Does glucosamine and chondroitin work for arthritis

[malernee]

LANCET - Volume 357, Number 9268 19 May 2001

Correspondence

Glucosamine sulphate and osteoarthritis

Sir--Jean Yves Reginster and colleagues (Jan 27, p 251)1
claim to have shown long-term combined structure-modifying
and symptom-modifying effects of glucosamine sulphate on
osteoarthritis. However, as we understand their findings,
they show no clear correlation between the modifying effects
on structure and symptoms of glucosamine, since patients
with relief of symptoms are not identical to those
experiencing a structural improvement.

As Tim McAlindon states in the Commentary (Jan 27, p 247),2
the clinical relevance of the primary outcome measure for
structure modification--ie, joint-space nar-rowing--is not
clear. In our opinion, the difference in favour of
glucosamine becomes even more doubtful given the mean
difference of 0·24 mm after 3 years and, even more
importantly, its lower 95% confidence limit of 0·01 mm
(intention-to-treat analysis) or 0·02 mm (per-protocol
analysis).

Symptom assessment is reported only at baseline and at 3
years. Indeed, symptoms were scored every 4 months, as
reported at the meeting of the American College of
Rheumatology in Boston 1999.3 Thus, crucial data for the
assessment of glucosamine's clinical efficacy in the course
of this chronic disease are withheld. Furthermore,
meaningful baseline imbalances between treatment groups are
neglected. The total Western Ontario and McMaster
Universities (WOMAC) index, as well as the subscales for
pain and function are about 10% lower in the placebo group
than in the glucosamine group. Absolute score indices at
study end are not presented. Hence, the impact of this
potential bias cannot be assessed.

Moreover, table 3 and figure 2 apparently display discordant
study results: the WOMAC score is reported as worsening by
10% in the placebo group in table 3 as well as in the text,
but figure 2 shows improvement in the subscales for pain and
function in this group by 5% and 10%, respectively. Those
two subscales, however, account for 90% of the total WOMAC
score. Finally, calendar dates are missing for the whole
study period. Overall, from our point of view, the reported
data are scarce, incomplete, and inconsistent.

*Jutta Halbekath, Regine Lehnert, Hans Wille


LANCET - Volume 357, Number 9252 27 January 2001

Commentary

Glusoamine for osteoarthritis: dawn of a new era?

Osteoarthritis (OA) is a disease with formidable
public-health impact1 that has been dogged by negative
attitudes among physicians ("wear and tear") and low
expectations of the value of treatment. Non-steroidal
anti-inflammatory drugs (NSAIDs) are the commonest
symptomatic treatment for OA but have major adverse effects2
and might even worsen the osteoarthritic process.3 Although
inestimable resources have been poured into the development
of a panoply of NSAIDs, scarce currency has been given to
the notion that progression of OA could be retarded
pharmacologically, let alone by a nutritional product.4 The
report of the clinical trial in today's Lancet may radically
change this situation.

The 3-year randomised placebo-controlled trial suggests that
an oral agent, glucosamine sulphate, retards the progression
of symptomatic knee osteoarthritis. The study is a landmark
in OA research, not only for its scientific results, but
also for highlighting vexing issues in this area.

The quest for disease-modifier in OA is long overdue, and
this contender comes from an unexpected quarter. The idea
that glucosamine has such effects originates from the notion
that consumption of cartilage derivatives could provide
substrates for cartilage repair, but doubts about its
absorption and metabolic fate have fuelled scepticism about
its therapeutic potential.5 Even if this small aminosugar
could be absorbed and distributed intact to articular
cartilage, how it would be incorporated in the growth of
matrix oligosaccharides is not clear. This dilemma has
stimulated several recent studies, which have shown that
oral glucosamine sulphate is absorbed and distributed to
joint tissues, and that it has anti-inflammatory and
anabolic properties.6 Despite these observations,
glucosamine remains a compound whose potential to influence
cartilage destruction awaits a robust mechanistic
explanation.

It could be argued that the importance of a good biological
explanation is reduced by the demonstration of therapeutic
efficacy in a robust clinical trial. Certainly, the study by
Jean-Yves Reginster and colleagues shows many hallmarks of a

well-conducted trial, including rigorous descriptions of
randomisation, blinding, and allocation concealment, as well
as use of state-of-the-art approaches to measurement of
outcome. Even so, some elements of the methods merit
attention. As recommended by expert consensus, the study
used change in width of medial tibiofemoral joint space as
its primary measure of the biological effect.7 Precise
measurement of this variable is contingent on standardised
radiographic techniques, and could be biased when the
presence of pain impairs the ability of participants to
extend the knee fully.8 How much this theoretical limitation

translates into real bias is unclear, but there are also
fundamental questions about the relevance of width of
radiographic joint space as a single measure of biological
severity in knee OA. The use of this measure derives from
the conceptualisation of OA as a disorder of progressive
hyaline-cartilage loss, and the belief that
hyaline-cartilage thickness correlates with width of
radiographic joint space. In fact, recent
magnetic-resonance-imaging studies have highlighted the
panarticular nature of knee OA and have shown that mild to
moderate joint-space loss reflects meniscal extrusion rather
than hyaline-cartilage erosion.9 Even more troublesome is
the common clinical observation that radiographic severity
is one of the least important of the predictors of outcomes
that matter, such as pain and physical function.10

Although much of the hype will relate to radiographic
outcome, it is the well-validated WOMAC algofunctional
scores that give the strongest indication of the potential
of glucosamine to provide long-term benefits for people with

knee OA. In fact, the results are impressive; patients
assigned to glucosamine experienced significant improvements
in pain and disability that were sustained for the 3 years
of the study, whereas the scores among the placebo group
worsened. Furthermore, adverse-event rates were not higher
than those associated with placebo. These findings are
consistent with those seen in previous symptom-based
studies of glucosamine.11 Even though the effect sizes are
modest, glucosamine sulphate could play an important part in
the long-term therapy of OA.

