Pyruvate and lactate as local prognostic biomarkers of patient outcome after achilles tendon rupture

Abstract

Background: Acute Achilles tendon rupture (ATR) is a frequently disabling injury, which exhibits unclear variability in long-term functional and patient-reported outcomes. Biomarkers from early healing, which have been shown to be prognostic of long-term outcome would facilitate the development of improved treatment methods.

Hypothesis/purpose: The aim of this study was to assess essential metabolites pyruvate and its product lactate, as early biomarkers in relation to long-term functional- and patient-reported outcome after ATR.

Study design: Prospective cohort study.

Methods: A total of 124 patients (103 men, 21 women; mean age 40 ± 7 years) with ATR, treated with uniform anesthetic and surgical technique, were prospectively assessed. At two weeks post-injury pyruvate and lactate concentrations were assessed in both the injured and uninjured limbs using microdialysis followed by enzymatic quantification. The ratios of the concentration in the injured versus uninjured limb of pyruvate (pyruvate-r) and lactate (lactate-r) were calculated as well as the lactate/pyruvate ratios (L/P-r). At 12 months, patient-reported outcome was examined using self-reported questionnaires; Achilles tendon Total Rupture Score (ATRS), Foot and Ankle Outcome Score (FAOS), and physical activity score. At 12 months, functional outcome was studied using the validated heel-rise test.

Results: Elevated pyruvate-r, at two weeks, was significantly associated with total ATRS (R = 0.254, P = 0.028), less loss in physical activity (R = 0.241, P = 0.039), less experience of pain in FAOS (R = 0.275, P = 0.032), and a higher number of heel-rise repetitions on injured side (R = 0.230, P = 0.040) at 12 months. Increased lactate-r was related with less strength limitations in the calf (R = 0.283, P = 0.011), while the elevated lactate-pyruvate ratio, notably, was related to more limitations in walking on uneven surface (R = -0,243, P = 0.027). The findings were verified by multiple linear regression taking confounding factors into consideration.

Conclusion: This study established that the metabolite pyruvate is a good potential biomarker, prognostic of patient outcome at the one-year follow-up after ATR surgery. These novel findings suggest that local biomarkers could be developed at an early-stage screen for new ATR treatments.

Keywords: achilles tendon; biomarker; healing; lactate; lactate-pyruvate ratio; patient-reported outcome measures; pyruvate; rupture.