Disease of Bone Development (Handy Pants) Flashcards Preview

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

What are bones made up of?

A

65% Inorganic: calcium hydroxyapatite

35% Organic: collagen

2
Q

What gives bone its strength/hardness? structure?

A

strength/hardness = calcium hydroxyapatite

structure = collagen

3
Q

bone that has not mineralized

A

osteoid

4
Q

How long does it take to mineralize bone

A

12 - 15 days

5
Q

puripotential mesenchymal stem cells

A

osteoprogenitor cells

6
Q

CBFA-1

A

stimulates osteoprogenitor cells to become osteoblasts

7
Q

What cells form bone?

A

osteoblasts

8
Q

What cells reabsorb remodel bone?

A

osteoclasts

9
Q

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

A

osteocytes

10
Q

What is osteoid made of? What makes osteoid?

A

type I collagen

Osteoblasts

11
Q

Multinucleated bone cell

A

osteoclast

12
Q

Cells have PTH receptors to mediate osteoclast activity

A

osteoblast

13
Q

cells that are encased in bone

A

osteocytes

14
Q

canaliculi

A

contain osteocytic cell processes to allow osteocytes to communicate

15
Q

howship lacunae

A

resorption pit containing osteoclast

16
Q

osteoblasts that are surrounded by matrix =

A

osteocyte

17
Q

What cells initiate mineralization

A

osteoblasts

18
Q
A

ostoclast

19
Q
A

osteoblast

20
Q
A

osteocyte

21
Q

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

A

macrophages

i.e. both from mesenchymal stem cells

22
Q

Describe the interactions needed for osteoclast differentiation

A

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
Q

Osteoprotegerin (OPG)

A

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

24
Q

What other cytokines are needed for osteoclast differentiation?

A

IL-1, 3, 6, 11

GM-CSF and M-CSF

25
Q

anlage

A

cartilaginous model of the future bone

26
Q

Growth plate

A

cartilage between ossification centers

27
Q

____ –> cartilage –> bone

A

mesenchyme

28
Q

Describe the normal long bone structure/its parts

A

Diaphysis: central portion

Metaphysis: between diaphysis and epiphysis

Epiphysis: end of long bones

29
Q

What part of the long bone contains growth plates?

A

epiphysis

30
Q

Why are children more prone to osteomyelitis than adults?

A

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
Q

How is mature bone different than growing bone?

A
  • epiphyseal plate stopped growing
  • metaphyseal vessels penetrate the cartilage plate
  • transverse bars of bone separate the growth plate from the metaphysis
32
Q

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

A

OSTEOGENESIS IMPERFECTA (“brittle bone diseases“)

33
Q

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

A

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
Q

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

A

II

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

35
Q

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

A

type I = make too little pro-α1(1)

36
Q

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

A

type IV = Pro-α2(1) is too short

37
Q

mode of inheritance for OI

A

autosomal dominant (type II may by AR or AD)

38
Q

4 major clinical criteria for diagnosis of OI

A

2 of the following are needed for Dx:

  • osteoporosis
  • blue sclera
  • dentingenesis imperfecta (=abnl teeth)
  • premature otosclerosis (causes hearing loss)
39
Q

characteristically associated with heritable disorders of connective tissue?

A

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

40
Q

What causes the blue discoloring of the sclera?

A

thinning of the sclera allows the underlying choroid to become visible

41
Q

OI congenita vs OI tarda

A

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

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

42
Q

Short extremities, normal trunk, large head, normal mentation

A

achondroplasia

43
Q

What is the pathogenesis of achondroplasia

A

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

44
Q

risk factor for new mutations leading to achondroplasia

A

advanced paternal age

45
Q

Is sexuality or intelligence affected in achondroplasia

A

no

46
Q

mode of inheritance for achondroplasia

A

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

47
Q

What is a danger to life in achondroplasia?

A

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

48
Q

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

A

osteopetrosis

49
Q

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

A

F: dysfunctional osteoclasts

50
Q

pathogenesis of osteopetrosis

A

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
Q

How is the bone different in osteopetrosis?

A

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
Q

NF-kB intracell signaling pathway activated by

A

RANKL binding RANKR to signal osteoclast differentiation

53
Q

What is the definition of osteoporosis

A
  1. low bone mass
  2. microarchitectural deterioration of bone tissue

–> leading to bone fragility and increased fracture risk

54
Q

What the the common fracture sites in osteoporosis?

