1-3: Metabolic Bone diseases Flashcards
What is the composistion of bone?
- 65% inorganic material
- calcium hydroxyapatite (Ca10(PO4)6(OH)2)
- 99% of Calcium, 85% of the Phosphorus, 65% Sodium, Magnesium in body
- Organic
- Bone cells
- Matrix (Collagen)
What is the epiphysis, metaphysis and diaphysis of bone?
How can you devide bones anatomically?
Into
- long
- sesamoid
- flat
- short/cuboid
- irregular
bones
How can you classify bone Macroscopically?
Can devide into
- trabecular/cancellous/spongy bone
- Cortical/compact bone
How can you classify bone on a microscopic level?
- Lamellar (mature) bone
- Woven (immature) bone
What is calcellous bone?
Trabercular Bone
- 20% of human skeleton
- axial (center of body)
- highly metabolic active
- large surface area
- 15-20% calcified
What is cortical bone/skeleton?
What are its characteristics?
Long bones
- appendicular
- 80-90% calcified
- mainly structural, mechanical, and protective
Explain the microanatomy of cortical bone
- Osteons (made up of several concentric lamellar) surrounding a central canal
- All surrounded by a Circumferential lamellae
Explain the microanatomy of cancellous bone
Trabecular bone
- Made up of interconnected trabeculae
- All arranged in lamellars (but without central canal)
What is the role of osteocytes?
How do they fulfill this function in the bone remodeling cycle?
- They are the “brain of the bone”, embedded in mature bone and sense damage
- If damage sensed: activation of immature osteoclasts via apoptosis + RANKL receptor
What is the role of osteoclasts?
What are their characteristics?
What is their function in the bone remoddling cycle?
Are multinuclear cells that resorb/remove bone
- get activated via RANKL/RANK
- Resorb damaged/old bone
What are osteoblasts?
What is their role in the bone-remodelinc cycle?
produce osteoid to form new bone
Identify the different bone cells
What are the riasons why you would perform a bone biopsy?
- Confirm the diagnosis of a bone disorder
- Find the cause of or evaluate ongoing bone pain or tenderness
- Resolve problems that can’t the solved by radiology alone
- Investigate an abnormality seen on X-ray
- For bone tumour diagnosis (benign vs malignant)
- To determine the cause of an unexplained infection
- To evaluate therapy performance
What are the different types of bone biopsy that can be performed?
- Closed
- needle
- for core biopsy
- Open
- for inacessible/large areas
What is the most commonest site for bone biopsy?
Why?
A transiliac biopsy because all types of bone can be seen
Which stains are available for bone biopsys?
What are they used for respectively?
- H&E
- Masson - Goldner Trichrome
- mineralised vs unmineralised bone
- Tetracycline/Calcein labelling
- bone turnover (2 flourescent injection with a break ov several days –> dye is incorporated into bone –> measure thickness between 2 lines)
What is oeteoporosis (per definition)?
Defines as BMD (bone mieral density) of T-score -2.5 SDV (T-score= peak bone mass in 25 Yr old)
What is the difference between primary and secondary osteoporosis?
- Due to age+ menopause
- Due to drugs, systenic disease
What is the difference between high and low turnover osteoporosis?
Osteoporosis generally: more bone is resorbed than produced
High turnover= a lot is produced but even more resorbed
Low turnover= little production and a little more resorbtion
Which part of the bone is primarily affected by osteoporosis?
How?
Mainly the trabercular bone
–> fewer, thinner and free floatin trabercular bone sections
What are the histological findings of osteoporotic bone?
Fever, thinner free floating trabercular bone
(Histopathology might be useful in determining high vs. low turnover disease but for diagnosis/ follow up biochemistry + imaging more useful)
What are the radiological abnormalities you can observe in osteoporosis?
- Loss of cortical bone/thinning of cortex
- Loss of trabeculae
- Codfish vertebrae
- Insufficiency fractures
- areas of increased uptake of a bone scan due to stress fracture
- bone oedema
- Sclerosis: attempted healing of fractured bone
What is a “cod fish vertebra”?
When can it be seen?
Biconcave deformity of vertebrae Seen in
- Osteoporosis
- Osteomalacia
What is a looser zone?
Pseudo/insufficicnecy fractures at high tensile stress areas
- Medial proximal femur
- Lateral scapula
- Pubic rami
- Posterior proximal ulna Ribs
What is the difference between an insuficiency fracture and a looser zone?
Looser zone are a sub-type of insufficiency fractures (= normal force on abnormal bone causes fracture) that usually only traversing part way through a bone, usually at right angles to the involved cortex
Looser zones are associated with osteomalacia and rickets
Which biochemical tests would you perform to investigate osteoposis?
Why?
Mainly to exclude other reasosn:
In primary osteoporosis all findings should be normal (there might be high uring Ca2+ levels) but exclude
- Vit D: deficiency
- any 2nd endocrine causes
- Primary hyperparathyroitidsm (high PTH)
- hyperthyroidism (high T3, supressed TSH)
- Hypogonadism (low Testosterone)
- Exclude multiple myeloma
What is osteomalacia/rickets?
What are the commonest reasons?
