Fracture Types and Repair

Fractures

• Fractures are defined as the loss of bone integrity

Fracture Classification

• Simple fracture: Overlying skin remains intact
• Compound fracture: Bone communicates with the skin surface
• Comminuted fracture: The bone is fragmented
• Displaced fracture: The ends of the bone at the fracture site are not aligned
• Stress fracture: Bone is damaged due to increased physical activity and repetitive loads
• Greenstick fracture: Occurs in infants with soft bones and extends only partially through the bone
• Pathologic fracture: Results from a disease process such as a tumor

Fracture Repair

• Bone repair is genetically mediated
• Immediately post-fracture, hematoma formation provides a fibrin mesh for fracture sealing
• Inflammatory cell influx, fibroblast ingrowth, and capillary proliferation lead to granulation tissue formation
• Degranulated platelets and inflammatory cells release PDGF, TGF-β, and FGF
• Osteoprogenitor cells are activated in the periosteum, medullary cavity, and surrounding soft tissues, leading to osteoclastic and osteoblastic activity.
• Soft Tissue Internal Callus or Procallus: Provides anchorage but lacks structural rigidity for weight bearing
• Within 2 weeks of injury, activated osteoprogenitor cells form subperiosteal trabeculae of woven bone in the medullary cavity
• Procallus transforms into bony callus and enables fx stabilization
• Endochondral ossification: Bridging fx bone ends with a contiguous network of newly deposited bone trabeculae increases mineralization, stiffness, and strength of callus to bear weight
• Healing completes through restoration of the medullary cavity
• Inadequate immobilization results in delayed union or nonunion of the fracture
• If nonunion persists, the malformed callus undergoes cystic degeneration with a luminal surface lined by synovial-like cells, forming a false joint or pseudoarthrosis

Osteomyelitis

• Osteomyelitis: Inflammation of bone and marrow, secondary to bacterial, viral, fungal, or parasitic infection
• In about 50% of patients, the specific organism is unidentified
• Pyogenic osteomyelitis is a bacterial infection that spreads hematogenously, extends from a contiguous site or results from direct implantation, such as traumatic injury.
• Staphylococcus aureus accounts for 80% to 90% of culture-positive pyogenic osteomyelitis cases
• Escherichia coli, Pseudomonas, and Klebsiella are etiological agents also
• Haemophilus influenzae and group B streptococci occur in neonates
• Sickle cell disease predisposes to Salmonella infection

Acute Osteomyelitis

• Proliferation and recruitment of neutrophils within 48 hours, along with necrosis of bone cells and marrow.
• Bacterial infection leads to a subperiosteal abscess when bacteria infect the periosteum
• Periosteal lifting impairs blood supply
• Necrosis and soft tissue abscesses follow periosteal rupture, which opens to the skin as draining sinuses
• Dead bone, or sequestrum, forms, crumbles, and releases fragments into sinus tracts, leading to a chronic stage called CLOACAE in 5-25% of cases
• Chronic inflammation stimulates bone resorption, fibrosis, and reactive bone deposition
• New bone forms a living shell, called an involucrum, around devitalized, infected bone.
• X-ray may reveal a lytic focus of bone destruction surrounded by sclerosis
• Draining osteomyelitis reveals a drainage tract in the subperiosteal shell of viable new bone, or involucrum, and inner native necrotic cortex, or sequestrum

Seronegative Spondyloarthropathies

• Undefined microbial antigens cross-react with musculoskeletal system components to cause this Seronegative Spondyloarthropaty
• The triggering antigens cause T-cell responses
• The conditions are immune-mediated
• This is a heterogeneous group of disorders
• Absence of rheumatoid factor
• Pathologic changes occur in ligamentous attachments, not the synovium
• Sacroiliac joint involvement
• Association with HLA-B27
• Bony proliferation leading to ankylosis (fusion)
• Examples include ankylosing spondylitis, infectious arthritis, and reactive arthritis

Ankylosing Spondylitis

• Characterized by destruction of articular cartilage and bony ankyloses
• Sacroiliac and vertebral apophyseal joints located between tuberosities and processes are involved
• Low back pain and spinal immobility typically manifest during the second and third decades of life
• Approximately 90% of patients test positive for HLA-B27
• The role of HLA-B27 in the disease process remains unknown
• Infectious arthritis due to microorganisms is characterized by hematogenous dissemination, direct inoculation, or contiguous spread from soft tissue such as abscess or osteomyelitis

