Ossification and Bone Disease Flashcards
What does endochondral ossification involve?
The replacement of a pre-existing hyaline cartilage template by bone
What is endochondral ossification the mechanism for?
The development of most of the bones in the body
Where is endochondral ossification particularly important?
Mostly in long bones
Where does endochondral ossification occur?
Foetus
What does endochondral ossification in the foetus form?
The skeleton
What part of long bones become ossified first?
Diaphyses
What is the precursor for most bones?
A hyaline cartilage model
What happens in endochondral ossification?
Cartilage is mineralised to form bone
What do growing bones have?
Growth plates of hyaline cartilage
How long does the femur continue to grow for?
Into adulthood
How does the femur continue to grow into adulthood?
By continuous production of cartilage
On what side does cartilage change into bone in long bones?
Shaft side
What happens after the cessation of long bone growth?
The epiphyseal plate disappears
How much bone is present in a 5-6 week old embryo?
None- it’s purely the hyaline cartilage model
When does endochondral ossification occur?
In a 5-6 week embryo
What happens in a 5-6 week old embryo?
A collar of periosteal bone appears in the shaft
What happens in an 8-12 week old fetus?
- The central cartilage calcifies
- Nutrient artery penetrates
- Formation of the primary ossification centre
What does the nutrient artery provide?
Bone-depositing osteogenic cells
What happens regarding bone development postnatal?
- Medulla becomes calcified bone
- Cartilage forms epiphyseal growth plates
- Epiphyses develop secondary centres of ossification
What happens regarding bone development prepubertally?
Epiphyses ossify and growth plates continue to move apart
What is the result of the moving apart of the growth plates?
Bone lengthening
What happens regarding bone development in a mature adult?
NAME?
How does bone increase in length?
Endochondral ossification
How does bone increase in girth?
Periosteal ossification
What is periosteal ossification?
Intramembranous ossification
What extends from the growth plate when a bone is growing?
Columns of calcified cartilage
What happens to the columns of calcified cartilage in growing bone?
It becomes mineralised
What are the 5 zones of the epiphyseal growth plates?
- Zone of reserve cartilage
- Zone of proliferation
- Zone of hypertrophy
- Zone of calcified cartilage
- Zone of resorption
What is not happening in the zone of reserve cartilage?
- Cellular proliferation
- Active matrix production
What happens in the zone of proliferation?
NAME?
What happens in the zone of hypertrophy?
NAME?
What happens in the zone of calcified cartilage?
NAME?
What is calcified matrix in direct contact with in the zone of resorption?
The marrow cavity
What happens in the zone of resorption?
Small blood vessels and connective tissue invade the region occupied by the dying chondrocytes, leaving the calcified cartilage in spicules between them
What happens are the cartilage spicules in the zone of resorption?
Bone is laid down
Where does intramembranous ossification take place?
Within condensations of mesenchymal tissue
Does intramembranous ossification involve the replacement of a pre-exisiting hyaline cartilage template?
No
What kind of bonds develop by intramembranous ossification?
Flat bones
Give 5 bones that develop by intramembranous ossification?
- Skull bones
- Maxilla
- Mandible
- Pelvis
- Clavicle
How does the clavicle develop?
NAME?
What does intramembranous ossification contribute to?
Thickening of bones at periosteal surface
What kind of growth occurs due to intramembranous ossification?
Appositional growth
What happens in intramembranous ossification of flat bones in the fetus?
Mineral deposits within the many trabeculae radiate outwards from a central point, the early primary ossification centre
Is intramembranous ossification complete in a newborn?
No
What is the advantage of the incompletion of intramembranous ossification in the newborn/
Makes scalp able to withstand trauma
What does the periosteum of newly forming flat bones contain?
Osteoprogenitor cells for bone deposition
What happens to osteoprogenitor cells?
They will merge to form woven immature bone
What does newly formed bone contain?
Bone marrow, blood vessels and mesenchymal tissue
What does compact bone of the skull during postnatal development have?
Osteocytes, osteons, Haversian and Volkmann’s canals
What is the result of the components of the compact bone of the skull during postnatal development being what they are?
Make it indistinguishable from bone arising from endochondral ossification
What is the inheritance pattern of osteogenesis imperfecta?
Autosomal dominant
What is osteogenesis imperfecta a disorder of?
Connective tissue
What causes osteogenesis imperfecta?
Mutations in the gene for type I collagen
What does osteogenesis imperfecta affect?
- Skeleton
- Joints
- Ears
- Ligaments
- Teeth
- Sclerae
- Skin
Why is osteogenesis imperfecta of medicolegal importance?
Because of the possible confusion with multiple fractures caused by deliberate injury
How can osteogenesis imperfecta be seen?
NAME?
Where is growth hormone (GH) synthesised and stored?
Anterior pituitary
What effect can abnormal GH levels have before puberty?
- Excessive GH can cause gigantism
- Insufficient GH can affect epiphyseal cartilage and cause pituitary dwarfism
Why can excessive GH cause gigantism?
Through promotion of epiphyseal growth plate activity
What can abnormal GH levels cause in an adult?
Excessive GH may cause an increase in bone width
Why can’t excessive GH cause gigantism in an adult?
There are no longer any epiphyseal growth plates
How can GH cause an increase in bone width in an adult?
By promoting periosteal growth
What is increased bone width known as?
Acromegaly
What is increased GH production in adults normally caused by?
A benign tumour of the pituitary gland
Why are sex hormones important in bone development?
They influence the development of ossification centres
What are the sex hormones?
- Androgens in men
- Oestrogen’s in women
Both hormones present in each sex
What is the role sex hormones?
