Osteoarthritis

1
Osteoarthritis (OA)

• OrDegenerative Joint Disease
• DEFINATION
• Osteo Related to bone system
• Arthritis Arthro itis
• ? ?
• Joint Inflammation
  
• Condition in which one/ more joints are inflamed
• So OA is a condition in which one or more joints
  are inflamed involving the loss of cartilage

2
It is progressive disorder of joints which is
caused by gradual loss of cartilage
resulting in
development of bony spurs and crysts at the
margins of the joints. In addition to damage and
loss of articular cartilage, there is remodelling
of subarticular bone, osteophyte formation,
ligamentous laxity, weakening of periarticular
muscles, and, in some cases, synovial
inflammation These changes may occur as a
result of an imbalance in the equilibrium between
the breakdown and repair of joint tissue
3

• The most common joints involved
• Distal Interphalangeal joints
• Proximal Interphalangeal joints
• Carpometacarpal joints of thumb
• Weight Bearing joints (Hip, knee)
• Metatarsophalangeal joints of the foot
• Cervicle and lumbar vartebrae

4
The articular cartilage is slippery tissue that
covers the end of the bones in the
joints Healthy cartilage allows bones to
glid over each other
helps to absorb shock of movement
5
In OA the top layer of cartilage breaks down and
wear away ? Rubbing of bones under the cartilage
? Due to which there is Pain Swelling
Loss of motion of
joints ? Over the time joint
may lose its normal shape and also there is
growth of bony spurs on the edge of the joint
? Bits of bones/cartilage can break off and float
inside the joint space ? Which cause more pain
and damage
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• So in OA there is progressive distruction of
  articular cartilage and also there is involvement
  of
• Diarthrodial joint
• Synovium
• Capsule
• Subchondral bone
• Surrounding ligaments
• Muscles
• Changes in structure and function of this
  tissues leads to clinical
• Osteoarthritis
• Which is characterized by
• Joint pain
• Tenderness
• Decrease range of motion
• Weakness
• Joint instability
• Disability
  

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Classification
? ?
Primary OA Secondary OA
(idiopathic) (Due to
some other disease)
A. Localised Hands Hip Kn
ee Spine B.
Generalised Small joints Large joints Mixed
C. Erosive osteoarthritis

• Congenital and developmental disorders, bone
  dysplasias
• ii) Post-surgery / injury meniscectomy
• iii) Endocrine acromegaly,
• iv) Metabolic hemachromatosis, ochronosis,
  Marfan syndrome, Ehler-Danlos syndrome, Paget
  disease, gout, pseudogout, Wilsons disease,
  Hurler disease, Gaucher disease
• v) Rheumatologic rheumatoid arthritis
• vi) Neurological Charcot joints.

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Epidemiology OA is one of the core reason for
disability Nearly everyone who lives long is
affected by OA at any point of life, most
probably after the age of 55 to
60. Approximately 15 of population is
affected by OA
? ?
? ?
50 of those 85
of those over 65
age over 75 age OA is most widely
assessed in studies using the Kellgren and
Lawrence (KL) score. The overall grades of
severity are determined from 0 to 4 and are
related to the presumed sequential appearance of
osteophytes, joint space loss, sclerosis and
cysts
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• The World Health Organization (WHO) adopted
  these criteria as the standard for
  epidemiological studies on OA
• Prevalence of osteoarthritis varies with
• Age
• Gender
• Genetics
• Ethic Group
• Specific Joint Involved
• Method For Diagnosis

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AGE With increasing age the prevalence OA also
increases Generally for person age 25
75,prevalence is estimated 12 and for those with
age over 70, it is 60 70 affectet
Hip OA ? ? AGE ? ? Hand
OA ? ?
? ?
? Age 30 40 Age gt70
Knee OA Age 40
Age 80 Pre 1.6 Pre 14
? ?
Pre 5 Pre 65
Age
gt25 Age 55
Pre
5 Pre 12
12
Gender ? ?
Age gt 50
Age gt60 Men are more affacted
Women are more

affacted(26) Due to higher rate of sports and
Due to repeated use of Injuries

weight bearing joints Genetics
? ?
Pre 9
Pre 4 White
population Black Asian
population Prevalence of OA is 22 to 39 in
India
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• Etiology
• The etiology of OA is multifactorial
• Many patients have more than one risk factor for
  developing the OA.
• The most common risk factor for the development
  of OA includes
• Obesity
• Occupation
• Participation in certain sports (Often)
• History of joint trauma
• Genetic
• Age
• Sex
• Bone density
• Joint location

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Obesity Increased body weight is strongly
associated with hip, knee, and hand OA Obesity
often precedes OA and contributes to its
development, rather than occurring as a result of
inactivity from joint pain In a three-decade
Framingham Study, the highest quintile of body
mass was associated with a higher relative risk
of knee OA (relative risk of 1.5 to 1.9 for men
and 2.1 to 3.2 for women). The risk of
developing OA increases by about 10 with each
additional kilogram of weight, and in obese
persons without OA, weight loss of even 5 kg
decreases the risk of future knee OA by one-half.

