53 terms

Non-neoplastic Bone and Joint Disease

- most common disease of the growth plate
- is the most common form of dwarfism
- autosomal dominant, point mutation in gene that encodes FGF receptor 3 (constant activation of this receptor --> inhibition of cartilage formation)
- gain of function mutation (normally, FGFR3 inhibits cartilage proliferation
- disorganized and narrowed zone of proliferation in growth plate
- premature bone formation seals the plate
- intramembranous (periosteal) bone formation is normal
- mainly long tubular bones affected
- short extremities, relatively normal trunk, enlarged head with bulging forehead and depression of root of nose
- normal intelligence and life span
thanatophoric dwarfism
- mutation of FGFR3 different from achondroplasia (but is also a gain of function mutation)
- much less common form of dwarfism
thanatrophoric dwarfism
- lethal (perinatal age...die at birth or soon after)
- limb shortening and small chest
- death from respiratory insufficiency
- affects all bones, not just longitudinal ones
- histologically, shows diminished proliferation of chondrocytes and poor columnization in the zone of proliferation
osteogenesis imperfecta
- type 1 collagen disease
- abnormal collagen and brittle bones
type II osteogenesis imperfecta
type I osteogenesis imperfecta
- this type = lethal in utero, multiple intrauterine fractures
- this type = normal life spain, increased number of fractures, blue sclerae, hearing loss, misshapen teeth
osteogenesis imperfecta
- too little bone
- cortical thinning, attenuated trabeculae, hypercellular woven bone
- increased bone porosity due to decrease in bone mass (localized or generalized)
- bone is too lite and porous
- complications include fracture of femoral neck, pelvis, spine
- also pulmonary embolism or pneumonia secondary to fractures (cause of 40,000-50,000 deaths each year)
- shape of bone collapses, sinks in
senile osteoporosis
- low turnover variant (bone doesn't remodel as quickly)
- osteoblasts from older individuals have reduced reproductive and biosynthetic potential
- age-related bone loss (.7% per year)
- *Haversian system widened
postmenopausal osteoporosis
- high turnover variant (but slow process, so don't see enzyme abnormalities)
- hormone-dependent acceleration of bone loss after menopase (estrogen deficiency)
- decreased estrogen = increased secretion of cytokines = stimulation of osteoclast recruitment
- up to 50% trabecular bone loss
- osteoclasts absorb bone more than it is produced
- *vertebral collapse
disuse osteoporosis
- mechanical forces are important stimuli for normal bone remodeling
- muscle contraction important source of skeletal loading
- decreased physical activity leads to bone loss
- vitamin D
- calcium
- genetic polymorphism in _____________ receptor molecule leads to variation in maximum bone mass
- _________ intake is also important
- thinned trabeculae, microfractures, vertebral collapse (postmenopausal variant), cortex thinned, Haversian system widened (senile variant)
- specialized radiographic imaging required for diagnosis
in postmenopausal women, decreased estrogen levels promote increased osteoclastic activity by increasing production of cytokines with recruit and activate osteoclasts by increasing _________ expression while reducing OPG synthesis
Paget disease
- increased osteoclastic activity with numerous absorption pits, then prominent osteoblasts lining bone surfaces
- adjacent marrow hypervascular
- focal increase in bone mass
Paget disease
- woven bone formation followed by lamellar bone with mosaic pattern (jigsaw puzzle)
- prominent cement lines* annealing haphazardly oriented units of lamellar bone
Paget disease
- bone is thicker, but structurally abnormal and therefore breaks easily because it is weaker
- coarsely thickened trabeculae and cortices that are soft and porous --> increased vulnerability to deformation and fracture
axial skeleton (spine) and proximal femur
most common sites for Paget disease
serum alkaline phosphatase
What is increased in Paget disease and is a sign of increased bone turnover?
Paget disease
- pain, deformities (bowing of femur/tibia), increased blood flow may lead to high output cardiac failure (AV shunting), malignant transformation (high grade sarcoma) in 5-10% of patients with severe polyostotic disease
comminuted frature
a fracture in which the bone has broken into a number of pieces (bone is splintered)
displaced fracture
a fracture in which the bone ends are not aligned
- non-union
- psuedoarthrosis
- infection
complications which inhibit fracture healing (3)
osteonecrosis (avascular necrosis)
- bone necrosis secondary to ischemia
- due to mechanical vascular interruption (fracture), corticosteroids (unknown mechanism), thrombosis and embolism (sickle cell anemia), vasculitis/radiation injury, increased intraosseous pressure, venous HTN, often unknown (idiopathic*)
osteonecrosis (avascular necrosis)
- medullary infarcts involve cancellous bone and marrow (cortex not affected due to collateral blood flow)
- subchondral infarct
- dead bone
subchondral infarct
- part of osteonecrosis
- chronic pain (collapse of dead bone leads to severe osteoarthritis)
medullary infarct
- part of osteonecrosis
- often silent, rarely undergoes malignant transformation to high-grade sarcoma
creeping substitution
- in the healing response, osteoclasts resorb the necrotic trabeculae; however, those that remain act as scaffolding for the deposition of new bone in a process known as ___________________
pyogenic osteomyelitis
- almost always bacterial
- infection is hematogenous (most common), contiguous, or direct implantation
- S. aureus is most common organism (80-90%), but can be others
- metaphysis and epiphysis
- metaphysis
- epiphysis (due to growth plate closure)
pyogenic osteomyelitis location:
- neonates?
