Bone Pathology Flashcards
(91 cards)
1
Q
Secondary
Bone Tumors
A
-
Metastatic tumors
- Most frequent malignant tumors found in bone
- Predominant occurrence in adults > 40 yrs and children in first decade of life
- Multifocal
- Predilection for the marrow in the axial skeleton (vertebrae, pelvis, ribs and cranium) and proximal long bones
- Tumors resulting from contiguous spread of adjacent soft tissue neoplasms
2
Q
Metastatic Origins
A
Most common malignancies producing skeletal metastases:
-
Adults:
- Prostate, breast, kidney, and lung
- Thyroid and colon cancers
- Melanoma
-
Children:
- Neuroblastoma
- Rhabdomyosarcoma
- Retinoblastoma
3
Q
Osteoarticular System
Primary Tumors
A
- Relatively uncommon ⇒ 2,400 cases of primary bone sarcoma/year in US
- Benign tumors more common
- Occur mostly in the first three decades of life
- Clinical hx including age, location of tumor and radiological data are very important to diagnosis
4
Q
Most Common
Benign Tumors
A
- Osteochondroma
- Non-ossifying fibroma
- Enchondroma
5
Q
Most Common
Malignant Tumors
A
Excluding malignant neoplasms of marrow origin:
- Osteosarcoma
- Chondrosarcoma
- Ewings sarcoma
6
Q
Bone Tumors
Features
A
-
Some able to dedifferentiate
- eg., enchondroma or a low-grade chondrosarcoma transforming into a high-grade sarcoma
-
Tendency of high-grade sarcomas to arise in damaged bone
- Sites of bone infarcts
- Radiation osteitis
- Paget’s disease
7
Q
Primary Bone Tumor
Classifications
A
8
Q
Age of Onset
A
Predominant occurrence in first 3 decades of life
9
Q
Common Tumors
Ages 0-10
A
10
Q
Common Tumors
Ages 10-20
A
11
Q
Common Tumors
Ages 20-40
A
12
Q
Common Tumors
Ages 40+
A
13
Q
Bone Tumor
Frequent Locations
A
-
Distal femur and proximal tibia most common
- Both benign and malignant
- Bones with highest growth rate
- Many lesions favor certain bones or sites
14
Q
Bone Tumors
Location Preference
A
15
Q
Bone Tumors
Imaging Studies
A
- Most bone tumors have relatively specific radiographic presentations
- In some cases, dx can be confidently made based on radiographic features alone
-
Can provide clues about clinical behavior
- Estimate tumor growth rate
- Expansive or infiltrative growth patterns characteristic of locally aggressive and malignant tumors
- Modalities:
- Plain Radiograph
- CT
- MRI ⇒ method of choice for local staging
-
Bone Scintigraphy ⇒ highly sensitive but relatively non-specific
- Main role in detection of suspected metastases in the whole skeleton
16
Q
Bone Tumors
Radiologic Features
A
Radiographic examination should answer the following questions:
- Location
-
Type of bone (flat, tubular)
- If long bone affected ⇒ where lesion is centered
- Cortex or medulla
- Epiphysis, metaphysis or diaphysis
- If long bone affected ⇒ where lesion is centered
-
Underlying bone abnormality (eg., bone infarct, Paget’s disease)
- High-grade sarcomas tend to arise in damaged bone
-
Multifocality
- Malignant > benign
- Benign lesions tend to show symmetrical distribution
-
Well-defined margin, rim of sclerotic bone?
- Presence strongly suggests a benign non-growing or slow growing lesion
-
Cortical expansion or destruction?
- Findings seen with locally aggressive or malignant tumors
- Periosteal reaction and, if so, of what type
-
Patterns of Mineralization (calcification or ossification)
- Helpful in identification of bone-producing and cartilage producing tumors
- Is there a soft tissue mass?
