Diseases of bone

- Pyogenic osteomyelitis
- Tubercular osteomyelitis
- Syphilitic bone disease

Fractures:
 Traumatic and non-traumatic fracture
 Complete and incomplete fracture
 Closed or compound fracture
 Comminuted or displaced fractures

TUMORS OF BONE
A. Primary tumors

Histologic type Benign Malignant

Haematpoietic (40%) -------------------------- 1. Myeloma
2. Malignant lymphoma
Chondrogenic(20%) 1. Osteochondroma 1. Chondrosarcoma
2. Chondroma 2. Dedifferentiated
3. Chondroblastoma chondrosarcoma
4. Chondromyxoid 3. Mesenchymal
fibroma chondrosarcoma
Osteogenic (19%) 1. Osteoma 1. Osteosarcoma
2. Osteoid osteoma
3. Osteoblastoma
Fibrogenic tumors 1. Fibrous cortical defect 1. Fibrosarcoma
2. Non-ossifying fibroma 2. Malignant fibrous
3. Fibrous histiocytoma histiocytoma
4. Desmoplastic fibroma
Tumors of unknown origin 1. Giant cell tumor
2. Unicameral bone cyst
3. Aneurysmal bone cyst
Neuroectodermal ---------------------- 1. Ewing’s Sarcoma
Notochordal ---------------------- 1. Chordoma

B. Secondary tumors

OSTEOMYELITIS
 Osteomyelitis denotes inflammation of bone and marrow.
 Virtually it always implies infection
 Osteomyelitis may manifest as a primary solitary focus of disease or
 It may be a complication of systemic disease
 All types of organisms including virus, parasites, fungi and bacteria can produce osteomyelitis.
  But infection caused by certain pyogenic bacteria and mycobacteria are most common.
 Pyogenic osteomyelitis is almost always caused by bacteria and the organisms may reach the
bone by:
1. Direct hematogenous spread
2. Extension from a contiguous site
3. Direct implantation.
 In children’s most cases of osteomyelitis are hematogenous in origin and develops in the long
bones.
 The inciting bacteremia may stem from trivial injuries to the mucosa such as occur during
defecation or vigorous chewing of hard foods or minor infections of the skin.
 In adults, osteomyelitis occur as a complication of open fractures, surgical procedures and
diabetic infections of foot.

Microorganism involved in osteomyelitis

1. Staphylococcus is responsible for 80-90% of cases. These organism express receptors for
bone matrix components such as collagens, which facilitates their adherence to the bone
tissue.
2. Individuals with genito-urinary infection and who are IV- drug user organisms involved are E.
coli, Pseudomonas and klebseilla.
3. Mixed bacterial infection are seen in the setting of direct spread or inoculation of organsims
during surgery.
4. H. influenza and group-B streptococci are frequent pathogen in the neonatal period.
5. Salmonella infection in patients with sickle cell disease

Location of infection within a bone is influenced by osseous vascular circulation which varies with
age.
1) In the neonate, the metaphyseal vessels penetrate the growth palate resulting in frequent
infection of the metaphysis, ephiphysis or both.
2) In children localization of infection in the metaphysis is typical.
3) In adults after growth plate closure, the bacteria seed into the epiphysis and subchondral
region.

Pathogenesis

Once in the bone, the bacteria proliferate and induce acute inflammatory reaction

The entrapped bone undergoes necrosis within first 48 Houirs

The bacteria and inflammation spread within the shaft of the bone and may percolate
through the haversion system

It then reaches the periosteum

v
In children the periosteum is loosely
v attached to the cortex ; so sizeable periosteal
abscessvmay form
v
That can tract for long distance along
v the bone surface
v
v
v
v
 Lifting the periosteum further impairs the blood supply to the affected region
v
The ischemic injury causes segmentalv bone necrosis
v
The dead pieces of bone is known vas sequestrum
vv
Rupture of periosteum leads to softvv tissue abscess
vv
And eventually formation of a draining
vv sinus
v
v
 In infants and uncommonly in adults the infection of epiphysis may spread to the joint
producing suppurative arthritis.
 Which can cause destruction of articular cartilage and permanent disability
 An analogous process involves the vertebra in which the infection destroys the hyaline cartilage
and the plate of IV disc and spreads into adjacent vertebra.

