Bones Path Part 1

Question 1

When is peak bone mass achieved?

Answer 1

Early adulthood after cessation of skeletal growth. *teens with eating disorders

4th decade skeletal mass decreases!

Question 2

RANK promotes bone growth or breakdown?

OPG?

Answer 2

RANK (& RANKL) promote bone breakdown! stimulate NF-kB for osteoclast propagation.

OPG promotes bone building! Prevents RANKL interaction with RANK propagating bone building

Question 3

Other modulators: Estrogen, testosterone & Vit. D–breakdown or build?

PTH, IL-1, glucocorticoids?

Answer 3

Estrogen, testosterone & Vit. D build

PTH, IL-1, glucocorticoids breakdown

Question 4

What is brachydactyly?

Answer 4

Short terminal phalanges of thumb and big toe. HOXD13

Question 5

What is cleidocranial dysplasia?

Answer 5

AD, patent fontanelles, WORMIAN BONES, short height, primitive clavicles, delayed closure of the cranial sutures RUNX2

Question 6

What is achondroplasia?

Answer 6

Dwarfism
AD, FGFR3 GoF mut.
Shortened proximal extremities, norm. trunk length & no change to longevity, intelligence or reproductive abilities.

Question 7

What is thanatophoric dysplasia

Answer 7

Most common LETHAL form of dwarfism.
FGFR3 GoF mut. (different than achondroplasia). Die soon after birth and have a small chest cavity and head, in addition to the short limbs.

Question 8

What is Osteogenesis imperfecta? What type of collagen does it affect?

Answer 8

OI: type 1 collage dz and most common inherited DO of connective tiss. Defined by ACCORDION LIKE SHORTENING OF LIMBS and blue sclerae.

Question 9

Which type of OI is the worst and best? Describe each

Answer 9

Type II - is the most severe and usually fatal in utero. Resp. problems (underdeveloped lungs) with numerous fractures and sever bone deformities.
Type I - less severe, pts live normal life spans, loose joints, brittle teeth and hearing loss in 20’s-30’s. Triangular faces

Question 10

Differentiate OI types III & IV

Answer 10

Both are of intermediate severity with IV being of less severity. Barrel chests and triangular faces with brittle teeth and hearing loss possible. Short stature
Type III - tinted sclerae, more severe bone deformity and poor muscle development
Type IV - white sclerae, mild-mod. bone deformity

Question 11

What is osteopetrosis? What enzyme is deficient?

Answer 11

aka Marble bone or Albers-Schonberg dz
Mut. in CLCN7 gene. Deficient carbonic anhydrase 2 (CA2).

Bones lack medullary cavity (Erlenmeyer Flask) & CN compression

Can result in RTA from lack of CA2. Impaired function of osteoclasts.

Question 12

In osteopetrosis, which form is the severe and which is the milder form?

Answer 12

AR is the severe form:
Infantile type found in Mediterranean & Arab races. Optic atrophy, DEAFNESS, and facial paralysis. Anemia and hydrocephaly

AD is the mild form:
Adolescence or adulthood characterized by repeat fractures and mild cranial n. deficits and anemia.

Question 13

What is mucopolysaccharidoses?

Answer 13

Lysosomal storage dz, mostly acid hydrolase enzymes affected. Accumulation of mucopolysaccharides in the chondrocytes & extracellular spaces. Leads to short stature, chest wall abnormalities & malformed bones

Question 14

Differentiate osteopenia from osteoporosis

Answer 14

Osteopenia is decreased bone mass 1-2.5 SD below the mean.

Osteoporosis is osteopenia severe enough to incr. risk of bone breaks (at least 2.5 SD). Atraumatic or vertebral compression fractures are indications. Common groups are senile & postmenopausal.

Question 15

5 main contributors to osteoporosis path.

Answer 15

1. Age related changes - senile or low turnover variant.
2. Decr. physical activity - immobility, paralysis, astronauts in zero gravity
3. Genetics
4. Ca2+ nutritional state - Ex. adolescent girls with insufficient ca2+ intake -> restricted peak bone mass -> predisposition later in life.
5. Hormonal influences - Estrogen deficiency -> high turnover variant.

Question 16

If a pt was treated with Tamoxifen for breast cancer, what should we be concerned with?

Answer 16

Increased risk for osteoporosis

Question 17

Osteoporosis morphology

Answer 17

Normal bone with decr. quantity.
Postmenopausal has incr. osteoclast activity. Vertebral bodies have thinned/perforated trabeculae causing microfractures and vertebral collapse. Thinning of the cortex.