In the face of such results, the medical profession
customarily tackles the usual questions about who might
benefit and who should pay, but the situation for
glucosamine is complicated. It is licensed in parts of
Europe as a drug, but is already widely available in the UK
and the USA as a nutritional supplement. Since glucosamine
is generally self-prescribed, the likely primary beneficiary

of this trial will be the nutritional-product industry
rather than the pharmaceutical company that sponsored the
trial, even though the results may not be eneralisable to
the highly variable formulations of nutritional products.
Although health-care professionals generally expect to be
involved in medical decisions of public-health importance,
the reality is that they are not regarded as a repository of
objective advice about nutritional products12 and are
generally kept out of the loop. This situation must change.
It is time for the professsion to accommodate the
possibility that many nutritional products may have valuable
therapeutic effects and to regain the credibility of the
public at large.

Tim McAlindon

Arthritis Center, Boston University Medical Center, Boston
MA 01228, USA (e-mail:tmcalind@bu.edu)

1 van Saase JL, van Romunde LK, Cats A, Vandenbroucke JP,
Valkenburg HA. Epidemiology of osteoarthritis: Zoetermeer
survey. Comparison of radiological osteoarthritis in a Dutch

population with that in 10 other populations. Ann Rheum Dis

1989; 48: 271-80. [PubMed]

2 Zeidler H. Epidemiology and NSAID induced gastropathy. J
Rheumatol 1991; 28: (suppl) 2-5. [PubMed]

3 Newman NM, Ling RS. Acetabular bone destruction related to

non-steroidal anti-inflammatory drugs. Lancet 1985; 2:
11-14. [PubMed]

4 Reginster JY, Gillot V, Bruyere O, Henrotin Y. Evidence of

nutriceutical effectiveness in the treatment of
osteoarthritis. Curr Rheumatol Rep 2000; 2: 472-77.
[PubMed]

5 Constantz RB. Hyaluronan, glucosamine and chondroitin
sulfate: roles for therapy in arthritis? In: Kelley WN,
Harris ED, Ruddy S, Sledge CB, eds. Textbook of
rheumatology. Philadelphia: WB Saunders, 1998.

6 Deal CL, Moskowitz RW. Nutraceuticals as therapeutic
agents in osteoarthritis: the role of glucosamine,
chondroitin sulfate, and collagen hydrolysate. Rheum Dis
Clin North Am 1999; 25: 379-95.

7 Altman R, Brandt KD, Hochberg MC, Moskowitz R. Design and
conduct of clinical trials in patients with osteoarthritis:
recomendations from a task force of the Osteoarthritis
Research Society. Osteoarthritis Cartilage 1996; 4: 217-43.

[PubMed]

8 McAlindon TE, LaValley MP, Gulin JP, Felson DT.
Glucosamine and chondroitin for treatment of osteoarthritis:

a systematic quality assessment and meta-analysis. JAMA
2000; 283: 1469-75. [PubMed]

9 Adams JG, McAlindon T, Dimasi M, Carey J, Eustace S.
Contribution of meniscal extrusion and cartilage loss to
joint space narrowing in osteoarthritis. Clin Radiol 1999;
54: 502-06. [PubMed]

10 Odding E, Valkenburg HA, Algra D, Vandenouweland FA,
Grobbee DE, Hofman A. Associations of radiological
osteoarthritis of the hip and knee with locomotor disability

in the Rotterdam Study. Ann Rheum Dis 1998; 57: 203-08.
[PubMed]

11 Buckland-Wright JC, Wolfe F, Ward RJ, Flowers N, Hayne C.

Substantial superiority of semiflexed (MTP) views in knee
osteoarthritis; a comparative radiographic study, without
fluoroscopy, of standing extended, semiflexed (MTP), and
schuss views. J Rheumatol 1999; 26: 2664-74. [PubMed]

12 McCarty MF. The neglect of glucosamine as a treatment for

osteoarthritis: a personal perspective. Med Hypotheses
1994; 42: 323-37. [PubMed]

[malernee]

Structural and Symptomatic Efficacy of Glucosamine and Chondroitin in Knee Osteoarthritis
A Comprehensive Meta-analysis

Florent Richy, MSc; Olivier Bruyere, MSc; Olivier Ethgen, MSc; Michel Cucherat, MSc, PhD; Yves Henrotin, MSc, PhD; Jean-Yves Reginster, MD, PhD


Arch Intern Med. 2003;163:1514-1522.

Objective To assess the structural and symptomatic efficacy of oral glucosamine sulfate and chondroitin sulfate in knee osteoarthritis through independent meta-analyses of their effects on joint space narrowing, Lequesne Index, Western Ontario MacMaster University Osteoarthritis Index (WOMAC), visual analog scale for pain, mobility, safety, and response to treatment.

