Bone repair and disease (SA) Flashcards
To describe bone metabolism and explain the signalling between osteoblasts and osteoclasts
- Contributes to calcium homeostasis under the influence of PTH, calcitonin and vitamin D - PTH stimulates osteoclasts - PTHR found on osteoblasts - PTH binding to osteoblasts stimulates expression of RANKL on osteoblasts - RANKL can then bind to RANKR on the surface of osteoclasts, thus activating the cells - Osteoblasts also produce osteoprotegrin, which binds to RANKL - preventing resorption - Osteoprotegrin:RANKL ratio determines bone resorption
Explain the process of fracture repair in bone
Periosteum breached, blood clot forms → Fibrous granulation tissue → Provisional callus (hyaline cartilage) → Bony callus (osteoprogenitor cells → osteoblasts) → Bony union → Remodelled to form oriented lamellar bone, allows forces to be absorbed
To list the types of bone disease and describe some features of diseases of each type
Congenital bone disease Acquired bone disease Bone infection & inflammation Bone necrosis and infarction Bone tumours
To describe the main congenital diseases of bone
Brittle Bone Disease Achondroplasia
To describe the pathological features of acquired/metabolic bone diseases and how these relate to normal bone turnover and regulation
Osteoporosis Rickets/Osteomalacia Paget’s disease Hyperparathyroidism
Describe Achondraplasia
- Mutation in FGFR3, increased activation - This inhibits chondrocyte proliferation, affecting the growth plates - Growth plates become disorganised. Growth of long bones is stunted
2 mechanisms of bone growth
1. Endochondral: Bone growth from a hyaline cartilage template. Allows for the formation of long bones. Primary and secondary ossification centres seen
2. Intramembranous: Bone growth from a fibrous membrane template. Allows the formation of flat bones.
Congenital bone disease: Describe Brittle Bone Disease (osteogenesis imperfecta)
- Defective collagen chain, disrupts triple helix formation
- ‘Fragile skeleton’
- Many types, range of outcomes
Extra-skeletal manifestations: Skin, joints, blue sclera
Congenital bone disease: Describe Achondraplasia
- Mutation in FGFR3, increased activation - This inhibits chondrocyte proliferation, affecting the growth plates - Growth plates become disorganised. Growth of long bones is stunted - Presentation: Lordosis, bowed legs and stunted extremities
Congenital bone disease: Osteopetrosis
- Reduced osteoclast activity –> defective bone remodelling - Osteoclasts cannot excrete hydrogen to dissolve bone minerals - Bone = ‘Stone bone’ but brittle - Bone marrow transplant may be used - Presentation: Fractures, spinal nerve compression (due to excess bone), recurrent infection
Metabolic/Acquired bone disease: Describe osteoporosis
- Normal mineralisation of bone - Trabeculae are thinned, cortex thinned eventually - Affects areas with lots of trabecular bone e.g. vertebrae, wrists, neck of femur - Increases in: Old age, menopause (loss of oestrogen, increases osteoclast activity), reduced activity, prolonged steroid use, some endocrine diseases
Metabolic/Acquired bone disease: Describe Osteomalacia (mature bones) and Rickets (growing bones)
- Failure of mineralisation, leading to soft bones - Resultant of vitamin D deficiency (causes: diet, sunlight, malabsorption, renal disease) - Presentation: Bone pain, bowing of the legs. Early signs include swelling of the epiphyses of the bone and costochondral cartilage. Diagnosis: X-ray and low serum Vit. D Treatment: Supplementation
Metabolic/Acquired bone disease: Describe Hyperparathyroidism
Increased PTH secretion → Increased stimulation of osteocytes to resorb bone → Ca released into plasma → FAILURE TO REDUCE PTH SECRETION (negative feedback lost)
Types
PRIMARY: Tumour
SECONDARY: Low serum Ca caused by renal disease, causes hyperplasia of PTH glands. Can be caused by kidney disease
Metabolic/Acquired bone disease: Describe Paget’s
- Excessive bone resorption by osteoclasts followed by haphazard bone formation. Immature woven bone seen.
- The high turnover results in high metabolic demand: Heart failure may be caused by this
- Causes bone pain and nerve impingement
- Increases the risk of osteosarcoma, nerve compression and fracture.
Summarise the 4 types of metabolic bone disease
Paget’s: Normal mineralisation but overactive osteoclast resorption but haphazard bone formation. Osteoporosis: Increase osteoclast activity leads to thinning of trabecular, and eventually cortical, bone. Loss of bone mass. Osteomalacia/Rickets: Inadequate mineralisation of bone Hyperparathyroidism: Failure in the PTH feedback mechanism leading to increased PTH and therefore stimulation of osteoclasts Chronic renal failure –> Osteomalacia and hyperparathyroidism