Failure to mineralise immature (woven) bone–> normally due to
- Vit D deficiency
- PO4 deficiency
What are the histopathological finding in osteomalacia?
Increased unmineralised/ woven bone
What are the radiological finding in rickets?
Rickets= osteomalacia before growth plate closes
- Osteopenia, Looser’s zone, Codfish vertebrae, Bending deformities
- +
- Indistinct/frayed metaphyseal margin
- Widened growth plate without calcification
- Cupping/splaying metaphyses due to weight
bearing
- Enlargement of anterior ribs
What are the radiological signs in osteomalacia?
Mature skeleton
- Osteopenia
- Looser’s zones
- Codfish vertebrae
- Bending deformities
How would the biochemical findings look in Someone with rickets/ osteomalacia?
- Calcium N/low
- Phosphate N/low
- Alk phos High
- 25(OH)Vit D Low
- PTH High (secondarily to compensate)
•Urine
- Phosphate High
What are the signs and symptoms of a child with rickets?
Lack of play, often due to
- Bone pain and tenderness (axial)
- Muscle weakness (proximal)
- Age dependent deformity
- Myopathy
- Hypotonia
- Short stature
- Tenderness on percussion
What is the effect and role of FGF-23?
It is involved in regulating phosphate levels
- produced by osteoclasts
- trigger PO4 excretion
- inhibit Vit D activation
What are the biochemical findings of someone with primary hyperparathyroidism?
- High Ca2+
- High PTH
- Low Po4
- High Vit D
What are the radiological finding in someone with Hyperparathyroidism?
Causes increased bone resorbtion leading to
- Subperiosteal
- irregular bone borders
- Subchondral
- dark areas below chondyles
- Intracrotical
- “Brown tumours”–> osteitis fibrosa cystica (replacement of bone matrix with connective tissue)
What is renal osteodystrophy?
It is a combination of skeletal changes resulting from chronic renal disease
Explain the effects and clinical features of renal osteodystrophy
- Increased bone resorption (osteitis fibrosa cystica)– Osteomalacia
- – Osteosclerosis
- – Growth retardation
- – Osteoporosis
What are the radiological changes that can be seen in renal osteodystrophy?
- Osteomalacia and osteoporosis
- Secondary hyperparathyroidism
- Subperiosteal erosions, brown tumours
- Sclerosis – vertebral endplates giving a rugger jersey spine
- Soft tissue calcification (vessels, cartilages)
What would be the biochemical findings in Pagets disease?
Increased Alkaline phosphatase, otherwise normal (might have increased Ca2+) (+increased bone formation)
What would be the radiological findings in Pagets disease?
- Cortical thickening
- Bone expansion
- Coarsening of trabeculae
- Osteolytic, osteoclerotic and mixed lesions
- Osteoporosis circumscripta
- cranial loss of bones/cycts
What are the different stages of Pagets disease?
- Osteolytic
- Osteolytic-osteosclerotic
- Quiescent osteosclerotic
What are the histological finding in someone with pagets disease?
Dependant on the phase:
- thickened cortex
- high number of osteoclasts
- woven bone
What are the clinical symptoms of someone with Pagets disease?
- pain
– microfractures
– nerve compression (incl. Spinal N and cord)
– skull changes may put medulla at risk
– deafness
– +/- haemodynamic changes, cardiac failure
– hypercalcaemia
– Development of sarcoma in area of involvement 1%
What is the difference between pathology and a radiological signs?
A Pathology
- A disease process that gives rise to symptoms, signs,biochemical disturbances and changes in imaging appearance.
Radiological sign
- A change in imaging appearance, whether structural or functional, that may point towards a pathology
Which test are run in a bone profile?
- Calcium
- Corrected calcium
- Phosphate
- Alkaline Phosphatase
What is corrected calcium?
It takes into account the total calcium and the albumnin levels (–> if low albumin levels–> calcium will be higher for that patient)
What is the role of Alkaline phosphatase?
There is a liver and a bone form
It is involved in:
- essential for mineralisation
- regulates concentrations of phosphocompounds
–> often high in conditions with high bone formation (Osteomalacia, Bone metastases, Hyperparathyroidism, Hyperthyroidism)
Explain the effect of Calcium in the loop of Henle
Basically acts like a loop diuretic:
Inhibits the Cl+/NA+/K+ cotransporter for reabsorbtion of water and ions
–> Induces diuresis
What is the Fanconi syndrome?
It is damage to the proximal tubule of the kidney resulting in
- causes phosphaturia
- stops 1α hydroxylation of Vit D
due to
- multiple myeloma
- heavy metal poisoning: lead, mercury
- drugs: tenofovir, gentamycin
- congenital disease: Wilsons, glycogen storage diseases
Which biochemical marker of bone formation and resorbtion can be used in the monitoring of osteoporosis treatment?
Explain its origin
Formation
- P1NP = Procollagen type 1 N-terminal Propeptide, measured in blood (terminal ends of collagen precursor –> not used anymore
- but Mainly Alkaline Phosphatase
Resorbtion
- serum CTX
- urine NTX –> crossliks of collagen molecules that are released during bone break down
