PATHOLOGY OF BONE

Dody Novrial
Department of Pathology, JSU
 PATHOLOGY OF BONE
 Bone is a complex tissue, composed of a large and
varied cell component. All of which are subject to
disease.
 Bone has great structural stability, being in constant
turnover.
 Pathology of bone can be divided into:
• Developmental (genetic) Disorders
• Metabolic Disorders
• Inflammation
• Neoplasia
GENETIC DISORDERS

 A large number of bone disorders are of

genetic origin, either hereditary and
familial or related to new mutations.
 They range from innocuous (eg
extradigits) to the extreme (eg
ACHONDROPLASIA
ACHONDROPLASIA (dwarfism)
 An autosomal dominant disease which
often arises by spontaneous mutation
  impaired proliferation of cartilage in
the epiphyse
  resulting in decreased growth of the
long bones
 Clinically: patients have
disproportionately large head and body
with shortened arms and legs.
OSTEOGENESIS IMPERFECTA
 OI also known as Brittle Bone Disease
 Affected infants sustain Multiple
Fractures in utero or during birth 
stillborned or died in infancy
  variety of gene mutations. Some
mutations produce more lethal forms
 Wide range of severity, varying
abnormalities in the synthesis of type I
collagen (90% of bone matrix)
OSTEOGENESIS IMPERFECTA
 A number of hereditary disorders which
have common abnormalities in the
synthesis of type I collagen
  resulting the defect of the bones,
eyes, ears, joints and teeth
 Severe form: Extremely fragile bones led
to fractures before or at birth, rarely
survive, or infant with multiple fractures
Less severe form
 Present as recurrent fractures beginning
in early childhood.
 Patient have blue sclerae, abnormally
formed teeth, hearing impairment or
deafness due to fracture of middle ear
ossicles, lax joints dyslocation and
kyphoscoliosis.
 Morphologically: reduced bone mass
with very thin cortical bone.
METABOLIC DISORDERS
 Osteoporosis
 Rickets/osteomalacia
 Osteitis fibrosa cystica
 Osteitis deformans (Paget’s disease of
bone)
OSTEOPOROSIS
 Extremely common disorder characterized by
reduction of bone mass that may prejudice its
structural integrity and predispose to fracture
  asymptomatic at the onset 
microfractures, skeletal distorsion become
painfully disabling.
 The “too little bone” remains its normal
composition (normal composition of protein
matrix and mineral)
OSTEOPOROSIS, osteopenia
 The most common metabolic disease
 The incidence increases with age, typically a
disorder of post-menopausal females, although
males are equally susceptible
 Frequency of post-menopausal osteoporosis
(F:M= 2:1 to 3:1).
 25% women sustain fractures by age of 65 and
50% by age of 90.
 OSTEOPENIA (too little bone) responsible for
million fractures (mainly vertebrae, hips, wrists)
OSTEOPOROSIS

