osteomalacia

Question 1

Definition of osteomalacia

Answer 1

disorder of mineralisation of the bone matrix - the osteoid

normal amount of bone but mineral content is low - excess uncalcified osteoid and cartilage

Question 2

definition of rickets

Answer 2

disorder of defective mineralisation of cartilage in the epiphyseal growth plates of children

when defective mineralisation occurs in growth

Question 3

2 mechanisms of aetiology of osteomalacia

Answer 3

vit D def

renal phosphate wasting

Question 4

summarise how vit D def = osteomalacia

Answer 4

lack of sunlight exposure

dietry def or malabsorption (small bowel disease eg coeliac/IBD, extensive bowel surgery, gastrectomy, pancreatic insufficiency)

low 25-hydroxylation of vit D (liver disease, anticonvulsants)

low 1ahydroxylation (renal osteodystrophy, CKD, hypoparathyroidism, mutation in genes encoding 1a hydroxylase)

vit D resistance - mutations in the vit D receptor gene

Question 5

summarise how renal phosphate wasting can cause osteomalacia

Answer 5

fanconi’s syndrome (phosphaturia, glycosuria, amino aciduria)

renal tubular acidosis (type 2)

hereditary hypophosphataemic rickets (X linked or autosomal dominant)

tumour induced osteomalacia - oncogenic hypophosphtaemia - raised tumour production of phosphatonin fibroblast growth factor 23 (FGF-23) - hyperphosphaturia = myalgia and weakness

Question 6

epidemiology of osteomalacia

Answer 6

uncommon in industrialised countries

more common in females

Question 7

symptoms of osteomalacia

Answer 7

bone pain - especially axial skeleton

weakness

malaise

Question 8

symptoms of rickets

Answer 8

hypotonia

growth retardation

skeletal deformities

apathy in infants

knock kneed

bowed legs

ill

Question 9

signs of osteomalacia

Answer 9

bone tenderness

prox muscle weakness

waddling gait

signs of hypocalcaemia:

• trousseau’s sign - inglation of the sphygmomanometer cuff to above SBP for >3min = tetanic spasm of wrist and fingers
• chvostek’s sign - tapping over facial nerve = twitching of ipsilateral facial muscles

Question 10

signs of rickets

Answer 10

bossing of frontal and parietal bones

swelling of costochondral junctions (rickety rosary)

bow legs in early childhood

knock knees in later childhood

short stature

features of hypocalcaemia

Question 11

investigations for osteomalacia

Answer 11

• blood
  
  • low or normal Ca2+
  • low phos
  • high AlkPhos
  • low 25(OH)vit D (except in resistance)
  • in renal failure - low 1,25(OH)2-vit D
  • high PTH - secondary hyperPTH
  • UE
  • ABG - pts with renal tubular acidosis have normal anion gap hyperchloraemic met aciodosis
• high phosphate excretion - if renal phosphate wasting not cause of hypophosphataemia, fractionak excretion of phosphate should be <5%
• XR
  
  • normal or osteopenia
  • looser’s zones or pseudofractures (radiolucent bands) in ribs, scapular, pubic rami or upper femer
• bone biopsy after double tetracyclon labelling
  
  • tetracycline deposited at mineralisation front as a band
  • after 2 courses separated by days, distance between bands is low in osteomalacia
  • not usually performed because cdx from Hx, Ex, lab and radiology
  • shows incomplete mineralisation
• muscle biopsy if proximal myopathy is normal
• XR

Question 12

XR in osteomalacia

Answer 12

loss of cortical bone

apparent partial fractures w/o displacement - especially on lateral border of the scapula, inferior femoral neck, medial femoral shaft ie Looser’s zones

cupped, ragged metaphyseal surfaces seen in ricket’s

Question 13

managment of osteomalacia

Answer 13

Vit D and Ca replacement

• in dietary insufficiency - calcium D3 forte tablet/12h PO
• in malabsorption/hepatic disease - ergocalciferil up to 1mg/day, or parenteral calcitriol eg 7.5mg/mo
• renal disease or vit D resistence - alfacalcidol (1a-hydroxy-vit D) 250ng-1mcg daily, or calcitriol 250ng-1mcg daily - adjust dose according to plasma Ca

monitor 24hr urinary Ca, serum Ca, phosphate, AlkPhos, PTH, vit D

treat underlying cause - advice on diet and sunlight exposure

X-linked hypophosphtaemia - oral phosphate and 1,25 (OH)2 vit D

Question 14

complications of osteomalacia

Answer 14

bone deformaties

hypocalcaemia can cause epileptic seizure

cardial arrythmias,

hypocalcaemic tetany

depression

alfacalcidol and calcitriol can cause dangerous hypercalcaemia

Question 15

prognosis of osteomalacia

Answer 15

symptoms and radiology improve with treatment

bone deformaties in children are permenant

Question 16

metabolism of vit D

Answer 16

from diet (fish/eggs), or synthesised in skin from 7-dehydrocholesterol

activated by hydroxylation into 1, 25 - (OH)2 vit D in liver and kidney

Question 17

mechanism of tumour induced osteomalacia

Answer 17

high fibroblast growth factor - 23 (FGF-23)

causes high renal phosphate loss (phosphate diabetes)

Question 18

Vit D resistant rickets

Answer 18

exists in 2 forms

Type 1 - low renal 1a hydroxylase activity

Type 2 - end organ resistence to 1,25-dihydroxy-vitamin D3 - point mutation in the receptor

both treated with large doses of cacitriol

Question 19

x-linked hypophosphtaemic rickets

Answer 19

dominantly inherited - defect in renal phosphate handling

(due to mutations in the PEX and PHEX genes which encode an endopeptidase)

rickets develops in early childhood and is associated with poor growth

plasma phos is low, ALP high, phosphaturia

treatment - high oral doses of oral phosphate and calcitriol