Morphology
Morphological changes depends on the stage :
1. Acute
2. Sub-acute or chronic and
3. On the location of infection

 Neutrophilic infiltration.
 Necrosis of bone cells and marrow ensues within first 48 hours.
 Bacteria and inflammation spread longitudinally and may percolate throughout the haversian
systems to reach the periosteum.
 Sub-periosteal abscess formed.
 Sequestrum formation occur.
 Draining sinus is formed.

 After 1st week CICs become more numerous and their cytokines stimulate
1. Osteoblastic resorption of bone,
2. Ingrowths of fibrous tissue and
3. Deposition of reactive bone at the periphery
4. When the newly deposited bone forms a sleeve of living tissue around segment of
devitalized infected bone, it is known as involucrum.

 Brodie abscess is a small intra-osseous abscess, that frequently involvers the cortex and is
walled off by reactive bone,
 Sclerosing osteomyelitis of Garre: Typically develops in the jaw and is associated with extensive
new bone formation and obscure much of the underlying osseous structure.

Clinical features of osteomyelitis

  Hematogenous osteomyelitis may manifest as an acute systemic illness with malaise, chills,
fever, leukocytosis, marked intense to throbbing pain over the affected region.
 The presentation may be subtler with only unexplained fever particularly in infants or only
localized pain without fever in adults.
 Characteristic radiographic finding is a lytic focus of bone.

Pattern of distribution
1. Femur – 23 to 29%
2. Tibia – 19 to 26 %
3. Pelvic girdle – 3 to 14%
4. Humerus – 5 to 13%
5. Fibula – 4 to 10%
6. Calcaneus – 4 to 11%
7. Spine – 1 to 4 %
8. Radius – 1 to 4 %
9. Clavicle – 1 to 3%
10. Metatarsal – 1 to 2%
11. Hand – 1 to 2 %
12. Ulna – 1 to 2%
13. Ribs, sternum, mandible, maxilla, skull, patella, talus – <1%

Complications of osteomyelitis
1. Chronic osteomyelitis
2. Pathologic fracture
3. Secondary osteomyelitis
4. Endocarditis
5. Sepsis
6. Development of squamous cell carcinoma in the sinus tract

Tubercular osteomyelitis
 The patients are usually adolescents or young adults
 It may also develop in the immune-compromised individuals.
 Approximately 1 to 3% of individuals with pulmonary or extra-pulmonary tuberculosis has
osseous infection.
 The organism are usually blood borne and orginate from a focus of active visceral disease during
initial stages of primary infection.
 Direct extension from a pulmonary focus to a rib or from trachea-bronccial lymph node to
adjacent vertebra.
 The bony infection is usally solitary and in some cases may be the only manifestation of the
disease.
 Individuals with immune-deficeincy may have multiple bone involvement
  The spine (40% cases, especially of thoracic and lumber vertebra) followed by knee and hip are
the most common site of skeletal involvement.
 TB osteomyelitis is more destructive and resistant to control than pyogenic osteomyelitis.
 In the spine (pott’s disease) the infection breaks through IV disc to involve multiple vertebra and
extends into soft tissue forming abscess.

Clinical features
- Pain on motion
- Localized tenderness
- Low grade fever, chills and weight loss

Complications
1. Scoliotic or kyphotic deformities
2. Spinal cord compression
3. TB-arthritis
4. Sinus formation
5. Psoas abscess
6. Amyloidosis

Skeletal syphilis
 In congenital syphilis the bone lesions begin to appear in the 5th month of gestation and are fully
developed at birth.
 It produces osteo-chondritis and periostitis.
 In acquired bone disease develop in the tertiary stage. ( within 2 – 5 years)
 Gummata appear in the nose palate skull and extremities.
 Syphilic saber shin is produced by reactive periosteal bone deposition.

Osteosarcoma
- Osteosarcoma is defined as a malignant mesenchymal tumor in which the cancerous cells
produce bone matrix.
- It is the most common malignant tumor of the bone, exclusive for 20% of primary bone
caners.
- It shows bimodal age distribution:
o 75% occurs in patients younger than age 20 years
o A smaller 2nd peak in the elderly

- The tumor arise from metaphyseal region of long bone of the extremities in about 60% of
the cases.
- Any bone may be involved however in persons with age 25 years and the incidence in flat
and long bone is almost equal.

