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bone remodeling
process of skeletal maintenance after skeletal growth is complete
bone remodeling cycle
Bone resorption by osteoclasts followed by
bone formation by osteoblasts
• Resorption and new bone formation should be
equal
• 1 cycle = ~ 4 months
osteon
unit of mature bone
osteoclasts
monocyte/macrophage precursors in myeloid stem cell lineage
bone resorption process
osteoclasts
protein and mineral components of bone removed→ tunnel in the osteon
soluble factors recruit osteoblasts
bone formation
Osteoblasts
• Bone marrow stromal stem cells
• Deposit organic matrix (osteoid) on wall of osteon
canal
control of bone metabolism and remodeling
osteoblasts mediate osteoclast activity
receptor for RANKL found on osteoclast
osteoprotegerin (OPG)
osteoblasts mediate osteoclasts activity
Release RANKL (receptor activator of nuclear factor
kappa-B ligand), which induces osteoclast activity
RANK-receptor for RANKL found on osteoclasts
binding of RANKL to RANK promotes osteoclast
differentiation and proliferation
OPG (osteoprotergerin)
blocks action of RANKL
osteopenia
Found in all metabolic bone diseases
• Bone mass less than expected
for individual
decrease in bone mass
mechanisms of osteopenia
↓ in bone formation
• Inadequate bone mineralization
• ↑ bone deossification
osteoporosis
porous bone
Bone resorption exceeds bone formation
• ↓ bone density and strength
• Loss of mineralized bone mass
risk factors of osteoporosis
Non modifiable
• Aging: > 50 years
• Postmenopausal biologic females
• Small bone structure
• Family history - genetics
• Modifiable
• Calcium and Vit D intake LOW
• Lifestyle
• ETOH, smoking, high protein diet, sedentary, etc
• Drug related
• Disease related
on-
Prolonged corticosteroid use causes
Suppressing bone formation by osteoblasts
• Accelerating bone resorption by osteoclasts
• Decreased intestinal absorption of calcium causing hypocalcemia
postmenopausal causes
decrease in estrogen→ increase in RANKL and decrease in OPG
clinical manifestations of osteoporosis
Usually a silent process
• #1 manifestation: skeletal fracture
• Hip fractures common
• ↓ height r/t collapsed vertebrae
• Kyphosis
scan for osteoporosis
Bone Mineral Density (BMD) scan
• DEXA (dual energy x-ray
absorptiometry)
• T-score
• Quick, noninvasive
treatment of osteoporosis
Weight-bearing exercise,
calcium and vitamin D
supplements, bisphosphonates
osteomalacia
Inadequate mineralization of bone
• softening of the bones but not loss of bone matrix
causes of osteomalacia
Calcium/Vitamin D deficiency
• Phosphate deficiency
• ↑ among elderly – dietary calcium and vitamin D deficiencies
• Renal rickets
• Renal failure
• Inability to activate vitamin D
• Inability to reabsorb phosphate
manifestations of osteomalacia
bone pain, tenderness
increase risk of pathologic fractures
treatment of osteomalacia
Treat underlying cause
• Vitamin D and calcium supplements
• ↑ exposure to sunlight
rickets in children
Failure or delay in calcification of
cartilaginous growth plates and
bone
manifestations of rickets in children
Deformed bones
• Bowing of legs
• Stunted growth
• Difficulty ambulating
• Bone pain
• Increased risk for pathologic
fractures
Paget disease
2nd most common bone disease
Localized areas of excessive bone turnover, disorganized osteoid
formation
pathophysiology of Paget disease
Regions of rapid osteoclastic bone resorption
• Disorganized, poor-quality osteoblastic bone formation
• Mosaic pattern with cement lines
• Bone marrow fibrosis, ↑ vascularity
• Weak, brittle, bowed bones, unable to support weight
• ↑ risk pathologic fractures
manifestations of Paget disease
Single lesion or multiple in different bones
Skull – HA, tinnitus, vertigo, hearing loss
• Spine – kyphosis
• Pain, stiffness, pathologic fractures
• Cardiovascular disease → heart failure
• ↓ ventilatory capacity
• Mental deterioration
1-2% are
all affected by rheumatoid arthritis
biologic females are
3 times more likely to get rheumatoid arthritis
peak for rheumatoid arthritis
50-75 years old
rheumatoid arthritis pathophysiology
Autoimmune inflammatory disorder
• Immune attack synovial tissue
• Genetic predisposition (HLA on MHC II) +
immune trigger
• T-cell mediated immune response
• Synovial fluid inflammation
• Joint destruction
• Antibody/antibody complex
• Activation of complement
• ↑ cytokine production
• Angiogenesis
• Generation of synovial cells
• Pannus invasion
• Irreversible damage
Rheumatoid Arthritis: Clinical
Manifestations
Insidious onset
• Systemic manifestations
• fatigue, weakness, anorexia, fever, elevated ESR
• Limited ROM
• Early pain, later fibrosis
• Stiffness lasting > 30 minutes to several hours
• Most frequent:
• fingers, hands, wrists, knees, and feet
• Bilateral and symmetric
• Joint deformities
