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Achilles Tendon Tissue Turnover Prior to and Immediately After Acute Rupture in Humans

Achilles Tendon Tissue Turnover Prior to and Immediately After Acute Rupture in Humans

Allan Cramer, MD, PhD, DENMARK Grith Højfeldt, PhD, DENMARK Jakob Agergaard, PhD, DENMARK Gerrit van Hall, Prof., DENMARK Jesper Olsen, PhD, DENMARK Per Hölmich, DMSc, Prof., DENMARK Michael Kjaer, Prof., MD, DENMARK Kristoffer W. Barfod, MD, PhD, DENMARK

Sports Orthopedic Research Center – Copenhagen (SORC-C), Arthroscopic Center, Department of Orthopedic Surgery, Copenhagen University Hospital, Amager-Hvidovre, Denmark , Hvidovre, DENMARK

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Sports Medicine

Summary: A higher than normal collagen tissue turnover occurs in the human Achilles tendon prior to rupture.


Rupture of the Achilles tendon (ATR) is frequent and results in activation of tendon cells and collagen expression, but it is unknown to what extent the turnover of tendon matrix is altered prior to or associated with tendon rupture. In addition, it is hypothesized that rupture results in a pronounced collagen synthesis already in the early phase after injury.


To characterize tendon tissue turnover prior to and immediately after acute rupture in humans.

Materials And Methods

The study included patients (n=18) eligible for operation after ATR. At inclusion, the patients ingested deuterium oxide (2H2O) orally, and on the day of surgery (within 14 days of injury) they got a 3-hours flood-primed infusion of a 15N-proline tracer. During surgery, the patients had one biopsy taken from the ruptured part of the Achilles tendon and one 3-5 cm proximal to the rupture as a control. The biopsies were analyzed for the level of carbon-14 (14C), as well as incorporation of 2H-alanine (from 2H2O) and 15N-proline to calculate long-term tendon turnover prior to rupture and the fractional synthesis rate (FSR) of tendon collagen formation in the days after rupture, respectively.


Both the rupture and the control samples showed consistently lower levels of 14C than found in healthy human tendons previously, indicating increased tendon turnover in a fraction (48% newly synthesized) of the Achilles tendon synthesizing new tissue for a prolonged period already prior to rupture. Over the first days after rupture the synthesis rate for collagen was relatively constant, and the average synthesis rate on the day of surgery (2-14 days after rupture) was 0.025%/h irrespectively of time after rupture and site of sampling (rupture vs control). No differences were found in FSR between rupture and control in the days after rupture.


The higher than normal collagen tissue turnover in the human Achilles tendon prior to rupture supports tendon tissue changes preceding injury. In addition, no marked increase in tendon collagen tissue turnover occurred in the first two weeks after Achilles tendon rupture. This favors the view that a rise in formation of new tendon collagen is not an immediate phenomenon during regeneration of ruptured tendons in humans.

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