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Orthopedics · 4 min read · September 27, 2026
From the course: Preventing Knee Osteoarthritis: A Systematic Review of Randomized Trials · 0.5 contact hours
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Can knee osteoarthritis be prevented? Very few randomized trials have tested the question, and most of the strategies they tested did not show a clear effect. In a systematic review published in JOSPT Open in 2026, Almeida Silva and colleagues found three eligible trials. The one promising result came from a low-intensity self-management lifestyle program: among women with a body mass index (BMI) of 25 or higher, fewer developed knee pain over one year than in a comparison group that attended a single education session. The authors describe the evidence as uncertain and ask readers to interpret even that result with caution.
Knee osteoarthritis has no cure. The burden estimate the authors cite projects 642 million cases worldwide by 2050, a 75% increase over 2020. They name obesity and previous knee injury among the major risk factors, along with impaired muscle function, which makes prevention a reasonable question to put to the trial evidence.
The authors separated prevention into two levels:
Trials that treated established, symptomatic osteoarthritis were outside the review's scope.
The team registered the review in advance with PROSPERO (CRD42023391750), followed the PRISMA reporting guidelines, and searched MEDLINE, EMBASE, CINAHL, PEDro and the Cochrane Library through June 10, 2025. Of more than 56,000 records, 272 were read in full. Five reports describing three randomized trials, with 1,481 participants in total, met every criterion.
One eligibility rule shaped the result. The outcome of interest, such as knee pain, had to be absent when participants entered the trial, so each trial had to be measuring something new appearing rather than something already present changing. Pairs of reviewers worked independently at every step, from screening to rating risk of bias with version 2 of the Cochrane tool. Because the trials differed too much from one another, the authors described the findings narratively instead of pooling them.
| Strategy | Participants and follow-up | What the authors reported |
|---|---|---|
| Self-management lifestyle program | 525 community-based women in New Zealand, 12 months | No clear difference overall; fewer new cases of knee pain among women with a BMI of 25 or higher |
| Diet and exercise | 407 women in the Netherlands, 30 and 72 months | No clear effect on new knee osteoarthritis |
| Oral glucosamine | Same Dutch trial | No clear effect on new knee osteoarthritis |
| Diet and exercise plus glucosamine | Same Dutch trial | No clear effect on new knee osteoarthritis |
| Intra-articular sprifermin injections | 549 adults in eight countries, 60 months | No clear difference in knee replacement at any dose or schedule |
The lifestyle program was low in intensity by design. Women attended one interactive group session, worked through a manual at home, received monthly text message reminders and had one telephone coaching call over the year. The program's messages centered on small behavior changes, goal setting and self-monitoring, including self-weighing. Among women with a BMI of 25 or higher, the risk of developing knee pain at 12 months was roughly 70% lower than in the education-session group. That estimate came from a secondary analysis within a single small trial, not from a preplanned primary comparison.
The Dutch trial counted a new case of knee osteoarthritis four different ways, including joint space narrowing and Kellgren-Lawrence grading. None of the four definitions separated the groups at either follow-up.
The authors state that the small number of trials, more than any trial's result, is the central finding. Every included trial addressed secondary prevention, and none tested primary prevention. Four of the five reports were rated at high risk of bias overall and the fifth raised some concerns; selective reporting of results was the domain of greatest concern.
Most end points were imaging findings rather than symptoms, and the authors note that knee osteoarthritis is better identified by clinical symptoms than by imaging. The trials also defined a new case differently, which is part of why the results could not be combined. No controlled trial addressed prevention after an anterior cruciate ligament or meniscus injury, and none tested interventions targeting muscle weakness, although both are established risk factors.
In their key points, the authors write that lifestyle-based prevention may be most effective when it is targeted to higher-risk groups, such as women with overweight or obesity. They state that current evidence is insufficient to support or refute diet and exercise, glucosamine, the two combined, or sprifermin as ways to prevent or slow knee osteoarthritis or to reduce the need for joint replacement.
For future trials, the authors call for primary prevention studies that address obesity, knee injury and muscle weakness directly. They also ask for outcomes that matter to patients, such as pain intensity and function, standard definitions of a new case so trials can be compared, and stronger designs with proper blinding and larger samples. One large trial is already underway: the Osteoarthritis Prevention Study is testing a combined diet and exercise program over 48 months in women with obesity who have no structural knee disease at the start.
The randomized trial evidence is limited. In their 2026 systematic review, Almeida Silva and colleagues found three eligible trials. Only a self-management lifestyle program showed a promising result, and only among women with a BMI of 25 or higher. No trial has yet tested primary prevention.
In the Dutch trial included in the review, oral glucosamine, alone or combined with diet and exercise, showed no clear effect on new knee osteoarthritis at 30 or 72 months. The authors judged the evidence insufficient to support or refute glucosamine for prevention.
The one trial that tested a diet and exercise program in women found no clear effect on new knee osteoarthritis by any of the four definitions it used. The authors describe this evidence as uncertain, and a larger trial of diet and exercise in women with obesity is now in progress.
Almeida Silva HJ, Perea J, Dantas G, Ferrari AV, Wolden M, Salvini TF, de Campos TF. Intervention strategies for preventing knee osteoarthritis: a systematic review. JOSPT Open. 2026;4(3):264-275. doi:10.2519/josptopen.2026.0155
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