Glucosamine for Arthritis by mikesanye


									                           Glucosamine for Arthritis
                   Research Based Evidence on Efficacy
Introduction                                                        statistical superiority of glucosamine. Four of these had
In spite of glucosamine gaining publicity for its effectiveness     dichotomous outcomes for calculating number needed to treat
in arthritis, very few physicians actually know that definite       (NNTs), which ranged from 1.7 to 6.3 in individual trials.
evidence is there that glucosamine was an effective treatment       Overall the NNT was 5.0 (3.5 to 8.9). This means that one of
for arthritis. This was followed up by trying to find papers and    every five patients with arthritis who were treated with
assess what evidence was there.                                     glucosamine, would have short term benefits in terms of
                                                                    reduced pain and tenderness, who would not have had if they
                                                                    had been given a placebo.
This involved MEDLINE searching for articles on
glucosamine, finding Internet pages which featured                    ctive-controlled
                                                                    A ctive-controlled trials
glucosamine, and reference lists from retrieved articles.           Three trials compared glucosamine with NSAID
                                                                    (phenylbutazone or ibuprofen). There was no difference
                                                                    between ibuprofen (1.2 g/day) and oral glucosamine (1.5 g/
Results                                                             day).
Eight randomized trials involving oral or intramuscular
glucosamine were found and the results are in the table below.
Articles on intra-articular injection, or where the material used   A dverse effects
was not clearly defined as glucosamine were excluded, as            Few adverse effects or study withdrawals were reported for
were non-randomized case series. All those included examined        glucosamine. They tended to occur less frequently with
oral and/or intramuscular glucosamine in patients with arthritis    glucosamine than with NSAID. A large open study of 1208
over periods of up to eight weeks. Most had well-described          arthritis patients taking oral glucosamine 1.5 g/day for 13 to
methods and six had quality scores of 3 or more on a five-          99 days had 28 patients who stopped taking glucosamine
point scale. Oral doses of glucosamine sulphate were 1.5            because of adverse effects. Those adverse effects reported
grams a day, and intramuscular doses were 400 mg two or             in more than 1% of patients were epigastric pain/tenderness,
three times a week.                                                 heartburn, diarrhea and nausea.

Placebo -controlled trials                                          Comment
Five trials compared glucosamine with placebo. All showed           It was surprising to find as many as eight randomized trials.

                        Outcomes for oral or intramuscular glucosamine in arthritis
 Trial              Administration       Outcome                       Glucosamine Placebo Relative                 NNT
                                                                       response    response benefit                 (95% CI)
                                                                                            (95% CI)
 Pujalte et al,           Oral           Improved pain and             8/10             2/10        4.0             1.7
 1980                                    tenderness at 6-8 weeks                                    (1.1 to 14)     (1.1 to 4.0)
 Crolle &                 Oral           Symptom free at 3 weeks 4/15                   0/15        100             3.8
 D’Este, 1980                                                                                                       (2.0 to 27)
 Rovalti, 1992            Oral           Responder at 4 weeks          66/126           46/126      1.4             6.3
                                                                                                    (1.1 to 1.9)    (3.6 to 26)
 Reichelt et al,     Intramuscular       Responder at 6 weeks          40/79            23/76       1.7             4.9
 1994                                                                                               (1.1 to 2.5)    (2.8 to 19)
 Combined                                                              118/230          71/227      1.6             5.0
                                                                                                    (1.3 to 2.1)    (3.5 to 8.9)
                                                                                                               Continued on page 5...

