Response of knee ligaments to prolotherapy in a rat injury model

Am J Sports Med. 2008 Jul;36(7):1347-57. doi: 10.1177/0363546508314431. Epub 2008 Feb 29.


Background: Prolotherapy is an alternative therapy for chronic musculoskeletal injury including joint laxity. The commonly used injectant, D-glucose (dextrose), is hypothesized to improve ligament mechanics and decrease pain through an inflammatory mechanism. No study has investigated the mechanical effects of prolotherapy on stretch-injured ligaments.

Hypotheses: Dextrose injections will enlarge cross-sectional area, decrease laxity, strengthen, and stiffen stretch-injured medial collateral ligaments (MCLs) compared with controls. Dextrose prolotherapy will increase collagen fibril diameter and density of stretch-injured MCLs.

Study design: Controlled laboratory study.

Methods: Twenty-four rats were bilaterally MCL stretch-injured, and the induced laxity was measured. After 2 weeks, 32 MCLs were injected twice, 1 week apart, with either dextrose or saline control; 16 MCLs received no injection. Seven uninjured rats (14 MCLs) were additional controls. Two weeks after the second injection, ligament laxity, mechanical properties (n = 8), and collagen fibril diameter and density (n = 3) were assessed.

Results: The injury model created consistent ligament laxity (P < .05) that was not altered by dextrose injections. Cross-sectional area of dextrose-injected MCLs was increased 30% and 90% compared with saline and uninjured controls, respectively (P < .05). Collagen fibril diameter and density were decreased in injured ligaments compared with uninjured controls (P < .05), but collagen fibril characteristics were not different between injured groups.

Conclusion: Dextrose injections increased the cross-sectional area of MCLs compared with saline-injected and uninjured controls. Dextrose injections did not alter other measured properties in this model.

Clinical relevance: Our results suggest that clinical improvement from prolotherapy may not result from direct effects on ligament biomechanics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthralgia / prevention & control
  • Biomechanical Phenomena
  • Complementary Therapies / methods*
  • Glucose / administration & dosage*
  • Inflammation / chemically induced
  • Injections, Intra-Articular
  • Joint Instability / pathology
  • Joint Instability / physiopathology
  • Joint Instability / therapy*
  • Medial Collateral Ligament, Knee / injuries*
  • Medial Collateral Ligament, Knee / physiopathology
  • Medial Collateral Ligament, Knee / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Sclerosing Solutions / administration & dosage*


  • Sclerosing Solutions
  • Glucose