Reactive Arthritis (Reiter’s Syndrome)

• Reactive arthritis presents as a triad of symptoms
• The triad consists of arthritis, non-gonococcal urethritis or cervicitis, and conjunctivitis
• Mono or oligoarticular arthritis
• Triggered by intestinal infections, such as Salmonella, Shigella, and Campylobacter
• Occurs following sexually transmitted diseases and Chlamydia trachomatis infections
• Rarely, proceeds group A streptococcal infections
• The condition is RF negative and HLA-B27 positive
• Common in young adults
• 50% experience recurrent arthritis, tendonitis, lumbosacral pain
• Active disease lasting >6 months indicates chronic reactive arthritis
• Initial acute-onset asymmetric oligo-arthritis typically affects the knee and causes inflammatory low back pain
• Inflammation presents at insertions of the Achilles tendon and plantar fascia, heel swelling, digit inflammation, joint stiffness, and lower back pain.
• Extra-articular manifestations include conjunctivitis, uveitis, dysuria, pelvic pain, urethritis, balanitis, cervicitis, mucosal ulcers, skin rashes, and cardiac valvular disease

Lyme Arthritis

• Lyme arthritis is caused by the spirochete Borrelia burgdorferi spread by deer ticks (Ixodes)
• It is the leading arthropod-borne disease in the US, particularly in New England, the mid-Atlantic states, and the upper Midwest
• Classic Lyme disease affects multiple organ systems and has three clinical stages
• Early localized stage presents with an initial skin infection, followed by organism dissemination to other cutaneous sites, cranial nerves, heart, and meninges
• Untreated or late disseminated disease presents as migratory arthritis (Lyme arthritis) in 80% of cases, months after infection, lasting weeks to months
• Anti-Borrelia antibodies are present in serology
• Arthritis occurs in 10% of Borrelia infections, and is often treated at earlier stages, and cured
• One or two joints are affected i.e. knees, shoulders, elbows, and ankles
• Lyme rash often presents as a bull's-eye with circles around the middle
• The rash is typically round, red, and at least 2 inches across
• It grows to 10-12 inches across within days
• It is warm to the touch
• Not itchy or painful
• Occurs anywhere on the body
• Lyme arthritis is a sparse superficial and deep lymphocytic infiltrate
• It has an unremarkable epidermis
• Epidermal and or dermal necrosis
• Treatment involves doxycycline, amoxicillin, or cefuroxime axetil and yields cure rates of 90%

Fibrous Dysplasia

• Fibrous dysplasia is a benign tumor
• All components of normal bone
• Structures do not differentiate into mature structures
• Occurs during skeletal development
• Pathogenesis involves various somatic gain-of-function mutations in GNAS1.
• Results in constitutive activation of G s protein, which results in cellular proliferation and inhibition of osteoblast differentiation,
• Presence of intramedullary lytic lesions with bowing and cortical bone thinning occurs
• Histologically, curvilinear trabeculae of woven bone exhibit moderately cellular fibroblastic proliferation
• Histo: No prominent osteoblastic rimming
• Clinically exhibits: pain, swelling, pathologic fractures, and severe bone deformity.
• Early Monostotic fibrous dysplasia occurs during early adolescence and affects femur, tibia, ribs, jawbones, and calvarium.
• Asymptomatic, can cause pain, discrepancies in limb length, and pathologic fracture.
• Treated by curettage which is commonly recurrent
• Polyostotic fibrous dysplasia develops earlier and presents later in adulthood, affecting the femur, skull, and tibia
• Craniofacial involvement occurs
• It is progressive with crippling deformities, and fractures;
• Bisphosphonates can reduce bone pain
• Rare malignant transformation into sarcoma can occur
• McCune-Albright Syndrome: Syndrome involves precocious sexual development, especially in girls
• Additional features: hyperthyroidism, pituitary adenomas, growth hormone secretion, and primary adrenal hyperplasia
• A unilateral cafe-au-lait spot lesion occurs on the same side of body

Simple Bone Cyst (Unicameral Bone Cyst)

• Incidental finding
• Not a neoplasm
• Fluid-filled lesion with a fibrous lining
• Occurs during the first 20 years of life
• Located near the growth plate of long bones
• May reoccur or disappear with maturity
• Cyst enlargement may cause a fracture

