Parathormone(PTH)

Composition and Mechanism of action:

• Endogenous PTH is an 84-amino-acid peptide that is largely responsible for calcium homeostasis
• Although chronic elevation of PTH, as occurs in hyperparathyroidism, is associated with bone loss (particularly cortical bone), PTH can also exert anabolic effects on bone
• Unlike antiresorptive therapies that reduce bone resorption, parathyroid hormone (PTH) is an anabolic agent that enhances osteoblastic bone formation.
• Biologic activity of the intact hormone resides within the N-terminal 1-34 fragment; fragments from the mid- and C-terminal regions lack biologic activity.
• Teriparatide is a synthetic polypeptide hormone that contains the 1-34 amino acid fragment of recombinant human PTH (rhPTH [1-34]), a sequence identical to the biologically active N-terminal region of the 84-amino acid human PTH.
• They bind to specific cell-surface receptors on target cells in bone and kidney with high affinity.
• Daily single-dose administration causes a transient increase in serum PTH concentration, promoting new bone formation on both cancellous and cortical bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity
• Continuous infusions, which result in a persistent elevation of PTH, lead to greater bone resorption than daily injections.
• Whereas daily injections of PTH increase bone volume, the net effect of continuous infusions is a decrease in bone volume.
• Daily PTH injections build bone by uncoupling bone turnover as the serum PTH level rises above normal for several hours, then falls below normal for many hours.
• The pattern of changes in serum PTH, combined with the pattern of elevation in biochemical markers of bone remodeling (increases in bone formation markers followed by increases in bone resorption markers), suggests a pathway through which daily PTH injection may temporarily uncouple bone turnover
• Teriparatide produces increases in bone mass and mediates architectural improvements in skeletal system
• These effects are lower when patients have been previously exposed to bisphosphonates, possibly in proportion to the potency of the antiresorptive effect

Dosage and uses:

• 20 microgm PTH exogenous PTH analogue (1-34hPTH; teriparatide) is used as a single daily SC injection for the treatment of postmenopausal osteoporosis in women with a high risk of fracture.
• These patients include women with a history of osteoporotic fracture, multiple risk factors for fracture, intolerance with osteoporosis therapy, or failure with therapy
• Teriparatide is also FDA-approved for the treatment of men with primary or secondary hypogonadal osteoporosis who are at high risk of fracture.
• After a 20-μg SC injection, PTH reaches peak serum concentration in approximately 30 minutes and declines to nondetectable levels within 3 hours.
• Combining PTH with antiresorptives has demonstrated even greater improvements in BMD that persist for at least 1 year after PTH is discontinued.

Adverse effects and Special Precautions:

• Side effects of teriparatide are generally mild and can include muscle pain, weakness, dizziness, headache, and nausea. Hypercalcemia can occur and symptoms typically appear 4 to 6 hours after injection
• Orthostatic hypotension can occur
• PTH should be used with caution in patients with urolithiasis and dose reduction is necessary in patients with renal insufficiency
• Teriparatide is not recommended for women who are pregnant or nursing.
• Teriparatide should not be prescribed for patients at increased risk for osteosarcomas, including patients with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, children or young adults with open epiphyses, or patients who have undergone prior radiation therapy of the skeleton.
• In addition, teriparatide should not be administered to patients with preexisting hypercalcemia, bone metastases, or a history of skeletal malignancies or metabolic bone diseases other than osteoporosis