CHAPTER 312 OSTEOARTHRITIS Hemoglobinopathies

OA ~ Degenerative joint disease EPIDEMIOLOGY AND RISK FACTORS

• Failure of diarhtrdial (movable, synovial-line) joint • Most common joint disease
• Primary/Idiopathic OA is the most common form • Knee OA: leading cause of chronic disability in developed
• Secondary OA due to underlying cause countries
Classification Diseases
Idiopathic • Age (in older individuals) → MOST POWERFUL RISK FACTORS
Hands Heberden’s nodes
Bouchard’s nodes  Men: hip OA
Erosive IP arthritis
1st CMC joint  Women: OA of IP joints and thumb base
Feet Hallux valgus
Hallux rigidus • Race
Contracted toes  Chinese: lower incidence for hip OA than whites
(hammer/cock-up toes)  South African least common for IP OA especially hip OA
Talonavicular
Knee Medial compartment • Genetic factors
Lateral compartment
Patellofemoral compartment  Mother and sister of a woman with DIP OA (herberden’s
Hip Eccentric (superior) nodes) have higher possibility of having OA
Localized Concentric 9axial, medial)
Diffuse (coxae senilis) • Major Joint Trauma
Spine Apophyseal joints
Intervertebral joints (disks)  Anterior cruciate insufficiency or meniscus damage → OA
Spondylosis (osteophytes)  Trimalleolar fracture → ankle OA
Ligamentous (hyperostosis,  Ballet dancer : Ankle OA
Forestier’s disease, diffuse  Baseball players : Elbow OA
idiopathic skeletal
 Prize fighters : MCP OA
hyperostosis
Other Glenohumoral
• Obesity
single Acromioclavicular
sites Tibiotalar  Knee and hand OA
Sacroiliac  Women > Men
Tempormandibular
Generalized Includes 3 or more of the areas listed above Risks Factors for OA
Secondary Age Repetitive stress 9vocational)
Acute Female sex Obesity
Trauma Race Congenital/developmental defects
Chronic (occupational, sports)
Legg-Calve-Perthes Genetic factors Prior inflammatory joint disease
Congenital hip Major joint trauma Metabolic/endocrine disorders
Localized disease
dislocation
Slipped epiphysis
Unequal LE length PATHOLOGY
Valgus/varus • Loss of articular cartilage, organ AO, synovial joint, subchondral
Congenital Mechanical factors deformity
bone, synovium , meniscus, ligaments, neuromuscular apparatus
Hypermobility
• In load-bearing areas of the articular cartilage
syndromes
Epiphyseal dysplasia
Spondyloepiphyseal
Bone dysplasias Thickening of cartilage
dysplasia
(with patchy synovitis)
Osteonychondystrophy
↓
Onchronosis (alkaptonuria)
Hemochromatosis Breached integrity of joint
Metabolic (cartilage softens and bone thins)
Wilson’s disease
Gaucher’s disease ↓
Acromegaly Fibrillation (vertical clefts)
Hyperparathyroidism ↓
Endocrine DM Deep cartilage ulcers that may extend to bone
Obesity ↓
Hypothyroidism Weak fibrocarilaginous bone
Calcium deposition Calcium pyrophosphate dihydrate deposition ↓
diseases Apatite arthropathy Metabolically active cartilage
Fracture (osteophytes)
Avascular necrosis ↓
Localized
Infection Hypocellular cartilage
Other bone and Gout ↓
joint disease RA Remodelling and hypertrophy
Paget’s disease Appositional bone growth in subchondral region
Diffuse
Osteopetrosis (sclerosis in x-ray)
Osteochondritis Bone abrasion like ivory (eburnation)
Neuropathic Charcot joints Periarticular muscle wasting
Kashin-Beck
Endemic
Mseleni
Miscellaneous Frostbite
Caisson’s disease
PATHOGENESIS
• Load on articular cartilage is generated by contraction of them
muscles that stabilize or move the joint
• However it is too thin to serve as a sole shock absorber in the
joint that additional protective mechanisms are provded by
subchondral bone and periarticular muscles
• Functions of articular cartilage
 Provides smooth bearing surface so that bones glide
effortlessly over each other with joint movement (with
help of synovial fluid)
 Prevents concentration of stresses so that bones tdo not
shatter when the joint is loaded
• Settings at which OA develops
 Normal biomaterial properties + excessive loading of the
joint causes the tissues to fail
