Pathology of Bone Flashcards
(126 cards)
1
Q
Non-neoplastic Bone Disease
A
Fractures of healthy bone
Osteoporosis (especially post-menopausal and senile types) - and associated fractures
Osteomalacia
Osteomyelitis
Avascular (aseptic) bone necrosis/infraction
Paget’s disease of bone
Congenital bone disorders
2
Q
If see osteopenia (generalized decrease in bone mineralization) - Diff dx
A
Osteoporosis, osteomalacia, malignancy, rare hereditary disorders
3
Q
Neoplasms involving bone
A
metastatic tumors to skeleton
hemic malignancyes (myeloma/plasmacytoma or lymphoma, acute leukemia)
4
Q
Primary bone tumor/tumor-like lesions
A
Benign and malignant
Relatively uncommon (more common in children)
5
Q
Misc. tumor-like diseases which can involve bone
A
- Histiocytosis X (Langerhan’s histiocytosis)
- Mast cell disease
- Hyperparathyroidism (osteitis fibrosa cystica)
- Others: bone cysts, fibrous dysplasia
6
Q
Pathological fracture
A
•fracture through diseased bone—usually refers to fracture through tumorous or tumor-like bone
7
Q
Periosteum pathologically
A
painful when irritated (trauma, injury), also lays down bone –> thickening of bone
8
Q
Serum alkaline phosphatase
A
Marker for osteoblastic disease, also liver disease w/ bile obstruction (in kids, worry about osteoblastic bone disease - adults, more likely liver defect)
If no other liver lab markers elevated, older person w/ elevated SAP – Paget’s
9
Q
Osteoporosis - ____ faster than _____
A
Osteoclasts (resorption) faster than osteoblasts (bone building)
10
Q
Biggest danger to kids w/ trauma near epiphyseal plateor osteomyelitis
A
Disrupt epiphyseal cartilage (blood vessel invasion) –> stop growth
11
Q
Decreased serum Ca (free) –>
A
increased parathyroid hormone –> increase bone resorption –> increase serum calcium
12
Q
Vit D sources
A
diet and skin synthesis
*** Issues w/ no sun and malabsorption
13
Q
Vit D processing
A
Skin synthesis, liver metabolism, kidney/PTH –> Vitamin D (OH)2 - active in skeleton
Renal Disease –> Major skeletal consequences
14
Q
Kidney + PTH –>
A
increased production of Vit D(OH)2, tubular resorption of Ca++, tubular excretion of phosphate
15
Q
Required for normal mineralization of bone osteoid
A
Vit D(OH)2
16
Q
For healthy bone, need
A
Ca, P (diet)
Vit D (diet, skin synthesis)
gut (absorbing Ca, P, Vit D)
kidney (makes Vit D (OH)2, resorbs/excretes Ca, P)
parathyroids (master gland for Ca, bone metabolism)
17
Q
High serum ca
A
Needs to be explained (hyperparathyroidism or cancer?)
18
Q
Steps of Bone healing
A
Blood clot in fracture site, ingrowth of fibrous tissue, neovascularization
Near fracture –> knows needs to become cartilaginous - then osteocartilaginous - then bone again
Cartilage callus –> woven bone callus –> remodeling into good bone
19
Q
Complications of fractures through healthy bone
A
Mal-alignment
Non-union/mal-union/pseudoarthrosis
Osteomyelitis (compound fractures)
Growth disturbance (epiphyseal plate injury in children)
Arthritis (if fractures affects articular surface)
Fat embolism syndrome (w/in days of fx)
Immobilization complications (thrombophlebitis/thromboembolism, osteoporosis of immobilized bone)
20
Q
Type of osteopenia d/t bone atrophy caused by imbalance of bone remoding process
A
Osteoporosis
21
Q
Osteoporosis: clinical manifestations
A
no clinical manifestations until fracture - often trivial injury fractures
Vertebral fractures most common - compression usually acute/painful but wedge fracture usually painless
22
Q
Types/Associations of Osteoporosis
A
- POSTMENOPAUSAL/SENILE types
- Due to excess corticosteroids (endogenous or exogenous)
- Hyperparathyroidism (slow leech)
- Hyperthyroidism (measure TSH)
- Poor nutrition/malabsorption
- Immobilization
- Hypogonadism
- Multiple other disease associations
23
Q
Ability of kidneys to ___________ becomes impaired with age
A
hydroxylate Vit D(OH)1 to Vit D(OH)2
24
Q
Age/menopause /w osteoporosis
A
