5.2 - Ossification and Bone Disease Flashcards
Match the component of bone to its corresponding percentage. 1. Type I collagen 2. Non-collagen proteins 3. Calcium hydroxyapatite 4. Water 65%, 23%, 10%, 2%
Calcium hydroxyapatite: 65%
Type I collagen: 23%
Water: 10%
Non-collagen proteins: 2%
What is diploe?
The spongy bone layer separating the inner and outer layers of the cortical bone of the skull
What type of bone would you find at the internal and external surfaces of flat bone?
Cortical
What type of bone would you find in the central regions of flat bone?
Spongy
Brittle bone disease is also known as ___.
Osteogeneses imperfecta
How many types of osteogenesis imperfecta are there?
8
What is the genetic basis for type I-IV osteogenesis imperfecta?
Mutation on COL1A1 or COL1A2, which code for type I collagen
What is the inheritance pattern for type I-IV osteogenesis imperfecta?
Autosomal dominant
What is the incidence of osteogenesis imperfecta?
1/10,000 births in the US
Osteogenesis imperfecta has systemic implications (i.e., affects skeleton, joints, ears, ligaments, teeth, sclera, and skin). Why is this so?
Results from defective synthesis of collagen, which is present all over the body
What is the genetic basis for type I osteogenesis imperfecta?
Loss of COL1A1 gene -> insufficient collagen
What is the genetic basis for type II osteogenesis imperfecta?
Altered function of COL1A1 gene or COL1A2 gene -> abnormal collagen
Compare the genetic basis for type I and II osteogenesis imperfecta.
Type I: loss of COL1A1 gene -> insufficient collagen
Type II: altered function of COL1A1 gene or COL1A2 gene -> abnormal collagen
What is the mildest form of osteogenesis imperfecta?
Type I
What is the most common form of osteogenesis imperfecta?
Type I
What is the most severe form of osteogenesis imperfecta?
Type II
List 6 symptoms of type I osteogenesis imperfecta.
- Blue sclera
- Fusion of auditory ossicles
- Frequent fractures
- Unstable joints
- Thin bones
- Abnormally curved bones
Why might someone with osteogenesis imperfecta experience hearing loss?
Fusion of auditory ossicles
What are the auditory ossicles?
Three tiny bones in the middle ear responsible for transmitting sound
Why might someone with osteogenesis imperfecta be of shorter stature?
Defective synthesis of type I collagen hinders bone growth
Why is type II osteogenesis imperfecta lethal?
Almost all the bones fracture during labour or delivery
Why might osteogenesis imperfecta have medicolegal importance?
Can be mistaken for fractures caused by child abuse
What is another name for somatotropin?
Growth hormone (GH)
Where is growth hormone synthesized?
Anterior pituitary
Which hormone promotes growth of epiphyseal cartilage?
Growth hormone (GH)
What is the impact of excessive growth hormone (GH) before puberty?
Gigantism through promotion of epiphyseal growth plate activity
What is the impact of insufficient growth hormone (GH) before puberty?
Pituitary dwarfism due to lack of epiphyseal growth plate activity
How does excessive GH before puberty cause gigantism?
Promotion of epiphyseal growth plate activity
How does insufficient GH before puberty cause pituitary dwarfism?
Lack of epiphyseal growth plate activity
What is the most common form of proportionate dwarfism?
Pituitary dwarfism
What is the impact of excessive growth hormone (GH) after puberty?
Acromegaly (i.e., increase in bone width)
In adults, excessive GH causes acromegaly. It cannot cause gigantism. Why?
Epiphyseal growth plates have closed
List 3 symptoms of acromegaly.
- Enlarged hands
- Enlarged feet
- Enlarged facial features
What is acromegaly?
Increase in bone width due to excessive growth hormone after puberty
What gives rise to the pubertal growth spurt?
Increase in androgens and estrogens stimulates osteoblast activity and inhibits osteoclast activity
Sex-hormone producing tumours can trigger early sexual maturity. How might this inhibit bone growth?
Premature closure of epiphyseal growth plates
Deficiency in sex hormones can delay sexual maturity. How might this lead to prolonged bone growth and tall stature?
Delayed closure of epiphyseal growth plates
What is cretinism?
Stunted physical and mental growth due to congenital hypothyroidism
What is the most common cause of cretinism?
Iodine deficiency in the mother’s diet during pregnancy
How would you treat neonatal hypothyroidism?
Administration of thyroxine
List 3 processes mediated by thyroxine.
- Metabolic rate
- Neural maturation
- Bone growth
Why are thyroid hormones important for bone development?
Stimulate bone growth
Compare the importance of thyroid hormones in the bone development of infants and adults.
Infants: big effect
Adults: inconsequential; bone development largely mediated by PTH
Approximately how many people in the UK suffer from osteoporosis?
3 million
Describe, in broad terms, how osteoporosis reduces bone mineral density.
