Mhd - #10 & 11 - Bone Pathology I & Ii

Front 1

What is unmineralized bone called?

Back 1

osteoid

Front 2

Which cells synthesize, transport, arrange proteins of bone matrix?

Back 2

osteoblasts

Front 3

Which cells initiate mineralization?

Back 3

osteoblasts

Front 4

Which cells have cell surface receptors which bind numerous
hormones (PTH, Vitamin D, Estrogen)?

Back 4

osteoblasts

Front 5

Osteoblasts once surrounded by matrix are:

Back 5

osteocytes

Front 6

Which cells are responsible for bone resportion?

Back 6

osteoclasts

Front 7

How many bones in the human body?

Back 7

206

Front 8

Term for fusion of two adjacent digits:

Back 8

Syndactylism

Front 9

Term for development of long spider-like digits:

Back 9

Arachnodactylism

Front 10

Most common disease of growth plate:

Back 10

Dwarfism (Achondroplasia)

Front 11

Mode of inheritance of achrondroplasia:

Back 11

autosomal dominant

Front 12

Mutated gene in Achondroplasia:

Back 12

FGFR3

Front 13

Normal role of FGFR3?

What does mutation cause at cellular level?

Back 13

Normally inhibits cartilage proliferation

1. Mutation leads to constant activation
2. Reduced chondrocyte proliferation in the growth plate
3. Premature deposition of bone seals the growth
plate

Front 14

Clinical features of Achondroplasia:

Back 14

1. Shortened proximal extremities
2. Trunk of relatively normal length
3. Enlarged head with bulging forehead
4. Depression at root of nose
5. Normal longevity, intelligence, reproductive
status

Front 15

What disease is known as "brittle bone disease"?

Back 15

osteogenesis imperfecta

Front 16

What type of collagen is affected in osteogenesis imperfecta?

Back 16

type I collagen

Front 17

Mode of inheritance of osteogenesis imperfecta:

Back 17

autosomal dominant

autosomal recessive (perinatal lethal form)

Front 18

Clinical features of osteogenesis imperfecta:

Back 18

1. Multiple fractures
2. Blue sclera
3. Small mis-shapen teeth
4. Deafness

Front 19

Goals of treatment of osteogenesis imperfecta:

Back 19

1. Maximize mobility/function
2. Minimize fracture risk
3. Pain control
4. Psychosocial

Front 20

The inorganic component of bone is called:

Back 20

calcium hydroxyapetite

Front 21

Growth plate related to what type of bone formation?

Back 21

endochondral

Front 22

What is the #1 metabolic bone disease in U.S.?

Back 22

osteoporosis

Front 23

Osteoporosis is characterized by what change in bone density:

Back 23

decrease in bone density

Front 24

Underlying causes of secondary osteoporosis:

Back 24

1. hyperthyroidism
2. hyperparathyroidism
3. corticosteroid use
4. immobilization
5. hypogonadism
6. anticonvulsants (Dilantin)

Front 25

How much bone density is lost per year in men and women:

Back 25

men: 0.2-1% per year

women: same as men before menopause; 3-5% after menopause

Front 26

Risk factors for osteoporosis:

Back 26

1. Age
2. Female
3. Caucasian
4. Asian
5. Family history
6. Small body frame
7. Calcium deficiency
8. Decreased exercise
9. Estrogen deficiency

Front 27

Changes that occur in post-menopausal women which leads to osteoporosis:

Back 27

1. decreased seroum estrogen
2. increased IL-1, IL-6, TNF-alpha
3. increased expression of RANK and RANKL
4. increased osteoclast activity

Front 28

What bones are affected most by osteoporosis?

What happens to the bone?

Back 28

Entire skeleton affected

Most affected: vertebra, wrist, ribs, pelvis

thinned trabeculae

Front 29

What does RANK and RANKL do?

Back 29

RANK (receptor) is on monocytes and preosteoclast cells. They bind RANKL which is on osteoblasts --> osteoclastogenesis.

Front 30

Signs of vertebral fractures in osteoporotic patients:

Back 30

1. Loss of height
2. kyphoscoliosis
3. Dowager’s hump

Front 31

Complications of osteoporosis:

Back 31

1. pulmonary embolism
2. pneumonia

Front 32

Can we catch osteoporosis early?