               Glucosamine sulfate: An Over view
Description                                                           This amount is extremely less compared to the amount of
Glucosamine is an aminopolysaccharide (a combination of an            sugar and carbohydrates normally consumed as part of the
amino acid - glutamine and a sugar - glucose). Glucosamine is         daily diet.
concentrated in joint cartilage where it is incorporated in longer
chains known as glycosaminoglycans (GAGs) and finally into            Dosage
very large structures known as proteoglycans. The                     No dose-response studies have been conducted with
proteoglycans function to attract water into the joint space for      glucosamine supplements. Virtually all oral supplementation
lubrication of the cartilage during movement.                         studies on glucosamine have used 1500 mg per day -
                                                                      usually in 3 divided doses of 500 mg each. While this level
Principle                                                             appears to be an effective dose, there is no information to
Glucosamine has been claimed to reverse osteoarthritis, protect       suggest that a higher does would work better or faster - or
joints and tendons from injury and decrease inflammation. The         that a lower dose would be less effective. A common
principle behind glucosamine supplementation is that the              supplementation strategy, which can decrease the daily cost
glucosamine is delivered to the joint space and incorporated          of supplements, is to consume 1500 mg of glucosamine per
into proteoglycans of joint cartilage to maintain structure and       day for the first 60-90 days of your regimen, followed by a
repair damage. Glucosamine may also stimulate chondrocytes            reduced intake of 250-750 mg per day as a “maintenance
to begin producing healthy new cartilage matrix (both collagen        level.” Following the initial 60-90 day period, dosage levels
and proteoglycans).                                                   can be increased or decreased based on individual pain
                                                                      and stiffness levels.
Scientific Support
There are numerous European studies showing a clear benefit           Suggested Readings
of glucosamine supplements for relief of joint pain and stiffness     1.    Barclay TS, Tsourounis C, McCart GM. Glucosamine. Ann Pharmacother
associated with arthritis. Many of the studies have been              2.    da Camara CC, Dowless GV. Glucosamine sulfate for osteoarthritis. Ann
criticized for lack of scientific control, short duration and small         Pharmacother 1998;32(5):580-87.
                                                                      3.    Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in
size, but recent meta-analyses of the smaller studies have                  osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen
supported the beneficial role of glucosamine supplements as                 hydrolysate. Rheum Dis Clin North Am 1999;25(2):379-95.
                                                                      4.    Delafuente JC. Glucosamine in the treatment of osteoarthritis. Rheum
a safe and effective approach to treating osteoarthritis. In                Dis Clin North Am 2000;26(1):1-11.
general 1-3 months of glucosamine supplementation seems to            5.    Denham AC, Newton WP. Are glucosamine and chondroitin effective in
be more effective than a placebo and at least as effective as               treating osteoarthritis? J Fam Pract 2000;49(6):571-72.
                                                                      6.    Donohoe M. Efficacy of glucosamine and chondroitin for treatment of
analgesic and non-steroidal anti-inflammatory drugs                         osteoarthritis. JAMA 2000;284(10):1241;discussion 1242.
(NSAIDs), like acetaminophen and ibuprofen, in reducing the           7.    Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine
                                                                            hydrochloride in the treatment of pain of osteoarthritis of the knee. J
joint pain of osteoarthritis.                                               Rheumatol 1999;26(11):2423-30.
                                                                      8.    Leeb BF, Schweitzer H, Montag K, Smolen JS. A meta analysis of

                                                                            chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol
Occasional symptoms of gastrointestinal discomfort have               9.    Leffler CT, Philippi AF, Leffler SG, Mosure JC, Kim PD. Glucosamine,
                                                                            chondroitin, and manganese ascorbate for degenerative joint disease of
been noted, but no significant adverse effects have been                    the knee or low back: a randomized, double-blind, placebo-controlled
noted with glucosamine supplementation. Although there                      pilot study. Mil Med 1999;164(2):85-91.
                                                                      10.   Mautone G. Efficacy of glucosamine and chondroitin for treatment of
have been no long-term safety studies conducted in                          osteoarthritis. JAMA 2000;284(10):1241;discussion 1242.
humans, animal studies on glucosamine have found it to                11.   McAlindon TE, LaValley MP, Felson DT. Efficacy of glucosamine and
                                                                            chondroitin for treatment of osteoarthritis. JAMA 2000;284(10):1241.
be non-toxic. There are certain doubts regarding the safety           12.   McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and
of glucosamine in diabetics as it contains glucose.                         chondroitin for treatment of osteoarthritis: a systematic quality assessment
                                                                            and meta-analysis. JAMA 2000;283(11):1469-75.
                                                                      13.   Rindone JP, Hiller D, Collacott E, Nordhaugen N, Arriola G. Randomized,
Therefore, it has minimal effect on the blood glucose level.                controlled trial of glucosamine for treating osteoarthritis of the knee.
However, it is good to moniter blood glucose level in diabetic              West J Med 2000;172(2):91-4.
                                                                      14.   Towheed TE, Anastassiades TP. Glucosamine and chondroitin for treating
patients taking glucosamine. However, the dosages of                        symptoms of osteoarthritis: evidence is widely touted but incomplete.
glucosamine necessary to heal OA is small (500-3000 mg/d).                  JAMA 2000;283(11):1483-84.