16
Recent data suggest that OA is associated with
the metabolic syndrome, suggesting a possible
common pathogenic mechanism involving metabolic
abnormalities and systemic Inflammation. It is
also likely that vascular disease may both
initiate and hasten disease progression in
OA. This could be due to venous occlusion,
stasis or microembolic disease leading to
episodic reduction in blood flow through small
vessels within the subchondral bone.
Subchondral ischaemia may subsequently reduce
nutrient delivery and gas exchange to articular
cartilage in addition to direct deleterious
effects on the bone itself.
17
Occupation There is increased risk of OA for
those who are in occupation requiring Prolong
Standing Kneeling Squatting
Lifting/Moving Heavy Objects ?
?Miming
Factory Work Car
paintery Repetitive motion also contributes to
hand OA with dominant hand usually affected Risk
OA depends on type and intensity of physical
activity
18
Sports Damage to articular cartilage due to
sports greatly increase the risk of OA Meniscal
damage (common in athlete) also increase the risk
of knee OA 1.Because of loss of proper load
bearing and shock absorption 2.Increase focal
load on cartilage and subchondral
bones Trauma AGE AT INJURY DOSE MATTER As older
individuals who damage ligaments tends to
develope OA more rapidly than young people with
similar injury Trauma early in life ?Increased
risk of OA
19
Genetic Factors A number of recent studies
discovered the presence of over 80 gene mutations
involved in the pathogenesis of OA ,among which
the most relevant one is a single nucleotide
polymorphism. This one, called rs143383 and
located in the 3' untranslated region (3'UTR) of
the growth and differentiation factor 5 gene
(GDF5), is responsible for the development,
maintenance and repair of synovial joints Genes
for Vitamin D receptors (VDR) and insulin-like
growth factor 1(IGF-1) also seem to be involved
in the patho-physiologic pathways of OA It also
includes genes related to inflaamation,bone
morphogenetic protiens, protease/ its inhibitors
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Pathophysiology
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Normal Articular Cartilage Articular Cartilage
Possesses ? Viscoelastic Properties
?Which
provides 1.
Lubrication With Motion
2. Shock absorbency during rapid
movement 3.
Load Support In Synovial joints Articular
cartilage is found between synovial cavity on one
side and narrow layer of calcified tissue
overlying subchondral bone on onther side
22
Charactristics of Articular Cartilage 1.Cartilage
is easily compressed lossing up to 40 of its
original hight when load is applied
?
Compression increase area of contact

? Disperse force more evenly to undelying
bone,tendon, ligament, muscles 2.Cartilage is
frictionless Togather with compresibility ,
this enables smooth movement in joint and
distributes load across joint tissue to prevent
damage and stabilize the joint
23
Structure of Cartilage Cartilage is
having ? 1.Strength 2.Low co-efficiant of
friction 3.Copressiblity These all is derived
from its unique structure So,the cartilage is
composed of complex, hydrophilic , Extra-
cellular matrix It contains ?75 to 85 Water
2 to 5 Chondrocytes (the
only cell in cartilage)
Collagen Protiens
Proteoglycans Hyaluronic
Acid Molecules
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Two Major Structure of Cartilage

• Type II Collagen
• Tightly woven, triple helical structure which
  provides TENSILE STRENGTH to cartilage

• Aggrecans
• In which there is Proteoglycan linked with
  hyluronic acid, having negative charge.
• The strong electrostatic repulsion of
  proteoglycan gives cartilage the ability to
  withstand further compression

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• Normal Cartilage turn over
• ?
• Helps repair and restore cartilage
• ?
• Respond to usual demand of loading and physical
  activity
• In healthy adult cartilage chondrocyte metabolism
  is slow with dynamic balance between anabolic
  process
• Metabolism is premoted by
• Groth factors
• - Bone morphogenetic protien 2
• - Insulin like groth factor-1
• - tranforming growth factor
• 2. Catabolism
• Proteolysis
• Stimulated by MMPs, TNF-?, Interlukein-1,
  Other cytokines