Back 32

1. Not detectable on X-Ray until 30-40% bone
mass lost

2. Blood calcium, phosphorous, alkaline phosphatase levels NOT diagnostic

Front 33

Prevention and treatment of osteoporosis (5):

Back 33

1. Exercise
2. Calcium and vitamin D
3. Bisphosphonates
4. Estrogen replacing agents
5. Recombinant PTH (Forteo) - given in a pulsatile fashion; high levels all the time favors bone resorption

Front 34

Etiology of rickets/osteomalacia:

Back 34

Etiology = Vitamin D deficiency

Front 35

Pathology of rickets (kids) and osteomalacia (adults):

Back 35

1. bone mineralization defect
2. decreased mineral content of bone
3. relative increase in osteoid*
4. bones are soft

Front 36

Explain Vitamin D deficiency (figure 9-24):

Back 36

There is inadequate substrate for the renal hydroxylase (1), yielding a deficiency of 1,25(OH)2D (2), and deficient absorption of calcium and phosphorus from the gut (3), with consequent depressed serum levels of both (4). The hypocalcemia activates the parathyroid glands (5), causing mobilization of calcium and phosphorus from bone (6a). Simultaneously, the parathyroid hormone (PTH) induces wasting of phosphate in the urine (6b) and calcium retention. Consequently, the serum levels of calcium are normal or nearly normal, but the phosphate is low; hence, mineralization is impaired (7).

Front 37

What is bone process is abnormal due to vitamin D deficiency?

Back 37

bone modeling/remodeling

Front 38

What problem would cause fractures and microfractures?

Back 38

vitamin D deficiency --> rickets/osteomalacia

Front 39

Lab findings in adults with osteomalacia:

Back 39

1. Low normal calcium
2. Low (to low normal phosporous)
3. Decreased vitamin D
4. Elevated alkaline phosphatase

Front 40

Rickets causes a problem with:

Back 40

GROWING BONES

Front 41

Where is the problem with rickets:

Back 41

Deficient mineralization of the growth plate

Front 42

Signs of Rickets:

Back 42

1. Enlarged joints
2. Rachitic Rosary
3. Pigeon Breast Deformity
4. Bowing of legs
5. Occipital bones flattened
6. Parietal bones buckled inward
7. Frontal bossing/squared appearance of head (excess osteoid)

Front 43

Treatment of rickets:

Back 43

vitamin D

Front 44

Causes of primary hyperparathyroidism (3):

Back 44

Hyperplasia
Adenoma
Carcinoma

Front 45

Causes of secondary hyperparathyroidism:

Back 45

Prolonged hypocalcemia stimulates PTH hypersecretion

Front 46

How does increased PTH cause bone resorption?

Back 46

increased PTH levels are detected by receptors on osteoblasts which initiate release of mediators that stimulate osteoclast activity

Front 47

Pathology of hyperparathyroidism:

1. what causes the skeletal manifestations?
2. what bone type is affected?
3. what is dissecting osteitis?

Back 47

1. skeletal issues due to unabated osteoclastic bone resoption

2. affects cortical bone (thinned cortex) more than cancellous bone

3. Dissecting osteitis - osteoclasts tunnel into trabeculae (“railroad tracks”)

Front 48

Findings in hyperparathyroidism:

Back 48

1. microfractures
2. Brown tumors - microfractures and secondary hemorrhages eleicit influx of macrophages and ingrowth of reactive fibrous tissue

Front 49

What is the hallmark of severe hyperparathyroidism?

Back 49

Generalized osteitis fibrosa cystica (von Recklinghausen disease of bone) = increased bone cell activity, peritrabecular fibrosis, cystic brown tumors

Front 50

Signs/symptoms of hyperparathyroidism:

Back 50

1. Decreased bone mass
2. Pain
3. Fractures: stress fractures

Front 51

Control of hyperparathyroidism can lead to:

Back 51

bone changes regress

Front 52

Cause of scurvy:

Back 52

vitamin C deficiency

Front 53

Why is vitamin C needed important for bone formation?

Back 53

Vitamin C deficiency causes defect in hydroxylation of procollagen (formation of hydroxyproline) and suppressed rate of collagen synthesis.

In growing kids, vitamin C deficiency causes defect in formation of osteoid matrix resulting in deformed bones.

