Non-Metabolic Bone Disease Flashcards
What is the ultimate difference in scarring which occurs between healing by first and second intention?
First intention - less granulation tissue is formed, often full regeneration is possible if wound is made from fully regenerative cells, and ECM remodelling occurs overtime with accumulation of collagen.
Second intention - much larger acute inflammation, size of granulation tissue, persistence of inflammation, and MYOFIBROBLASTS will need to close the wound via wound contracture.
What is a compound fracture vs comminuted fracture vs displaced fracture
Compound = “open” fracture -> open when the overlying skin is also sliced open in the traumatic process
Comminuted - fragmented bone
Displaced - bones become malaligned -> will need surgery to realign
What is the definition of a pathologic fracture?
Fracture occurring secondary to pre-existing bone disease (i.e. Paget disease)
Occur due to minimal trauma (normally would not break the bone. I.e. fragility fractures)
What is meant by procallus and soft callus in fracture repair?
Procallus - acute inflammation and edema with phagocytosis and ingrowth of granulation tissue. This forms an organizing hematoma.
Soft callus -> first stage in formation of a bony callus -> cartilaginous scaffold assembled by activated chondroblasts. Will appear as a black area (cartilage) on X-ray
What happens in the reparative and remodelling phases of fracture repair?
Reparative - Soft callus is formed then replaced by bony callus (made from osteoprogenitor cells -> osteoblasts)
Remodeling - Takes weeks to years -> woven bone made in bony callus is replaced by lamellar bone
What are typical things which impede the normal wound healing / fracture repair?
- Infection -> local or systemic, most common
- Inadequate blood supply to granulation tissue / callus
- Decreased host immune response (needed for inflammation, callus formation and remodeling)
- Wound disruption -> if not debrided, or mechanical stressors
- Vitamin C or D deficiency
What can happen to a bone if there is excessive wound disruption?
- Delayed union or non-union - fracture pieces don’t come together
- Pseudoarthrosis - a false joint appears in bone, allowing it to bend
What is the most common way that osteomyelitis occurs / infection spreads to bone? Common spot in bone?
Minor skin or mucosal injury leads to a bacteremia which seeds bone (hematogenously spread)
Commonly seeds metaphysis, especially in children if the growth plate is open (lots of blood flow to growing growth plate, with decreased blood flow rate)
Are children or adults more likely to get septic arthritis from osteomyelitis?
Adults -> bacteria can cross the growth plate after it closes, allowing bacterial access to epiphysis
What are two situations which commonly lead to localized spread of bacteria to cause osteomyelitis?
- Diabetics - foot ulcers can allow spread to underlying bone
- Compound fracture - skin is open and can lead to direct seeding into broken bone
What is the most common causative organism of osteomyelitis? What are other possible causes in sexually active young adults and sickle cell patients?
S. aureus
However, Salmonella in sickle cell disease or N. gonorrhea are common causes in sexually active adult.
What characterizes the acute phase of osteomyelitis how might it spread to the skin surface?
Acute inflammation and exudative edema, first affecting medullary bone (Since it is so vascular), then spreads to less vascular cortical bone -> periosteum, adjacent muscle / soft tissue -> sinus tract to the skin
What forms during the acute phase of osteomyelitis and what will be seen in the lacunae?
The lacunae should become empty as the immune system sequesters off the abscess = “Sequestrum” = lytic abscess. This decreases vascular supply to the abscess.
When will the chronic phase be seen in osteomyelitis? What structure forms?
Seen with inadequate treatment or decreased host immune response
Granulation tissue influxes, along with chronic inflammatory infiltrate. Will form the involucrum -> new subperiosteal bone which surrounds the sequestrum. Sequestrum gradually resorbed by osteoclasts.
What portion of the bone will be absent from the involucrum?
The natural window where the sinus tract cut through the periosteum -> killed regenerative periosteal cells so no involucrum could be formed
What is a Brodie abscess and where is it?
A small, localized site of osteomyelitis totally surrounded by involucrum
-> typically seen in the metaphysis of children
What is sclerosing osteomyelitis of Garre?
