BOSTON—New research suggesting that alterations in the meniscus contribute a large proportion to variations in joint space narrowing (JSN) may have ramifications for how clinical trials of disease-modifying osteoarthritis drugs are conducted. David J. Hunter, MD, a rheumatologist at Boston University Medical Center in Boston, reported the findings in the August issue of Arthritis & Rheumatism.1

"A large proportion of the variance in joint space change is made up of change in the meniscus." —David J. Hunter, MD
The new research, part of the Boston Osteoarthritis of the Knee Study, shows that meniscus position and degeneration accounted for a substantial proportion of the variance in JSN among 264 knee osteoarthritis (OA) patients. This calls into question the assumption that JSN changes in OA are attributable only to hyaline articular cartilage damage.

"We would advocate measuring the hyaline articular cartilage directly using magnetic resonance imaging (MRI), or at least recognizing that when measuring JSN on a radiograph, other factors such as the meniscus can affect the variability of this outcome [in clinical trials of new disease-modifying agents]," Dr. Hunter told CIAOMed.

The major structural endpoint for many trials of disease-modifying agents is the change or lack of change in radiographic joint space. "Our data would suggest that if change in hyaline articular cartilage is your outcome of interest, a large proportion of the variance in joint space change is made up of change in the meniscus," Dr. Hunter said. "Careful consideration of the likely tissue target for new pharmacologic interventions and the modality of measurement for this tissue target need to be ascertained before accepting a measurement endpoint technique that may not be optimal."

In the new study, cartilage and meniscal degeneration were scored on MRI in the medial and lateral tibiofemoral joints with a semiquantitative grading system. Researchers conducted fluoroscopically-positioned weight-bearing posteroanterior x-rays at 0, 15, and 30 months.

The new study used the ordinal measure of JSN. "Optimally, we would have performed the analyses using the continuous joint space width (JSW) measurement," Dr. Hunter said. "This is not optimal for assessing the lateral joint space, and in this study most of the variability in medial continuous JSW was seen in persons with a relatively normal JSW and may reflect pseudo-widening and/or changes in participant positioning, but it would be worth assessing if the same findings in our study can be replicated using the continuous JSW measure."

He added that further assessment of the differences between acquiring MRI in a weight bearing position and when lying supine is also necessary to evaluate the impact of positional changes on these measures.

"For other studies where the radiographic joint space was used as the primary endpoint if a significant effect was seen," says Dr. Hunter, "the agent may also be having an effect on the meniscus. In the absence of a significant effect, it may mean that the radiographic joint space was not adequately specific for the structural outcome of interest, and we would encourage measuring the tissue target directly."

Reference

1. Hunter DJ, Zhang YQ, Tu X, et al.  Change in joint space width. Hyaline articular cartilage loss or alteration in meniscus. Arthritis Rheum. 2006;54:2488-2495.