Total Joint Replacement after Glucosamine Sulphate Treatment in Knee Osteoarthritis: Results of a Mean 8-Year Observation of Patients from Two Previous 3-Year, Randomised, Placebo-Controlled Trials

in Osteoarthritis and Cartilage (2008), 16(2), 254-60

OBJECTIVE: To assess the incidence of Total Joint Replacement (TJR) during the long-term follow-up of patients with knee osteoarthritis (OA) formerly receiving treatment with glucosamine sulphate or ... [more ▼]

OBJECTIVE: To assess the incidence of Total Joint Replacement (TJR) during the long-term follow-up of patients with knee osteoarthritis (OA) formerly receiving treatment with glucosamine sulphate or placebo. METHODS: Knee OA patients participating in two previous randomised, placebo-controlled, double-blind, 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement. RESULTS: Out of 340 patients with at least 12 months of treatment, 275 (i.e., 81%) could be retrieved and interviewed for the present evaluation: 131 formerly on placebo and 144 on glucosamine sulphate. There were no differences in baseline disease characteristics between groups or with the patients lost to follow-up. The mean duration of follow-up was approximately 5 years after trial termination and treatment discontinuation, making up a total of 2178 patient-years of observation (including treatment and follow-up). Total knee replacement had occurred in over twice as many patients from the placebo group, 19/131 (14.5%), than in those formerly receiving glucosamine sulphate, 9/144 (6.3%) (P=0.024, chi-square test), with a Relative Risk that was therefore 0.43 (95% confidence interval (CI): 0.20-0.92), i.e., a 57% decrease compared with placebo. The Kaplan Meier/Log-Rank test survival analysis confirmed a significantly decreased (P=0.026) cumulative incidence of total knee replacements in patients who had received glucosamine sulphate. A pharmacoeconomic analysis in a subgroup of subjects suggested that patients formerly on glucosamine sulphate had recurred to less symptomatic medications and use of other health resources than those from the placebo group during the last year of follow-up. CONCLUSIONS: Treatment of knee OA with glucosamine sulphate for at least 12 months and up to 3 years may prevent TJR in an average follow-up of 5 years after drug discontinuation. [less ▲]

Assessment of joint space narrowing with conventional standing antero-posterior radiographs: relief in mild-to-moderate pain is not a confounder in recent osteoarthritis structure-modifying drug trials

in Osteoarthritis and Cartilage (2006), 14(Suppl. A), 14-18

Objective: Knee pain relief has been suggested to potentially alter radioanatomic positioning in conventional standing antero-posterior knee radiographs. This study was performed to determine whether this ... [more ▼]

Objective: Knee pain relief has been suggested to potentially alter radioanatomic positioning in conventional standing antero-posterior knee radiographs. This study was performed to determine whether this is always the case and in particular if it applied to two recent randomised, placebo-controlled trials showing both symptom- and structure-modification with glucosamine sulfate in knee osteoarthritis. Design: Patients in the two studies were selected if they completed the 3-year evaluations and, irrespectively of treatment, (1) were pain-improvers in that they underwent Western Ontario and McMaster Universities (WOMAC) osteoarthritis index (WOMAC) pain decrease at least equal to the mean improvement observed with glucosamine sulfate, or (2) if their baseline standing knee pain (item #5 of the WOMAC pain scale) was "severe" or "extreme" and improved by any degree at the end of the trials. Changes in minimum joint space width were then compared between treatments. Results: Knee pain was of mild-to-moderate severity in the two original studies and in all patient subsets identified here. Obviously, there were more pain-improvers in the glucosamine sulfate than in the placebo subsets (N 76 vs 57 in pooling the two studies), but WOMAC pain scores improved to the same extent (over 50% relative to baseline). Notwithstanding such a major pain relief, patients in the placebo subsets of both studies suffered a definite mean (SE) joint space narrowing, that was of -0.22 (0.15) mm in the pooled analysis, and that was not observed with glucosamine sulfate: +0.15 (0.07) mm; P= 0.003. Similar evidence was found in the smaller subsets with at least severe baseline standing knee pain improving after 3 years. Conclusions: Knee pain relief did not bias the report of a structure-modifying effect of glucosamine sulfate in two recent long-term trials, possibly due to the mild-to-moderate patient characteristics. Consensus deliverables should acknowledge that the potential limitations of conventional standing antero-posterior radiographs should not be overestimated since they may not apply to all patient populations and to all studies using this gold standard technique. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. [less ▲]

Responders to glucosamine sulfate in knee osteoarthritis

in Osteoporosis International (2004), 12(SB), 76

Tibial subchondral sclerosis and femoral osteophytes are linked to symptomatic and structural severity of knee osteoarthritis

in Osteoarthritis and Cartilage (2001), 9(Suppl.B), 22

Glucosamine sulfate significantly reduces progression of knee osteoarthritis over 3 years : a large randomized, placebo-controlled, double-blind, prospective trial

in Osteoarthritis and Cartilage (2000), 8

The Effect of Sodium Monofluorophosphate Plus Calcium on Vertebral Fracture Rate in Postmenopausal Women with Moderate Osteoporosis. A Randomized, Controlled Trial

in Annals of Internal Medicine (1998), 129(1), 1-8

BACKGROUND: Fluoride is effective in increasing trabecular bone mineral density (BMD) in the spine, but its efficacy in reducing vertebral fracture rates and its effect on BMD at cortical sites are ... [more ▼]

BACKGROUND: Fluoride is effective in increasing trabecular bone mineral density (BMD) in the spine, but its efficacy in reducing vertebral fracture rates and its effect on BMD at cortical sites are controversial. OBJECTIVE: To study the effect of low-dose fluoride (sodium monofluorophosphate [MFP]) plus a calcium supplement over 4 years on vertebral fractures and BMD at the lumbar spine and total hip in postmenopausal women with moderately low BMD of the spine. DESIGN: Randomized, double-blind, controlled clinical trial. SETTING: Outpatient clinic for osteoporosis at a university medical center. PATIENTS: 200 postmenopausal women with osteoporosis (according to the World Health Organization definition) and a T-score less than -2.5 for BMD of the spine. INTERVENTION: Women were randomly assigned (100 patients per group) to continuous daily treatment for 4 years with 1) oral MFP (20 mg of equivalent fluoride) plus 1000 mg of calcium (as calcium carbonate) or 2) calcium only. MEASUREMENTS: Lateral spine radiographs were taken at enrollment and at each year of follow-up for detection of new vertebral fractures (defined as a reduction > or =20% and > or =4 mm from baseline in any of the heights of a vertebral body). Nonvertebral fractures were also recorded. All analyses were done with the intention-to-treat approach. RESULTS: Radiologic follow-up was possible for 164 of 200 patients (82%). The rate of new vertebral fractures during the 4 years of the study was lower in the MFP-plus-calcium group (2 of 84 patients; 2.4% [95% CI, 0.3% to 8.3%]) than in the calcium-only group (8 of 80 patients; 10% [CI, 4.4% to 18.8%]). The difference between the groups was 7.6 percentage points (CI, 0.3 to 15 percentage points) (P = 0.05). A moderate but progressive increase in BMD of the spine (10.0% +/- 1.5% at 4 years) was found for MFP plus calcium compared with calcium only (P < 0.001), whereas the more modest increase in BMD of the total hip seen with MFP plus calcium (1.8% +/- 0.6%) did not differ from the increase seen with calcium only. CONCLUSIONS: Low-dose fluoride (20 mg/d) given continuously with calcium for prolonged periods can decrease vertebral fracture rates compared with calcium alone in patients with mild to moderate osteoporosis. [less ▲]