- Diminished PTH secretion by parathyroid glands in response to hypocalcemic stimulus (post-menopausal patients)
- Increased osteoclastic activity upost-menopausal women
- Decreased ability of osteoblasts to make matrix
25
•Common osteoporosis = diagnosis of \_\_\_\_\_\_\_
Remember the often more treatable / reversible causes of \_\_\_\_\_\_\_\_
Decreased bone mineralization (osteopenia) ___________ osteoporosis
•Common osteoporosis = diagnosis of exclusion
Remember the often more treatable / reversible causes of secondary osteoporosis
Decreased bone mineralization (osteopenia) does not automatically = osteoporosis
26
Biggest complication of kyphosis
Shrinking thoracic cavity - difficult clearing of lung - pneumonia/infection
27
Major historical risk factors for osteoporosis in women
* Postmenopausal (within 20 years after menopause)
* White or Asian
* Premature menopause
* Positive family history
* Short stature and small bones
* Leanness
* Low calcium intake
* Inactivity
* Nulliparity
* Gastric or small-bowel resection
* Long-term glucocorticoid therapy
* Long-term use of anticonvulsants
* Hyperparathyroidism
* Thyrotoxicosis
* Smoking
* Heavy alcohol use
28
Most common fractures in osteoporosis (appendicular)
Proximal femur (intertrochanteric or intracapsular), proximal humerus, distal radius (colles')
29
Preventrion osteoporosis
umaximize peak bone mass (teens/young adults)
uencourage weight-bearing exercise and Ca supplementation
30
Labs osteoporosis
•to exclude secondary causes of osteoporosis/osteopenia
- serum Ca, P, alkaline phosphatase, 250H–Vit D, TSH, sometimes PTH (renal insufficiency or malabsorption)
31
Testing osteoporosis
Bone desnitometry
## Footnote
uoffer to all women \>= 65 yrs and to any woman \<65 yrs if risk factors or unexplained fractures present
32
Most anti-osteoporosis meds \_\_\_\_\_\_
inhibit bone resorption
33
Osteoporosis: Biochemical serum markers of bone formation and resorption:
currently NOT sufficiently standardized or studied to provide meaningful diagnostic or therapeutic guidance for individual patients
34
Primary hyperparathyroidism
•Hypercalcemia due to primary hyperplasia or NEOPLASTIC enlargement of parathyroid glands
35
Bony clinical presentation of primary hyperparathyroidism
* Spectrum of bony changes due to variable degrees of osteoclastic bone resorption—ranging from subtle subperiosteal cortical erosions to diffuse osteoporosis to tumor-like skeletal change (osteitis fibrosa cystica/"Brown tumor")
* Favors resorption of cortical bone over trabecular bone
Measure PTH levels
\*\*\*Used to find these cases w/ renal failure
36
Primary hyperparathyroidism pathology
•: osteoclastic bone resorption/peritrabecular fibrosis = osteitis fibrosa
37
Primary hyperparathyroidism complications
Fractures
Constitutional symptoms; metabolic impairment of kidneys; muscle weakness; neuropsychiatric syndromes (all direct effects of Ca++)
Renal stone disease
•NOTE: Secondary hyperparathyroidism (renal disease) may also produce gross skeletal change.
38
Prognosis - primary hyperparathyroidism
Good - remove adenoma, reversible
39
Screening hyperparathyroidism
asymptomatic and detected on biochemical screening studies
primary type — Ca and ¯P
40
Hypercalcemia major causes (from labs)
90% of all cases due to malignancy and hyperparathyroidism
41
Decreased bone mineralization w/ excess osteoid
Osteomalacia
42
Osteomalacia - d/t
interference w/ calcium, phosphate, or vitamin D metabolism (need to know what's causing that interference)
43
Osteomalacia: Radiologically appears \_\_\_\_\_\_\_\_
osteopenic (like osteoporosis)
44
Osteomalacia: May present w/ \_\_\_\_\_\_\_\_\_\_\_\_
diffuse skeletal pain (without fracture) - vs osteoporosis (sxs w/ fracture)
45
Osteomalacia associations
Environmental: classic childhood rickets
–Poor diet; ¯ sun exposure in northern latitudes
Intestinal malabsorption—commonest cause of Vit D deficiency in USA (celiac?)