 Reasonable load + inferior material properties
• Predisposing factors for OA
 Repeated oscillation
 Repetitive impact loading
• OA changes
 Occurs at sites subject to greatest compressive loads
 Due to subtle congenital or developlmental defects
• Clinical conditions that reduce the ability of the cartilage or
subchondral bone to deform
 Ochronosis: accumulation of homogentistic acid polymers
→ stiffening of cartilage
 Osteopetrosis: stiffness of subchondral trabeculae
 Osteoporosis: abnormally soft bone; protective against OA
THE EXTRACELLULAR MATRIX OF NORMAL ARTICULAR CARTILAGE
• Components of articular cartilage
 Proteoglycans: Responsible for the compressive stiffness of
the tissue and ability to withstand load
 Collage: provides tensile strength and resistance to shear
 Lysosomal proteases (cathepsins): Degrade the components
of intracellular matrix at low pH
 Metalloporteinases (stromelysin, collagenase, gelatinase):
Degrade the components of extracellular matrix at neutral
pH
 IL-1
 Normal cartilage turnover
 Stimulates synthesis and secretion of latent MMPs and
of tissue plasminogen activator
 Suppresses PG syntheis by chondrocyte, inhibiting
matrix repair
 Plasminogen: synthesized by chondrocyte or may enter the
cartilage from the synovial fluid
 Plasminogen and stromelysin: activate latent MMPs
  Loss of PGs
• Inhibitors of matrix degrading enzymes
 Tissue inhibitor of metalloproteinase (TIMP) and
plasminogen activator inhibitor-1 (PAI-1): synthesized by
chondrocyte and limits degradative activity of MMPs and
plasminogen activator
 TIMP and PAI-1 is destroyed or present in concentrations
that are insufficient relative to those fa tive enzymges,
stromelysin and plasmin
 Stromelysin: degrade protein core of PG and activate latent
collagenase
 Stromelysin + Plasmin = active protease responsible for
matrix degradation
• Stimulators of matrix biosynthesis
 Polypeptide mediators (IGF-1 & TGF-β)
 Stimulate PG biosynthesis
 Regulate matrix metabolism in normal cartilage
 Play a role in matrix repair in OA
 Modulate catabolic and anabolic pathways of
chondrocytemetabolism
 Mechanical loading: modulates chondrocyte metabolism
 Static laoding inhibits synthesis of PGs and protein
 Loads of relatively brief duration may sitmulate matrix
biosynthesis
PATHOPHYSIOLOGY OF CARTILAGE CHANGES IN OA
• Primary changes in OA
 Change in arrangement and size of collagen fibers
 Biochemical data consistent with the presence of a defect
in the collagen network of the matrix due to disruption of
the “glue” that binds adjacent fibers
 Irreversible
• Cartilage loss
 “Wear” contributes to cartilage loss
 Nitric Oxide
 IL-1, TNF & shear stress stimulate synthesis of NO by
chondrocytes
 NO stimulates synthesis of MMPs
 MMPs accounts for loss of cartilage in matrix
 IL-1, MMPs, plasmic and cathepsin areinvlveed in
breakdown of articular cartilage
• Repair of cartilage
 TIMP & PAI-1 stabilizethe systemic temporarily
 GFs (IGF-1& TGF-β) repair, heal or stabilize process
• Pathophysiology
Cartilage damage
↓
↑PG concentration → Thickening of cartilage
(Compensated OA)
↓
Repair tissue does not hold well under mechanical stress
↓
↓PG synthesis → full thickness loss of cartilage
(End-stage OA)
• Traumatic injury
 Swelling
 Alteration in biomechanical properties
 Cell death
 Changes in biosynthesis of matrix macromolecules
 Degradation of collagen
 ↑MMP gene expression
• Extent of above changes due to direct mechanical damage vs.
cell-mediated degradation
 Injury → ↑responsiveness of the chondrocyte to stimulation
by cytokines
 Injury → diffusion of cytokines into the matrix
 Unlike in knee cartilage: GAGs loss from ankle cartilage is
not increased after mechanical injury of the tissue and
exposure to cytokines
CLINICAL FEATURES
• Deep ache localized to the involved joint
• Aggravated by use and relieved by rest
 Involves 3 r more joints (DIP, PIP)
• Octurnal apin in advanced oA of the hip andmay be enervating
