Outline endochondral ossification
- Bone formation in cartilage model, which is reabsorbed and replaced by long bone
- Begins as primary centre of ossification in the shaft (diaphysis) and later the secondary centres form at each end (epiphysis)
- Growth in diameter is by deposition of bone at the periphery of the shaft
- Growth in length occurs at the cartilaginous epiphyseal growth plate
Outline intramembranous ossification
- Bone development starts in highly vascularised connective tissue (Eg flat bones of skull)
- This focus of activity is the primary centre of ossification
- Mesenchymal cells differentiates into osteoblasts which are surrounded by collagen fibres and ground substances
- Osteoblasts secrete uncalcified matrix (osteoid), which later becomes calcified
- Osteoblasts become osteocytes (embedded in osteoid)
Describe osteogenesis imperfecta
- Characterised by bone fragility
- Predisposes the sufferer to fractures and other deformities (other connective tissue abnormalities of eyes, tooth, joints, teeth and skin)
- Multiple fractures are present at, or before birth, these often fatal
- Defect in Type I collagen
Explain the importance of Vitamin D in normal bone development
- Both dietary and synthesised vitamin D (in skin under influence of sunlight) is essential for normal ossification as it is involved in the absorption of calcium and phosphate by the small intestine
- In it's absence a poorly mineralised, pliable matrix known as osteoid (the uncalcified matrix secreted by osteoblasts) is formed
- Affected bones are unable support the body weight and bend
Describe the histological changes occurring in osteoporosis
- Bone density is reduced to a point where there is risk of fractures
- The collagen framework and deposited minerals are broken down much faster than they are formed Osteoclast activity > osteoblast activity
- Medullary canals in the centre of the bone become enlarged and gaps develop in the lamellae, making the bone fragile
List the most common risk factors for osteoporosis
- Women are more susceptible because of rapidly falling levels of oestrogen after the menopause - Poor diet
- Insufficient exercise
- Achondroplasia is a congenital and often hereditary skeletal disorder, caused by failure of proliferation and column formation of epiphyseal cartilage cells
- The defect is in endochondral bone formation
- Impairs longitudinal growth of tubular bones
Describe the histology of a achondroplasia sufferer
- Epiphyseal growth plates are thin
- There are few cells in the proliferating zone
- Hypertrophic cartilage cells form irregular columns
- The zone of provisionally calcified cartilage is small and does not provide adequate scaffolding for bone matrix deposition by metaphyseal osteoblasts
What does excessive growth hormone cause (bone)?
In the adult, increase in the length does not occur because of the lack of epiphyseal growth plate cartilage, however bone increase in width by periosteal growth Acromegaly - long bones become very thick
What does lack of growth hormone cause (bone)?
What cells provide the starting point for intramembranous ossification?
What is the genetic basis of osteogenesis imperfecta?
What is the potential medicolegal importance of osteogenesis imperfecta?
Mutation in gene for type I collagen means that a person is more susceptible to fracture, multiple fractures could lead to concerns regarding deliberate injury
What are the two types of osteoporosis?
Type I - affects post-menopausal women only due to increase in osteoclast number due to decrease in oestrogen
Type II - occurs in elderly (above 70) of both sexes due to attenuated osteoblast function
Why is osteoporosis an important consideration in elderly patients?
Elderly people are more likely to fall and so osteoporosis will increase the likelihood of fractures when falls happen which can have severe clinical consequences
What is the genetic cause of achondroplasia?
Autosomal dominant point mutation
Describe the appearance of an achondroplasia sufferer
- Short limbs
- Vault of skull enlarged
- Small face
- Flattened bridge of nose
- Normal trunk length
What is acromegaly?
Excessive growth hormone in adults leads to increase in bone diameter due to promoting periosteal growth
What is the effect of excess growth hormone?
Before puberty - Gigantism
Adults - Acromegaly
What results as a result of thymine deficiency?
What is the consequence of precocious sexual maturity?
Epiphyseal growth plates fuse prematurely which retards bone growth
What is the role of sex hormones on bone?
Influence appearance and development of ossification centres