Bone

Question 1

Cause of achondroplasia

Answer 1

Activating mutation in fibroblast growth receptor 3 (FGFR3); AD
FGF3 inhibits growth, becomes over-expressed

Question 2

Achondroplasia - clinical features, what is not affected

Answer 2

Short extremities, normal sized head and chest

Mental function, fertility and life span are not affected

Question 3

Achondroplasia - what type of bone formation is affected

Answer 3

Endochondral bone formation: characterized by the formation of a cartilage matrix that is replaced with bone
ex/ long bones

vs. intramembranous bone formation: bone formed without a preexisting cartilage matrix
ex/ flat bones (skull and rib cage)

Question 4

OI: what type of defect

Answer 4

Autosomal dominant defect in collagen type I synthesis

Question 5

OI: clinical features

Answer 5

Multiple fractures, blue sclera (scleral collagen thins revealing underlying choroidal veins), hearing loss

Question 6

Osteopetrosis is due to poor…

Answer 6

osteoclast function

Question 7

Important genetic variant for osteopetrosis

Answer 7

Carbonic anhydrase II mutation -> loss of acidic environment necessary for bone resorption

Question 8

Clinical features of osteopetrosis (5)

Answer 8

1. Bone fractures
2. Anemia, thrombocytopenia, and leukopenia with extramedullary hematopoiesis
3. Vision and hearing impairment (impingement on CN)
4. Hydrocephalus (narrowing of foramen magnum)
5. Renal tubular acidosis - seen with CAII mutation, lack of CA results in decreased tubular reabsorption of HCO3- leading to metabolic acidosis

Question 9

Treatment of osteopetrosis

Answer 9

Bone marrow transplant (osteoclasts are derived from monocytes)

Question 10

Rickets/Osteomalacia is due to…

Answer 10

defective mineralization of osteoid (due to low Vitamin D). Osteoblasts normally produce osteoid which is then mineralized with calcium and phosphate to form bone.

Question 11

Rickets most commonly arises before age 1 and presents with what four deformities?

Answer 11

Pigeon breast deformity
Rachitic rosary
Bowing of the legs (seen in ambulating children)
Frontal bossing (enlarlged forehead due to osteoid deposition on the skull)

Question 12

Laboratory findings: Osteomalacia

Answer 12

Low Ca++, Phosphate
High PTH
High Alkaline phosphatase

Question 13

Osteoporosis shows a reduction in which type of bone?

Answer 13

Trabecular (cancellous or spongy)

Question 14

What factors influence peak bone mass? What causes bone mass to be lost more quickly?

Answer 14

Diet, exercise and genetics attribute to peak bone mass

Lack of weight bearing exercise (space travel), poor diet and decreased estrogen (menopause)can cause bone mass to be lost more quickly

Question 15

Laboratory findings: Osteoporosis

Answer 15

Calcium, phosphate, PTH and alkaline phosphatase are all normal!

Question 16

What causes Paget’s disease? At what age is this usually seen?

Answer 16

Imbalance between osteoclast and osteoblast function (localized - does not involve the entire skeleton)
Etiology unknown - possibly viral
>60 years

Question 17

Paget disease biopsy will show…

Answer 17

Mosaic pattern of lamellar bone

Question 18

Clinical features of Paget disease of bone (5)

Answer 18

Increased hat size
Bone pain (micro fractures)
Hearing loss (impingement on cranial nerve)
Lion-like facies (craniofacial bones)
Isolated elevated alkaline phosphatase

Question 19

Complications of Paget disease

Answer 19

High-output cardiac failure - due to formation of AV shunts in bone
Osteosarcoma (osteoblasts become mutated)

Question 20

Where does the bacteria seed in osteomyelitis in adults vs. kids?

Answer 20

Adults - Epiphysis

Kids - Metaphysis

Question 21

6 common causes of osteomyelitis and what they are associated with -

Answer 21

Staph aureus - most common cause (90% of cases)
N gonorrhoeae - sexually active young adults
Salmonella - sickle cell disease
Pseudomonas - diabetics or IV drug users
Pasteurella - associated with dog or cat bite/scratches
Mycobacterium tuberculosis - usually involves the vertebrae (Pott disease)

Question 22

Clinical features of osteomyelitis (sequestrum vs. involucrum)

Answer 22

Bone pain with systemic signs of infection (fever, leukocytosis)
Lytic focus (abscess - sequestrum) surrounded by sclerosis (involucrum) of bone on x-ray

Question 23

What is the most common benign soft tissue tumor in adults? In children?

