Disease of Bone Development (Handy Pants) Flashcards Preview

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Flashcards in Disease of Bone Development (Handy Pants) Deck (101):
1

What are bones made up of?

65% Inorganic: calcium hydroxyapatite

35% Organic: collagen

2

What gives bone its strength/hardness? structure?

strength/hardness = calcium hydroxyapatite

structure = collagen

3

bone that has not mineralized

osteoid

4

How long does it take to mineralize bone

12 - 15 days

5

puripotential mesenchymal stem cells

osteoprogenitor cells

6

CBFA-1

stimulates osteoprogenitor cells to become osteoblasts

7

What cells form bone?

osteoblasts

8

What cells reabsorb remodel bone?

osteoclasts

9

What cells sense mechanical stress and regulate serum calcium and phosphorus?

osteocytes

10

What is osteoid made of? What makes osteoid?

type I collagen

Osteoblasts

11

Multinucleated bone cell

osteoclast

12

Cells have PTH receptors to mediate osteoclast activity

osteoblast

13

cells that are encased in bone

osteocytes

14

canaliculi

contain osteocytic cell processes to allow osteocytes to communicate

15

howship lacunae

resorption pit containing osteoclast

16

osteoblasts that are surrounded by matrix =

osteocyte

17

What cells initiate mineralization

osteoblasts

18

Q image thumb

ostoclast

19

Q image thumb

osteoblast

20

Q image thumb

osteocyte

21

Osteoclasts are derived from the same stem cells that produce _______.

macrophages

i.e. both from mesenchymal stem cells

22

Describe the interactions needed for osteoclast differentiation

RANK ligand on osteoblast membrane assc with RANK receptor on osteoclast precursor cell surface

         +

M-CSF binds M-CSF receptor on osteoclast precursor cell surface

23

Osteoprotegerin (OPG)

secreted by stromal cells/osteoblasts to prevent the binding of RANK ligand to the RANK receptor --> inhibits osteoclast differentiation and therefore bone reabsorption

24

What other cytokines are needed for osteoclast differentiation?

IL-1, 3, 6, 11

GM-CSF and M-CSF

25

anlage

cartilaginous model of the future bone

26

Growth plate

cartilage between ossification centers

27

____ --> cartilage --> bone

mesenchyme

28

Describe the normal long bone structure/its parts

Diaphysis: central portion

Metaphysis: between diaphysis and epiphysis

Epiphysis: end of long bones

29

What part of the long bone contains growth plates?

epiphysis

30

Why are children more prone to osteomyelitis than adults?

children have a richer blood supply (or is it the other way around? the pic makes me think it might be but I cannot tell from the wording...)

31

How is mature bone different than growing bone?

-epiphyseal plate stopped growing

-metaphyseal vessels penetrate the cartilage plate

-transverse bars of bone separate the growth plate from the metaphysis

32

A family of diseases having in common mutations in the type I collagen genes.

OSTEOGENESIS IMPERFECTA ("brittle bone diseases“)

33

Briefly describe the collagen defects assc with each type of OI (I-IV)

I. make too little pro-α1(1)

II. Pro-α1(1) is too short = collagen made but degraded intracellularly

III. Triple helix doesn't form well

IV. Pro-α2(1) is too short

34

in what type of OI are bones break in utero or during birth, killing the child

II

= Pro-α1(1) is too short and collagen made but degraded intracellularly

35

In what type of OI do pts have normal statue, lax joints, and are hard of hearing?

type I = make too little pro-α1(1)

36

In what type of OI do pts have short stature and somewhat fragile bones?

type IV = Pro-α2(1) is too short

37

mode of inheritance for OI

autosomal dominant (type II may by AR or AD)

38

4 major clinical criteria for diagnosis of OI

2 of the following are needed for Dx:

-osteoporosis

-blue sclera 

-dentingenesis imperfecta (=abnl teeth)

-premature otosclerosis (causes hearing loss)

39

characteristically associated with heritable disorders of connective tissue?

blue sclera OI > pseudoxanthoma elasticum, Ehlers-Danlos syndrome, and Marfan disease >>> iron deficiency, rheumatoid arthritis, or myasthenia gravis

40

What causes the blue discoloring of the sclera?

thinning of the sclera allows the underlying choroid to become visible

41

OI congenita vs OI tarda

congenita = is clinically severe, and survival beyond childhood is uncommon.

tarda = much milder course, and patients may live to an advanced age.

