Disorders of musculoskeletal function

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