Kathmandu University

School of Science
Department of Pharmacy
• Osteoarthritis is a chronic
muscoskeletal condition
characterized by degenerative
disorder of the joints.
• Osteoarthritis can affect weight-
bearing and non-weight-bearing
joints, and may involve single or
multiple joints but it most commonly
affects the knee, hip, and small joints
of the hand.
• Osteoarthritis was previously thought
to be the consequences of ageing,
thereby leading to the term
degenerative joint disease. However,
it is now thought to be the result of
complex interplay of multiple factors.
• Osteoarthritis is uncommon under the age of 35 years with 0.1 % of people affected between the age
of 25-34 years
• 80% of people are affected by the age of 55 years.
• It occurs in all populations irrespective of race, climate or geographical location
• Females are more affected by osteoarthritis than men

• Osteoarthritis - Deaths by sex and age group in United States of America-2020

 Osteoarthritis Rheumatoid Arthritis

This type of arthritis pain tends to RA is an inflammatory condition

develop gradually and intermittently where immune system attacks the
Onset
over several months or years when tissues in joints causing pain and
bone rubs against bone. stiffness that worsens over time.

Osteoarthritis is common in the hip, RA can appear in any joint, its most
Location knee, lower back, neck, feet and common targets are the hands,
finger joints wrists, and feet.

Mild morning stiffness is common in

Morning stiffness doesn't began to
osteoarthritis and often goes away
improve for an hour or longer.
Type of after just a few minutes of activity.
Occasionally, prolonged joint
stiffness The same type of stiffness may
stiffness in the morning is the first
happen during the day after resting
symptom of RA
the joint for an hour or so.
• Osteoarthritis is classed as either primary or as secondary to a diagnosed cause.
⚬ Primary Osteoarthritis
⚬ Secondary Osteoarthritis

Primary Osteoarthritis
• In primary osteoarthritis the exact cause is unknown(idiopathic). This is the most
commonly diagnosed form of osteoarthritis and is considered to occur largely due to “wear
and tear” over time. People tend to develop this type of osteoarthritis starting from the age
of 55 or 60. It may be localized to certain joints; therefore, primary OA is usually subdivided
by:

⚬ Localized Osteoarthritis: Most commonly affects the hands, feet, hip, knees, and spine,
and less commonly the shoulder, and wrist joint.

⚬ Generalized Osteoarthritis: Generalized osteoarthritis is a subset of osteoarthritis in

which three or more joints or groups of joints are affected. It is often referred to as GOA
and may be referred to as polyarticular osteoarthritis and multi-joint osteoarthritis.
• Osteoarthritis is classed as either primary or as secondary to a diagnosed cause.
⚬ Primary Osteoarthritis
⚬ Secondary Osteoarthritis

