Skeletal Syphilis and Osteomyelitis Complications

Bone Composition

• Bone consists of 65% inorganic elements like calcium hydroxyapatite, and 35% organic components like cells and proteins.

Organic Components

Osteoprogenitor Cells

• Pluripotent mesenchymal stem cells located near bony surfaces.

Osteoblasts and Surface Lining Cells

• Synthesize, transport, and arrange the matrix proteins.
• Initiate the process of mineralization.

Osteocytes

• More numerous than osteoblasts in a ratio of 10:1.
• Control second-to-second fluctuations in serum calcium and phosphorus levels.

Osteoclasts

• Responsible for bone resorption.

Proteins

• Osteoblast-derived proteins include Type 1 collagen, cell adhesion proteins, osteopontin, calcium-binding proteins, osteonectin, proteins involved in mineralization, osteocalcin, enzymes like collagenase and alkaline phosphatase, growth factors, and cytokines.
• Proteins concentrated from serum include ẞ2-microglobulin and Albumin.

Bone Growth and Development

• Homeobox genes provide the blueprint for skeletal morphogenesis.
• Mesenchymal cells differentiate into chondrocytes and osteoblasts.
• Chondrocytes lead to cartilage formation.
• Osteoblasts lead to bone formation.

Primary Center of Ossification

• The periosteum in the midshaft produces osteoblasts that deposit the beginnings of the cortex.

Secondary Center of Ossification

• A similar sequence of events in the epiphyses removes cartilage, entrapping a plate of the cartilage model between expanding ossification centers, forming the physis or growth plate.

Developmental Abnormalities in Bone Cells, Matrix, and Structure

• Defects can occur in nuclear proteins and transcription factors, hormones and signal transduction mechanisms, extracellular structural proteins, folding and degradation of macromolecules, and metabolic pathways.
• Development anomalies includes failure of bone development such as congenital absence of a phalanx, rib, or clavicle; formation of extra bones such as supernumerary ribs or digits; fusion of adjacent digits known as syndactyly; development of long spider-like digits; failure of closure of the spinal column and skull known as craniorachischisis.

Achondroplasia

• The most common disease of the growth plate and a major cause of dwarfism.
• Involves a defect in paracrine cell signaling.
• Manifests as a reduction in the proliferation of chondrocytes in the growth plate (FGFR3).
• Results in shortened proximal extremities, a trunk of relatively normal length, and an enlarged head with bulging forehead and conspicuous depression of the root of the nose.

Thanatophoric Dwarfism

• Most common lethal form of dwarfism.
• Caused by a mutation in FGFR3.
• Leads to micromelic shortening of the limbs, frontal bossing with relative macrocephaly, a small chest cavity, and a bell-shaped abdomen.
• Histologic examination of the growth plate shows diminished proliferation of chondrocytes and poor columnization in the zone of proliferation.

Type 1 Collagen Diseases (Osteogenesis Imperfecta)

• Also known as brittle bone disease.
• Involves mutations in the genes coding for the α1 and α2 chains of the collagen molecule.
• Results in cortical thinning and attenuation of trabeculae.
• May cause blue sclerae, hearing loss, and dental imperfections like small, misshapen, and blue-yellow teeth.

Mucopolysaccharidoses

• Group of lysosomal storage diseases caused by deficiencies in enzymes that degrade dermatan sulfate, heparan sulfate, and keratan sulfate.
• Skeletal manifestations result from abnormalities in hyaline cartilage, such as the cartilage anlage, growth plates, costal cartilages, and articular surfaces.
• Characteristics include short stature, chest wall abnormalities, and malformed bones.

Osteopetrosis

• Also known as marble bone disease or Albers-Schönberg disease.
• Involves reduced osteoclast bone resorption, leading to diffuse symmetric skeletal sclerosis.
• There are four types: infantile malignant osteopetrosis, type II carbonic anhydrase deficiency, and autosomal-dominant types I and II.
• Bones lack a medullary canal, with bulbous and misshapen ends in long bones, known as Erlenmeyer flask deformity.
• Neural foramina are small, compressing exiting nerves.
• Primary spongiosa persists, filling the medullary cavity, leaving little room for hematopoietic marrow and preventing mature trabeculae formation.
• Bone is not remodeled and remains woven in architecture.

Diseases with Decreased Bone Mass

• Includes Osteoporosis.

Diseases Caused by Osteoclast Dysfunction

• Includes Paget Disease.

Diseases Associated with Abnormal Mineral Homeostasis

• Includes Rickets and Osteomalacia, Hyperparathyroidism, and Renal Osteodystrophy.

