MS - Path (Bone disorders)

Question 1

What is achondroplasia? What physical traits are versus are not affected, and why/why not?

Answer 1

Failure of longitudinal bone growth (endochondral ossification) => short limbs. Membranous ossification is not affected => large head relative to limbs

Question 2

What is the molecular defect in achondroplasia, and what impact does that have?

Answer 2

Constitutive action of fibroblast growth factor receptor (FGFR3) actually inhibits chondrocyte proliferation.

Question 3

What percentage of mutations leading to achondroplasia occur spontaneously, and with what condition are such mutations associated? Otherwise, what mode of inheritance does Achondroplasia exhibit?

Answer 3

> 85% of mutations occur sporadically and are associated with advanced paternal age, but the condition also demonstrates autosomal dominant inheritance.

Question 4

Of what condition is Achondroplasia a common cause?

Answer 4

Common cause of dwarfism

Question 5

How does Achondroplasia affect life span and fertility?

Answer 5

Normal life span and fertility.

Question 6

In general, what bone and lab findings define osteoporosis?

Answer 6

Trabecular (spongy) bone loss mass and interconnections despite normal bone mineralization and lab values (serum Ca2+ and [PO4]3-)

Question 7

How is osteoporosis diagnosed?

Answer 7

Diagnosed by a bone mineral density test (DEXA) with a T-score of < or = -2.5

Question 8

What habit can cause osteoporosis?

Answer 8

Can be caused by long-term exogenous steroid use

Question 9

What musculoskeletal complication can result from osteoporosis? What are 3 signs/symptoms of this condition?

Answer 9

Can lead to Vertebral crush fractures - acute back pain, loss of height, kyphosis

Question 10

What are the types of osteoporosis?

Answer 10

Type I (Postmenopausal) & Type II (Senile osteoporosis)

Question 11

What is the mechanism behind Type I osteoporosis?

Answer 11

Postmenopausal: Increased bone resorption due to decreased estrogen levels

Question 12

What patient populations does Type II osteoporosis affect?

Answer 12

Senile osteoporosis: Affects men and women > 70 years old

Question 13

What 2 fractures are associated with Type I (Postmenopausal) osteoporosis?

Answer 13

(1) Femoral neck fracture, (2) Distal radius (Colles) fracture

Question 14

What is the prophylaxis for Type II (Senile) osteoporosis?

Answer 14

Prophylaxis: Regular weight-bearing exercise and adequate calcium and vitamin D intake throughout adulthood

Question 15

What are 5 treatments for Type II (Senile) osteoporosis?

Answer 15

Treatment: (1) Bisphosphonates (2) PTH (3) SERMs (4) Rarely calcitonin; (5) Denosumab (monoclonal antibody against RANKL)

Question 16

What is Denosumab? For what specific condition is it used as treatment?

Answer 16

Denosumab (monoclonal antibody against RANKL); Type II (senile) Osteoporosis

Question 17

What is another name for Osteopetrosis?

Answer 17

Osteopetrosis (Marble bone disease)

Question 18

What is the defect in Osteopetrosis, and what effect(s) does it have on the bone?

Answer 18

Failure of normal bone resorption due to defective osteoclasts => thickened, dense bones that are prone to fracture

Question 19

What hematologic effect does osteopetrosis have, and why?

Answer 19

Bone fills marrow space => pancytopenia, extramedullary hematopoiesis.

Question 20

What phenotypic effect do mutations related to osteopetrosis have? Give an example of such a mutation.

Answer 20

Mutations (e.g., carbonic anhydrase II) impair ability of osteoclast to generate acidic environment necessary for bone resorption

Question 21

How does osteopetrosis appear on x-ray?

Answer 21

X-rays show show bone-in-bone appearance

Question 22

What complications can result from osteopetrosis, and why?

Answer 22

Can result in cranial nerve impingement and palsies as a result of narrowed foramina

Question 23

What is a potential cure for Osteopetrosis, and why?

Answer 23

Bone marrow transplant is potentially curative as osteoclasts are derived from monocytes

Question 24

What deficiency causes Osteomalacia/Rickets? In which patient population is each of these conditions seen?

Answer 24

Vitamin D deficiency; Osteomalacia in adults, Rickets in children

Question 25

Explain the pathophysiology of Osteomalacia/rickets as it relates to the gross appearance of bone in these patients.

Answer 25

Due to defective mineralization/calcification of osteoid => soft bones that bow out.

Question 26

Explain the pathophysiology of Osteomalacia/rickets as it relates to the lab findings in these patients.

