Teriparatide is a form of parathyroid hormone consisting of the first (N-terminus) 34 amino acids, which is the bioactive portion of the hormone. It is an effective anabolic (promoting bone formation) agent used in the treatment of some forms of osteoporosis. It is also occasionally used off-label to speed fracture healing. Teriparatide is identical to a portion of human parathyroid hormone (PTH) and intermittent use activates osteoblasts more than osteoclasts, which leads to an overall increase in bone.
|Trade names||Forteo/Forsteo, Teribone|
|Metabolism||Hepatic (nonspecific proteolysis)|
|Elimination half-life||Subcutaneous: 1 hour|
|ECHA InfoCard||100.168.733 |
|Chemical and physical data|
|Molar mass||4117.72 g/mol g·mol−1|
|3D model (JSmol)|
Recombinant teriparatide is sold by Eli Lilly and Company under the brand name Forteo/Forsteo. A synthetic teriparatide from Teva Generics has been authorised for marketing in European territories. Biosimilar product from Gedeon Richter plc has been authorised in Europe. On October 4, 2019 the US FDA approved a recombinant teriparatide product, PF708, from Pfenex Inc. PF708 is the first FDA approved proposed therapeutic equivalent candidate to Forteo.
Teriparatide has been FDA-approved since 2002. 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.
Teriparatide can be used off-label to speed fracture repair and treat fracture nonunions. It has been reported to have been successfully used to heal fracture nonunions. Generally, due to HIPAA regulations, it is not publicized when American athletes receive this treatment to improve fracture recovery. But an Italian football player, Francesco Totti, was given teriparatide after a tibia/fibula fracture, and he unexpectedly recovered in time for the 2006 World Cup. It has been reported that Mark Mulder used it to recover from a hip fracture Oakland A's for the 2003 MLB playoffs and Terrell Owens to recover from an ankle fracture before the 2005 Super Bowl.
Teriparatide is administered by injection once a day in the thigh or abdomen.
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.
Patients should not start teriparatide until any vitamin D deficiency is corrected.
Adverse 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 was approved by the 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.
Combined teriparatide and denosumab
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. Moreover, the combination therapy group showed a significant decrease in their bone formation marker, indicating that denosumab, an antiresorptive agent, might actually counteract the effect of teriparatide, a bone formation anabolic agent, in bone formation.
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