Liver or renal disease (impaired hydroxylation of Vit D)
Rare congenital/inborn errors of metabolism
–Deficient Vit D hydroxylation
–Renal tubular phosphate leak
–End organ resistance to Vit D (OH)2
46
Osteomalacia biochemical profile
* serum alkaline phosphatase (\>90%)
* Low serum Ca or P (50%)
* Decreased urinary Ca excretion (33%)
* PTH (40%) - not as high as in hyper PTism
* Decreased 1, 25 dihydroxyvitamin D3 (50%)
47
Classic rachitic picture (children)
Widened/distorted growth plates
Bowed legs due to softened bone
Fractures
48
Renal osteodystrophy/osteomalacia:
Due to progressive destruction of second hydroxylation step of Vit D
Most commonly a combination of 2° hyper-parathyroidism as well as abnormal mineralization (mixed uremic osteodystrophy)
Can produce "renal rickets" in children
49
Infection of bone
osteomyelitis
50
Primary vs secondary mode of acquisition
* "Primary" mode of acquisition: hematogenous spread to bone from often occult source elsewhere (more common in kids)
* "Secondary" mode of acquisition: spread to bone from adjacent contiguous infection (joint infection/other soft tissue infection) - commonly diabetic ulcers w/ MRSA
51
Direct infection mode
e.g., compound fractures allowing direct injection of common bacteria onto raw fracture surfaces; orthopedic procedures ± prosthetic devices
52
Hematogenous subtype pyogenic/suppurative type osteomyelitis
Commonest in children/young adults
Favors long bones: usually begins in metaphyseal region
Half the cases have no obvious "seeding" source of
infection elsewhere in the body
Adults tend to have vertebral infection
Dx: blood or direct bone culture (children may be culture negative)
53
Common pathogens osteomyelitis
Staphylococcus aureus (95% of cases without predisposing morbidity)
Streptococcus
Hemophilus influenzae (now uncommon)
Gram-negative bacilli
NOTE: Patients with sickle-cell anemia tend to get salmonella osteomyelitis (worry w/ food posisoning)
54
Sxs osteomyelitis (common bacterial type)
Bone pain, erythema, swelling — fever/chills variable
Early infection (\<10 days) often not detectable by routine x-ray
–bone scans/MRI scans better at early detection
55
Pathology Osteomyelitis
Most infections begin in metaphyseal marrow space
Possibilities:
– Resolution of infection while still a small nidus
– Walled-off chronic infection (Brodie's abscess)
– Advanced infection: Subperiosteal and intramedullary spread, Death of bone (sequestrum), Periosteal new bone formation
56
Suppruative osteomyelitis longterm/chronic complications
Suppurative arthritis (adjacent joints)
Sinus tracks to skin
Growth disturbance (children)
Deformity
Amyloidosis (secondary seen in longterm inflammation)
57
Commonest causes of direct extension/injection osteomyelitis in adults
–Compound fractures
–Contamination during orthopedic surgical procedures
–Extension from adjacent joint/soft tissue infection; diabetic vascular disease
–Causative bugs, Rx, and complications similar to hematogenous type
58
Treatment suppurative osteomyelitis
Need early/timely dx and tx to avoid chronic
## Footnote
Aggressive (usually I.V.) antibiotic therapy
± Surgical drainage/debridement
Occasionally amputation for chronic cases
59
Tuberculous Osteomyelitis (spread, location in body, severity, incidence)
* Usually 2° to hematogenous spread from lungs
* Prefers spine (Pott's disease) and long bones
* Highly destructive osteomyelitis with tendency to involve neighboring joints
* Relatively rare form of osteomyelitis in U.S.A. except in Third World immigrants and immunosuppressed patients
60
Fungal osteomyelitis common causes and spread
•Blastomycosis (more here) and coccidioidomycosis (Southwest):
Commonest causes of fungal osteomyelitis in non-immunosuppressed patients
Almost always 2° to hematogenous spread from lungs; original pulmonary infection may have gone undiagnosed or be asymptomatic
Bacterial much more common
61
Syphilitic osteomyelitis
VERY RARE
Risk currently towards fetus
62
best way to diagnose osteomyelitis at early stage
MRI
63
Bone infarcts due to ________ of ____________ causations
Most common identifiable causes
•Bone infarcts due to ischemia of varying/often poorly understood causations
Commonest identifiable causes are fractures, corticosteroid Rx, and alcoholism
64
Avascular Bone necrosis/infarction most commonly affects:
femoral head:
Can be 2° to subcapital fractures of femoral neck
Causes necrosis of bone with slippage of articular cartilage
65
Legg-Calve-Perthes disease