17
Q
Periosteal Reactions
A
- Periosteum responds to traumatic stimuli or pressure from an underlying growing tumor by depositing new bone
- Radiographic appearance of response reflects the degree of aggressiveness of the tumor
18
Q
Benign and Non/Slow-Growing
Lesions
A
- Well-circumscribed and shows a geographic pattern of bone destruction with a sclerotic rim
- Slow-growing tumors provoke focal cortical thickening ⇒ solid periosteal reaction or “buttress”
19
Q
Rapidly Growing
Lesions
A
- May still show a well-demarcated zone of bone destruction (geographic pattern) but will lack a sclerotic rim
- With continued growth, may show cortical expansion
- Periosteal reactions include:
- Codman’s triangle ⇒ elevation of periosteum to a significant degree, forming an acute angle
- “Onion-skinning” ⇒ seen in Ewing sarcoma
- Spiculated “hair-on-end” appearance due to periosteal new bone formation
20
Q
Osteoid
A
Malignant osteoid can be recognized radiologically as cloud-like or ill-defined amorphous densities with haphazard mineralization
Pattern is seen in osteosarcoma
21
Q
Chondroid
A
Usually easier to recognize cartilage vs osteoid by the presence of focal stippled or flocculent densities, or in lobulated areas, as rings or arcs of calcifications.
22
Q
Bone Tumors
Histologic Evaluation
A
-
Most important histologic features to consider:
- Pattern of growth (eg., sheets of cells vs. lobular architecture)
- Cytologic characteristics of the cells
- Presence of necrosis and/or hemorrhage and/or cystic change
- Matrix production
- Relationship between the lesional tissue and the surrounding bone (eg., sharp border vs. infiltrative growth)
- Dx of bone tumor requires clinical, radiological, and histologic appearances
- Biologically different types of tumors may have overlapping histologic features
23
Q
Osteoid Osteoma
Overview
A
Benign, bone-producing neoplasm
- Small size w/ limited growth potential
- Lesional tissue ⇒ “nidus”
- Small radiolucent focus < 1 cm
- Either within the cortex or adjacent to it
- Predominantly in males 10-25 y/o
-
50% of cases in the femur and tibia
- Femoral neck is one of the most common anatomic sites
24
Q
Osteoid Osteoma
Effects
A
- Causes extensive reactive changes in surrounding tissues
- Produces prostaglandin/prostocyclin-mediated effects
- Induces exuberant, reactive, periosteal sclerosis, soft tissue edema and pain
25
Osteoid Osteoma
Gross Appearance
* If nidus removed intact ⇒ circumscribed portion of **red, trabecular bone \< 1 cm in size**
* Either within the cortex or adjacent to it
* XR shows a **small, intracortical, radiolucent focus (nidus), surrounded by dense reactive periosteal bone**
26
Osteoid Osteoma
Microscopic Appearance
Lesional tissue ("nidus") **well-demarcated** from the surrounding sclerotic bone
Composed of **thin, often interconnected spicules of osteoid and woven bone** rimmed by **osteoblasts**
**Osteoclast-like giant cells** can be seen
Intervening **fibrous stroma** shows **prominent vascularity**
Both osteoblasts and stromal cells are **without significant nuclear atypia**
27
Osteoid Osteoma
Differential Diagnosis
1. Osteoblastoma
2. Intracortical osteosarcoma ⇒ significant nuclear atypia and invasive growth pattern are indicative of malignancy
28
Osteoblastoma
Overview
* **Larger than 1.5 cm**
* **Slowly and progressively growing neoplasms**
* Term "**aggressive osteoblastoma**" is applied to _large, locally destructive lesions that mimic a low-grade osteosarcoma_ on microscopic examination
* Peak incidence during **2nd and 3rd decades of life**
29
Osteoblastoma
Clinical Behavior