Answer 23

Lipoma (benign tumor of adipose tissue)

Rhabdomyosarcoma (rhabdomyoblast is characteristic cell, desmin positive, most common sites include head/neck/vagina)

Question 24

What is cardiac rhabdomyoma associated with?

Answer 24

Tuberous sclerosis (rare genetic disease that causes benign tumor growth in the brain and other vital organs)

Question 25

Most common malignant soft tissue tumor in adults?

Answer 25

Liposarcoma (lipoblast is characteristic cell - adipose precursor cell)

Question 26

Metastatic bone tumors are more common than primary. What type of lesion do they produce?

Answer 26

Osteolytic (punched out) lesions | Exception - prostatic carcinoma classically produces osteoblastic lesions

Question 27

Chondroma vs. Chondrosarcoma (location)

Answer 27

Chondroma is a benign tumor of the cartilage. It usually arises in the medulla of small bones of the hands and feet Chondrosarcoma is a malignant cartilage-forming tumor. Usually arises in the medulla of the pelvis or central skeleton

Question 28

Osteoma most commonly arises where? Associated with what?

Answer 28

Benign tumor of bone Surface of facial bones Associated with Gardner syndrome (multiple benign tumors and colon polyps)

Question 29

What is an osteoid osteoma? Who does it most commonly occur in? Where? What does it present as?

Answer 29

Benign tumor or osteoblasts (produce osteoid) surrounded by a rim of reactive bone Occurs in young adults (<25 ), more common in males Arises in the cortex of long bones (femur) Presents as bone pain that resolves with aspirin

Question 30

How is an osteoblastoma different from and osteoid osteoma?

Answer 30

Osteoblastomas are similar but larger (>2cm), arise in the vertebrae and present as bone pain that does not respond to aspirin

Question 31

Osteochondroma: What is it, from where, what can it transform to?

Answer 31

A tumor of the bone with a cartilaginous cap Arises from a lateral projection of the growth plate (metaphysics); bone is continuous with the marrow space Overlying cartilage can transform (rarely) to chondrosarcoma

Question 32

What is the most common benign tumor of bone?

Answer 32

Osteochondroma

Question 33

Osteosarcoma - Proliferation of what? Most common in what age group? Arises where? How does it present?

Answer 33

Malignant proliferation of osteoblasts Peak incidence in teenagers (bimodal, also seen in elderly) Arises in metaphysics of long bones (usually distal femur or proximal tibia - around the knee) Presents as a pathological fracture (tumor weakens the bone) or bone pain with swelling

Question 34

Imaging sign seen with osteosarcoma | Biopsy

Answer 34

Destructive mass with a 'sunburst' appearance and lifting of the periosteum (Codman triangle) Biopsy shows pleomorphic cells that produce osteoid (pink)

Question 35

Risk factors for osteosarcoma

Answer 35

Familial retinoblastoma, Paget disease, radiation exposure

Question 36

Giant cell tumor (what is it, what age, where does it arise, prognosis, appearance on x-ray)

Answer 36

Tumor comprised of multinucleated giant cells and stromal cells Occurs in young adults Arises in the epiphysis of long bones (distal femur or proximal tibia - knee) Locally aggressive, may recur Soap bubble appearance on x-ray

Question 37

Soap bubble appearance on x-ray is associated with what tumor?

Answer 37

Giant cell tumor

Question 38

What is the only bone tumor that arises in the epiphysis?

Answer 38

Giant cell tumor

Question 39

Ewing sarcoma (what, where, who, x-ray, biopsy, translocation and prognosis)

Answer 39

Malignant proliferation of poorly-differentiated cells derived from neuroectoderm. Arises in the diaphysis of long bones; usually in male children (>15). Onion skin appearance on x-ray (layering of new bone by periosteum). Biopsy reveals small, round blue cells that resemble lymphocytes (can be confused with lymphoma or chronic osteomyelitis). t(11;22) translocation is characteristic. Often presents with metastasis, responsive to chemotherapy

Question 40

Onion skin appearance on x-ray

Answer 40

Ewing sarcoma

Question 41

Where do these tumors occur? Osteoma Osteoid osteoma Osteochondroma Osteosarcoma

Answer 41

Osteoma - surface of facial bones Osteoid osteoma - cortex of long bones Osteochondroma - lateral projection of the growth plate (metaphysis) Osteosarcoma - metaphysis

Question 42

Where do these tumors occur? Giant cell tumor Ewing sarcoma Chondroma Chondrosarcoma

Answer 42

Giant cell tumor - epiphysis Ewing sarcoma - diaphysis Chondroma - medulla of hands and feet Chondrosarcoma - medulla of pelvis or central skeleton