Secondary Osteoarthritis
• In secondary osteoarthritis there is a link to specific cause.
• This form of osteoarthritis results from conditions that induce a change in the
microenvironment of the cartilage.
• Such conditions include significant trauma, congenital joint abnormalities, metabolic
defects (e.g., Wilson disease), infections, diseases (e.g., neuropathic), and disorders that
alter the normal structure and function of cartilage (e.g., Rheumatoid Arthritis, gout).
• Secondary osteoarthritis tends to appear in relatively young individuals aged
approximately 45 or 50.
• Gender: There is an increased risk of development of OA. The effect of female gender risk
of hand osteoarthritis peaks around menopausal, with more 3.5-fold higher rates in
women aged 50-60 yrs. while compared with men of similar age.
• Trauma: Fracturing a bone (common during sports) increases the likelihood of a person
developing OA in the injured joint. Unfortunately, this also means that the person is more
likely to suffer from OA at a younger age than those who have primary OA
• Obesity: In a single leg stance, 3-6 times a person’s body weight is transmitted across the
knees. Therefore, it stands to reason that an increase in body weight would result in
additional force across the knees during walking. This weight bears down on the joints
(particularly in the knees and hips) and causes them to wear away faster.
• Sedentary lifestyle: Not only does this promote weight gain but inactivity is also correlated
with weaker muscles and tendons surrounding the joints. This increases the risk of
developing OA because the muscles are not strong enough to keep the joints correctly
aligned, stable and supported. It is because of this that it is so important to engage in low-
impact activities that emphasize stretching, strengthening, posture, and range of motion.
These include aerobics, swimming and yoga.
• Heredity: Epidemiological studies of family history have recently
shed evidence of a genetic influence on OA (particularly in the
hands, knees and hips). Twin studies have shown that
heritability varies depending on the afflicted joint but overall,
they suggest a heritability of OA of 50% or more. Studies have
also suggested the involvement of specific chromosomes (e.g.
2q, 9q, 11q, and 16p) and genes such as CRTM (cartilage matrix
protein), CRTL (cartilage link protein), and collagen II, IX, and XI.
• Joint overuse: This is either due to repetitive joint use in an
occupation or during leisurely activity. One reason this happens
during work is that over long days, the muscles will gradually
become tired and no longer serve as effective joint protectors.
• Other conditions: These may include peripheral neuropathies and neuromuscular disorders that put
abnormal stress on the joint. Diseases that cause inflammation, such as rheumatoid arthritis, can increase
your risk of getting osteoarthritis later in life.
• Pain: In osteoarthritis the joint pain is worse with use, worse as the day goes on, and feels better with rest.
• Stiffness: The stiffness of OA is mostly felt after inactivity, and can usually be relieved by gently stretching or
moving the affected area. Osteoarthritis can cause morning stiffness, but it usually lasts for less than 30
minutes,
• Mild swelling: In osteoarthritis the joints may feel achy and tender, but they might not look very swollen or
feel warm. There may be more swelling after physical activity, and more swelling as the condition becomes
more advanced.
• Bone Spurs: Extra bits of bone may be deposited around affected joints in osteoarthritis, making the ends
of the fingers look somewhat deformed, for instance, or make the base of the big toe look larger.
• Reduced Flexibility: Joints affected by
osteoarthritis may have a decreased range of
motion, which can compromise movement.
Osteoarthritis in the hips makes it more difficult
to bend over. Osteoarthritis in the knees means
the legs may not be able to bend as completely.
• Clicking or cracking sound: The clicking or
cracking that people may hear when they move
joints affected by osteoarthritis are the sounds of
bones rubbing together without enough
cartilage to cushion them.
• Asymmetry: The clicking or cracking that people
may hear when they move joints affected by
osteoarthritis are the sounds of bones rubbing
together without enough cartilage to cushion
them.
• The first changes that occur in the body due to OA primarily affect the articular cartilage.
• OA also affects bone, synovial membrane, capsule, ligament and muscle.
• Articular Cartilage covering the ends of the bones where they meet at the joint.

• Cartilage consists of water and the matrix, which is a gel-like substance containing
different types of protein:
• Collagen
• Proteoglycans
• Non-collagenous proteins

• Articular Cartilage provides:

• Virtually frictionless movement of joints
• Resistance to tension by Type II collagen (degraded by metalloproteinase in OA)
• Resistance to compression by Proteoglycans (degraded by metalloproteinase in OA)
 Articular Cartilage
• In OA, The articular cartilage may erode or become
irregular, split, or frayed.
• Erosion occurs, often central & frequently in weight
bearing areas.
• Fibrillation, which causes softening, splitting and
fragmentation of the cartilage, occur in both weight
bearing & non-weight bearing areas.
• Collagen fibers split and there is disorganization of the
proteoglycan collagen relationship such as H20 is
attracted into cartilage, which causes further softening
and flaking.
• These flakes of cartilage break off and may be impacted
between the joint surfaces causing locking and
inflammation.
 Articular Cartilage
• Inflammatory mediators play a pivotal role in the
initiation and continuation of the OA process.
• The source of such mediators may be local from
joint cells(chondrocytes) but also may be systemic
from other tissues such as adipose tissue (i.e.,
adipokine) released in blood flow and then reaching
the joint via the subchondral bone vasculature.
• They secrete enzymes known as matrix
metalloproteinase responsible for degradation of
articular cartilage in OA:
• Collagenase
• Protease
• This causes matrix remodeling and leads to
secondary inflammatory changes in subchondral
bone and synovium.
Bone(Eburnation)
• Bone surface become hard & polished as there
is loss of protection from the cartilage.
• Cystic cavities form in the subchondral bone
because eburnated bone is brittle and micro
fractures occur.
• Osteophytes form at the margin of the
articular surface, which may get projected into
the it.
• Or into capsule & ligament, bone of the
weight-bearing joint
• There is alteration in the shape of the femoral
head which becomes flat and mushroom
shaped.
Synovial Membrane
• Soluble inflammatory mediators, such as
cytokines and chemokines, are increased in
synovial fluid (SF) in OA and promote synovitis.
• The cause of synovial inflammation in OA is still
unclear but hypothesized either as a result of
foreign body reaction of synovial cells to
degraded cartilage products inside the joint, or
as a primary trigger of OA process.
• Synovial cells are thought to produce
inflammatory mediators, activate
chondrocytes, and propagate cartilage
breakdown.
• Synovitis has been shown to correlate with
symptom severity and rate of cartilage
degeneration
Grade Description

