Osteoarthritis is a degenerative joint disease characterized by breakdown of articular cartilage and bone changes. It commonly affects weight-bearing joints and is a leading cause of disability. Risk factors include obesity, joint injury, genetics, and aging. Symptoms include joint pain and stiffness that worsens with use and improves with rest. Diagnosis is based on symptoms and confirmed with x-ray findings. Treatment focuses on reducing pain and inflammation, maintaining joint function, and managing other risk factors through lifestyle changes, physical therapy, braces, medications like acetaminophen, NSAIDs, or surgery for advanced cases.

1. Musculoskeletal disorders therapeutics
By: Tsegaye Melaku
[B.Pharm, MSc, Clinical Pharmacist]
3-January-2017
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et +251913765609
Chapter 2
Osteoarthritis
1

2. Learning Objectives
Upon completion of the chapter, you will be able to:
Explain the pathophysiologic mechanisms involved in the development
of osteoarthritis (OA).
Identify risk factors associated with OA.
Recognize the clinical presentation of OA.
Determine the goals of therapy for individual patients with OA.
Formulate a rational pharmacologic & non-pharmacologic plan for
patients with OA.
Modify an unsuccessful treatment strategy for OA.
Develop monitoring parameters to assess effectiveness and adverse
effects of pharmacotherapy for OA.
2

3. Mini case
K.P, a 60-year-old male, presented to JUSH with complaints of deep aching pain
and stiffness in both of his knees. The patient reported that this pain was initially
felt at work when lifting heavy materials, but more recently he had experienced
pain in the absence of any physical activity or exertion. KP's past medical history
is significant for diabetes, hyperlipidemia, obesity, and asthma. His medication
history includes metformin 500 mg twice daily, glyburide 10 mg daily, simvastatin
10 mg daily, albuterol 2 puffs PRN and acetaminophen 325 mg daily for the last
3 months for pain. The patient reported that he is no longer able to walk due to
the severity of his pain. KP's past social history included 30 years as a
construction worker and infrequent alcohol consumption (two drinks per week).
The patient's age (>50 years old), radiographic identification of joint space
narrowing and osteophyte formation, and past medical and occupational history
supported a diagnosis of osteoarthritis.
 Clinical sign and sxs pertinent to OA??
 Risk factors??
 Optimal management??
 Monitor and evaluate??
3

4. Introduction: Osteoarthritis
Earlier perceived as: progressive destruction of articular cartilage.
OA is a degenerative disease of diarthrodial (synovial) joints,
characterized by
Breakdown of articular cartilage
Proliferative changes of surrounding bones
Weight-bearing joints (e.g., hips and knees) are most susceptible,
also hands.
Causes tremendous morbidity and financial burden (high
prevalence and involve critical joints)
4
Articular cartilage, synovium, capsule,
and subchondral bone, surrounding
ligaments and muscles

5. Epidemiology[1]
Most common form of arthritis/joint disease.
15% of the population is affected.
Strongly related to age
OA of the knee joint: 70% of the population over 60 yrs of age
Leading cause of chronic mobility disability.
~ ~11.6 million in US by 2020.
Most common reason for total-hip and knee replacement.
5
50% of those over 65 yrs
85% of aged at least 75 yrs

6. Radiological evidence found in over 90 % of the population (8th
decade of life)
Attributed annual cost (medical care and lost wages) ~ $65 million
in US.
Women exhibit a higher prevalence of hip and knee OA than men
They have more generalized disease.
More likely to have inflammation of the proximal(Bouchard’s
nodes) and distal interphalangeal (Heberden’s nodes) joints
of the hands.
6
Epidemiology[2]

7. Etiology/Risk factors
Multifactorial.
Many patients have >1 risk factor.
The most common risk factors:
Obesity,
Occupation,
Participation in certain sports,
Hx of joint trauma, and a genetic predisposition.
NB: Patients with osteoporosis are also less likely to have OA
 (Opposite influences of body weight on bone strength and OA risk).
7