Excessive, reparative bone formation caused by osteomyelitis which affects predominately the jaw (mandible)
Will appear like areas of Paget disease in the jaw.
What is Pott disease and what muscle is commonly involved?
Vertebral tuberculous osteomyelitis -> commonly involves iliopsoas muscle
pg. 176 of FA
How can TB osteomyelitis be told apart from regular osteomyelitis?
TB will form necrotizing granulomas
TB will also lead to increase in monocytes / lymphocyte cell count, whereas other forms of osteomyelitis are characterized by neutrophil infiltrate
What are two rarer complications of chronic osteomyelitis?
- Secondary AA amyloidosis - chronic inflammation
2. Squamous cell carcinoma - can occur with chronic sinus tract formation to skin and regeneration
What is the mechanism of the most common type of dwarfism? What’s the inheritance pattern?
FGF3 receptor mutation -> constitutive activation -> impaired growth of cartilage within the growth plate.
Lack of endochondral ossification -> failure of longitudinal growth and short limbs
inheritance = autosomal dominant with full penetrance
What are the physical features of achondroplasia? Why?
Short limbs -> lack of endochondral ossification
Large head (macrocephaly) with flat nose -> intramembranous ossification is not affected
How does the growth plate look in achondroplasia?
Looks disorganized, with cartilage growing more randomly (no nice columns of chondrocytes), going crazy. Looks a bit more hypercellular and disorganized to me than it does acellular for sure.
What does the growth plate look like in osteopetrosis? Why?
Growth plate has lots of residual cartilage which should have been resorbed but has not
-> overgrowth of atypical, malformed bone
This is due to osteoclast dysfunction, most commonly due to an autosomal dominant abnormality in carbonic anhydrase 2.
What are the consequences of bone overformation in osteopetrosis?
- Increased susceptibility to fractures with thick woven bones (Erlenmeyer flash deformity of ulna / radius)
- Narrowing of skull foramina -> cranial nerve deficits and hydrocephalus (foramen magnum narrowing)
- Obliteration of marrow space due to bone overgrowth
What will occur due to obliteration of marrow space in osteopetrosis? What is the treatment for this condition?
Anemia and pancytopenia, leading to increased susceptibility for infections.
Extramedullary hematopoiesis will cause hepatosplenomegaly.
Treatment is hematopoietic stem cell transplant -> osteoclasts are derived from monocytes.
What is osteonecrosis also called, what is it, and what are the three most common causes?
Avascular necrosis - Ischemic necrosis of bone due to compromised blood supply.
- Trauma
- Glucocorticoid use
- Excessive alcohol intake
How can direct injury to the bone vascular supply occur?
- Physical trauma
- Radiation therapy - affects vessels
- Thermal trauma - i.e. vasoconstriction / vascular injury (burns / frostbite)
Where does avascular necrosis commonly occur, and what types of emboli predispose?
Femoral head
- Fat emboli
- Air emboli - i.e. Caisson disease
- Septic emboli
What are the causes of fat emboli which cause avascular necrosis?
- Alcohol abuse -> explains alcoholism as a cause. Increases your triglyceride levels
- Corticosteroid excess -> also causes dyslipidemia
- Pancreatitis -> increased triglycerides due to circulating lipases
What conditions cause avascular necroiss by compressing the vascular supply of the bones?
- Corticosteroids and alcohol use -> increased intramedullary adiposity -> less blood can move thru
- Gaucher disease -> glucocerebrosides accumulate in bone marrow and increase interosseous pressure
Give how the following conditions predispose to AVN:
Sickle cell disease, polycythemia vera, SLE, rheumatoid arthritis, infection, pregnancy, malignancy
Sickle cell - sludging of microvasculature
P vera - sludging of microvasculature
SLE - vasculitis, hypercoagulability
RA - vasculitis
Infection - hypercoagulability
Pregnancy - hypercoagulability and impaired venous drainage by uterus
Malignancy - hypercoagulability
Why does chemotherapy and bisphosphonates predispose to AVN?
