Bone - Important Concepts

Question 1

Endochondrial ossification

Answer 1

Bones of axial and appendicular skeleton and base of skull.
Cartilage (Chondrocytes) –> Woven bone (osteoclasts and osteoblasts) –> Lamellar bone

In adults, woven bone occurs after fractures and in Paget disease.

Question 2

Membranous ossification

Answer 2

Bones of calvarious and facial bones
Woven bone (osteoclasts and osteoblasts) --> lamellar bone
(unlike endochondrial ossification which has a cartilage phase first)

Question 3

What do osteoblasts differentiate from?

What do osteoclasts differentiate from?

Answer 3

Mesenchymal stem cells in the periosteum ( membrane that covers the outer surface of all bones,[1] except at the joints of long bones)

Monocytes / macrophages

Question 4

What are osteoclasts?

Answer 4

Multinucleated cells - they dissolve bone by secreting acids and collagenases.

Question 5

Low effects of PTH versus high effects?

Answer 5

Low levels - anabolic effects

Chronic high PTH - catabolic effects - osteitis fibrosis cystica

Question 6

Estrogen effects on bone?

Answer 6

Inhibits apoptosis in osteoblasts

Induces apoptosis in osteoclasts

Question 7

What happens with estrogen deficiency?

Answer 7

Excess remodeling cycles and bone resorption –> osteoporosis

Question 8

Failure of longitudinal bone growth and endochondrial ossification

Answer 8

Achondroplasia, caused by FGFR-3 mutation on chromosome 4, which constitutively activates it, autosomal dominant. Membranous ossification is not affected so large head relative to limbs.

Question 9

Achondroplasia

Answer 9

Achondroplasia, caused by FGFR-3 mutation on chromosome 4, which constitutively activates it, autosomal dominant. Membranous ossification is not affected so large head relative to limbs.

Associated with advanced paternal age. >85% of mutations occur sporadically.

Question 10

For osteoporosis what will lab values look like?

Answer 10

Normal

Question 11

How is osteoporosis diagnosed?

Answer 11

DEXA scan with T score < -2.5

Question 12

Type I osteoporosis

Answer 12

Postmenopausal - increased bone resorption due to decreased estrogen levels.

Associated with femoral neck fracture, distal radius / Colles fractures

Question 13

Type II osteoporosis

Answer 13

Senile osteoporosis - affects men and women > 70 years old.

Question 14

Treatment of osteoporosis

Answer 14

Bisphosphonates, PTH, SERMs

Rarely calcitonin, denosumab (monoclonal antibody against RANKL)

Question 15

Failure of normal bone resorption due to defective osteoclasts. Thickened, dense bones prone to fracture. Pancytopenia. Extramedullary hematopoiesis. Cranial nerve impingement.

Answer 15

Osteopetrosis (marble bone disease)

Question 16

Osteopetrosis (marble bone disease)

Answer 16

Failure of normal bone resorption due to defective osteoclasts. Thickened, dense bones prone to fracture. Pancytopenia. Extramedullary hematopoiesis. Cranial nerve impingement.

Mutations such as carbonic anhydrase II impair ability of osteoclast to generate acidic environment necessary for bone resorption.

Cure with bone marrow transplant - osteoclasts are derived from monocytes.

Question 17

X ray showing bone-in-bone appearance

Answer 17

Osteopetrosis

Question 18

How can you cure osteopetrosis?

Answer 18

Bone marrow transplant - osteoclasts are derived from monocytes

Question 19

What is Vitamin D deficiency called in adults vs children?

Answer 19

Osteomalacia - adults

Rickets - children

Question 20

Lab values in osteomalacia / rickets?

Answer 20

Decreased Ca and PO4, increased ALP and PTH

Increased PTH causes decreased PO4
Decreased vitamin D causes decreased serum calcium
Osteoblasts are hyperactive leading to increased ALP

Question 21

Increased ALP, no other lab abnormality
Increased hat size
Hearing loss

Answer 21

Paget disease of the bone / osteitis deformans

Question 22

Osteitis deformans

Answer 22

Another name for Paget disease of the bone

Question 23

Mosaic pattern of woven and lamellar bone - long bone chalk-stick fractures

Answer 23

Paget disease of the bone

Question 24

What causes Paget disease of the bone?

