The patient is a 63-year-old male who is a supervisor in an sailboat assembly plant. His height is 1.7 meters (5
8) and weight is 90 kg. The patient presented to his primary physician with persistent, moderate, aching pain in the right
knee that began about a year ago and has become progressively worse with functional limitation. The pain is associated with
stiffness that is worse on Thursday and Saturday mornings (he tours the plant on Wednesday nights and bowls in a league on
Friday nights).
The patients past medical history is significant for inferior wall myocardial infarction 4 years prior and is status
post successful angioplasty. The patient also has mild type II diabetes mellitus and a 25 pack-year history of smoking. Borderline
hypertension (146/94) and overweight are other chronic health problems. His family medical history is negative for osteoarthritis
and rheumatoid arthritis.
Medications include glyburide 10 mg/d and prophylactic aspirin 81 mg/d (for cardioprotection). Although he had been prescribed
anti-hypertensive medication in the past, he is not currently utilizing this therapy. The patient admits taking occasional
ibuprofen and acetaminophen for knee pain.
Differential Diagnosis: Physical examination revealed localized tenderness of the right knees and pain on passive motion.
Pain was also elicited by holding the patella against the femur as the patient contracted his quadriceps. Marginal osteophytes
were palpated and patellofemoral crepitus was noted upon flexion. There was limitation of joint motion on extension with both
passive and active motion. Physical examination also revealed hard painless enlargements of the fourth and fifth distal interphalangeal
(DIP) and, proximal interphalangeal (PIP) joints as well as, the second and third metacarpophalangeal (MCP) joints of the
left hand, and minor limitation of motion of the left wrist.
X-ray studies of the right knee showed several tibio-femoral osteophytes and mild medial joint compartment narrowing.
Soft tissue calcification was noted in the medial collateral ligament. With the exception of mild hypertension, the patients
vital signs were within normal limits.
The differentiation of osteoarthritis (OA) from other disorders of the musculoskeletal system depends on a correlation
of clinical, laboratory, and radiographic findings. Osteoarthritis represents several disease subsets (e.g., OA of the knee,
hip, hand) leading to similar clinical and pathologic alterations.
Variants of the disease, such as primary generalized OA and erosive inflammatory OA, have different clinical, pathologic
and radiographic findings.
The symptoms of primary OA are typically localized to the affected joints, usually the DIP, PIP, first carpometacarpal
(CMC) joints, and hip and knee. Rarely are the MCP, wrist, elbow, or shoulder joints involved, except after trauma (secondary
OA). Primary generalized OA is characterized by diffuse polyaarticular involvement, whereas erosive inflammatory OA is mainly
limited to the DIP and PIP joints of the hands.
Rheumatoid arthritis may be difficult to differentiate from erosive OA. However, the pattern of joint involvement is
of diagnostic value because RA usually affects the PIP and MCP joints as well as the wrist and carpal joints and peripheral
joints elsewhere. The DIP joints are seldom involved in rheumatoid arthritis.
Pseudogout syndrome or chondrocalcinosis articularis may simulate OA when low-grade arthralgias result from the
presence of calcium pyrophosphate dihydrate (CPPD) crystals in synovial fluid; the pattern of arthritis often involves wrists,
knees, and hips.
Pigmented villonodular synovitis (PVNS) is a rare disorder that may involve the synovium of joints, bursa, or tendon
sheaths. Monoarticular involvement is typical, with the knee most commonly affected.
Clinically, patients with osteoarthritis of the knee have pain that is typically worse with weight-bearing and improved
with rest, morning stiffness, and gel phenomenon, and often have tenderness to palpation, crepitus on motion, and/or limitation
of joint motion. Pain is the cardinal symptom of OA and is usually aching in character and poorly localized. Although onset
is usually insidious, pain is most often the reason the patient with OA will seek assistance from the physician. In knee OA,
patients will most commonly describe their pain as involving the entire joint.
Stiffness on awakening in the morning is also a common complaint in knee OA. Such stiffness is of short duration, rarely
lasting more than 15-30 minutes. Articular gelling, a transient stiffness lasting only several flexion-extension cycles, is
extremely common in the lower extremity joints of elderly patients.
This occurs often in the absence of other symptoms of OA and follows prolonged inactivity. Compartment-directed (patellofemoral,
medial and lateral tibio-femoral) crepitus has a high degree of diagnostic specificity and sensitivity for OA of the knee.
Limitation of motion often develops as the disease progresses, owing to joint-surface incongruity, muscle spasms and
contracture, capsular contracture, and mechanical block from osteophytes and loose bodies.
The patients history and signs and symptoms, such as short-term stiffness and patellofemoral crepitus, were suggestive
of primary osteoarthritis of the knee. Involvement of PIP and DIP joints was also consistent with a diagnosis of OA, but involvement
of other joints was atypical (MCP joints and wrist). Therefore, further diagnostic tests were conducted to rule out other
forms of arthritis in the differential diagnosis.
