Medical PPt for medical students and professionals

1. GSPATNAIK
osteoarthritis

2. Osteoarthritis
(Degenerative Joint Disease)
Epidemology
Most common form of arthritis worldwide
Occurs most in women and in adults over
age 45
Occurs in 80% of people over 55 years of age
Affects >40 million people in US (1 in 6)
23% experience limitation of activities
Cost in medical care and lost wages ~$95
billion
(Elders, 2000; Loeser et al, 2001; Merskey et al, 1994)

3. Definition of Osteoarthritis
“Osteoarthritis (OA) is a degenerative joint disease,
occurring primarily in older persons, characterized by erosion
of the articular cartilage, hypertrophy of bone at the margins
(i.e., osteophytes), subchondral sclerosis, and a range of
biochemical and morphologic alterations of the synovial
membrane and joint capsule. Pathologic changes in the late
stages of OA include softening, ulceration, and focal
disintegration of the articular cartilage; synovial inflammation
also can occur.”
Harris: Kelley's Textbook of Rheumatology, 7th ed.
“Despite its prevalence, the precise etiology,
pathogenesis, and progression of OA remain
beyond our understanding…”

4. Osteoarthritis
Pathophysiology
Progressive loss of articular cartilage
Chondrocytes produce metalloproteinases that degrade
cartilage and cause fissuring, pitting, erosion, and denuded
areas
Subchondral bone thickens and osteophytes, or bone spurs,
form
Synovium thickened (contains moderate amount of
lymphocytes, plasma cells)
Joint capsule and ligaments hypertrophied
(Loesser et al, 2001; Wall et al, 1994)

5. Osteoarthritis
Clinical Characteristics
Deep aching pain, poorly localized
May occur in one or two joints or be generalized
Pain occurs in involved joint and is relieved by rest
Joint stiffness in morning and after periods of inactivity
Aching “night pain” is common
If pain is severe on activity and asymptomatic at rest, evaluate for
neurogenic claudication
(Loesser et al, 2001)

6. What Causes the Pain?
Cartilage is aneural, so the joint pain
must arise from other structures:
 Subchondral bone: microfractures, meduallary
hypertension with bone angina
 Osteophytes: stretching of nerve endings in the
periosteum
 Ligaments: stretch
 Joint capsule: inflammation, distention
 Synovium: inflammation
 Periarticular muscle: spasm
 Neuronal plasticity (central sensitization)

7. What Causes the Destruction?
Biomechanical Forces?
OA is mechanically driven
Biochemical Forces?
Chemically mediated
Cytokine activation

8. Associated Risk Factors
Risk Factors and Possible Causes:
 Age
 Female versus Male sex
 Obesity
 Lack of Osteoporosis
 Occupation
 Sports Activities
 Prior injury
 Muscle weakness
 Propioceptive deficits
 Acromegaly
 Calcium crystal deposition disease
Up-To-Date 2005 Risk Factors for and Possible
Causes of Osteoarthritis

9. Osteoarthritis
Diagnosis
History: age, functionality, degree of pain, stiffness, time of
occurrence (e.g., morning, at rest, during activity)
Physical examination: range of motion, tenderness, bony
enlargement of joint
Laboratory findings: radiograph, CBC, synovial fluid analysis
(Loesser et al, 2001; Manek et al, 2000)

10. Radiographic Appearance
Radiographic Criteria:
Loss of joint space
Subchondral sclerosis or cyst
formation
Presence of new bone formation or
osteophytes
Bone demineralization, osteopenia,
extra-articular changes would suggest
other diagnoses.

11. Synovial Fluid Analysis

12. Osteoarthritis
Treatment Considerations: First, perform a
comprehensive assessment of pain and function
Mild-to-moderate pain Paracetamol/ NSAIDs
Moderate-to-severe pain Tramadol and Paracetamol
combination
Severe arthritis pain: COX-2
drugs and non-specific
NSAIDs do not provide
substantial relief
Strong Opioids
Drug therapy ineffective and
function severely impaired
Surgical Treatment
(ACR, 2000; APS, 2002; Manek et al, 2000)

13. Do Oral Medications (Tylenol,
NSAIDs) help or hurt?

14. Paracetamol
Is Paracetamol effective for
Osteoarthritis?
Is Paracetamol the drug of
choice?
Is it safe?
Acetaminophen has clearly been demonstrated to be effective in
the treatment of the pain of OA when c/w placebo, with a NNT
of 3.6 for 50% pain reduction when using 1000mg.
Acetaminophen is the drug of choice in both the ACR and EULAR
guidelines.
Acetaminophen has been demonstrated to be safe in
doses up to 4gm/day.

15. Traditional NSAIDs
Are NSAIDs more effective than paracetamol ?
Are some NSAIDs more efficacious than others?
Do I need to elevate the dosage to an “anti-
inflammatory” range?
Do NSAIDs destroy cartilage in the long term?
Cochrane Review 1997: no evidence to assess clinical
differences among the various NSAIDs. Decisions should be
made upon safety, acceptability and cost.
No…as OA is principally non-inflammatory NSAIDs should clearly
be titrated for clinical effect.
Consensus expert opinion and clinical data appear to state that in
the treatment of mild to moderate osteoarthritis acetaminophen
and NSAIDs have comparable efficacy.
There is no reliable evidence in human models by clinical
trials that NSAIDs are either chondroprotective or
chondrodestructive.

