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Teriparatide is a synthetic derivative of parathyroid hormone (PTH), specifically consisting of the first 34 biologically active amino acids from the N-terminus. It has proven to be extremely effective in treating certain forms of osteoporosis by promoting bone formation.
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What Is Teriparatide?
Teriparatide, an anabolic agent, is a derivative of parathyroid hormone (PTH) comprised of the first biologically active 34 amino acids from the N-terminus. This synthetic form of PTH is successfully employed in treating certain types of osteoporosis, as it promotes bone formation. Teriparatide is a recombinant human parathyroid hormone analog (PTH 1-34), exhibiting an exact match with the 34 N-terminal amino acids found in the 84-amino acid human parathyroid hormone.
Teriparatide Peptide Structure
Peptide Sequence: Ser Val Ser Glu Ile Gln Leu Met His Asn Leu Gly Lys His Leu Asn Ser Met Glu Arg Val Glu Trp Leu Arg Lys Lys Leu Gln Asp Val His Asn Phe-OH
Molecular Formula: C181H291N55O51S2
Molecular Weight: 4117.77 g·mol−1
PubChem CID: 16129682
Teriparatide is prescribed for specific conditions: postmenopausal women with osteoporosis, men with primary or hypogonadal osteoporosis to increase bone mass, and both men and women with osteoporosis due to sustained systemic glucocorticoid therapy.
This medication is remarkably effective in promoting bone growth, with notable outcomes such as an 8% increase in bone density in the spine after a year of use and a significant reduction in the risk of fragility fractures.
Teriparatide notably reduces the risk of hip fractures by over half; however, it does not have a significant impact on the risk of arm or wrist fractures.
Mechanism of action
Osteoporosis arises when there is an imbalance between bone formation and bone resorption. In certain conditions like sex steroid deficiency, rheumatoid arthritis, and specific malignancies, resorption outpaces formation due to heightened bone turnover. Antiresorptive treatments, such as estrogen, raloxifene, bisphosphonates, and calcitonin, act by inhibiting both aspects of bone remodeling, but they primarily slow down resorption rather than promoting formation.
Teriparatide, on the other hand, represents a groundbreaking anabolic, or bone-building drug, where bone formation is stimulated more than resorption. Initially, this may seem counterintuitive to clinicians, as elevated levels of parathyroid hormone (PTH) in hyperparathyroidism typically lead to reduced bone mineral density (BMD) and increased fracture risk.
Research has shed light on the mechanism behind this phenomenon. After administering PTH, bone formation quickly follows as it increases osteoblast formation and inhibits osteoblast apoptosis. This leads to a rise in bone turnover and formation.
Intermittent administration of Teriparatide increases the number of bone-forming osteoblasts, while continuous administration increases the number of bone-resorbing osteoclasts. Overall, each cycle of PTH results in a net increase in bone mass. Importantly, the bone formed under this treatment resembles “good” bone, as demonstrated by histomorphometry and peripheral quantitative CT (pqCT), exhibiting enhanced trabecular width and number, similar in structure to bone found in younger individuals. This remodeling process predominantly occurs in bone areas subjected to mechanical stress.
Teriparatide is not recommended for individuals with open epiphyses, metabolic bone diseases, Paget’s Disease of bone, bone metastases, a history of skeletal malignancies, or prior external beam or implant radiation therapy involving the skeleton. In both animal studies and one human case report, there were indications that extended use of Teriparatide for over two years might be associated with the development of osteosarcoma in test subjects.
Effects on Calcium and Phosphate Homeostasis
Teriparatide exhibits similar actions to the body’s natural parathyroid hormone (PTH) concerning calcium and phosphate regulation, resulting in increased serum calcium levels and decreased serum phosphate levels. These effects stem from the well-established impact of PTH on both the kidneys and bones.
Within the kidneys, PTH stimulates the reabsorption of calcium in the distal tubules while inhibiting phosphate reabsorption in the proximal tubules. Additionally, it activates the 1-alpha-hydroxylase enzyme located in the proximal tubules. This enzymatic activity converts filtered 25-hydroxyvitamin D into the most active form of vitamin D, known as 1,25-dihydroxy vitamin D.
In bone, Teriparatide facilitates the mobilization of calcium from the bone matrix into the bloodstream, contributing to the overall regulation of calcium and phosphate homeostasis in the body.
|Dimensions||10 × 10 × 20 mm|