No specific diagnostic laboratory abnormalities exist in primary OA, but are important in excluding other forms of arthritis
in the differential diagnosis. In primary OA, the erythrocyte sedimentation rate (ESR) is usually normal and serum rheumatoid
factor (RF) and antinuclear antibody are negative. An increase in ESR and positive serum RF point to a diagnosis of rheumatoid
arthritis. The radiographic appearance of primary OA may be normal if the pathologic changes are sufficiently mild; however,
radiographic changes may be noted as the disease progresses. Anteroposterior and lateral views are useful. Joint-space narrowing
occurs as a result of degeneration and disappearance of articular cartilage, and subchondral bony sclerosis (eburnation) is
noted as increased bone density.
Osteophytes are characteristic of primary OA. Radiological changes in rheumatoid arthritis include erosions localized
in or adjacent to the involved joints. In pigmented villonodular synovitis, radiographs of the knee may appear normal or may
show a periarticular soft tissue density, expansion of the suprapatellar pouch and local osseous changes confined to the patellofemoral
articulation. The typical presentation is a noncalcified capsular soft-tissue mass of the knee, without bony abnormalities.
Magnetic resonance imaging (MRI) is particularly useful in differentiating internal joint derangement and pigmented
villonodular synovitis from osteoarthritis. In pigmented villonodular synovitis, MRI can demonstrate key diagnostic features,
such as joint effusion, elevation of the joint capsule, hyperplastic synovium and low signal intensity resulting from hemosiderin
deposition.
The synovium contains areas of void signal intensity due to hemosiderin, interspersed with increased signal from both
inflammation and fat. Although useful in diagnosis, MRI is not specific for pigmented villonodular synovitis, since rheumatoid
synovitis may show a similar signal pattern. However, MRI in patients with suspected PVNS may decrease the time until diagnosis,
aid in preoperative planning, and may be a non-invasive method of long-term follow up for possible recurrence
Laboratory findings were negative for serum RF and ESR was 10 mm/h. As noted previously, anteroposterior and lateral
films of the right knee revealed mild medial joint-space narrowing and marginal osteophyte formation characteristic of primary
OA. Subchondral eburnation was present.
Films of the left hand showed degeneration of the fourth and fifth DIP and PIP joints. A detailed re-examination of the
patients medical history revealed an episode of acute trauma to the left hand in 1960 as a result of an company training accident.
Based on the presenting signs and symptoms, radiographic films, and laboratory values, a diagnosis was made of primary
patellofemoral OA of the right knee accompanied by traumatic secondary OA of the left hand. The former diagnosis was supported
by the presence of predisposing risk factors for osteoarthritis.
Laboratory findings were negative for serum RF and ESR was 10 mm/h. As noted previously, anteroposterior and lateral
films of the right knee revealed mild medial joint-space narrowing and marginal osteophyte formation characteristic of primary
OA. Subchondral eburnation was present.
Films of the left hand showed degeneration of the fourth and fifth DIP and PIP joints. A detailed re-examination of the
patients medical history revealed an episode of acute trauma to the left hand in 1959 as a result of an army training accident.
Based on the presenting signs and symptoms, radiographic films, and laboratory values, a diagnosis was made of primary
patellofemoral OA of the right knee accompanied by traumatic secondary OA of the left hand. The former diagnosis was supported
by the presence of predisposing risk factors for osteoarthritis.
Although the role of obesity in the etiology of OA requires further definition, a positive relation with knee OA has
been demonstrated in multiple studies.In a large, randomized, controlled study in knee OA, twice daily celecoxib 50-200 mg
and naproxen 500 mg produced significant improvements in mean WOMAC composite score from baseline and were significantly better
than placebo (both P less than or equal to .05). Likewise, rofecoxib provides similar pain relief to ibuprofen and diclofenac
in patients with osteoarthritis of the hip or knee. The CLASS trial found significantly fewer (P = .04) upper GI ulcer complications
with celecoxib 400 mg twice daily than nonselective NSAIDs in aspirin nonusers.
Qualitatively similar findings were described in an analysis of data pooled from eight double-blind, randomized controlled
trials of rofecoxib versus traditional NSAIDs and placebo. Unlike traditional NSAIDs, COX-2 specific inhibitors do not have
a clinically significant effect on platelet aggregation or bleeding time. Results from the SUCCESS VI trial suggest COX-2
specific inhibitors differ in their effects on blood pressure, edema, and other cardiorenal measures.
The Ulm Osteoarthritis Study, a multicenter cross-sectional survey of patients with advanced hip and knee osteoarthritis,
recently showed that obesity and overweight were associated with bilateral knee OA, but not bilateral hip OA nor generalized
OA. Results from a subanalysis of a clinical study found the link between obesity and subsequent osteoarthritis persisted
after controlling for serum uric acid level and physical activity level, and was strongest for persons with severest radiographic
disease.
