Teriparatide

What it is

The body’s own parathyroid hormone consists of 84 amino acids and is the main regulator of calcium and phosphate balance. Teriparatide corresponds exactly to its first 34 amino acids, the active section, hence the designation rhPTH(1-34). It is produced by genetic engineering in bacteria.

The manufacturer Eli Lilly brought it to market as Forsteo, in the US as Forteo. The European approval dates from June 10, 2003. There are now several biosimilars, that is, copies of biological products, for example Movymia since January 11, 2017, Terrosa or Livogiva.

In the biohacking world, teriparatide stands alongside its younger relative abaloparatide. Neither is a research peptide; both are tested medicines with a summary of product characteristics and pharmacovigilance. Interest beyond osteoporosis focuses mainly on the healing of bones and tendons.

How it works

Bone is constantly being broken down and built up. Parathyroid hormone can trigger both; according to the summary of product characteristics, the effect depends on how the bone is exposed to the hormone. Once-daily administration stimulates the bone-forming cells more than the bone-resorbing ones and lets new bone substance grow on the trabeculae inside and on the outer layer.

The rhythm follows from the pharmacology. The half-life after injection is about 1 hour. The calcium level in the blood rises slightly, reaches its maximum after 4 to 6 hours and is back at baseline after 16 to 24 hours.

In humans the chain of effects has been measured, from the bone formation markers in the blood through bone density to the fracture rate. In the pivotal trial, bone density in the lumbar spine rose by 9 percentage points more under the approved dose than under placebo.

What the studies show

Neer et al., NEJM 2001

The pivotal trial with 1,637 postmenopausal women who already had vertebral fractures. They injected one of two doses of teriparatide or placebo daily, followed for a median of 21 months. New vertebral fractures occurred in 14 percent under placebo and in 5 and 4 percent in the two teriparatide groups, relative risk 0.35 and 0.31. Low-trauma fractures outside the spine fell from 6 to 3 percent. The higher dose brought more bone density but no additional fracture protection and more side effects. The trial was stopped early because bone tumors had occurred in rats.

VERO, Lancet 2018

Double-blind comparison with dummy preparations on both sides, 1,360 women with severe osteoporosis, 680 per group, 24 months of teriparatide versus risedronate. Primary endpoint new vertebral fractures, met: 5.4 versus 12.0 percent, relative risk 0.44. Clinical fractures 4.8 versus 9.8 percent. Fractures outside the spine 4.0 versus 6.1 percent, not statistically significant. Funded by Eli Lilly.

Saag et al., NEJM 2007

428 women and men who had been taking cortisone for at least 3 months, 18 months double-blind teriparatide versus alendronate. Bone density of the lumbar spine rose by 7.2 versus 3.4 percent. New vertebral fractures 0.6 versus 6.1 percent, fractures outside the spine 5.6 versus 3.7 percent with no significant difference. Elevated calcium levels were more frequent under teriparatide.

Aspenberg et al., J Bone Miner Res 2010

The most important study on the healing question: 102 women with a distal radius fracture at the wrist, 8 weeks of placebo or one of two teriparatide doses. The primary comparison, higher dose versus placebo, missed its target (p = 0.523). Only in a post hoc analysis did the fracture heal under the lower dose after a median of 7.4 instead of 9.1 weeks.

Where the data stop

Protection against hip fractures has not been demonstrated; the summary of product characteristics says so explicitly. In men, bone density is well supported, but a significant effect on fracture frequency is not. Even in the comparison with risedronate, the advantage for fractures outside the spine remained statistically uncertain.

The hope for faster healing has not been fulfilled in studies so far. A meta-analysis of 5 randomized trials with 380 patients found better function but no faster or more frequent healing on X-ray and no reduced pain. In femoral neck fractures (159 patients), 17 percent under teriparatide needed repeat surgery, under placebo 14 percent. In pelvic fractures (35 patients), 50 versus 53 percent had healed after 3 months, although physical performance improved only under teriparatide. After rotator cuff repair at the shoulder (50 patients), a triple-blind trial found no difference after 1 year, re-tears in 8.7 versus 10 percent. There are no data for healthy people without osteoporosis.

Status, approval and legal

Approved in the EU since June 10, 2003 as Forsteo, plus several biosimilars. Indications: osteoporosis in postmenopausal women and in men at high fracture risk, and osteoporosis caused by long-term cortisone therapy. Prescription-only. According to the summary of product characteristics, 20 micrograms once a day under the skin, for a total of no more than 24 months, and this treatment should not be repeated in a lifetime; this is information from the summary of product characteristics, not a usage recommendation. In the US, Forteo is approved; there the boxed warning on bone tumors was removed in 2020, and use beyond 2 years can be considered if fracture risk remains high. Use for healing fractures or tendons is off-label. In the German translation of the 2026 WADA Prohibited List, teriparatide is not listed by name; anyone who competes in sport should clarify this with NADA in advance.

Safety

In the studies, 82.8 percent under teriparatide and 84.5 percent under placebo reported at least one adverse event. The most common are nausea, limb pain, headache and dizziness. During the first applications, blood pressure can drop briefly on standing up within 4 hours. Uric acid was above the normal range in 2.8 percent, under placebo in 0.7 percent. In the comparison with abaloparatide, hypercalcemia was more frequent under teriparatide, 6.4 versus 3.4 percent. It is not used in pregnancy and breastfeeding, with pre-existing elevated calcium, severe kidney failure, other bone metabolic diseases such as Paget’s disease, unexplained elevated alkaline phosphatase, prior radiation of the skeleton, bone cancer or bone metastases, or with open growth plates. Caution with digitalis. Rats treated for almost their whole lives developed osteosarcomas in a dose-dependent manner. In humans, a 15-year US surveillance showed no increased risk: 3 observed cases after teriparatide versus 4.17 expected.

Sources

• Neer et al., NEJM 2001 – pivotal trial, 1,637 women
• Kendler et al., Lancet 2018 – VERO, teriparatide versus risedronate
• Saag et al., NEJM 2007 – glucocorticoid-induced osteoporosis, teriparatide versus alendronate
• Orwoll et al., J Bone Miner Res 2003 – bone density in 437 men
• Aspenberg et al., J Bone Miner Res 2010 – distal radius fracture, 102 women
• Shi et al., PLoS One 2016 – meta-analysis on fracture healing
• Guity et al., JB JS Open Access 2025 – rotator cuff, triple-blind
• Gilsenan et al., J Bone Miner Res 2021 – 15 years of osteosarcoma surveillance
• EMA – Forsteo, summary of product characteristics (German)
• Krege et al., JBMR Plus 2022 – removal of the boxed warning in the US