Osteoclast activity outweighs osteoblast activity
Osteoporosis is associated with reduced mechanical strength and increased susceptibility to fracture. What type of bone is most commonly affect by osteoporosis?
Spongy
What are the 3 most common sites of fractures in osteoporosis?
- Wrists
- Hips
- Spine
Why are elderly people more susceptible to osteoporotic fractures?
Bone mass declines with age
At what age does bone density peak?
25-30
At what age does bone density begin to decline?
~40
What is the first line pharmacological treatment for osteoporosis?
Bisphosphonates
How do bisphosphonates treat osteoporosis?
Inhibit osteoclast activity
Which type of osteoporosis is associated with post-menopausal women?
Type 1
Which type of osteoporosis is associated with aging past 70?
Type 2
Which type of osteoporosis results in increased osteoclast activity?
Type 1
Which type of osteoporosis results in decreased osteoblast activity?
Type 2
Compare type 1 and type 2 osteoporosis.
Type 1: a.k.a. postmenopausal osteoporosis, onset in age 45 to 55, results in increased osteoclast activity
Type 2: a.k.a. senile osteoporosis, onset in age 70+, results in decreased osteoblast activity
List 8 risk factors for osteoporosis.
- Old age
- Female
- Estrogen deficiency (e.g., menopause)
- Hypogonadism
- Long term steroid treatment
- Diet (poor calcium or Vitamin D)
- Immobility
- Family history
Which ethnicity reaches higher peak bone density?
Black
What is the recommended calcium intake for postmenopausal women?
800 mg/day
Why might elderly confined INDOORS be at greater risk of osteoporosis?
Vitamin D deficiency hinders bone mineralization
Why might prolonged bed rest increase risk for osteoporosis?
Physical activity is needed to remodel bone
Which might application of a cast increase risk for osteoporosis?
Immobility hinders bone remodelling
Why might kidney disease increase risk for osteoporosis?
Decreased renal activation of vitamin D3 hinders bone mineralisation
What is the most common cause of short-limbed dwarfism?
Achondroplasia
What is the inheritance pattern for achondroplasia?
Autosomal dominant (nb: homozygous condition is LETHAL)
Explain the genetic basis for achondroplasia.
Point mutation in the FGFR3 gene (encodes for fibroblast growth factor receptor 3) promotes early growth plate closure
The inheritance pattern for achondroplasia is autosomal dominant. However, more than 80% of people with achondroplasia are born to parents without the condition. What accounts for this?
Spontaneous mutation
Two parents with achondroplasia have a child. Which phenotype would be lethal, and what are the odds that the child is born with the phenotype?
Homozygous dominant
25%
Two parents with achondroplasia have a child. Which phenotype would result in a child who presents with achondroplasia, and what are the odds that the child is born with the phenotype?
Heterozygous
50%
Two parents with achondroplasia have a child. Which phenotype would result in a living child without achondroplasia, and what are the odds that the child is born with the phenotype?
Homozygous recessive
25%
What is a synonym of calcitriol?
Vitamin D3
What is the cholesterol precursor for vitamin D3?
7-dehydrocholesterol
Which vitamin results from the hydroxylation of 7-dehydrocholesterol in the liver and kidney?
Vitamin D3
How is 7-dehydrocholesterol converted to vitamin D3?
Hydroxylated in the liver and kidney
What are the 2 ways that vitamin D increases bone mineralization?
- Increases availability of Ca+ by increasing its absorption in the intestine
- Directly stimulates bone remodeling
What is osteomalacia?
Softening of the bone; caused by INSUFFICIENT MINERALIZATION
What Is rickets?
Childhood version of osteomalacia
List 3 deficiencies that can cause insufficient mineralization of bone (i.e., osteomalacia or rickets).
- Vitamin D
- Calcium
- Phosphate
In the UK, which ethnic demographic most commonly suffers from rickets?
Asian immigrant families
In rickets, insufficient mineral deposition leads to bones becoming soft and malformed. List 3 characteristic malformations.
- Bowed legs
- Skull bossing
- Rickety rosary
List 3 risk factors for vitamin D deficiency.
- Poor dietary intake
- Lack of sunshine
- Liver or kidney disease
What are 4 common symptoms of osteomalacia?
- Bone pain
- Back pain
- Muscle weakness
- Increased risk of fracture
What are the 4 most common sites of fracture for osteomalacia?
- Femoral neck
- Pubic ramus
- Spine
- Ribs
What cellular changes occur in osteomalacia?
Trabeculae weakened by thick layers of non-mineralized osteoid
Which hormone inhibits osteoclast activity?
Calcitonin
Which hormone opposes the actions of PTH?
Calcitonin
Compare rickets and osteomalacia.
Rickets: affects children, affects growing bone
Osteomalacia: affects adults, affects bone remodeling
Why is the skull unaffected in achondroplasia?
Disease leads to premature closing of growth plates, affecting endochondral ossification; skull undergoes intramembranous ossification
