Acute Bone Pathologies (Fractures, Necrosis, Tumors, Osteomyelit
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acute pathologies of bone and cartilage
Overview
- Bone fractures (and their repair)
- Osteonecrosis (aka avascular necrosis)
- Osteomyelitis (especially from staph aureus)
- Bone Tumors (notably, the malignant bone tumor: osteosarcoma).
Bone Fractures & Healing
- Closed, simple = Skin is intact
- Compound = Skin is open
Closed/Simple
Nondisplaced
- Nondisplaced means there isn't any angulation or separation in the plane of cleavage of bone.
- Complete fractures means there is discontinuity between the fragments of bone on both sides of the fracture.
- Transverse
- Runs at a right angle to the length (the long axis) of the long bone.
- Linear
- Run longitudinal along the length of the long bone.
- Oblique
- Run at a 45 degree angles to the long axis.
- Spiral
- Spiral fractures appear similar, but encircle the long axis of the long bone.
- Comminuted
- Comprises 3 or more fragments of bone (like shards of bone).
- Greenstick fracture
- A partial fracture.
- Buckle fracture
- aka, Torus fracture: buckling of the cortex (this is a common form of forearm fracture).
- Segmental fracture
- A segment of bone shaft is isolated between proximal and distal fracture lines.
- The fracture is open (aka compound), which means there is disruption of the overlying skin.
healing fracture
We show a histopathologic slide of a healing fracture.
- Can see the fracture line and the forming callus.
Four key stages of bone healing
- Inflammation
- This occurs at < 48 hours. When the bone fractures and the blood vessels are disrupted, hematoma is formed, the inflammation stage is triggered.
- Soft Callus
- ~ 72 hours. Hematoma is replaced by granulation tissue.
- Hard Callus
- Soft callus transitions to woven bone.
- Remodeling
- Woven bone transitions to lamellar bone.
Many of the acute bone pathologies present with bone fracture.
osteonecrosis
Aka avascular necrosis
- The femoral head is the most common site of disease pathology.
- Osteonecrosis causes a painful infarction of the medullary cavity of the bone with and without the bone cortex.
- Vascularization of the femoral head is key aspect of this disorder:
- The lateral femoral circumflex artery supplies the femoral neck.
- The medial femoral circumflex artery supplies the femoral head but that it is supplied, primarily, by lateral epiphyseal arteries.
- Key causes of osteonecrosis with the acronym: CASTLS
- Corticosteroids
- This is by far and away the most common cause and an important warning in both acute steroids and chronic administration.
- Alcoholism, which is likely related to the "T", which stands for….
- Trauma
- Sick cell disease is the "S".
- Legg-Calvé-Perthes disease, an idiopathic juvenile avascular necrosis of the femoral head, which means there is vascular insufficiency of the femur head (again, this region of bone is particularly susceptible to vascular infarction).
- Slipped capital femoral epiphysis for the last "S" for, which is exactly what its name says: the femoral head (at the epiphysis) slips off the neck of the femur (usually spontaneously in adolescents during periods of rapid growth).
- Other less common causes but notable causes include:
- Dysbarism ("the bends")
- Gaucher disease.
osteomyelitis
- Inflammation of bone secondary to bone infection.
We see an axial slice of a lumbosacral vertebral column.
- The vertebral body (VB), a portion of the vertebral arch (VA) (a transverse process), which encases the spinal canal (SC), which houses nerve roots.
- Can see the looming paraspinal abscess that has formed within the paraspinal muscles and invades the veretebral column, causing osteomyelitis.
- Pyogenic osteomyelitis is most often caused by staph aureus, which we show as gram + cocci in clusters.
- We've just walked through a classic pathogenesis of osteomyelitis – staph aureus builds up in surrounding tissue and invades bone: the inciting incident can be minor (a skin infection, a dental procedure or profound (as in this case), a spine procedure)
Other key organisms that cause osteomyelitis are:
- TB (mycobacterium), which we show on acid-fast staining.
- When it involves the spine is called Pott disease (aka tuberculous spondylitis) due to infection of the vertebral bodies that can destroy their way through the spine.
- Syphilis, which we show on dark-field microscopy; it's an important cause of both congenital and acquired osteomyelitis.
We address the osteomyelitic changes with these infections further in the microbiology/immunology sections.
Bone-forming tumors
- Osteosarcoma is a classic example of the sunburst pattern of a dreaded malignant bone tumor.
- Key kinds of bone tumors and then their localization and histological features:
- Key bone forming tumors are osteoid osteomas and their vertebral spine counterparts: osteoblastomas.
- They are benign and arise between 10 – 20 years of age.
- Malignant bone tumors that also arise between 10 – 20 years of age.
Cartilage-forming tumors
Osteochondromas
- Key cartilage-forming tumors are osteochondromas.
- They are benign and tend to occur in boys who are less than 25 years old.
- Whereas chrondosarcomas are malignant and arise between 40 – 60 years of age.
Bony tumors of unknown origin
Ewing sarcoma
- Key bony tumors of unknown origin are Ewing sarcoma, which is a malignant tumor that affects boys less than 15 years old.