Methods An exhaustive systematic research of randomized, placebo-controlled clinical trials published or performed between January 1980 and March 2002 that assessed the efficacy of oral glucosamine or chondroitin on gonarthrosis was performed using MEDLINE, PREMEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Contents, BIOSIS Previews, HealthSTAR, EBM Reviews, manual review of the literature and congressional abstracts, and direct contact with the authors and manufacturers of glucosamine and chondroitin. Inclusion, quality scoring, and data abstraction were performed systematically by 2 independent reviewers who were blinded to sources and authors. Conservative approaches were used for clear assessment of potential efficacy.

Results Our results demonstrated a highly significant efficacy of glucosamine on all outcomes, including joint space narrowing and WOMAC. Chondroitin was found to be effective on Lequesne Index, visual analog scale pain, mobility, and responding status. Safety was excellent for both compounds.

Conclusions Our study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds. Regarding the relatively sparse data on glucosamine and joint space narrowing and the absence of data on structural effects of chondroitin, further studies are needed to investigate the relationship among time, dose, patient baseline characteristics, and structural efficacy for an accurate, disease-modifying characterization of these 2 compounds.


From the Faculty of Medicine, Department of Public Health, Public Health and Epidemiology, University of Liège, Liège, Belgium (Messrs Richy, Bruyere, and Ethgen and Dr Reginster); Bone and Cartilage Metabolism Research Unit, World Health Organization Collaborating Center for Public Health Aspects of Osteoarticular Disorders, Liège (Messrs Richy, Bruyere, and Ethgen and Drs Henrotin and Reginster); and Cochrane French Center, Lyon, France (Dr Cucherat). The authors have no relevant financial interest in this article.






THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES


Other articles noted: 25 Jul 03 to 7 Nov 03
Evid Based Nurs 2004;7:e1-1.
FULL TEXT

Structural and Symptomatic Efficacy of Glucosamine and Chondroitin: Relevant Financial Interest?--Reply
Reginster
Arch Intern Med 2004;164:339-339.
FULL TEXT

Structural and Symptomatic Efficacy of Glucosamine and Chondroitin: Relevant Financial Interest?
Jobanputra
Arch Intern Med 2004;164:338-339.
FULL TEXT

Glucosamine improves joint mobility for 1 in 5 patients with osteoarthritis
BMJ 2003;327:0-0.
FULL TEXT

[malernee]

Arzneimittelforschung. 2004; (5): 286-92.
In vitro intestinal degradation and absorption of
chondroitin sulfate, a glycosaminoglycan drug.
Barthe L, Woodley J, Lavit M, Przybylski C, Philibert C,
Houin G.

Chondroitin sulfate (CAS 24967-93-9, CS) is a natural
polymer of a disaccharide consisting of glucuronic acid and
N-acetyl glucosamine which is sulfated either in the 4 or 6
position. It is administered orally as a slow acting drug to
treat osteoarthritis, though there is much debate about its
effectiveness and its mode of action, given that
macromolecules are not normally absorbed in the
gastrointestinal (GI) tract. Initially using a
spectrophotometric assay, the stability of CS was tested in
the presence of both tissues and lumenal contents of
stomach, small intestine, cecum and colon. There was no
degradation by the contents of the stomach or small
intestine or in any of the tissues. Degradation only took
place in the contents of the colon and particularly the
cecum. Using 14C-radiolabelled CS it was shown that the
cecum contents degraded CS down to the component
disaccharides. The 14C-radiolabelled CS was also used to
investigate the transport of CS across the different parts
of the GI tract in vitro. The CS was transported across the
small intestine in low amounts in the intact form, probably
by the mechanism of endocytosis. In the colon and the cecum,
higher amounts of radioactivity were transported, but most
of the radioactivity was in the form of the degradation
products, the disaccharides. This study shows that small
amounts of CS may cross the upper intestine intact, but in
the distal GI tract the molecule is effectively degraded,
presumably by the enzymes in the intestinal flora.

[malernee]

1: Am Fam Physician 2003 Jan 15;67(2):339-44 Related Articles,Links

Alternative therapies for traditional disease states: osteoarthritis.

Morelli V, Naquin C, Weaver V.

Family Practice Residency Program, Louisiana State University Health Sciences Center, Kenner, Louisiana 70065, USA.

Americans spend more on natural remedies for osteoarthritis than for any other medical condition. In treating osteoarthritis, glucosamine and chondroitin sulfate, two of the molecular building blocks found in articular cartilage, are the most commonly used alternative supplements. In randomized trials of variable quality, these compounds show efficacy in reducing symptoms, but neither has been shown to arrest progression of the disease or regenerate damaged cartilage. Although few clinical trials on S-adenosylmethionine exist, preliminary evidence indicates that it relieves pain to a degree similar to that of nonsteroidal anti-inflammatory drugs but with fewer side effects. Clinical trials of dimethyl sulfoxide offer conflicting results. Neither ginger nor cetyl myristoleate has proven clinical usefulness.

[guest]

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[guest]

RHEUMATOID ARTHRITIS

General Information
One concern I have about all over-the-counter arthritis treatments is that
the patient may have undiagnosed rheumatoid arthritis. If treated early with
disease-modifying drugs, the course of the disease can be changed and the
deformities and disabilities can be reduced. If patients try a series of
home remedies before getting a proper diagnosis, it may be too late for the
disease-modifying drugs to work.



RHEUMATOID ARTHRITIS

General Information
Rheumatoid arthritis is an uncommon joint disease that usually affects small or toy breeds of dogs. It can affect dogs as young as 8 months of age.
The disease first appears as lameness that shifts from leg to leg, with swelling of the affected legs. Within weeks to months, the disorder settles in particular joints. Radiographs (x-rays) of involved joints show destruction of bone. As the disease progresses, the joints may dislocate and appear deformed.
The cause of rheumatoid arthritis is unknown, but the disease probably results from a defect in the immune system.