Locations
1. Usually arise in the metaphyseal region of long bone of extremities
 2. 50% in the knee i.e. Distal femur or proximal tibia

Pathogenesis
o Patients with germline mutations of retinoblastoma gene are at 1000 times greater risk
o Loss of heterozygosity, structural rearrangements or point mutations in the RB gene also
present in 60 – 70% of patients
o Abnormalities in the gene such as p53 , CDK4, p16, INK4A have also been implicated.

Morphology
 Subtypes of osteosarcoma
a. According to anatomic position of bone involved
1. Intramedullary
2. Intracortical or
3. Surface tumor
b. Histologic variants
1. Osteoblastic
2. Chondroblastic
3. Fibroblastic
4. Telangiectatic
5. Small cell
6. Giant cell
c. Degree of differentiation
1. Primary (underlying bone is UR)
2. Secondary (pagets disease, irradiation, benign tumors)

Grossly:
 Bulky tumors are gritty, gray white
 The tumor destroy the surrounding cortex and produce soft tissue mass
 The tumor spreads extensively in the medullary canal, infrequently they penetrate epiphysis
plate.
 Areas of hemorrhage and cystic change may be present.

Microscopically:
 The tumor cells vary in size and shape and frequently have large hyper-chromatic nuclei
 Bizzare tumor giant cells are common as are mitosis.
 The formation of bone by tumor cell is characteristics of osteosarcoma.
 The neoplastic bone has a coarse, lacelike architecture but is also deposited in broad sheets or
as primitive trabeculae.

Histopathologic findings
 Other matrices like cartilage or fibrous tissue may be present in varying amounts.
 Vascular invasion is present in upto 50%
Clinical course:
1. Osteosarcoma is present as painful and progressively enlarging mass.
2. Sometimes a sudden fracture of the bone is the first symptom,.
3. Codman triangle: the tumor frequently breaks through the cortex and lifts the periosteum. It is a
triangular shadow between the cortex and the raised ends of periosteum on x-ray. It is
characteristic but not diagnostic of this tumor.

*The neoplasm spreads through blood stream

*About 10 – 20 % patients has pulmonary metastasis.
*Long term survival is 60 – 70% with the use of recent treatment
*Chemotherapy and limb salvage therapy.

OSTEOMA
 Round to oval sessile tumor that project from the sub-periosteal or endosteal surfaces of the
cortex.
 Usually solitary and are detected in middle aged individuals.
 Most often on or inside skull or facial bone.
 They are composed of woven or lammelar bone, deposited in cortical pattern with haversian
systems.
 Impinge on eye or brain or sinus obstruction.

OSTEOID OSTEOMA
 It is benign tumor and is less than 2 cm in greatest dimension about 70% patients in their teens
and twenties.
 It can arise in any bone, 50% cases involve femur and tibia. Most frequently it involves the
cortex less frequently within medullary cavity.
 Osteoid osteomas are painful lesions and the pain is due to elaboration of prostaglandins. The
pain is nocturnal and is relieved by aspirin.

CHONDROSARCOMA
 It is a malignant tumor of cartilage forming tissue.
 Commonly arise from central portion of the skeleton including pelvis, shoulder, ribs.
 The clear cell variants originates in the epiphysis of long tubular bones.

Classification of chondrosarcoma
According to sites
1. Central or intramedullary
2. Peripheral or juxtacortical or surface
Histological types
1. Myxoid and or hyaline (conventional, 90%)
 2. Clear cell
3. Dedifferentiated
4. Mesenchymal

Morphological findings of chondrosarcomas

1. Conventional chondrosarcomas composed of malignant hyaline or myxoid cartilage.
2. Nodules of gray-white, translucent tissue, glistening tissue.
3. Predominantly myxoid variants, the tumor are viscous and gelatinous.
4. Spotty calcification are typically present.
5. Central necrosis may create cystic space.
6. The adjacent cortex is thickened or eroded
7. The tumor grows with broad pushing fronts.

