2 Metabolic Bone disease: Biochemistry + Radiology Flashcards
What is the normal range for Plasma [Ca2+] ?
2.15 – 2.56 mMol/L
What are the major types of imaging when looking at bone ?
Looking at density:
- X-rays
- CT
- Bone densitometry
- MRI – measure biochemical composition
- Radionuclide bone scans – measures bone turnover, tracer goes to areas of increased osteoblast activity e.g. joints, fractures, tumour site
Why is imaging useful ?
- It reveal structural failures e.g. fractures + ligamentous injuries
- It serves as proxy to metabolic dysfunction
What are radiological sings of osteoporosis?
- Loss of cortical bone (outer white lining)/thinning of cortex
- Loss of trabeculae
- Insufficiency fractures
what are insufficiency fractures?
stress fractures due to normal stress on abnormal bones
what are common sites of insufficiency fractures?
- sacrum
- underside of femoral neck, - vertebral bodies,
- pubic rami
What would you see in the imaging of insufficiency fractures?
a) XR/CT =
1. Initially normal
2. Can get periosteal reaction + callus
3. More commonly increased sclerosis around fracture lines
b) MRI: bone oedema, i.e. low signal on T1, high signal on T2 and STIR
c) Bone scan: increased osteoblastic activity i.e. increased uptake
when diagnosing osteoporosis by DEXA:
you get T-score:
Z score:
what do these scores mean?
Gives T-score: in relation to white adult pre-menopausal females
o And Z-score where ref. database is age + sex matched
o T score:
- 1.5 to -2.5 = _______
< -2.5 =
o T score:
- 1.5 to -2.5 = osteopenia,
< -2.5 = osteoporosis
What are radiological signs of osteomalacia?
- Too much un-mineralised osteoid may develop Looser’s zone
- May cause compensatory secondary hyperparathyroidism –> if calcium stays low
- Radiology depends on age + closure of growth plate
What is meant by Looser’s Zone?
when might it appear?
looser’s zone = type of insufficiency fractures/psuedofractures at high tensile stress areas
- E.g. medial proximal femur, lateral scapula, pubic rami, posterior proximal ulna, ribs
= radiological sings of osteomalacia
What do Looser’s zone look like?
o Typically, look like short, lucent lines w irregular sclerotic margins (below)
Osteomalacia Adult patient with mature skeleton (closed growth plate):
what are signs you might observe?
- Osteopenia
- Looser’s zones
- Codfish vertebrae = biconcave bone appearance (sup/inf) in both osteoporosis + osteomalacia
- Bending deformities
Osteomalacia Child patient with unclosed growth plate
what are signs you might observe?
same as adult
–> but changes would be centered mainly on growth plates
What are radiological signs of rickets ?
- Indistinct/frayed metaphyseal margin
- Widened growth plate w/o calcification
- Cupping/splaying metaphyses due to increased weight bearing on soft bone
- Enlargement of anterior ribs
- Osteopenia
What are radiological signs of hyperparathyroidism ?
Primary:
- see bone resorption
Secondary (e.g. due to CKD):
- see bone resorption AND increased density
Bone resorption common sites: o Subperiosteal o Subchondral o Intracortical (within bone) o Brown Tumours, large lytic bone lesion (hyperparathyroidism, cancer, etc.)
Renal Osteodystrophy = special type of primary / secondary hyperparathyroidism
Renal Osteodystrophy = special type of primary hyperparathyroidism
What are radiological signs of renal osteodystrophy?
- Osteomalacia + osteoporosis
- May cause secondary hyperparathyroidism, leading to:
- -> Subperiosteal erosions, brown tumours
–> Sclerosis – vertebral endplates giving rugger jersey spine = vertebrae have thick top and bottom but less dense centre
–> Soft tissue calcification (e.g. around vessels or cartilages)
What are radiological signs of paget’s disease?
- Cortical thickening
- Bone expansion (usually doesn’t cross joint)
- Coarsening of trabeculae
- Osteolytic, osteosclerotic, and mixed lesions
- Osteoporosis circumscripta – see lucent (pale) spaces, holes in bones
* Paget’s tends to affect 1 BONE, and probably not adjacent bones
cancellous bone metabolically active / inactive
cancellous bone metabolically active
calcium you take in about ______ /day
1 g /day
how many % of Ca is protein bound?
how many % of Ca is free ionized ?
how many % of Ca is protein bound?