0 None definite absence of x-ray changes of osteoarthritis

1 Doubtful doubtful joint space narrowing and possible osteophytic linning

2 Minimal definite osteophytes and possible joint space narrowing

moderate multiple osteophytes, definite narrowing of joint space and

3 Moderate
some sclerosis and possible deformity of bone ends

large osteophytes, marked narrowing of joint space, severe sclerosis

4 Severe
and definite deformity of bone ends
• No diagnostic tool for OA has been validated for use in routine clinal practice. diagnosis based
on the:
⚬ Patient's history
⚬ Physical examination of affected joints
⚬ Radiographic findings
⚬ Differential Diagnosis

• Patients' history includes questions about the duration and severity of symptoms and the
patient’s ability to perform simple daily tasks.
• A complete evaluation of a patient with OA would include classification of the disease,
identification of the joints involved radiological and clinical staging, notation of any physical
deformities (contracture or atrophy), and assessment of the patient’s functional capacity.
• Radiographic evaluation is necessity for diagnosing OA.
• With disease progression, joint space narrowing due to cartilage degeneration, fractures in
sub-chondral bone, and osteophyte (bone spurs) and cysts along the joint margin are visible
 Compassion of the principal radiographic features in OA and RA

Features OA RA

Joint Spaces Reduced Reduced

Erosions No Yes

Osteophytes Yes No

Bone Density at joints Increased(sclerosis) Reduced(porosis)

Bone cysts Yes No

 Radiograph of a hand affected by osteoarthritis showing (1)
Hands affected by OA: (1)Heberden nodes (2) Bouchard nodes
joint space narrowing, (2) osteophytes, and (3) joint
destruction. Also note changes at carpometacarpal joint (4),
which are very common in osteoarthritis.
Radiograph of the hips showing (1) joint space narrowing and (2) osteophyte formation
Radiograph of the knee in (A) anteroposterior and (B) lateral views showing (1) joint space narrowing and (2) osteophyte formation.
• Arthroscopy is a procedure for diagnosing joint problems in which a narrow tube attached to a
fiber-optic video camera through a small incision is inserted. The view inside your joint is
transmitted to a high-definition video monitor.
• On arthroscopy normal cartilage is smooth, white and glistening, while osteoarthritic cartilage
is yellow, irregular and ulcerated.
 Differential Diagnosis
• Joint aspiration(Arthrocentesis) : Arthrocentesis is a procedure that is performed to obtain
synovial fluid from within a joint capsule, both for diagnostic and for therapeutic purposes. It is
done to rule out septic arthritis, rheumatoid arthritis and gout.
• Markers of inflammation, such as erythrocyte sedimentation rate and C-reactive protein level,
are typically normal.
• Immunologic tests, such as antinuclear antibodies and rheumatoid factor, should not be
ordered unless there is evidence of joint inflammation or synovitis, which makes autoimmune
arthritis a more likely diagnosis.
• A uric level test should be done to suspect out gout.
01 Control Pain
Maintain Mobility
and Function
04
02 Minimize Disability