Osteoporosis

• Characterized by increased porosity of the skeleton due to reduced bone mass.
• Pathogenesis:
  • Age-related changes.
  • Reduced physical activity.
  • Genetic factors.
  • Nutritional state.
  • Hormonal influences.

Paget Disease (Osteitis Deformans)

• Characterized by collage of matrix madness.
• Stages:
  • Osteolytic.
  • Mixed osteoclastic-osteoblastic stage.
  • Osteosclerotic.
• Results in gain in bone mass.
• Pagetic bone is enlarged with thick, coarsened cortices and cancellous bone.

Distribution

• Monostotic: 15%.
  • Commonly affects tibia, ilium, femur, skull, vertebra, and humerus.
• Polyostotic: 85%.
  • Commonly affects pelvis, spine, and skull.
• Axial skeleton or proximal femur: 80%.
• Uncommon in ribs, fibula, and small bones of the hands and feet.

Clinical Manifestations

• Pain - most common symptom.
• Leontiasis ossea - Bone overgrowth in the craniofacial skeleton.
• Platybasia - invagination of the base of the skull and compression of the posterior fossa structures..
• Severe secondary osteoarthritis.
• Chalkstick-type fractures in long bones of the lower extremities.
• Compression fractures of the spine lead to spinal cord injury and kyphoses.
• High-output heart failure or exacerbation of underlying cardiac disease.

Complications

• Benign lesions: giant cell tumor.
• Giant cell reparative granuloma.
• Extraosseous masses of hematopoiesis.
• Sarcoma: accounts for 0.7-0.9% of all patients, and 5-10% with severe polyostotic cases.
• Can include osteosarcoma, malignant fibrous histiocytoma, or chondrosarcoma, that arise in the long bones, pelvis, skull, and spine.

Rickets and Osteomalacia

• Involve a defect in matrix mineralization due to lack of vitamin D or disturbances in its metabolism.

Rickets

• Occurs in children, leading to deranged bone growth and skeletal deformities

Osteomalacia

• Occurs in adults where bone formed during remodeling is undermineralized, results in osteopenia and predisposes to insufficiency fractures.

Hyperparathyroidism

Primary Hyperparathyroidism

• Autonomous hyperplasia or a tumor (adenoma) of the parathyroid gland.

Secondary Hyperparathyroidism

• Caused by prolonged states of hypocalcemia resulting in compensatory oversecretion of PTH.

Osteoclastic Activity

• Increased osteoclast activity leads to decreased bone mass.
• The entire skeleton is affected, leading to fractures and deformities.
• Caused by the stress of weight bearing, resulting in joint pain and dysfunction.

Cortical Bone

• Cortical bone (subperiosteal, osteonal, and endosteal surfaces) is affected more than cancellous bone.
• Thinned cortices and the loss of the lamina dura around the teeth.
• The x-ray pattern is often identified along the radial aspect of the middle phalanges of the index and middle fingers.

Cortical Cutting Cones

• Composed of a spearhead arrangement of osteoclasts that bore along and enlarge haversian and Volkmann canals.

Dissecting Osteitis

• Occurs in cancellous bone where osteoclasts tunnel into and dissect centrally along the length of the trabeculae, creating the appearance of railroad tracks; results in decreased bone density, or osteopenia

Osteitis Fibrosa Cystica

• Also called von Recklinghausen disease of bone.
• Often severe hyperparathyroidism.
• Hallmark includes increased bone cell activity, peritrabecular fibrosis, and cystic brown tumors, where reactive tissue is created by the influx of influx of multinucleated macrophages and an ingrowth of reparative fibrous tissue.

Renal Osteodystrophy

• Characterized by increased osteoclastic bone resorption.
• Delayed matrix mineralization (osteomalacia).
• Osteosclerosis.
• Growth retardation.
• Osteoporosis.
• Two Types:
  • High-turnover osteodystrophy characterized by high increased bone resorption and formation
  • Low-turnover or aplastic disease, which include adynamic bone and osteomalacia.

Fractures

• Complete or incomplete.
• Classified as closed (simple) or compound in which the fracture site communicates with the skin surface.
• If comminuted, the bone is splintered
• If displaced, the ends of the bone at the fracture site are not aligned.

Pathologic Fracture

• A break that occurs in bone already altered by a disease process.