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Joint Protective Mechanisms 1.Muscle Bridging The
Joints 2.Sensory receprtors in feedback loops
to regulate muscle and tondon function 3.
Supporting ligaments 4. Subchondral bones having
shock absorbent properties Note Articular
cartilge is avascular and aneural and
chondrocytes are nourised by synovial fluid
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• OA Cartilage
• OA begins with damage to articular cartilage,
  which is due to
• Trauma or other injury
• Excess joint loading by obesity / other reason
• Instability or injury of the joint that causes
  abnormal loading
• Devlopement of OA is due to
• Local mechanical influence
• Genetic factor
• Inflammation
• Chondrocyte function
• Which leads to loss of articular cartilage

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When there is damage to articular
cartilage ? Increase activity of chondrocytes to
remove and repair the damage Depending on
degree of damage the balance between breakdown
and resynthesis of cartilage can be lost
? Which leads to increase breakdown of cartilage
? Ultimately, loss of cartilage
Destruction of aggrecans by proteolytic enzyme
is consider to play a key role
31
There is also involvement of collagen receptors
named DDR-2 , located on chodrocyte cell
surface In healthy cartilage ,DDR-2 is inactive
,which is masked by aggrecan from contact with
collegen Damage to cartilage ? Triggers
aggrecan destruction ? Exposure of DDR-2 to
collagen ? Active DDR-2 increase activity of
MMP-13 ? Which destroy collagen Collagen
breakdown products further stimulate DDR-2,in
which more collagen is destroyed
32
Huge research work has been done on genes
involved in OA which shows that In OA ,
expression of hundreds of genes of cartilage
tissue are affected which alters chondrocyte
phenotype In addition to articular cartilage
there is also role of subchondral bone in OA In
OA , subchondral bone release vasoactive peptides
and MMPs Neovascularization and subsequent
increase in permeability of the adjacent
cartilage occurs and contributes to further
cartilage loss
33
Substantial loss of cartilage cause joint space
narrowing and leads to painful and deformed
joints The remaining catilage softens and
devlopes fibrillation(Verticle cleft ) and there
is splittting and further loss of cartilage and
exposure of underlying bone As cartilage is
destroyed and the adgecent subchondral bone
undergoes pathologic changes, cartilage is eroded
completely, leaving denuded subchondral bone
which becomes dence , smooth and glistening A
more brittle, stiffer bone results, with
decreased weight-bearing ability and development
of sclerosis and microfractures The joint
capsule and synovium also show pathologic
changes in OA.
34
Inflammation, noted clinically as synovitis, may
result from release of inflammatory mediators
from chondrocytes, such as prostaglandins
Inflammation is localized to the affected joint,
in contrast to that seen in rheumatoid or other
inflammatory arthritides. The pain in OA is not
due to distruction of cartilage but arise from
the activation of nociceptive nerve ending within
the joint by mechanical and chemical irritants
35
So,the slow progressive changes in OA consist of
an increase in water content, loss of PG, and
reduction of PG aggregates of cartilage. The
cartilage is subsequently unable to repair
itself. Alterations in metabolism of
subchondral bone adjacent to articular cartilage
appear necessary for continued cartilage
destruction. Eventually, progressive loss of
articular cartilage and increasing subchondral
sclerosis lead to an abnormal and painful joint.
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Clinical Represntation
Age Usually elderly Gender Age lt45 more common
in men Age gt45 more common in women Symptoms ?Pai
n Deep, aching character Pain on motion Pain with
motion early in disease Pain with rest late in
disease ? Stiffness in affected joints Resolves
with motion, recurs with rest Usually lt30
minutes duration Often related to weather ?
Limited joint motion May result in limitations
activities of daily living
Signs, history, and physical examination Monarticu
lar or oligoarticular asymmetrical
involvement Hands Distal interphalangeal joints
Heberdens nodes Proximal interphalangeal
joints Bouchards nodes First
carpometacarpal joint Osteophytes give
characteristic square appearance of the hand
Knees Patellofemoral compartment
involvement Pain related to climbing
stairs Transient joint effusions Typically
noninflammatory synovial fluid
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Hips Pain during weight-bearing
activities Stiffness, especially after
inactivity Limited joint motion Spine L3 and L4
involvement is most common in the lumbar
spine Signs and symptoms of nerve root
compression Radicular pain Paresthesias Loss of
reflexes Muscle weakness associated with the
