Genetic & Metabolic Bone Disorders

Question 1

What are the two general components of bone?

Answer 1

Organic and inorganic

Question 2

What are the components of the organic component of bone?

Answer 2

Cells and matrix proteins

Question 3

What are the cells that are in the organic part of bone? (4)

Answer 3

Osteoprogenitor cells
Osteoblasts
Osteocytes
Osteoclasts

Question 4

What are the components of the matrix in organic bone?

Answer 4

Collagen type I

Non-collagenous proteins

Question 5

What is the main component of inorganic bone?

Answer 5

calcium hydroxyapatite

Question 6

What is unmineralized bone called?

Answer 6

Osteoid

Question 7

What are osteoprogenitor cells?

Answer 7

Pluripotential mesenchymal cells that can form osteoblasts

Question 8

What is the function of osteoblasts?

Answer 8

Synthesize and transport protein and osteoprotegerin, and initiate mineralization

Question 9

What is the function of the RANK-L protein?

Answer 9

receptor on osteoblasts that binds to RANK receptor on osteoclasts to stimulate osteoclastic bone resorption

Question 10

What is the precursor cell to osteoclasts?

Answer 10

Hematopoietic progenitor cells (fused monocytes/ Macrophages)

Question 11

What is the role of osteoprotegerin?

Answer 11

Decoy receptor for RANKL, to prevent osteoclast activation

Question 12

What are osteocytes? What is their function?

Answer 12

• Osteoblasts that have become surrounded by matrix

- Regulate daily serum Ca levels

Question 13

How do osteoclasts appear histologically?

Answer 13

Multiple nuclei

Question 14

Where is osteoprotegerin found?

Answer 14

Osteoclasts

Question 15

How do osteocytes communicate with one another?

Answer 15

canaliculi

Question 16

What is osteoid?

Answer 16

Unmineralized organic matrix that is lined by osteoblasts

Question 17

What are the lacunae in which osteoclasts reside?

Answer 17

Howship lacunae

Question 18

What part of the bone do osteoclasts not resorb?

Answer 18

Bone lined by osteoid or unmineralized cartilage

Question 19

What is woven bone and laminar bone?

Answer 19

Woven bone = Collagen deposited in a random arrangement

Lamellar bone = bone deposited in an orderly, parallel arrangement

Question 20

Where is woven bone usually present?

Answer 20

Fetal skeleton, at the growth plates, and in processes where there is very rapid bone production

Question 21

True or false: Woven bone is almost always pathologic in adults

Answer 21

True

Question 22

Where is lamellar bone located?

Answer 22

Only type of bone in adults

Question 23

What are the 4 types of lamellar bone?

Answer 23

• Concentric
• Interstitial
• Inner circumferential
• Outer circumferential

Question 24

Which is more sturdy–lamellar bone or woven bone?

Answer 24

Lamellar bone

Question 25

What type of bone comprises calluses?

Answer 25

Woven bone

Question 26

What are the causes of woven bone deposition in adults?

Answer 26

- calluses - Fibrous dysplasia - Areas surrounding tumors or infection

Question 27

Which has more osteocytes: woven or lamellar bone?

Answer 27

Lamellar bone

Question 28

What is an osteon?

Answer 28

Haversian canal + surrounding circular lamellar bone

Question 29

What lines woven bone?

Answer 29

Osteoblasts

Question 30

What are type I - IV of collagen?