8. Obesity Occupation and Sports
Excess joint loading
OA of the knee, hip, and hand
Obesity often precedes OA (not
due to inactivity)
Higher relative risk of knee OA.
Risk of developing OA increases
by ~10% with each additional kg
of weight.
Weight loss of even 5 kg (11 lbs)
decreases the risk of future knee
OA by 50%.
Occupations requiring prolonged
standing, kneeling, squatting, lifting or
moving of heavy objects, such as
shipbuilding, mining, some types of
factory work, carpentry, and farming.
Repetitive motion (hand OA), with the
dominant hand usually affected.
Sports: wrestling, boxing, baseball
pitching, cycling, and football
(professional >>recreational)
8

9. Trauma Genetic Factors ???
Traumatic injury to articular
cartilage
Meniscal damage (knee OA)
 Loss of proper load bearing and
shock absorption
 Increased focal load on cartilage
and on subchondral bone.
Quadriceps muscle weakness (knee
OA)
 Loss of maintaining joint stability.
Knee malalignment
Genetic links have been shown with
OA of the first metatarsophalangeal
joint and with generalized OA.
Heberden nodes: 2 fold higher risk if
the woman's mother had them
Shown in twin studies (39% to 65%,
60%, and 70% for hand, hip, and
spine OA, respectively).
Genes related to inflammation (e.g.
IL1, IL-10), Wnt signaling (FRZB,
LRP5), bone morphogenetic proteins
(BMP2, BMP5, and GDF5), and
proteases or their inhibitors
9

10. Classification
10
Subdivided by etiology
 No identifiable cause
 Most common.
 Associated with a known
cause rheumatoid or
another inflammatory
arthritis, trauma,
metabolic or endocrine
disorders, and
congenital factors.

11. Pathophysiology of OA
11

12. Normal Cartilage
Articular cartilage possesses viscoelastic properties that
provide
Lubrication with motion,
Shock absorbency during rapid movements, and
Load support.
In synovial joints, articular cartilage is found between the
synovial cavity on one side and a narrow layer of calcified
tissue overlying subchondral bone on the other side.
12

13. Cont’d…
Cartilage is easily compressed, losing up to 40% of its original
height when a load is applied.
Compression increases the area of contact and disperses force
more evenly to underlying bone, tendons, ligaments, and muscles.
Cartilage is almost frictionless, and together with its
compressibility  this enables
Smooth movement in the joint.
Distributes load across joint tissues  to prevent damage.
Stabilizes the joint.
13

14. Cont’d…
Cartilage
Composed of a complex, hydrophilic, extracellular matrix (ECM).
It is approximately 75% to 85% water and 2% to 5%
chondrocytes (the only cells in cartilage),
It contains collagen proteins, smaller amounts of several other
proteins, proteoglycans, and long hyaluronic acid molecules.
14

15. Osteoarthritic Cartilage[1]
Local mechanical influences, genetic factors, inflammation, and
aberrant chondrocyte function   loss of articular cartilage.
At a molecular level: change in extracellular and intracellular
molecules (chondrocyte regulation, phenotypic changes, proteolytic
degradation of cartilage components,, and the joint synovium.
15

16. Damage to articular cartilage chondrocyte activity increases in
an attempt to remove and repair the damage
Depending on the degree of damage, the balance between
breakdown and resynthesis of cartilage can be lost, and a vicious
cycle of increasing breakdown can lead to further cartilage loss.
Destruction of aggrecans by the proteolytic enzyme: play a key
role.
16
Osteoarthritic Cartilage[2]

17. Current postulate of pathogenesis: collagen receptor(DDR-2)
 Located on the chondrocyte cell surface
In healthy cartilage, DDR-2 is inactive, masked from contact with
collagen by aggrecans.
Damage to cartilage triggers aggrecans destruction  exposing
DDR-2 to collagen active DDR-2  increases activity of MMP-13,
which destroys collagen.
Collagen breakdown products  further stimulate DDR-2
(vicious circle continued).
17
Osteoarthritic Cartilage[3]