Important Points in Treatment
1. Rheumatoid arthritis is difficult to treat, and lifetime treatment is usually necessary. The condition may improve dramatically at first, but, as time passes, it may become unresponsive. Very potent anti-cancer drugs are often used in treatment. This necessitates close monitoring of the dog's general health with periodic laboratory tests.
2. Medication: Give all the medication as directed. Call the doctor if you cannot carry out the prescribed treatment.
3. Activity: The pain of rheumatoid arthritis naturally restricts activity. Do not force your pet to exercise or allow it to jump from furniture, steps, etc.
4. Special instructions:


Notify the Doctor if Any of the Following Occur
o Your dog's signs worsen.
o Your dog's signs recur after apparent recovery.
o Your dog's general health changes.
ARTHRITIS

General Information
Arthritis is inflammation of a joint. It can occur in any joint, including the spine and jaw. Signs of arthritis include painful or stiff joint movement, joint swelling, and a grating sensation during joint movement. Arthritis can also cause fever and redness of the skin over the joint.
Polyarthritis is inflammation of several joints at the same time. It is often associated with complex internal diseases.
Causes of arthritis include degeneration from aging, inherited condition, infection, injury, blood diseases, allergic or immune-mediated disease, and cancer.

Important Points in Treatment
1. Radiographs (x-rays) and laboratory tests are necessary to determine the type and extent of the arthritis. Follow-up examinations during treatment are necessary to evaluate the response to
therapy.
2. Arthritis is usually a controllable rather than a curable disease. Therapy is designed to minimize discomfort and delay or prevent progression of disease.
3. Medication: Give all medication as directed. Call the doctor if you cannot give the medication.
4. Activity: Follow the instructions checked.
Allow normal exercise.
Restrict exercise as follows:

5. Diet: Follow the instructions checked.
Feed the normal diet.
A special diet is necessary. Feed as follows:

6. Special instructions:

Notify the Doctor if Any of the Following Occur
o Your pet's discomfort or lameness increases.
o Your pet develops new signs.
o Your pet is reluctant to eat or seems unusually thirsty.
o There is swelling of or drainage from a joint.


Disease Modifying Treatment for Feline Rheumatoid Arthritis
Vet Comp Ortho Trauma 18[2]:94-99 May'05 Brief Communications 15 Refs

F. Y. Hanna
3 Rosebery Ave., Hampden Park, Eastbourne BN2 2QA UK; Email: Rosebery3@tisCali.Co.UK
Feline erosive polyarthritis includes the more common periosteal proliferative polyarthritis (PPP) and the rarely seen rheumatoid arthritis (RA). During the past three years, 12 patients with definite feline rheumatoid arthritis, which did not respond well to conventional therapy, were treated with 7.5 mg of Methotrexate and 70 mg Leflunomide, given weekly by the oral route. The average age of the cats was 5.9 years (range 2.5 to 10 years). Siamese cats were over represented. Seven of the 12 (58%) cats showed a marked improvement, usually within four weeks. Once maximum improvement was obtained the dosage was decreased. Serious toxicity was not noted and carcinogenetic effect was not seen during the course of this study. [Summary]
******
Canine Rheumatoid Arthritis

Stacy Gronefeld, BA; Holly A. Moore, DVM; Kenneth S. Latimer, DVM, PhD

Class of 2006 (Gronefield) and Department of Pathology (Moore, Latimer), College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388



Introduction

Canine rheumatoid arthritis is an erosive polyarthritis. It is a noninfectious, inflammatory, immune-mediated disease. Rheumatoid arthritis in dogs is not very common, and it has no sex predilection. It occurs mainly in small and toy breed dogs. Rheumatoid arthritis has been reported to occur in dogs from 8 months to 8 years of age, with the most common occurrence being 2 to 6 years of age. Rheumatoid arthritis is a chronic problem that can result in joint deformity.1,3,4

Etiology

The specific cause of rheumatoid arthritis is unknown. It has been speculated that canine distemper virus and the body’s immune response to this virus may play a role in the development of canine rheumatoid arthritis. Other possibilities are that type II collagen serves as an autoantigen4 and that some type of altered host immunoglobulin (IgG) is the inciting antigen that stimulates the immune response. Autoantibodies subsequently are formed and directed against the altered host immunoglobulin. These autoantibodies are called rheumatoid factors. The autoantibodies form complexes with the altered IgG molecules, and these immune complexes are deposited in the synovium of the joints. Inflammatory mediators are then activated, leading to a severe, erosive polyarthritis known as rheumatoid arthritis.3,4

Clinical Signs Associated with Rheumatoid Arthritis

Animals with rheumatoid arthritis often present with discomfort or pain in their joints. This can be seen as a shifting leg lameness or difficulty rising, walking up steps, and impaired ambulation. The joints that are most commonly affected are the carpal and tarsal joints. Affected joints may display signs of inflammation such as excessive warmth and/or swelling on palpation. Anorexia and malaise often are observed by the owner. The dog also may display a persistent fever. Splenomegaly and muscle wasting also have been reported with rheumatoid arthritis.1

Clinicopathologic Findings

Hemogram - A dog with rheumatoid arthritis can have a normal hemogram or may have leukocytosis, neutrophilia, and/or hyperfibrinogenemia. These changes reflect a generalized inflammatory process but do not lead to a specific diagnosis of rheumatoid arthritis.1

Synovial Fluid Analysis - Diagnostic indicators of rheumatoid arthritis usually are not present in the hemogram of diseased dogs. Synovial fluid analysis is more diagnostic of this condition. Arthrocentesis of multiple joints should be performed on a suspect animal. The complete synovial fluid analysis is composed of five major categories including physical appearance of the fluid, a mucin clot test, determination of protein concentration, performance of a nucleated cell count, and cytologic evaluation of the fluid.2 Serology also may be helpful if rheumatoid arthritis is suspected.

