Bone Metabolism and Calcium

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Bone Metabolism and Calcium
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Bone

• Function
• Supports the body and protects vital organs
• Reservoir of calcium and phosphate
• Composition
• Calcium, phosphate, magnesium and sodium
• Hard calcified connective tissue consisting of
  different types of cells (osteoprogenitor cells,
  osteoblasts, osteocytes and osteoclasts)
• Calcified extracellular matrix formed mainly of
  Collagen
• Osteocalcin (protein) and Osteonectin
  (glycoprotein)

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Types of bone cells

• There are four cell types
• Osteoprogenitor cells are proliferating cells
  appearing on bone surface that differentiate into
  osteoblasts
• Osteoclasts are the cells involved in bone
  resorption (bone breakdown), by releasing
  lysosomal enzymes. They are large cells that
  dissolve the bone. They come from the bone marrow
  and are related to white blood cells. They are
  formed from two or more cells that fuse together,
  so the osteoclasts usually have more than one
  nucleus. They are found on the surface of the
  bone mineral next to the dissolving bone.

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• Osteoblasts are cells that synthesize and secrete
  the osteoid (collagen) and then calcify it. They
  are the cells that form new bone. They also come
  from the bone marrow and are related to
  structural cells. They have only one nucleus.
  Osteoblasts work in teams to build bone. They
  produce new bone called "osteoid" which is made
  of bone collagen and other protein. Then they
  control calcium and mineral deposition. They are
  found on the surface of the new bone.
• Osteocytes are inactive osteoblasts that have
  completed their function in matrix formation.
  They are cells inside the bone. Some of the
  osteoblasts turn into osteocytes while the new
  bone is being formed, and the osteocytes then get
  surrounded by new bone. They are not isolated,
  however, because they send out long branches that
  connect to the other osteocytes. These cells can
  sense pressures or cracks in the bone and help to
  direct where osteoclasts will dissolve the bone.

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Physiological Role of Calcium

• Maintain the integrity of the skeleton
• Calcium phosphate incorporated into bone and
  teeth
• Control of biochemical processes
• Intracellular
• Activity of a large number of enzymes
• Conveying information from the surface to the
  interior of the cell (2nd messenger)
• Extracellular
• Muscle contraction and nerve function
  (neurotransmitter release into synapse)
• Blood clotting (cofactor for enzymes involved in
  blood clotting)
• Release of peptide/amine hormones from endocrine
  cells

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• The biochemical role of Calcium requires that its
  blood plasma concentrations be precisely
  controlled
• Normal concentration of about 9 mg/dl must be
  maintained within small tolerances despite
• variations in dietary calcium levels
• variation in demand for calcium
• Humans and other mammals have an effective
  feedback mechanism for regulating plasma
  concentration of calcium Cap

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Calcium in the Body

• 99 body calcium in skeleton
• 0.9 intracellular
• 0.1 extracellular
• Exists in free and bound states, 50 bound
• Albumin (40 total calcium)
• Phosphate and citrate (10 total calcium)

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Major sites of Calcium regulation
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The hormones that regulate calcium homeostasis

• Parathyroid hormone (PTH) secreted in response to
  low blood calcium concentration. Increases
  calcium by
• Stimulating renal conversion of 25-(OH)D3 to
  1,25-(OH)2D which increases intestinal Ca
  absorption.
• Directly stimulates renal Ca absorption and
  PO43- excretion.
• Stimulates osteoclastic resorption of bone
• 1,25(OH)2D (vitamin D metabolite)
• Increases GI absorption of dietary Ca
• Stimulates both osteoblast and osteoclast
  activity according to the concentration of Ca in
  the blood
• Mineralization of bone
• Calcitonin secreted in response to high calcium
  in blood
• Inhibit osteoclastic resorption of bone
• Increases renal Ca and PO43- excretion

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Feedback mechanism that controls calcium
homeostasis

• Four organs
• the parathyroid glands,
• intestine,
• kidney,
• and bone
• together determine the parameters of calcium
  homeostasis.

• , positive effect -, negative effect 1,25 D,
  1,25-dihydroxy vitamin D ECF, extracellular
  fluid PTH, parathyroid hormone.