Paget Disease (Osteitis Deformans)

Osteitis Deformans is characterized by a repeated

cycle of bone formation and destruction that results
in a net gain in bone mass.
However, the newly formed bone is disordered and
weak, leading to disfiguration of bone structure.
Paget Disease typically manifest in mid to late
adulthood. It has a mixed prevalence worldwide but
its incidence is decreasing.

Paget Disease (Osteitis Deformans)

The cyclic stages are as follows:
Osteolytic Stage- repetitive episodes of frenzied, regional
osteoclastic activity and bone resorption
Mixed Osteoclastic-Osteoblastic Stage- exuberant bone
formation
Osteosclerotic Stage- apparent exhaustion of cellular activity.

Causes of Paget Disease

Paramyxovirus
Infection

Interleukins 1
Interleukin 6
MCSF

SQSTMI gene
mutation

Increased
osteoclast
activity

Paget
Disease

Clinical Findings
MONOSTOTIC (15-20%)

POLYOSTOTIC (80%)

Tibia

Proximal Femur

Ilium

Axial Skeleton

Femur

Skull

Vertebrae

Humerus

Clinical Findings
Mild (usually) skeletal, neuromuscular and cardiovascular changes
Increased serum alkaline phosphatase and urinary hydroxyproline
Warm skin and subcutaneous tissue overlying lesions
High-output congestive heart failure
Deformed, brittle bone structure
Nerve impingement
Chalk stick (transverse) fractures of long bones

Morphology
Osteolytic phase Osteoclasts are numerous, abnormally large, and have increased numbers of
nuclei.
Mixed Osteoclastic-Osteoblastic Stage-
Osteoclasts persist, but the bone surfaces become lined by prominent
osteoblasts.
The marrow is replaced by loose connective tissue containing osteoprogenitor
cells, as well as numerous blood vessels needed to meet the increased
metabolic demands of the tissue.
The newly formed bone may be woven or lamellar, but eventually all of it is
remodeled into abnormal lamellar bone with a pathognomonic mosaic pattern.

Morphology
Osteosclerotic Stage The periosseous fibrovascular tissue recedes and is replaced by normal
marrow.
The resulting cortex is softer than normal and prone to deformation and
fracture under stress.

Osteonecrosis (Avascular Necrosis)

Osteonecrosis is cellular death (necrosis) of bone
components due to interruption of the blood supply.
Without blood, thebonetissue dies and
thebonecollapses.
Most cases of bone necrosis are due to fracture or
occur after corticosteroid use, but in many instances
the etiology is unknown.

Causes of Osteonecrosis
Steroid administration
Vascular compression
Thromboembolic disease
Primary vessel disease
Sickle cell crisis

Clinical Findings
Pain during physical activity
Limited range of motion
Bone collapse

Morphology
The cortex is usually not affected because of collateral
blood supply.
Overlying articular cartilage receives nutrition from
synovial fluid.
Medullary morphology:
Dead bone with empty lacunae
Interspersed areas of fat necrosis and insoluble calcium soap

Achondroplasia
The most common form of dwarfism.
Caused by activation of point mutations in fibroblast
growth factor receptor 3 (FGFR3)
Function of FGFR3:
Inhibit the proliferation and function of growth plate
chondrocytes

Achondroplasia
Disorder is usually inherited in autosomal dominant
fashion but may also arise from spontaneous mutations
Clinical findings:

Short stature
Shortening of the proximal extremities
Bowing of the legs
Frontal bossing
Midface hypoplasia
Disorganization and hypoplasia of growth plate cartilage