5/27/2024

OSTEITIS DEFORMANS
Paget’s Disease of Bone

Paget's disease, which is characterized by thickening and disturbance of the architecture of bone, that fractures
easily due to imbalance between osteoblast and osteoclast activity; first osteoclast overactive, then both equal
activity, then osteoblast overactive

is very common, Most cases are asymptomatic.

Age: fourth decade of life
Sex : males > females
Site:
Monostotic (15%): Tibia, ilium, femur, skull, vertebra, humerus
Polyostotic (85%): Pelvis, spine, skull

Pathogenesis & Etiology :

• The cause is -Unknown, maybe viral.
• The finding of virus-like particles in affected bones has suggestion that Paget's disease may represent a virus
infection of bone
Infection of osteoclasts by a slow virus (measles, paramyxovirus, or both) in different areas of bones

The disease progresses through 3 stages:

I. Initial osteolytic stage:
• In the first stage, there is irregular osteoclastic resorption of bone
II) Mixed osteoclastic/osteoblastic stage :
• In the second stage, osteoblasts react by actively laying down new bone, which balances the osteolysis
and maintains the total bone volume
III) sclerotic stage:
• Finally, there is a sclerotic phase in which osteoblastic activity is greatly in excess of osteoclastic
resorption, leading to marked thickening of bony trabeculae and cortex

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• Clinic features :
• Early Paget's disease is asymptomatic
• Skull is commonly affected Hearing and vision loss – compressed of cranial nerves
• Thickening of bone may cause deformities  Lion like face and increased hat size
• Vertebral bodies -kyphosis
• Bone pain - due to micro fractures
• Biopsy M/E: mosaic pattern of lamellar bone
• Serum calcium, phosphorus, and parathyroid hormone levels are normal. Serum alkaline
phosphatase levels are greatly elevated, reflecting the marked osteoblastic activity
• Complication
1- Hypervascularity of bone  acts as arteriovenous shunt  high-output heart failure
2- Bone sarcoma: (1%) Osteosarcoma & fibrosarcoma

mosaic pattern

Diseases of joints/types

• Synovial or nonsynovial
• Synovial joints: also called diarthroses; contain joint space between ends of
bones, joints covered by hyaline cartilage, strengthened by dense fibrous capsule
continuous with periosteum of bones and an inner synovial membrane; joint is
reinforced by ligaments and muscles; presence of joint space allows wide range of
motion.
• Nonsynovial joints: also called solid joint or synarthrosis; no joint space present;
provides structural integrity and minimal movement

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Arthritis: inflammatory disease of joints

1. Suppurative arthritis
2. Tuberculous arthritis
3. Degenerative joint disease (OSTEOARTHRITIS)
4. Rheumatoid arthritis (autoimmune)
5. Gout and gouty arthritis

1. Suppurative arthritis:

• Due to seeding of joint during bacteremia, most commonly due to Staphylococcus, Streptococcus, gram
negative rods; rarely syphilis
• Also due to postsurgical infection
• Neonates: often due to osteomyelitis
• Young women: most commonly due to gonorrhea (gram negative intracellular diplococci, which is
associated with multiple joint involvement, including the knee)
• Sickle cell disease: Salmonella
• Risk factors:
• immune deficiencies, severe illness, joint trauma, chronic arthritis, intravenous drug abuse
• Symptoms:
• sudden development of acutely painful and swollen joint with restricted range of motion, systemic
findings
• Sites: usually single joint (knee, hip, shoulder)
• Micro: neutrophils infiltration

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2. Tuberculous arthritis:

•Route : from adjacent tuberculous osteomyelitis or through blood

stream
•Joint : hip , knee , ankle
•Micro: tuberculous reaction : caseous destruction of joint structure
.

3. Degenerative joint disease: osteoarthrosis (osteoarthritis )

Definition:
• non-inflammatory disorder of progressive erosion of articular cartilage associated with aging, trauma,
occupational injury
• non-inflammatory arthritis (no redness or swelling in joints). Synovial fluid accumulates but
• lymphocyte infiltrate are not seen. Lymphocyte infiltrate are hallmark in inflammatory arthritis - gout and RA
• Risk factors -Obesity - Age - Trauma
• The most common form of arthritis
• degenerative disease of joints
• Sites: men-hips, women-knees and hands; also first metatarsophalangeal joint, lumbar spine; usually one joint
or same joint bilaterally, at least initially

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Osteoarthritis pathogenesis

1. Normal articular 3. Patchy loss of cartilage

cartilage Revealing bare bone
Fibrosis of bone
Eburnation

4. lips of new Bone

( osteophytes)
Extensive loss of cart.
Cystic degen. of
2. Fragmentation underlying bone
+ thinning of cartilage

• Gross:
• early changes are even degeneration of hyaline cartilage of articular surface and possible cartilage
fragmentation sloughing of cartilage .
• Eburnation (polished exposed bone)
• Subchondral bone sclerosis
• cysts: (synovial fluid forced into fractures via ball valve-like mechanism)
• Pieces of bone might fall off in joint space (joint mice
• osteophytes: (bony outgrowths at margins of articular surface)
• Loose bodies: floating of portion of articular cartilage that breaks off