* **Tend to arise in the axial skeleton**
* Involves **spine** and **sacrum** in ~ 40% of cases
* 2nd most frequent site is the **mandible**, followed by other **craniofacial bones**
* **Do not produce prostaglandin/prostocyclin-mediated tissue reaction**
* May grow to a considerable size ⇒ **bone expansion and cortical destruction**
* **Recurrences in ~ 20% of cases**
* **No metastases**
30
Osteoblastoma
Appearance
_Radiology:_
* XR ⇒ **well-circumscribed, _low metaphyseal_, radiolucent lesion** containing **matrix-type radiodensities**
* No sclerotic rim
* Affects long bones and vertebrae
_Histology:_
* Resembles osteoid osteoma
* **Osteoblasts** and **osteoclast-like giant cells** surround interconnected **spicules of osteoid and woven bone**
* Intervening fibrous stroma shows **prominent vascularity**
* **No significant cellular atypia**
31
Osteosarcoma
Overview
**Malignant tumor** composed of **neoplastic mesenchymal cells** synthesizing **osteoid or immature bone.**
* Presence of **malignant osteoid** distinguishes an osteosarcoma from other sarcomas
* **Preferentially affects rapidly growing parts of the skeleton**
* Distal femur and proximal tibia (50% of cases)
* Proximal humerus
* Elderly ⇒ tends to involve axial skeleton and flat bones
* **Metaphysis** is the most common site in long bones
32
Osteosarcoma
Epidemiology
* **Most common primary sarcoma of bone**
* _Bimodal age distribution:_
* **Peak incidence in 2nd decade of life** ⇒ _most active skeletal growth_
* \< 5% of cases occur in children younger than 10 years
* **In the elderly** ⇒ usu. seen in association with a _pre-existing bone disease_
* Paget's, radiation osteitis, or bone infarct
33
Osteosarcoma
Classification
* _Subdivided into:_
* **Intramedullary** (largest group)
* **Intracortical**
* **Surface osteosarcomas**
* _Subclassified_ into **high-grade and low-grade**
* Based on the degree of differentiation
34
Osteosarcoma
Appearance
_Histologic findings can be extremely variable_
* Composed of **highly pleomorphic cells** and **haphazard deposits of osteoid**
* **Anaplastic** cellular features and **mitotic activity**
* _Malignant osteoid:_
* **Lace-like pattern**
* **Haphazardly arranged trabeculae of woven bone**
* ± Foci of neoplastic **cartilage**
May appear identical to MFH ⇒ minimal osteoid production
May contain masses of malignant cartilage or numerous giant cells
35
Osteosarcoma
Histologic Variants
* Osteoblastic (≈ 50%)
* Chondroblastic
* Fibroblastic
* Telangietatic
* Small cell
* Giant cell
36
Osteosarcoma
Disease Course and Treatment
* One of the **most aggressive** and **highly lethal** tumors
* _Most powerful predictor of outcome_ is the **histologic response of the tumor to pre-operative chemotherapy**
* Tumor necrosis following tx graded according to the following system:
* Grade 1 - 0-50% necrosis
* Grade 2 - 51-90%
* Grade 3 - 91-99%
* Grade 4 - 100% necrosis
* ≥ 90% tumor necrosis ⇒ nearly 90% 5-year disease-free survival
* \< 90% tumor necrosis ⇒ 14% 5-year disease-free survival in pts with
* **Metastases extremely common**
* Usu. to **lungs, bones, and liver**
37
Osteochondroma
Overview
**Cartilage-capped outgrowth attached to the underlying bone by a bony stalk.**
* Can be **solitary or multiple**
* **Multiple Hereditary Exostosis** ⇒ multiple osteochondromas
* AD hereditary disease
* More likely to undergo malignant transformation (\<1%)
* Most common skeletal sites are the **metaphyses of long bones**
* It does not occur in bones with membranous type of ossification
* **M:F = 3:1**
* _When skeletal maturity is reached_, **osteochondromas usually stop growing**
