Teriparatide, sold under the brand name Forteo, is a form of

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates serum calcium and phosphate through its actions on the bone, kidneys, and small intestine. PTH incre ...

(PTH) consisting of the first (

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

) 34

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s, which is the portion of the hormone activating the

Parathyroid hormone 1 receptor Parathyroid hormone/parathyroid hormone-related peptide receptor, also known as parathyroid hormone 1 receptor (PTH1R), is a protein that in humans is encoded by the ''PTH1R'' gene. PTH1R functions as a receptor for parathyroid hormone ( PTH) and ...

. It is an effective

anabolic Anabolism () is the set of metabolic pathways that construct macromolecules like DNA or RNA from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catab ...

(promoting bone formation) agent used in the treatment of some forms of

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

. Teriparatide is a recombinant human parathyroid hormone analog (PTH 1-34). It has an identical sequence to the 34 N-terminal amino acids of the 84-amino acid human parathyroid hormone.

Medical uses

Teriparatide is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of postmenopausal women with osteoporosis; for the increase of bone mass in men with primary or hypogonadal osteoporosis; and treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy. 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. Teriparatide cuts the risk of hip fracture by more than half but does not reduce the risk of arm or wrist fracture.

Contraindications

Teriparatide is contraindicated for those with open epiphyses, metabolic bone diseases,

Paget's Disease of bone Paget's disease of bone (commonly known as Paget's disease or, historically, osteitis deformans) is a condition involving Bone remodeling, cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone ...

, bone metastases, history of skeletal malignancies, or prior external beam or implant 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 two years of use.

Adverse effects

Adverse effects of teriparatide include headache, nausea, dizziness, and limb pain. Teriparatide has a theoretical risk of

osteosarcoma An osteosarcoma (OS) or osteogenic sarcoma (OGS) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchyme, mesenchymal origin (and thus a sarcoma) and that exhi ...

, 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 more than twice the incidence in the population over 60 years old (0.4 in 100,000). Teriparatide versus Placebo Adverse effects

Teriparatide versus Placebo Adverse effects

Mechanism of action

Teriparatide is a portion of human

(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.

Society and culture

Legal status

Teriparatide was approved for medical use in the United States in 1987. Teriparatide (Forteo) was approved by the FDA in November 2002, for the treatment of

in men and

postmenopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

women who are at high risk for having a fracture. In October 2019, the US FDA approved the recombinant teriparatide product with brand name Bonsity.

Biosimilars

Recombinant teriparatide is sold by

Eli Lilly and Company Eli Lilly and Company, Trade name, doing business as Lilly, is an American multinational Medication, pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 count ...

under the brand names Forteo and Forsteo. In June 2020, Alvogen, Inc, Pfenex Inc.'s commercialization partner, launched teriparatide injection (Bonsity) in the United States. Teriparatide injection was developed by Pfenex Inc and approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) in October 2019. Teriparatide injection is pharmaceutically equivalent to Forteo (that is, has the same active ingredient in the same strength, dosage form and route of administration) and has been shown to have comparable bioavailability. These characteristics allowed the product to be approved under a 505(b)(2) NDA for which Forteo was the reference drug. It may provide a lower-cost teriparatide option for increasing bone density in patients at high risk for fracture, and is FDA-approved for the same indications as Forteo, which means it can be used for the same patients as Forteo, including new patients and those currently responding to treatment. Teriparatide was approved for medical use in the European Union in June 2003. A synthetic teriparatide from Teva Generics has been authorized for marketing in the European Union. Biosimilar product from Gedeon Richter plc has been authorized in the European Union. In October 2019, the US FDA approved a recombinant teriparatide product. In June 2020, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(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. Osnuvo was approved for medical use in Canada in January 2020. Sondelbay was approved for medical use in the European Union in March 2022. On 10 November 2022, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kauliv, intended for the treatment of osteoporosis. The applicant for this medicinal product is Strides Pharma Cyprus. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Kauliv was approved for medical use in the European Union in February 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Research

Teriparatide is undergoing a clinical trial with

zoledronic acid Zoledronic acid, also known as zoledronate and sold under the brand name Zometa among others, by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bon ...

as a treatment for

osteogenesis imperfecta Osteogenesis imperfecta (; OI), colloquially known as brittle bone disease, is a group of genetic disorders that all result in bones that bone fracture, break easily. The range of symptoms—on the skeleton as well as on the body's other Or ...

to reduce the risk of broken bones.

Combined teriparatide and denosumab

Combined teriparatide and

denosumab Denosumab, sold under the brand name Prolia among others, is a human monoclonal antibody used for the treatment of osteoporosis, treatment-induced bone loss, metastasis, metastases to bone, and giant cell tumor of bone. The most common side ef ...

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.

References

{{Portal bar , Medicine Drugs developed by Eli Lilly and Company Osteoporosis drugs Parathyroid hormone receptor agonists