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Anatomy and Metabolism of Bone

Parathormone!!navigator!!

= key modulator of calcium homeostasis

Origin: chief cells of 4 parathyroid glands

Major stimulus: low levels of serum calcium ions (action requires vitamin D presence)

Target organs:

  • BONE: mobilization of calcium at bone surface ←↑ in osteoclastic activity
  • KIDNEY:
    1. ↑renal tubular absorption of calcium
    2. ↓tubular reabsorption of phosphate (+ amino acids) = phosphaturia
    3. ↑hydroxylation of 25-OH vitamin D (see below under vitamin D metabolism)
  • GUT:↑ absorption of calcium + phosphorus

Major function:

  • increase of serum calcium levels
  • increase in serum alkaline phosphatase (50%)

Vitamin D Metabolism!!navigator!!

required for

  1. adequate calcium absorption from gut
  2. synthesis of calcium-binding protein in intestinal mucosa
  3. parathormone effect (→ stimulation of osteoclastic + osteocytic resorption of bone)

Biochemistry:

inactive form of vitamin D3 present through diet / exposure to sunlight (photoconversion of 7-dehydrocholesterol in skin to cholecalciferol)

  • vitamin D3 is converted into 25-OH-vitamin D3 by liver
  • 25-OH-vitamin D3 is converted into 1,25-OH vitamin D3 (biologically most active form = hormone) by kidney
    1. ↑intestinal absorption of calcium
    2. binds to intranuclear receptors within bone → production of mediators for calcium mobilization + mineralization of organic matrix

Stimulus for conversion: (1) Hypophosphatemia

(2) PTH elevation

Action:

(a) BOWEL:(1) ↑ absorption of calcium from bowel
(2) increased absorption of phosphate from distal small bowel
(b) BONE:(1) proper mineralization of osteoid
(2) mobilization of calcium + phosphate (potentiates parathormone action)
(c) KIDNEY:(1) ↑ absorption of calcium from renal tubule
(2) ↑ absorption of phosphate from renal tubule
(d) CELL:binds to receptor on nucleus → activation of genes involved in calcium homeostasis

Calcitonin!!navigator!!

secreted by parafollicular cells of thyroid

Major stimulus: increase in serum calcium

Target organs:

(a) BONE:(1) inhibits parathormone-induced osteoclasis by reducing number of osteoclasts
(2) enhances deposition of calcium phosphate; responsible for sclerosis in renal osteodystrophy
(b) KIDNEY:inhibits phosphate reabsorption in renal tubule
(c) GUT:increases excretion of sodium + water into gut

Major function: decreases serum calcium + phosphate

Outline