Treatment of
osteoporosis, as an antiosteoporotic, in the treatment of
bone and mineral disease and disorders, bone metabolism
regulator, blood calcium regulator, and as a diagnostic aid
(pseudohypoparathyroidism; hypocalcemia).
Human rPTH (1-34) has been produced by recombinant
technologies, is now approved, and will soon be available
for the treatment of osteoporosis. It is given subcutaneously,
25 μg/day cyclically for 12 to 18 months, to increase
bone density in individuals with a history of fractures,
severe osteopenia, or osteoporosis. PTHrP (1-36)
has also been synthesized and is in early clinical trials.
Parathyroid hormone (PTH) exerts its effects on bone and kidney cells. This hormone plays a role in calcium homeostasis. PTH is secreted from the chief cells of the parathyroid gland in response to low extracellular calcium levels or higher levels of extracellular phosphate. PTH deficiency or excess PTH are associated with hypoparathyroidism and hyperparathyroidism, respectively.
Parathyroid Hormone Human Recombinant (C181H290N55O51S2) produced in E.Coli is a single, non-glycosylated, polypeptide chain containing 34 amino acids and having a molecular mass of 4117.8 Dalton.
The PTH is purified by proprietary chromatographic techniques.
Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calciumin the blood, whereas calcitonin (a hormone produced by the parafollicular cells of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptorin three parts of the body: In the bones- It enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone.
In the kidney- It enhances active reabsorption of calcium from distal tubules and the thick ascending limb.
In the intestine- It enhances the absorption of calcium in the intestine by increasing the production of vitamin D and upregulating the enzyme responsible for 1-alpha hydroxylationof 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D) which effects the actual absorption of calcium (as Ca2+ ions) by the intestine via calbindin.
Recombinant Human full length PTH 1-84 has potential as an anti-osteoporotic agent, due to its properties as a bone formation stimulant, it increases bone turnover, stimulating osteoblasts and reducing both vertebral and non vertebral fractures.