Front 54

Problems associated w/ vitamin C deficiency (fig 9-30):

Back 54

1. defective and insufficient formation of osteoid which leads to deformation of bones (usually kids)

2. weakness in blood vessel walls --> hemorrhages, purpura, ecchymoses

3. gingiva w/ hemorrhages, swelling
4. wound healing impaired

Front 55

sources of vitamin C:

Back 55

Milk
liver
fish
fruits
vegetables

Front 56

Who is at risk of vitamin C deficiency?

Back 56

1. Elderly
2. Alcoholics
3. Food faddists
4. Infants – formulas without supplementation
5. Sailors

Front 57

Scurvy treatment:

Back 57

vitamin C supplementation

Front 58

Disease characterized by "matrix madness" or a "mosaic pattern" and its pathology:

Back 58

Paget Disease of bone (Osteitis Deformans):
-initially there is increased haphazard bone destruction (osteolysis)
-eventually bone is replaced by vascular connective tissue and poorly organized bone --> increased* thickness of cortex and trabeculae, but the bone is soft b/c the matrix is poor (bone lacks structural strength)

Front 59

Outcome of Paget Disease:

Back 59

1. Increased bone mass
2. Disordered bone stx
3. Structurally unsound

Front 60

3 stages of Paget Disease:

Back 60

1. Osteolytic
2. Mixed osteolytic-osteoblastic
3. Osteosclerotic

Front 61

Etiology of Paget Disease:

Back 61

Slow virus infection of osteoclasts: Paramyxovirus

Induce IL-6 secretion
Stimulate osteoclast activity

Front 62

What dz produced bones with "jigsaw-like" appearance?

Back 62

Paget disease

Front 63

When does Paget disease begin?

Back 63

mid-adulthood (50-60)

Front 64

Bones affected by Paget disease:

Back 64

Monostotic (15%): Tibia, ilium, femur, skill, vertebra, humerus

Polyostotic (85%): Pelvis, spine, skull

(i.e. usually multiple bones affected)

descending order of affected bones: tibia, pelvis, femur, skull, spine

Front 65

Why do people w/ Paget dz have pain?

Back 65

1. Microfractures
2. Bone overgrowth compressing nerves, spinal

Front 66

Problems caused by Paget disease (3):

Back 66

1. Secondary arthritis
2. High output heart failure* - heart is working fine, but blood detours to bone (increased blood flow causes arteriovenous shunt)
3. Sarcoma development: 5-10%; osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma
4. bone overgrowth (i.e. leontiasis ossea: thickening of the skull and craniofacial bones) --> bone deformities
5. involvement of the ossicles --> hearing loss

Front 67

How can Paget disease be recognized?

Back 67

1. radiographs
2. bone scan

Front 68

Lab signs of Paget Disease:

Back 68

Elevated serum alkaline phosphatase**

Serum calcium, phosphorous unaffected

Front 69

Treatment of Paget Disease:

Back 69

1. Acetaminophen, NSAIDS
2. Bisphosphonates
3. Calcitonin

Front 70

What causes osteonecrosis (avascular necrosis)?

What areas are affected, which are spared?

Back 70

bone infarction (bone and marrow)

affected: medullary cavity of metaphysis or diaphysis

spared: cortex is spared due to collateral blood flow

Front 71

Causes of ischemia leading to osteonecrosis:

Back 71

Mechanical (fracture)
Corticosteroids
Thrombosis/embolism
Vessel injury (vasculitis, radiation)
Vascular compression

Front 72

Etiology of osteonecrosis:

Back 72

Trauma
Corticosteroids
Infection
Dysbarism
Radiation therapy
Connective tissue
Sickle cell anemia*
Tumors
Pregnancy
Idiopathic

Front 73

Signs of subchondral infarcts in osteonecrosis:

Back 73

1. pain
2. collapse of bone
3. secondary arthritis

Front 74

Signs of medullary infarcts (i.e. center of long bones):

Back 74

most are clinically silent

Front 75

What is Tuberculous Osteomyelitis?

Back 75

TB goes to bone:
-spine: thoracic and lumbar > cervical and sacral (Pott disease)
-knees and hips most common sites of skeletal involvement

1-3% of patients w/ pulmonary TB get this

Front 76

How can Tuberculous Osteomyelitis manifest itself?

