Chapter 26: Bones and Joints

Question 1

Type of Bone formation:
Bones of axial and appendicular skeleton, base of skull
Cartilaginous model of bone is first made by chondrocytes (CT matrix). Osteoclasts and osteoblasts later replace (calification and mineralization) w/woven bone and then remodel to lamellar bone. Growth plates expand with proliferation of chondrocytes
In adults, woven bone occurs after fractures and in Paget disease

Answer 1

Endochondral ossification

Question 2

Type of Bone formation:
Bones of calvarium and facial bones.
Woven bone formed directly w/o cartilage
Later remodelled to lamellar bone

Answer 2

Membranous ossification

Intramembranous

Question 3

How do osteoblasts build bone?

Answer 3

Secrete collagen and catalyzing mineralization

Differentiate from mesenchymal stem cells in periosteum

Question 4

How do osteoclasts resorb bone? Ie. bone break down

Answer 4

Multinucleated cells that dissolve bone by secreting acid and collagenase. Differentiate from monocytes/macrophages.

Question 5

How does estrogen protect bone?

Answer 5

Inhibits apoptosis in bone-forming osteoblasts and induced apoptosis in bone-resorbing osteoclasts. If estrogen deficient (postmenopause), excess remodeling cycles and bone resorption lead to osteoporosis.

Question 6

Failure of longitudinal bone growth at growth plate (endochondral ossification) => short limbs
Membranous ossification no affected => large head relative to limbs
Dwarfism, normal lifespan and fertility
Due to what mutation?

Answer 6

Achondroplasia
ACTIVATING MUTATION/constitutive activation in fibroblast growth receptor 3 (FGFR3) related to increased paternal age
Overexpression inhibits growth/chondrocyte proliferation

Question 7

trivia: which famous Game of Thrones character has a condition due to impaired cartilage proliferation in the growth plate

Answer 7

Peter dinklage! Tyrion Lannister. DUHH bitches. Too easy.

Question 8

Trabecular (spongy) bone loses mass and interconnections despite normal bone mineralization and lab values (Ca and phosphate).
How do you diagnose?
Can be caused by long term exogenous steroid use
Bone pain and Increased risk for fractures, vertebral crush fractures (acute back pain, loss of height, kyphosis)

Answer 8

Osteoporosis

DEXA scan T-score

Question 9

Postmenopausal: increased bone resorption due to decreased estrogen levels
Femoral neck fractures, distal radius (Colles) fracture

Answer 9

Type 1 osteoporosis

Question 10

Senile: affects men and women > 70 yo
Prophylaxis: regular weight bearing exercise and adequate calcium and vit D intake throughout adulthood
Treatment?

Answer 10

Type 2 osteoporosis
Treat: bisphosphonates, PTH, SERMS, rarely calcitonin, denosumab (monoclonal antibody against RANK-L), weight bearing exercise, vit D, calcium

Question 11

Congenital defect of bone, weak bone
AD defect in Type I collagen synthesis
Multiple fractures of bone
Blue sclera
Hearing loss (middle ear bones easily fracture)

Answer 11

Osteogenesis imperfecta

“brittle bone disease”

Question 12

Inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily
Due to poor osteoclast function
Due to what enzyme defect?
Bone fractures
Anemia, thrombocytopenia, leukopenia with extramedullary hematopoiesis (due to bony replacement of the marrow)
Vision and hearing impairment (impingement of CN)
Hydrocephalus (narrowing of foramen magnum)
Renal tubular acidosis (metabolic acidosis from CA2 mutation)
Treatment?

Answer 12

Osteopetrosis
“stone bone disease” “marble bone disease”
carbonic anhydrase II mutation leads to loss of the acidic environment required for bone resorption (need acidic env to remove calcium from bone)
Treat: bone marrow transplant, osteoclasts are derived from monocytes

Question 13

Defective mineralization/calcification of osteoid => soft bones that bow out.
Due to Decreased Vit D => decreased serum calcium => increased PTH secretion => decreased serum phosphate
Hyperactivity of osteoblasts => increased Alk Phos (osteoblasts require alkaline env to build bone)

Answer 13

Rickets in children

Osteomalacia in adults

Question 14

Abnormal bone mineralization
Low Vit D
Pigeon-breast deformity
Frontal bossing (enlarged forehead)
Rachitic rosary (osteoid deposition at the costochondral jxn)
Bowing of the legs

Answer 14

Rickets

Question 15

Common, localized disorder of bone remodeling caused by increase in both osteoblastic and osteoclastic activity. Doesn’t involve entire skeleton.
3 stages:
1) osteoclastic (lytic)
2) mixed
3) osteoblastic (sclerotic)
Unknown cause: maybe viral
Thick, sclerotic bone that fractures easily
Long bone chalk-stick fractures
Mosaic pattern of lamellar and woven bone

Answer 15

Paget Disease of Bone

Question 16

Bone pain
Increasing hat size
Hearing loss
Lion-like facies
Isolated elevated alk phos (normal Ca, phosphate, PTH)
What are two complications to worry about?

