Chapter 26: Bone, joint, soft tissue

Question 1

What pathways are involved in osteoprogenitor differentiation into osteoblasts?

Answer 1

• RUNX2/CBFA1 transcription factor network

- WNT/beta catenin signalling

Question 2

Define dysplasia and dysostosis

Answer 2

Dysplasia: mutations in regulators of skeletal organogenesis which have a global effect on bone development
Dysostosis: Localized problems in migration of mesenchyme; may be due to homeobox mutations

Question 3

What is achondroplasia and what causes it?

Answer 3

• most common disease of the growth plate and cause of dwarfism
• caused by mutation in FGFR3 which causes constitutive activation and thereby suppresses growth

Question 4

What are general categories of osteoporosis causes?

Answer 4

Primary: senile, postmenopausal, idiopathic
Endocrine: Hyperparathyroid, hyper/hypothyroid, hypogonadism, diabetes
Neoplasia: Myeloma, carcinoma
GI: malnutrition, malabsorption, vitamin deficiencies (C, D)
Drugs: anticoagulants, chemotherapy, steroids, alcohol
Miscellaneous: OI, immobilization, homocytinuria, anemia

Question 5

How does PTH affect bone?

Answer 5

• binds to receptors on osteoblasts, which increased RANK signalling and thereby increased osteoclast activity
• von Recklinghausen disease of bone: increased bone activity, peritrabecular fibrosis, cystic brown tumors

Question 6

What are brown tumors?

Answer 6

• caused by excessive PTH
• excessive bone loss leading to microfractures and hemorrhage that result in ingrowth of reparative tissue resulting in brown tumor formation

Question 7

What is renal osteodystrophy?

Answer 7

Chronic renal failure causes phosphate retention which induces secondary hyperparathyroidism
-Hypocalcemia also results from decreased Vit D production by failing kidneys
PTH increases serum calcium
Hyperparathyroidism increased osteoclast activity

Overall result is increased bone resorption, growth failure and osteoporosis

Question 8

Causes of osteonecrosis

Answer 8

Dysbarism
Drugs: steroids
Trauma
Radiation
Connective tissue disorders
Pregnancy
Gaucher disease
Sickle cell and other anemia
Alcohol abuse
Chronic pancreatitis
Tumors
Epiphyseal disorders

Question 9

What is rheumatoid factor?

Answer 9

An autologous antibody to the Fc portion of IgG (mostly IgM)

-may not be the cause but is a marker of RA

Question 10

What are secondary causes of gout?

Answer 10

Overproduction of uric acid due to increased nucleic acid turnover (leukemias) or inborn metabolic errors (HGPRT deficiency)
Reduced excretion of uric acid due to renal disease

Question 11

What translocation can be seen in giant cell tumor of tendon sheath and PVNS?

Answer 11

t(1;2) CSF1-promoter of collagen VI alpha 3 gene

-causes overexpression of CSF1 which is an attractant for macrophages