MSK: 419 - 421

Question 1

What process is inhibited in achondroplasia?

Answer 1

Impaired endochondral ossification because of impaired cartilage proliferation in the growth plate

Question 2

What is the inheritance of hereditary achondroplasia?

Answer 2

Autosomal dominant

Question 3

What is the mutation in achondroplasia?

Answer 3

Activating mutation of fibroblast growth factor receptor (FGFR3)

Question 4

Is membranous ossification affected in achondroplasia?

Answer 4

No

Question 5

What does a patient with achondroplasia look like?

Answer 5

Head that appears relatively large (actually normal sized because membranous ossification is unaffected) with short limbs (from impaired endonchondral ossification)

Question 6

Are most achondroplasia mutations hereditary or sporadic?

Answer 6

Sporadic

Question 7

What other condition can achondroplasia cause?

Answer 7

Dwarfism

Question 8

How does achondroplasia affect life span, fertility, and mental function?

Answer 8

They are all normal

Question 9

How is osteoporosis diagnosed?

Answer 9

Bone mineral density test (DEXA) with a T score of < -2.5

Question 10

Long term use of what medication can lead to osteoporosis?

Answer 10

Steroids

Question 11

What happens in osteoporosis?

Answer 11

Trabecular (spongy) bone loses mass and interconnections despite normal bone mineralization

Question 12

What is a major complication of osteoporosis?

Answer 12

Vertebral crush fractures - acute back pain, loss of heigh, kyphosis

Question 13

What are the 2 types of osteoporosis?

Answer 13

Type 1 - postmenopausal

Type 2 - senile

Question 14

Senile osteoporosis typically affects men and women greater than what age?

Answer 14

70

Question 15

Why are postmenopausal women at increased risk of osteoporosis?

Answer 15

Decreased estrogen levels

Question 16

What 2 fractures are common in postmenopausal women with osteoporosis?

Answer 16

1. Femoral neck

2. Distal radius (Colles)

Question 17

Describe different prophylaxis treatments for senile osteoporosis.

Answer 17

1. Regular weight-bearing exercise

2. Adequate calcium and vitamin D intake throughout adulthood

Question 18

How can we treat senile osteoporosis?

Answer 18

Bisphosphonates, PTH, SERMs, rarely calcitonin, denosumab (monoclonal antibody against RANKL)

Question 19

What is another name for osteopetrosis?

Answer 19

Marble bone disease

Question 20

Which cells are defective in osteopetrosis?

Answer 20

Osteoclasts

Question 21

Describe the bones in osteopetrosis.

Answer 21

Thickened and dense but prone to fracture

Question 22

Why do we see pancytopenia and extramedullary hematopoiesis in osteopetrosis?

Answer 22

Bone fills the marrow space

Question 23

What is the cure for osteopetrosis?

Answer 23

Bone marrow transplant - osteoclasts are derived from monocytes so allows the patient to make normal monocytes/osteoclasts

Question 24

What is the classic mutation in osteopetrosis and how does that lead to the disease?

Answer 24

Mutation in carbonic anhydrase II impairs the formation of an acidic environment which is necessary for bone resorption so the osteoclast is inhibited in its activity

Question 25

Why does osteopetrosis sometimes present with vision and hearing impairment?

Answer 25

Cranial nerve impingement and palsies as a result of narrowed foramina

Question 26

How does the mutation in osteopetrosis affect the kidney?

Answer 26

Can lead to renal tubular acidosis (impairment of carbonic anhydrase II)

Question 27

What is the major deficiency in osteomalacia/rickets?

Answer 27

Vitamin D

Question 28

Does osteomalacia/rickets occur in kids/adults?

Answer 28

Rickets - children | Osteomalacia - adults

Question 29

Describe the pathogenesis of osteomalacia/rickets.

Answer 29

Vitamin D deficiency --> defective mineralization/calcification of osteoid --> soft bones that bow out (rickets) or weak bones that fracture (osteomalacia)

Question 30

Describe the lab values of vitamin D, calcium, PTH, serum phosphate, and ALP in osteomalacia/rickets.

Answer 30

Decreased: vitamin D, calcium, phosphate Increased: PTH, ALP

Question 31

How does ALP affect osteoblastic/osteoclastic activity?

Answer 31

Promotes osteoblastic activity by forming an alkaline environment

Question 32

What bone disease has an increase in both osteoblastic and osteoclastic activity?

Answer 32

Paget disease of bone

Question 33

What is another name for Paget disease of bone?

Answer 33

Osteitis deformans

Question 34

Describe the serum levels of Ca, phosphorus, and PTH in Paget disease of bone.

Answer 34

Normal

Question 35

What are the 4 stages in Paget disease?

Answer 35

1. Lytic - osteoclasts 2. Mixed - osteoclasts + osteoblasts 3. Sclerotic - osteoblasts 4. Quiescent - minimal osteoclast/osteoblast activity

Question 36

What are 2 complications of Paget disease of bone?

Answer 36

1. High-output heart failure | 2. Progression to osteogenic sarcoma

Question 37

What does Paget disease of bone look like on H&E stain?

Answer 37

Mosaic pattern of woven and lamellar bone

Question 38

Is Paget disease of bone localized or more systemic?

Answer 38

Localized

Question 39

What are some common symptoms of Paget disease of bone?

Answer 39

Bone pain, increased hat size, lion-like face, hearing loss (from auditory foramen narrowing)

Question 40

What is avascular necrosis?

Answer 40

Ischemic damage leading to infarction of bone and marrow

Question 41

What is another name for avascular necrosis?

Answer 41

Osteonecrosis

Question 42

What are 5 causes of osteonecrosis?

Answer 42

Trauma, Caisson disease, high-dose corticosteroids, alcoholism, sickle cell

Question 43

What is the most common site of osteonecrosis?

Answer 43

Femoral head (due to insufficiency of medial circumflex femoral artery)

Question 44

What are the abnormal lab values in osteoporosis?

Answer 44

None - serum Ca, PO4, ALP, PTH are all normal

Question 45

What serum lab value might be abnormal in osteopetrosis?

Answer 45

Decreased calcium in severe, malignant disease

Question 46

What serum lab value is abnormal in Paget disease?

Answer 46

Increased ALP

Question 47

What are the lab values for serum Ca, PO4, ALP, and PTH in hypervitaminosis D?

Answer 47

Decreased: PTH Increased: Ca, PO4 Unchanged: ALP

Question 48

What are two causes of hypervitaminosis D?

Answer 48

1. Over-supplementation | 2. Granulomatous disease (e.g. sarcoidosis)

Question 49

What is the major endocrine problem in osteitis fibrosa cystica?

Answer 49

Hyperparathyroidism

Question 50

What causes "brown tumors" in osteitis fibrosa cystica?

Answer 50

Fibrous replacement of bone, subperiosteal thinning

Question 51

When do we typically see osteitis fibrosa cystica?

Answer 51

Compensation for end stage renal disease