• Boutonnière’s deformity
• Swan-neck
• Rheumatoid nodule
seven S’s
Sunrise stiffness
• Soft feeling in joints with nodules
and pain
• Swelling with warmth
• Symmetrical
• Synovial
• Systemic (fever, fatigue, anemia,
heart, lungs)
• Stages
treatment of rheumatoid arthritis
Treatment aimed at
• relieving symptoms
• maintaining joint function and range of motion
• minimizing systemic involvement
• delaying disease progression
Systemic Lupus Erythematosus (SLE)
Chronic systemic inflammatory autoimmune disease
• Can affect any and all organ systems
• Etiology largely unknown
• Females (85%) > males
• More common in African Americans, Hispanics, and Asians than in Caucasians
• Most cases occur between 15 and 44yo
environmental trigger of systemic lupus erythematosus
Ultraviolet (UV) light
• Chemicals (e.g., drugs, hair dyes)
• Infectious agents
• Medications
type 3 hypersensitivity reaction to systemic lupus erythematous
Formation of autoantibodies and immune complexes (IgG, IgA)
• B cell hyperreactivity
• Autoantibodies against nuclear and cytoplasmic cell components
presence of 4 systemic lupus erythematous
facial rash
arthralgias
arthitis
renal disorder
treatment of systemic lupus erythematous
Management of acute and chronic symptoms
• Prevent loss of organ function
• ↓ exacerbations
• Avoid triggers
• Pharmacologic therapy (corticosteroids, immunosuppressants)
• Minimize disability
• Prevent complications from drug therapy
• Pharmacologic therapy
pharmacologic therapy of systemic lupus erythematous
NSAIDs
• Corticosteroids – CNS and renal effects
• Immunosuppressive drugs
ankylosing spondylitis
chronic inflammation of axial skeleton
Erosion of sites where tendons and ligaments
attach
bony overgrowth of the vertebra
manifestations of ankylosing spondylitis
lower back pain
loss of ROM
kyphosis with extension of neck
acute anterior uveitis
weight loss, fever, fatigue
treatment of ankylosing spondylitis
Controlling pain
• NSAIDS
• Proper posture
• Muscle-strengthening exercises
• Smoking cessation
• DMARDs may be considered
osteoarthritis
Slow, progressive destruction of
the articular cartilage of weight-
bearing joints
• “Wear & tear” arthritis
• Degenerative and inflammatory
• Most prevalent form of arthritis
risk factors of osteoarthritis
age
• 85% > 70 years of age
• Genetics
• Body habitus
• Joint trauma
• Long-term mechanical stress
pathophysiology of osteoarthritis
Loss of articular cartilage
• Joint cartilage attempts to repair
self → inflammation → synovitis
• Osteophyte formation
• Bony outgrowths (spurs)
• Cartilage contains more water, less
collagen
• Cartilage becomes weak, rough,
eroded
• No longer protects the surface of the
bone
basis of osteoarthritis
Damage and death of chondrocytes → crack in articular cartilage
• Influx of synovial fluid promotes further loss of cartilage
Cartilage gradually worn away due to the influx of synovial fluid → deeper crack
• New blood vessels grow in from epiphysis and fibrocartilage is deposited
Fibrocartilage plug cannot support weight-bearing function of cartilage
• Wears away and exposes subchondral bone plate → thickness and sclerosing
• Further cracking → formation of subchondral bone cyst, influx of synovial fluid
• Regrowth of articular surface → osteophyte formation (bone spur
manifestations of osteoarthritis
Sudden or insidious
• Pain usually worsens with
activity, relieved by rest
• Crepitus may be evident with
ROM
• Usually a single weight-bearing
joint is initially involved
• Progresses to other joints as they
try to protect initial join
diagnosis of osteoarthritis
History and PE
• X-Rays
• ESR usually normal
treatment of osteoarthritis
Tylenol
• NSAIDs
• Corticosteroid injections
• Surgery: severe pain or reduced joint function
gout
crystal induced arthopathy (inflammation disorder)
hyperuricemia uric acid, sodium rate crystals in joints, and crystals deposit in connective tissue
gout risk factors
70% of males
peak age of 40-50 years
Diet high in purine rich foods:
• meats, alcohol, seafood, and high
fructose corn syrup
• Dehydration
• Drugs - Thiazide diuretics
can hyperuricemia occur without gout symptoms?
yes it can
acute gout manifestations
typically monoarticular
• first metatarsal joint
• tarsal joints, ankles, heels, knees, wrists, fingers, and elbows
• Often begins at night
• May be precipitated by:
• excessive exercise, certain medications, foods, alcohol
• Onset of pain typically is abrupt
• May last for days or weeks
inter critical gout manifestations
may be months or years between flares
chronic tophaceous gout manifestations
10 or more years after the first gout attack
diagnosis of gout
Monosodium urate crystals in
the joint
treatment of gout
Reduce inflammation
• NSAIDs
• Corticosteroids
• Drugs to reduce uric acid
• Xanthine oxidase inhibitors
• Diet and activity changes