Physical Appearance

Normal synovial fluid should appear clear, colorless to pale yellow or straw colored, and lack turbidity. Viscosity also is evaluated with appearance. Synovial fluid is very viscous because it contains a high amount of hyaluronic acid. Normal viscosity is suggested when a strand of synovial fluid reaches 2 cm or greater before breaking. Viscosity also may be evaluated by examining a cytologic preparation of synovial fluid in which normal viscosity may cause cells to be arranged in rows. Rheumatoid arthritis is an inflammatory process and the number of cells in the synovial fluid will be increased. Increased cellularity causes the synovial fluid to appear more turbid than expected. Also, joint effusion dilutes the hyaluronic acid in the synovial fluid, causing a decrease in viscosity. Decreased viscosity is detected when the synovial fluid strand breaks before 2 cm in length. A suggestion of decreased viscosity also may be visualized on a smear when the cells are randomly distributed instead of appearing in rows.1,2

Mucin Clot Test

Mucin is hyaluronic acid. A mucin clot test is an assessment of the quality and quantity of hyaluronic acid. With this test, synovial fluid is expelled into 7N glacial acetic acid. The acetic acid causes the mucin to form a clot. Synovial fluid containing normal mucin will appear as clear fluid with a tight, ropy clot. Joint effusion from inflammation will dilute the hyaluronic acid, resulting in the formation of turbid fluid with a more friable mucin clot.2

Determination of Protein Concentration

Synovial fluid protein concentration is often measured by refractometry. Normal synovial fluid has a protein content of <1.0 g/dL (this value will be less than the bottom of the scale of most hand-held refractometers). Joint trauma and inflammation will increase the protein concentration of the synovial fluid. Therefore, an animal with rheumatoid arthritis will have an increased protein concentration in their synovial fluid.1,2

Nucleated Cell Count

Only nucleated cells are counted either by manual methods or automated analyzer. Healthy dogs may have a synovial fluid nucleated cell count of up to 1,500 cells/µl. Rheumatoid arthritis is an inflammatory process, causing an inflammatory synovitis. The total number of nucleated cells in the synovial fluid is moderately to markedly increased in an animal with rheumatoid arthritis.2

Cytologic Evaluation

The most important part of the synovial fluid analysis is cytologic evaluation. Often, only a small amount of synovial fluid can be obtained. In this case, it should be used for cytologic study in preference to other forms of analysis. A wedge smear is made of the synovial fluid and stained with Romanowsky stain. Normal synovial fluid contains many mononuclear cells including macrophages and a few small, well differentiated lymphocytes (Fig. 1). Less than 10% of the total nucleated cell count consists of neutrophils.


Figure 1. Infrequent large mononuclear cell in the synovial fluid from a healthy dog (Wright stain).

Depending on the cellular content, synovial fluid can be classified as one of the following: normal, degenerative, inflammatory, or acute hemorrhage. Synovial fluid with inflammation can be further classified as either infectious or noninfectious, depending on the presence of microorganisms and the appearance of the neutrophils. Noninfectious inflammation in small animals is often associated with trauma or an immune-mediated process. In rheumatoid arthritis, the nucleated cell count is markedly increased (from >10,000 cells/µl to 100,000 cells/µl). The neutrophil is predominant cell type found in the synovial fluid (Fig. 2). Mononuclear cells also may be increased in number, but the neutrophil count alone can be >5,000 cells/µl.1,2


Figure 2. Numerous neutrophils in the synovial fluid of a dog with rheumatoid arthritis (Wright stain).

Serology

In addition to routine synovial fluid analysis, serology also can aid in the diagnosis of canine rheumatoid arthritis. Serology will detect the rheumatoid factors (RF; autoantibodies directed against the altered IgG). A RF titer = 1:16 is considered a positive test result that is suggestive of rheumatoid arthritis. Positive serological tests are found in 20-70% of affected dogs; however, false positive test results can occur in dogs with other systemic inflammatory disorders. For this reason, a positive RF titer is not a definitive diagnostic test for rheumatoid arthritis. All of the clinical signs and diagnostic findings must be taken into account when interpreting the serological test.1,3

Summary

The earlier a diagnosis of rheumatoid arthritis can be made, the sooner treatment can begin. Early treatment is necessary to avoid irreversible damage to the joints. Medical treatment can involve the following: immunosuppressive drugs, gold salts, and/or nonsteroidal anti-inflammatory drugs. Aspirin has been used for palliative treatment. Immunosuppressive treatment usually involves the administration of prednisone and/or azathioprine or cyclophosphamide. Azathioprine is usually preferred as the second drug of choice because cyclophosphamide may have serious side-effects when used long-term. The dog should be re-examined and the synovial fluid should be re-evaluated 1 month after beginning treatment. Even with appropriate treatment, most dogs with rheumatoid arthritis will have a deterioration of their health status over time.3

Canine rheumatoid arthritis is an uncommon disorder in dogs. However, rheumatoid arthritis should be considered in any dog with a noninfectious, erosive polyarthritis. In addition to clinical signs, radiographic evidence of joint erosion, serologic testing, and laboratory analysis of synovial fluid may assist in disease diagnosis. Dogs with rheumatoid arthritis have synovial fluid that is thin and cloudy in appearance. Cytologically, rheumatoid arthritis is characterized by a noninfectious inflammatory appearance with the main cell type being neutrophils.

