Pathology: Bone/Joint Flashcards
Composition of Bone
60% Mineral (inorganic) - Ca, PO4 crystals arrayed in a protein matrix - Resist compressive forces 30% Organic: - CT - Resistance to bending and/or torsion
Osteoclasts
- Hematopoietic stem cell (bone marrow) -> monocyte -> tissue macrophage -> osteoclast
- Breakdown bone
- Highly active - high energy requirements
- Short lifespan
- Many nuclei
- Polarised
- Creates ‘sealing zone’ with bone where it releases enzymes and acid -> causes bone breakdown
Osteoblasts
- Lay down osteoid which then becomes mineralised
Bone Strength
= bone quality and bone density
- Determines fracture risk
Regulators of Bone Metabolism
Endocrine - Parathyroid hormone - Estrogen - Vit D Autocrine - OPG - RANKL - Sclerostin - Inflam cytokines Drugs - Bisphosphates - Calcitonin
Bone Resorption Control
- Controlled by RANKL:OPG ratio
- More OPG = no resorption
- More RANKL = bone resorption
Osteoporosis
- Systemic skeletal disorder characterised by a decrease in total bone mass and density
- Diagnosis: BMD 2.5 SD below mean peak in young adults of same race and T score -2.5 (measured by DXA)
Osteoporosis: Morphology
- Global disease ie all bones affected
- Trabecular bone is initially effected, then cortical bone
- Preferential loss of trabecular bone in various regions
- Decreased bone density
- Normal mineral content in remaining bone
Osteoporosis: Prevention
- Nutrition: Vit D
- Exercise
- Smoking cessation
Osteoporosis: Treatment
- Anti resorptive agents e.g. bisphosphonate, oestrogen analog, selective oestrogen receptors modulators (SERMs)
- Anabolic agents
- RANKL antibody (denosumab)
- Calcium and Vit D supplement
Metabolic Diseases: Rickets and Osteomalacia
Rickets: - rare in developed countries - developing bones in children, 6-24 months Osteomalacia: - the disease in adults - under mineralised in remodelling
- Balanced bone formation and resorption
- Defective mineralisation of the organic matrix of the skeleton
- Less mineralised trabecular bone/unit
Aetiology: Rickets
Nutritional - Lack of Vit D in diet - Lack of calcium and phophorus - In association with malabsorption - Inadequate sunlight Vitamin D dependent: gene abnormalities Vitamin D resistant: hypophosphatemia, decrease phosphate
Aetiology: Osteomalacia
Insufficient calcium absorption
- Deficiency of/or resistance to Vit D
Phosphate deficiency
- Increased renal loss or decreased intestinal absorption
Rickets and Osteomalacia
- Softer and weaker bones
- Tendency to become bowed (especially in children)
- Maybe loss of trabecular bone and cortical thinning
- Fractures occur with normal load levels
Treatment - Identify underlying cause and treat
- Calcium and Vit D
Paget’s Disease
- 3rd decade of life
- Male > female
- 3-5% of Australians
- Genetic predisposition and environmental trigger
Paget’s Disease: Pathophysiology
- Abnormal bone structure
- High bone turnover
- Increased osteoclast and osteoblast activity
- Skull, pelvis, spine and long bones of the arm and thigh
Cartilage
- Made up of chondrocytes and matrix
- Chondrocytes produce the matrix
Arthritis
- 100 forms
- 3.85 million people in Aus
Main types: osteoarthritis, rheumatoid arthritis and gout
Osteoarthritis
- Degenerative joint disease
- Destruction of the articular cartilage
- Degeneration of the articular cartilage
OA: Pathogenesis
Changes in articular cartilage and in subchondral bone
Chondrocytes shift from reparative to degenerative role
- Some inflammation SECONDARY to cartilage damage
- Production of inflammatory cytokines -> stimulate cchondrocytes to secrete degradative enzymes e.g. MMPs
- Decrease tissue inhibitors of MMPs
- Deficiency of growth factors e.g. IGF
- Bones under the cartilage to rub together, causing pain, swelling, and loss of motion of the joint
Rheumatoid Arthritis
- Systemic chronic disease
- Autoimmune disease
- Mainly characterised by inflammation of the lining or synovia of the joints
RA: Aetiology
- Bodies immune system attackso own cartilage
- Exact cause unknown
- More common in women - hormonal influence?
- Rection to an infection?
- Ageing immune system?