* Continued growth may signify malignant transformation
* **Clonal origin** of sporadic & hereditary forms supported by **clonal cytogenetic abnormalities**
* Deletions of regions q24 of chromosome 8 (EXT1 locus) and p11-12 of chromosome 11 (EXT2 locus) ⇒ **inactivation of EXT1 and EXT2 genes**
38
Osteochondroma
Appearance
* XR ⇒ **pedunculated bony outgrowth @ proximal tibial metaphysis**
* _Histology_:
* Cortex and medulla are continuous with those of the lesion
* **Mature trabecular and cortical bone**
* **Uniform, cartilaginous cap** with stippled calcifications
* Mature, focally calcified hyaline cartilage
* \< 1 cm thick
39
Chondroma
Overview
**Common, benign, intramedullary bone tumor composed of mature hyaline cartilage.**
* Wide age distribution
* Peak incidence during 3rd and 4th decades of life
* Limited growth potential
* Many lesions remain small and asymptomatic
40
Chondroma
Appearance
* _Three characteristic features:_
* **Vague lobularity** (“soap bubbles”)
* **Abundant cartilaginous matrix**
* Can be focally calcified
* **Low cellularity**
* **Clustered and scattered chondrocytes** with small, uniform, darkly-stained nuclei
* Occasional bi-nucleated chondrocytes present
* **No mitotic figures**
41
Ollier's Disease
* Rare, _non-hereditary_ disorder
* Characterized by **multifocal proliferation of dysplastic cartilage (enchondromatosis)**
* Usually dx in children and adolescents between 10 and 20 years of age
* **Very high risk of malignant transformation (20% - 30%)**
* Usually to chondrosarcoma
42
Marfucci’s Syndrome
**Multiple cartilaginous tumors associated with hemangiomas**
Similar to Ollier’s
43
Enchondromas
* Associated with **pain** and **fracture or thinning of the overlying cortex**
* _Long bones_ ⇒ suspicious for malignancy
* _Small bones_ ⇒ no dx of chondrosarcoma unless a tumor permeates into soft tissue
44
Chondroblastoma
Overview
* **Rare, benign neoplasm**
* Occurs in the **2nd decade of life** (75%) ⇒ growth plates are still open
* One of two neoplasms of **incompletely differentiated cartilage**
* The other neoplasm is chondromyxoid fibroma
* **70% arise in the proximal humerus and at the knee**
* Long bones ⇒ almost always occurs in the **epiphysis**
* Recurrence rate ~ 10% within the bone or in the adjacent soft tissue
* It can occasionally produce "benign", clinically non-progressive lung implants
45
Chondroblastoma
Appearance
* **Irregular** but **circumscribed**, radiolucent **epiphyseal lesion** surrounded by **reactive bone sclerosis**
* **Highly cellular** tumor consisting of **sheets of round to polygonal chondroblasts**
* Folded or clefted nuclei
* Fine chromatin pattern
* Occasional inconspicuous nucleoli
* **Stains ⊕ for S-100**
* **Mitotic activity is low**
* Multiple small foci of **immature bluish-pink chondroid** ⇒ vaguely _lobular appearance_
* **Multinucleated giant cells** scattered throughout lesion
* Are of different cell line and stain **⊕ for histiocytic markers (CD68)**
* **"Chicken-wire" calcification** is virtually pathognomonic of chondroblastoma
46
Chondroblastoma
Differential Diagnosis
* **Giant Cell Tumor (GCT):**
* Also occurs @ epiphysis but in skeletally mature individuals
* Lacks chondroid matrix
* ⊖ staining with S-100
* **Chondromyxoid fibroma:**
* Centered in the metaphysis and lacks calcification
* **Clear cell chondrosarcoma:**
* Epiphyseal tumor of pts \> 40 y/o
* Malignant chondrocytes and characteristic large cells with clear cytoplasm
47
Chondromyxoid Fibroma
Overview
* Benign tumor
* **Occurs in pts \< 40 y/o**
* **Peak incidence is between ages 10 and 20**
