Skeleton and Metabolism (MS system)

Question 1

Functions of bone

Answer 1

• Structure: give structure and shape to body
• Mechanical: sites for muscle attachment
• Protective: vital organs and bone marrow
• Metabolic: reserve of calcium and other minerals

Question 2

What is bone?

Answer 2

Inorganic 65%:

• calcium hydroxyapatite (Ca10(PO4)6(OH)2)
• storehouse for 99% of calcium in body
• 85% of phosphorus, 65% sodium, magnesium

Organic 35%:
- bone cells and protein matrix

Question 3

Endocrine regulation of bone

Answer 3

• Parathyroid hormone
• Thyroid hormone
• Growth hormone
• Insulin like growth factor
• Oestrogen

Question 4

Calcium homeostasis

Answer 4

• from the GI tract to soft tissue and kidney and to bones and reverse
• GI tract has calcium intake of approx 1g/day
• kidney has calcium excretion into urine and is moderated by reabsorption
• bone is reservoir to maintain homeostasis

Question 5

Parathyroid hormone (PTH)

Answer 5

• low calcium stimulates PTH release
• PTH stimulates resorption via RANKL/OPG
• PTH also stimulates osteoblast differentiation
• intermittent PTH treatment is anabolic
• continuous PTH treatment is catabolic
• PTH causes Ca2+ from bone to be released into bloodstream
• active vitamin D3 production
• high calcium and D3 inhibit PTH production

Question 6

Calcium homeostasis summary

Answer 6

• low serum calcium stimulates PTH production in parathyroid glands
• PTH acts to increase serum calcium concentration by:
• increase bone resorption
• increase calcium reabsorption in kidneys
• stimulates active vitamin D3 production, increasing calcium absorption in gut
• high serum calcium and active vitamin D3 inhibit PTH production

Question 7

Osteocytes

Answer 7

• osteocytes are endocrine cells
• embedded in lacunae in mature bone
• connected via processes through. canalicular channels
• form a mechanosensory network throughout bone
• they communicate with systemic circulation as well as bone cells
• high serum phosphate stimulates FGF23 syntheses in osteocytes

Question 8

FGF23

Answer 8

• Fibroblast Growth Factor
• In 2000, activating mutations in GFG23 were identified in patients with autosomal dominant hypophosphatemic rickets
• acts to increase phosphate excretion in kidney
• FGF23 actions to reduce serum phosphate:
• decreases phosphate reabsorption in kidneys
• inhibits PTH production (decrease release of phosphate via bone resorption)
• inhibits active vitamin D3 production (decrease phosphate absorption in gut)

Question 9

What is a metabolic bone disease?

Answer 9

• a group of diseases that cause reduced bone mass and reduced bone strength
• due to imbalance of various chemicals in the body (vitamins, minerals, hormones, etc)
• causes altered bone cell activity, rate of mineralisation or changes in bone structure
• eg of disease is osteoporosis

Question 10

Rickets/ Osteomalacia

Answer 10

• defective mineralisation of normally synthesised bone matrix
• rickets in children
• effectively two types:
  1) deficiency of vitamin D3 (causing hypocalcemia)
  2) deficiency of phosphate
• oncogenic osteomalacia (mesenchymal tumours producing excess FGF23)

normal bone:
- mostly mature mineralised bone, little unmineralised osteoid
osteomalacia:
- little mature mineralised bone, mostly unmineralised osteoid

outcomes:

• bone pain/tenderness
• fracture
• proximal weakness
• bone deformity

Question 11

Hyperparathyroidism

Answer 11

Excess PTH:

• hypercalcemia
• hypophosphatemia

Primary:

• parathyroid adenoma (85-90%)
• chief cell hyperplasia

Secondary:

• chronic renal deficiency
• vit D deficiency
• Osteiris fibrosa cystica

Question 12

Hyperparathyroidsm (Mnemonic)

Answer 12

• stones (kidney stones)
• bones (pain from osteitis fibrosa cystica and excess bone resorption)
• abdominal moans (acute pancreatitis)
• psychic groans (psychosis and depression)