osteonecrosis of femoral head (? due to trauma), especially ages 4-8 (boys 5:1)
66
Avascular bone necrosis/infarction associations
Fractures, Legg-Calve-Perthers, Corticosteroid therapy, Alcoholism, Gaucher's ds, SLE, Sickle Cell anemia, Caisson's ds
67
Caisson's disease
The bends
Nitrogen comes out too fast - bones are kind of least of the worries
68
Subchondral infarcts
typically cause pain w/ activity
69
Medullary infarcts
usually clinically silent unless large (e.g., hemoglobinopathy, Caisson's disease)
70
Multiple infacts
especially with chronic corticosteroid Rx
71
Complications of avascular bone necrosis/infarction
2° degenerative joint disease
Bone growth deformities (childhood)
Pathologic fracture
72
Paget's disease of bone (pearls)
| (Osteitis deformans)
Elderly
Anglosaxon ancestry (strong family hx)
Elevated serum alkaline phosphatase
Deformed bone
73
Paget's - which bones and how many
May involve multiple bones (polyostotic─most patients) or localized to a single bone (monostotic)
Prefers larger bones (skull, pelvis, tibia, femur, spine)
74
Paget's - focal acceleration of bone resoprtion followed by haphazard new bone formation
3 phases
Lytic - inc. osteoclasts w/ bone resorption, inc vascularity
Mixed - inc. osteoclasts w/ inc osteoblasts, inc vascularity
Sclerotic - most characteristic radiologically (osteoblastic phase)
75
Paget's clinical/imaging featurse
* Most patients asymptomatic
* Widening / bowing of long bones
* Distorted / widened pelvic bones
* General weakening of affected bone causing increased fractures
76
Paget's sxs
* principally pain (due to fractures, compression of cranial or spinal nerve roots by foraminal encroachment, or secondary degenerative joint disease due to subchondral bone deformity).
* Sometimes skin overlying an affected bone is warm during lytic / vascular phase (high output CHF possible in polyostotic disease).
77
Radionuclide bone scan - Pagets
Sensitive for early phase ds
78
Paget's Widening of Bone
•Widening of bone favors Paget's disease over other pathology HALLMARK
X-ray features usually typical to experienced radiologist; occasionally may mimic malignant bone disease (need Bx)
79
Paget's Lab
serum alkaline phosphatase typical for active disease
–Suspect Paget’s biochemically if: Older patient, Isolated alkaline phosphatase level, Normal serum calcium, No hepatobiliary disease
80
Complication w pagets
bone sarcoma, severe polyostotic ds
81
82
Cause of Pagets
Current theory:
–Due to a latent viral infection of osteoclasts in a genetically susceptible person
83
Congenital bone disorders
* Localized absence or duplication of a bone(s)
* Malformation of craniopsinal axis (spina bifida, meningomyelocele, meningoencephalocele)
* Achondroplasia
* Osteogenesis imperfecta
* Osteopetrosis
* Bone disease associated with mucopolysaccharidosis
84
Osteogenesis imperfecta
•Congenital disorders of type 1 collagen
Either qualitatively abnormal or quantitatively too little
Result: insufficient / inadequate collagen for normal osteoid production --\> risk of fractures
85
Osteogenesis imperfecta (variants)
Variable degrees of osteopenia/osteoporosis
Variable tendencies for fracture depending on genetic subtype
–Spectrum from type II variant, fatal in utero to type 1 variant with fracture tendency that lessens post-puberty
86
Tumors/Tumor-like lesions involving brain (Sxs)
•Whether primary or secondary (metastatic) type, symptoms often are nonspecific:
Pain and/or swelling
Pathologic fracture
87
Tumors of bone (Xray Features)
•valuable for predicting:
Along with age—likelihood of primary vs metastatic lesion
Ability to subtype primary bone tumors by location and x-ray character
Usually accurate in separating benign from malignant lesions
88
Bone tumors classified as:
osteolytic (demineralizing effect) - (i.e. myeloma)
osteoblastic (increased bone density relative to normal bone) (i.e. metastatic prostate cancer)
mixed osteolytic/osteoblastic features
89
Most common sources of metastatic tumor to skeleton
lung, breast, prostate
Almost every known malignancy is capable of metastasizing to bone
Larger bones usually perfered (but can be any)
90
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ are the most common malignancies involving bone
Metastatic tumors to skeleton
91
Classical myeloma clinical presentation
Multifocal osteolytic lesions with bone pain
Often associated hypercalcemia
Fractures common
92
Plastocytoma of bone
•localized tumor of plasma cells—eventually tends to evolve towards classic myeloma
93
Hemic malginancies affecting bone
Classic myeloma
