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Bone Metabolism. CM Robinson Senior Lecturer Royal Infirmary of Edinburgh. Outline. Normal bone structure Normal calcium/phosphate metabolism Presentation and investigation of bone metabolism disorders Common disorders of bone metabolism. Normal Bone Structure.

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bone metabolism

Bone Metabolism

CM Robinson

Senior Lecturer

Royal Infirmary of Edinburgh

outline
Outline
  • Normal bone structure
  • Normal calcium/phosphate metabolism
  • Presentation and investigation of bone metabolism disorders
  • Common disorders of bone metabolism
normal bone structure
Normal Bone Structure
  • What are the normal types of bone in the mature skeleton?
  • Lamellar
    • Cortical
    • Cancellous
  • Woven
    • Immature
    • Healing
    • Pathological
slide4
What is the composition of bone?
  • The matrix
    • 40% organic
      • Type 1 collagen (tensile strength)
      • Proteoglycans (compressive strength)
      • Osteocalcin/Osteonectin
      • Growth factors/Cytokines/Osteoid
    • 60% inorganic
      • Calcium hydroxyapatite
  • The cells
    • osteo-clast/blast/cyte/progenitor
bone structure
Bone structure
  • Structure of lamellar bone?
  • Structure of woven bone?
bone turnover
Bone turnover
  • How does normal bone grow……..
    • In length?
    • In width?
  • How does normal bone remodel?
  • How does bone heal?
bone turnover1
Bone turnover
  • What happens to bone……….
    • in youth?
    • aged 20-40’s?
    • aged 40+?
    • aged over 70?
calcium metabolism
Calcium metabolism
  • What is the recommended daily intake?
  • 1000mg
  • What is the plasma concentration?
  • 2.2-2.6mmol/L
  • How is calcium excreted?
  • Kidneys - 2.5-10mmol/24 hrs
  • How are calcium levels regulated?
  • PTH and vitamin D (+others)
phosphate metabolism
Phosphate metabolism
  • Normal plasma concentration?
  • 0.9-1.3 mmol/L
  • Absorption and excretion?
  • Gut and kidneys
  • Regulation
  • Not as closely regulated as calcium but PTH most important
slide10
PTH
  • Physiological role
  • Production related to plasma calcium levels
  • Control of calcium levels
    • target organs
      • bone - increased Ca/PO4 release
      • kidneys
        • increased reabsorption of Ca
        • increased excretion of PO4
      • gut - indirect increase in calcium reabs by stimulting activation of vitamin D metabolism
calcitonin
Calcitonin
  • Physiological role
  • Levels increased when serum Ca >2.25mmol/L
  • Target organs
    • Bone - suppresses resorption
    • Kidney - increases excretion
vitamin d cholecalciferol
Vitamin D (cholecalciferol)
  • Sources of vit D
  • Diet
  • u.v. light on precursors in skin
  • Normal daily requirement
  • 400IU/day
  • Target organs
    • bone - increased Ca release
    • gut - increased Ca absorption
slide13
Normal metabolism

Vit D

25-HCC (Liver)

Ca/PTH

1,25-DHCC 24,25-DHCC

(Kidney) (Kidney)

