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.

See Also: Bone Formation

Bone Metabolism Regulators

Bone metabolism is regulated by:

Hormones:

  1. Parathyroid hormone (PTH)
  2. Calcitonin
  3. Sex Hormones (estrogen, androgens)
  4. Growth Hormone
  5. Thyroid Hormones

Steroids:

  • Vitamin D
  • Gluco-corticosteroids
Bone Metabolism
Bone Metabolism

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, while it 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 of Phosphate 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.

Bone Metabolism and vitamin D
Bone Metabolism and vitamin D

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, and may also have a role in fracture healing and in reducing vertebral compression fractures in high turnover osteoporosis.

Bone Metabolism and calcitonin
Bone Metabolism and calcitonin

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.

References

  1. Millers Review of Orthopaedics -7th Edition Book.
  2. Campbel’s Operative Orthopaedics 12th 500Medition book.
  3. Shahi M, Peymani A, Sahmani M. Regulation of Bone Metabolism. Rep Biochem Mol Biol. 2017 Apr;5(2):73-82. PMID: 28367467; PMCID: PMC5346273.