affected nerve root Feet Typically involves the
first metatarsophalangeal joint Other sites, less
commonly involved Shoulder, elbow,
acromioclavicular, sternoclavicular, and
temporomandibular joints
Observation on joint examination Bony
proliferation or occasional synovitis Local
tenderness Muscle atrophy Limited motion with
passive/active movement Deformity Radiologic
evaluation Early mild OA Radiographic
changes often absent Progression of OA Joint
space narrowing Subchondral bone sclerosis
Marginal osteophytes Late OA Abnormal
alignment of joints Effusions Characteristics of
synovial fluid High viscosity Mild leukocytosis
Laboratory values ESR
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Treatment Goals (1) to educate the patient,
caregivers, and relatives (2) to relieve pain
and stiffness (3) to maintain or improve joint
mobility (4) to limit functional impairment
and (5) to maintain or improve quality of life
Treatment of OA
Non-pharmacological Treatment 1.Diet 2.Physical
And Occupational Therapy 3.Surgery
Pharmacological Treatment 1.Analgesics Oral
Topical 2.NSAIDs 3. Glucosamine
Chondroitin 4.Hyluronate Injection 5.Narcotic
Analgesics 6.Disease Modifying Drugs
40
Diet Excess weight increases the biomechanical
load on weight-bearing joints, and is the single
best predictor of need for eventual joint
replacement. Weight loss is associated with
decreased symptoms and Disability Even 3-5 kg of
weight loss can decrease the biomechanical force
on a weight-bearing joint. Although dietary
intervention for overweight OA patients is
reasonable, weight loss usually requires a
motivated patient and a structured weight-loss
program. Diet with low fat (calories) and high
fibre as well as balanced diet should be taken to
decrease weight
41
Physical And Occupational Therapy Physical
therapywith heat or cold treatments and an
exercise program Which helps to maintain and
restore joint range of motion and reduce pain and
muscle spasms. Warm baths or warm water soaks
may decrease pain and stiffness. Exercise
programs and quadriceps strengthening can improve
physical functioning and can decrease disability,
pain, and analgesic use by OA patients. The
decision about whether to encourage walking
should be made on an individual basis. With weak
or deconditioned muscles,the load is transmitted
excessively to the joints, so weight-bearing
activities can exacerbate symptoms.
42
However, avoidance of activity by those with hip
or knee OA leads to further deconditioning or
weight gain. A program of patient education,
muscle stretching and strengthening,and
supervised walking can improve physical function
and decrease pain in patients with knee OA.
43
Surgery Surgery can be recommended for OA
patients with functional disability and/or severe
pain that is unresponsive to conservative
Patients with mild knee OA, an osteotomy may
correct the misalignment of knee Knee
arthroscopy or lavage have been recommended for
short-term relief of pain, a recent study showed
these two procedures to be equivalent to
surgery Experimental but potentially restorative
approaches involve Soft tissue grafts,
Penetration of subchondral bone, Cell
transplantation, and Use of growth factors
44
Pharmacological Therapy Things to be taken in
concern 1.Adverse effect of the drug given for
OA 2.As OA is usually seen in old age people with
some other conditions they Pharmacological
treatment should be done with so much
causion 3.Always combine non pharmacological
therapy with pharmacological one for more
improvement
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Analgesics Acetaminophen is used as first-line
drug therapy for pain management in OA, due to
its relative safety, efficacy, and lower cost
compared to NSAIDs Pain relief with
acetaminophen can be similar to that obtained
with NSAIDs, although some patients will respond
better to NSAIDs. Some studies have shown
comparable efficacy for acetaminophen and NSAIDS,
others have reported that patients experienced
better pain control with NSAIDs than with
acetaminophen, and that OA patients preferred
NSAIDs to acetaminophen
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Mechanism Of Action Acetaminophen is thought to
work within the central nervous system to
inhibit the synthesis of prostaglandins, agents
that enhance pain sensations. Acetaminophen
prevents prostaglandin synthesis by blocking the
action of central cyclooxygenase. Kinetics Acetam
inophen is well absorbed after oral
administration (bioavailability is 60 to 98),
achieves peak concentrations within 1 to 2 hours,
is inactivated in the liver by conjugation with
sulfate or glucuronide, and its metabolites are
renally excreted Efficacy Comparable relief of
mild to moderate OA pain has been demonstrated
for acetaminophen at 2.6 to 4 g/day
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ADR Hepatotoxicity, and Possibly renal