Answer 24

Increase in both osteoblastic and osteoclast activity

Question 25

What are patients with Paget at risk of ?

Answer 25

Osteogenic sarcoma

Question 26

Stages of Paget?

Answer 26

Lytic - osteoclasts Mixed - osteoclasts and osteoblasts Sclerotic - osteoblasts Quiescent - minimal osteoclast/osteoblast activity

Question 27

Marked thickening of the calvarium

Answer 27

Could be associated with Paget disease of the bone

Question 28

Most common site of osteonecrosis

Answer 28

Femoral head, due to insufficiency of medial circumflex femoral artery

Question 29

Causes of avascular necrosis

Answer 29

Trauma HIgh dose corticosteroids Alcoholism Sickle cell

Question 30

Lab findings in primary hyperparathyroidism vs secondary hyperparathyroidism

Answer 30

``` Ca up, PO4 down, ALP up, PTH up Ca down (binds PO4, forming insoluble calcium phosphate, also not enough vitamin D), PO4 up (because usu ESRD so PO4 excretion is compromised), ALP up, PTH up ```

Question 31

Soap bubble appearance on X ray

Answer 31

Giant cell tumor (picture giants bathing in a soapy bubble bath).

Question 32

Giant cell tumor

Answer 32

``` 20-40 years old. Epiphyseal end of long bones. Locally aggressive benign tumor often around the knee. Soap bubble appearance on X-ray Multinucleated giant cells. ```

Question 33

Osteochondroma

Answer 33

Males < 25. Most common benign tumor. Mature bone with cartilaginous cap. Rarely transforms to chondrosarcoma. Can occur anywhere that cartilage forms bone - the long bone of the legs, scapula, etc. Formation of new bone on surface of bone.

Question 34

2nd most common primary malignant bone tumor after multiple myeloma

Answer 34

Osteosarcoma

Question 35

Exostosis

Answer 35

Possibly another name for osteochondroma

Question 36

Osteosarcoma

Answer 36

Bimodal distribution - 10-20 years old primarily, >65 secondarily. Predisposing factors: Paget disease of the bone, bone infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome (germline p53 mutation) Metaphysis of long bones, often around the knee. Codman triangle - from elevation of periosteum Sunburst pattern on X-ray Aggressive - treat with surgical en bloc resection (with limb salvage) and chemotherapy

Question 37

What does osteochondroma sometimes transform into?

Answer 37

Chondrosarcoma

Question 38

Ewing sarcoma

Answer 38

Boys < 15 years old Commonly appears in the diaphysis of long bones, pelvis, scapula, and ribs Anaplastic small blue cell malignant tumor. Extremely aggressive with early metastasis, responsive to chemotherapy. Onion skin appearance in bone Assocaited with t(11;22) translocation.

Question 39

Anaplastic small blue cell malignant tumor that appears in the diaphysis of the long bone of a 10 year old boy.

Answer 39

Ewing sarcoma

Question 40

Onion skin appearance in bone

Answer 40

Ewing sarcoma Osteomyelitis Osteogenic sarcoma Not pathognomonic of Ewing sarcoma

Question 41

Chondrosarcoma

Answer 41

Rare, malignant cartilaginous tumor that is usually located in pelvis, spine, scapula, humerus, tibia, or femur. May be primary in origin or from osteochondroma. Expansile glittering mass within the medullary cavity.

Question 42

Sarcoma

Answer 42

Cancer of mesenchymal origin - rarer than carcinoma

Question 43

Carcinoma

Answer 43

Malignant tumor of epithelial cells.

Question 44

Someone presents to you with a p53 mutation. What bone tumor do they most likely have?

Answer 44

Osteosarcoma

Question 45

Most bone tumors seem to occur in which gender?

Answer 45

Males