* **30% occur at the knee area**
* Long bones ⇒ involves the **metaphysis** **or meta-diaphysis** and is **often eccentric**
* ± Secondary **aneurysmal bone cyst** formation
48
Chondromyxoid Fibroma
Clinical Behavior
**Recurrence rate averages 15%-20%**
Large or recurrent lesions may be **locally aggressive**
49
Chondromyxoid Fibroma
Appearance
* **Well-defined, expansile lytic lesion**
* **Centered at the metaphysis**
* **Bordered by a sclerotic rim**
* Moderately cellular **chondromyxoid tissue** with _two characteristic features:_
* **Vague lobularity** caused by alternating highly cellular and less cellular areas
* ↑ Cellularity @ periphery of lobules
* **Mildly** **pleomorphic**, **angular and stellate cells** set in bluish-pink **chondromyxoid stroma**
50
Chondromyxoid Fibroma
Differential Diagnosis
* Chondroblastoma
* Chondrosarcoma
51
Chondrosarcoma
Overview
**Malignant, cartilage-producing tumor**
* Patient age is typically **30-50 years**
* **Extremely rare in children** ⇒ almost always high grade
* Most chondroid tumors in children and adolescents are chondroblastic osteosarcomas
* _Common sites_:
* **Bones of the trunk** including the **pelvis**
* **Long bones** such as the **femur** and **humerus**
* **Osteochondroma, enchondroma and fibrous dysplasia** may undergo _malignant transformation_ into a chondrosarcoma
52
Chondrosarcoma
Appearance
* **Large, lobulated, ill-defined lesion**
* Centered in the **distal femoral metaphysis**
* Moderately cellular, **lobulated** **cartilaginous** tumor
53
Chondrosarcoma
Clinical Behavior
**Aggressiveness predicted by histologic grade.**
Based on three parameters:
1. Cellularity
2. Degree of nuclear atypia
3. Mitotic activity
54
Chondrosarcoma
Grade 1
* Very similar to enchondroma with **higher cellularity** and **mild cellular pleomorphism**
* **Small nuclei** show **open chromatin pattern** and small nucleoli
* Frequent binucleated cells
* **Mitoses are very rare**
* **Locally aggressive** and **prone to recurrences** but **usually do not metastasize**
55
Chondrosarcoma
Grade 2
* **Cellularity higher** than Grade 1 tumors
* **Moderate cellular pleomorphism**
* Plump nuclei
* Frequent bi-nucleated cells
* Occasional bizarre cells
* **Mitoses are rare**
* **± Foci of myxoid change**
* **~ 10% to 15% of Grade 2 chondrosarcomas produce metastases**
56
Chondrosarcoma
Grade 3
* **High cellularity**
* **Marked pleomorphism**
* **↑ N/C ratio**
* Many bizarre cells
* **Frequent mitoses** (more than 1 per hpf)
* These are high grade tumors with **significant metastatic potential**
57
Non-Ossifying Fibroma (NOF)
Overview
**Common, non-neoplastic, self-healing fibrous tissue forming tumor**
* Occurs in **skeletally immature individuals**
* **Usu. between 5-20 y/o**
* Small lesions usu. incidental radiological findings
* Larger lesions occupying \> ½ of bone diameter ⇒ **± pathologic fracture**
* Usu. a **solitary lesion** in the **metaphysis or meta-diaphysis** of the **long bone** at the **knee, distal tibia or proximal humerus**
* Can resemble GCT
* Epiphyseal location and occurrence in adults
58
Non-Ossifying Fibroma (NOF)
Radiologic Findings
**Sharply demarcated, lucent, loculated, meta-diaphyseal lesion surrounded by a rim of sclerotic bone.**
* Predominantly involves the **lateral portion** of the bone ⇒ **eccentric location**
* Produces **mild cortical expansion**
* _Large lesions_ can involve the **entire diameter of the bone** expanding the cortex
* Dx by XR alone if located in the typical skeletal site and in appropriate age group
59
Non-Ossifying Fibroma (NOF)
HIstology
* Moderately cellular