 Evident Heberden’s nodes
• (+) Morning stiffness (<20 minutes)
 (+)Flare’ups ofinflammation marked by soft tissue swelling,
• Usually NO systemic manifestations redness and warmth
Causes of joint Pain and Patients with OA
Source Mechanisms  ↑ESR but (-)RF
Synovium Inflammation (due to)
 Phagocytosis of shards of cartilage and THUMB BASE
bone from the abraded joint surface
 2nd most frequently affected area
 Release from the cartilage of soluble
matrix macromolecules or crystals of  Swelling, tenderness and crepitation
calcium pyrophosphate or hydroxyapatite)  Loss of motion and strength
 X-ray: squared appearance due to osteophytes
 Antigens derived from cartilage matrix
sequestered in collagenous tissues of the  Pain with pinch → adduction of the thumb and contracture of
join → low-grade synovitis the 1st web space or compensatory hyperextension of the first
Subchondral bone Medullary hypertension, microfractures MCP and swan-neck deformity of the thumb
Osteophyte Stretching of periosteal nerve endings
Ligaments Stretch
HIP
Capsule Inflammation, distention
• Due to congenital or developmental defects of the hip
Muscle Spasms
• Pain referred to inguinal area, buttock or proximal thigh
• Physical examination
• Pain invoked through flexion (initially) and internal rotation
 Localized tenderness
(exacerbation of pain)
 Bony or soft tissue swelling
 Bony crepitus • Limited ROM: internal rotation → extension → adduction →
 Synovial effusions flexion (due to capsular fibrosis and/or buttressing osteophytes)
 Warmth over joint
 Periarticular muscle atrophy
IN ADVANCED CASES
 Gross deformity KNEE
 Bony hypertrophy • May involve medial or lateral femorotibial compartment and/or
 Subluxation patellofemoral compartment
 Marked loss of joint motion • Bony hypertrophy (osteophytes) and tenderness
• Small effusions
• Bony crepitus
LABORATORY AND RADIOGRAPHIC FINDINGS • Medial : varus (bowleg) :: Lateral : valgus (knock knee)
• Radiographic findings • (+)Shrug sign (pain with manual compression of patella agains
 Joint space narrowing femur during quadriceps contraction) = Patellofemoral OA
 Subchondral bone sclerosis • Chondromalacia patellae
 Subchondralcysts  Syndrome of patellofemoral pain in teenagers and young
 Osteophytosis adults
 Change in contour due to bony remodling  More common in females
 Subluxation  Due to abnormal quadriceps angle, patella alta, trauma
 Softening and fibrillation of cartilage on posterior aspect of
• Laboratory testing (For secondary OA) patella
 ESR  Anterior knee pain & (+)Shrug sign
 Serum chemistry  Tx: Analgesics or NSAIDs and physical therapy
 Blood counts
 Urinalysis
 Synovial fluid analysis SPINE
• Involve apophyseal joints, IVD and paraspinous ligaments
 WBC < 2,000/µL • Spondylosis: degerative disk disease
 Mononuclear predominance • Diagnosis: reserved in patients with apophyseal involvement
• Localized pain and stiffness
OA AT SPECIFIC JOINT SITES • Nerve root compression → radicular pain & motor weakness
INTERPHALANGEAL JOINTS  From osteophyte blockade of a neural foramen
• Heberden’s nodes (DIP): most common form of idiopathic OA  From prolapse of degenerated disk
• Bouchard’s nodes (PIP)  From subluxatio of an apophyseal joint
• May present with pain, redness, swelling • OA similar to DISH but DISH…
• Gelatinous dorsal cysts may develop at the insertion of the  Occur in middle-aged and elderly
digital extensor tendon into the base of the distal phalanx  Men > Women
 Ligamentous classification and ossification in anterior
Erosive OA spinal ligaments (flowing wax) on anterior vertebral bodies
 DIP and PIP invoveld  (+)RADIOLUCENCY BETWEEN NEWLY DEPOSITED BONE AND
 More destructive VERTEBRAL BODY
 X-ray: collapse of subchondral plate with bony ankylosing  Preserved disk spaces and normal sacroiliac * apophyseal
 Severe deformity and functional impairment joints
 Extensively infiltrated with mononuclear cell