Osteoclasts do not function well after chemotherapy.
Bisphosphonates decrease ability of osteoclasts to remodel jaw which is subjected to repeated trauma -> increased risk of necrosis
What is seen microscopically in AVN?
Necrotic bone, usually affecting cancellous (very vascular) bone first -> leads to empty osteocyte lacunae. Hematopoeitic cells and adipose tissue become necrotic, with saponification.
Creeping substitution -> osteoclasts rapidly breaking down bone, and osteoblasts proliferating and trying to keep up but cannot replace fast enough due to poor blood supply.
What are the consequences of medullary infarction in AVN? Where in the bone does this occur?
Often stable, producing few symptoms unless alot of bone is involved.
Occurrs in the metaphysis or diaphysis.
What are the symptoms of a subchondral infarction and where does this occur? How does this appear grossly? What are the complications?
“Subchondral” = below articular cartilage.
Very painful, especially with activity and weight-bearing. Can result in fractures and secondary osteoarthritis.
Occurs in the epiphysis of long bones, especial femoral head. There will be a pale, wedge-shaped infarct (bone is an end-arterial system).
What radiographic sign is often seen with avascular necrosis causing subchondral infarction?
Crescent sign -> separation of pale infarcted bone from the articular cartilage
-> comes loose due to necrosis of underlying bone.
There will be a tiny area of lucency around the femoral head where it occurred.
Who tends to get non-hematopoietic bone neoplasms and is it more common for them to be benign or malignant?
benign»_space; malignant
Tends to occur in children / young adults because they have the rapidly dividing bone
If it occurs in older adults, it is probably associated with a pre-existing bone disease (i.e. Paget) or inflammatory bone disorders, and is more likely malignant
What is the most common malignancy of bone and where does it tend to occur / why?
Metastases to bone
Tends to occur multifocally in the axial skeleton and limb girdles -> sites of red bone marrow in adults, which have a high vascularity (increased hematogenous seeding).
What causes osteolytic bone lesions in malignancy, and which cancers often spread to bone?
Caused by caner cells producing factors which cause osteoclasts to lyse bones
Cancers spreading to bone are usually carcinomas -> lung, breast, prostate, kidney, thyroid, but can be sarcomas
Remember prostate cancer is BLASTIC
Where do primary non-hematopoietic bone tumors typically occur and how do they often present?
Typically in the long bones of the extremities, where growth is occurring.
There are some exceptions to this rule.
Presentation is variable -> incidental radiography finding in asymptomatic patient to a palpable mass / pathologic fracture
Do benign or malignant tumors often have sclerotic borders around them? How is the ultimate decision of benign / malignant made?
Typically benign tumors are well-delineated like this because they are slow-growing.
Ultimate decision is made on collaboration between radiologist and pathologist. Often, the pattern of mineralization is characteristic of specific tumors and cannot be seen by the pathologist alone.
What is prognosis of sarcomas based on?
Unlike carcinomas, both the stage AND the grade are prognostically very important for non-hematopoeitic malignancies of bone
What is typically seen on peirpheral smear of multiple myeloma? Why?
Red blood cell rouleaux formation -> high amount of proteins in the plasma (due to monoclonal spike) will lead to loss of repulsion of RBCs from eachother -> become sticky and form stacks
Often due to over-excretion of AL amyloid (light chains) which can cause Bence Jones proteinuria with cast nephropathy
Do benign bone tumors typically transform into sarcomas? How are they treated?
No, it is very rare, but is more common in syndromes associated with multiple benign lesions.
They can be observed, but are often treated with conservative excision, especially if diagnosis is uncertain
What is an osteoma and where does it typically occur?
A benign, slowly enlarging tumor of cortical bone, usually arising on flat b ones of skull.
Usually asymptomatic
What is an osteoid osteoma and who tends to get it? Where does it appear?
A benign tumor of osteoblasts, mostly occuring in adolescent males
Tends to occur in lower extremity long bones, in the cortical region (i.e. diaphysis of femur)
How does an osteoid osteoma appear radiologically?
