Bone Disorders B&B

Question 1

what is the most severe form of osteopetrosis, and what is the genetic cause?

Answer 1

osteopetrosis = thick bones, due to defective osteoclast activity

autosomal recessive (infantile) form: mutated carbonic anhydrase type II gene —> inability to make H+, which is needed by osteoclasts

therefore, may also have RTA

Question 2

autosomal recessive vs autosomal dominant osteopetrosis

Answer 2

osteopetrosis = thick bones, due to defective osteoclast activity

autosomal recessive (infantile) form: mutated carbonic anhydrase type II gene —> inability to make H+, which is needed by osteoclasts (therefore, may also have RTA) - most severe form

autosomal dominant form (Albers-Schonberg disease): milder, presents in adolescence (identified by x-ray)

Question 3

what are the potential complications associated with osteopetrosis? (3)

Answer 3

osteopetrosis = thick bones, due to defective osteoclast activity

—> bones prone to fracture
—> pancytopenia due to excess bone growth into medullary cavity
—> cranial nerve compression due to excess bone growth in skull (vision loss, deafness, facial paralysis)

[potentially curable with bone marrow transplant because osteoclasts are derived from monocyte/macrophage lineage]

Question 4

how is the growth plate affected by rickets?

Answer 4

growth plate thickens as chondrocytes expand (disorganized growth)

osteoblasts lay down osteoid but it cannot be mineralized —> bone thickens from osteoid accumulation and grows distorted (epiphyseal widening, bowed legs/genu varum, swelling at costochondral junctions, etc)

Question 5

in which sites does rickets vs osteomalacia occur?

Answer 5

rickets - growth plates (children only)

osteomalacia - areas of bone turnover (children and adults)

Question 6

what are the 2 classic x-ray findings of osteomalacia?

Answer 6

1. pseudofractures - looks like a white line
2. Looser zone - looks like a black space

caused by repaired stress fractures which are inadequately mineralized + erosion of bone by arterial pulsations

Question 7

what is the best indicator for vitamin D status in a patient? explain

Answer 7

inert vitamin D from diet/sun undergoes hydroxylation twice:

1. liver —> 25-OH (calcidiol), storage form
2. kidney —> 1,25-OH2 (calcitriol), active form

serum calcidiol / 25-OH is best measurement because this is the storage form and is unaffected by PTH activity

Question 8

what occurs in Paget’s Disease?

Answer 8

aka osteitis deformans, focal bone disorder in older patients (~70yo) of excessive bone remodeling, due to abnormal osteocytes (—> increased bone alkaline phosphatase)

new bone is abnormally large and deformed —> enlarged skull, cranial nerve compression, radiculopathy, erythema over affected areas (hypervascularity)

Question 9

what are the stages of Paget’s Disease? (3)

Answer 9

[focal bone disorder of excessive/ abnormal remodeling in older patients]

1. initial/ osteolytic phase: osteocytes breakdown bone
2. mixed/ osteolytic-osteoblastic phase: growth and destruction
3. final/ osteosclerotic phase: bone formation dominates + hypervascularity of bone

Question 10

what is the hallmark morphology of Paget’s Disease?

Answer 10

[focal bone disorder of excessive/ abnormal remodeling in older patients]

mosaic pattern of lamellar bone with cement lines - looks patchy

Question 11

what is the most common complication of Paget’s Disease?

Answer 11

[focal bone disorder of excessive/ abnormal remodeling in older patients]

most common complication/ characteristic fracture - ”chalkstick fracture”, bone snaps clean in half like a stick of chalk

Question 12

what is a rare but dangerous cardiac consequence of Paget’s Disease? why does this occur?

Answer 12

[focal bone disorder of excessive/ abnormal remodeling in older patients]

hypervascularity occurs with excessive bone remodeling —> AV fistulas form in new bone, which bypass the resistance vessels (arterioles) —> high output heart failure

Question 13

osteitis fibrosa cystica

Answer 13

classic bone disease of hyperparathyroidism —> hypercalcemia + low phosphate

bone pain + fractures

x-ray: subperiosteal bone resorption + brown tumors

Question 14

what are the 2 classic x-ray findings of osteitis fibrosa cystica

Answer 14

[classic bone disease of hyperPTH]

1. subperiosteal bone resorption: indented edges of fingers
2. brown tumors (osteoclastoma): collections of giant osteoclasts, appear as black circles

Question 15

patient has a bone disorder. blood shows high PTH and high phosphate. what is the root cause of their osteodystrophy?

Answer 15

renal failure ! can’t get rid of phosphate despite high PTH