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Osteoarthritis
loss of 0.14±0.61mm after two years (p=0.001 compared with fact that the procedure was not blinded for measurement of JSW to
baseline). In contrast, there was no change in mean JSW for the 150 the sequence of the radiographs (i.e. baseline, month 16, month 30),
patients receiving CS (0.00±0.53mm; p = insignificant compared with are potential methodological issues that deserve further debate.
baseline). Similar results were found for minimum JSN. The differences
in loss of joint space between the two groups were significant for Glucosamine Sulphate
mean JSW (0.14±0.57mm; p=0.04) and for minimum JSW Glucosamine is an aminosaccharide, acting as a preferred substrate for
(0.12±0.52mm; p=0.05). the biosynthesis of glycosaminoglycan chains and, subsequently,
for the production of aggrecan and other proteoglycans and cartilage.
…doxycycline did not have an effect
To test the long-term effects of glucosamine sulphate (GS) on the
progression of OA knee joint structural changes and symptoms, 212
on joint-space narrowing in the
patients with knee OA were randomly assigned in a double-blind
contralateral knee; therefore, the
fashion to continuous treatment with GS 1500mg or placebo once
daily for three years.
7
Weight-bearing, anteroposterior radiographs of
two co-primary end-points were
each knee were taken at enrolment and every year for three years.
not successfully met and this study
Total mean JSW of the medial compartment of the tibiofemoral joint
was assessed by digital image analysis based on a validated
should be considered a failure.
computerised algorithm. After thee years, placebo-treated patients
had an average JSN of -0.31mm (range: -0.48 to -0.13), while no JSN
Diacerein (-0.06mm, range: -0.22 to 0.09) occurred in the group treated with GS
In a randomised, double-blind, placebo-controlled three-year study, (p=0.043). Furthermore, the percentage of patients who experienced
507 patients with primary OA of the hip – according to American a clinically relevant (>0.5mm) mean JSN after three years was
College of Rheumatology (ACR) criteria – received diacerein 50mg or significantly lower in the GS group (15%) than in the placebo group
placebo twice daily.
5
The minimal hip JSW was measured by a central (30%; p=0.013).
reader on annual pelvic digitalised radiographs using a 0.1mm
graduated magnifying glass. No significant difference in the rate of A five-year follow-up evaluation of patients from this trial was
joint-space loss was found between the two groups in the intention- performed to assess long-term outcomes of disease progression after
to-treat analysis. In the study completers, however, joint-space loss the end of the study.
8
The primary end-point of this follow-up study
was significantly reduced in the diacerein group (-0.18±0.25mm) was the occurrence of OA-related joint surgery. Of the 177 patients
compared with the placebo group (-0.23±0.23mm; p=0.042). In participating in this follow-up evaluation, 26 (14.7%) underwent
addition, the percentage of patients with definite joint-space loss
(>0.5mm, which was the measurement error counted as two SDs of
the intra-observer reproducibility) was smaller in the diacerein group
The structure-modifying effect of
than in the placebo group (50.7 versus 60.4%; p=0.036). Total hip
glucosamine sulphate was later
replacement of the signal hip during the study and during the three
months following discontinuation of the study treatment was confirmed by a similar trial in a
performed in 87 patients: 14.5% in the diacerein group and 19.8% in
population of 202 subjects from both
the placebo group. The comparison of the two groups showed a trend
in favour of diacerein treatment that did not reach statistical
sexes with a slightly worse degree of
significance (p=0.29), but it should be emphasised that the study was
knee osteoarthritis.
not powered for this outcome measure.
Doxycycline OA-related lower-limb surgery during the follow-up. Twice as many
The structural effect of doxycycline was recently assessed in 431 obese patients from the former placebo group underwent surgery, with a
women aged 45–64 years with unilateral radiographic knee OA who 48% decrease in risk with GS that was borderline statistically
were randomly assigned to receive 30 months of treatment with significant (p=0.06). The time-to-event analysis confirmed the results
doxycycline 100mg or placebo twice daily.
6
The co-primary end-points of the crude primary outcome, indicating a decreased cumulative
were the evolution of JSN in the index knee (which exhibited incidence of OA-related lower limb surgeries for the patients formerly
radiographic evidence of established OA at baseline) and in the on GS (p=0.05). When only total hip and/or knee replacements were
controlateral knee (in which radiographic evidence of tibiofemoral OA considered, the trend was similar, with over 40% reduction in risk
was absent at baseline). After 16 months of treatment, the mean SD after GS, but the level of probability was lower and showed a trend
loss of JSW in the index knee in the doxycycline group was 40% lower only towards the significance threshold (p<0.2).
than that in the placebo group (0.15±0.42 versus 0.24±0.54mm);
after 30 months, it was 33% lower (0.30±0.60 versus 0.45±0.70mm). The structure-modifying effect of GS was later confirmed by a similar
In contrast, doxycycline did not have an effect on JSN in the trial in a population of 202 subjects from both sexes with a slightly
contralateral knee; therefore, the two co-primary end-points were not worse degree of knee OA.
9
In this trial, the sparing effect of GS
successfully met and this study should be considered a failure. The use 1,500mg/day on the rate of progression of the disease was statistically
of a manual measurement of JSW instead of the most updated significant as early as the first year, and remained so until the end of
automated technologies following X-ray digitalisation, as well as the the three-year follow-up. The authors also described a significant
28 EUROPEAN MUSCULOSKELETAL REVIEW 2007
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