|Trade names||Forteo, Forsteo, Teribone, Bonsity|
|Drug class||Parathyroid hormone (PTH)|
|Side effects||Pain, nausea, rash, depression, problems with teeth|
|Defined daily dose||20 ug OD|
|Metabolism||Liver (nonspecific proteolysis)|
|Elimination half-life||Subcutaneous: 1 hour|
|Chemical and physical data|
|Molar mass||4117.77 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Teriparatide, sold under the brand name Forteo among others, is a form of parathyroid hormone (PTH) used to treat osteoporosis. It may be used in those in who bisphosphonates do not work or those at very high risk. It is given by injection under the skin. It may be used for up to two years.
Common side effects include pain, nausea, rash, depression, and problems with the teeth. Other side effect may include an increased risk of osteosarcoma, anaphylaxis, low blood pressure with standing. It consists of the active portion of PTH and works by promoting bone formation.
Teriparatide was approved for medical use in the United States in 2002 and Europe in 2003. In the United Kingdom a month supply costs the NHS about £240 as of 2021. This amount in the United States costs about 3,900 USD.
It is effective in growing bone (e.g., 8% increase in bone density in the spine after one year) and reducing the risk of fragility fractures. When studied, teriparatide only showed bone mineral density (BMD) improvement during the first 18 months of use. Teriparatide should only be used for a period of 2 years maximum. After 2 years, another agent such a bisphosphonate or denosumab should be used in cases of osteoporosis although repeat administration has been used in hypophosphatasia, where biphosphonates are contraindicated.
Teriparatide cuts the risk of hip fracture by more than half but does not reduce the risk of arm or wrist fracture.
There is tentative evidence that it may help heal fracture nonunions.
It is used at a dose of 20 ug per day for up to 2 years.
Teriparatide should not be prescribed for people who are at increased risks for osteosarcoma. This includes those with Paget's Disease of bone or unexplained elevations of serum alkaline phosphate, open epiphysis, or prior radiation therapy involving the skeleton. In the animal studies and in one human case report, it was found to potentially be associated with developing osteosarcoma in test subjects after over 2 years of use.
Side effects of teriparatide include headache, nausea, dizziness, and limb pain. Teriparatide has a theoretical risk of osteosarcoma, which was found in rat studies but not confirmed in humans. This may be because, unlike humans, rat bones grow for their entire life. The tumors found in the rat studies were located on the end of the bones which grew after the injections began. After nine years on the market, there were only two cases of osteosarcoma reported. This risk was considered by the FDA as "extremely rare" (1 in 100,000 people) and is only slightly more than the incidence in the population over 60 years old (0.4 in 100,000).
Mechanism of action
Teriparatide is a portion of human parathyroid hormone (PTH), amino acid sequence 1 through 34, of the complete molecule (containing 84 amino acids). Endogenous PTH is the primary regulator of calcium and phosphate metabolism in bone and kidney. PTH increases serum calcium, partially accomplishing this by increasing bone resorption. Thus, chronically elevated PTH will deplete bone stores. However, intermittent exposure to PTH will activate osteoblasts more than osteoclasts. Thus, once-daily injections of teriparatide have a net effect of stimulating new bone formation leading to increased bone mineral density.
Teriparatide is the first FDA approved agent for the treatment of osteoporosis that stimulates new bone formation.
Teriparatide was approved by the US Food and Drug Administration (FDA) on 26 November 2002, for the treatment of osteoporosis in men and postmenopausal women who are at high risk for having a fracture. The drug is also approved to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. On October 4, 2019, the US FDA approved a recombinant teriparatide product, Teriparatide Injection (previously referred to as PF708 and Bonsity) from Pfenex Inc. Teriparatide Injection is the first FDA approved proposed therapeutic equivalent candidate to Forteo.
Teriparatide injection was developed by Pfenex Inc and approved by the US Food and Drug Administration (FDA) on October 4, 2019.Biosimilar product from Gedeon Richter plc has been authorised in the European Union. On October 4, 2019, the US FDA approved a recombinant teriparatide product.
In June 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of the biosimilar products Qutavina and Livogiva. Qutavina and Livogiva were approved for medical use in the European Union in August 2020.
Combined teriparatide and denosumab increased BMD more than either agent alone and more than has been reported with approved therapies. Combination treatment might, therefore, be useful to treat patients at high risk of fracture by increasing BMD. However, there is no evidence of fracture rate reduction in patients taking a teriparatide and denosumab combination. The first such trial was published by Leder et al. in Lancet in 2013 with further data subsequently published in JCEM in a trial of post menopausal osteoporotic women demonstrating larger bone mineral density increases in the spine and hip with combination therapy compared to either drug alone.
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