Congenital and metabolic bone disorders

Question 1

Inheritance of achondroplasia

Answer 1

Autosomal dominant

Question 2

Mutation in achondroplasia

Answer 2

FGFR3 on chromosome 4, inhibits endochondral growth

Question 3

Narrow and disorganizes zones of proliferation and hypertrophy of bone

Answer 3

Achondroplasia

Question 4

Laron dwarfism

Answer 4

Pituitary dysfunction or secondary to a mutation in growth hormone receptor

Question 5

Inheritance of osteogenesis imperfecta

Answer 5

Autosomal dominant

Question 6

Deficiencies in type I collagen synthesis related to defects in EC structural proteins

Answer 6

Osteogenesis imperfecta

Question 7

Mutation in osteogenesis imperfecta

Answer 7

COL1A1 and COL1A2 genes encoding alpha-1 and -2 chains of type 1 collagen due to replacement of glycine

Question 8

Group of rare genetic disorders characterized by reduced bone resorption due to deficient osteoclast development or function

Answer 8

Osteopetrosis

Question 9

Mutations and inheritance associated with osteopetrosis

Answer 9

TCIRG1 –> AR
CLCN7 –> AD
CA-II –> AR

Question 10

Normal function of TCIRG1

Answer 10

Makes an osteoclast proton pump

Question 11

Normal function of CLCN7

Answer 11

Osteoclast chloride channel

Question 12

Albers-Schonberg disease

Answer 12

Osteopetrosis caused by CLCN7 mutation

Question 13

Normal function of CA-II

Answer 13

Generates protons and facilitates the resorption pit acidification by osteoclasts

Question 14

Deposited bone tends to woven instead of lamellar

Answer 14

Osteopetrosis

Question 15

Inheritance of infantile osteopetrosis

Answer 15

Autosomal recessive

Question 16

Inheritance of adult osteopetrosis

Answer 16

Autosomal dominant

Question 17

Treatment for osteopetrosis

Answer 17

Hematopoietic stem cell transplantation –> osteoclasts are derived from

Question 18

Radiologic features of osteopetrosis

Answer 18

Lack of medullary canal with misshapen ends of long bones

Question 19

Histologically normal bone that is decreased in quantity

Answer 19

Osteoporosis

Question 20

Three phases of Paget disease

Answer 20

Initial osteolytic stage
Mixed osteoclastic-osteoblastic stage
Burned-out quiescent osteosclerotic stage

Question 21

Marked by increased, but disordered and structurally unsound bone mass

Answer 21

Paget disease or osteitis deformans

Question 22

Haphazardly oriented lamellae are joined by a prominent cement line

Answer 22

Paget disease

Question 23

Mutation in Paget disease

Answer 23

SQSTM1 resulting in increased NFkB activity

Question 24

Platybasia

Answer 24

Flattening of base of skull causing impingement in Paget disease

Question 25

Increased alkaline phosphatase and urinary excretion of hydroxyproline with normal Ca, phosphorous, and PTH

Answer 25

Paget disease

Question 26

Complications of Paget disease

Answer 26

Osteosarcoma or fibrosarcoma
High output heart failure

Question 27

3 skeletal abnormalities associated with hyperparathyroidism

Answer 27

Osteoporosis
Brown tumors
Osteitis fibrosa cystica

Question 28

Secondary hemorrhage, macrophage recruitment, and ingrowth of reparative fibrous tissue that creates a mass lesion

Answer 28

Brown tumor

Question 29

Combination of increased bone cell activity, peritrabecular fibrosis, and cystic brown tumors

Answer 29

Generalized osteitis fibrosa cystic or von Recklinghausen disease of bone

Question 30

Clinical features of hyperparathyroidism

Answer 30

Stones - kidney stones
Bones - skeletal changes
Moans - depression
Groans - GI irregularities

Question 31

Manifestations of renal osteodystorphy

Answer 31

Osteopenia/porosis
Osteomalacia
Secondary hyperparathyroidism
Growth retardation

Question 32

3 mechanisms through which kidney disease causes skeletal abnormalities

Answer 32

Tubular dysfunction
Secondary hyperparathyroidism
Decreased biosynthetic function (vit D)

Question 33

Normal Ca, phosphate, alkaline phosphatase and PTH

Answer 33

Osteoporosis

Question 34

Normal or decreased CA, normal PTH and phosphate, increased alkaline phosphatase

Answer 34

Paget disease

Question 35

Decreased Ca and phosphate, increased alkaline phosphatase and PTH

Answer 35

Osteomalacia or Rickets

Question 36

Increased Ca, alkaline phosphatase, and PTH. Decreased phosphate

Answer 36

Osteitis fibrosa cystica in primary hyperparathyroidism

Question 37

Decreased Ca. Increased phosphate, alkaline phosphatase, and PTH.

Answer 37

Secondary hyperparathyroidism in CKD