16. COX2 Inhibitors
 What are those COX enzymes again?
 COX breaks down arachadonic acid into
prostaglandins.
 COX1: responsible for normal
physiologic processes like GI protection
and platelet aggregation.
 COX2: involved in the inflammatory
response.
 These new drugs are either called COX2
inhibitors or COX1 sparing.
 COX3 and so on are coming!

17. New FDA Recommendations
April 6, 2005
The three COX2 agents are associated with an increased
risk of serious adverse CV events c/w placebo.
Data from large clinical trials do not demonstrate a
significant increased CV risk of the COX2 agents over the
non-selective NSAIDs.
The COX2 agents reduce the incidence of GI ulcers
visualized at endoscopy.
Box warning label for all prescription NSAIDs including
increased risk of CV events.

18. NSAIDs and Gastric Protection
High risk identification:
Age >65 years
Anti-coagulant use
Prior GI bleeding
Use of oral steroids
H. Pylori
If history of GI bleed, test and treat
If asymptomatic, consider “test and treat”
Treatment options:
NSAID and PPI
If no inflammation ,Tramadol/paracetamol
combination

19. Opioids
Is there a role for opioid analgesia in
osteoarhtritis?
Is there a role for chronic therapy with
opioid analgesics?
Yes…all the guidelines and UpToDate recommend considering narcotic
analgesia for acute exacerbations unresponsive to conventional therapy.
Tramadol is specifically identified by the ACR as well as UpToDate as the
initial agent of choice.
Yes…some patients may require chronic therapy with Tramadol. ACR
guidelines support Tramadol therapy when other treatments have failed
or are not appropriate. American Pain Society guidelines for
nonmalignant pain should be followed.

20. Use of Nonsteroidal Antiinflammatory Drugs
An Update for Clinicians: A Scientific Statement
From the American Heart Association
Elliott M. Antman, MD; Joel S. Bennett, MD;
Alan Daugherty, et al: Circulation.
2007;115:1634-1642.

22. When are Chondroprotective Agents,
like Glucosamine and Intra-Articular
Hyaluronic Acid indicated, if at all?

23. Glucosamine
Glucosamine sulfate and chondroitin sulfate are particularly popular
treatments for osteoarthritis.
Several early studies demonstrated that glucosamine was superior to
placebo and comparable to NSAIDs for knee OA. (manufacturer
supported)
Other studies measuring changes in joint space narrowing suggested a
“chondroprotective” effect against articular cartilage loss.

24. Glucosamine Sulfate
How does it work?
Thought to stimulate chondrocytes to make
proteoglycans.
Thought to possibly inhibit cartilage
catabolic enzymatic activity.
Some hypothesize the sulfate may be key to
the effect.
Real mechanism of action is largely
unknown.

25. Glucosamine
Cochrane Review 2005: WOMAC outcomes of pain, stiffness and
function did not show a superiority of glucosamine over placebo for both
Rotta and non-Rotta preparations of glucosamine. Glucosamine was as safe
as placebo
NIH multi-centered trial:
Glucosamine and chondroitin alone or in combination did not
reduce pain effectively in the overall group of patients
Exploratory analyses suggest that the combination of glucosamine and
chondroitin may be effective in the subgroup of patients with moderate-
to-severe knee pain
European trials that showed a benefit with glucosamine used as
glucosamine sulfate; most of the American trials—including GAIT—
used glucosamine hydrochloride
Clegg DO et al. (2006), N Engl J Med 354(8):795-808

26. Glucosamine
Using Glucosamine:
Safe, however, questions exist as to adverse
effects, purity and efficacy..
Trial of 1500 mg/d for 6 to 8 weeks is not
unreasonable in an informed patient.

27. Hyalgan
Synovial fluid is an ultrafiltrate of plasma
modified by the addition of hyaluronic acid
(HA), which is produced by the synovium.
In osteoarthritis, the HA is decreased and
compromised.
Exogenous supplementation of intraarticular
HA is thought to support changes in the
character of synovial fluid.

28. Hyalgan
What’s the Evidence?
Cochrane Review 2005
Viscosupplementation is an effective treatment for OA
of the knee with beneficial effects: on pain, function
and patient global assessment; and at different post
injection periods but especially at the 5 to 13 week
post injection period.
Questions?
Is HA superior to corticosteroid injections or saline
injections?
Do HA injections result in lower utilization of
NSAIDs?

29. Hyalgan
Using Hyalgan:
Indications: indicated for the treatment of osteoarthritis
not responsive to non-pharmacologic measures and to
simple analgesics.
Requires sterile technique, remove joint effusion if
present prior to injection.
Three to five weekly injections recommended.
Is it safe?
No concern of inhibition of prostaglandins.
Post-injection synovitis is described, and can last up to
three weeks.

30. Who needs to see an Orthopedic
Surgeon, and When?

31. Indications for Arthroscopy
Severe symptomatic OA that has failed to
respond to non-surgical management.
Evidence on clinical assessment of either:
Loose bodies
Mechanical symptoms: locking, giving way, or
catching.

32. Indications for High Tibial Osteotomy
 Indications for osteotomy
Age less than 60 years
Unicompartmental arthritis
10 to 15 degrees of varus deformity on
weightbearing radiographs
Preoperative motion arc of at least 90
degrees
 Flexion contracture less than 15 degrees
Ability and motivation to effectively and
safely perform rehabilitation

33. Indications for Total Joint Replacement
The main indication for total knee
arthroplasty is for relief of pain
associated with arthritis of the knee in
patients who have failed non-operative
treatments.
- American Academy of Orthopedics