References

1. Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, Diseases of the Dog and Cat, 5th ed. Philadelphia, W.B. Saunders Co., 2000, pp.78, 1879-1880, 1885.

2. Latimer KS, Mahaffey EA, Prasse KW (eds): Duncan & Prasse’s Veterinary Laboratory Medicine: Clinical Pathology, 4th ed. Ames, Iowa State Press, 2003, pp. 318-321.

3. Nelson RW, Couto CG (eds): Small Animal Internal Medicine, 2nd ed. St. Louis, Mosby, Inc., 1998, pp. 1070, 1085-1087, 1210.

4. Tizard, IR: Veterinary Immunology, An Introduction, 7th ed. Philadelphia, W. B. Saunders Co., 2004, pp.405-408.

Acknowledgement

The black and white photograph of the Australian Shepherd is from Tracy Machado's Canine Massage website and is used with permission.


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is an uncommon joint disease that usually affects small or toy breeds of dogs. It can affect dogs as young as 8 months of age.
The disease first appears as lameness that shifts from leg to leg, with swelling of the affected legs. Within weeks to months, the disorder settles in particular joints. Radiographs (x-rays) of involved joints show destruction of bone. As the disease progresses, the joints may dislocate and appear deformed.
The cause of rheumatoid arthritis is unknown, but the disease probably results from a defect in the immune system.

Important Points in Treatment
1. Rheumatoid arthritis is difficult to treat, and lifetime treatment is usually necessary. The condition may improve dramatically at first, but, as time passes, it may become unresponsive. Very potent anti-cancer drugs are often used in treatment. This necessitates close monitoring of the dog's general health with periodic laboratory tests.
2. Medication: Give all the medication as directed. Call the doctor if you cannot carry out the prescribed treatment.
3. Activity: The pain of rheumatoid arthritis naturally restricts activity. Do not force your pet to exercise or allow it to jump from furniture, steps, etc.
4. Special instructions:


Notify the Doctor if Any of the Following Occur
o Your dog's signs worsen.
o Your dog's signs recur after apparent recovery.
o Your dog's general health changes.
ARTHRITIS

General Information
Arthritis is inflammation of a joint. It can occur in any joint, including the spine and jaw. Signs of arthritis include painful or stiff joint movement, joint swelling, and a grating sensation during joint movement. Arthritis can also cause fever and redness of the skin over the joint.
Polyarthritis is inflammation of several joints at the same time. It is often associated with complex internal diseases.
Causes of arthritis include degeneration from aging, inherited condition, infection, injury, blood diseases, allergic or immune-mediated disease, and cancer.

Important Points in Treatment
1. Radiographs (x-rays) and laboratory tests are necessary to determine the type and extent of the arthritis. Follow-up examinations during treatment are necessary to evaluate the response to
therapy.
2. Arthritis is usually a controllable rather than a curable disease. Therapy is designed to minimize discomfort and delay or prevent progression of disease.
3. Medication: Give all medication as directed. Call the doctor if you cannot give the medication.
4. Activity: Follow the instructions checked.
Allow normal exercise.
Restrict exercise as follows:

5. Diet: Follow the instructions checked.
Feed the normal diet.
A special diet is necessary. Feed as follows:

6. Special instructions:

Notify the Doctor if Any of the Following Occur
o Your pet's discomfort or lameness increases.
o Your pet develops new signs.
o Your pet is reluctant to eat or seems unusually thirsty.
o There is swelling of or drainage from a joint.


Disease Modifying Treatment for Feline Rheumatoid Arthritis
Vet Comp Ortho Trauma 18[2]:94-99 May'05 Brief Communications 15 Refs

F. Y. Hanna
3 Rosebery Ave., Hampden Park, Eastbourne BN2 2QA UK; Email: Rosebery3@tisCali.Co.UK
Feline erosive polyarthritis includes the more common periosteal proliferative polyarthritis (PPP) and the rarely seen rheumatoid arthritis (RA). During the past three years, 12 patients with definite feline rheumatoid arthritis, which did not respond well to conventional therapy, were treated with 7.5 mg of Methotrexate and 70 mg Leflunomide, given weekly by the oral route. The average age of the cats was 5.9 years (range 2.5 to 10 years). Siamese cats were over represented. Seven of the 12 (58%) cats showed a marked improvement, usually within four weeks. Once maximum improvement was obtained the dosage was decreased. Serious toxicity was not noted and carcinogenetic effect was not seen during the course of this study. [Summary]
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Canine Rheumatoid Arthritis

Stacy Gronefeld, BA; Holly A. Moore, DVM; Kenneth S. Latimer, DVM, PhD

Class of 2006 (Gronefield) and Department of Pathology (Moore, Latimer), College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388