Answer 30

``` I = bone II = cartilage III = reticular IV = BM ```

Question 31

What, generally, is achondroplasia?

Answer 31

Fusion of the epiphyseal plates before full maturity

Question 32

What is the genetic cause of achondroplasia?

Answer 32

Reduction in the proliferation of chondrocytes in developing growth plates d/t pt mutation in FGFR3

Question 33

What is the normal role of FGFR3?

Answer 33

Inhibition of normal proliferation of chondrocytes at the growth plate (this is constitutively active in achondroplasia)

Question 34

True or false: achondroplasia is usually inherited

Answer 34

false--most are sporadic mutations

Question 35

If achondroplasia is inherited, what inheritance pattern does it follow?

Answer 35

AD

Question 36

True or false: homozygotes for FGFR3 mutation is lethal

Answer 36

True--Small chest wall = respiratory failure

Question 37

What happens to the ones of proliferation in achondroplasia?

Answer 37

hypertrophied, narrowed, and disorganized

Question 38

Which bones are usually short in achondroplasia?

Answer 38

All bones from formed cartilage

Question 39

True or false: mental and reproductive development in achondroplasia is usually normal

Answer 39

True

Question 40

What happens to the trunk with achondroplasia?

Answer 40

Normal length

Question 41

What are the five zones of normal epiphyseal plate growth?

Answer 41

1. Reserve zone 2. proliferation 3. hypertrophy 4. Mineralization 5. Spongiosa

Question 42

What happens to the zones of epiphyseal plates with achondroplasia?

Answer 42

Disorganization with transverse bars of bone sealing of plate growth

Question 43

How is the head relative to the rest of the body with achondroplasia?

Answer 43

Enlarged with frontal bossing

Question 44

What is the defect with osteogenesis imperfecta?

Answer 44

Abnormalities of type I collagen synthesis results in extreme bone fragility and thinning of bone cortex and trabeculae

Question 45

What is the genetic cause of osteogenesis imperfecta, and what is the inheritance pattern?

Answer 45

Mutations in alpha 1 and 2 collagen chains AD

Question 46

What is type I OI?

Answer 46

increased risk of fracture, but is usually not deforming

Question 47

What is type II OI?

Answer 47

Lethal--multiple fractures in utero with fetal demise

Question 48

What is OI type III and IV?

Answer 48

Progressive deformities

Question 49

What happens to the bone with OI?

Answer 49

Thinning of the cortex and trabeculae, with reduced numbers of trabeculae

Question 50

What are the eye findings with OI?

Answer 50

Blue sclerae

Question 51

What are the dental findings of patients with OI?

Answer 51

Amber, yellowish brown or translucent

Question 52

What may happen to hearing with OI?

Answer 52

Decreased

Question 53

True or false: patients with OI have a normal survival rate

Answer 53

True

Question 54

What happens to the bones in type III and IV OI?

Answer 54

Bowing and breaking

Question 55

What is osteopetrosis?

Answer 55

Marble bone disease--group of genetic diseases caused by decreased osteoclastic bone resorption, leading to diffuse skeletal sclerosis

Question 56

What is the inheritance pattern of Osteopetrosis?

Answer 56

AR malignant | AD benign

Question 57

What is the major cellular issue with osteopetrosis?

Answer 57

Defective osteoclastic activity, leading to abnormally thickened, heavily mineralized, and brittle bone

Question 58

What causes the hematological abnormalities with osteopetrosis?

Answer 58

Encroachment on the bone marrow leads to reduced cellular proliferation

Question 59

What are the features of the clinical presentation of osteopetrosis?

Answer 59

- Anemia/ thrombocytopenia - Increased fractures - CN palsies from compression - Increased infx susceptibility

Question 60

What is the role of bone marrow transplant with osteopetrosis?

Answer 60

helpful--provides progenitor cells which produce normal osteoclasts, which can reverse many of the skeletal abnormalities

Question 61

What are the primary causes of osteoporosis?

Answer 61

Menopause | Age

Question 62

What are the common secondary causes of osteoporosis?

Answer 62

Glucocorticoid induced | Immobilization induced

Question 63

What, generally, is the pathophysiology of osteoporosis?

Answer 63

Reduction of bone mass

Question 64

What are the histological findings of osteoporosis?

Answer 64

- Cortex and trabeculae are thinned, but remain of normal composition - Increase porosity of the bone

Question 65

By the time you're able to diagnose osteoporosis be x-ray, what percent of bone is lost?

Answer 65

40%

Question 66

What bones are particularly affected with osteoporosis?

Answer 66

Trabecular bone, such as, weight bearing bones

Question 67

what is the role of estrogen in preventing bone formation?

Answer 67

- Increased production of osteoprotegerin | - Increase in collagen synthesis by osteoblasts

Question 68

What happens when estrogen levels fall with bone formation?

Answer 68

- Increased production of RANKL | - Decreased osteoprotegerin

Question 69

What are wedge fractures?

Answer 69

When the anterior column of the vertebral body is compressed, leading to kyphosis, but usually with preservation of the spinal cord

Question 70

What are burst fractures?

Answer 70

Axial load disrupts the anterior, middle, and/or posterior columns, frequently leading to disruption of the spinal cord

Question 71

What happens to the vertebral bodies with osteoporosis?

Answer 71

Shorten

Question 72

How do glucocorticoids cause osteoporosis? (3)

Answer 72

Increase in osteoclast survival, decrease in osteoblastogenesis, and increased apoptosis of osteocytes

Question 73

What causes rickets and osteomalacia?

Answer 73

Defective mineralization caused by vit D deficiency

Question 74

What is the effect of rickets in children?

Answer 74

heaping of unmineralized matrix leads to softening of bones and increased fractures

Question 75

What are the causes of Vit D deficiency in the developed world?

Answer 75

malabsorption syndromes | Liver/kidney disease

Question 76

What are the s/sx of osteomalacia?

Answer 76

- generalized pain - fractures - Mottled areas of bone lucency

Question 77

What are the s/sx of rickets?

Answer 77

- bowing of the legs - Frontal bossing - Pectus carinatum

Question 78

What is the Rachitic rosary? What causes it?

Answer 78

- The prominent knobs of bone at the costochondral joints of rickets patients - Bones grow in thickness, but not length

Question 79

What happens histologically with osteomalacia?

Answer 79

More osteoid, causing a more malleable bone