Aneurysmal Bone Cyst (ABC)

• Multiloculated blood-filled spaces affect all ages, mostly in adolescence and often in femur, tibia, or vertebral body
• X-ray shows; expansive, well-circumscribed lytic lesion has well-defined margins and shows central lysis with thin sclerotic shell of reactive bone,
• Multiple blood-filled cystic spaces divided by thin, tan-white septa composed of plump spindle cells, multinucleated osteoclast-like giant cells, and reactive woven bone lined by osteoblasts 70% have chromosome 17p13 rearrangements within plump spindle cells resulting in the fusion of the USP6 coding region with promoters of genes highly expressed in osteoblasts
• Clinic Manifestations: Localized pain and swelling with resulting lesion and nerve compression
• Benign but locally aggressive
• Treatment involves curettage or excision with a 10% to 50% recurrence rate

Ganglion & Synovial Cysts

• Ganglion cysts are 1.5 cm near a joint capsule/tendon sheath, common on wrists, firm, fluctuant, pea-sized translucent nodules
• Composed of cystic or myxoid connective tissue degeneration
• The cyst wall lacks a cell lining and it may be multilocular
• Synovial cysts are herniation of synovium through a joint capsule or massive enlargement of a bursa
• Popliteal Synovial Cyst, known as Baker cyst, is associated with rheumatoid arthritis
• The cyst's lining resembles synovium
• The Cyst and synovium :hyperplastic and Cyst contains inflammatory cells and fibrin

Primary Bone Tumors

• Rare and outnumbered by metastases and affect long bones of extremities
• Asymptomatic, identified incidentally
• May be painful, slow-growing, or cause pathologic fracture
• Clinical presentation, radiographic appearance, patient age, lesion location, and microscopic appearance are important for determination
• In the first three decades, these affect skeletal growth rate
• Manifestations occur in Distal femur and proximal tibia
• Benign are more common than malignant Bone Tumors
• Age is the most important clinical factor for diagnosis
• Painful lesions indicate: malignancy or locally aggressive tumor

Benign Tumors

• Osteoid osteoma and osteoblastoma are histologically similar tumors that differ in size, site of origin, and symptoms
• Malignant transformations are rare
• Round-to-oval in shape, well-circumscribed masses, with hemorrhage and tan tissue
• Micro: trabeculae of woven bone rimmed by one layer of prominent osteoblasts
• The connective tissue exhibits dilation and congested capillaries
• Reactive bone surrounds the actual neoplasm, or nidus a small mineralized radiolucent core
• Osteoid osteoma can be treated by radiofrequency ablation
• Osteoblastoma: curettage or en bloc excision removes large pieces of tissue

Osteoid Osteoma

• Benign with no malignant potential
• It is less than 2 cm in size
• Those under 25 years old are affected
• Occurs in long bones and on the surface of facial cones or skull
• Gardner’s Syndrome can cause it: Familial Adenomatous Polyposis + osteomas and soft tissue tumors
• It is slow-growing, and has no clinical significance unless there is obstruction or cosmetic issues
• Characterized by Nocturnal bone pain relieved by Aspirin and NSAIDs due to an excess of prostaglandin E2 produced by a proliferating osteoblast
• Clinical Presentation: A thick rim of reactive cortical bone, it can be only found upon investigation

Osteoblastoma

• Greater than 2cm in size
• More common in males under 25 years old
• Arises in spine
• Pain which is not nocturnal and will not be relieved by aspirin or other NSAIDS

Osteochondroma (Exostosis)

• It is common
• Mass attached to the skeleton by a bony stalk capped by cartilage.
• 85% are solitary/sporadic
• 15% of the AD multiple hereditary exostosis syndrome
• Patients may be single or have multiple solitary osteochondromas
• Occurs in late adolescence or early adulthood
• Men affected more commonly than women
• Occurs in bones of endochondral origin
• Occurs in the metaphysis near the growth plate of long tubular bones
• Palpable to the touch
• Slow-growing and cause pain through nerve impingement
• Histology: disorganized growth plate, undergoes endochondral ossification
• The cartilage cap is lined by perichondrium, and is contiguous and mature

Chondroma (Enchondroma)