Back 76

1. Hematogenous spread
2. Direct extension
3. Spread via draining lymphatics

Usually solitary focus
AIDS - multifocal

Front 77

Pott disease?

Back 77

-Spine (Pott Disease)
-Thoracic and lumbar vertebra
-Intervertebral disks breached
-Multi-level involvement
-Soft tissue abscesses
-Knees, hips

Front 78

Symptoms of Tuberculous Osteomyelitis:

Back 78

1. Pain, fever, weight loss
2. Compression fractures
3. Scoliosis, kyphosis
4. Neurologic defects

Front 79

Primary bone neoplasms:
common or uncommon?
who gets it?

Majority of bone neoplasms are benign or metastatic:

Back 79

Uncommon
Children & adolescents > adults
Benign or malignant
Age, location, radiographic appearance tissue examination

majority of bone neoplasms are METASTATIC

Front 80

Primary bone neoplasms arise where:

3 most common?

Back 80

Hematopoietic 40%
Chondrogenic 22%
Osteogenic 19%
Histiocytic
Fibrogenic
Vascular
Lipogenic
Neurogenic
Unknown origin 10%

Front 81

What is an osteoma?

Back 81

-Benign tumor
-Composed of dense (sclerotic) well-formed bone
-Extends from surface of cortical bone

Front 82

Who gets osteomas?
What bones are affected?
What problems can they cause?

Back 82

Middle aged men
Cranial and facial bones
Slow growing
Often clinically insignificant

Obstructs sinus cavity
Eye impingement
Cosmetic issues

Front 83

Disease associated w/ multiple osteomas:

Back 83

Gardner's syndrome

Front 84

What is an osteoid osteoma?

Back 84

-Benign
-Haphazard bone and osteoid
-Haphazardly arranged trabeculae of woven bone -rimmed by osteoblasts
-Stroma - loose connective tissue, vascular
-Arises in cortex of femur, tibia
-Less than 2cm

Front 85

Who gets osteoid osteoma?
What is the main symptom?

Back 85

Men <25 years old (5-25)

PAIN!
Prostaglandin E2
Nocturnal
Relieved with aspirin

Front 86

What is the most common primary malignant bone tumor?

Back 86

osteosarcoma (osteogenic sarcoma)

Front 87

Common sites of osteosarcomas?

Back 87

Medullary cavity of the metaphysis of long bones

(60% arise close to knee: distal femur and proximal tibia)

Front 88

Histo appearance of osteosarcoma:

Back 88

anaplastic mesenchymal cells intermixed w/ osteoid (and sometimes cartilage)

Front 89

What is Codman triangle?

Back 89

an irregular radiographic shadow b/w cortex and raised end of periosteum

Front 90

Mutations causing osteosarcoma?

Back 90

RB gene mutations:
1. Hereditary retinoblastoma: 1000x risk of osteosarcoma
2. Sporadic mutations

P53, Cyclin D1, MDM2 mutations

Front 91

Who gets osteosarcoma?

How does it present?

Back 91

men > women
majority < 20yo (but older peak associated w/ predisposing factors such as Paget disease)

presents as painful, enlarging mass

Front 92

Where does osteosarcoma metastasize to?

what treatments used for osteosarcoma and how successful?

Back 92

metastasizes to lungs

treatment: chemotherapy, limb salvage (60% long-term survival)

Front 93

What is an enchondroma?:

Composed of what?
Arises where?

Back 93

-Benign neoplasm
-Composed of hyaline cartilage
-Arises within metaphysis of short tubular bones of hands and feet

Front 94

Symptoms of enchondroma:

Back 94

-aymptomatic usually
-painful on occassion

Front 95

Disease where people develop multiple enchondromas:

Back 95

Ollier disease

Front 96

What is a chondrosarcoma?

Back 96

=Malignant neoplasm composed of malignant hyaline and myxoid cartilage
-Varies in degrees of differentiation
Central portion
-Arise in central portions of skeleton: pelvis, shoulder, ribs

Front 97

histo of chondrosarcoma:

Back 97

...

Front 98

How is Chondrosarcoma graded?

Back 98

Grade 1 – Low grade
Grade 2
Grade 3 – High grade: Very hypercellular, pleomorphic, bizarre tumor giant cells

grade is important for outcome

Front 99

Who gets Chondrosarcoma?

How does it present?

Metastases and prognosis?

Treatments?