- children?
- adults?
pyogenic osteomyelitis
- acute systemic illness or more subtle symptoms
- X ray findings: lytic focus surrounded by sclerosis
- bone biopsy may be necessary to culture organism
- complications include fracture, endocarditis, sepsis, squamos cell carcinoma
pyogenic osteomyelitis
sequestrum, draining sinus, involucrum, Brodie abscess
- sequestrum
- draining sinus
- involucrum
- Brodie's abscess
- dead piece of bone
- rupture of the periosteum leads to a soft-tissue abscess and the eventual formation of a _____________
- when the newly deposited bone forms a sleeve of living tissue around the segment of devitalized infected bone, it is known as an ____________
- is a small intraosseous abscess that frequently involves the cortex and is walled off by reactive bone
tuberculous osteomyelitis
- 1-3% of pulmonary or extra-pulmonary TB
- usually solitary but may be multifocal
- festers for years
- sites most commonly involved: spine, knees, hips
- more destructive and more difficult to control than pyogenic osteomyelitis
Pott disease
- when tuberculous osteomyelitis involves the spine, it is called _______________
- the infection breaks through the intervertebral discs to involve multiple vertebrae and extends into the soft tissues forming abscesses
Skeletal syphilis
- congenital intrauterine or acquired infection
- bones frequently involved if acquired include the nose, palate, skull, and extremities
- saber shin is produced by massive reactive periosteal bone deposition on the medial and anterior surfaces of the tibia
- if congenital, lesion appear in 5th month of gestation and are fully developed at birth
- most common joint disease
- progressive erosion of articular cartilage (not an inflammatory disease)
- primary = idiopathic (aging phenomenon)
- secondary = predisposing condition such as development deformity, diabetes, marked obesity, repeated trauma (athletes)
- alterations in proteoglycans and collagen lead to decreased tensile strength and secretion of cytokines
- chondrocyte proliferation followed by fibrillation
- sclerosis and remodeling of underlying bone
- eburnation
- deep pain
- osteophytes may cause nerve compression
- typically only few joints involved (hip, knees, lumbar/cervical spine, interphalangeal and first carpometacrapal and tarsometatarsal joints
- Herberden nodules (osteophytes at DIPs)
- joint mice
rheumatoid arthritis
- thick, hyperplastic synovium with villous fronds
- prominent lymphoplasmacytic infiltrate
- organizing fibrin may float in joint space "rice bodies"
rheumatoid arthritis
- juxtaarticular erosions
- pannus (fibrocellular mass of synovium and stroma containing inflammatory cells and fibroblasts, causes erosion of cartilage --> late sequelae: fibrous and bony ankylosis
rheumatoid arthritis
- occur in areas subject to pressure (ulnar aspects of forearms and elbows)
- vasculitis if disease is severe in small to medium arteries (possible complication of vasculitis is gangrene)
often happens after a meal rich in protein (meat)
- swollen joints
- acute arthritis: dense neutrophilic infiltrate
- chronic tophaceous arthritis: urate deposits encrust articular surfaces, eventually leading to ankylosis
- urate crystals needle shaped, negatively birefringent
- are defined as large aggregations of urate crystals surrounded by inflammatory cells and multinucleated foreign body giant cells
- white, cheesy looking material
- characteristic of gout
- articular cartilage, ligaments, and soft tissue
- usually affects distal extremities (toes)
- cardiovascular disease including aterosclerosis and HTN is common
gouty nephropathy
- when deposition of urate crystals in medulla causes the formation of stones
pseudogout (chondrocalcinosis) (CCPD)
- crystals deposit in the articular matrix, menisci, and intervertebral discs --> seeding into the joint --> inflammatory response with neutrophils produce damage
pseudogout (chondrocalcinosis) (CPPD)
- chalky white friable deposits, weakly positive birefringent (rarely deposit in masses to form tophi)
- more square, not needle shaped
- crystals stain as blue-purple aggregates