                       Glucosamine vs. Chondroitin
                                           Do We Need Both?
It is estimated that 63 to 85 percent of people over age 65, if       Furthermore, a continuing net loss of the water-loving GAGs
they were x-rayed, would show the signs of osteoarthritis. Of         produces a progressive cartilage dehydration status.
this significant number, 35 to 50 percent already suffer the
typical symptoms of pain, stiffness, swelling, and limited range                            difference
                                                                      Glucosamine: Making a difference
of movement in one or more joints. Though often associated            Healthy cartilage regularly produces its own glucosamine in
with being older, symptomatic osteoarthritis also plagues a           order to stimulate its metabolism:
younger set, not uncommonly starting around 45 years of age.          ! to maintain sufficient levels of matrix structural
The joint changes of osteoarthritis can bring about a significant        macromolecules
loss in the quality of life, and may foretell a future of crippling   ! to produce sufficient levels of water-loving GAGs, thereby
joint impairment.                                                        insuring optimal hydration
                                                                      ! and to facilitate balance between repair breakdown
Why is there so much enthusiasm for                                      enzymes and build-up enzymes
glucosamine sulfate?
Since the early 1980’s, international research has demonstrated       The mere fact of a gradually declining cartilage mass, probably
that osteoarthritis could be arrested with glucosamine sulfate        means that production of glucosamine for whatever set of
supplementation, if caught before the onset of irreversible joint     reasons, is not keeping pace with need. Supplied as a dietary
damage. Glucosamine is a simple molecule that is available as         supplement, glucosamine sulfate readily enters into cartilage
a supplement in several forms: glucosamine sulfate, glucosamine       metabolism, stimulating increased levels of collagen,
hydrochloride and N-acetyl-glucosamine. The glucosamine               proteoglycans, and the GAGs. Chondroitin sulfate and the other
sulfate (GS) form (stabilized with a mineral salt, such as sodium     GAGs also inhibit the breakdown enzymes, thus suppressing
chloride or potassium chloride) is the only form consistently         excessive cartilage breakdown in relation to need. The greater
shown in clinical trials to be effective for people with              GAG presence translates into greater water content with the
osteoarthritis. Significant reductions in joint pain, stiffness,      dual benefits of better shock absorption and better nourishing
tenderness, and swelling, as well as increased joint performance      of the chondrocyte cells. All in all, glucosamine sulfate
are the hallmarks of glucosamine sulfate. Even when                   supplementation in the majority of cases successfully arrests
researchers compared it to non-steroidal anti-inflammatory drug       the process of deterioration, stabilizing the cartilage status.
therapy (NSAID), like ibuprofen, the glucosamine sulfate led
to greater improvements in pain reduction and measurably better       When glucosamine stimulates GAG production, the
joint performance. There are now over 300 scientific studies          chondrocyte cells must find substantial supplies of sulfate to
affirming enthusiasm over glucosamine sulfate.                        be incorporated into the GAG molecular structure. It is sulfate
                                                                      that imparts to the GAGs their ‘magnetic power’ for water.
Cause of cartilage deterioration                                      GAG production is halted if adequate sulfate is not found. It
The general consensus among researchers is that the gradual           does not automatically follow that the body will be able to
deterioration of cartilage comes, not from years of inevitable        supply enough sulfate. As far back as the 1930’s researchers
wear and tear per se, but from protracted metabolic imbalance         demonstrated that those suffering from osteoarthritis were
in the basic repair process dealing with wear and tear damage.        deficient in sulfates. Some informed consumers have been
The normal repair process consist of enzymatically breaking           confused by the availability of glucosamine hydrochloride
down damaged collagen and proteoglycans, along with their             supplements, because they know that the worldwide research
attached water-loving glycosaminoglycans (GAGs), and                  has only used glucosamine sulfate. This variety does supply
systematically replacing them with newly created collagen             glucosamine, but fails to provide the critically important sulfate
and proteoglycans. A condition of deterioration ensues, when          component. Some authorities doubt that glucosamine
breakdown enzymes dominate the repair process. The                    hydrochloride supplements could perform as consistently as
imbalance favouring excessive matrix breakdown, leads to a            glucosamine sulfate, since sulfate could be critically deficient
net loss overtime of collagen, proteoglycans, the GAGs, and           in many osteoarthritis sufferers. It seems prudent then, to
crucial water. The imbalance is manifested as thinning, pitting,      choose a supplement that also supplies the sulfate component
cracking, and erosion of the cartilage mass.                          to insure GAG production.