Introduction

Canine rheumatoid arthritis is an erosive polyarthritis. It is a noninfectious, inflammatory, immune-mediated disease. Rheumatoid arthritis in dogs is not very common, and it has no sex predilection. It occurs mainly in small and toy breed dogs. Rheumatoid arthritis has been reported to occur in dogs from 8 months to 8 years of age, with the most common occurrence being 2 to 6 years of age. Rheumatoid arthritis is a chronic problem that can result in joint deformity.1,3,4

Etiology

The specific cause of rheumatoid arthritis is unknown. It has been speculated that canine distemper virus and the body’s immune response to this virus may play a role in the development of canine rheumatoid arthritis. Other possibilities are that type II collagen serves as an autoantigen4 and that some type of altered host immunoglobulin (IgG) is the inciting antigen that stimulates the immune response. Autoantibodies subsequently are formed and directed against the altered host immunoglobulin. These autoantibodies are called rheumatoid factors. The autoantibodies form complexes with the altered IgG molecules, and these immune complexes are deposited in the synovium of the joints. Inflammatory mediators are then activated, leading to a severe, erosive polyarthritis known as rheumatoid arthritis.3,4

Clinical Signs Associated with Rheumatoid Arthritis

Animals with rheumatoid arthritis often present with discomfort or pain in their joints. This can be seen as a shifting leg lameness or difficulty rising, walking up steps, and impaired ambulation. The joints that are most commonly affected are the carpal and tarsal joints. Affected joints may display signs of inflammation such as excessive warmth and/or swelling on palpation. Anorexia and malaise often are observed by the owner. The dog also may display a persistent fever. Splenomegaly and muscle wasting also have been reported with rheumatoid arthritis.1

Clinicopathologic Findings

Hemogram - A dog with rheumatoid arthritis can have a normal hemogram or may have leukocytosis, neutrophilia, and/or hyperfibrinogenemia. These changes reflect a generalized inflammatory process but do not lead to a specific diagnosis of rheumatoid arthritis.1

Synovial Fluid Analysis - Diagnostic indicators of rheumatoid arthritis usually are not present in the hemogram of diseased dogs. Synovial fluid analysis is more diagnostic of this condition. Arthrocentesis of multiple joints should be performed on a suspect animal. The complete synovial fluid analysis is composed of five major categories including physical appearance of the fluid, a mucin clot test, determination of protein concentration, performance of a nucleated cell count, and cytologic evaluation of the fluid.2 Serology also may be helpful if rheumatoid arthritis is suspected.

Physical Appearance

Normal synovial fluid should appear clear, colorless to pale yellow or straw colored, and lack turbidity. Viscosity also is evaluated with appearance. Synovial fluid is very viscous because it contains a high amount of hyaluronic acid. Normal viscosity is suggested when a strand of synovial fluid reaches 2 cm or greater before breaking. Viscosity also may be evaluated by examining a cytologic preparation of synovial fluid in which normal viscosity may cause cells to be arranged in rows. Rheumatoid arthritis is an inflammatory process and the number of cells in the synovial fluid will be increased. Increased cellularity causes the synovial fluid to appear more turbid than expected. Also, joint effusion dilutes the hyaluronic acid in the synovial fluid, causing a decrease in viscosity. Decreased viscosity is detected when the synovial fluid strand breaks before 2 cm in length. A suggestion of decreased viscosity also may be visualized on a smear when the cells are randomly distributed instead of appearing in rows.1,2

Mucin Clot Test

Mucin is hyaluronic acid. A mucin clot test is an assessment of the quality and quantity of hyaluronic acid. With this test, synovial fluid is expelled into 7N glacial acetic acid. The acetic acid causes the mucin to form a clot. Synovial fluid containing normal mucin will appear as clear fluid with a tight, ropy clot. Joint effusion from inflammation will dilute the hyaluronic acid, resulting in the formation of turbid fluid with a more friable mucin clot.2

Determination of Protein Concentration

Synovial fluid protein concentration is often measured by refractometry. Normal synovial fluid has a protein content of <1.0 g/dL (this value will be less than the bottom of the scale of most hand-held refractometers). Joint trauma and inflammation will increase the protein concentration of the synovial fluid. Therefore, an animal with rheumatoid arthritis will have an increased protein concentration in their synovial fluid.1,2

Nucleated Cell Count

Only nucleated cells are counted either by manual methods or automated analyzer. Healthy dogs may have a synovial fluid nucleated cell count of up to 1,500 cells/µl. Rheumatoid arthritis is an inflammatory process, causing an inflammatory synovitis. The total number of nucleated cells in the synovial fluid is moderately to markedly increased in an animal with rheumatoid arthritis.2

Cytologic Evaluation

The most important part of the synovial fluid analysis is cytologic evaluation. Often, only a small amount of synovial fluid can be obtained. In this case, it should be used for cytologic study in preference to other forms of analysis. A wedge smear is made of the synovial fluid and stained with Romanowsky stain. Normal synovial fluid contains many mononuclear cells including macrophages and a few small, well differentiated lymphocytes (Fig. 1). Less than 10% of the total nucleated cell count consists of neutrophils.


Figure 1. Infrequent large mononuclear cell in the synovial fluid from a healthy dog (Wright stain).

Depending on the cellular content, synovial fluid can be classified as one of the following: normal, degenerative, inflammatory, or acute hemorrhage. Synovial fluid with inflammation can be further classified as either infectious or noninfectious, depending on the presence of microorganisms and the appearance of the neutrophils. Noninfectious inflammation in small animals is often associated with trauma or an immune-mediated process. In rheumatoid arthritis, the nucleated cell count is markedly increased (from >10,000 cells/µl to 100,000 cells/µl). The neutrophil is predominant cell type found in the synovial fluid (Fig. 2). Mononuclear cells also may be increased in number, but the neutrophil count alone can be >5,000 cells/µl.1,2


Figure 2. Numerous neutrophils in the synovial fluid of a dog with rheumatoid arthritis (Wright stain).

