Congenital and Acquired Disease of Bone Development Flashcards Preview

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Flashcards in Congenital and Acquired Disease of Bone Development Deck (55):
1

____ is bone that has not been mineralized

osteoid

2

What are osteoprogenitor cells?

Pluripotential mesenchymal stem cells. Under CBFA-1 stimulation they can become osteoblasts. They can also become macrophages.

3

____ sense mechanical stress and regulate serum calcium and phosphorous

osteocytes

4

_____ mediates osteoclasts and have PTH receptors

osteoblasts

5

Composition of osteoid

type 1 collagen, 90% of organic part

6

Role of osteoblasts

synthesize osteoid, initiate mineralization, become surrounded by matrix and become osteocytes, mediate osteoclast activity, have PTH receptors

7

_____ are incased in bone and communicate through canaliculi

osteocytes

8

Osteoclasts require what cytokines for differentiation?

IL1,3,6,11, GM-CSF, M-CSF

9

Where do osteoclasts reside?

resorption pits, howship lacunae

10

____ are multinucleated cells responsible for resorption and remodeling.

osteoclasts.

11

What pararcine signals allow precursor cells to produce functional osteoclasts?

Osteoblast/ stromal cell membrane-associated RANK ligand (RANKL) binds to its receptor RANK located on the cell surface of osteoclast precursors. This interaction in the background of macrophage colony-stimulating factor (M-CSF) causes the precursor cells to produce functional osteoclasts

12

what does osteoprotegerin do?

Stromal cells also secrete osteoprotegerin (OPG) which acts as a decoy receptor for RANKL, preventing it from binding the RANK receptor on osteoclast precursors. Consequently OPG prevents bone resorption by inhibiting osteoclast differentiation

13

_____ is the cartilage between ossification centers.

growth plate

14

Growth plate is in which part of the bone?

epiphysis

15

Why are children more prone to osteomyelitis?

richer blood supply

16

Describe the blood supply in growing bone vs mature bone

Growing: blood is supplied to growth plate in epiphysis.In mature bone, metaphyseal vessels penetrate the cartilage plate

17

OI is a family of diseases having in common mutations in _____.

type 1 collagen genes

18

What are the classic subtypes of OI

1- too litte pro-a1 made. 2-Pro-a1 is too short (lethal in urtero. 3) triple helix doesnt form well. 4) pro-a2 is too short

19

OI mode of inheritance

most are AD; 2 is either recessive or new AD

20

What are the 4 major clinical criteria of OI?

osteoporosis, blue sclerae, dintinenesis imperfecta, premature otosclerosis

21

Is OI the only thing you see blue sclera with?

No- things like ehlers danlos and rarely anemia, RA, and myasthenia gravis

22

What are the 2 clinical types of OI?

congenital and tarda

23

_____ is the most common cause of inherited dwarfism and is AD.

Achondroplasia

24

What causes achondroplasia?

reduction in chondrocytes at growth plate,

25

What is the specific mutation associated with achondroplasia?

receptor for fibroblast growth factor 3

26

What do limbs look like with achondroplasia?

short extremities with abnormally wide ends. normal trunk, large head with large forehead, deep set nose, prominent supraorbital ridges

27

What is a danger to life with achondroplasia?

deformity at the foramen magnum where minor trauma can cause compression of brain stem.

28

_____ is a known risk factor for new mutations with achondroplasia.

advanced paternal age

29

What do xrays of osteopetrosis show?

long bones without medullary cavities and misshapen, bulbous ends. Diffusely sclerotic.

30

What causes osteopetrosis?

a failure of osteoclasts to resorb bone tissue, resulting in bone marrow
becoming occluded by weak, woven bone. The bone is brittle (breakable) and crowds marrow; patients are typically neutropenic and anemic.

31

Bones in osteopetrosis lack a _____.

medullary canal

32

Describe the ARO variant of osteopetrosis and how it is treated.

The most severe form of human osteopetrosis is the
malignant, infantile, autosomal recessive variant (ARO). ARO occurs because of specific mutations in genes responsible for osteoclast function. Despite a decrease in resorption, osteoclast numbers are normal or increased. These ‘‘osteoclast-rich’’ cases suggest that the osteoclast defect does not affect osteoclast formation but rather lies in their mature functional capacity. Providing osteoclast precursors via bone marrow
transplantation successfully treats these patients.

33

Describe osteopetrosis caused by LOF RANK mutation

very low number of osteoclast in bone

34

What is the role of RANK in osteoclasts?

Osteoclasts and their precursors bear a membrane receptor called RANK which activates the NF-kB signaling pathway and is instrumental in osteoclast differentiation. Activation occurs when the ligand of RANK is present. RANKL is synthesized by osteoblasts and mesenchymal stem cells.

35

______ is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk

osteoporosis

36

What are some major risk factors for osteoporosis?

age over 70, menopause before 45, hypogonadism, fragility fracture, hip fracture in parents, GC, malabsorption, high bone turnover, anorexia, BMI<18, immobilization, chronic renal failure, transplantation

37

What are some moderate risk factors for osteoporosis?

estrogen deficiency, low calcium intake, primary hyperparathyroidism, RA, hyperthyroidism, diabetes mellitus, smoking, alcohol excess, anticonvulsants, bechterew disease

38

What is involved in the pathogenesis of osteoporosis?

Increased bone loss due to formation that does not match resorption or increased number of remodeling units. With menopause, there is increased IL1,6,and TNF, decreased estrogen, and increased RANK and osteoclast activity. With aging, there is decreased replicative activity of progenior cells, physical activity, activity of osteoblasts.

39

What might you see with osteoporosis on X ray and histology?

compression fractures, thin trabeculae with microfractures

40

____ is associated with high early mortality with osteoporosis.

hip fracture

41

What is Paget disease?

Unbalanced and excessive osteoclast and osteoblast function; increased bone turnover

42

What are different patterns of pagets disease?

Osteolytic, mixed osteolytic-osteoblastic, osteoblastic and burnt-out stages

43

What does Paget's do to the bone?

Mosaic pattern of lamellar bone; skull and long bones; deforms bones

44

Etiology of Paget's

Painful, mid-adulthood; Northern Europeans

45

People with Pagets are predisposed to

osteogenic sarcoma, chondrosarcoma, and malignant fibrous histiocytoma

46

Key clinical points of Pagets

thick skull, deafness, kyphosis, pain, bowed legs

47

A young patients that has osteosarcoma can present in older age with ____

Pagets

48

______ is failure of the bone to mineralize properly in adults.

osteomalacia

49

What should you consider first as the cause of osteomalacia?

Vitamin D or calcium

50

What does osteomalacia/Rickets look like histologically?

Surfaces of bony trabeculae are covered by thicker than normal layer of osteoid

51

Look at renal osteodystrophy slide?

what is this?!

52

What causes primary hyperparathyroidism? Secondary?

Primary: adenoma. Secondary: prolonged hypocalcemia

53

What does hyperparathyroidism result in?

stimulation of osteoclast and bone resorption

54

What are 3 different things that can result from hyperparathyroidism?

Dissecting osteitis
– Osteoclasts bore into center of trabeculae
– X-ray: railroad tracks along length of bone and decrease in bone density (osteopenia)
Brown tumors: microfractures and hemorrhage; hemosiderin deposition; fibrosis
Osteitis fibrosa cystica: Increased bone activity + peritrabecular fibrosis + cystic brown tumors

55

Osteitis fibrosa cystica has what 2 compenents?

hemorrhagic cysts and brown tumors