   there                      chondroitin
Is there a need for combining chondroitin                           whether improvements are clinically significant. Chondroitin
                                                                    sulfate and polysulfate did not prevent osteoarthritis from
sulfate with glucosamine?                                           occurring in previously normal joints. In joints already affected,
Chondroitin sulfate (CS) is a much larger and more complex
                                                                    oral chondroitin sulfate did not prevent progression.
molecule than GS. Like glucosamine, it is a major constituent
of cartilage and has been the subject of many clinical trials.
Many people with osteoarthritis take combinations of CS and         Er ratic absorption with chondroitin
                                                                    Erratic                  chondroitin
GS or glucosamine HCl. This practice may be based on the            Oral absorption of chondroitin sulfate has been a controversial
suggestion, made in a best-selling book, that GS and CS in          topic within the nutritional community. Many researchers feel
combination have stronger effects than either supplement alone.     that due to the size of the chondroitin sulfate molecule (which
Although this idea may sound appealing, and may be harmless,        is many times larger than the glucosamine molecule), intact
it is based only on anecdotes and hypotheses. The theory that       absorption is impossible. They further feel that the fragments
GS and CS work synergistically in the treatment of                  that are absorbed do not have significant biologic effects. When
osteoarthritis remains unproven. To date, no clinical trials have   compared to the glucosamine molecule, the percentage of
compared glucosamine/chondroitin combinations with either           chondroitin sulfate that is absorbed is considerably less.
of the supplements taken individually.                              Glucosamine, when taken in the sulfate or hydrochloride form,
                                                                    has an absorption profile of 90-98% in humans. In contrast
One preliminary trial found that the combination of glucosamine     three European studies have shown that purified,
HCl (1,600 mg per day), CS (1,200 mg per day), and calcium          pharmaceutical grade chondroitin sulfate had only a 13%
ascorbate (1,000 mg per day) was effective at reducing joint        absorption rate when ingested orally by humans.
noise, pain, and swelling in people with osteoarthritis of the
temporomandibular joint (TMJ, or jaw joint). However, this          Conclusion
study was not well controlled and the outcomes measured             So, it is quite evident from the above studies that addition of
were highly subjective. Moreover, participants in this study        chondroitin sulfate to glucosamine offers no significant benefit
were allowed to use aspirin and ibuprofen, so the exact effects     to the patient. Glucosamine alone is a significant provider of the
of the nutrient combination cannot be accurately assessed.          GAGs, and there is no need to provide readymade GAGs in the
                                                                    form of chondroitin sulfate as all the glucosamine gets converted
Similarly, the combination of glucosamine HCl (1,500 mg per         to GAGs. Also, addition of chondroitin unnecessarily escalates