toxicity Drug Drug Intrection Isoniazid can
increase the risk of hepatotoxicity. Chronic
ingestion of maximal doses of acetaminophen may
intensify the anticoagulant effect in patients
taking warfarin, Food decreases the maximum
serum concentration of acetaminophen by
approximately one-half.
48
Non Steroidal Anti - Iflammatory
Drugs MOA Blockade of prostaglandin synthesis
through inhibition of cyclooxygenase (bothCOX-1
andCOX-2 enzymes) is the principal mechanism by
which NSAIDs relieve pain and inflammation
49
Kinetics High oral availability, high protein
binding, and absorption as active drugs (except
for sulindac and nabumetone, which require
hepatic conversion for activity). The most
important difference in NSAIDs is a serum
half-life ranging from 1 hour for tolmetin to 50
hours for piroxicam, impacting the frequency of
dosing and potentially, compliance with therapy.
Elimination of NSAIDs largely depends on
hepatic inactivation, with a small fraction of
active drug being renally excreted. NSAIDs
penetrate joint fluid, reaching about 60 of
blood levels
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ADR Minor complaintsnausea, dyspepsia, anorexia,
abdominal pain, flatulence, and diarrhea To
minimize these symptoms, NSAIDs should be taken
with food or milk, except for enteric-coated
products, which should not be taken with milk or
antacids All NSAIDs have the potential to cause
GI bleeding. Possible Mechanism
For this Unionized NSAIDs enter gastric mucosal
cells, release hydrogen ions, and are
concentrated (ion trapped) within cells, with
cell death or damage. Gastric mucosal injury
can also result from NSAID inhibition of
gastroprotective prostaglandins.
51
COX-2 inhibitors pose a decreased risk of GI
toxicity compared to nonspecific NSAIDs, an
especially important consideration when treating
those at risk for clinically significant GI
adverse effects. NSAIDs may cause kidney
diseases, Acute renal insufficiency, Hyperkalemia
, and Renal papillary necrosis Clinical
features of these NSAID-induced renal syndromes
Increased serum creatinine Increased blood urea
nitrogen, Hyperkalemia, Elevated blood
pressure, Peripheral edema, and Weight gain.
52
Mechanisms of NSAID injury include direct
toxicity, and inhibition of local prostaglandins
that promote vasodilation of renal blood
vessels and preserve renal blood flow. COX-2
inhibitors also have potential for renal
toxicity COX-2 activity has been demonstrated
in a variety of sites in the kidney and is
upregulated in salt-depleted states
Importantly,COX-2 inhibitors decrease urinary
prostaglandins and cause sodium and potassium
retention, as do nonspecific NSAIDs
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Drug Intrection Lithium, Warfarin, Oral
hypoglycemics, High-dose methotrexate, Antihypert
ensives, Angiotensin-converting enzyme
inhibitors, ß-blockers, and diuretics.
55
Topical Therapies Topical products can be used
alone or in combination with oral analgesics or
NSAIDs. Capsaicin, isolated from hot peppers,
releases and ultimately depletes substance P from
afferent nociceptive nerve fibers. Substance P
has been implicated in the transmission of pain
in arthritis, and capsaicin cream has been shown
in four controlled studies to provide pain relief
in OA when applied over affected joints To be
effective, capsaicin must be used regularly, and
it may take up to 2 weeks to work. It is well
tolerated, except that some patients experience a
temporary burning sensation at the site of
application. Although use is recommended four
times a day, a twice-daily application may
enhancelong-term adherence and edequate effet
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GLUCOSAMINE AND CHONDROITIN These substances
stimulate proteoglycan synthesis from
articular cartilage in vitro Chondroitin and
glucosamine are superior to placebo in
alleviating pain from knee or hip OA. In
studies, chondroitin sulfate showed similar
analgesic benefits to diclofenac A recent
meta-analysis of glucosamine and chondroitin
indicated that both agents had efficacy in
reducing pain and improving mobility, and that
glucosamine reduced joint space narrowing further
more were associated with slower loss of
cartilage than placebo, in knees affected by OA
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CORTICOSTEROIDS Intra-articular glucocorticoid
injections can provide excellent pain relief,
particularly when a joint effusion is present
Aspiration of the effusion and injection of
glucocorticoid are carried out aseptically,and
examination of the aspirate to exclude
crystalline arthritis or infection is
recommended. The therapy is generally limited
to three or four injections per year because of
the potential systemic effects of steroids, and
because the need for more frequent injections
indicates little response to the
therapy. Systemic corticosteroid therapy is not
