Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: Results of the two‐year multinational knee osteoarthritis structural arthritis study

Bingham, Clifton O.; Buckland‐Wright, J. C.; Garnero, Patrick; Cohen, Stanley; Dougados, Maxime; Adami, Silvano; Clauw, Daniel J.; Spector, Timothy D.; Pelletier, Jean Pierre; Raynauld, J.-P.; Strand, Vibeke; Simon, Lee S.; Meyer, J. M.; Cline, Gary A.; Beary, John F.

doi:10.1002/art.22160

Cited by 333 publications

(263 citation statements)

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“…Secondary data analyses were conducted on subjects enrolled in the placebo arm of a 2-year multinational study of the effects of a bisphosphonate, risedronate, on OA symptoms and radiographic progression (Knee OA Structural Arthritis [KOSTAR]), which has been described elsewhere (9). The original data set consisted of 622 men and women ages 39 -80 years in North America (n ϭ 310) and Europe (n ϭ 312) who were randomized to the placebo arm.…”

Section: Methodsmentioning

confidence: 99%

“…In the original parent study for our analysis, radiographic progression of the entire group was only 0.088 mm over 2 years in the European cohort and 0.13 mm in the North American cohort, which was significantly less than an anticipated rate of 0.20 mm per year. When analyzed using a stringent criterion (Ͼ0.6 mm or 3 ϫ smallest detectable difference), only a small proportion of individuals (13%) would be classified as having significant JSN, or "progressors" (9).…”

Section: (3)mentioning

confidence: 99%

“…Subjects were persons with mild to moderate knee OA who were recruited into the largest multinational drug development trial to date (n ϭ Ͼ2,400) and had been assigned to the placebo arm with well-characterized symptoms over 2 years (9). Changes in JSW and symptoms served as primary end points.…”

Section: (3)mentioning

confidence: 99%

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Identifying common trajectories of joint space narrowing over two years in knee osteoarthritis

Bartlett

Ling

Mayo

et al. 2011

Arthritis Care & Research

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Objective. Little is known about the natural history of knee osteoarthritis (OA). We sought to identify common patterns of joint space narrowing (JSN) in well-characterized knee OA patients in the placebo arm of a 2-year international study. Methods. We performed secondary data analyses of 622 adults ages 39 -80 years in North America (n ‫؍‬ 310) and Europe (n ‫؍‬ 312) with symptomatic knee OA. Fluoroscopically positioned semiflexed anteroposterior radiographs were obtained at 0, 12, and 24 months. Group-based trajectory modeling was used to identify distinctive groups of individuals with similar trajectories of JSN, taking into account sex, age, and body mass index. Results. Seven groups were identified. Four exhibited joint space width (JSW) stability over 2 years representing the most common trajectory (71%), which was unrelated to initial JSW. Atypical courses included slow, rapid, and moderate progressors; most had significant JSN at study entry. Slow progressors (20%) had a mean JSN of 0.2 mm over 2 years. Only 2% of the sample demonstrated rapid JSN (2.1 mm), while 7% had JSN of 0.7 mm. Rapid progressors tended to be men, while slow and moderate progressors were older and heavier. Conclusion. Most (70%) people with OA demonstrated no significant JSN over 2 years; 20% showed slow progression, 7% had moderate, and 2% had rapid JSN. Progressors tended to have less JSW at study entry and were older and heavier; rapid progressors were more likely to be men. Understanding common patterns of the course of knee OA may offer new opportunities to target those at greatest risk of disability.