Small (<2cm), well-circumscribed, intracortical mass
The center is radiolucent -> composed of osteoid and woven bone made by osteoblasts
The outside is radiodense -> margin is formed by reactive lamellar bone
What are the clinical symptoms of osteoid ostoma and what is the treatment?
Presents as bone pain which is worse at night. The pain is released by aspirin (or other NSAIDs). **
Complete excision of nidus (middle) is curative, and reactive bone will return to normal.
What is an osteochondroma also called? Is it common? When does it arise? What is the feared complication?
Exostosis = “bone growing out”
It is the most common benign tumor of bone
It commonly arises sporadically in males <25. It can be multiple in younger children a hereditary autosomal dominant form
Complication: Cap can become chondrosarcoma
Where do osteochondromas typically form, and what are they? When do they stop growing?
Most commonly the knee, they are polypoid growths from the metaphysis (often distal femur) growing directly from the growth plate, with a hyaline cartilage cap.
They are attached to a stalk, and grow by normal endochondral ossification, contiguous with underlying bone. They stop growing at puberty (when growth plate fuses)
What is a enchondroma and who tends to get them?
Benign tumor of cartilage.
Cartilage tumors are rule-breakers -> tend to occur in young to middle-aged adults (20s-30s)
Where do enchondromas tend to appear and what do they look like on X-ray?
Tend to appear in the medulla of small tubular bones of hands and feet, contiguous with metaphysis.
They appear as well-circumscribed, mostly radioLUCENT masses made of hyaline cartilage, surrounded by a thin bony rim.
Hands may be large if there are multiple.
What is a fibrous cortical defect vs non-ossifying fibroma?
These are both extremely common developmental abnormalities due to excessive proliferation of fibrous tissue in bone marrow
Fibrous cortical defect - small, incidental lesions which usually regress
Nonossifying fibroma - Large lesion, may persist
Where do fibrous cortical defects and nonossifying fibromas arise, and what problems do they cause?
Often arise in the metaphysis of long bones
Problem: since they are just made of fibroblasts, large ones (nonossifying fibromas) can weaken the bones and make it susceptible to fractures
How does a nonossifying fibroma appear on X-ray?
A well-delineated, subcortical radioLUCENT mass (since fibroblasts are not calcified), often with a rim of activated macrophages and thin reactive bone.
What has gone wrong in fibrous dysplasia?
Typically an GNAS1 (G protein locus) gain of function mutation which induces cellular proliferation, and interrupts proliferation from osteoprogenitor cells (fibroblast-like) to osteoblasts
Dysplasia = abnormal growth. Does NOT indicate premalignant.
Is fibrous dysplasia most often monostotic or polyostotic? Who gets the latter?
Usually monostotic and sporadic.
Polyostotic in:
- McCune Albright syndrome - pg53
- Mazabraud syndrome -> in association with soft tissue myxomas
What are the features of McCune Albright syndrome?
Usually polyostotic fibrous dysplasia, precocious puberty, and large, irregular cafe au lait macules (these are often the size of multiple dermatomes. Much larger than NF-1)
Remember the G protein is fucked up because G protein is also messed up in pseudohypoparathyroidism which causes ALBRIGHT hereditary osteodystrophy
Where do fibrous dysplasias commonly arise, and what is one unique place?
They typically arise on long bones of extremity / pelvis
Also arise on RIBS and CRANIOFACIAL bones -> two quite unique places
How do fibrous dysplasia look under the microscope and histologically?
Microscope - haphazard mixture of fibroblasts (immature osteoprogenitor cells) with scattered immature bony trabeculae (osteoblast differentiation was inhibited)
X-ray - “ground-glass” appearance, as the lesions have slightly more character than non-ossifying fibromas since there is some bone present
What are the complications of fibrous dysplasia?
Pathologic fractures and malignant transformation is possible
What are the two types of bone cysts?
- Solitary bone cyst - single cyst filled with clear, serous fluid which often regresses
- Aneurysmal bone cyst - Rapidly-growing, locally aggressive, multilocular (multiple cavities), filled with blood (aneurysmal). Tends to be expansive and surrounded by an egg-shell like bony rim.