factors affecting bone turnover
Factors affecting bone turnover
  • Other hormones
  • Oestrogen
    • gut - increased absorption
    • bone - decreased re-absorption
  • Glucocorticoids
    • gut - decrease absorption
    • bone - increased re-absorption/decreased formation
  • Thyroxine
    • stimulates formation/resorption
    • net resorption
factors affecting bone turnover1
Factors affecting bone turnover
  • Local factors
  • I-LGF 1 (somatomedin C)
    • increased osteoblast prolifn
  • TGF
    • increased osteoblast activity
  • IL-1/OAF
    • increased osteoclast activity (myeloma)
  • PG’s
    • increased bone turnover (#’s/inflammn)
  • BMP
    • bone formation
factors affecting bone turnover2
Factors affecting bone turnover
  • Other factors
  • Local stresses
  • Electrical stimuln
  • Environmental
    • temp
    • oxygen levels
    • acid/base balance
bone metabolic disorders
Bone metabolic disorders
  • Presentation?
  • Skeletal abnormality
    • osteopenia - osteomalacia/osteoporosis
    • osteitis fibrosa cystica - replacement of bone with fibrous tissue usually due to PTH excess
  • Hypercalcaemia
  • Underlying hormonal disorder
  • When to investigate?
    • Under 50
    • repeated fractures or deformity
    • systemic features or signs of hormonal disorder
bone metabolic disorders1
Bone metabolic disorders
  • Assessment
  • History
    • duration of sx
    • drug rx
    • causal associations
  • Examn
  • X-rays - plain and specialist (cort index/Singh index/DEXA)
  • Biochemical tests
  • Bone biopsy
biochemical tests
Biochemical tests
  • Which investigations?
  • Ca/PO4 - plasma/excretion
  • Alkaline phosphatase/osteocalcin (o’blast activity)
  • PTH
  • vit D uptake
  • hydroxyproline excretion
osteoporosis
Osteoporosis
  • Definition?
  • Decrease in bone mass per unit volume
  • Fragility (perfn of trabecular plates)
  • Primary (post-menopausal/senile) Secondary
primary osteoporosis
Primary osteoporosis
  • Post-menopausal
  • Aetiology?
  • Menopausal loss 3% vs 0.3% previously
  • Loss of oestrogen - incr osteoclastic activity
  • Risk factors?
  • Race
  • Heredity
  • Build
  • Early menopause/hysterectomy
  • Smoking/alcohol/drug abuse
  • ?Calcium intake
primary osteoporosis1
Primary osteoporosis
  • Post-menopausal
  • Clinical features?
  • Prevention and treatment?
  • General health measures/diet
  • HRT
  • Bisphosphonates
  • Calcium
  • Vitamin D
primary osteoporosis2
Primary osteoporosis
  • Senile
  • Aetiology?
  • 7-8th decade steady loss of 0.5%
  • physiological manifestation of aging
  • Risk factors?
  • Prolonged uncorrected post-menopausal loss
  • chronic illness
  • urinary insuff
  • muscle atrophy
  • diet def/lack of exposure to sun/mild osteomalacia
primary osteoporosis3
Primary osteoporosis
  • Senile
  • Clinical features?
  • as for post-menopausal
  • Treatment?
  • general health measures
  • treat fractures
  • as for post-menopausal (HRT not acceptable)
secondary osteoporosis
Secondary Osteoporosis
  • Aetiology?
  • Nutrition - scurvy, malnutr,malabs
  • Endocrine - Hyper PTH, Cush, Gonad, Thyroid
  • Drug induced - steroid, alcohol, smoking, phenytoin
  • Malignancy - ca’tosis, myeloma (o’clasts), leukaemia
  • Chronic disease - RA, AS, TB, CRF
  • Idiopathic - juvenile, post-climacteric
  • Genetic -OI
  • Clin features?
  • Investigation?
  • Treatment?
osteomalacia
Osteomalacia
  • Definition?
  • Rickets - growth plates affected, children
  • Osteomalacia - incomplete mineralisation of osteoid, adults
  • Types - vit D def, vit-D resist (fam hypophos)
  • Aetiology?
  • Decr intake/production(sun/diet/malabs)
  • Decreased processing (liver/kidney)
  • Increased excretion (kidney)
osteomalacia1
Osteomalacia
  • Clinical features?
  • In child
  • In adult
  • Investign
  • Ca/PO4 decr, alk ph incr, Ca excr decr
  • Ca x PO4 <2.4
  • Bone biopsy
osteomalacia2
Osteomalacia
  • Types
  • Vitamin D deficient
  • Hypophosphataemic
    • growth decr +++ and severe deformity with wide epiphyses
    • x-linked dominant
    • decreased tubular reabs of PO4
    • Ca normal but low PO4
    • Rx PO4 and vit D
osteomalacia vs osteoporosis
Osteomalacia vs osteoporosis

Osteomal Osteopor

Ageing fem, #, decreased bone dens

Ill Not ill

General ache Asympt till #

Weak muscles normal

Loosers nil

Alk ph incr normal

PO4 decr normal

Ca x PO4 <2.4 Ca x PO4 >2.4

hyperparathyroidism
Hyperparathyroidism
  • Excessive PTH
  • Due to prim (adenoma), sec (hypocalc), tert (second hyperact -> autonomous overact)
  • Osteitis due to fibr repl of bone
  • Clin feat - hypercalc
  • Invest - Calc incr, PO4 decr, incr PTH
  • Rx surg
renal osteodystrophy
Renal osteodystrophy
  • Combination of
  • osteomalacia
  • secondary PTH incr
  • osteoporosis/sclerosis
  • CF - renal disorder, depends on predom pathology
  • Rx - vit D or 1,25-DHCC
  • renal disorder correction
pagets
Pagets
  • Bone enlargement and thickening
  • Incr o-clast/blast activity -> increased tunrover
  • Aet - unknown but racial diff ?viral
  • CF - M=F, >50, ache but not severe unless fracture or tumour
  • Inv - x-ray app characteristic, alk ph is increased and increased hydroxyproline in urine
  • Rx - bisphos, calcitonin
endocrine disorders
Endocrine disorders
  • Cushings
  • Hypopituitarism - GH def - prop dwarf or Frohlich adiposogenital syndrome
  • Hyperpituitarism - gigantism or acromegaly
  • Hypothyroidism - cretinism or myxoedema
  • Hyperthyroidism - o’porosis
  • Pregnancy - backache, CTS, rheumatoid improves SLE gets worse
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