• Benign tumor of hyaline cartilage: in medullary cavity (enchondromas) and on bone surface ( juxtacortical chondromas).
• Patients aged 20-50+
• Asymptomatic but can cause painful or pathological fractures
• Well-circumscribed nodules usually 3cm
• Gray-blue, translucent cut surface.
• Heterozygous mutations in IDH1 and IDH2 genes
• Histology: hypocellular lesion with hyaline cartilage. Chondrocytes are generally normal
• If periphery exhibits endochondral ossification, a peripheral endochondral ossification must be noted
• Circumscribed lucency appears on x-ray with central irregular calcifications, a sclerotic rim, and intact cortex
• Treatment: Usually observation or curettage
• Rare for chondromas to undergo sarcomatous transformation outside of Ollier disease and Maffucci syndrome

Ollier disease and Maffucci syndrome

• Characterized by nonhereditary disorders characterized by multiple enchondromas
• Enchondromas confined to one side and limbs.
• Increased risk chondrosarcoma at about 25-30% near 40 years of age
• Increased risk gliomas, pancreatic and juvenile granulosa cell tumors of the ovary
• Syndromes can exhibit multiple spindle cell hemangiomas
• Patients are at greater risk for other developing malignancies, including brain gliomas

Giant Cell Tumor (Osteoclastoma)

• It is Rare to find benign tumors made of multinucleated, osteoclast-type giant cells which means it is locally aggressive
• 4% metastasize to lungs or regress spontaneously
• rarely fatal
• knee, involving distal femur or proximal tibia are affected
• Patients experience, arthritis-like symptoms, and pathologic fractures
• May destroy the overlaying cortex resulting in bulging soft tissue mass
• Macroscopically, they are reddish-brown masses that undergo cystic degeneration
• Histology: uniform oval mononuclear tumor cells and abundant osteoclast-type giant cells with 100 or more nuclei with necrosis and mitotic activity
• X-ray: "Soap Bubble" indication
• Therapy: curettage, and 40-60% of the locally treated cases will reoccur

Osteosarcoma

• Most common primary malignant tumor of the bone at 20%
• Bimodal distribution with those occurring before 20 years of age, and a smaller peak in older adults
• Related to Paget's disease or bone infarcts
• Caused by Prior radiation
• More prevalent in males
• Prefers the metaphyseal region of long bones.
• ~50% of near the knee in distal femur or proximal tibia
• The tumors are Bulky, gritty, with gray-white color, hemorrhage and tumors
• Destroy the cortices produces soft tissues masses and extend into the medullary canal replacing hematopoietic Marrow
• Pleomorphism or large hyperchromatic nuclei with bizarre tumor giant cells and abundant mitoses Extensive necrosis with intravascular invasion
• Composed of malignant tumor cells that make unmineralized or mineralized osteoid bone
• All cases of tumors are assumed to have occult metastases at the time of its diagnosis
• Can affect many Hematogenous metastasis, such as lungs, bones, brain and more.
• 5-year survival rate of <20 with metastatic, recurrent, and secondary osteosarcoma

Clinical and Genetic Features;

• Pain and path fractures
• It has a peak onset in fast growing individuals during Adolescents.
• in a Growth Plate and rapidly expanding bones
• Genetic Ab with Chrom aberrations are usually mutated such as: RB with 70% or sporatic OST
• Germin Mutation w TP to those with the Li Fraumell Syndrome for example cancer in breast, brain cancers
• CDAKNZA encodes w/ 2 Tumor Suppresses that Inacti Xray: destructive, mixed lytic and blastic mass infiltrative The cortex lifts and breaks resulting Reactive periosteal formations Sun burst stretched- fibers form rapidly

Ewing Sarcoma

Malignant and and primitive tumor cells which make 6- 10% primary malignant bone tuma Most occur with children and affects of those 80% are under the age of 20. Boys has greater chance with it (African and Asian) Diaphysis of the long tuma the femurs humerus and the ribs Pain, Systemic symptoms fever and and inflammation and the ESR and more. Tumos are lytic and deposit

Chondrosarcomas

• Enlarging and most are malignant Conventional clear and variant tumors. Patients older than 40 and man will twice the rate and spread as foci

Metastatic Bone Tumors

• Affects Metastatic Cancers & primary bone, direct extention Mechanisms for tumors include: lymphatic, dissemination, and/or hematogenous intraspinal seeding and Adults: skeletal metastases from Prostate, breast, kidney, and lung cancers and with Children with: neuroblastoma, Wilms Osteosacoma is in all X ray: may lysis the forms