Bone Physiology PDF

Two types of bones: cortical (compact/lamellar) vs trabecular (medullary/cancellous/spongy) Bone matrix consists of osteoid (mainly type I collagen fibers) and hydroxyapatite (calcium and phosphate) crystals which allow the bone to have both tensile and compressive strengths. Three major cell type...

Two types of bones: cortical (compact/lamellar) vs trabecular (medullary/cancellous/spongy) Bone matrix consists of osteoid (mainly type I collagen fibers) and hydroxyapatite (calcium and phosphate) crystals which allow the bone to have both tensile and compressive strengths. Three major cell types: Osteoblasts Osteoclasts Osteocytes  C BONE MATRIX components Organic (30-35%) Osteoid Type I Collagen GAGs (chondroitin sulfate, keratin sulfate, hyaluronic acid) Non-collagen proteins (osteocalcin, osteonectin, osteopontin) Inorganic (65-70%) Calcium phosphate as hydroxyapatite crystals: Ca10(PO4)6(OH)2 Other minerals A THE BONE CELLS osteoblast, osteoclast, osteocyte Osteoblasts – Bone formation Osteoclasts – Bone resorption Osteocytes – Mechanosensor, transport Osteoblasts form bone by secreting proteins into the extracellular matrix. Type I collagen, osteocalcin and other proteins form osteoid which acts as scaffold for deposition of minerals. Alkaline phosphatase (ALP) breaks down pyrophosphate (PPi), which prevents calcium and phosphate precipitation, thereby promotes bone mineralization. ALP levels are associated with bone formation and are used as a clinical marker of bone formation. Ca2+ and PO43– (Pi) form hydroxyapatite crystals which is the main inorganic component of the bone. Other minerals also helps strengthened the bone. Osteoblasts express RANK ligand (RANKL) which binds to RANK (receptor activator of nuclear factor κB) on the surface of osteoclasts and activates them. Osteoprotegerin (OPG), also produced by osteoblasts, competitively binds to RANKL and prevents it from activating RANK. PTH stimulates osteoclast function through osteoblasts. Calcitriol stimulates osteoblast differentiation and increase OPG release. A sustained increase in PTH levels promotes bone resorption by indirectly increases osteoclastic activity. Resorp bone Express RANK Stimulated by RANKL and inhibited by calcitonin (transiently) Form seal around the area where they work and create Howship’s lacuna under it. Release acid (created by enzyme carbonic anhydrase) into the Howship’s lacuna to dissolves calcium and phosphate, and release proteolytic enzymes to break down collagen fibers.  AB BONE REMODELING formation & resorption iers enbaum res, 4th ed , 2016 Bone remodeling is the cycle of bone formation and resorption regulated by the balance between RANK and OPG from osteoblasts, with additional input from hormones (PTH, vitamin D, and calcitonin) and osteocytes. The body uses bone remodeling to preserve structural integrity of the skeleton and to maintain calcium homeostasis.  AB BONE REMODELING formation & resorption Adapted from Bern e y, th ed , 201 AB BONE REMODELING formation & resorption ‐ Surrounded by bone fluid which is high in calcium and phosphate due to transport and release by osteocytes. (High concentration of calcium and phosphate and the lack of precipitation inhibitors such as pyrophosphate [PPi] promote deposition of calcium phosphate [CaPO4]) ‐ Form gap junctions with each other and osteoblasts (transfers signals and minerals) ‐ Sense mechanical loading on the bone by sensing the movement of bone fluid and electrical field (piezoelectricity). ‐ Can both inhibit and stimulate osteoblasts. Most of calcium in the body is in bone in the form of hydroxyapatite crystals. Intracellular calcium levels are kept low by sequestering calcium in organelles such as mitochondria and endoplasmic reticulum. The levels of calcium ion in the body are tightly regulated within a narrow range due to calcium ion’s important roles in several physiological processes. Extracellular calcium concentration are much higher (~10,000 fold) than intracellular calcium concentration, maintaining a large concentration gradient between the two compartments. About half of the total calcium in extracellular fluids is in ionized form (Ca2+), the rest is either bound to albumin (40%) or complexed with anions such as phosphate and citrate (10%). Three hormones are involved in regulating calcium levels. Parathyroid hormone (PTH) increases serum calcium levels by three mechanisms. PTH increases bone resorption and renal reabsorption of calcium. Furthermore, PTH also stimulates activation of vitamin D in kidney which is essential for vitamin D action. PTH, however, decreases renal phosphate reabsorption. Note that short‐term PTH effects promote bone formation but prolonged high PTH levels will lead to bone resorption. Active vitamin D (calcitriol) increases serum calcium levels by increasing intestinal calcium absorption (via its genomic effect resulting in synthesis of calbindin which is required for calcium absorption). It increases reabsorption of both calcium and phosphate in kidney. It also stimulates both osteoblastic and osteoclastic activities resulting in increased bone turnover. Calcitonin (CT) decreases serum calcium by inhibiting dietary calcium absorption, osteoclastic bone resorption, and renal reabsorption of calcium. The regulation of phosphate levels in the body is closely related to that of calcium. The hormones that regulate calcium levels also regulate phosphate but their actions vary. PTH increases resorption of bone, hence releasing phosphate into the ECF. It also inhibits reabsorption of phosphate in kidney so the overall effect of PTH on phosphate level is to decrease phosphate levels in the body. Calcitriol increases bone turn over so the effect on phosphate could be minimal. However, calcitriol increases intestinal absorption and renal reabsorption of phosphate. The overall effect of calcitriol hence is increasing phosphate levels in the body. Calcitonin prevents bone resorption and renal reabsorption of phosphate. The effect on the phosphate pool is net decrease in phosphate due to increase renal loss.