42

Short extremities, normal trunk, large head, normal mentation

achondroplasia

43

What is the pathogenesis of achondroplasia

AD mutation in fibroblast growth factor 3 causing a reduction in chondrocytes at growth plate --> impaired formation of the LONG bones (endochondral process)

44

risk factor for new mutations leading to achondroplasia

advanced paternal age

45

Is sexuality or intelligence affected in achondroplasia

no

46

mode of inheritance for achondroplasia

AD and often due to a new mutation (advanced paternal age)

47

What is a danger to life in achondroplasia?

deformity at the foramen magnum, where minor trauma can dislocate the skull from the neck bones and compress the brainstem

48

long bones without medullary cavities and misshapen, bulbous ends and increased # of irregular bony trabeculae

osteopetrosis

49

T or F: there is an increased number of osteoclasts in osteopetrosis

F: dysfunctional osteoclasts

50

pathogenesis of osteopetrosis

carbonic anahydrase II deficiency --> osteoclast dysfunction

or

RANKL loss of function mutation --> osteoclasts are not activated --> low # of osteoclasts in bone

 

-> lacking ability to reabsorb tissue --> bone marrow is occluded with weak, woven bone

51

How is the bone different in osteopetrosis?

W - Woven bone occluding marrow

I - Increased # of Irregular bony trabeculae

B - Bulbous ends U - residual strips of

Unremodeled cartilage

M - lack of Meduallry canal/cavaties and trabeculaeor Marrow

S - diffusely Sclerotic bone

WI BUMS get osteoporosis from their cheese

52

NF-kB intracell signaling pathway activated by

RANKL binding RANKR to signal osteoclast differentiation

53

What is the definition of osteoporosis

1. low bone mass

2. microarchitectural deterioration of bone tissue

--> leading to bone fragility and increased fracture risk

54

What the the common fracture sites in osteoporosis?

wrist, hip, and spine

**30% of women 50+ will have one or more vertebral fractures

55

What are the major risk factors for osteoporosis?

  • Age > 70
  • Menopause < 45
  • Hypogonadism
  • Fragility Fracture
  • Hip Fracture in Parents
  • Glucocorticoids
  • Malabsorption
  • High Bone Turnover
  • Anorexia Nervosa
  • BMI < 18
  • Immobilisation
  • Chronic Renal Failure
  • Transplantation

56

What are the moderate risk factors for osteoporosis?

  • Estrogen Deficiency
  • Calcium Intake < 500 mg/d
  • Primary Hyperparathyroidism
  • Rheumatoid Arthritis
  • Bechterew Disease
  • Anticonvulsants
  • Hyperthyroidism
  • Diabetes Mellitus
  • Smoking
  • Alcohol Excess

57

What is the pathogenesis of osteoporosis?

reabsorbed cavity too large + newly formed packet of bone too small --> formation does not match absorption + increased numbers of remodeling units = increased bone loss

58

How does menopause contribute to pathogeneis of osteoporosis?

decreased serum estrogen

increased IL-1, 6, and TNF

increased RANK expression --> increased osteoclast activity

59

How does aging contribute to the pathogenesis of osteoporosis?

-decreased replication of osteoprogenitor cells

-decreased synthetic activity of osteoblasts

-decreased biologic activity of matrix bound growth factors

-decreased physical activity

60

What is the mortality rate for:

1 year after hip fracture:

   <75 yo

    75-84

    >85 yo 

10 years after hip fracture and >/= 85 yo

7%

21%

33%

 

95%

61

Unbalanced and excessive osteoclast and osteoblast function; increased bone turnover

paget disease of bone

62

What does paget disease of bone predispose a person to?

osteogenic sarcoma

chondroscarcoma

malignant fibrous histiocytoma

63

epidemiology of paget disease of bone

mid adult

northern european

64

Clinical features of paget disease of bone

Thick skull

Deafness

Kyphosis

Pain

Bowed legs

65

irregular lamellar bone

sclerotic phase of paget

66

Irregular thick, coarse cortex

paget disease of bone

67

Describe vit D/Ca metabolism

ingest vit D or made in skin and enters the bloodstream. In the liver it is converted into 25(OH)D. This goes to the kidney where it is made into:

  1. 1, 25 (OH)2D --> intestine told to abs Ca -->
  2. 24, 25(OH)2D --> actives parathyroid to make PTH--> kidneys reabsorb Ca and bone releases Ca

==> Ca into the blood

68

Failure of the bone to mineralize properly in an adult

osteomalasia

69

of inadequate intake of vitamin D and/or calcium in childhood

rickets

70

Adults with dietary calcium deficiency or malabsorption are prone to ...

osteomalasia --> bone pain and fractures

71

What will blood test reveal in a pt with renal osteodystrophy?

hypocalcemia

hyperphosphatemia

increased PTH

72

osteomalacia + Increased bone formation in spine and long bones but decreased TOTAL bone mass

renal osteodystrophy

73

What causes hypocalcemia in renal osteodystrophy?

loss of nephron mass -->

1. decreased renal production of 1, 25(OH)2D --> decreased gut abs of Ca

2. decreased renal excretion --> hyperphosphatemia --> hypocalcemia

74

secondary hyperparathyroidism

renal osteodystrophy due to hypocalemia

(from def 1, 25(OH)2D/loss of nephron mass)

75

primary hyperparathyroidism is due to...

secondary hyperparathyroidism is due to...

adenoma

prolonged hypocalcemia with compensatory hyper-secretion

76

Results in release of mediators that stimulate osteoclasts and bone resorption

PTH secretion

77

X-ray: railroad tracks along length of bone and decrease in bone density (osteopenia)

dissecting osteitis due to hyperparathydroidism (renal osteodystrophy)

78

Q image thumb

brown tumor hyperparathyroidism (renal osteodeystrophy)

79

deformed teeth

OI

80

limb bones are short, with abnormally wide ends

achondroplasia

81

residual strips of unremodeled cartilage

osteopetrosis

82

Q image thumb

Surfaces of bony trabeculae (black) are covered by a thicker than normal layer of osteoid (red) = osteomalasia/rickets

83

Q image thumb

thin trabeculae that is typical of osteoporosis

84

affects skull and long bones

paget disease of bone

85

diffusely sclerotic bone

osteopetrosis

86

Q image thumb

hyperparathyroidism (renal osteodeystrophy)

These photomicrographs of a brown tumor show fibroblasts admixed with osteoclasts and numerous activated osteoclasts at the edge of a trabecula.

87

Q image thumb

blue gray within pink trabecular bone in osteopetrosis = unremodeled cartilage bc osteoclasts dysfunction

88

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

paget disease of bone

89

pts are usually neutropenic and anemic

osteopetrosis

90

von Kossa stain

osteomalasia/rickets

calcified tissue is black

91

Cortical bone resorption > cancellous bone

hyperparathyroidism (renal osteodeystrophy)

92

woven bone occluding marrow

osteopetrosis

93

Surfaces of bony trabeculae (black) are covered by a thicker than normal layer of osteoid (red)

osteomalasia

94

lack of meduallry canal and trabeculaeor marrow

osteopetrosis

95

trilineage hematopoiesis is markedly reduced

osteopetrosis

96

Q image thumb

Osteitis fibrosa cystica showing numerous hemorrhagic cysts (middle) and brown tumors (far right)

97

Brown tumors

renal osteodeystrophy

=macrophages react to micro- fractures and hemorrhage

98

is replacement of normal cancellous bone with coarse, thick bundles of trabecular bone

paget disease of bone

99

Diagnosis?

Radiographs (anteroposterior and lateral views) of this 32 week male stillborn fetus indicate the following: Skull: Minimal mineralization at the skull base only. Long Bones: General demineralization; short, telescoped long bones secondary to in utero fractures. The provisional zones of calcification are preserved (ends of long bones are sharp). Ribs: Beaded appearance secondary to multiple fractures.

OI

100

Q image thumb

Paget Disease of Bone Humerus showing lytic (1), mixed (2), and sclerotic (3) phases, all in the same bone.

101

osteitis fibrosis cystica WHY?

renal osteodeystrophy

=increased bone activity + peritrabecular fibrosis + cystic brown tumors DUE to hyperparathyroidism