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clinical features
• pain
• morning stiffness
• swelling of joints
• no evidence of acute inflammation
• X-ray:
• Narrow joint space due to loss of cartilage osteosclerosis
and bone cysts; and osteophytes)

4. Rheumatoid arthritis
Definition:
• A slowly progressive autoimmune disease characterized by progressive and potentially
deforming arthritis with productionof rheumatoid factor and extra-articular
manifestations.
• causes symmetrical polyarthritis
• Sites: causes symmetrical polyarthritis of small bones of hand affected first (MCP, PIP joints of
hands and feet), then wrist, elbow, knee
• Incidence
• Female > male
• 20-40yrs
• Genetics - Associated with HLA-DR4

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• Pathophysiology:
• Triggered by exposure of immunogenetically susceptible host to arthitogenic microbial
antigen Parvovirus B19 may be important in pathogenesis
• autoimmune reaction then occurs with T helper activation and release of inflammatory
mediators and cytokines that destroys joints
• circulating immune complexes deposit in cartilage, activate complement, cause cartilage
damage
• Produces nonsuppurative proliferative Synovitis leading to formation of pannus (granulation tissue over the
articular cartilage)
• may progress to Fibrous and bony ankylosis joint fusion & joint distortion, • damage of cartilage,

Rheumatoid arthritis
gross:
• inflamed joints have edematous, thick, hyperplastic synovium
• progressive destruction of joint
• fibrosis >>> so increased deformity + restriction of movement

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clinical features
• morning stiffness that improves with day
• Symmetric PIP involvement
• Fever, malaise, myalgia, wt loss (systemic autoimmune signs)
• Rheumatoid nodules
• Vasculitis
• Baker cyst (swollen bursa behind knee)
• Pleural effusion, LAD, interstitial lung disease
• Labs –
• Positive rheumatoid factor (IgM against Fc of IgG)
• Presence of neutrophils and protein in synovial fluid

5. Gout and gouty arthritis

• Definition
• Deposition of mono sodium urate crystals in joint Crystals arise due to hyperuricemia (uric acid
is nucleotide breakdown product) followed by chronic gouty arthritis :
• Occurs either by too much uric acid in blood
• Or not enough filtration by kidney
• Presentation:
• Most commonly seen as highly inflammatory monoarticular arthritis in great toe (podegra)
• Acute inflammation (crystals activate macrophage)
• chronic and formation of gout Tophi (palpable masses) - UA crystals in soft tissue and joints which eventually
damages joints

Site Great toe, ankle, heel and wrist are affected

Cause>
• Primary gout , (90%), idiopathic
• Secondary gout, (10%), associated with some
diseases as leukemia, renal disease

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• Gross: chalky white appearance of gouty deposits

• Micro: early - edematous synovium with acute and chronic inflammatory infiltrate
• late - tophi (large aggregates of urate crystals, granulomatous inflammation,
hyperplastic fibrotic synovium

Gout: tophus
the image shows white deposits of gouty tophi around the distal interphalangeal joint and in the
surrounding soft tissue of the skin.

Muscle and Neuromuscular Junction pathology

• Dermatomyositis:
• Def: Inflammation of skin and skeletal muscle
• Cause: Unknown; some associated with carcinoma
• Presentation: Bilateral proximal muscle weakness; distal muscles can be affected late -
Rash on upper eyelids (heliotrope rash); malar rash - Red papules on elbows, knuckles
and knees (Gottron papules)
• Biopsy: Perimysial inflammation (CD4+) with perifascicular atrophy on biopsy

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Polymyositis
Def: Inflammation of skeletal muscle only
Presentation: Other than skin involvement, mimics dermatomyositis (bilateral
proximal muscle weakness
Biopsy: Endomysial inflammation (CD8+) with necrotic muscle fibers

X-linked muscular dystrophy:

Def: Degenerative disease with muscle wasting due to bad
dystrophin protein and replacement of muscle by fat.
Types:
1. Duchenne muscular dystrophy
• Caused due to Deletion of dystrophin gene
• Presents as proximal muscle weakness at 1 year age;
distal muscles involved later
• Calf pseudohypertrophy characteristic finding
(filled with fat)
• Death due to cardiac or respiratory failure; myocardium
commonly involved
2. Becker muscular dystrophy
• Caused due to mutation of dystrophin gene
• Clinically milder disease

Myasthenia gravis
• Def: Ab against postsynaptic Ach receptor at NM junction
• Commonly seen in women 15% of cases associated with thymic hyperplasia
or thymoma
• Presentation:
• Muscle weakness that worsens with use and improves with rest
• Early eye involvement - ptosis and diplopia (MOST MUSCULAR DISEASE SPARE
EYES)
• Treatment - Thymectomy improves symptoms Use anti-
cholinesterase agents to increase Ach in synapse

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Lambert-Eaton syndrome
• Def: Ab against presynaptic Ca channel at NM junction
• Seen as paraneoplastic syndrome; commonly in small cell carcinoma of lung
• Presentation:
• Muscle weakness that improves with use and worsens with rest
• Treatment -Resection of cancer resolves disease - Anti-cholinesterase
don't help

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