Maintain or Improve
QoL
05
Decrease Joint
03 Stiffness
Non-pharmacotherapy

Pharmacotherapy

Surgical Intervention
• Foods to avoid:
⚬ Red meat and fried foods. Fried foods and red meat contain high levels of advanced
glycation end products (AGEs), which are known for stimulating inflammation.
⚬ Sugars
⚬ Dairy
⚬ Refined carbohydrates
⚬ Alcohol and tobacco
• Properly position the neck and back while sleeping.
• Lose weight if you are obese
• Exercise daily
• Avoid frequent motion of joint and bending of joints
• Use appropriate footware
• Transcutaneous electrical nerve stimulation (TENS): This uses a low-voltage electrical current
to relieve pain. It provides short-term relief for some people with knee and hip osteoarthritis
• Paracetamol
• NSAIDS
⚬ Salicylates
⚬ Propionic Acid: ibuprofen, naproxen
⚬ Acetic Acid: diclofenac, indomethacin
⚬ Oxicams: piroxicam
• Opiates
• Tramadol
• Topical agents
• Cyclooxygenase inhibitor: celecoxib
• Glucocorticoids: Cortisone injection
• Hyaluronic acid: sodium hyaluronate, hylan
G-F 20
• Glucosamine/ chondroitin sulfates and s-
adenosylmethionine
• The nonprescription analgesic acetaminophen is the drug of choice for pain relief for non
inflammatory osteoarthritis.
• The ACR guidelines emphasize the use of acetaminophen as first-line treatment for osteoarthritis
of the knee and hip.
• This analgesic can significantly improve function and decrease pain.
• Therapeutic doses of acetaminophen produce minimum adverse effects, but hepatotoxicity can
occur, especially in patients who consume large quantities of alcohol.
• Dose: 1,000 mg four times a day or 650 mg every four hours (up to a maximum of 4 g/day)

• NSAIDs block a specific enzyme called cyclooxygenase (or COX) used by the body to make
prostaglandins.
• By reducing production of prostaglandins, NSAIDs help relieve the discomfort of fever and reduce
inflammation and the associated pain.
 Mechanism of Action
• These are recommended as first-line therapy. However, selection is challenged by patient age, co
morbidities and polypharmacy and by the drug’s benefit/risk balance all of which together influence
the risk of cardiovascular (CV), gastrointestinal (GI) and renal adverse events (AEs). The elderly are at
higher risk for these side effects.
• Other risk factors for NSAID-induced GI bleed include prior peptic ulcer disease and concomitant
steroid use.
• Potential renal toxicities of NSAIDs include azotemia, proteinuria, and renal failure requiring
hospitalization.
• Hematologic and cognitive abnormalities have also been reported with several NSAIDs.
• In elderly patients, and those with a documented history of NSAID-induced ulcers, traditional non-
selective NSAIDs should be used with caution, usually in lower dose and in conjunction with a
proton pump inhibitor.
• For diclofenac sodium, the recommended daily administration is 100–150 mg/day, divided into three
daily doses
Mechanism of Action
Corticosteroids have both anti-inflammatory and
immunosuppressive effect, but their mechanism of
action is complex. Corticosteroids act directly on
nuclear steroid receptors and interrupt the
inflammatory and immune cascade at several levels.
By this means, they reduce vascular permeability and
inhibit accumulation of inflammatory cells,
phagocytosis, production of neutrophil superoxide,
metalloprotease, and metalloprotease activator, and
prevent the synthesis and secretion of several
inflammatory mediators such as prostaglandin and
leukotrienes. The clinical anti-inflammatory reflections
of these actions are decreases in erythema, swelling,
heat, and tenderness of the inflamed joints and an
increase in relative viscosity with an increase in
hyaluronic acid (HA) concentration
• Patients who suffer from painful flares of osteoarthritis in the knee may benefit from intra-
articular injections of corticosteroids, such as methylprednisolone or triamcinolone.
• Short-term pain relief can be obtained with aspiration of the joint fluid followed by intra-
articular injection of the corticosteroid when the joint is painful and swollen.
• Injections should not be made in the joints more than three or four times a year to prevent
potential cartilage damage from repeated injections.
• Patients may have to consider surgical intervention if they require more than three to four
shots per year to control symptoms.
• Injections of a corticosteroid into the joint might relieve pain for a few weeks.
• Doctors numb the area around the joint, then places a needle into the space within the joint
and inject medication.
• Opioids can be considered for patients with severe osteoarthritic pain that does not respond to
nonopioid analgesic agents.
• These agents are not recommended for prolonged time periods because they cause
constipation and increase the fall risk, especially in the elderly.