- And giant cell tumor (aka osteoclastoma, because of its osteoclast-like appearance), which is a benign tumor that affects individuals who are 20 – 40 years of age.
Bone Anatomy
In order to understand the localization and histopathology of these bone tumors, we need to review some basic bone anatomy. Generally, bone divides into two forms:
Bone Histologies
- Compact bone (aka cortical bone), the outer dense bony layer.
- Spongy bone (aka trabecular, cancellous, or medullary bone), the inner bony meshwork.
Bone Regions
- Delineate the diaphysis, which is the shaft.
- Comprises the marrow cavity.
- Metaphyses comprises spongy bone.
- Epiphyses, which are the ends – the sites of articulation.
- The epiphyseal line (the ultimate regression of the growth plate) separates the epiphysis and metaphysis.
Collagenous Structures
- The bone is lined in the following collagenous structures:
- Periosteum along the shaft, which is derived from a condensation of outer connective tissue.
- Endosteum, centrally, which is derived from derived from a condensation of inner connective tissue, and which helps separate the marrow cavity, internally, from the compact bony matrix that encapsulates it.
- Articular cartilage, which is derived from hyaline cartilage.
- In osteoarthritis, this cartilage has worn out and the epiphyses from adjacent bones grind on one another.
The Marrow Cavity
- The marrow cavity is filled with red marrow (hematopoetic marrow, which are red blood cell and white blood cell precursors) and yellow marrow (adipose tissue).
We show a histological slide of normal marrow:
- Ttrabeculae at the edge of the slide.
- Hhematopoetic cells and then one of the fat droplets.
- At birth, marrow is red, but progressively transforms to yellow marrow with age.
We show a slide of hypocellular marrow:
- It's easy to appreciate that the ratio of fat droplets to hematopoetic cells is much greater here than in the normal marrow.
- The ribs, vertebrae, sternum, and ilia, which maintain their red marrow longer – we can remember this by the fact that the sternum is a good site for bone marrow aspiration.
- This transformation is a dynamic process based on the demands for red blood cells.
- Certain states produce hypercellular marrow, such as chronic hypoxemia, which will cause conversion of bone marrow from yellow back to red.
- Notice the abundance of hematopoetic cells in comparison to fat cells.
Bone Tumor Localization & Histopathology
- Osteoid osteomas are benign tumors that grow out of cortical bone (usually of the femur or tibia) and present with nocturnal pain.
- Alternatively, their spine counterpart, osteoblastoma, grows out of the vertebral arch (the posterior spine), specifically the laminae and pedicles of the spine.
- We show a histopathological slide of osteoblastoma, which demonstrates its haphazard trabeculae of woven bone, lined with prominent osteoblasts – indicate the bone trabeculae and rimming of prominent osteoblasts.
- Again, malignant transformation rarely occurs and osteoid osteoma is treated with radiofrequency ablation whereas osteoblastoma is typically excised.
- We show a malignant osteosarcoma grow out of the medullary cavity at the metaphysis in a sunburst pattern.
- Specifically, it extends from medulla to lift periosteum (sunburst pattern).
- There are several key predisposing factors to osteosarcoma:
- Retinoblastoma
- TP53 mutation (germline 53 mutation), which is present in ~ 70% of families with LiFraumeni syndrome (a hereditary cancer predisposition syndrome, specifically to osteosarcoma, soft tissue sarcomas, leukemias, brain, breast, and adrenal cortical carcinomas).
- Paget disease of bone
- Additional tumor suppressor and cell cycle gene mutations can lead to osteosarcoma, including: INK4a, MDM2, CDK4.
- Osteochondroma is a benign bony exostosis with cartilaginous cap that arises from the metaphysis near the growth plate (especially near the knee). Exostosis refers to new bone formation.
- Ewing sarcomas are malignant tumors that typically arise from the diaphysis of long bones, specifically from the medullary cavity.
- We show that the tumor expands outward to invade the cortical bone, periosteum, and soft tissue that surrounds it.
- Ewing sarcoma histopathology: anaplastic small blue cells and the small clear cytoplasm surrounds them.
- Importantly, note that from a genetics standpoint, this tumor is most commonly associated with a (11;22)(q24;q12) translocation.
- The translocation generates an in-frame fusion of the Ewing sarcoma gene on chromosome 22 to the FLI1 gene.
- Giant cell tumors typically arise from the epiphysis of long bones (again, like osteochondromas around the knee – distal femur/proximal tibia) that destroy the overlying cortex and form a bulging soft tissue mass with a thin shell of bone.
- We show a histopathological slide of a giant cell tumor.
- Many nuclei.
- Indicate that these are osteoclast-type multinucleated giant cells, which is, again, why they are referred to as osteoclastomas (vs the osteoid osteomas, which had prominent osteoblastomas).
- They are said to have a "soap-bubble appearance on XRay".
- They express high levels of RANKL, which shouldn't come as a surprise, as we learned about in its relation to osteoclast activity in the chronic bone pathologies tutorial.
- We learn about chordoma in the neuroembryology section as it relates to persistence of notochord tissue – it typically arises in the clivus and sacrum.