plasmacytoma of bone
lymphoma
leukemia
94
Lymphoma
Most non-Hodgkin's lymphomas involve bone at some time during their course
May cause sufficient focal tumefaction to compromise bone strength ® pathological fracture
Rarely can see 1° lymphoma of bone
95
Leukemia
By definition, always affects bone marrow
Clinically can produce diffuse/multifocal bone or joint pain (especially ALL in children)
May produce skeletal changes 2° to expanded marrow spaces
Occasionally can produce localized tumefaction of bone
96
Osteoblastic hallmark for
prostate cancers in males
97
Osteolytic hallmark for
myeloma
98
Primary bone tumors mostly arise in _______ (location) and ________ (population)
Metaphyses of long bone
Kids
99
Most common primary benign tumors
–Osteochondroma
–Giant cell tumor
–Chondroma
–Osteoid osteoma
–Fibroma (metaphyseal fibrous defect)\*\*
100
Most common malignant primary tumors
Osteogenic sarcoma (osteosarcoma) - BAD, most common in kids
Chondrosarcoma - most common in adults
Lymphoma
Ewing's sarcoma - one of most aggressive
Chordoma - bottom or top of spine
\*\*Again, children
101
Osteosarcoma vs chondrosarcoma
* Osteosarcoma is the commonest primary malignant tumor of children/young adults
* Chondrosarcoma is the commonest primary malignant tumor of middle-aged/older adults
102
Benign vs malignant preference for location w/ primary bone tumors
* Most benign cartilage tumors (chondromas) tend to involve the small bones (hands and feet)
* Most malignant cartilage tumors (chondrosarcomas) tend to involve the larger bones (long bones, pelvis, ribs, spine)
103
Sarcomas tend to spread via \_\_\_\_\_\_
hematogenous route (rather than lymph nodes like carcinoma), ie. go to lungs
104
Tx primary bone tumor cancers
Aggressive
surgery, chemo, and/or radiation
105
Giant Cell Tumors
Primary bone tumor
## Footnote
* "intermediate" between benign and malignant states
* 50% recur following simple curettage
can be locally aggressive
•Some can metastasize to lungs
106
Metaphyseal fibrous defect
* Fibroma, fibrous cortical defect
* Commonest bone lesion
* Regarded as a non-neoplastic developmental defect
* Can be found in one-third of children
* Often regress spontaneously
* Occasionally are large enough to compromise bone strength/cause pathological fracture
107
Conditions taht may simulate primary/metastaic bone tumors
* Osteomyelitis
* Paget’s disease
* Hyperparathyroidism
* Fibrous dysplasia
* Exuberant callus (healing fracture site)
* Avulsion fractures
* Assorted benign cysts
* Histiocytosis X
* Bone infarcts
* Mast cell disease
* Giant cell reparative granuloma
108
tx osteosarcoma
Pre-op tx and amputation
109
Most common primary malignant bone tumor of adolescents/young adults
Osteogenic sarcoma
110
Osteosarcoma sxs
pain, pathologic fracture
111
Osteosarcoma favors _________ (location)
•metaphyseal regions of large long bones (esp. knee)
112
Variants osteosarcoma
common high-grade / aggressive types (grade 3-4)
–40% mortality rate
ulow-grade types
–curable by adequate surgical excision alone
113
Tx failurs of osteosarcoma associated w/
local recurrence and pulmonary/other metastases
114
Osteosarcoma may be secondary to
Paget's, prior irradiation, old bone infarcts (link to retinoblastoma gene mutations?)
115
\_\_\_\_\_\_ bone osteosarcoma more curable
jaw
116
Commonest primary bone tumor of middle-aged/older adults
swelling, pain
117
Chondrosarcoma sxs
swelling, pain
118
chondrosarcoma prefers _______ bones
larger long bones, central skeleton
especially pelvis, rare in small bones
119
Chondrosarcoma may grow to _________ before dx
very large size (especially pelvis)
usually typical xray features (hallmark)
120
Multiple variants chondrosarcoma
Most common are low-grade tumors with slow growth and delayed risk of metastasis
Xray features to differentiate
121
Chondrosarcoma tx
adequate surgical excision (can be very late metastasis)
122
Most aggressive/lethal of all primary bone tumors
Ewing's sarcoma
123
Ewing's sarcoma usually affects ________ and prefers _______ bone
* Usually affects a younger age group than osteogenic sarcoma (esp. peripubertal ages)
* Prefers diaphysis of long bones & flat bones of pelvis
124
Diff Dx Ewing's Sarcoma
•Some patients: The x-ray features with fever & leukocytosis may mimic osteomyelitis
125
Histology EWing's sarcoma
Composed of small, morphologically undifferentiated tumor cells now known to be primitive neuroectodermal neoplasm (PNET)
–Usually t(11;22)
–Resembling leukemia, lymphoma, neuroblastoma, Wilm’s tumor, small cell Ca
126
