Normal bone metabolism is a sequence of bone turnover (osteoclast activity) and formation (osteoblast activity).

Bone Metabolism functions largely involve the homeostasis of calcium and phosphate.

Bone Metabolism Regulators

Bone metabolism is regulated by:

  • Hormones:
    • Parathyroid hormone (PTH)
    • Calcitonin
    • Sex Hormones (estrogen, androgens)
    • Growth Hormone
    • Thyroid Hormones
  • Steroids:
    • Vitamin D
    • Gluco-corticosteroids

Calcium

  • More than 99% of the body’s calcium is stored in bones.
    • Approximately 400 mg of calcium is released from bone daily.
  • Calcium absorption:
    • Calcium is absorbed in the duodenum by active transport.
    • Calcium is absorbed in the jejunum by passive diffusion.
  • Primary homeostatic regulators of serum calcium are PTH and 1,25(OH)2-vitamin D3.

Dietary requirement of calcium:

  • Approximately 600 mg/day for children.
  • Approximately 1300 mg/day for adolescents and.
  • young adults (ages 10-25 years).
  • 750 mg/day for adults (ages 25-50 years).
  • 1200-1500 over the age of 50.
  • 1500 mg/day for pregnant women.
  • 2000 mg/day for lactating women.
  • 1500 mg/day for postmenopausal women and for.
  • patients with a healing fracture in a long bone.

Phosphate

  • A key component of bone mineral:
    • Approximately 85% of the body’s phosphate stores are in bone.
  • Also important in enzyme systems and molecular interactions as a metabolite and buffer.
  • Daily requirement is 1000 to 1500 mg.

Parathyroid hormone (PTH)

  • PTH is synthesized in and secreted from chief cells of the (four) parathyroid glands.
  • PTH helps regulate plasma calcium.
    • Decreased calcium levels in extracellular fluid stimulate β2 receptors to release PTH, which acts at the intestines, kidneys, and bones.
  • PTH directly activates osteoblasts.
  • PTH:
    • Modulates renal phosphate filtration.
    • May accentuate bone loss in elderly persons.
    • PTH-related protein and its receptor have been implicated in metaphyseal dysplasia.

Vitamin D

  • It’s activated by ultraviolet radiation from sunlight or utilized from dietary intake.
  • Vitamin D hydroxylated to 25(OH)-vitamin D3 in the liver, and hydroxylated a second time in the kidney to one of the following:
    • 1,25(OH)2-vitamin D3, the active hormone.
    • 24,25(OH)2-vitamin D3, the inactive form.
  • 1,25(OH)2-vitamin D3 works at the intestines, kidneys, and bones.
  • It maintains normal serum calcium levels by activating osteoclasts for bone resorption and increasing intestinal absorption of calcium (increase serum Ca++)
  • And promotes the mineralization of osteoid matrix.

Calcitonin

  • Calcitonin produced by clear cells in the parafollicles of the thyroid gland.
  • Increased extracellular calcium levels cause secretion of calcitonin.
  • Calcitonin inhibits osteoclastic bone resorption:
    • Osteoclasts have calcitonin receptors.
    • Calcitonin decreases osteoclast number and activity.
  • It Decreases serum calcium level.
  • May also have a role in fracture healing and in reducing vertebral compression fractures in highturnover osteoporosis.

Estrogen

  • Estrogen prevents bone loss by inhibiting bone resorption.
  • Estrogen therapy decreases bone formation:
    • Supplementation is helpful in postmenopausal women only if started within 5 to 10 years after onset of menopause.

Corticosteroids

  • Corticosteroids affects bone metabolism by increase bone loss and decrease bone formation.
    • Decrease gut absorption of calcium by decreasing binding proteins.
  • Decrease bone formation (especially cancellous) by inhibiting collagen synthesis and osteoblast productivity.

Thyroid hormones

  • Thyroid hormones increase bone resorption and can lead to osteoporosis.
  • Regulates skeletal growth at the physis by Stimulates:
    • Chondrocyte growth
    • Type X collagen synthesis
    • Alkaline phosphatase activity

Growth hormone

  • Causes positive calcium balance by increasing gut absorption of calcium more than it increases urinary excretion.
    • Insulin and somatomedins participate in this effect.

Growth factors

  • Transforming growth factor (TGF)-β, PDGF, monokines, and lymphokines have roles in bone and cartilage repair.