 Over 95% cases are primary type: unknown cause

 Bone remodelling occurs throughout life. Normally
balance between: bone resorbsion by osteoclasts
and restoration of the bone by osteoblasts.
 A number of factors produced locally may parcipitate
in this process: IL-1, TNF, PDGF,TGF-b,IGF-
1.(stimulate osteoclast / osteoblast activity)
  results of imbalance of bone formation &
resorbsion: loss of the bone.
 OSTEOPOROSIS
 Formation outpace resorbsion: until about age 25-
30; Balance (35-40); resorbsion outpace formation
(>40)
 F&M: 0.3-0.5% bone loss annually, after 40 F: 2-
5%. The precise basis of bone loss is unclear, it is
likely to be multifactorial.
 Estrogen deficiency in F, androgen def.in M.
Evidence: increased bone loss in young women
after oophorectomy, ability estrogen therapy to
prevent bone loss in post menopausal women.
 But once osteoporosis appears, Estrogen adm
have very little effect (may not restore bone loss)
Estrogen acts is still unkown
 Invitro: bone cells have estrogen
receptor, but cannot demonstrable
invivo. (still debate)
 Estrogen act indirectly in promoting the
release of osteoblasts activating factors
(local synthesis)??
Many other influences that may
contribute to bone loss
 Hereditary predisposision
 Increased level of PTH
 Decreased level of calsitriol
 Dietary deficiency of vit.D
 Decreased level of physical activity
 Inadequate of calcium speeds the loss,
adequate intake and absorsion of Ca
slows it
Secondary osteoporosis
 Uncommon
 Hyperparathyroidism  increased bone
resorbsion
 Increased level of glucocorticoid
(exogenous or Cushing’s syndrome) 
suppress bone formation
 Clinical Course
 Bone pain
 Microfracture or collapse of vertebral bodies. Other
common sites: lower end of radius,femoral neck (>age
70).
 X-ray: increased in radiolucency of bone
 Photon-absorptiometry,
 Quantitative the mineral content of the bone help differ
with osteopeni caused by osteomalasia or osteitis fibrosa
 Serum level of alkaline phosphatase, calcium and
phosphorus within normal limits.
 Ca supplementation, estrogen,etidronate
(biphosphonate) are used in the prevention of primary
osteoporosis
 Osteoporosis, morphology
 Systemic disorder affecting entire skeleton
 Bone loss is most severe in area that contain large
amount of trabecular bone
 Vertebra and wrist are early target. As the disease
advances  the femoral neck.
 These are often the site of fractures.
 Bone trabeculae and bone cortices are thin
resulting bone fractures.
 Although reduce mass, have same composition of
normal bone, adequate mineralisation, no
unmineralizied matrix
 OSTEOMALACIA/RICKETS
 Both due to vit.D deficiency (caused by dietary
inadequacy,lack to exposure to sun
shine,intestinal malabsorpsion,chronic renal
disease etc)
 Rickets occure in children, while osteomalacia in
adults.
 Characterized primary by inadequate
mineralization of bone matrix. No initial decreased
in mass, osteoid is correspondingly increased
 OSTEOMALACIA/RICKETS
 Characterized clinically by a “pigeon breast”
deformity of the thoraxic cage, a beading
(“rachitis rosary”) along costochondral
junctions, lumbal lordosis, and bowed legs.
 Changes in Osteomalacia similar to those
seen in rickets, but common manifestation
include frontal bossing, deformity of weight
bearing bones, and incomplete pathologic
fractures.
 OSTEOMALACIA/RICKETS
 Deficites in the mineralization of the newly
formed bone matrix  resulting soft,
osteopenic bones.
 Before epiphyse has closed  skeletal
deformities such as bowing of the leg and rib
deformity (Rickets).
 Osteomalacia (adult) marked by osteopenia
with inadequate mineralized bones,
susceptible to fractures / pseudofractures
OSTEOMALACIA/RICKETS
 The basic morphologic changes in rickets and
osteomalacia resulting from the defective
mineralization is excess of osteoid.
 This excess involve both the thickness and
proporsion of trabecular surface covered,
along with widening of osteoid seams
  bone is poorly mineralized, deformation
during skeletal growth, and fractures/ pseudo
fractures in adults.
OSTEITIS FIBROSA CYSTICA
 Associated with advanced primary
hyperparathyroidism (von Reckling Hausen)
 The basic lesion is osteoclastic resorbtion of
bone with fibrous replacements. Cysts may
form within fibrous tissue. The mandible and
maxilla are initially affected but the entire
skeletal system may develop
 So called brown tumors containing giant cells
may also be seen in advanced cases.
 OSTEITIS DEFORMANS
(Paget’s disease of bone)

 Obscure etiology (adenovirus in osteoclast/blast)

