Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Role of parathyroid hormone, vitamin D and calcitonin in Bone Remodeling Dr Agha Shafique Department of Biochemistry Bone Remodeling Bone remodeling is a continuous process of bone resorption and bone formation for the purpose of maintaining normal bone mass: Bone Deposition is the apposition or formation of new bone as a normal physiologic process. Bone Resorption is a process involving the breakdown of bone by specialized cells known as osteoclasts CALCIUM Calcium is the most important mineral of the body About 99% of calcium is present in bones and teeth, 1% is present outside the skeletal tissue Calcium has wide variety of functions Calcium cont… Functions: Development of bones & teeth Muscle contraction Nerve transmission Blood coagulation Calmodulin mediated action Act as intracellular messenger Parathyroid Hormone Human PTH is a linear polypeptide that contains 84 a.a residues. It is synthesized as part of larger molecule containing 115 a.a residues (pre-proPTH). Actions of Parathyroid Hormone PTH act directly on bones to increase bone resorption & mobilize Ca 2+. In addition to increasing plasma Ca2+ , PTH increases phosphate excretion in urine. This phosphaturic action is due to a decrease in reabsorption of phosphate in the proximal tubules. Actions of PTH cont… PTH also increases reabsorption of Ca2+ in the distal tubules PTH also increases the formation of 1,25 dihydroxy Cholecalciferol, and this increases Ca2+ absorption from intestine Actions of PTH cont… On longer time scale, PTH stimulates osteoclasts and osteoblasts with the effect osteoclasts predominating so that more Ca2+ is mobilized from bone. Regulation of secretion of PTH Circulating ionized calcium acts directly on the parathyroid gland in a negative feedback fashion to regulate the secretion of PTH. Regulation of PTH cont… when the plasma Ca2+ level is high ,PTH secretion is inhibited and the Ca2+ is deposited in bones. When it is low, secretion is increased and Ca2+ is mobilized from the bones . Role of vitamin D The active transport of Ca2+ & PO4 from intestine is increased by metabolite of vitamin D. Vitamin D3 which is also called cholecalciferol is produced in skin from 7dehydrocholesterol by action of sunlight. Role of vitamin D cont… In liver vitamin D3 is converted to 25hydroxycholecaciferol(25-OH D3). It is then converted to 1,25 dihydroxycholecalciferol (calcitriol ) in the proximal tubules of kidney. Role of vitamin D cont… In addition to increasing Ca2+ absorption from the intestine, it also facilitates Ca2+ reabsorption in the kidneys. It acts on bones, where it stimulates calcium uptake for deposition as calcium phosphate. Thus calcitriol is essential for bone formation Role of vitamin D cont… The formation of 1,25 dihydrocholicalciferol in the kidneys which is catalyzed by 1alpha hydroxylase is regulated in feed back fashion by plasma Ca2+ & PO4. Its formation is facilitated by PTH and when the plasma Ca2+ level is low, PTH secretion is increased. Calcitonin Human calcitonin has M.W 3500 and contains 32 amino acid residues. Calcitonin is not secreted until the plasma calcium level reaches approximately 9.5mg/dl and that above this calcium level . Plasma calcitonin is directly proportionate to plasma calcium . Actions of Calcitonin Calcitonin lowers the circulating calcium and phosphate levels. It exerts its calcium lowering effect by inhibiting bone resorption. This action is direct, and calcitonin inhibits the activity of osteocalsts. Rickets It is due to deficiency of Vitamin D during childhood. The full-blown condition in children is characterized by weakness and bowing of weight bearing bones, dental defects and hypoclacemia. Osteomalacia – It is due to deficiency of vitamin D during adulthood, results from demineralization of bones, especially in women who have little exposure to sunlight, often after several pregnancies. . THANKS