- Treatment of Primary and Secondary Osteoarthritis of the Knee [Entered Retrospectively]
- Objectives: Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage or debridement. Data Sources: We abstracted data from: 42 randomized, controlled trials (RCTs) of viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on arthroscopy. The search included foreign-language studies and relevant conference proceedings. Review Methods: The review methods were defined prospectively in a written protocol. We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract. Where randomized trials were few, we sought other study designs. We independently assessed the quality of all primary studies. Results: Viscosupplementation trials generally report positive effects on pain and function scores compared to placebo, but the evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large (n=1,583), high- quality, National Institutes of Health-funded, multicenter RCT showed no significant difference compared to placebo. Glucosamine sulfate has been reported to be more effective than glucosamine hydrochloride, which was used in GAIT, but the evidence is not sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose metabolism are short term, or if longer (e.g., 3 years), excluded patients with metabolic disorders. The best available evidence for arthroscopy, a single sham-controlled RCT (n=180), showed that arthroscopic lavage with or without debridement was equivalent to placebo. The main limitations of this trial are the use of a single surgeon and enrollment of patients at a single Veterans Affairs Medical Center. No studies reported separately on patients with secondary OA of the knee. The only comparative study was an underpowered, poor-quality trial comparing viscosupplementation to arthroscopy with debridement. Conclusions: Osteoarthritis of the knee is a common condition. The three interventions reviewed in this report are widely used in the treatment of OA of the knee, yet the best available evidence does not clearly demonstrate clinical benefit. Uncertainty regarding clinical benefit can be resolved only by rigorous, multicenter RCTs. In addition, given the public health impact of OA of the knee, research on new approaches to prevention and treatment should be given high priority.
- Authors of Report
- Methodology description
- The review methods were defined prospectively in a written protocol. A technical expert panel provided consultation. The draft report was also reviewed by other experts and stakeholders.
We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract that reported on one or more of the interventions among patients with primary or secondary osteoarthritis of the knee; and reported at least one outcome of interest. Primary outcomes were pain, function, quality of life and adverse effects.
Our search had no language restrictions and used these electronic databases:
• MEDLINE® (through March 29, 2007)
• EMBASE (through March 16, 2006)
• Cochrane Controlled Trials Register (through November 27, 2006).
EMBASE was updated with abbreviated searches through November 27, 2006. Additional sources were 2004–2006 conference proceedings of the American Association of Orthopedic Surgeons (AAOS), American College of Rheumatology (ACR) and the Osteoarthritis Research Society International (OARSI). Product inserts of U.S.-marketed viscosupplements were consulted. There were few RCTs on arthroscopy or comparative outcomes, so we also sought nonrandomized comparative trials and, for arthroscopy, administrative database analyses and case series (n>50). Because several comprehensive systematic reviews with meta-analyses on viscosupplementation and glucosamine/chondroitin had been published, we focused on detailed review of existing meta-analyses, supplemented by primary studies where necessary.
Of 1,842 citations, 451 articles were retrieved and 98 selected for inclusion:
• Six meta-analyses (N=41 trials) and one additional trial of viscosupplementation
• Six meta-analyses (N=16 trials) and five additional trials of glucosamine/chondroitin
• 23 articles on arthroscopy.
A single reviewer screened citations for article retrieval; citations judged as uncertain were reviewed by a second reviewer. The same procedure was used to select articles for inclusion in the review. A single reviewer performed data abstraction and a second reviewed the evidence tables for accuracy. However, study quality was appraised by dual independent review. All disagreements were resolved by consensus.
The quality of RCTs and quasi-experimental studies were assessed using the general approach developed by the U.S. Preventive Services Task Force (Harris, Helfand, Woolf, et al. 2001). Assessment of the quality of systematic reviews and meta-analyses were guided by a quality rating method reported by Oxman and Guyatt (1991). The framework proposed by Carey and Boden (2003) was used to assess the quality of case series.
- This systematic review of the literature will address the following key questions regarding managing patients with OA of the knee with three interventions: intra-articular injections of viscosupplements; oral glucosamine and chondroitin; and, arthroscopic lavage and debridement.
1. What are the clinical effectiveness and harms of each intervention in patients with primary OA of the knee?
2. What are the clinical effectiveness and harms of each intervention in patients with secondary OA of the knee?
3. How do the short-term and long-term outcomes of each intervention differ by the following subpopulations: age, race/ethnicity, gender, primary or secondary OA, disease severity and duration, weight (body mass index), and prior treatments?
4. How do the short-term and long-term outcomes of each intervention compare for the treatment of primary OA of the knee; and secondary OA of the knee?
*** The systematic review data of this published project was retrospectively imported into SRDR by the Brown EPC on behalf of the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center and the Agency for Healthcare Research and Quality (AHRQ). For access to the full report available on the AHRQ website, follow this link: http://archive.ahrq.gov/downloads/pub/evidence/pdf/oaknee/oaknee.pdf ***
- Funding Source
- The Agency for Healthcare Research and Quality (AHRQ)