 Characterized by uncoordinated bone resorption and
absorpsion  skeletal deformation.
 3 phase: viral infection (paramyxovirus)osteolytic phase,
mixed stage (osteolysis and osteogenesis), osteosclerotic
stage
 Occur after age 40 (3% in eldery)
 Monoostotic or polyostotic, may involve any bones
 Bizzare bone modelling results in a tile-like or mozaic pattern
(pathognomonic in Paget’s d)
 May present with pathologic fracture
FIBROUS DYSPLASIA
 Uncommon disease, unknown cause 
development disorder
 Marked by focal area of disorder
maturation of bone, leaving a loose,
whorled fibrous tissue punctuated by
island and strand of woven bone.
INFLAMMATION/INFECTION
INFECTION
 2 most important type of infection: pyogenic
osteomyelitis and tuberculosis of bone.
 PYOGENIC:
1. By hematogenous spread
2. From a contiguous infection
3. Direct traumatic introduction
Haematogenous seeding most common in
developing countries.
PYOGENIC OSTEOMYELITIS
 Haematogenous osteomyelities is
caused by Staphylococcus aureus (less
frequently Pseudomonas and Klebsiella,
E coli etc).
 Mixed infections more common following
compound fractures. Anaerob frequently
associated with dental problems
PYOGENIC OSTEOMYELITIS
 Often begin in the metaphyseal region of the
long bones, where capillary flow is least active
 In adults, jaw and the spine are often the site
of infection.
 suppurative reactions  penetrate the
endoosteum and transverse the haversian
system to reach periosteum (periostitis)
subperiosteal abcess.
 Further expansion lead to single/multiple sinus
tracts into the soft tissue (sometime through
the skin)
 PYOGENIC OSTEOMYELITIS
 In adults the periosteum is tightly attached
to articular margin extension into the joint
space is uncommon
 In infant, the periosteum is attached more
losely & the epiphyseal plate is vascularized
 infection may spread either directly into
the joint space or tract along the
periosteum.
PYOGENIC OSTEOMYELITIS
 Detachment of large areas of the periosteum
 necrosis small/large fragments of the bone
(sequestrum)
 In occasional, the infection become walled
off, creating a LOCALIZED (BRODIE’S)
ABCESS  may spontanous sterilization or
become chronic nidus of infection  reactive
osteoblastic activity lead to new bone
formation  producing INVOLUCRUM that
encloses the inflammatory focus.
 PYOGENIC OSTEOMYELITIS

 Vertebral osteomyelitis: subligamentous

spread to adjacent vertebral bodies.
 Penetration into the sheaths of the psoas
muscle  infection to inguinal region.
 If the lesion does not heal, chronic
osteomyelitis may developed with continued
inflammation and sinus tract formation.
TUBERCULOSIS OF THE BONE
 Clinical problem in developing countries where
the incidence of tb still high
 Seeding bone occurs from hematogenous
route.
 Unlike pyogenic osteomyelitis, tb tend to
extend into joint spaces.
 The long bones of extremitas and spine
(POTT’S DISEASE) are favored sites.
 In spine, tb osteomyelitis can lead serious
deformities (KYPHOSIS, SKOLIOSIS) due to
destruction.
 Histologic reaction is typical of tb
NEOPLASIA
 Majority tumors of bone are metastatic, the
most common: prostate, breast, lung,
kidney,colon and thyroid.
 Most frequent site: vertebra,rib, skull, pelvis.
 Primary bone are uncommon, but importance
of several reasons:
1.Excluding multiple myeloma, 40% are
malignant.
2.Affect young person, early decade of life
3.80% occur about the knee, while amputation
was necessary, therapy was saved not only
limb but life
CHONDROGENIC TUMOR
 EXOSTOSIS (Osteochondroma)
 ENCHONDROMA
 CHONDROSARCOMA (Chondrogenic
sarcoma)
OSTEOCHONDROMA
 Also known as exostoses
 Asymptomatic, locally tender.
 Arise from abberant lateral growth of
epiphyseal cartilage,producing
mushroom shaped
ENCHONDROMA
 Benign neoplasm
 Arise within the cortex of tibia and femur
(near the end),
 Painfull, lytic lesion occur in the
diaphysis of long bones (femur and tibia
most frequently)
 Patient under age 30 (first 2 decade of
life)
CHONDROSARCOMA
 Malignant cartilagineous skeletal tumor
 Differ with Osteosarc: Rarely arise before age
35, grow slowly,prognosis much better
 Metastasis hematogenously to the lung
 5 YSR: 90% to 40%.
 Begin in the medullary portion of the bone 
progressive extend within medular cavity 
cortex: New bone formation in advanced (x-
ray: enclosing shell)
 Micr: chondroblast with atypical nuclei
BONE-FORMING TUMOR