- Induce secondary sexual characteristics
- Give rise to pubertal growth spurt
What can be bought about sex hormone producing tumours?
Precocious sexual maturity
What effect can precocious sexual maturity have on bone growth?
Retards it
Why can precocious sexual maturity retard bone growth?
Because of premature closure (fusion) of epiphyses
What can happen if sex hormone is deficient?
Epiphyseal plates may persist later into life than they normally would, leading to prolonged bone growth and tall stature
What kind of effects do neonatal hypothyroidism have?
Deleterious
How can the deleterious effects of neonatal hypothyroidism be reversed?
Prompt administration of thyroxine
What can happen if thyroid hormone deficiency is left untreated?
It can lead to infant with permanent neurological and intellectual damage, and a number of other abnormalities, including short stature
What is osteoporosis?
A metabolic bone disorder in which mineralised bone is decreased in mass to the point that it no longer provides adequate mechanical support
What does osteoporosis always reflect?
Enhanced bone resorption relative to formation
What always characterises osteoporosis?
Depletion of bone mass
What is loss of mass within the trabecular structure particular relevant to?
Increased susceptibility to bone fracture
What is happening in osteoporotic bone?
Holes are being produced by osteoclasts, but not being replaced by osteoblasts
What is osteoporosis associated with ageing a result of?
Incomplete filling of osteoclast resorption bays
What may happen in the vertebrae of an osteoporosis sufferer?
NAME?
What is the result of the effect of osteoporosis on the vertebrae?
Stooping, as the vertebrae become wedge shaped
Who is osteoporosis a risk factor for?
The elderly
When done bone mass peak?
25-35 years
What is the problem with hip fractures?
They have complications in 12-20% of cases
How does risk of hip fracture differ among sexes in whites?
2x higher in women
How does risk of vertebral fracture differ among sexes in whites?
3x high in women
What is the most common form of osteoporosis?
Primary- type 1 and 2
Who does type 1 osteoporosis occur in?
Post menopausal women
What is type 1 osteoporosis due to?
Increased osteoclast number
Why do post menopausal women have a increase osteoclast number?
Due to oestrogen withdrawal
Who does type 2 osteoporosis occur in?
Elderly people, generally after age of 70
What causes type 2 osteoporosis?
Attenuated osteoblast function
What are the risk factors for osteoporosis?
- Genetic
- Insufficient calcium intake
- Insufficient calcium absorption
- Exercise
- Cigarette smoking
What ethnic group is less prone to osteoporosis?
Blacks
Why are blacks less prone to osteoporosis?
Because they have a higher peak bone mass than whites or asians
Why does calcium absorption decrease with age?
Due to decreased renal activation of vitamin D
When may vitamin D levels be a factor in osteoporosis?
NAME?
What may cause the immobilisation of bone?
NAME?
What does immobilisation of bone lead to?
Acceleration of bone loss
What is needed to maintain bone mass?
Physical activity
Who is cigarette smoking a risk factor for osteoporosis?
Women
What is one of the most common forms of short limb dwarfism?
Achondroplasia
In what respects are achondroplastic dwarfs normal?
- They have normal mentation
- Average lifespan
What causes achondroplasia?
An autosomal dominant point mutation in the fibroblast growth factor receptor-3 gene (FGFR3), causing a gain of function
What is the result of the gain in function of the FGFR3 gene?
- Decreased endochondrial ossification
- Inhibited proliferation of chondrocytes in growth plate cartilage
- Decreased cellular hypotrophy
- Decreased cartilage matrix production
What is the appearance of a sufferer of achondroplasia?
- Very short limbs
- Normal length trunk
- Vault of the skull enlarged
- Small face
- Bridge of nose often flattened
What % of achondroplasia cases are a result of a new mutation?
More then 80%
What happens in 2 parents with achondroplasia have a child?
- 25% chance child will die soon after birth
- 50% chance child heterozygous, and has achondroplasia
- 25% chance child will have normal phenotype
Why is there a 25% chance that the child of two achondroplastic parents will die shortly after birth?
The homozygous condition is fatal
How does the growth plate differ in a person with achondroplasia?
NAME?
How does the body obtain vitamin D?
NAME?
What happens to vitamin D in the body?
It undergoes hydroxylation in the liver, and then further hydroxylation in the kidney to form active 1,25-dihydroxyvitamin D
What does 1,25-dihydroxyvitamin D do?
NAME?
What does the opposite of vitamin D?
PTH
Who does rickets occur in?
Children
What happens in rickets?
Bones do not harden due to a deficiency in vitamin D
Among whom is rickets most common in the UK?
Asian immigrant families
Why is rickets more common in asian immigrant families?
The pigmentation of their skin means they can’t take vitamin D from the sun as well
Why is there not adequate bone rigidity in rickets?
Insufficient calcium deposition
What happens to the bones in rickets?
They become soft and malformed
What happens in extreme cases of rickets?
Distortion of the skull bone, leading to bossing
What is rickets rosary?
Enlargement of the costochondral junction of the ribs
What is the adult counterpart of rickets?
Osteomalacia
What causes osteomalacia?
Significant calcium deficiency or lack of vitamin D
What can lead to calcium deficiency or vitamin D lack?
- Poor diet
- Lack of sunshine
- Intestinal malabsorption
- Liver/kidney disease
What are the common symptoms of osteomalacia?
- Back ache
- Bone ache
- Muscle weakness
What has happened to the bones in osteomalacia?
The trabeculae of cancellous bone have abnormally large amount of non-mineralised bone (osteoid) covering their trabecular surface
What is the result of insufficient mineralisation of trabeculae?
They are weakened
What are the most common fracture sites?
- Femoral neck
- Pubic ramus
- Spine
- Ribs
