Indications
Teriparatide is prescribed for the treatment of osteoporosis. It is used in individuals who are at high risk of fractures, including postmenopausal women, men with primary or hypogonadal osteoporosis, and individuals with glucocorticoid-induced osteoporosis. Its primary purpose is to enhance bone strength and reduce the likelihood of fractures.
Pharmacodynamics
Teriparatide functions as an analog of parathyroid hormone (PTH) and plays a crucial role in stimulating bone formation in both men and women. It significantly increases skeletal mass and elevates markers of bone formation, such as bone-specific alkaline phosphatase (BSAP) and procollagen I carboxy-terminal propeptide (PICP), thereby enhancing bone strength. Similar to endogenous PTH, teriparatide influences calcium and phosphate homeostasis, leading to a temporary increase in serum calcium levels and urinary calcium excretion. Clinical trials have also demonstrated its effect in causing transient phosphaturia and mild, temporary reductions in serum phosphorus concentration.
Absorption
Following subcutaneous administration of a 20 microgram dose, teriparatide exhibits an absolute bioavailability of approximately 95%. The peptide reaches peak serum concentration within about 30 minutes, and its levels diminish to non-quantifiable status within three hours.
Metabolism
Although specific metabolism studies on teriparatide have not been conducted, it is posited that the peripheral metabolism of parathyroid hormone occurs predominantly through non-specific enzymatic mechanisms in the liver.
Mechanism of Action
Teriparatide exerts its effects on the skeletal system by mimicking the actions of parathyroid hormone (PTH), an endogenous hormone critical in regulating calcium and phosphate metabolism in bones and the kidneys. PTH operates by binding to specific receptors, influencing bone metabolism and calcium absorption. When PTH is present in excess, as seen in hyperparathyroidism, it can lead to increased osteoclast activity and heightened bone resorption. Notably, the impact of PTH is contingent upon both dosage and the pattern of exposure-where continuous exposure favors bone resorption, whereas intermittent low doses predominantly encourage bone formation. Similarly, teriparatide's action is also dependent on its administration pattern. When administered once daily, teriparatide preferentially stimulates osteoblastic activity, encouraging new bone formation on trabecular and cortical bone surfaces. This action is facilitated by teriparatide binding to PTH type 1 receptors (PTH1R), which are G-protein coupled receptors found on osteoblasts, osteocytes, and renal tubular cells. This binding activates downstream signaling pathways, such as protein kinase A (PKA) and protein kinase C (PKC), which enhance bone anabolic effects. Teriparatide also increases the expression of cytokines and growth factors that support both osteoclast and osteoblast activities while downregulating sclerostin, a known inhibitor of bone formation, thereby promoting osteoblast differentiation and contributing to improved bone health.