Answer 26

Low vitamin D => low serum calcium => high PTH secretion => low serum phosphate. Hyperactivity of osteoblasts => high ALP (osteoblasts require alkaline environment)

Question 27

What is another name for Paget disease of the bone?

Answer 27

Paget disease of bone (osteitis deformans)

Question 28

Is Paget disease of bone common? What kind of disorder is it, and what causes it?

Answer 28

Common, localized disorder of bone remodeling caused by increase in both osteoblastic and osteoclastic activity

Question 29

What are the lab findings associated with Paget disease of bone?

Answer 29

Serum Ca2+, phosphorus, and PTH levels are normal. High ALP.

Question 30

What histology characterizes Paget disease of bone?

Answer 30

Mosaic pattern of woven and lamellar bone

Question 31

What kind of fractures characterize Paget disease of bone?

Answer 31

Long bone chalk-stick fractures

Question 32

What cardiologic complication may result from Paget disease of bone, and why?

Answer 32

Increased blood from increased arteriovenous shunts may cause high-output heart failure

Question 33

What risk is increased with Paget disease of bone?

Answer 33

Increased risk of osteogenic sarcoma

Question 34

What 2 physical exam findings characterize Paget disease?

Answer 34

(1) Hat size can be increased (note marked thickening of calvarium) (2) Hearing loss is common due to auditory foramen narrowing

Question 35

What are the stages of Paget disease, and what cell(s) act(s) during each?

Answer 35

Stages of Paget disease: (1) Lytic - osteoclasts (2) Mixed - osteoclasts + osteoblasts (3) Sclerotic - osteoblasts (4) Quiescent - minimal osteoclast/osteoblast activity

Question 36

What imaging finding may indicate Paget disease of bone?

Answer 36

marked thickening of calvarium

Question 37

Why is hearing loss common in Paget disease?

Answer 37

Hearing loss is common due to auditory foramen narrowing

Question 38

What is another name for Osteonecrosis?

Answer 38

Osteonecrosis (avascular necrosis)

Question 39

What is Osteonecrosis? In general, how does it present?

Answer 39

Infarction of bone and marrow, usually very painful

Question 40

What are 4 causes of Osteonecrosis (avascular necrosis)?

Answer 40

Caused by trauma, high-dose corticosteroids, alcoholism, sickle cell.

Question 41

What is the most common site of Osteonecrosis (avascular necrosis), and why?

Answer 41

Most common site is femoral head (due to insufficiency of medial circumflex femoral artery).

Question 42

What change does Osteoporosis cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?

Answer 42

(1) No change (2) No change (3) No change (4) No change

Question 43

What change does Osteopetrosis cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?

Answer 43

(1) No change/Decrease (2) No change (3) No change (4) No change

Question 44

What change does Paget disease cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?

Answer 44

(1) No change (2) No change (3) Increase (4) No change

Question 45

What change does Osteomalacia/Rickets cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?

Answer 45

(1) Decrease (2) Decrease (3) Increase (4) Increase

Question 46

What bone description characterizes each of the following: (1) Osteoporosis (2) Osteopetrosi s (3) Paget disease (4) Osteomalacia/Rickets?

Answer 46

(1) Low bone mass (2) Dense, brittle bones (3) Abnormal "mosaic" bone architecture (4) Soft bones

Question 47

In what ways can Osteopetrosis affect Ca2+ levels, and in what context(s)?

Answer 47

Normal or low serum Ca2+; Ca2+ decreased in severe, malignant disease

Question 48

What change does Hypervitaminosis D cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?

Answer 48

(1) Increase (2) Increase (3) No change (4) Decrease

Question 49

What are 2 causes of Hypervitaminosis D?

Answer 49

Caused by over-supplementation or granulomatous disease (e.g., sarcoidosis)

Question 50

What are the 2 types of osteitis fibrosa cystica? What change does each cause in the following lab values: (1) Serum Ca2+ (2) [PO4]3- (3) ALP (4) PTH?

Answer 50

PRIMARY HYPERPARATHYROIDISM: (1) High (2) Low (3) High (4) High; SECONDARY HYPERPARATHYROIDISM: (1) Low (2) High (3) High (4) High

Question 51

What physical finding characterizes osteitis fibrosa cystica, and what causes this?

Answer 51

"Brown tumors" due to fibrous replacement of bone, subperiosteal thinning

Question 52

What are 4 potential causes of primary hyperparathyroidism?

Answer 52

Idiopathic or parathyroid hyperplasia, adenoma, carcinoma

Question 53

In what context does secondary hyperparathyroidism often occur, and why?

Answer 53

Often as compensation for ESRD (low [PO4]3- excretion and production of activated vitamin D)