1. Well moderately or poorly differentiated types. These varies in degree of cellularity, cytologic
atypia and mitosis.
2. Low grade lesions demonstrate mild hypercellularity and the chondrocytes have plump,
vesicular, hyper-chromatic nuclei with small nucleoli.
3. Two or more nuclei per cell and two or more cell per lacuna.
4. Portion of the matrix frequently mineralized and the cartilage undergo endochondral
ossification.
5. High grade tumors show extreme pleomorphism with bizarre tumor giant cells and mitosis.

EWING’S SARCOMA
 Ewing’s sarcoma is a primary malignant small round cell bone tumor of children.
 It is a member of the family of small round cell neoplasm of bone and soft tissue generally
known as primitive neuro-ectodermal tumor(PNET)
 Ewing’s sarcoma and PNET accounts for 6-10% of primary malignant bone tumor

Location
1. Are in the diaphysis of long tubular bones, especially femur and the flat bones of pelvis.

Clinical features
1. Painful enlarging masses
2. The affected site is tender, warm and swollen.
3. Some have systemic manifestation that mimic infection, including fever, raised ESR, anemia and
leukocytosis.
4. Plain radiographs shows destructive lytic tumor with permeative margins that extends into the
surrounding soft tissues. The characteristic periosteal reaction produces layers of reactive bone
deposited in an onion-skin fashion.

Morphology
Grossly: The tumor is soft, tan-white and frequently contains areas of hemorrhage and necrosis.
Histology:
- Sheets of uniform small, round cells that are slightly larger and more cohesive than
lymphocytes.
- They have scant cytoplasm, which may appear clear (rich in glycogen)
- Homer-Wright rosettes indicates a greater degree of neuroectodermal differentiation.
(round groupings of cells with a central fibrillary core)
- Little stroma present
- Geographic necrosis may be prominent
- Few mitotic figures relative to dense cellularity of the tumor.

Small round cell tumors

1. Ewing’s sarcoma
2. Rhabdomyosarcoma
3. Neuroblastoma
4. Nephroblastoma
5. Retinoblastoma
6. Hepatoblastoma
7. Medulloblastoma

Giant cell tumor

GCT contain profuse multi-nucleated osteoclast-type giant cell, hence often called osteoclastoma.
Location
- Involves both epiphysis and metaphysis of long bones in adults.
- In adolescents, they are limited to the metaphysis.
- Majority arise in the distal femur and proximal tibia
- But virtually any bone can be affected.
Radiological findings of GCT
1. Most tumors are solitary but multi-centric lesion may occur especially in the distal extremity.
2. The tumor erode into the subchondral bone plate and destroy the overlying cortex.
3. Radiologically an entirely lytic, expansile lesion in the epiphysis usually without bone sclerosis or
periosteal reaction.

Microscopic findings of GCT

 The tumor is composed of uniform oval mononuclear stromal cells that constitute the
proliferating component of the tumor.
 Scattered with in the background and are numerous osteoclast like giant cells.
 The giant cells have 100 or more nuclei.
 Hemorrhage, necrosis, hemosiderin deposits and reactive new bone formation are common.

Giant cell containing lesions of bone

1. Giant cell tumor of bone
 2. Aneurysmal bone cyst
3. Metaphyseal fibrous defect
4. Giant cell reparative granuloma
5. Giant cell containing fibrous lesions.

Common bone diseases (genetic defects)

 Disease associated with defect in extra-cellular structural protein:
1. Osteogenesis imperfect (type-1 collagen)
2. Achondrogenesis-II (type-2 collagen)
3. Hypochondrogenesos
4. Sticker syndrome
5. Multiple epiphyseal dysplasia
6. Schmid metaphyseal chondrometaplasia
 Developmental anomalies in bone cell, matrix and structure due to transcription factor
producing abnormalities
1. Synpolydactyly
2. Waardenberg syndrome
3. Greig syndrome
4. Oligodnitia
5. Nail patelle syndrome
 Developmental anomalies associated with abnormal proliferation and maturation of
chondrocytes.
1. Brtachdactyly
2. Achondroplasia
3. Hypochondroplasia
4. Thanatrophic dwarfism
5. Crouzon syndrome