Generalized OA TREATMENT
Goals:
• Reduce pain
• Maintain mobility
• Minimize disability PHARMACOLOGIC THERAPY
NSAIDs and Acetaminophen
NONPHARMACOLOGIC MEASURES (KEYSTONE IN OA) • Slow cartilage damage?
Reduction Of Joint Loading
• Correction of poor posure • Anti-inflammatory/Analgesic
• Support for excessive lumbar lordosis • Decrease joint pain
• Avoid excessive loading • Improve mobility
• Avoid prolonged standing, kneeling and swatting • Disadvantages: GI symptoms, ulceration, hemorrhage and death
• Lose weight Risk Factors For Upper Gastrointestinal Adverse Events
• Rest periods during the day in Patients Taking NSAIDs
• Thermoplastic splint blocks flexion can reduce pain, improve Increasing age History of UGIT bleeding
overall hand function and reduce muscle spasm Comorbidity (poor or fair general health) Anticoagulation
• Use of cane/crutches or walker Oral glucocorticoids Combination NSAID therapy
History of peptic ulcer Increasing NSAID dose
Patellar Taping
• For OA of patellofemoral compartment Selective COX-2 Inhibitors
• Medial taping to reduce pain on kneeling, squatting or climbing • For patients NSAIDs-associated GI catastrophe
stairs • No greater efficacy than nonselective NSAIDs but with lower
• Simple and inexpensive incidence of GI bleeding
• Maintain with isometric exercises to strengthen the vastus
medialis obliquus component of the quadriceps muscle Glucocorticoid Injection
• Facilitates realignment of the patella ona long-term basis • Symptomatic relief, given intra-articularly