day), CS (1,200 mg per day), and manganese ascorbate (228           the cost of therapy. To conclude, glucosamine therapy has been
mg per day) was evaluated in a double-blind trial and was           found to improve joint function significantly in osteoarthritis
associated with significant symptom reduction and                   patients and there appears no added benefit of combining
improvement on x-ray for osteoarthritis of the knee (less so        chondroitin with glucosamine.
for spine). However, subjects were allowed to use
acetaminophen for pain, and comparative effects of a                Suggested Readings
glucosamine HCl/chondroitin sulfate combination and the
                                                                    1.   Murray MT. Which is better: Aged versus fresh garlic; glucosamine sulfate
individual nutrients were not examined.                                  versus chondroitin sulfate. Am J Natural Med 1997;4:5-8.
                                                                    2.   McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and
                                                                         chondroitin for treatment of OA. A systematic quality assessment and
One double-blinded randomized controlled trial, comparing                meta-analysis. JAMA 2000;283:1469-75.
chondroitin sulfate with placebo, evaluated joint space in          3.   Adebowale AO, Cox DS, Liang Z, Eddington ND. Analysis of glucosamine
patients with symptomatic hand osteoarthritis. One hundred               and chondroitin sulfate content in marketed products and the caco-2
                                                                         permeability of chondroitin sulfate raw materials. J Am Nutraceutical
sixty-five Caucasian patients, aged 40 to 70 years, were                 Assoc 2000;3:37-44.
randomized to receive either a 50 mg intramuscular injection        4.   Theodosakis J, Adderly B, Fox B. The Arthritis Cure. New York: St.
                                                                         Martin’s Press, 1997.
of chondroitin polysulfate, twice weekly, for 8 weeks, every 4      5.   Shankland WE 2nd. The effects of glucosamine and chondroitin sulfate
months, versus placebo, or 400 mg of oral chondroitin sulfate,           on osteoarthritis of the TMJ: a preliminary report of 50 patients. Cranio
3 times a day, versus placebo. Osteoarthritis progression in        6.   Leffler CT, Philippi AF, Leffler SG, et al. Glucosamine, chondroitin, and
the metacarpalphalangeal and interphalangeal joints was                  manganese ascorbate for degenerative joint disease of the knee or low
assessed with radiographs over 3 years. Evaluators used the              back: a randomized, double-blind, placebo-controlled pilot study. Mil Med
Anatomic Lesion Progression Scale to assess the development         7.   Verbruggen G, Goemaere S, Veys EM. Systems to assess the progression of
of osteophytes and joint space narrowing, with or without                finger joint osteoarthritis and the effects of disease modifying osteoarthritis
                                                                         drugs. Clin Rheumatol 2002;21:231-43.
subchondral bone changes, to determine osteoarthritis               8.   Murray, Michael T. Glucosamine sulfate versus chondroitin sulfate.
progression. This scale makes it very difficult to determine             American Journal of Natural Medicine 1997;4(4):7.