1) Defect in metabolic pathway

a. Osteoporosis
2) Osteoclast dysfunction
a. Paget’s disease
3) Abnormal mineral hemostasis
a. Ricket and osteomalacia
b. Renal osteodystrophy
c. Hyperparathyroidism
Other diseases
4) Infections
a. Pyogenic osteomyelitis
b. Tubercular osteomyelitis
c. Skeletal syphilis
5) Fracture of bone
6) Tumors of bone
OSTEOPOROSIS
 Osteoporosis is a disease characterized by increased porosity of bone resulting from reduced
bone mass.
 The associated structural changes predispose the bone to fracture.
 Osteoporosis may be:
1. Generalized
2. Localized

Categories of generalized osteoporosis

 Primary
1. Post-menopausal
2. Senile
 Secondary (endocrine disorders)
1. Hyperparathyroidism
2. Hypothyroidism and Hyperthyroidism
3. Hypogonadism
4. Pituitary tumors
5. Diabetes type-1
6. Addison’s diseases
 Secondary osteoporosis (neoplasia)
1. Multiple myeloma
2. Carcinomatosis
 Secondary osteoporosis( gastrointestinal)
1. Malnutrition
2. Malabsorption
3. Hepatic insufficiency
4. Vit-C, Vit-D deficiency
 Idiopathic
 Secondary due to drugs
1. Anticoagulatns
2. Corticosteroids
3. Anticonvulsants
4. Alcohol
 Miscellaneous causes
1. Osteogenesis imperfect
2. Immobolization
3. Pulmonary disease
4. Homocystinuria
5. Anemia

PATHOGENESIS

Genetic factors
Physical activity Peak bone mass Nutrition

Menopause

-Decereased serum estrogen

-Increased serum IL-1, IL-6 and TNF level
-Increased expression of RANK, RANKL gene
-Increased osteoclast activity

Osteoporosis

Aging

-Decreased replication of osteo-progenitor cells

-Decreased synthetic activity of osteoblasts
-Decreased activity of matrix bound growth factors
-Increased osteoclast activity
-Reduced physical activity

Osteoporosis

Clinical features of osteoporosis

 Vertebral fractures more frequently occur in thoracic or lumbar region are painful
 Multilevel fractures can cause significant loss of height
 Various deformities like lumber lordosis, Kyphoscoliosis
 Fracture of neck of femur, pelvis or spine

Morphology
 In senile osteoporosis, the cortex is thinned to subperiosteal and endosteal resorption by
increased osteoclastic activity
 And the haversian system are widened
 In the vertebral bodies trabecular plates become perforated and thinned.

OSTEOMALACIA
 Refers to accumulation of un-mineralized bone matrix. (comparable to rickets in a young
person.)
 Resulting from a diminished rate of mineralization. Bone matrix is formed but calcification is
incomplete
 Caused by congenital or acquired metabolic abnormality.
PAGET DISEASE (Osteitis deformans)
 Collagen matrix madness
 Furious osteoclastic bone resorption
 Period of hectic bone formation
 Finally marked diminution of bone cell activity

Paget’s disease is divided into

1. Initial osteolytic stage, followed by
2. Mixed osteoblastic-osteoclastic stage ends with predominance of osteoblastic activity
3. A burnt out quiescent osteoclerotic stage
The net effect is a gain in bone mass.

Clinical features
 Mild adulthood
 Five to eleven percent of population of European populations are affected
 It affects one bone (monostotic) and affects tibia, ilium, femur, skull, vertebra or humerous
 It may affect multiple bones (polyostotic in 15%) spine pelvis and skull
 Paid due to micro-fracture and bone overgrowth compress spinal or cranial nerves
 Serum alkaline phosphate increases and urinary excretion of hydroxyproline.

Histopathology
 It is due to skin viral infection by a para-myxovirus.
 Virus induce release of IL-6 from infected cells
 Osteoclasts are abnormal in this disease and are hyper-responsive to vitamin-D and RANKEL
1. Histologic hallmark is the mosaic pattern of lamellar bone
2. Haphazardly oriented units of lamellar bones.
In the initial phase osteoclast cells may be seen in the resorption pits.

HYPERPARATHYROIDISM
 May be primary or secondary
 Entire skeleton is affected. Severe form is known as Osteitis fibrosa cystica
 Secondary hyper-parathyroidism is less severe and skeletal abnormalities are milder
 The bone loss predisposes to micro-fracture and secondary hemorrhages that elicit an influx of
multinucleated macrophages and an ingrowth of reparative fibrous tissue creating a mass of
reactive tissue known as brown tumor.