* **Uniform spindle cells** in a **storiform pattern** w/ bland appearance
* **Scattered giant cells**
* Multiple collections of **foamy histiocytes (xanthoma cells)**
* **± Hemosiderin-laden MΦ**
* Mitotic figures are easily found averaging 4 per 10 hpf
* No atypical mitoses
60
Jaffe-Campanacci
Syndrome
Multiple **non-ossifying fibromas** & cutaneous **cafe au lait spots**
61
Benign Fibrous Histiocytoma
* Lesions w/ **histologic features of NOF** but occur in **unusual locations**
* **Pelvis, ribs or vertebrae**
* Designation controversial and is not generally accepted
62
Fibrous Dysplasia
Overview
**Benign fibro-osseous lesion**
* Considered a **hamartoma**
* Occurs sporadically during the **period of skeletal growth (10-25 y/o)**
* **Intramedullary location**
* Most common locations include the **long bones (ribs, femur, tibia, jaw and humerus)** in the **metaphysis or diaphysis**
* Hallmark of FD is **inability of tissue @ affected site to produce mature lamellar bone**
* Arrested @ level of woven bone
63
Fibrous Dysplasia
Types
_Two forms:_
* **Monostotic** (70% of cases)
* **Polyostotic**
* **McCune-Albright syndrome**
* FD, cutaneous café au lait pigmentations, and precocious puberty
* **Mazabraud's syndrome**
* FD in close proximity to soft tissue myxomas
64
Fibrous Dysplasia
Overview
* _Three characteristic histologic features:_
* **Thin wavy spicules of woven bone** (“Chinese characters")
* **Lack of osteoblastic rimming or osteoclastic activity**
* **Moderately cellular, bland fibrous background**
* In children ⇒ stromal mitoses may be frequent (1 to 5 per hpf)
* In adults ⇒ mitotic figures are very rare to absent
65
Giant Cell Tumor
Overview
**Relatively uncommon, locally aggressive neoplasm**
* **4% of all primary bone tumors**
* Affects **skeletally mature individuals**, **20-50 y/o**
* Extremely rare in children and patients older than 60 years
* **Centered in the epiphysis**
* **65% in the distal femur, proximal tibia and distal radius**
* May affect **any long bone, pelvis, sacrum, and spine (3%)**
66
Giant Cell Tumor
Clinical Behavior
* **± Bone destruction and soft tissue invasion**
* **Intravascular invasion in 30% of cases**
* Not correlated with local aggressiveness or development of pulmonary implants
* _Common secondary changes:_
* **Hemorrhage and necrosis**
* **Fibrohistiocytic (xanthomatous) change**
* **Aneurysmal bone cyst formation**
* _Complications:_
* **Pathologic fractures**
* **Malignant transformation** (dedifferentiation)
* **Local recurrences common if not completely excised (40% - 60%)**
* May involve bone and/or soft tissue
67
Giant Cell Tumor
Appearance
* _Radiologic appearance:_
* **Well-defined, lytic lesion**
* **Eccentrically located** in the **distal epiphysis**
* **Subchondral and metaphyseal extension**
* _Histology:_
* **Multinucleated giant cells**
* **Small, ovoid, mononuclear stromal cells**
* Monocyte/MΦ derived
* Poorly defined cytoplasmic borders and bland nuclei
* **Mitoses average 4 per 10 hpf**
* No atypical mitoses
* **± Areas of prominent fibrohistiocytic changes**
* **Storiform arrangement** of stromal cells
* Clusters of **foamy histiocytes (xanthoma cells)**
68
Ewing’s Sarcoma (ES)
Overview
* 80% of cases occur in pts **5-20 y/o**
* Most common sites:
* **Diaphysis of femur, tibia and humerus**
* **Pelvis and ribs**
* Askin tumor of the chest if in ribs
* **Arises in the medullary cavity**
* **Invades cortex and periosteum**
* Fequently produces a **soft tissue mass**
* **Positive for CD99/O13**
* Chromosomal translocation ⇒ **EWS-FLI-1 fusion gene**
69
Ewing’s Sarcoma (ES)
vs.
