., Journal of Clinical Investigation, 1999;104(4):439–446)
• Formation outpaces resorption in the “anabolic window” — bone formation markers rise within weeks and precede the rise in resorption markers, producing net gains in trabecular bone and cortical thickness; lumbar spine BMD increased roughly 9-13 percentage points more than placebo over a median 21 months in the pivotal trial (Neer et al., New England Journal of Medicine, 2001;344(19):1434–1441)
• Dose-pattern dependence demonstrated in animals — two-year daily dosing in Fischer 344 rats produced large, dose-dependent increases in bone mass alongside proliferative bone lesions including osteosarcoma, the finding that shaped the original US label (Vahle et al., Toxicologic Pathology, 2002;30(3):312–321)
• Sequence matters after stopping — gains erode without follow-on antiresorptive therapy; in the DATA-Switch extension, switching from teriparatide to denosumab further increased BMD, whereas switching from denosumab to teriparatide produced transient bone loss (Leder et al., Lancet, 2015;386(9999):1147–1155)

Research status

Teriparatide has the deepest fracture-outcome evidence base of any peptide osteoporosis drug.

• Fracture Prevention Trial — Neer et al., N Engl J Med, 2001;344(19):1434-41. 1,637 postmenopausal women with prior vertebral fractures randomized to 20 or 40 mcg daily or placebo. New vertebral fractures fell by 65% (20 mcg) and 69% (40 mcg); nonvertebral fragility fractures fell by about half. The trial was stopped early (median observation 21 months, planned longer) when the rat osteosarcoma finding emerged, which is why the label trial exposure topped out near 2 years (median exposure 19 months on the label).
• Men with osteoporosis — Orwoll et al., J Bone Miner Res, 2003;18(1):9-17: 437 men, median 11 months of randomized treatment, significant spine and femoral neck BMD gains versus placebo. This is a BMD study, not a fracture-endpoint study.
• Glucocorticoid-induced osteoporosis — Saag et al., N Engl J Med, 2007;357(20):2028-39: 428 patients, 18 months; lumbar spine BMD +7.2% with teriparatide versus +3.4% with alendronate, with fewer new vertebral fractures (0.6% vs 6.1%); nonvertebral fractures did not differ (5.6% vs 3.7%).
• Head-to-head versus a bisphosphonate — VERO, Kendler et al., Lancet, 2018;391(10117):230-240 (NCT01709110, Phase 4, 1,360 randomized, 680 per arm): over 24 months, new vertebral fractures occurred in 5.4% on teriparatide versus 12.0% on risedronate (risk ratio 0.44), and clinical fractures in 4.8% versus 9.8%; nonvertebral fragility fractures (4.0% vs 6.1%) did not reach significance.
• Sequential therapy — DATA-Switch, Leder et al., Lancet, 2015;386(9999):1147-55, established that an antiresorptive should follow teriparatide to preserve gains.
• Osteosarcoma surveillance — the FDA-mandated 15-year US postmarketing study (Gilsenan et al., J Bone Miner Res, 2021;36(2):244-251) identified 3 teriparatide-exposed adult osteosarcoma cases against 4.17 expected (standardized incidence ratio 0.72, 90% CI 0.20-1.86). On this and claims-database evidence, FDA approved supplement S-054 on November 16, 2020, removing the boxed warning and the hard 2-year lifetime cap.
• Once-weekly regimen (Japan) — the TOWER trial (Nakamura et al., J Clin Endocrinol Metab, 2012;97(9):3097-3106) showed vertebral fracture reduction with 56.5 mcg weekly teriparatide; this regimen (Teribone) is approved in Japan but not in the US.

Fracture-healing, nonunion, and periodontal indications remain off-label and investigational, with small or inconsistent trials.

Common dosage forms

Prescription teriparatide is supplied as a single-patient, multi-dose prefilled pen for daily subcutaneous injection; the reference product delivers 20 mcg per dose (560 mcg in 2.24 mL, 28 doses). Bonsity and the ANDA generics are approved at the same 560 mcg/2.24 mL (250 mcg/mL) strength and the same 20 mcg daily dose. Japan markets a once-weekly 56.5 mcg presentation. Research vendors sell PTH(1-34) as lyophilized powder in vials, sometimes labeled by the acetate salt; the pharmaceutical API also appears as a bulk acetate powder.

Key considerations

• Regulatory status — FDA approved since 2002 for postmenopausal osteoporosis at high fracture risk, for increasing bone mass in men with primary or hypogonadal osteoporosis, and for glucocorticoid-induced osteoporosis; the FDA Approved status reflects that FDA-approved drug products containing the molecule exist. The first two ANDA generics (Teva, ANDA 208569; Apotex/Ambio, ANDA 211097) were both approved on November 16, 2023, and Amphastar’s (ANDA 213641) followed on December 12, 2025; generic pens are now widely listed. The current Forteo label is revised August 2026 (supplement S-059, approved August 3, 2026), which added Hypersensitivity Reactions (anaphylaxis, angioedema, urticaria) as a Warnings and Precautions item under a class-wide FDA safety labeling change for parathyroid hormone products. Lilly has discontinued the older 0.75 mg/3 mL pen strength, but the product itself remains marketed.
• The 2020 label revision — the boxed osteosarcoma warning and the 2-year lifetime limit were both removed on November 16, 2020 (S-054). Osteosarcoma remains a non-boxed warning, the label notes there are limited data on risk beyond 2 years of use, and it now says use beyond 2 years “should only be considered” if the patient remains at or returns to high fracture risk. It is not a license for indefinite use, and patients with open epiphyses, Paget disease, prior skeletal radiation, or bone metastases remain outside the labeled population.
• Naming confusions — teriparatide is PTH(1-34). Abaloparatide (Tymlos, approved April 2017 for women and December 2022 for men) is a PTHrP(1-34) analog, a different molecule with its own trial program (ACTIVE). Full-length PTH(1-84) was Natpara, approved for hypoparathyroidism rather than osteoporosis; Takeda discontinued its manufacture globally at the end of 2024. Palopegteriparatide (Yorvipath, approved August 2024) is a long-acting prodrug of PTH(1-34) for hypoparathyroidism, not an osteoporosis product and not interchangeable with teriparatide. Research-market “PTH 1-34” labels frequently blur these distinctions.
• Evidence gaps — fracture-endpoint data come overwhelmingly from postmenopausal women; the male and glucocorticoid indications rest mainly on BMD and small vertebral-fracture counts. Bone gains reverse after discontinuation unless followed by an antiresorptive, so the drug is one step in a sequence rather than a stand-alone course.
• Safety signals in the literature — transient hypercalcemia, orthostatic hypotension and dizziness in the first doses, hyperuricemia, and injection-site reactions are the consistent findings; hypersensitivity was added to the warnings in 2026. The rat osteosarcoma signal is dose- and duration-dependent and has not been reproduced in 15 years of US human surveillance.