Morphology
 Increased osteoclastic activity
 Sub-periosteal bone resorption thinning of cortex
 Thinning of cortices , loss of lamina dura around the teeth
 X-ray shows cortical cutting cones on the radial aspect of index and middle finger
 Decreased bone density or osteopenia
RENAL OSTEO-DYSTROPHY
 All skeletal changes in chronic renal disease is called renal dystrophy. It is characterized by
1. Osteoclastic resorption of bone (mimicking ostitis fibrosa cystica)
2. Delayed matrix mineralization
3. Osteosclerosis
4. Growth retardation
5. Osteoporosis

FRACTURES
It can be defined as loss of bone integrity due to mechanical injury and/or diminished bone strength.
 Traumatic and non-traumatic fractures are the most common pathologic condition of bone.
 Bone is unique in its ability to repair itself.
 It can completely reconstitute itself by reactivating the process that normally occurs during
embryogenesis.

The speed of return depends upon

1. Age of patient
2. Nutrition of the patient
3. Severity/ type of the fracture
4. Vascularity of the area
5. Type of the treatment

Fractures may fail to heal because of

1. Improper immobilization
2. Complete devascularization
3. Persistent infection and
4. Interposition of soft tissue
5. Inadequate levels of Ca2 & PO4
6. Vitamin deficiency
7. Diabetes mellitus

Fractures can be classified as

1. Complete fracture
2. Incomplete fracture
3. Closed fractures – the overlying tissue is intact
4. Compound fracture – fracture site communicates with skin surfaces

Types of fractures
1. Comminuted fracture ----- when the bone is splintered or displaced, when the ends of the bone
is not aligned
2. Pathological fracture ----- if break occurs in a bone already altered by a disease processes
3. Stress fracture ----- is a slowly developing fracture that follows a period of increased physical
activity.
Stages of repair
 Formation of soft tissue callus--------------------------
Immediately after fracture rupture of blood vessel results in a hematoma. This fills the fracture
gap and surrounds the area of bone injury.
The blood clot provides a fibrin mesh which helps to seal off the fracture site.
Influx of inflammatory cells, fibroblasts and new capillary vessels occur into the fibrin mesh.
 Platelets and inflammatory cells release PDGF, TGF-β, FGF and other cytokines.
Activation of osteoprogenitor cells in the periosteum and medullary cavity and surrounding soft
tissue.
Stimulation of osteoblastic and osteoclastic activity
At the end of first week, the hematoma is organized and the fractured ends of the bone are
remodeled.
This fusiform and predominantly uncalcified tissue is called soft tissue callus.

OSTEOPETROSIS
 Also known as marble bone disease refer to as group of rare genetic disease
 It is characterized by reduced bone resorption and diffuse symmetrical skeletal sclerosis due to
impaired formation or function of osteoclasts.
 The bones are abnormally brittle and fracture easily like a piece of chalk.

Pathogenesis :
Defect in CA2 gene which encode enzyme carbonic anhydrae
CA is required by osteoclasts and renal tubular cells.
Absence of CA2 prevents osteoclasts from acidifying the resorption pits and solubilizing hyrdoxy-
apetite. It also blocks acidification of urine.
It may be autosomal dominant or recessive

STAGES OF BONE REPAIR AFTER FRACTURE

Stage 1 : Hematoma is formed immediately after fracture. The hematoma takes a fusiform shape.
Stage 2: Acute inflammation occurs due to trauma. Fluid exudates and neutrophil infiltration occurs.
Stage 3: Macrophage activity increases, Neutrophils are replaced by macrophages (demolition phase)
Stage 4: Formation of granulation tissue by the end of first week. The hematoma is organizing,
neovascularization and fibrogenesis occur from periosteum and endosteum. This is called a soft tissue
callus.
Stage 5: woven bone and cartilage formation:
Osteoblasts and chondroblasts are derived from periosteum. The calcified hard tissue is called bony
callus, which consists of three zones:
a. External callus : sub-periosteal
 b. Internal callus : in medullary cavity
c. Intermediate callus : in the central area
Stage 6: Lamellar bone formation –
The woven bone and cartilage are removed with the formation of lamellar bone.
Stage 7: Remodeling – the original bone structure is formed and osteoblastic laying down of bone.