Non-tumoral diseases of bone

Question 1

Number of bones connected by joints

Answer 1

206

Question 2

Osteoprogenitor cells

Answer 2

pluripotent mesenchymal stem cells found in the vicinity of all bony surfaces

Question 3

Osteoblasts

Answer 3

synthesize, transport, and arrange the many proteins of matrix and initiate the process of mineralization

Question 4

Osteoclasts

Answer 4

responsible for bone resorption

Question 5

Osteocytes

Answer 5

help to control calcium and phosphate levels in the microenvironment, detect mechanical forces and translate them into biologic activity

Question 6

RANK (receptor activator for nuclear factor kB)

Answer 6

a. Member of TNF family
b. Expressed on cell membrane of preosteoclasts and mature osteoclasts
c. Stimulated by RANKL

Question 7

RANKL

Answer 7

a. Expressed by osteoblasts and marrow stromal cells

b. Stimulates RANK which leads to activation of NF-kB which in turn stimulates osteoclasts

Question 8

Osteoprotegerin

Answer 8

Blocks the actions of RANKL

Question 9

Endochondral ossification

Answer 9

cartilaginous model made by chondrocytes

axial and appendicular skeleton and base of skull

Question 10

Intramembraneous ossification

Answer 10

formed directly directly without cartilage, instead on fibrous stroma

Question 11

Congenital disorders of bone and cartilage

Answer 11

Achondroplasia, Thanatophoric dwarfism, Osteogenesis imperfecta, Osteopetrosis

Question 12

Achondroplasia

Answer 12

a. Most common form of dwarfism – failure of longitudinal bone growth (endochondral ossification)
b. Intramembranous ossification unaffected (large head relative to limbs)
c. Autosomal dominant, 85% sporadic mutations
i. In fibroblast growth factor receptor 3 (FGFR3) causes it to be constitutively on -> normally inhibits bone growth, negatively affects long bone growth

Question 13

Thanatophoric dwarfism

Answer 13

lethal variant of dwarfism

a. Caused by missense or point mutations in FGFF3 (like achondroplasia)
b. Shortening of limbs, frontal bossing of the skull, extremely small thorax -> most children die within 48 hours of birth from respiratory failure

Question 14

Osteogenesis imperfecta

Answer 14

“Brittle bone disease”

a. Most common form is autosomal dominant mutations in the genes that encode the alpha1 and alpha2 chains of type 1 collagen
i. Type I – mild OI, live normal lifespan
ii. Type II – severe form, usually death in 1st year of life
iii. Type III – also severe OI, many fractures early in life, bone deformities, wheelchair bound, shorter lifespan
iv. Type IV – moderately severe OI, need braces of crutches, life expectancy is normal or near normal
b. Manifestations: multiple fractures with minimal trauma, blue sclera
c. Histology: trabeculae are not as finely formed, look paler pink

Question 15

Osteopetrosis

Answer 15

“marble bone disease”

a. Mutations (carbonic anhydrase II) impair ability of osteoclast to generate acidic environment necessary for bone resportion -> thickened, dense bone that are prone to fracture
b. Bone fills the marrow space -> pancytopenia, extramedullary hematopoiesis (hepatospenomegaly); fractures cause hearing loss, renal tubular acidosis
c. Ehrlenmeyer flask deformity is common
d. Cranial nerve impingement and palsies as a result of narrowed foramina
e. Treat with BM transplant

Question 16

Acquired diseases of bone

Answer 16

Osteoporosis, Paget disease of bone, Rickets and Osteomalacia, Hyperparathyroidism

Question 17

Osteoporosis

Answer 17

a. Trabecular bone loses mass and interconnections despite normal bone mineralization and lab values
b. Can lead to rib fractures and vertebral compression fractures (acute back pain, loss of height, kyphosis (rounding of the back))
c. Postmenopausal women are most commonly affected – increased bone resorption due to a decrease in estrogen levels
d. Treat with calcium, vitamin D, bisphosphonates, PTH analogs, denosumab

Question 18

Paget disease of bone

Answer 18

“Osteitis deformans”

a. Common in whites from England, France, Austria, Germany, Australia, New Zealand, and the US; after 60 years old
b. Localized disorder of bone remodeling caused by increased in both osteoblastic and osteoclastic activity
c. Histology: mosaic pattern of lamellar bone which is likened to a jigsaw puzzle and is produced by prominent cement lines that anneal haphazardly oriented units of lamellar bone
d. Stages of Paget disease
i. Lytic - osteoclast
ii. Mixed – osteoclast + osteoblast
iii. Sclerotic - osteoblasts
iv. Quiescent – minimal osteoclast/osteoblast activity
e. 1-10% risk of osteogenic sarcoma; most live normal lives
f. Pain, hearing loss, HAT does not fit anymore

Question 19

Rickets and Osteomalacia

Answer 19

a. Rickets = children; osteomalacia = adults
b. Vitamin D deficiency (usually malabsorption) -> defective mineralization/calcification of osteoid, leading to soft bones that bow out
c. Histology: trabeculae are pale pink
d. Osteopenia and insufficiency fractures result

Question 20

Hyperparathyroidism

Answer 20

a. Increased PTH concentrations -> stimulate osteoclast activity
b. Histology: osteoclasts invade the marrow cavity, breaking down all trabeculae
c. Osteitis fibrosis cystica – influx of macrophages and ingrowth of reparative fibrous tissue to microfracture site creates a brown tumor

Question 21

Closed fracture

Answer 21

when the overlying tissue is intact

Question 22

Compound fracture

Answer 22

when the fracture site communicates with the skin surface

Question 23

Comminuted fracture

Answer 23

when the bone is splintered

Question 24

Displaced fracture

Answer 24

when the ends of the bone at the fracture site are not aligned

Question 25

Pathologic fracture

Answer 25

break occurs in bone altered by a disease process

Question 26

Stress fracture

Answer 26

slowly developing fracture that follows a period of increased activity in which the bone is subjected to new repetitive loads

Question 27

Nonunion of fractures

Answer 27

occurs when inadequate immobilization permits constant movement at the fracture site so that the normal constituents of callus do not form
- Pseudoarthrosis – when a nonunion allows too much motion along the fracture gap, the central portion of the callus undergoes cystic degeneration and the luminal surface can become lined by synovial-like cells -> false joint

Question 28

Avascular necrosis (osteonecrosis)

Answer 28

• Infarct of bone or marrow, usually very painful
• ASEPTIC – “Alcoholism, Sickle cell disease, Storage, Exogenous/endogenous corticosteroids, Pancreatitis, Trauma, Idiopathic, Caisson”
• Common site is femoral head; see on X-ray, V-shaped dark areas that is necrotic bone
• Histology: dead bone with empty lacunae, fat necrosis, insoluble calcium soaps

Question 29

Osteomyelitis

Answer 29

• Most common infectious agent is S. aureus; In sickle cell disease, common infectious agent is Salmonella
• Acute, subacute, and chronic
  o Acute almost always caused by bacteria that reaches bone by hematogenous, direct extension, and trauma
  ♣ Entrapped bone undergoes necrosis within the first 48 hours, spread within shaft, reach periosteum
• Histology: in kids, abscess can form under the periosteum (since it is looser at a younger age); neutrophils kill bone; in chronic osteomyelitis, see chronic inflammatory cells with fibrous tissue deposition
• Treatment: 6 weeks of IV antibiotics in acute osteomyelitis

Question 30

Myositis ossificans

Answer 30

metaplasia of skeletal muscle to bone following muscular trauma

• May present clinically as a mass at the site of a known trauma
• Benign, may resorbed on their own