• •Tramadol is usually given as a rescue medication for symptomatic relief and can be
considered an option if NSAIDs fail.
• •Tramadol inhibits serotonin reuptake and inhibits norepinephrine reuptake, enhancing
inhibitory effects on pain transmission in the spinal cord.
• •Use of this central-acting oral analgesic allows for a lower dose of NSAIDs to be used.
• •The recommended dose is 50 mg given every 4 to 6 hours with a total daily dose not
exceeding 400 mg
• •. Adverse reaction: seizure, slows down breathing, addiction
Topical Capsaicin
• A pepper-plant derivative has been shown to
relieve pain relating to osteoarthritis better than
placebo.
• Capsaicin cream 0.025% applied four times a day
was effective in managing pain caused by
osteoarthritis of the knee, ankle, wrist and shoulder
in a double-blind, randomized controlled trial.
• One common side effect is a localized burning
sensation, and patients should be advised to wash
hands after application to avoid spreading to the
eyes or other mucous membranes.
• Capsaicin is available over the counter in
concentrations of 0.025%, 0.075% and 0.25%.
• Hyaluronic acid provides viscos elastic and lubricating properties to the joint.
• It is a major nonstructural component of the synovial and cartilage matrix makeup.
• The molecular weight and concentration of hyaluronic acid is thought to be decreased in
patients with osteoarthritis.
• The FDA has approved hylan G-F 20 and sodium hyaluronate injections for the treatment
of pain caused by osteoarthritis of the knee.
• The 2-mL dose is injected once weekly for three and five weeks, respectively.
• The injections are well tolerated however, local skin reactions and pain with injection have
been shown.
• Intra-articular injections must be administered using the aseptic technique, and the
aspirated joint fluid should be examined to rule out infections.
• Patients should minimize activity and stress on the joint for several days following an
intra-articular injection.
• These are alternative therapy supplement for osteoarthritis after experiencing side effects or
incomplete relief of symptoms from conventional medications

Glucosamine sulfates
• It is a popular treatment for osteoarthritis symptoms, is derived from oyster and crab
shells.
• A meta-analysis concluded that glucosamine may show efficacy over placebo in relieving
painful symptoms.
• Glucosamine is usually dosed at 1,500 mg per day in three divided doses.
• Supplements should be taken for at least a month before improvement occurs.
Chondroitin sulfates
• This has demonstrated efficacy by acting as a building block of proteoglycan molecules to
improve the symptoms of osteoarthritis.
• Chondroitin is derived mostly from shark and cow cartilage.
• Chondroitin is usually dosed at 1,200 mg per day in three divided doses and results may not be
achieved for at least a month.
• However, the use of the glucosamine and chondroitin is popular for the treatment of
osteoarthritis.
S-adenosylmethionine
• S-adenosylmethionine (SAMe) is a naturally occurring compound found in all living cells that is
commercially produced in yeast-cell cultures.
• Several studies have found SAMe to be more effective than placebo in improving pain and
stiffness related to osteoarthritis.
• Dosages range from 400 to 1,200 mg per day.
 Osteotomy

Joint Replacement

Total Joint Replacement

Osteotomy(Realigning bones)
• This approach works by fixing the malalignment
• If osteoarthritis has damaged one side of knee more
than the other, an osteotomy might be helpful.
• For e.g.: Tibial osteotomy for the middle
compartmental knee OA
• In a knee osteotomy, a surgeon cuts across the bone
either above or below the knee, and then removes or
adds a wedge of bone which shifts your body weight
away from the worn-out part of your knee.
Joint Debridement
• Also known as joint lavage
• It involves clearing out or irrigation of the debris from joints.
• Minimal invasive surgery

Arthroplasty
• As we know arthropathy is the inflammation of joint.
• Arthroplasty Involves the surgery of the joint inflammation.
• It is similar to Total joint replacement as it refers to the surgery that involves
insertion of prosthesis in place of the damaged joint.
Total Joint Replacement
• In joint replacement surgery, surgeon removes damaged joint
surfaces and replaces them with plastic and metal parts or ceramic
parts called as prosthesis.
• Mostly joint replacement is conducted at knee and joint at these sites
are more prone to arthritis.
• Surgery is believed to b riskier in obese patient, in older patients,
patients with heart, liver or kidney disease.
• Recovery after surgery requires few months.
• Surgery brings about reduction in the pain but side by side some
adverse effect can also occur
• Artificial joints can wear out or come loose and might eventually need
to be replaced.
 Procedure Indication

Moderate to severe symptoms without severe radiographic

Arthroscopic washout or ‘tidal irrigation”
changes, useful in diagnosis, mainly used for the knee

Moderate to severe symptoms, especially mechanical type,

Joint debridement
without advanced loss of articular cartilage

Occasionally used in early osteonecrosis or to relieve severe

Bony decompression pain

Pain relief and realignment of joints with severe symptoms

Osteotomy
and focal damage, but without complete loss of cartilage

Arthroplasty Severe symptoms with severe joint damage as well