Stress Fracture

• Slowly developing fracture that follows a period of increased physical activity when the bone is subjected to new repetitive loads

Osteonecrosis

• Also called avascular necrosis resulting from ischemia in medullary cavity of the metaphysis or diaphysis and the subchondral region of the epiphysis.
• Mechanisms include:
  • Fracture.
  • Corticosteroids.
  • Thrombosis and embolism.
  • Vessel injury (secondary to vasculitis, radiation therapy).
  • Increased intraosseous pressure with vascular compression.
  • Venous hypertension.

Disorders Associated with Osteonecrosis

• Idiopathic causes, trauma, corticosteroid administration, infection, dysbarism, radiation therapy, connective tissue disorders, pregnancy, Gaucher disease, sickle cell and other anemias, alcohol abuse, chronic pancreatitis, tumors, and epiphyseal disorders.

Characteristics of Medullary Infarcts

• Necrosis is geographic, involving cancellous bone and marrow.

Subchondral Infarcts

• Necrosis involves a triangular or wedge-shaped tissue segment, with the subchondral bone plate as its base and the center of the epiphysis as its apex.

• Dead bone has empty lacunae, surrounded by necrotic adipocytes that frequently rupture and release fatty acids, which bind calcium and form insoluble calcium soaps that can persist for life.

• Creeping substitution occurs when necrotic trabeculae are not resorbed by osteoclasts but act as scaffolding for new living bone deposition.

  • The pace of effectiveness is too slow in subchondral infarcts, leading to eventual collapse of necrotic cancellous bone, distortion, fracture, and sloughing of articular catilage.

• Subchondral infarcts cause chronic pain initially associated with physical activity, becoming progressively more constant with secondary changes; often collapse and can predispose severe seconday osteoarthritis.

• Medullary infarcts are clinically silent unless large, and occur in Gaucher disease, dysbarism, and hemoglobinopathies; remain stable over time and rarely become sites of malignant transformation.

Infections

Pyogenic Osteomyelitis

• Can reach bone through:
  • Hematogenous spread.
  • Extension from a contiguous site.
  • Direct implantation.
• Staphylococcus aureus is the infecting pathogen.
• Haemophilus influenzae : is the cause in nonimmunized children.
• Escherichia coli, Pseudomonas, and Klebsiella are agents that patients with genitourinary tract infections or IV drug users are commonly infected with.
• Salmonella is the common agent in patients with sickle cell disease.

Subperiosteal Abscesses

Children have loosely attached periosteum creating the potential for subperiosteal abscesses.

• Sequestrum: dead piece of bone.
• Suppurative and ischemic injury cause segmental bone necrosis
• Draining Sinus: Rupture of the periosteum leads to an abscess in the surrounding soft tissue.
• Involucrum: Sleeve of living tissue around a segment of devitalized bone.

Complications of Chronic Osteomyelitis

• Pathologic fracture.
• Secondary amyloidosis.
• Endocarditis.
• Sepsis.
• Development of squamous cell carcinoma in the sinus tract and sarcoma

Tuberculous Osteomyelitis

• Spreads through large areas of the medullary cavity, causing extensive necrosis.
• Affects spine (especially thoracic and lumbar vertebrae), knees, and hips.
• Pott diease is the term for the infection that breaks through intervertebral discs to involve multiple vertebrae and extends into soft tissues, forming abscesses,.
• Presents with pain on motion, localized tenderness, low-grade fevers, chills, weight loss, and cold fluctuant psoas abscess.

Skeletal Syphilis

• Congenital syphilis: the manifestations localize in areas of active enchondral ossification and in the periosteum.
• Acquired syphilis: seen 2-5 years after the initial infection, affecting nose, palate, skull, and extremities.
• Sabre shin is produced by massive reactive periosteal bone deposition on the medial and anterior surfaces of the tibia.

Histology

Edematous granulation tissue containing numerous plasma cells and necrotic bone, Gummata also occur in the acquired disease; spirochetes can be demonstrated in the inflammatory tissue by special silver stains.

Bone Tumors and Tumor Like Lesions

• Can be bone-forming tumors, cartilage-forming tumors, or fibrous and fibro-osseous tumors.

Osteoma

• Bosselated, round to oval sessile tumors project from the subperiosteal or endosteal surfaces.
• Slow-growing with litte clinical significance unless when they cause obstruction od a sinuc cavity or impinge on brain and eye.
• Do not transform into osteosarcoma.

Subperiosteal Osteomas

Arise on or inside the skull and facial bones. Usually solitary and detected in middle-aged adults.

Gardner Syndrome.