Primitive Neuroectodermal Tumor (PNET)
* Both are "**small round blue cell" tumors**
* **Similar neural phenotype**
* Positive for CD99/O13
* **Identical chromosomal translocation**
* t(11;22)(q24;q12) → EWS-FLI-1 fusion gene
* _Degree of neural differentiation distinguishes them from one another:_
* **EM** ⇒ cells are **undifferentiated** and show **prominent glycogen deposits**
* **PNET** ⇒ **neural differentiation**
* NSE and/or S100 positive
70
Ewing’s Sarcoma (ES)
Clinical Manifestations
* Frequently produces a **soft tissue mass**
* Tumor site is often **painful, swollen and warm**
* Patients may have **fever, elevated ESR and leukocytosis** mimicking infection
71
Ewing’s Sarcoma (ES)
Radiologic Appearance
* **Large destructive, diaphyseal lesion**
* Permeative periosteal reaction of a **"hair-on-end" or “onion-skin”** type
* MRI superior to XR in showing cortical disruption and soft tissue involvement
72
Ewing’s Sarcoma (ES)
Histology
* **Sheets of primitive cells** with **little histologic evidence of differentiation**
* **Mitotic rate is relatively low**
* Positive for **CD99/O13** immunostain
73
Osteoporosis (OP)
Overview
* **A common, severe, and debilitating disease**
* Estimated 15 million symptomatic cases in the U.S. and many more asymptomatic
* **More common in women, esp. post-menopausal women**
* Cause is unknown
74
Osteoporosis (OP)
Pathophysiology
* **↑ Bone resorption**
* Occurs as part of aging
* Especially ↑ in postmenopausal women
* **↓ Bone formation**
* **Overall organic to mineral matrix balance remains the same**
* **Spicules are smaller, thinner and more fragile**
* Bone looks the same histologically
* **Much weaker and thinner structurally**
75
Senile Osteoporosis
**OP seen in older people**
Development of the disease is due to **hormonal imbalances** that occur in the aged, especially post-menopausal women
76
Osteoporosis
Other Etiologies
* **Hereditary**
* **Osteogenesis imperfecta**
* **Exercise** ⇒ ↑ bone mass, ↑ bone density, and ↓ incidence of OP
* Females who exercise to amenorrhea (e.g. long-distance runners) are more susceptible to OP
* **Bone size** ⇒ smaller people at ↑ risk for OP
* **Greater incidence in whites than blacks**
* **Hormones** ⇒ those on steroids lose bone mass and are at risk
* **Long-term heparin** **therapy** ↑ risk of OP
77
Osteoporosis
Clinical Manifestations
↓ Structural integrity ⇒ fractures
_Most common sites of thinning due to OP:_
* **Neck of femur**
* **Vertebral column**
* Normal thickness
* Microfractures d/t thinning of the bone
* Can result in fracture of the spine & collapse of vertebral column
* **Metacarpals**
78
Osteoporosis
Diagnosis
* Best way to dx OP is by **dual photon beam densitometry**
* **Blood levels of calcium, phosphorus, and alkaline phosphatase will be normal**
* **XRs will also be normal**
79
Osteoporosis
Treatment
**Tx with estrogens, ↑ calcium, and calcitonin injections.**
* **Estrogens given to ↓ bone loss**
* ↑ Risk of endometrial carcinoma in post-menopausal woman
* ? ↑ risk of breast cancer
* Calcitonin shown to be successful in tx of OP
80
Osteomalacia (OM)
Overview
* **Most common remedial bone disease of the elderly**
* **Due to Vit D deficiency**
* Usu. d/t poor diet in the elderly
* Also seen in underdeveloped countries d/t poverty and poor diet
* **Inadequate calcium absorption** d/t ↓ Vit D
* **Widened organic matrix that is not mineralized**
81
Osteomalacia
Clinical Manifestations
* **Bending, bowing, and breaking of bones**
* **Overabundance of organic matrix**