Obesity seems to be a mechanical rather than a systemic risk factor for OA with the knee joint being especially susceptible.
Osteoarthritis has been associated with specific somatotypes; its prevalence is greater in stout individuals than thin ones.
Mechanical stress related to occupation or sports activities has been also implicated in the induction of OA. A study showed
a higher prevalence of OA of the knees, elbows and fingers in dock workers than age-matched civil servants. OA of the knee
is also more common in females than males when adjusted for age, body mass index (BMI), injury, chondrocalcinosis, and physical
activity.
The goals of the management of the patient with osteoarthritis continue to include control of pain and improvement in
function and health-related quality of life, with avoidance, if possible, of adverse effects of therapy. With significant
improvement in the understanding of the etiopathogenesis of OA, there has been new emphasis on potential preventive measures
and a more comprehensive approach to treatment. Guidelines for the management of OA of the knee have been developed and reported.
Several studies have reported that obese patients are more likely to experience progressive disease. Clinical studies
demonstrated a high frequency of involvement of the previously uninvolved contralateral knee within a 2-year period in obese
patients. Multivariate analysis of longitudinal data from another study showed that initial radiographic joint space narrowing,
body mass index, symptom duration, and global severity are predictors of progression of knee OA, with joint space narrowing
a strong predictor. The risk of progression in clinical OA patients with radiographic abnormalities is substantial. Rates
of progression are greatest in those with established radiographic abnormalities.
The patient was prescribed acetaminophen 500 mg twice daily for moderate knee pain by his primary care physician and
instructed to discontinue taking ibuprofen. He was also placed on a reduced sodium and low saturated fat diet, and a smoking
cessation program was initiated. Weight control was stressed.
The patient was scheduled for routine 6-month follow-up, but missed the appointment. He continued taking acetaminophen,
and subsequently increased the cardioprotective dose of aspirin to 650 mg three times daily because it helped the pain in
my knee. Thirteen months after the initial diagnosis, the patient scheduled an office visit because of increased right knee
pain and gnawing epigastric pain.
Physical examination revealed tenderness of the right knee with local inflammation and joint effusion. Mild pain on motion
was also noted in the left knee. Films showed further joint space narrowing in the right knee. An erosive gastric ulcer was
diagnosed by endoscopy. Studies for H. pylori were negative.
Aspirin was discontinued, and therapy for the ulcer was initiated with proton pump inhibitors with resolution of gastrointestinal
(GI) symptoms.
Acetaminophen was increased to 1000 mg four times daily with only limited improvement in knee symptoms. The patient
was seen at follow-up 3 months later; he had no further GI symptoms. His joint symptoms, however, had become more severe.
The patient was prescribed acetaminophen 500 mg twice daily for moderate knee pain by his primary care physician and
instructed to discontinue taking ibuprofen. He was also placed on a reduced sodium and low saturated fat diet, and a smoking
cessation program was initiated. Weight control was stressed.
The patient was scheduled for routine 6-month follow-up, but missed the appointment. He continued taking acetaminophen,
and subsequently increased the cardioprotective dose of aspirin to 650 mg three times daily because it helped the pain in
my knee. Thirteen months after the initial diagnosis, the patient scheduled an office visit because of increased right knee
pain and gnawing epigastric pain.
Physical examination revealed tenderness of the right knee with local inflammation and joint effusion. Mild pain on motion
was also noted in the left knee. Films showed further joint space narrowing in the right knee. An erosive gastric ulcer was
diagnosed by endoscopy. Studies for H. pylori were negative.
Aspirin was discontinued, and therapy for the ulcer was initiated with proton pump inhibitors with resolution of gastrointestinal
(GI) symptoms.
Acetaminophen was increased to 1000 mg four times daily with only limited improvement in knee symptoms.
The patient was seen at follow-up 3 months later; he had no further GI symptoms. His joint symptoms, however, had become
more severe.
According to the current 2000 American College of Rheumatology (ACR) Guidelines, nonpharmacologic therapy is the cornerstone
of OA pain management, regardless of disease severity. Numerous treatment modalities may be effective, including patient education,
self-management programs, weight loss (if overweight), aerobic exercise, range-of-motion exercises, muscle-strengthening exercises,
etc.
Commonly used aerobic exercises include walking, swimming, and (stationary) bicycle riding. A supervised program of fitness
walking and education improves functional status without worsening OA of the knee. The 2000 ACR Guidelines also recommend
that overweight patients with hip or knee OA lose weight.