Can cause multiple osteOMAS that form. Woven and lamellar bone is frequently deposited in a cortical pattern with haversian-like systems, and variants contain trabecular bone filled with hematopoietic marrow.

Osteoid Osteomas

• Less than 2cm in greatest dimension.
• 75% of patients are under 25.
• Men outnumber women 2:1.
• Predilection for the apendicular skelton as seen in 50% of femur and tibia cases.
• Located in the cortex and medullary cavity.
• Dramatic pain relieve with aspirin.
• Nocturnal with increasing severity, that is server in relation to szmall lesion.

Osteoblastoma

• More frequently involves the spine.
• Pain is dull, and non-responsive to salicylates.
• Does not iduce a marked bony response.
• Grossyl round to oval masses of hemorragic gritty tan tissue.
• Well circumsized
• Morass of randomly interconnecting trebeculae by osteoblasts

Osteosarcoma

• Malignant mesenchymal tumor where cancer cells produce bone matrix.
• Common primary malignant tumor of bone with approximately 29% of bone cancers found to be this pathology.
• Bimodal age distribution, where 75% of patients are under the age of 20 and in the elderly.
• Men are more common than women (1:6:1)
• The most common subtype is a prmiry solitary idramedially differentiated that produces a boney matric

Osteochondroma

• Also called an exostosis.
• Benign cartilagr capped outgrowth attached to the underlying bone by a boney stalk.
• Relatively common.
• Solitay or multiple.
• Long tubula bones commonly especially the the knee.
• Occasionally in pelvis scapula, and ribes..
• Rarely, short tubular bones as seen in hands and feet.
• Slow growing mass
• Painful

Chondroma

• Benign tumors of hylaine cartilge
• Found with enchondromas and withingthe medually cavity
• Found with subprriesteal or juxtacartical chondromas of bone
• Olier disease
• Multiple encodroamsesr
• Enchonromaotiossi

Chondrosarcoma

• Productikn if nreplasric cartirlfe,
• In contrast to encondhromas this rearly devolpes in destal
• Centralskeletions inclusing pelvic shoulder, and rifs

Clear vell

• Ipihyeals in log tubula bone

Firous Cordfical defect and Nonossifying fibroama

• Commo ifound in39/ 36 to S9 percent af al cjildre nold than s year.
• They devedmpemtal deficts
• All but in alcolense Sympomstatiocs Displassia has 3 patterns1) invomvment of bone (2) multapke , but never af all bones

Fibrosarcoma and Malegnent Fibous histoocytomas

• Mrtaphes of log ones and pelvic flat bone.
• Pahtoligic fractrues..
• Lytoc
• Oftem extend into the adjacent soft tissue.

Diseases of the skeletal muscle

• There are two types1
• -Type 1 sustains the force
• -NADH dark staining
• -Type 2 sudden moments

Reeactions of the muscle.fiber

• Destrucrfion af myoccyte s
• May be followed by myohpagacytostas
• Accumilationof intasytopasmic eposites
• Iffocurs when peripally locared atellite celkd proilfrate that
• Is located in the fibre in respinse to increased load either seeting of ewecise in pathologic conditions

Spinal musvulasr atomphg- iinfiantulw motor disease

• Progrresive
• Distrios anterioe horn cels
• Byegin in childohood and adolescnence
• For nxamal awinal trasnport integruty
• Weeming hoff disease
• Sma type 1. Most common form of dma
• Onset at birth
• Within 4 months of severe Hypotonia

X linked musculae

• Type two is is to be type two
• It is the most several and commen for
• There are i per 31 soo
• In the year 5 and in the year 19\y.
• Often aith elevared craetune with mnial abntmaloties on muscle
• Normal at birth
• Eraly motor nilestond are merton tonr
• Delayde waljin go

Linnb Girlde

affect pximital musculature on truink and limbs.

• Mutations on a srrcodlian protsin
• Syataines involuatry contraction
• A phenomenon whwere the disease tendd to increase in severty and age

In chanel

• Channrlpaties avutsomal dnimaital desasese

Pathogensis

• Yjperpelmis periofd paralysie
• Ithe code shreltla muscle

Oaramiyotomns

• Congneiatl
• Dirordef of childoodw herin mytonia

Mutattions inf genes that enfxides iron channel

Pathoegenes.

• Mallignant hyperwzrexioa Syndromw charscterazed thes triggered by ansteticsy

Examine long-term complications of chronic sinus tracts associated with osteomyelitis. Identify the spread mechanism of Pott disease and skeletal manifestations of congenital syphilis. Recognize skeletal syphilis findings and bone lesion characteristics.