* Matrix is not mineralized
* Normal bone takes 6-10 days to mineralize
* In OM, it takes 2-3 months to mineralize
82
Osteomalacia
Diagnosis
* **↓ Phosphorus**
* **Calcium is low to low normal**
* ↑ Bone turnover ⇒ **↑ alkaline phosphatase**
* _Biopsy_: **widening of osteoid seams**
83
Paget's Disease
Overview
"**Osteitis Deformans**"
* **Affects 3% of the population**
* **Primarily a disease of the elderly** (seen after age 40-50)
* By age 90, it affects 10% of males and 15% of females
84
Paget's Disease
Types
* **Monostotic** (15% of cases)
* Occurs at a single site
* Most common site is the **tibia**
* **Polyostotic** (85% of cases)
* Occurs at multiple sites
* Most common sites include the **spine and pelvis**
85
Paget's Disease
Stages
1. **Osteolytic stage**
* **Osteoclast ⊕ by virus and resorbs bone**
* Bone digestion ⇒ **↑ fibrous tissue and vascularity** between the bony spicules
* Can cause **red hot skin over the bone**
* **↑ Vascularity** ⇒ ± high out cardiac failure
2. **Osteolytic / osteoblastic stage**
* **Continued bone lysis**
* **↑ osteoblastic activity** ⇒ ↑ bone formation
* Balance b/t lysis & formation abnormal
* Resulting bone is not in normal Haversian canal structure
* Abnormal mineral deposition patterns
* **Mosaic pattern is pathognomonic for Paget’s**
86
Paget's Disease
Pathogenesis
* Believed to be caused by an **infection of the osteoclast by a Paramyxovirus**
* Thick bone made w/ poor structural integrity ⇒ **deformity & fracture**
* ↑ Osteoblastic activity ⇒ **osteogenic sarcoma in 1-10% of pts**
* Longer disease duration ⇒ ↑ likelihood of eventually developing osteogenic sarcoma
* Rapid rate of bone turnover called **Matrix Metabolic Madness**
87
Paget's Disease
Clinical Manifestations
* **Highest levels of alkaline phosphatase of any bone disease**
* **Most pts asymptomatic**
* Incidental findings on XR
* **Some pts present w/ pain or bone deformity**
* _Skeletal changes:_
* **Thickening of arms, tibia, femur, pelvis, and clavicles**
* **Skull is also thickened** but d/t loss of integrity and nl structure, if you fill the skull with water it will **leak like a sieve**
88
Fracture Types
* **Closed fracture** (simple)
* Skin intact
* **Complete** vs **incomplete** (greenstick)
* **Stable fracture** ⇒ broken ends line up and are barely out of place
* **Comminuted fracture**
* Bone shatters into three or more splintered spicules
* **Compound fracture** (open)
* Penetrates skin
* Most serious due to potential for infection
89
Fracture Repair
_Healing occurs in 4 stages:_
1. **Hematoma formation**
* Blood clot @ site of fx
2. **Soft callus formation**
* ⊕ collagen production @ ends of the bone ⇒ **fibrous procallus** (10-14 days)
* Fracture stable but weak
* Poor immobilization ⇒ shearing forces ⇒ abnormal collagen formation
* _Comminuted fx_ ⇒ splinters can stop formation of fibrous and cartilaginous tissue
* _Comminuted and compound fx_ ⇒ soft tissue invasion can delay collagen deposition and healing
* Chondrocytes start to form cartilage ⇒ **cartilaginous procallus**
* Poor immobilization ⇒ ± pseudoarthrosis
* Joint space w/o cartilage or bone formation ⇒ insufficient healing
3. **Hard callus formation**
* Immature spongy bone deposited onto cartilage matrix
4. **Bone remodeling**
* Lamellar bone deposition
90
Healing Fracture
Histology
91
Fracture
Complications
* **Malalignment**
* **Comminution** w/ bone spicules at fracture site
* **Inadequate immobilization**
* **Infection** ⇒ prevents healing from taking place