Pharmacotherapy therapy for pain management is most effective when combined with nonpharmacologic strategies. The 2000
ACR Guidelines indicate acetaminophen for initial use in patients with mild-to-moderate pain, but COX-2 selective inhibitors
or traditional NSAIDs with gastroprotective agents, when indicated, are the initial drugs of choice for patients with moderate-to-severe
pain, particularly in the presence of inflammation.
In patients at risk for upper GI adverse events (e.g., age greater than or equal to 65, comorbid medical conditions,
history of peptic ulcer disease), COX-2 selective inhibitors are recommended. Traditional nonselective NSAIDs with gastroprotective
agents are an alternative to COX-2 selective inhibitors.
Because the patient had several risk factors for an upper GI event, he was prescribed a COX-2 selective inhibitor, daily
rofecoxib 25 mg. He also received an intraarticular glucocorticoid injection for the increasingly severe right knee pain.
The importance of diet and lifestyle modifications was reinforced, and he was referred to a physical therapist that instituted
a daily exercise regimen. The patient was also encouraged to participate in a self-management program.
In general, intraarticular glucocorticoid injections should be limited to a maximum of four injections into any
single joint per year. According to the 2000 ACR Guidelines, intraarticular glucocorticoid injections are of value in the
treatment of acute knee pain in patients with OA, and may be particularly beneficial in patients who have signs of local inflammation
with a joint effusion.
When joints are painful and swollen, aspiration of fluid followed by intraarticular injection of a glucocorticoid
preparation (e.g., up to 40 mg triamcinolone hexacetonide) is an effective short-term method of decreasing pain and increasing
quadriceps strength. Injection can be used as monotherapy in selected patients or as an adjunct to systemic therapy with an
analgesic, a nonselective NSAID, or a COX-2 selective inhibitor.
At follow-up 1 month later, the pain in the right knee had improved. The patient claimed to be conscientiously following
the exercise and diet regimen, however, he presented with mild ankle edema and his weight had increased 1 kg. His sitting
blood pressure had also risen slightly to 150/96.
Conventional NSAIDs are widely recognized as causing edema and hypertension through fluid and electrolyte disturbances
and other events. Hypertension and renal manifestations characterized by edema can also be seen with COX-2 specific inhibitors.
However, there are differences between the frequency of these events with different COX-2 specific inhibitors and it appears
from studies (SUCCESS VI) that rofecoxib is more likely to cause increases in blood pressure and edema than celecoxib. This
suggests that although different COX-2 specific inhibitors are similar with respect to basic mechanisms, they differ in side-reactions
and other molecule-related responses.
Following cessation of rofecoxib and initiation of hydrochlorothiazide therapy, the patients blood pressure returned
to a level of 132/78 after approximately 3 weeks. At that time, the patient was begun on celecoxib 200 mg a day. At follow-up
1 month later, the patient described occasional mild right knee pain. On physical examination no tenderness or inflammation
of the knee was noted and the ankle edema had resolved. Blood pressure was 128/74 and his weight had decreased by 1.5 kg.
On review of medications, the patient claimed to be taking only those prescribed and no other "medicines," but admitted
taking Aleve (naproxen 220 mg) for occasional headache and glucosamine 500 mg/d obtained from a "health food store."
The 2000 ACR Guidelines recommend use of only a single NSAID at a time, except for concurrent use of a cardioprotective
dose of aspirin (81-325 mg/day) with other NSAIDs. While a number of studies support the efficacy of both glucosamine and
chondroitin sulfate for palliation of joint pain in patients with knee OA, the 2000 ACR Guidelines do not make specific recommendations
about their use because of methodologic considerations, including lack of standardized case definitions and standardized outcome
assessments, as well as insufficient information about study design in a number of published reports.
A pivotal clinical trial was conducted by the National Institutes of Health (NIH) in the treatment of patients with knee
OA found that glucosamine helped some,who were treated with the agent but,as for cartridge regeneration,the report was reserved,on
the cautious side..
In a large, randomized, controlled study in knee OA, twice daily celecoxib 50-200 mg and naproxen 500 mg produced significant
improvements in mean WOMAC composite score from baseline and were significantly better than placebo (both P less than or equal
to .05). Likewise, rofecoxib provides similar pain relief to ibuprofen and diclofenac in patients with osteoarthritis of the
hip or knee.
The CLASS trial found significantly fewer (P = .04) upper GI ulcer complications with celecoxib 400 mg twice daily
than nonselective NSAIDs in aspirin nonusers. Qualitatively similar findings were described in an analysis of data pooled
from eight double-blind, randomized controlled trials of rofecoxib versus traditional NSAIDs and placebo.
Unlike traditional NSAIDs, COX-2 specific inhibitors do not have a clinically significant effect on platelet aggregation
or bleeding time. Results from the SUCCESS VI trial suggest COX-2 specific inhibitors differ in their effects on blood pressure,
edema, and other cardiorenal measures.