Ossification And Bone Disease Flashcards
Describe the process of endochondral ossification:
The fetal skeleton is made of hyaline cartilage.
Initially, a collar of periosteal bone forms around the shaft of the bone.
The central cartilage calcifies, and a nutrient artery penetrates, which supplies osteogenic cells. This forms the primary ossification centre.
The medulla becomes cancellous bone, and cartilage forms the epiphyseal growth plates. This occurs after birth. Secondary ossification centres appear in the epiphyses.
The epiphyses ossify, leaving hyaline cartilage on the articulating surfaces. The epiphyseal growth plates continue to move apart, lengthening bone.
After puberty, the epiphyseal growth plates are replaced by bone.
What are the two methods of ossification?
Endochondral and intramembranous.
What are the five zones found at an epiphyseal growth plate?
Zone of reserve cartilage Zone of proliferation Zone of hypertrophy Zone of calcified cartilage Zone of resorption
Where is the epiphyseal growth plate is there no active matrix production or cell proliferation?
Zone of reserve cartilage
What happens in the zone of proliferation?
Chondrocytes divide, form columns, enlarge and secrete matrix.
What occurs in the zone of hypertrophy?
Cells enlarge, and matrix is compressed into linear bands between columns of cells.
What happens in the zone of calcified cartilage?
Cells begin to degenerate, matrix calcifies.
What occurs in the zone of resorption?
Blood vessels and connective tissue invade spaces left by chondrocytes, bone is laid down on spicules of calcified cartilage.
What is the role of intramembranous ossification?
Increasing the girth of long bones.
Ossification of bones of the skull (parietal, occipital, temporal, frontal), clavicle, etc.
How does intramembranous ossification occur?
Occurs within mesenchymal tissue - mesenchymal stem cells differentiate into osteoprogenitor cells, then into osteoblasts and osteocytes. Bone forms in spicules then connects to form trabeculae.
What is the inheritance pattern for osteogenesis imperfecta?
Autosomal dominant
What gene is affected in osteogenesis imperfecta?
The gene for type one collagen.
What is the frequency of osteogenesis imperfecta in the population?
1 in 10,000
What are the characteristics of osteogenesis imperfecta type 1?
Blue sclerae
Multiple fractures as child learns to sit and walk.
Condition improves with age.
Bones are thin, delicate and curved.
Progressive hearing loss - auditory ossicles fuse.
What characterises osteogenesis imperfecta type two?
It is a lethal perinatal disease, as almost all bones are broken during labour due to contractions of the uterus, or during delivery.
What characterises osteogenesis imperfecta type three?
It is progressive, many fractures, skeletal deformities and growth retardation.
What characterises osteogenesis imperfecta type four?
Like type one, but normal sclerae. Patients are aggressively treated with rods in the medulla of bones and other orthopaedic devices to prevent dwarfing consequences of multiple fractures.
Why is osteogenesis imperfecta of medicolegal importance?
Possible to confuse multiple fractures from deliberate injury with osteogenesis imperfecta.
What is the consequence of excessive growth hormone before puberty?
Gigantism - promotion of epiphyseal growth plate activity.
What is the consequence of insufficient growth hormone before puberty?
Pituitary dwarfism - affects epiphyseal cartilage.
What is the consequence of excessive growth hormone in adults?
Acromegaly - promotes periosteal growth. Cannot promote gigantism as there are no longer any epiphyseal growth plates.
What are the effects of sex hormones (androgens and oestrogens) on bone?
Sex hormones give rise to pubertal growth spurt.
Precocious sexual maturity can lead to premature fusion of epiphyses, short stature.
Sex hormone deficiency can mean epiphyseal growth plates persist for longer than they usually would - prolonged bone growth and tall stature.
What are the consequences of hypothyroidism in a newborn, and how can this be rectified?
Can lead to cretinism - neurological and intellectual damage, and short stature, characteristic facial features.
Prompt administration of thyroxine.
What is osteoporosis?
Decreased bone mass (more than 2.5 standard deviations below the bone mass of a 30yr old white woman, as measured by a dexa scan)
Due to enhanced osteoclast activity compared to osteoblast activity - incomplete filling of osteoclast absorption bays.
What are three characteristic fractures in osteoporosis?
Colles fracture
Compression fracture of vertebrae
Fractured neck of femur.
When does bone mass peak?
Age 25-35
When does bone mass start to decline?
5th or 6th decade
What are the two types of osteoporosis?
Type one - occurs in post menopausal women - osteoclast number increases in the absence of oestrogen
Type two - senile osteoporosis - occurs in both sexes after the age of 70, reflects attenuated osteoblast function.
What are the risk factors for osteoporosis?
Genetics including ethnicity (black people have higher bone density)
Smoking
Reduced calcium intake
Reduced calcium absorption/vitamin D/sunlight.
Lack of exercise/bed rest/application of cast.
What causes achondroplasia?
Autosomal dominant mutation causes increase in function of FGFR3 gene.
Leads to decreased endochondral ossification, inhibited proliferation of chondrocytes at epiphyseal growth plates, decreased cellular hypertrophy and decreased cartilage matrix production.
What is the result of being homozygous for the allele of the FGFR3 gene that causes achondroplasia?
Child dies soon after birth.
What is the physical appearance of someone with achondroplasia?
Short stature - enlarged vault of the skull, normal trunk length, short limbs. Small face, flat bridge of nose.
What percentage of cases of achondroplasia arise from a random mutation, rather than being inherited?
80%
What is the mean adult height of someone with achondroplasia?
131cm for males
125cm for females
What is rickets?
Vitamin D deficiency, poor absorption of calcium, leads to decreased mineralisation of bone.
Bones become soft and malformed, bossing of skull, enlargement of chostochondral junctions of ribs.
What is osteomalacia?
The counterpart of rickets in adults - leads to back ache, bone pain and muscle weakness.
What causes osteomalacia?
Calcium deficiency or vitamin d deficiency.
Insufficient sunlight, malabsorption, insufficient dietary intake, liver or kidney disease.
What is the appearance of trabeculae in cancellous bone in osteomalacia?
Large amount of osteoid (nonmineralised bone) covering the surface of trabeculae.
What are the commonest fracture sites in osteomalacia?
Neck of femur
Spine
Pubic ramus
Ribs