...continued from page 1

Glucosamine for Arthritis
While it is possible to criticise all of the trials to some extent,                                                                                Trials of oral and intramuscular

                                                                                              Percentage improved with glucosamine
                                                                                                                                                       glucosamine vs placebo
as a group they are no worse than others used to support
                                                                                                                                     100 –
commonly-used therapies. There is a consistent thrust of                                                                                           20
efficacy over placebo, and an inability to distinguish                                                                                80 –
glucosamine from NSAID. But all trials were relatively short-                                                                         60 –                252
term, and longer-term observations for adverse effects would
                                                                                                                                      40 –              155
be welcome.                                                                                                                                  30
                                                                                                                                      20 –                            Oral glucosamine
                                                                                                                                                                      IM glucosamine
The bottom line is that there is a body of evidence supporting                                                                         0–
the efficacy of oral and intramuscular glucosamine in arthritis.                                                                         0         20         40       60        80      100
                                                                                                                                                  Percentage improved with placebo
Suggested Readings
1.    W-D Mund-Hoyn. Konservative behandlung von Wirbelsäulenarthrosen mit        6.  LC Rovati. Clinical Research in osteoarthritis: design and results of short-
      glucosaminsulphat un phenylbutazone. Therapiewoche 1980;30:5922-28.             term and long-term trials with disease-modifying drugs. International
2.    JM Pujalte, EP Llavore, FR Ylescupidez. Double-blind clinical evaluation        Journal of Tissue Reaction 1992;XIV:243-51.
      of oral glucosamine sulphate in the basic treatment of osteoarthrosis.      7. H Müller-Fassbender, GL Bach, W Haase, LC Rovati, I Setnikar.
      Current Medical Research and Opinion 1980;7:110-14.                             Glucosamine sulphate compared to ibuprofen in osteoarthritis of the
3.    G Crolle, E D’Este. Glucosamine sulphate for the management of arthrosis:       knee. Osteoarthritis and Cartilage 1994;2:61-9.
      a controlled clinical investigation. Current Medical Research and Opinion   8. A Reichelt, KK Fuorster, M Fischer, LC Rovati, I Setnikar. Efficacy and
      1980;7:114-19.                                                                  safety of intramuscular glucosamine sulphate in osteoarthritis of the knee.
4.    E D’Ambrosio, B Casa, R Bompani, G Scali, M Scali. Glucosamine sulphate:        Arzneim-Forsch/Drug Research 1994;44:75-80.
      a controlled clinical investigation in arthrosis. Pharmacotherapeutica      9. AR Jadad, RA Moore, D Carroll, et al. Assessing the quality of reports of
      1981;2:504-08.                                                                  randomized clinical trials: is blinding necessary? Controlled Clinical Trials
5.    AL Vaz. Double-blind clinical evaluation of the relative efficacy of            1996;17:1-12.
      ibuprofen and glucosamine sulphate in the management of osteoarthrosis      10. MJ Tapadinhas, IC Rivera, AA Bignamini. Oral glucosamine sulphate in
      of the knee in out-patients. Current Medical Research and Opinion               the management of arthrosis: report on a multi-centre open investigation
      1982;8:145-49.                                                                  in Portugal. Pharmacotherapeutica 1982;3:157-68.

                   Glucosamine Sulfate in Osteoarthritis of the Knee
     Glucosamine sulfate is a drug used for the treatment of                      reduction of at least 3 points in the Lequesne’s index
     osteoarthritis (OA), based on its pharmacological and                        with a positive overall assessment by the investigator.
     metabolic activities on the cartilage and chondrocytes,
     complemented by mild anti-inflammatory properties and                        The Lequesne’s index was 10.6 ± 0.45 S.E.M. points
     a favorable pharmacokinetic profile. The aim of this study                   in both groups at the start of the study. This decreased to
     was to define the activity and safety of glucosamine                         7.45 ± 0.5 points in the treatment group (average 3.2) and
     sulfate on the symptoms of patients with OA, using a                         8.4 ± 0.4 points in the placebo group (average 2.2)
     multicenter, randomized, placebo-controlled, double-blind,                   (P < 0.05, Student’s t-test). The responder rate in the
     parallel-group study design.                                                 evaluable patients was 55% with glucosamine (N = 120)
                                                                                  vs 38% with placebo (N = 121). These proportions were
     The study included 252 outpatients with OA of the knee                       52% vs 37% in an intention-to-treat analysis (P = 0.014
     (Lequesne’s criteria), radiological stage between I and                      and 0.016, respectively; Fisher’s Exact Test). The
     III, and Lequesne’s severity index of at least 4 points                      medications were well tolerated throughout the study, with
     and symptoms for at least 6 months. Patients were                            no difference between the glucosamine and placebo
     treated with either placebo or oral glucosamine sulfate                      treated groups. It was concluded that glucosamine
     500 mg t.i.d. for 4 weeks, with weekly clinic visits.                        sulfate may be a safe and effective symptomatic Slow
     Responders to treatment were defined as patients with a                      Acting Drug for OA.

                                                  Source: Noack W, Fischer M, Forster KK, et al. Osteoarthritis Cartilage 1994;2(1):51-9.