Serology

In addition to routine synovial fluid analysis, serology also can aid in the diagnosis of canine rheumatoid arthritis. Serology will detect the rheumatoid factors (RF; autoantibodies directed against the altered IgG). A RF titer = 1:16 is considered a positive test result that is suggestive of rheumatoid arthritis. Positive serological tests are found in 20-70% of affected dogs; however, false positive test results can occur in dogs with other systemic inflammatory disorders. For this reason, a positive RF titer is not a definitive diagnostic test for rheumatoid arthritis. All of the clinical signs and diagnostic findings must be taken into account when interpreting the serological test.1,3

Summary

The earlier a diagnosis of rheumatoid arthritis can be made, the sooner treatment can begin. Early treatment is necessary to avoid irreversible damage to the joints. Medical treatment can involve the following: immunosuppressive drugs, gold salts, and/or nonsteroidal anti-inflammatory drugs. Aspirin has been used for palliative treatment. Immunosuppressive treatment usually involves the administration of prednisone and/or azathioprine or cyclophosphamide. Azathioprine is usually preferred as the second drug of choice because cyclophosphamide may have serious side-effects when used long-term. The dog should be re-examined and the synovial fluid should be re-evaluated 1 month after beginning treatment. Even with appropriate treatment, most dogs with rheumatoid arthritis will have a deterioration of their health status over time.3

Canine rheumatoid arthritis is an uncommon disorder in dogs. However, rheumatoid arthritis should be considered in any dog with a noninfectious, erosive polyarthritis. In addition to clinical signs, radiographic evidence of joint erosion, serologic testing, and laboratory analysis of synovial fluid may assist in disease diagnosis. Dogs with rheumatoid arthritis have synovial fluid that is thin and cloudy in appearance. Cytologically, rheumatoid arthritis is characterized by a noninfectious inflammatory appearance with the main cell type being neutrophils.

References

1. Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, Diseases of the Dog and Cat, 5th ed. Philadelphia, W.B. Saunders Co., 2000, pp.78, 1879-1880, 1885.

2. Latimer KS, Mahaffey EA, Prasse KW (eds): Duncan & Prasse’s Veterinary Laboratory Medicine: Clinical Pathology, 4th ed. Ames, Iowa State Press, 2003, pp. 318-321.

3. Nelson RW, Couto CG (eds): Small Animal Internal Medicine, 2nd ed. St. Louis, Mosby, Inc., 1998, pp. 1070, 1085-1087, 1210.

4. Tizard, IR: Veterinary Immunology, An Introduction, 7th ed. Philadelphia, W. B. Saunders Co., 2004, pp.405-408.

Acknowledgement

The black and white photograph of the Australian Shepherd is from Tracy Machado's Canine Massage website and is used with permission.


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[guest]

New Studies Give Mixed Signals About Glucosamine, Chondroitin Benefits

By Daniel DeNoon
WebMD Medical News Reviewed By Louise Chang, MD
on Monday, November 14, 2005

Nov. 14, 2005 -- Arthritis sufferers may -- or may not -- benefit from a pair of popular dietary supplements, two new clinical trials suggest.

One supplement is glucosamine, derived from the shells of crabs and lobsters. The other is chondroitin, usually derived from animal cartilage. These supplements are said to help relieve arthritis pain. They are also said to prevent the arthritic joint narrowing that causes one bone to grind against another.

Do these supplements really work? That is what two clinical trials -- a 1,583 patient study in the U.S. and a 318 patient study in Europe -- tried to find out. Researchers reported results from both studies at this week's annual scientific meeting of the American College of Rheumatology in San Diego.

"The supplements were not better than the placebo," Daniel O. Clegg, MD, tells WebMD. Clegg, chief of rheumatology at the University of Utah in Salt Lake City, led the NIH-sponsored U.S. study.

[malernee]

1: Vet J. 2006 Apr 27; [Epub ahead of print] Related Articles, Links


Randomised double-blind, positive-controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis.

McCarthy G, O'donovan J, Jones B, McAllister H, Seed M, Mooney C.

Department of Small Animal Clinical Studies, School of Agriculture, Food Science and Veterinary Medicine, College of Life Sciences, UCD Dublin, Belfield, Dublin 4, Ireland.

Thirty-five dogs were included in a randomised, double-blind, positive controlled, multi-centre trial to assess the efficacy of an orally-administered glucosamine hydrochloride and chondroitin sulfate (Glu/CS) combination for the treatment of confirmed osteoarthritis of hips or elbows. Carprofen was used as a positive control. Dogs were re-examined on days 14, 42 and 70 after initiation of treatment. Medication was then withdrawn and dogs were re-assessed on day 98. Response to treatment was based on subjective evaluation by participating veterinarians who recorded their findings at each visit. Dogs treated with Glu/CS showed statistically significant improvements in scores for pain, weight-bearing and severity of the condition by day 70 (P<0.001). Onset of significant response was slower for Glu/CS than for carprofen-treated dogs. The results show that Glu/CS has a positive clinical effect in dogs with osteoarthritis.

PMID: 16647870 [PubMed - as supplied by publisher]