Wedged Insoles/Orthoses Intraarticular Injection of Hyaluronan

• For patients with medial compartment knee OA and medial tibial • For patients who have failed a program of nonpharmacologic
therapy and simple analgesics
femoral compartment
• Pain on external adduction Opioids
• Reduce excessive loading on medial compartment of thek nee • Indications:
ands train on the lateral collateral ligament  Acute flares (when APAP or NSAID does not provide
• Lateral wedge insoles → ↓NSAID consumption adequate pain relief)
 Chronic OA pain
• Propylene mesh: Practical, inexpensive and washable  Nausea/Vomiting
Thermal Modalities  Constipation
• Heat: reduce pain and stiffness  Urinary retention
• Ice: better analgesia  Mental confusion
 Drowsiness
Exercise
 Respiratory depression
• Since OA due to overuse, not much exercise → ↑ risk for
 Mechanism of Action
hypertension, obesity, diabetes and cardiovascular disease
 Aerobic conditioning  µ-opioid agonist
 Walking, cycling, aquatic exercises  Inhibits reuptake of norepinephrine and serotonin
 For cardiovascular fitness
 Improve function and quality of life  Drug Interactions → Convulsions
 Exhibit improved gait and walking speed  TCA
 SSRI
• Disuse → Muscle atrophy  MAOI
 Strengthening exercise
Rubefacients/Capsaicin
• For patients who can’t take systemic analgesics and NSAIDs due
Patient Education to risk of adverse effects
• Encouragement, reassurance, advice about exercise and • Topical irritants/local heat to provide pain releif
recommendation of measures to unload arthritic joint
• Self-management
GLUCOSAMINE, CHONDROITIN SULFATE
Tidal Irrigation Of The Knee • Symptomatic benefit
• Copius irrigation of the OA knee through a large-bore needle • Chondroprotective?
• Flush out fibrin, cartilage shards and debris
ORTHOPEDIC SURGERY
Arthrosopic Debridement And Lavage • For patients with advanced OA in whom aggressive medical
• Alleviate knee pain management has failed
• Improve function • Arthroplasty: Relieve pain, increasing mobility
• Indications: • Osteotomy: eliminate concentration ofpeak dynamic loads and
 OA with loose bodies provide effective pain relief
 OA with flaps of cartilage
 OA with disruption of the meniscus CARTILAGE REGENERATION
• Disadvantage: fibrocartilage that resurfaces isinferior to normal
 Patients with symptomatic knee
hyaline cartilage in its ability to withstand mechanical laods
 Asymptomatic patients that do not benefit from
pharmacologic threapy
RATIONAL APPROACH TO NONSURGICAL MANAGEMENT OF OA
• Nonpharmacologic management: foundation of treatment of OA
pain
• Pharmacologic management: adjunctive or complementary role
in management of this disease
• Individualized approach
 Exercise:
Range of motion Weight
Instruction in joint Thermal Shoes with well- Intraarticular steroid infection if Acetaminophen
Week 0 cane Quadriceps loss (if
protection principles modalities cushioned soles effusion present 1g q4-6h up to 4g daily
strengthening obsess)
Aerobic conditioning

← Telephone call → Insufficient pain control

Week 2 Doing well
2wks ↓
↓ ↓
Capsaicin cream 0.025% qid Risk factors for GI adverse
Reduce Reinforce compliance with
Continue acetaminophen → eveny?
acetaminophen dose nonpharmacologic measures
1g q 4-6h prn up to 4g/d
↓
NO: Ibuprofen 400mg TD or QID
or Naproxen 250-75 mg BID
Reinforce compliance with YES: Salsalate 1g BID or
←
nonpharmacologic measures Naproxen 250-375 mg BID +
Misoprostol or PPI or
Selective COX-2inhibitor

← Telephone call →
WEEK 6 Doing well Insufficient pain control
4wks
↓ ↓ ↓
d/c Capsaicin
Increse salsalate to 1500mg Reinforce
Reduce ibuprofen or d/c
Reinforce compliance with BIDif tolerated, increase dose compliance with
salsalate dose to prn ibuprofen/naproxen
nonpharmacologic measures to achieve serum nonpharmacoloic
after 4 wks d/c selective Cox-2
concentration of 20-25 mg/d measures
inhibiotr

← Follow-up visit
WEEK 10 Doing well → Insufficient pain control → Medial RF OA? Or PF OA?
4wks
↓
Continue tramadol or Reinforce compliance Medial TF OA: wedged insole
Reinforce compliance with d/c Tramadol 25 mg/d titrated to 200-
acetaminophen/ with nonpharmacologic ←
nonpharmacologic measures salsalate 300mg/d or acetaminophen/codeine
codeine prn measures PF OA: pateollar taping

← Telephone call → Insufficient pain control

WEEK 14 Doing well
4wks ↓
Decrease salsalate Reinforce compliance with d/c tramadol or Risk factors for GI adverse
→
dose to prn nonpharmacologic measures acetaminophen/codeine event?
↓
NO: Naproxen 375-50mg BID
Reinforce compliance with YES: Naproxen 375-500mg BID +
←
nonpharmacologic measures Misoprostolor or PPI or
selective COX-2 inhiibtor
Doing well ← Telephone call → Insufficient pain control
WEEK 18
↓ 4wks ↓
Continue pharmacologic and nonpharmacologic measures Referreal to orthopedic surgeon