A

wrist, hip, and spine

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

55
Q

What are the major risk factors for osteoporosis?

A
  • 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
Q

What are the moderate risk factors for osteoporosis?

A
  • Estrogen Deficiency
  • Calcium Intake < 500 mg/d
  • Primary Hyperparathyroidism
  • Rheumatoid Arthritis
  • Bechterew Disease
  • Anticonvulsants
  • Hyperthyroidism
  • Diabetes Mellitus
  • Smoking
  • Alcohol Excess
57
Q

What is the pathogenesis of osteoporosis?

A

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
Q

How does menopause contribute to pathogeneis of osteoporosis?

A

decreased serum estrogen

increased IL-1, 6, and TNF

increased RANK expression –> increased osteoclast activity

59
Q

How does aging contribute to the pathogenesis of osteoporosis?

A
  • decreased replication of osteoprogenitor cells
  • decreased synthetic activity of osteoblasts
  • decreased biologic activity of matrix bound growth factors
  • decreased physical activity
60
Q

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

A

7%

21%

33%

95%

61
Q

Unbalanced and excessive osteoclast and osteoblast function; increased bone turnover

A

paget disease of bone

62
Q

What does paget disease of bone predispose a person to?

A

osteogenic sarcoma

chondroscarcoma

malignant fibrous histiocytoma

63
Q

epidemiology of paget disease of bone

A

mid adult

northern european

64
Q

Clinical features of paget disease of bone

A

Thick skull

Deafness

Kyphosis

Pain

Bowed legs

65
Q

irregular lamellar bone

A

sclerotic phase of paget

66
Q

Irregular thick, coarse cortex

A

paget disease of bone

67
Q

Describe vit D/Ca metabolism

A

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
Q

Failure of the bone to mineralize properly in an adult

A

osteomalasia

69
Q

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

A

rickets

70
Q

Adults with dietary calcium deficiency or malabsorption are prone to …

A

osteomalasia –> bone pain and fractures

71
Q

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

A

hypocalcemia

hyperphosphatemia

increased PTH

72
Q

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

A

renal osteodystrophy

73
Q

What causes hypocalcemia in renal osteodystrophy?

A

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
Q

secondary hyperparathyroidism

A

renal osteodystrophy due to hypocalemia

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

75
Q

primary hyperparathyroidism is due to…

secondary hyperparathyroidism is due to…

A

adenoma

prolonged hypocalcemia with compensatory hyper-secretion

76
Q

Results in release of mediators that stimulate osteoclasts and bone resorption

A

PTH secretion

77
Q

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

A

dissecting osteitis due to hyperparathydroidism (renal osteodystrophy)

78
Q
A

brown tumor hyperparathyroidism (renal osteodeystrophy)

79
Q

deformed teeth

A

OI

80
Q

limb bones are short, with abnormally wide ends

A

achondroplasia

81
Q

residual strips of unremodeled cartilage

A

osteopetrosis

82
Q
A

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

83
Q
A

thin trabeculae that is typical of osteoporosis

84
Q

affects skull and long bones

A

paget disease of bone

85
Q

diffusely sclerotic bone

A

osteopetrosis

86
Q
A

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
A

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

88
Q

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

A

paget disease of bone

89
Q

pts are usually neutropenic and anemic

A

osteopetrosis

90
Q

von Kossa stain

A

osteomalasia/rickets

calcified tissue is black

91
Q

Cortical bone resorption > cancellous bone

A

hyperparathyroidism (renal osteodeystrophy)

92
Q

woven bone occluding marrow

A

osteopetrosis

93
Q

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

A

osteomalasia

94
Q

lack of meduallry canal and trabeculaeor marrow

A

osteopetrosis

95
Q

trilineage hematopoiesis is markedly reduced

A

osteopetrosis

96
Q
A

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

97
Q

Brown tumors

A

renal osteodeystrophy

=macrophages react to micro- fractures and hemorrhage

98
Q

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

A

paget disease of bone

99
Q

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.

A

OI

100
Q
A

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

101
Q

osteitis fibrosis cystica WHY?

A

renal osteodeystrophy

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