Biomarkers could be used to prevent atrophy in ACL-deficient patients, study finds

BALTIMORE — ACL reconstruction is followed by a significant increase in pro-inflammatory biomarkers such as C-reactive protein and Interleukin-6, which in combination with elevated transforming growth factor-beta levels can contribute to and promote the development of muscle atrophy, according to a study presented at the American Orthopaedic Society for Sports Medicine Annual Meeting 2012, here.

“Patients [who sustain ACL tears] have significant muscle atrophy, and often when patients are discharged, 6 months or so after their tear, they still have strength deficits of around 40% or so,” Christopher L. Mendias, PhD, ATC, said during his presentation. With no known ways to prevent such atrophy, “we wanted to identify if there are any cytokines or signaling molecules that can actually induce muscle atrophy and if they are elevated in [these] patients — because then we could potentially target that and block some muscle atrophy, and that might be beneficial,” he said.

Biomarkers: patients vs. controls

Mendias and colleagues studied 18 patients who sustained complete non-contact ACL tears and underwent reconstructive surgery. They took blood samples preoperatively, at the time of surgery and at postoperative follow-up visits held several days, 2 weeks, 5 weeks, 12 weeks, 18 weeks and 26 weeks afterwards. They also took blood samples from 27 control subjects with no history of knee injury.

For both groups, the investigators looked for circulating levels of the biomarkers cartilage oligomeric matrix protein (COMP), C-reactive protein (CRP), Interleukin-6 (IL-6) and transforming growth factor-beta (TGF-ß).

The results reportedly showed elevated CRP and IL-6 levels and decreased COMP levels at the first postoperative follow-up. The analysis done at the second follow-up, however, revealed that COMP, CRP and IL-6 levels returned to baseline, but TGF-ß levels were elevated.

At the third postoperative follow-up, all levels returned to their preoperative states.

Preventing atrophy

“CRP had the most profound response,” Mendias said. “Right after surgery, CRP levels went up almost 50-fold, and then they fell quite rapidly so that by the second postoperative visit they were back down to basal levels.”

These findings may help physicians prevent atrophy in patients following ACL reconstruction, he noted.

“We think the combination of these factors — elevation of myostatin, TGF-ß, IL-6 and possibly some others — are driving that initial muscle atrophy we see in our ACL-deficient patients,” Mendias concluded. “That opens the door potentially for us possibly blocking this. In particular, myostatin has a lot of potential advantages in blocking it and preventing some of this muscle atrophy.”

Reference:

Mendias CL, Lynch EB, Sibilsky ER, et al. Changes in circulating biomarkers of cartilage turnover and inflammation after anterior cruciate ligament reconstruction and rehabilitation. Paper #37. Presented at the American Orthopaedic Society for Sports Medicine Annual Meeting 2012. July12-15. Baltimore.

Disclosure: Mendias has reported no relevant financial disclosures.