recommended in OA, given the lack of proven
benefit and the well-known adverse effects with
long-term use.
58
HYALURONATE INJECTIONS Agents containing
hyaluronic acid (HA) (sodium hyaluronate) are
available for intra-articular injection for
treatment of knee OA. High-molecular-weight HA
is an important constituent of normal cartilage,
with viscoelastic properties providing
lubrication with motion and shock absorbency
during rapid movements Endogenous HA also may
have anti-inflammatory effects because the
concentration and molecular size of synovial HA
decrease in OA, administration of exogenous HA
products has been studied, with the theory that
this could reconstitute synovial fluid and reduce
symptoms. Injections temporarily and modestly
increase viscosity. HA products are injected
once weekly for either 3 or 5 weeks.
59
Injections are well tolerated, although acute
joint swelling and local skin reactions,
including rash, ecchymoses, and pruritus have
been reported. HA injections may be beneficial
for patients unresponsive to other
therapies. These agents are expensive because the
treatment includes both drug costs and
administration costs. As a result, HA
injections are often used after less expensive
therapies have demonstrated lack of efficacy
60
DISEASE-MODIFYING DRUGS Disease-modifying drugs
are targeted not at pain relief but at
preventing, retarding, or reversing damage to
articular cartilage Most products have been
tested in animal models, and limited human data
are available. Thus far, OA is a disease whose
symptoms can be alleviated, but whose progress is
impossible to stop because of this, clinicians
were very interested to learn that both
chondroitin and glucosamine show
disease-modifying potential in patients with OA
Another approach is that of pharmacologic
agents that could mimic TIMPs and thus
potentially decrease cartilage destruction.
61
Heparinoid products that contain
glycosaminoglycans, sodium pentosan polysulfate,
and calcium pentosan polysulfate show promise in
preliminary work limited largely to animal models
and in vitro studies There is also recent
interest in the potential of cyclooxygenase-inhibi
ting nitric oxidedonor compounds to relieve OA
while sparing GI adverse effects.
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NARCOTIC ANALGESICS Low-dose narcotic analgesics
may be very useful in patients who experience no
relief with acetaminophen, NSAIDs,
intra-articular injections, or topical
therapy. These agents are particularly useful in
patients who cannot take NSAIDs due to renal
failure, or for patients in whom all other
treatment options have failed and who are at
high surgical risk, precluding joint
arthroplasty. Low-dose narcotics are the
initial intervention, usually given in
combination with acetaminophen. Sustained-release
compounds usually offer better pain
control throughout the day, and are used when
simple narcotics are ineffective.
63
If pain is intolerable and limits activities of
daily living, and the patient has sufficiently
good cardiopulmonary health to undergo a major
surgery, joint replacement may be preferable to
continued reliance on narcotics.
64
Guided By Samir Rabadiya, Associate Profesor
,Department Of Pharmaceutical Sciences Acknowled
gement Sachin Parmar,Associate Profesor
,Department Of Pharmaceutical Sciences Payal
Bhalodia,Associate Profesor ,Department Of
Pharmaceutical Sciences Rahul Solanki,BE
65
References Pharmacotherapy ,A Pathophysiological
Approch Joseph T. DiPiro, PharmD, FCCP Professor
and Executive Dean, South Carolina College of
Pharmacy, University of South Carolina, Columbia,
and Medical University of South Carolina,
Charleston Robert L. Talbert, PharmD, FCCP,
BCPS Professor, College of Pharmacy, University
of Texas at Austin Professor, Departments of
Medicine and Pharmacology, University of Texas
Health Science Center at San Antonio, Texas Gary
C. Yee, PharmD, FCCP Professor and Chair,
Department of Pharmacy Practice, College of
Pharmacy, University of Nebraska Medical Center,
Omaha, Nebraska Gary R. Matzke, PharmD, FCP,
FCCP Professor, Department of Pharmacy and
Therapeutics, School of Pharmacy, Renal-Electrolyt
e Division, School of Medicine, University of
Pittsburgh, Pittsburgh, Pennsylvania Barbara G.
Wells, PharmD, FASHP, FCCP, BCPP Dean and
Professor, School of Pharmacy, The University of
Mississippi, University, Mississippi L. Michael
Posey, BS Pharm President, PENS Pharmacy
Editorial and News Services, Athens, Georgia
66
Arthritis Research UK Obesity Action
Coalition Anna Litwic, MD Specialist Registrar
in Rheumatology Giuseppe Musumeci , Department
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Human Anatomy and Histology Section, School of
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95123 Catania, Italy F. Berenbaum yz Department
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