Back 99

>40 years
Men > women

Painful enlarging masses
Metastases to lungs, skeleton
Prognosis related to grade, size

5 year survival:
90% - Grade 1; 43% - Grade 3

Surgery
Some variants chemotherapy

Front 100

Chondrosarcoma...

Back 100

...

Front 101

What is Ewing Sarcoma/PNET?

Back 101

=Malignant neoplasm composed of small, round mesenchymal cells resembling lymphocytes

-Occurs in medullary cavity of long bones: femur, flat bones of pelvis

Front 102

What differentiates PNET from Ewing sarcoma?

Back 102

Neural differentiation – PNET

No neural differentation – Ewing Sarcoma

Front 103

Gene associated w/ Ewing Sarcoma?

Back 103

t(11;22)(q24;q12)
-EWS-FLI1 fusion gene
-Oncogene
-Protein = active transcription factor

Front 104

Who presents w/ Ewing Sarcoma?

How does it present?

Clinically can mimic?

Back 104

<20 year old (most 10-15 years)
Boys > girls
African Americans rarely

Painful, enlarging masses
Warm, tender, swollen
Fever, leukocytosis

mimics:

Front 105

Treatment of Ewing Sarcoma/PNET:

Survival?

Back 105

Chemotherapy, surgery
Radiation in some cases

75% 5 year survival
50% long term cure

Front 106

Majority of bone neoplasms are due to:

Back 106

BONE METASTASES

Front 107

What cancers can metastasize to bone?

Back 107

Any cancer, any bone
-Red marrow of axial skeleton
-Adults: Prostate, breast, kidney, lung
-Children: Neuroblastoma, Wilm’s tumor, Ewing sarcoma,
Rhabdomyosarcoma

Front 108

How can bone metastases spread?

Back 108

Direct extension
Lymphatic or hematogenous spread
Intraspinal seeding (Batson plexus of veins)

Front 109

Radiographic evidence of bone metastases? (3 types)

Back 109

-Lytic: Prostaglandins, interleukins, parathyroid hormone- related hormones; Osteoclast bone resorption stimulated

-Blastic: Osteoblastic bone destruction

-Mixed lytic and blastic

Front 110

What bone metastasis are mostly blastic?**

Back 110

prostate

Front 111

Mneumonic for lytic bone mets:

Back 111

"Bacon Lettuce Tomoato Ketchup and Mayo"

=Breast, Lung, Thyroid, Kidney, Multiple myeloma

Front 112

Mneumonic for blastic bone mets:

Back 112

"PITTA"

=Prostate*, Infamous lymphoma, Transitional cell CA, Treated breast, APUDoma (carcinoid)

Front 113

Problems assoc w/ bone metastases?

Treatments?

Back 113

1. Pathologic fractures
2. Pain: NSAIDS, opiates, adjuvant treatments, radiation Therapy

Front 114

Define: woven bone

Back 114

=osteoblasts deposit collagen in a random weave

-seen in fetal skeletaon and formed at growth plates

-always pathological in the adult

Front 115

Define: lamellar bone

Back 115

=deposited collagen in an orderly layer

-gradually replaces woven bone during growth

Front 116

Define: osteocyte

Back 116

-most numerous bone forming cells
-occupies a lacuna and has cytoplasmic processes that extend into canaliculi and make contact w/ other osteocytes

i.e. an osteocyte is an osteoblast surrounded by matrix

Front 117

Define: osteoblast

Back 117

=bone-forming cell (mesenchymal origin)
-synthesize, transport, and arrange matrix proteins

Front 118

Define: osteoclast

Back 118

=large, multinucleated cell (monocytic origin) that absorbs and removes osteous bone

Front 119

Define: callus

Back 119

=composite mass of tissue that forms at a fracture site to establish continuity b/w both ends of bones

Front 120

Define: osteopenia

Back 120

=decreased calcification or density of bone (decreased bone mass)

Front 121

Define: osteonecrosis

Back 121

=extensive bone death

(not caries = molecular death)

Front 122

Define: Rachitic rosary

Back 122

=row of beading seen at junction of ribs w/ their cartilages

Front 123

Define: renal osteodystrophy

Back 123

=generalized bone changes occurring in renal failure that resemble osteomalacia

Front 124

Define: frontal bossing

Back 124

=prominent forehead