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Doxycycline improves tendon and cartilage pathologies in preclinical studies: current concepts
  1. Robert S Dean1,
  2. David H Kahat2,
  3. Nathan R Graden2,
  4. Nicholas N DePhillipo1,3,
  5. Robert F LaPrade1
  1. 1 Sports Medicine, Twin Cities Orthopedics, Edina, Minnesota, USA
  2. 2 University of Minnesota Medical School, Minneapolis, Minnesota, USA
  3. 3 Orthopedic Department, Oslo Sports Trauma Research Center, Oslo, Norway
  1. Correspondence to Dr Robert F LaPrade, Twin Cities Orthopedics, Edina, MN 55435, USA; laprademdphd{at}


Matrix metalloproteinases (MMPs) are enzymes that are elevated during states of inflammation and have specifically been linked to cartilage, tendon and bone pathologies. Concentrations of these enzymes fluctuate naturally with various injury states, and these enzymes have been shown to be directly inhibited by doxycycline. Historically, doxycycline has been used exclusively for its antimicrobial properties, but recent studies have investigated the anti-inflammatory properties of doxycycline and its effects on musculoskeletal pathologies. This study sought to describe the current use of doxycycline for its MMP inhibitory properties in the setting of musculoskeletal pathologies. During preclinical studies, improved healing properties were noted acutely in tendon injuries following surgical repair and chronically in cartilage injuries, demonstrating decreased rates of joint space narrowing and improved cartilage quality. There is only one known clinical trial that has examined doxycycline use, and it reported that doxycycline can decrease the rate of joint space narrowing in patients with osteoarthritis. Furthermore, doxycycline was well tolerated with minimal side effects reported in both animal and human studies. While it can be reasonably inferred that the positive effects of doxycycline are related to its ability to inhibit MMP activity, further clinical research is warranted to investigate the use of doxycycline in orthopaedic and musculoskeletal pathologies. Level of Evidence: Current Concepts, Level IV.

  • inflammation
  • basic science
  • cartilage
  • tendon
  • biomechanics

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  • Contributors RD: primary writing contribution, data collection, idea generation. DK: primary writing contribution, data collection, data analysis, idea generation. NG: significant writing contribution, data collector, data analysis. NND: writing contribution, data collector, data analysis. RL: critical edits, manuscript writing, idea generation, directed manuscript production.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests RL reports grants and personal fees from Arthrex, Inc, grants from Linvatec, grants and personal fees from Ossur, grants and personal fees from Smith & Nephew, outside the submitted work.

  • Patient consent for publication Not required.

  • Ethics approval This was a systematic review and did not require approval from our institutions institutional review board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement There are no data in this work

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