Fig. 21.32 ). Although chondrocytes proliferate and continuously synthesize and secrete proteoglycans, degradation ultimately exceeds synthesis, and the composition of proteoglycans changes as the disease progresses. Meanwhile, MMPs secreted by chondrocytes degrade the type II collagen network. Cytokines and diffusible factors from chondrocytes and synovial cells, particularly TGF-β (which induces MMPs), TNF, prostaglandins, and nitric oxide, have been implicated in
OA (Fig. 21.32 ). Chronic, low-level inflammation contributes to the progression of the disease. Ultimately, chondrocyte loss and a severely degraded matrix mark the late stage of the disease.
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MORPHOLOGYIntheearlystagesofOA,chondrocytesproliferate,formingclusters.Concurrently,thewatercontentofthematrixincreasesandtheconcentrationofproteoglycansdecreases.ThenormallyhorizontallyarrangedcollagentypeIIfibersarecleaved,yieldingfissuresandcleftsatthearticularsurface(
Fig.21.33 ).This 1. CHONDROCYTE INJURY
Chondrocyte proliferation Degrade collagen Degrade proteoglycans IL-8 BMP MMPs Aggrecanases PGE2, NO, TNF TGF-˜2. EARLY OSTEOARTHRITIS Chondrocyte dropout Apoptosis Subchondral bone changes 3. LATE OSTEOARTHRITIS
Fig.21.32Schematicviewofosteoarthritis(OA).OAisthoughttobeinitiatedbychondrocyteinjury(1)inageneticallypredisposedpatientleadingtochangesintheextracellularmatrix.(2)Althoughchondrocytesmayproliferateandattempttorepairdamagedmatrix,continueddegradationexceedsrepairinearlyOA.(3)LateOAisevidencedbylossofbothmatrixandchondrocyteswithsubchondralbonedamage.
manifestsasagranularsoftarticularsurface.Eventually,full-thicknessportionsofthecartilagearesloughed.Thedislodgedpiecesofcartilageandsubchondralbonetumbleintothejoint,formingloosebodies(joint mice).Theexposedsubchondralboneplatebecomesthenewarticularsurface,andfrictionwiththeopposingsurfaceburnishestheexposedbone,givingittheappearanceofpolishedivory(bone eburnation) (
Fig.21.33 ).Smallfracturesthroughthearticulatingbonearecommon,andthefracturegapsallowsynovialfluidtobeforcedintothesubchondralregionsinaone-way,ballvalve–likemechanismformingfibrous-walledcysts.Outgrowths(osteophytes) developatthemarginsofthearticularsurfaceandarecappedbyfibrocartilageandhyalinecartilagethatgraduallyossify.Thesynoviumisusuallyonlymildlycongestedandfibrotic,anditmayhavescatteredchronicinflammatorycells.
Primary OA usually presents in patients they are in their 50s. If a young person has significant manifestations of OA, a search for some underlying cause should be made. Characteristic symptoms include joint pain that worsens with use, morning stiffness, crepitus, and limitation of range of movement. Impingement on spinal foramina by osteophytes results in cervical and lumbar nerve root compression and radicular pain, muscle spasms, muscle atrophy, and neurologic deficits. The joints commonly involved include the hips (