Answer 16

Paget Disease of Bone

1) High-Output cardiac failure due to formation of AV shunts in bone (increased blood flow)
2) Osteosarcoma b/c osteoblasts at stage 3 could become mutated

Question 17

Infarction of bone and marrow, usually very painful.
Caused by trauma, high-dose corticosteroids, alcoholism, sickle cell, caisson disease (gas emboli lodge in bone).
Most common site is femoral head (due to insufficiency of medial circumflex artery).
Osteoarthritis and fracture are major complications.

Answer 17

Avascular (asceptic) necrosis

Question 18

“Brown tumors” due to fibrous replacement of bone, subperiosteal thinning

Answer 18

Osteitis fibrosa cystica

Question 19

Brown tumors due to fibrous replacement of bone, subperiosteal thinning
Causes: Idiopathic or parathyroid hyperplasia, adenoma, carcinoma (Name type)
Labs: increased Ca, decreased phosphate, increased alk phos, increased PTH

Answer 19

Osteitis fibrosa cystica

Primary hyperparathyroidism

Question 20

Brown tumors due to fibrous replacement of bone, subperiosteal thinning
Causes: Compensation for end stage renal disease (decreased phosphate excretion and production of activated vit D)
Labs: decreased Ca, increased phosphate, increased alk phos, increased PTH

Answer 20

Osteitis fibrosa cystica
Renal osteodystrophy (result from chronic renal failure) result of 2ndary hyperparathyroidism

Question 21

Increase serum Ca, increased phosphate, decreased PTH, alk phos no change
Caused by over supplementation or granulomatous disease (sarcoidosis)

Answer 21

Hypervitaminosis D

Question 22

Benign tumor of bone
Commonly arises on surface of facial bones
Associated with Gardner syndrome

Answer 22

Osteoma

Gardner = FAP + fibromatosis of peritoneum + osteomas

Question 23

Benign tumor of osteoblasts (that produce osteoid) surrounded by a rim of reactive bone
Arises in cortex of long bones
Occurs in young adults

Answer 23

Osteoid osteoma

Question 24

Imaging: bony mass > 2cm, arises in vertebrae, bone pain does not resolve w/aspirin

Answer 24

Osteoblastoma

Question 25

Most common benign tumor of bone
tumor of mature bone with an overlying cartilage cap
Males

Answer 25

Osteochondroma

Question 26

2nd most common primary malignant bone tumor (after multiple myeloma)
Malignant proliferation of osteoblasts
Pathologic fracture or bone pain w/swelling
Imaging: lucent sunburst pattern on x-ray, MRI heterogenous mass w/periosteal elevation (Codman triangle)
Arises: metaphysis of long bones, distal femur or proximal tibia (around knee)

Answer 26

Osteosarcoma

Question 27

Who does osteosarcoma affect commonly? Risk factors?

Answer 27

Bimodal distribution:
10-20 yo
>65 yo
[RF: familal retinoblastoma, Paget disease, radiation, Li-Fraumeni syndrome (germline p53 mutation)]

Question 28

Locally aggressive benign tumor often around knee
Arises in epiphysis of long bones
20-40 yo adults
Soap bubble appearance on X-ray

Answer 28

Giant cell tumor

comprised of multinucleated giant cells and stromal cells

Question 29

Malignant proliferation of poorly differentiated (anaplastic) cells derived from neuroectoderm
Arises in diaphysis of long bones
Male children

Answer 29

Ewing sarcoma
Confused with lymphoma or chronic osteomyelitis
t(11;22)

11 + 22 = 33 (Patrick ewing’s jersey number)

Question 30

Benign tumor of cartilage

Usually arises in medulla of small bones of hands and feet

Answer 30

Chondroma

Question 31

Rare, malignant, cartilaginous tumor
Arises in medulla of pelvis or central skeleton, spine, scapula, humerus, tibia or femur
Men 30-60 yo
Expansile glistening mass w/i the medullary cavity

Answer 31

Chondrosarcoma