 OSTEOMA
 OSTEOID OSTEOMA
 OSTEOSARCOMA (Osteogenic
sarcoma)
OSTEOMA
 Rare benign tumor,
 Found in the skull, most commonly in the
head ands neck
 Localized, usually solitary,hard,
exophytic growths attached to the
surface of the bone
 Histologically composed of lamellar
bone, comprised of dense normal bone
 OSTEOID OSTEOMA
 Benign lesion
 Rarely exceed 1.5 cm in diameter,but painfull
 Occur in first 2 decade of life
 Arise within the cortex of the tibia and femur
(near the end): interlacing trabecular osteoid
surrounding bone are stimulated into
neoosteogenesis  dense sclerotic enclosing
shell (x-ray: radiolucent nidus enclosed with
sclerotic shell)
OSTEOID OSTEOMA
 Near periosteum this neoosteogenesis
may deform the external contour 
Excision.
 Recurrent, but rarely malignant
OSTEOSARCOMA
(osteogenic sarcoma)
 Most common primary bone tumor
 Affect young people age 10 to 25
 Femur, tibia and humerus are common sites,
75% occur on the knee
 Pain is early feature, metastatic (lung) at time
of diagnosis
 Usually begin in the medullary cavity,
penetrate outward through the cortical bone
 Histologic features may vary, but all produce
malignant osteoid
Osteosarcoma (2)

 Formation of osteoid or bone by tumor cells

 amount of osteogenesis are variably
 Most common primary bone cancer (+MM)
 Aggressive lesion, widespread metastasis
 Require early diagnosis and expert treatment
 Most often second decade of life
 Osteosarcoma (3)

 So-called primary osteosarcoma, situated on the

central region of the metaphysis long tubular bones
(distal femur, proximal tibia, proximal humerus)
 Evidence of genetic factors as the origin (LOH on
Rb focus on chromosome13q14)
 Secondary osteosarcoma occur on the background
of some predisposing influence such as Paget’s
disease of bone irradiation; in other location (jaws);
in later in life
 Osteosarcoma (4)
 Arise on the metaphyseal bone  progressive
extend to all direction  eroding the cortex,
invading surrounding tissue: producing
extraosseus mass.
 When penetrate the cortex, tumor lifts periosteum
 Codman’s triangle in x-ray (plane of outer space
of cortex and elevated periosteum)
 Macroscopic: Gray white mass, haemorrhage, and
cystic necrosis.
 Microscopic: anaplastic cells found on the lacunae
of osteoid, simulating osteocytes, hyperchromasia,
mitosis, bizzre looking giant cell
GIANTCELL TUMOR
 Over age 20
 Frequent site: end of long bones
 Bone or cartilage formation, numerous giant
cells on the background spindle fibroblast like
cells
 Benign or malignant depend on the present of
anaplastic features of fibroblas-like cells.
 Other bone tumor may contain giant cells.
 EWING’S SARCOMA

 Rare, but extremely malignant neoplasm

occur on older children and adolescence
(age10 to 15)
 Arising within marrow cavity (bones of the
head and neck), some on trunk, extremities
  consist of small, round hyperchromatic
cell (may be confused with metastasis
neuroblastoma
EWING’S SARCOMA
 DD: neuroblastoma, LNH,
rhabdomyosarcoma
 Widespread metastasis is common, the
prognosis is poor
 Reciprocal translocation between
chromosom 11 and 22
 Pain, tenderness, and fever
METASTATIC
 Bone is common site of disseminated
cancer, most of which are carcinoma.
 Common primary cancer which tend to
involve bone are prostate, lung, breast,
kidney, etc.