Metabolic Bone Disorders - 25-02-04

FRACTURES (Robbins pp 1229-1230, Fig: 28-17)

Three stages: 1) procallus, 2) bony union, 3) organisation of fracture callus

Procallus (Day 2-3): haematoma --> fibrin meshwork (framework for inflammatory cells) --> inflammatory cells migrate to release cytokines --> osteoprogenitor cells activate --> osteoblastic / osteoclastic activity occurs (periosteum, medullary cavity, soft tissues) --> haematoma organises (uncalcified tissue forms) --> procallus (weight bearing not possible).

Bony union (Day 5-6): osteoprogenitor cells deposit woven bone beneath periosteum --> activated mesenchymal cells in soft tissue differentiate into chondroblasts --> lay down cartilage --> as woven bone approaches cartilage endochondral ossification occurs --> bony union (bony callus, weight bearing possible)

Organisation of fracture callus (6 wks): woven bone is replaced by lamellar bone --> the excess callus (non-weight bearing callus) is resorbed --> bony alignment occurs --> medullary cavity is formed --> healing complete.

OSTEOPOROSIS (Robbins 1222, Fig 28-8)
What is it?: It is defined as the "loss of osteoid" and "bone mineral", collectively termed: "bone mass". 
Types: Various types exist. Most common is: senile osteoporosis. Others: Post-menopausal, idiopathic and 2nd osteoporosis due to metabolic bone disease, hypogonadism, corticosteroids, malnutrition, malabsorption. 

Bone loss is normal: Peak bone mass is achieved in early adulthood, and from then on we lose approximately 0.3-0.5% of bone each year. This is a normal process because the bone remodelling process is not completely effective. 

Pathogenesis factors (what affects peak bone mass - Fig 28-8): 1) Genetics (Vit D receptor polymorphism), 2) Nutrition (Calcium state - girls affected more), 3) Physical activity (mechanical forces are important stimuli for bone remodelling), 4) Age related factors (osteoblasts are less effective, growth factors have reduced "punch"), 5) Menopause (reduced oestrogen means cytokines: IL6, IL1, TNF-a are released by monocytes, bone marrow cells --> increased osteoclastic activity). 

Clinical course: Usually asymptomatic until skeletal fragility is advanced. 
Dx: DXA (dual energy X ray absorptiometry), CT --> both measure bone density.
Rx: Prevention is best therapy (HRT, Ca suppliments, exercise)

PAGET'S DISEASE (Robbins pp 1225, Fig28-12/13)
This has nothing to do with Paget's disease of the breast!!!
What is it?: Its when there is mixed osteoblastic & osteoclastic activity that eventually leads to gain in bone mass, but the new bone is majorly disorganised ("quality is better than quantity").
Pathogenesis: Caused by a slow virus infection of paramyxovirus --> viral particles resembling those of paramyxovirus have been found in osteoclasts (i.e.: particles of RSV & measles). No virus has been isolated till TODAY! Interestingly, IL-6 is said to be produced by osteoblasts in Paget's disease --> IL-6 is a potentiator or osteoclastic activity. 

Morphology (Fig 28-12): Three phases (overlapping): 1) osteolytic, 2) mixed clastic/blastic activity --> results in increased bone mass, 3) osteosclerotic. Pathognomic feature is: mosaic pattern of lamellar bone ("jigsaw puzzle"). 
Complications: pain (compression of spinal/cranial nerves), osteoarthritis, fractures, precipitates heart failure, osteosarcoma (dreaded complication). 

Clinical course: usually polyostotic (axial skeleton or proximal femur involved in 80% of cases), can present as hearing loss, bowing of long bones, osteosarcoma (1%). 
Dx: Usually an incidental finding on radiographs: 1) osteolytic areas, 2) mixed areas, 3) thickened coarse sclerotic areas. Radionuclide bone scanning is most reliable diagnostic tool: increased uptake of bone seeking radionuclides, elevated serum alkaline phosphatase and urinary hydroxyproline.

RICKETS AND OSTEOMALACIA (Robbins 1227, Fig 10-24)
What are they?: A group of diseases characterised by a defect in matrix mineralisation (vitamin D related most often). Rickets (affects growing bone) is a term for children, Osteomalacia (affects remodelling bone) is an adult term. 
Vitamin D: ingested + UV light radiation to skin --> absorbed in small intestine --> enters blood --> hydroxlasation in liver --> another hydroxylasation in kidney --> causes increased Ca2+ absorption by gut --> Ca2+ required for bone mineralisation. 

Now if you have decreased vit D: kidneys cannot hydroxylase it --> decreased Ca2+ absorption from gut --> hypocalcaemia --> increased parathormone secretion --> mobilises calcium from bone + phosphate excretion in urine increases (increased calcium retention) --> serum Ca2+ levels normal (normocalcaemia). Ca2+ levels normal --> creased bone mineralisation. 

HYPERPARATHYROIDISM (Robbins pp 1228, Fig 28-15)
What is it?: There is too much PTH in body. 
Types: Primary (adenoma, autonomic hyperplasia) & Secondary (prolonged hypocalcaemia)
Pathogenesis: PTH secreted --> binds to receptors in osteoblasts --> secrete osteoclast recruiting cytokines --> increased osteoclastic activity --> mobilisation of Ca2+ from bone (demineralisation). 
Morphology: cortical bone affected more severely than cancellous bone. CORTEX THINS. 

RENAL OSTEODYSTROPHY (Robbins pp 1229)
What is it?: This is a collective term used to describe all the skeletal changes that occur as a result of renal disease. 
The complications of CRF: 1) osteoporosis, 2) osteomalacia, 3) hyperparathyroidism
What happens?: CRF --> hyperphosphataemia --> 2nd hyperparathyroidism. Meanwhile serum Ca2+ drops due to kidney disease --> PTH stabilises this. CRF precipitates metabolic acidosis --> stimulates bone resorption. Other factors: aluminium deposition at site of mineralisation is found in dialysis patients --> aluminium interferes with mineralisation leading to osteomalacia. 

GOUT & PSEUDOGOUT - Refer to previous lecture notes on Arthritides. 

AVASCULAR NECROSIS (Robbins pp 1231, Fig 28-18)
What is it?: Bone necrosis 2nd to ischaemia
What causes bone ischaemia?: fracture, corticosteroids, thrombosis/embolism (nitrogen gas), vasculitis/radiation injury, venous hypertension. 
Where is it common?: medullary cavity of metaphysis/diaphysis & subchondral region below epiphysis. 
Morphology: wedge shaped subchondral infarct (pale yellow) with overlying viable articular cartilage (radiographically: "crescent sign"). Eventually the infarcted bone collapses with further detachment of overlying cartilage --> leading to 2nd osteoarthritis. 

BONE TUMOURS: briefly discussed in lecture. Most common tumour in bone = metastasis, most common primary tumour = multiple myeloma/lymphoma (44%). Bone tumours mentioned: osteosarcoma (Caudmann's triangle), osteochondroma (benign), chondrosarcoma, Ewing's sarcoma - highly malign.