18. Subchondral bone undergoes pathologic changes that may precede,
coincide with, or follow damage to the articular cartilage.
Allowing damage to articular cartilage to progress.
Subchondral bone releases vasoactive peptides and MMPs.
Neovascularization   increased permeability of the adjacent cartilage
  further to cartilage loss.
Substantial loss of cartilage  joint space narrowing   painful,
deformed joint
A more brittle, stiffer bone results, with decreased weight-bearing ability
and development of sclerosis and microfractures.
18

19. 19

20. 20

21. Clinical Presentation
Symptoms
Pain
Deep, aching character
Pain with motion early in
disease
Pain with rest late in disease
Stiffness in affected joints
Resolves with motion, recurs with
rest ("gelling" phenomenon)
Usually duration <30 minutes
Often related to weather
Limited joint motion
May result in limitations activities
of daily living
Instability of weight-bearing joints
21
Age <45 more common in men
Age >45 more common in women

22. 22
Monarticular or oligoarticular;
asymmetrical involvement
Hands
Distal interphalangeal joints
Heberden nodes (osteophytes
or bony enlargements)
Proximal interphalangeal joints
Bouchard's nodes (osteophytes)
First carpometacarpal joint
Osteophytes give characteristic
square appearance of the hand
(shelf sign)
Knees
Pain related to climbing stairs
Medial compartment involvement
Genu varum (bowlegged
deformity)
Lateral compartment involvement
Genu valgum (knock-kneed
deformity)
Transient joint effusions
Typically non-inflammatory
synovial fluid (WBC <2000/mm3
[<2 x 109/L])
Signs, history, and physical examination

23. 23

24. 24

25. 25

26. Hips
Groin pain during weight-
bearing activities
Stiffness, especially after
inactivity
Limited joint motion
Spine
L3 and L4 involvement
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
Characteristics of synovial fluid
High viscosity
Mild leukocytosis (<2000
WBC/mm3 [<2 x 109/L])
Laboratory values
No specific test
ESR and hematologic and
chemistry survey are normal
26

27. Diagnosis
History, P/E, radiography and laboratory testing.
The major diagnostic goals are
To discriminate between primary and secondary OA and
To clarify the joints involved, severity, and response to prior
therapies, providing a basis for a treatment plan.
27

28. Observation on joint examination Radiologic evaluation
Bony proliferation or
occasional synovitis
Local tenderness
Crepitus
Muscle atrophy
Limited motion with
passive/active movement
Deformity
Early mild OA
Changes often absent
Progression of OA
Joint space narrowing
Subchondral bone sclerosis
Marginal osteophytes
Late OA
Abnormal alignment of joints
Effusions
28

29. Cont’d…
For hip OA, a patient must have:
Pain in the hip plus
At least 2 of the following three:
ESR<20 mm/hr (<5.6 m/s),
Femoral or acetabular osteophytes on radiography, or
Joint space narrowing on radiography
 (sensitivity of 89% and a specificity of 91%).
29

30. Cont’d…
For knee OA, a patient must have:
Pain at the knee Plus
Osteophytes on radiography plus one of the following:
Age older than 50 years,
Morning stiffness no more than 30 minutes,
Crepitus on motion, bony enlargement, bony tenderness, or
palpable warmth.
Provides a sensitivity of 95% and a specificity of 69%.
30

31. For hand OA, a patient must have:
Hand pain (hand aching or stiffness) plus
At least three of the following four features:
Hard tissue enlargement of 2 or more of 10 selected joints.
Hard enlargement of two or more DIP joints
Fewer than three swollen metacarpophalangeal (MCP) joints
Deformity of at least 1 of the 10 selected joints
31

32. Treatment
Desired Outcome
Educate the patient, family members, and caregivers.
Relieve pain and stiffness.
Maintain or improve joint mobility.
Limit functional impairment.
Maintain or improve quality of life.
32

