Osteoarthritis,general info and pathology with easy flow diagrams

1. Or
Degenerative 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

7. 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

8. Classification
↙ ↘
Primary OA Secondary OA
(idiopathic) (Due to some other disease)
A. Localised
Hands
Hip
Knee
Spine
B. Generalised
Small joints
Large joints
Mixed
C. Erosive osteoarthritis
i) 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,
Wilson’s disease, Hurler disease, Gaucher
disease
v) Rheumatologic– rheumatoid arthritis
vi) Neurological– Charcot joints.

9. 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 (K&L) 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

10. The World Health Organization (WHO) adopted these criteria
as the standard for epidemiological studies on OA
Prevalence of osteoarthritis varies with
I. Age
II. Gender
III. Genetics
IV. Ethic Group
V. Specific Joint Involved
VI. Method For Diagnosis

11. 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 : >70 Knee OA Age : 40 Age : 80
Pre : 1.6 % Pre : 14% ↙ ↘ Pre: 5% Pre : 65%
Age : >25 Age : 55
Pre : 5% Pre : 12%

12. Gender
↙ ↘
Age > 50 Age >60
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

14. 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

15. 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

21. 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

24. 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

25. 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
1. Groth factors
- Bone morphogenetic protien 2
- Insulin like groth factor-1
- tranforming growth factor
2. Catabolism
3. Proteolysis
Stimulated by MMPs, TNF-ᾲ, Interlukein-1, Other cytokines

26. 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

29. OA Cartilage
OA begins with damage to articular cartilage, which is due to
1. Trauma or other injury
2. Excess joint loading by obesity / other reason
3. Instability or injury of the joint that causes abnormal loading
Devlopement of OA is due to
1. Local mechanical influence
2. Genetic factor
3. Inflammation
4. Chondrocyte function
Which leads to loss of articular cartilage

30. 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.

37. Age
Usually elderly
Gender
Age <45 more common in men
Age >45 more common in women
Symptoms
→Pain
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 <30 minutes’ duration
Often related to weather
→ Limited joint motion
May result in limitations activities
of daily living
Signs, history, and physical
examination
Monarticular or oligoarticular;
asymmetrical involvement
Hands
Distal interphalangeal joints
Heberden’s nodes
Proximal interphalangeal joints
Bouchard’s 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
Clinical Represntation

38. 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

39. 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 therapy—with 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

45. 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

46. 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
Acetaminophen 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

47. 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

50. ADR
Minor complaints—nausea, 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

54. Drug Intrection
Lithium,
Warfarin,
Oral hypoglycemics,
High-dose methotrexate,
Antihypertensives,
Angiotensin-converting enzyme inhibitors,
β-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

56. 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

57. 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-
inhibiting nitric oxide–donor compounds to relieve OA while
sparing GI adverse effects.

62. 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
Acknowledgement
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-Electrolyte 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 of Biomedical and Biotechnological Sciences, Human Anatomy and Histology
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V Tandon