Question 18

A 60 yo post-menopausal woman presents to the office with co loss of height. She is fair skinned and looks for have some lumbar lordosis or kyphoscholiosis. There is a SH of drinking lots of soda and smoking. What are you concerned of and what tests would you order?

Answer 18

Osteoporosis risk. DEXA-scan and blood tests for secondary causes.

Question 19

What is Paget Dz?

Answer 19

aka Osteitis deformans
Disordered increase in bone mass.
Majority of cases are polyostotic (involves mult. bones). Avg. age of dx is 70 yo. 40-50% is inherited. Sporadic form has SQSTM1 gene mut.

Question 20

What would you see on imaging and labs for a pt with Paget’s dz?

Answer 20

Mosaic pattern on lamellar bones in jig-saw like appearance with prominent cement lines. Chalk stick fractures of long bones. Incr. serum alk phos., norm. serum Ca2+ & Pi

Question 21

3 phases of Paget dz

Answer 21

1. Initial lytic phase - large osteoclasts with 100 nuclei
2. Mixed phase - clasts persist but many more blasts.
3. Final - coarsely thickened trabeculae & cortices. Soft & porous lacking structure or stability. Sarcomatous transformation possible.

Question 22

How to tx Paget’s?

Answer 22

Calcitonin & bisphosphonates

Question 23

What is the difference between Rickets and Osteomalacia?

Answer 23

Same condition of Vit. D deficiency/abnormal metabolism, diff. populations.
R - Pediatric form. Rachitic rosary of ribs
O - Adult form

Question 24

What is hyperparathyroidism & the difference between 1° and 2°?

Answer 24

Too much PTH! Normally, PTH incr. [Ca2+]serum when levels are low by activating osteoclasts and renal tubules for Ca2+ resorption, incr. Pi excretion and incr. Vit D synthesis.
1° - parathyroid autonomous PTH secretion
2° - underlying renal dz

Question 25

Hyperparathyroidism morph (3 skeletal abn)

Answer 25

Osteoporosis - most sever in phalanges, vertebrae & proximal femur
Brown tumors - microfractures from bone loss with infiltrative mac’s, hemosiderin dep. and hemorrhage -> mass of reactive brown tissue
Osteitis fibrosa cystica - clasts tunnel length of trabeculae (railroad tracks)

Question 26

Another name for osteonecrosis, common causes and what does the necrotic bone look like?

Answer 26

aka Avascular necrosis
From fractures or corticosteriod tx. Sickle cell pts can experience spontaneous medullary osteonecrosis.
Subchondral infarcts are triangular or wedge shaped

Question 27

Osteomyelitis most common cause & by demographics

Answer 27

Almost always a bacterial causation (STAPH A. in 80-90% of cases!)
Kids - hematogenous spread from trivial mucosa injuries or minor skin infections
Adults - Complications of open fractures or diabetic foot infections.

Question 28

Osteomyelitis gram (-) agents

Answer 28

E. coli, Pseudomonas, Klebsiella - UTI or IV drug abusers
Mixed bacteria - surgery or open fractures
H. Influenzae & Group B Strep
Salmonella - sickle cell pts
Neisseria - Pt’s with MAC deficiencies

Question 29

Osteomyelitis infection terms. Acute infection

Answer 29

Subperiosteal abscesses (kids)
Sequestrum - dead bone following subperisoteal abscess
Septic/suppurative arthritis in infants

Question 30

Osteomyelitis infection terms. Chronic infection

Answer 30

Chronic after first week.
Involucrum - newly deposited bone
Brodie abscess - small interosseous abscess usually, in the cortex, walled off by reactive bone.
Sclerosing osteomyelitis of Garre - mainly in children and young adults affecting the mandible. Often ass. with dental carries

Question 31

Mycobacterial osteomyelitis

Answer 31

Blood borne, bone infec may persist for years before detected.
Sx of low grade fevers, chills, wt loss.
*Histo: Caseous necrosis and granulomas

Question 32

What is another name for Pott’s dz?

Answer 32

Tuberculosis spondylitis
mycobacterial osteomyelitis, usually in the spine, breaks through bone and soft tissue. Causes permanent compression fractures

Question 33

What deformities are seen in congenital v. acquired syphilis?

Answer 33

Congenital syph. - saber shins

Acquired syph. - saddle nose