33. General Approach to Rx
Treatment for each OA patient depends on 
Distribution and severity of joint involvement,
Comorbid disease states,
Concomitant medications, and allergies
Management for all individuals with OA should begin with
Patient education,
Physical and/or occupational therapy, and
Weight loss or assistive devices if appropriate.
33

34. 1˚ objective of medication : alleviate pain.
Acetaminophen (scheduled) : 4 g/day (initially); if not
NSAIDs, possibly a COX-2-selective inhibitor (celecoxib)
Capsaicin or topical NSAID creams: adjuncts for pain control.
Joint aspiration followed by glucocorticoid
Offered concomitantly with oral analgesics or after their lack of
efficacy
Opioid analgesics : last option
Surgery (joint replacement): Intractable symptoms or significant loss
of function or
Medications on clinical trials : oral doxycycline, MMP inhibitors,
disease-modifying OA drugs, or cartilage transplantations
34

35. Non-pharmacologic Therapy
a) Diet
Need weight loss.
b) Physical and occupational Therapy
Heat or cold treatments
Warm baths or warm water soaks (decrease pain/stiffness).
Exercise program  restore joint range of motion and to reduce
pain and muscle spasms.
35

36. Cont’d…
c) Surgery
For patients with functional disability and/or severe pain
unresponsive to conservative therapy
Osteotomy  removal of bony tissue  for genu varum
("bowlegged" knees) or genu valgum ("knock-knees")
Arthroplasty Total joint replacement.
36

37. Pharmacologic Therapy
Drug therapy in OA is targeted at relief of pain.
OA is commonly seen in older individuals who have other medical
conditions Rx is often long term
So ???????
37

38. Cont’d…
For mild or moderate pain  topical analgesics or acetaminophen.
Acetaminophen at 2.6 - 4 g/day,
 325 to 650 mg every 4 to 6 hrs
 Total dose must not exceed 4 g daily
 If fail/there is inflammation NSAIDs
ASA 650 mg Qid,
Ibuprofen at 1,200 to 2,400 mg QD,
Naproxen 750 mg QD
38
Have comparable efficacy
Administered in a scheduled
manner.

39. Cont’d…
If acetaminophen is used in the setting of
Chronic alcohol intake or
With underlying liver disease,
39
Duration should be limited.
Dose should not exceed 2 g daily

40. NSAIDs & Selective COX-inhibitors
Non-selective NSAIDS and COX-2–selective NSAIDS superior to
acetaminophen  for improving symptoms and functional limitations.
Risk are GI and cardiovascular effects!!!!!
40

41. Cont’d…
41

42. 42
Cont’d…

43. 43
Cont’d…

44. 44

45. 45

46. 46

47. Topical Therapies
Can be used alone or in combination with oral analgesics or NSAIDs.
Capsaicin (hot peppers), releases and ultimately depletes substance
P from afferent nociceptive nerve fibers.
To be effective, capsaicin must be used regularly.
It may take up to 2 weeks to take effect.
Apply four times a day, a twice-daily (if adherence).
47

48. Corticosteroids
IA injections can provide excellent pain relief particularly when a
joint effusion is present.
After injection, the patient should minimize activity and stress on the
joint for several days.
Alleviate knee pain and stiffness caused by OA.
Triamcinolone 10 to 20 mg and methylprednisolone 20 to 40 mg 
preferred b/c of reduced solubility that allows the agents to remain in
the joint space longer.
48

49. Cont’d…
Limit to 3 or 4 injections/year due to the potential systemic effects.
The need for more frequent injections indicates little response to the
therapy.
Local A/Es  osteonecrosis, tendon rupture, and skin atrophy at the
injection site.
49

50. Hyaluronate Injections
IA hyaluronic acid (HA) sodium hyaluronate.
High-molecular-weight HA  an important constituent of synovial
fluid.
Endogenous HA have antiinflammatory effects.
 Because the concentration and molecular size of synovial HA
decreases in OA need administration of exogenous HA.
Most HA products are injected once weekly for either 3 or 5 weeks.
50