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Section: Methodsmentioning

confidence: 99%

Section: (3)mentioning

confidence: 99%

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Identifying common trajectories of joint space narrowing over two years in knee osteoarthritis

Bartlett

Ling

Mayo

et al. 2011

Arthritis Care & Research

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“…As reviewed by Roux and Richette, 77 antiresorptive agents, including bisphosphonates and cathepsin-K inhibitors, have demonstrated beneficial effects on structural progression in experimental animal models of OA, suggesting that treatments targeting bone may have a role in managing the disease. However, in humans, two randomised controlled trials of risedronate for knee OA failed to demonstrate a significant reduction in JSN over time, 78,79 and similarly a recent systematic review concluded that there was limited evidence that bisphosphonates are an effective treatment option for pain in OA. 80 Following these negative studies, there has been a recent resurgence of interest in manipulating bone turnover for the treatment of OA following the publication of the SEKOIA trial of strontium ranelate for the treatment of knee OA.…”

Section: Mechanisms Including Recent Insights From Genetic Studiesmentioning

confidence: 99%

Osteoarthritis and bone mineral density: are strong bones bad for joints?

et al. 2015

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Osteoarthritis (OA) is a common and disabling joint disorder affecting millions of people worldwide. In OA, pathological changes are seen in all of the joint tissues including bone. Although both cross-sectional and longitudinal epidemiological studies have consistently demonstrated an association between higher bone mineral density (BMD) and OA, suggesting that increased BMD is a risk factor for OA, the mechanisms underlying this observation remain unclear. Recently, novel approaches to examining the BMD-OA relationship have included studying the disease in individuals with extreme high bone mass, and analyses searching for genetic variants associated with both BMD variation and OA, suggesting possible pleiotropic effects on bone mass and OA risk. These studies have yielded valuable insights into potentially relevant pathways that might one day be exploited therapeutically. Although animal models have suggested that drugs reducing bone turnover (antiresorptives) may retard OA progression, it remains to be seen whether this approach will prove to be useful in human OA. Identifying individuals with a phenotype of OA predominantly driven by increased bone formation could help improve the overall response to these treatments. This review aims to summarise current knowledge regarding the complex relationship between BMD and OA.

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“…Only a small proportion of patients lose significant joint space in some studies of knee joint osteoarthritis or of treatments for knee OA [10][11][12]. The average rate of JSN is small in most studies [11,13].…”

Section: Discussionmentioning

confidence: 99%

Accuracy and Reproducibility of Radiographic Knee Joint Space Narrowing Measurements Referenced to the Mid-Coronal Plane

Hipp¹,

Goel²,

Newman³

et al. 2015

TOJ

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Introduction: Knee joint space narrowing (JSN) is a primary outcome measure in the progression of knee osteoarthritis and its treatment. JSN is most frequently determined from radiographs relying on the radiographic shadow of the anterior or posterior margins of the tibial plateau. Several studies address the confounding issues related to use of the anterior and posterior margins of the tibial plateau. An alternative strategy is to identify the mid-coronal plane of the tibial plateau and use that as a reference for measuring JSN. Methods: Radiographs with precisely defined changes in joint space width (JSW) were created from CT imaging of cadaver knees. The mid-coronal plane of the knee was used to measure JSW and calculate JSN. Radiographs and data from the Osteoarthritis Initiative study were used to assess reproducibility and compare mid-coronal plane measurements of JSN to previously reported methods. Results:The average absolute error in the measured versus known medial JSN was below 0.2 mm. The reproducibility was similar to previously published methods. There was a strong correlation between the mid-coronal plane measurements of JSN and JSN calculated using previously reported methods. There were several discrepancies between the two methods, suggesting that JSN for individual cases may depend on the method used to measure JSN. Discussion: This study describes an alternative to using the margins of the tibial plateau when calculating JSN. JSN measurements based on the mid-coronal plane of the knee, where cartilage changes are more likely to occur, may have advantages.

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Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: Results of the two‐year multinational knee osteoarthritis structural arthritis study

Cited by 333 publications

References 50 publications

Identifying common trajectories of joint space narrowing over two years in knee osteoarthritis

Identifying common trajectories of joint space narrowing over two years in knee osteoarthritis

Osteoarthritis and bone mineral density: are strong bones bad for joints?

Accuracy and Reproducibility of Radiographic Knee Joint Space Narrowing Measurements Referenced to the Mid-Coronal Plane

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