              Glucosamine Reduces Osteoarthritis Progression in
              Postmenopausal Women with Knee Osteoarthritis
  This study was conducted to investigate the effect of glucosamine sulfate on long-term symptoms and structure progression
  in postmenopausal women with knee osteoarthritis (OA). It consisted of a preplanned combination of two three-year, randomized,
  placebo-controlled, prospective, independent studies evaluating the effect of glucosamine sulfate on symptoms and structure
  modification in OA and post-hoc analysis of the results obtained in postmenopausal women with knee OA. Minimal joint
  space width was assessed at baseline and after 3 years from standing anteroposterior knee radiographs. Symptoms were
  scored by the algo-functional WOMAC index at baseline and after 3 years. All primary statistical analyses were performed
  in intention-to-treat, comparing joint space width and WOMAC changes between groups by ANOVA.

  Of 414 participants randomized in the two studies, 319 were postmenopausal women. At baseline, glucosamine sulfate and
  placebo groups were comparable for demographic and disease characteristics, both in the general population and in the
  postmenopausal women subset. After 3 years, postmenopausal participants in the glucosamine sulfate group showed no joint
  space narrowing [joint space change of +0.003 mm (95% CI, -0.09 to 0.11)], whereas participants in the placebo group
  experienced a narrowing of -0.33 mm (95% CI, -0.44 to -0.22; P < 0.0001 between the two groups). Percent changes after
  3 years in the WOMAC index showed an improvement in the glucosamine sulfate group [-14.1% (95%, -22.2 to -5.9)] and
  a trend for worsening in the placebo group [5.4% (95% CI, -4.9 to 15.7) (P = 0.003 between the two groups)].

  This analysis, focusing on a large cohort of postmenopausal women, demonstrated for the first time that a pharmacological
  intervention for OA has a disease-modifying effect in this particular population, the most frequently affected by knee OA.

                                                                                 Source: Bruyere O, Pavelka K, Rovati LC, et al.
                                                                                               Menopause 2004;11(2):138-43.

                            Structur Modifying Drug        OA
    Glucosamine Sulphate: A Str ucture Modif ying Dr ug in OA
Glucosamine sulphate has been shown in a large double-blind,      (169.1 ± 92.3 ng/mmol, P < 0.0001). There was no
placebo-controlled clinical trial to prevent structural damage    significant difference in the CTX-II response in the
and improve clinical symptoms of osteoarthritis (OA).             placebo group and the glucosamine treated group.
Researchers investigated whether early response in a newly        However, those with high cartilage turnover presented a
developed biochemical marker of collagen type II degradation      significant decrease in CTX-II after 12-month glucosamine
(CTX-II, CartiLaps ELISA) could reflect the long-term             treatment. Thus, three group with CTX-II concentrations
preservation of hyaline cartilage.                                above normal average + 1SD decreased 15.5% after 12-
                                                                  month therapy. The 12 months change in CTX-II in OA
Study subjects comprised 212 knee OA patients                     patients with elevated CTX-II at baseline correlated with
participating in a clinical trial of the effects of glucosamine   the change in average joint space width observed after
sulphate. Disease symptoms were assessed quarterly by             36 months (R = 0.43, P < 0.05). Increased baseline levels
WOMAC scoring and X-ray analysis was performed at                 of CTX-II were associated with a worsening of the
baseline and after 3 years. Urine samples were obtained           WOMAC index (P < 0.01).
at baseline and after 1, 2 and 3 years for measurement in
the CartiLaps assay. The measurements were corrected              The data indicates that measurement of urinary collagen
for creatinine. At baseline the patients had an average           type II C-telopeptide fragments enables the identification
concentration of urinary CTX-II of 222.4 ± 159.5 ng/mmol          of OA patients with high cartilage turnover who at the
creatinine. This was significantly above the CTX-II levels        same time are most responsive to therapy with structure
measured in urine samples from 415 healthy controls               modifying drugs.
                                                                                Source: Christgau S, Henrotin Y, Tanko LB, et al.
                                                                                         Clin Exp Rheumatol 2004;22(1):36-42.


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