bone metabolism cm robinson senior lecturer royal infirmary of edinburgh
TRANSCRIPT
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Bone Metabolism
CM RobinsonSenior Lecturer
Royal Infirmary of Edinburgh
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Outline
• Normal bone structure
• Normal calcium/phosphate metabolism
• Presentation and investigation of bone metabolism disorders
• Common disorders of bone metabolism
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Normal Bone Structure• What are the normal types of bone
in the mature skeleton?• Lamellar
– Cortical– Cancellous
• Woven– Immature– Healing– Pathological
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• 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
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Bone structure
• Structure of lamellar bone?
• Structure of woven bone?
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Bone turnover
• How does normal bone grow……..– In length?– In width?
• How does normal bone remodel?
• How does bone heal?
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Bone turnover
• What happens to bone……….– in youth?– aged 20-40’s?– aged 40+?– aged over 70?
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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)
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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
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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
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Calcitonin
• Physiological role
• Levels increased when serum Ca >2.25mmol/L
• Target organs– Bone - suppresses resorption– Kidney - increases excretion
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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
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• Normal metabolism
Vit D
25-HCC (Liver)
Ca/PTH 1,25-DHCC 24,25-DHCC (Kidney) (Kidney)
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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
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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
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Factors affecting bone turnover
• Other factors• Local stresses• Electrical stimuln• Environmental
– temp– oxygen levels– acid/base balance
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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
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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
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Biochemical tests• Which investigations?• Ca/PO4 - plasma/excretion• Alkaline phosphatase/osteocalcin
(o’blast activity)• PTH• vit D uptake • hydroxyproline excretion
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Osteoporosis
• Definition?• Decrease in bone mass per unit
volume
• Fragility (perfn of trabecular plates)
• Primary (post-menopausal/senile) Secondary
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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
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Primary osteoporosis
• Post-menopausal
• Clinical features?
• Prevention and treatment?• General health measures/diet• HRT• Bisphosphonates• Calcium• Vitamin D
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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
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Primary osteoporosis• Senile• Clinical features?• as for post-menopausal• Treatment?• general health measures• treat fractures• as for post-menopausal (HRT not
acceptable)
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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?
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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)
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Osteomalacia
• Clinical features?• In child• In adult
• Investign• Ca/PO4 decr, alk ph incr, Ca excr
decr• Ca x PO4 <2.4• Bone biopsy
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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
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Osteomalacia vs osteoporosis
Osteomal Osteopor Ageing fem, #, decreased bone densIll Not illGeneral ache Asympt till #Weak muscles normalLoosers nilAlk ph incr normalPO4 decr normalCa x PO4 <2.4 Ca x PO4 >2.4
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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
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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
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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
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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