Flashcards in Musculoskeletal 2 Deck (77)
Are osteoclasts multinucleated giant cells that are in the same family as macrophages?
What is the genetic defect that causes osteogenesis imperfecta?
Mutated a1 or a2 chains for type 1 collagen
What are the clinical features of osteogenesis imperfecta (12)?
1. Babies can be stillborn
2. Multiple fractures at birth
3. Osteopenia at birth
4. Blue sclera
5. Hearing loss
6. Short stature
7. Muscle hypotonia
8. Abnormal dentitions
9. Lax skin and ligaments
10. Broad forehead w/ triangular face
11. Scoliosis (progressive)
Do patients with osteogenesis imperfecta have normal intelligence?
What is the usual pattern of inheritance for osteogenesis imperfecta?
Describe the four types of osteogenesis imperfecta.
Type I, normal lifespan, bones fracture easily, blue sclera, hearing loss.
Type II, usually fatal in utero, or die shortly after birth from respiratory failure.
Type III, progressive deforming variant, rarely inherited as an autosomal recessive.
Type IV, somewhat similar to type I, more variable phenotype, NORMAL white sclera.
Achondroplasia is a congenital disorder of the ______ ______ and is the most common form of _______ (1/30,000).
congenital disorder of the growth plate and most common form of dwarfism.
What is the genetic mutation responsible for achondroplasia? Describe the protein product a little.
Point mutation in the fibroblast growth factor receptor 3 (FGFR3). It has kinase activity. The mutation ACTIVATES the receptor --> suppression of chondrocyte proliferation and growth plate expansion.
Name the disease: marked, disproportionate shortening of the proximal extremities, bowing of the legs, a lordotic (sway-backed) posture, disorganized growth plates, normal secondary ossification centers, and short and thick bones.
Does achondroplasia affect intramembranous ossification, or endochondral ossification? What is the significance of this?
Endochondral ossification - affects long bones and not the head.
What are the clinical features of achondroplasia (4)?
1. Large-appearing head - compared with the bones formed from facial cartilage.
2. Spine is of normal length, limbs are short.
3. Normal intelligence and life span.
4. Kyphoscoliosis with complications.
What are the treatments for achondroplasia?
GH, skeletal elongation (controversial)
Scurvy (vit. C deficiency, rickets and osteomalacia (vit. D deficiency), osteoporosis, and Paget disease (loss of osteoclast function) are all examples of _______ diseases of bone development.
Osteoporosis is characterized by increased _______ of the skeleton resulting from reduced ______ _____.
increased porosity, reduced bone mass
Is osteoporosis associated with an increase in bone fragility and susceptibility to fractures?
Can osteoporosis be localized or affect the entire skeleton?
What are the most common forms of osteoporosis?
Senile and postmenopausal osteoporosis.
In the case of osteoporosis, the spicules in bone are replaced by ____.
At what ages does bone mass reach its peak?
25-35 years old
What populations are more prone to osteoporosis?
Asians and white folks more than black folks
Is the risk of a 70-year old woman having a hip fracture 7 times higher than that of a 50 year old?
What is the most common fracture amongst people with osteoporosis?
In the neck and intertrochanteric region of the femur (hip fractures)
Females with osteoporosis experience vertebral fractures by a ratio of _____ to men.
The pathogenesis of osteoporosis is reflective of an imbalance of bone ________ by osteoblasts and bone ________ by osteoclasts, as well as osteoblast and stromal cell regulation of ______ _______.
imbalance of bone formation by osteoblasts and bone resorption by osteoclasts, as well as osteoblast and stromal cell regulation of osteoclast activation.
What causes secondary osteoporosis?
A variety of endocrine and genetic factors
Describe the two types of primary osteoporosis.
Type 1: increased osteoclast activity, usually seen in postmenopausal women.
Type 2: aka senile; decreased osteoblast activity, seen in elderly folk of both genders.
Describe how osteoclasts are activated.
RANK ligands on the surface of osteoblast and stromal cells bind to RANK receptors (activator for nuclear factor-kB) on osteoclast precursors + macrophage colony stimulating factor (M-CSF) --> precursor differentiation into an osteoclast.
If osteoclast activation isn't needed, osteoblast/stromal cells make osteoprotegerin (OPG), which binds to RANK ligand so it can't bind to RANK on precursor cells to activate them.
How does a decline in estrogen lead to bone loss?
No estrogen --> more cytokine production (IL-1, IL-2, IL-6, TNF) --> increased RANK-RANKL activity and decreased OPG --> too much osteoclast activation/differentiation.
Name two exogenous substances that can cause secondary osteoporosis.
1. Glucocorticoid therapy
2. Therapies against breast, prostate, etc. cancers