5/14/15

Patients who underwent knee replacement exhibited less cartilage thickness at baseline and, over time, greater lateral and location-independent femorotibial cartilage loss than those who did not get replacement, researchers said.

Furthermore, location-independent analysis of change in cartilage thickness predicted future knee replacement.

These were among the findings of a U.S.-European prospective cohort study published online in Arthritis Care and Research, and the first to identify differences in lateral femorotibial cartilage loss in the knees of patients who go on to have replacement compared with those of controls.

Previous nested case-control studies from the longitudinal Osteoarthritis Initiative (OAI) reported that medial but not lateral femorotibial compartment (LFTC) cartilage loss was significantly elevated in knees undergoing replacement in the subsequent year compared with those of matched controls. But no prospective OAI cohort study had examined how rates of cartilage loss over a defined interval relate to the advent of knee replacement in following years and to what extent location-independent analysis of subregional cartilage change predicts replacement.

To fill that gap, researchers led by Wolfgang Hitzl, PhD, a biostatistician at Paracelsus Medical Hospital in Salzburg, Austria, looked at alterations in femorotibial cartilage thickness from baseline to 12-month follow-up in patients undergoing replacement between 24 months and 60 months and those not having replacement.

“Discrimination of cartilage loss was greater for replacements occurring within 2 years after the measurement than for those occurring later,” wrote Hitzl and his associates. “The results confirm quantitative cartilage loss to be a potent structural outcome in clinical trials on DMOAD [disease-modifying osteoarthritis drug] efficacy.”

The researchers studied right knees from 531 patients in the cohort of the OAI, a longitudinal observational study conducted by the National Institutes of Health (NIH) in partnership with private industry. All had radiographic knee osteoarthritis of Kellgren-Lawrence grade (KLG) 2-4.

In another first, the study used segmentation of coronal fast low-angle shot magnetic resonance images to quantify cartilage thickness in 16 femorotibial subregions.

Of the 531 participants (63% women, mean age 63 ± 9 years, BMI 30 ± 4.8), 40 received a femorotibial replacement within 48 months. The higher the baseline KLG, the higher the percentage of replacement within 48 months.

At baseline, the replacement group had thinner medial and lateral femorotibial cartilage than controls: 6.05 ± 1.2 mm versus 7.12 ± 1.10 mm (-15.3%, P<0.001). And change in longitudinal cartilage thickness was significantly greater in replacements than in controls at the following sites: the total femorotibial joint (area under curve [AUC]=0.64); the lateral compartment (AUC=0.66); both tibiae (AUC ≥0.61); and the first nine of 16 ordered values of subregion change (AUC=0.64-0.69).

The differences were stronger in the 18 patients undergoing replacements at 24-36 months than in the 22 patients having replacement at 48-60 months.

The investigators noted that “quantitative loss in cartilage thickness may be a valuable drug target and a powerful marker for evaluating the efficacy of DMOAD intervention.” In addition, they wrote, “… our findings highlight the importance of cartilage loss in the LFTC, particularly in the LT [lateral tibia], in predicting replacement.”

Addressing study limitations, Hitzl and associates noted that only a subsample of the OAI was studied, and that replacements had more advanced radiographic disease than nonreplacements, although the analysis adjusted for that. Also, with the low sample size and small number of replacements observed, the investigation lacked sufficient power to separately study knees with primarily medial or lateral radiographic disease.