Where do bone cysts typically arise? Should you excise them?
Typically arise in the long bones of children
Aneurysmal bone cyst is frequently excised since it is so aggressive
What is the most common primary non-hematopoietic bone malignancy? What syndromes is it assocatied with?
Osteosarcoma
Associated with mutations in Rb and TP53, which are cell cycle regulators:
- Familial Retinoblastoma
- Li Fraumeni syndrome
Where does osteosarcoma tend to arise and what age groups are susceptible?
Tends to arise in metaphysis of the long bones, especially the knees
- Teenagers - teenage boys during their growth spurt
- Older adults - >65 years old, with predisposing bone disease -> i.e. Paget disease
Where does osteosarcoma spread grossly and microscopically?
Starts in medullary (trabecular) bone, as these are anaplastic osteoblasts.
Eventually extends into cortical bone, periosteum, and surrounding soft tissues, but the EPIPHYSIS is spared in the young (no blood vessels thru).
Microscopically - pleomorphic cells producing osteoid
How does osteosarcoma often appear radiologically?
Codman triangle - from malignancy lifting the periosteum off the surface of the bone
Sunburst pattern on X-ray - from reactive subperiosteal bone formation leading to fragmented densities
What are the clinical features of osteosarcoma? How is this cancer treated?
High alkaline phosphatase level (many osteoblasts), early hematogenous spread to the lungs (sarcomas have vascular invasion, direct to lung spread)
Treat with limb-salvage surgery / tumor resection and chemotherapy
What bone cancer is typically found in middle-aged to older males, and affects especially the proximal skeleton (pelvis > shoulders)?
Chondrosarcoma. Note, this affects axial skeleton much more than an enchondroma would (which affects hands and feet)
How aggressive is chondrosarcoma typically, and what is the treatment?
Typically a low-grade, indolent malignancy which makes it difficult to treat with chemotherapy (only rarely a sarcoma can arise within it).
Thus, treatment is complete excision, which often requires radical pelvic or shoulder excision with wide margins taken.
What bone tumor is related to a primitive neuroectodermal tumor? Who is it diagnosed in?
Ewing sarcoma
Diagnosed in white male children <15 years old
Where does Ewing sarcoma arise and what is its growth pattern?
Arises in the diaphysis of the long bone, beginning in central medullary cavity and invading through the cortex and periosteum into surrounding soft tissue.
What genetic change is associated with Ewing sarcoma?
11;22 translocation since #33 is Patrick Ewing’s number
Leads to fusion of EWS gene with a transcription factor gene that stimulates cell proliferation
What is seen microscopically and radiographically in Ewing sarcoma?
Microscopically - sheets of small round blue cells (neuroectodermal tumor) -> looks alot like lymphoma too
Radiographically - “Onion-skin” proliferation of subperiosteal bone as it pushes outward. Also Codman’s triangle triangle can be seen.
What is the prognosis of Ewing sarcoma, and what condition could it mimic?
Since it is so destructive, it causes lots of inflammation and may cause fever -> similar to osteomyelitis
It responds well to chemo / radiation since it is so aggressive
What is giant cell tumor caused by and is it benign or malignant?
Caused by neoplastic osteoblast precursors which stimulate osteoclast proliferation -> osteoclasts are the reactive giant cells to the malignancy “osteoclastoma”
It is a very aggressive benign entity, which can be classed as malignant, but rarely metastasizes.
Who tends to get giant cell tumors and where does it arise?
Tumor of young ADULTS (AFTER closure of epiphyseal plate, 20-40 years old)
Arises in the EPIphysis of the long bones, especially around the knee
What is the growth pattern of giant cell tumors? What can be seen on X-ray?
Soap bubble appearance on X-ray: Hemorrhagic, cystic mass which is osteolytic.
often hemorrhagic, with prominent giant cells.
Tumor remains localized in epiphysis of long bones, causing considerable destruction and frequently recurring after conservative excision.