51. Cont’d…
Preparations
Hyalgan, Euflexxa (20 mg sodium hylaronate/2 mL),
Supartz (25 mg sodium hylaronate/2.5 mL),
Synvisc (16 mg hylan polymers/ 2 mL),
Synvisc-One (48 mg hylan polymers/6 mL), and
Orthovisc (30 mg hyaluronan/2 mL).
Hyalgan and Supartz  weekly for five injections.
Synvisc, Euflexxa, and Orthovisc weekly for 3 injections.
51

52. Opioid Analgesics
Low dose opioid who experience no pain relief with
acetaminophen, NSAIDs IA injections, or topical therapy.
In patient who cannot take NSAIDs because of renal failure or
cardiovascular disease.
Patients in whom all other treatment options have failed.
In who are at high surgical risk, precluding joint arthroplasty are
also candidates for opioid therapy.
As many patients with OA are elderly, it is important to carefully use
opioids to promote safety.
52

53. Cont’d…
The following recommendations have been suggested to optimize
opioid therapy:
Use the least invasive route of administration,
Initiate one agent at a time, at a low dose,
Allow a sufficiently long interval between dose increases to allow an
assessment of efficacy and safety,
Use a long-acting preparation,
Therapy should be constantly monitored and adjusted if necessary,
Changing opioids may be necessary.
53

54. 54
Medication Dosage and Frequency Maximum Dosage
(mg/day)
Acetaminophen 325–650 mg every 4–6 hours or 1 g 3–4 times/day 4,000
Tramadol 50–100 mg every 4–6 hours 400
Acetaminophen/codeine 300 to 1000 mg/15 to 60 mg every 4 hours as
needed
4,000mg/360mg
Acetaminophen/oxycodone 325 to 650 mg/2.5 to 10 mg every 6 hours PRN 4,000mg/40mg
Capsaicin 0.025% or 0.075% Apply to affected joint 3–4 times per day
Glucosamine HCl/chondroitin
sulfate
500mg/400 mg 3 times/day 1,500/1,200
Aspirin, plain, buffered, or
enteric coated
325–650 mg every 4–6 hours for pain; anti
inflammatory doses start at 3,600 mg/day in
divided doses
3,600
Medications Commonly Used in the Treatment of Osteoarthritis

55. 55
Salsalate 500–1,000 mg 2–3 times a day 3,000
Diflunisal 500–1,000 mg 2 times a day 1,500
Choline salicylate 500–1,000 mg 2–3 times a day 3,000
Choline magnesium salicylate 500–1,000 mg 2–3 times a day 3,000
Etodolac 800–1200 mg/day in divided doses 1,200
Diclofenac 100–150 mg/day in divided doses 200
Indomethacin 25 mg 2–3 times a day; 75 mg SR once daily 200; 150
Ketorolac 10 mg every 4–6 hours 40
Nabumetone 500–1,000 mg 1–2 times a day 2,000
Fenoprofen 300–600 mg 3–4 times a day 3,200
Flurbiprofen 200–300 mg/day in 2–4 divided doses 300
Ibuprofen 1,200–3,200 mg/day in 3–4 divided doses 3,200
Ketoprofen 150–300 mg/day in 3–4 divided doses 300
Naproxen 250–500 mg twice a day 1,500
Naproxen sodium 275–550 mg twice a day 1,375
Oxaprozin 600–1,200 mg daily 1,800
Meclofenamate 200–400 mg/day in 3–4 divided doses 400
Mefenamic acid 250 mg every 6 hours 1,000
Piroxicam 10–20 mg daily 20
Meloxicam 7.5 mg daily 15
Celecoxib 100 mg twice daily or 200 mg daily 200 (400 for RA)
Medication Dosage and Frequency Max. Dosage
(mg/day)

56. Monitoring and evaluation
Clinical sign and symptoms
Effectiveness
Safety
56

57. 57