46%
how many % of Ca is free ionized ?
7%
decrease in Ca2+
[describe what happens]
PTH :
in bone:
in kidney :
PTH : increases
in bone: increase resorption
in kidney : increases Ca2+ absorption (via TRPV5/6 channel in DCT)
What is PTH - how many a.acid - dependent on: T1/2 = PTH receptor is also activated by =
- 84 amino acid peptide
- Mg dependent
- T1/2 = 8 min
- PTH receptor = activated also by PTH rP (high during breast feeding)
note: PTH has receptor on osteoblast
which signal through RANKL - to osteoclast to differentiate and absorb bone
-
Primary hyperparathyroidism =
- more common in females
- primarily due to adenoma
-
how would you diagnose primary HPT
- increase in ca2+ with PTH levels elevated / non suppressed (or in upper half of normal range)
what re clinical features of primary HPT
- symptoms are usually due to high ca:
- thirst
- poly uria
- tiredness
- fatigue
- muscle weakness
stones, abdominal moans, psychic groans
How does high serum calcium cause diuresis?
high serum calcium causes diuresis
ca receptors on cell –> switches off K+ recycling in ascending limb
which causes diuresis
–> increase dehydration
chronically elevated PTH causes increased / decreases cortical bone resorption
- increased / decreased bone turnover
chronically elevated PTH causes increased cortical bone resorption
- increased bone turnover
When would surgery be recommended for Primary HPT?
- serum Ca2+ > 0.25mmol/L
- high 24hr urine Ca2= > 10mmol
- reduced creatinine clearance
what biochemicals would you find in primary hyperparathyrodism?
describe how Vit D is metabolized by the liver and kidney
7 dehydrocholesterol –> cholecalciferol (via UV)
cholecalciferol –> 25 -cholecalciferol
25 -cholecalciferol
note:
most absorption of vit d in gut = paracellular
-
what is Rickets
inadequate Vit D activity leads to defective mineralisation of the cartilaginous growth
whatclincal features can hypocalcemia cause ?
- chvostek’s sign
- bronchospasm
- Trousseau’s sign
- cardiac failure
What could be some causes of rickets/ osteomalacia?
- dietary
- drugs
- small bowel malabsorption
- chronic renal failure
- rare hereditary conditions
What could be some causes of rickets/ osteomalacia?
- dietary
- drugs
- small bowel malabsorption
- chronic renal failure
- rare hereditary conditions
biochemistry in rickets/ osteomalacia
serum [Ca2+ ] =
serum [PO43- ] =
serum [Alk Phos ] =
serum [24(OH)vit D ] =
serum [Ca2+ ] low
serum [PO43- ] low
serum [Alk Phos ] High
serum [24(OH)vit D ] low
note:
FGF23 + PTH hormones causes loss of phosphate
NPT2a + NPT2c (channels) = in luminal membrane
wastes phosphate out of kidney
-
excess FGF23 can cause ____________
rickets / osteomalacia
–> increased renal phosphate wasting
when kidney proximal tubule damaged (falcon syndrome)
–> causes phosphaturia
why does this happen ?
damage to kidney proximal tubule affects 1 alpha hydroyxaltyon of vit D
when kidney proximal tubule damaged (falcon syndrome)
–> causes phosphaturia
why does this happen ?
damage to kidney proximal tubule affects 1 alpha hydroxylation of vit D
dense things like bone = white on XRAY + CT
Muscle + FAT = darker on XRAY + CT
-
vertebrae - should be paler
- if vertebrae = darker
oedema inside bone / sot tissue lesion
What is osteoporosis?
- decreased quantity of bone mass
- -> fragility fractures
- -> can cause deformity + pain
- -> with normal microvasculature
Note: FRAX risk assessment test
-
what is osteomalacia?
- decreases bone mineralisation
- -> forms osteopenic bone
- -> soft bone
- if there is too much unmineralized osteoid –> forms looser’s zone.
- can also form secondary hyperparathyroidism if Ca2+ remains low
What are the 3 phases of Paget’s Disease?
- lytic phase
- mixed lytic/sclerotic phase
- sclerotic phase
What is Paget’s disease?
- disease of bone remodeling
- -> causes bone pain/deformity/fractures
- -> patients = prone to osteogenic sarcoma
