title: Bisphosphonates reduce bone mineral loss at ligament entheses after joint injury.
abstract: OBJECTIVE
  To examine the effects of anterior cruciate ligament (ACL) insufficiency, and subsequent bisphosphonate (BP) antiresorptive therapy, on the bone mineral interface at the enthesis of remaining ligamentous restraints.
  
  
  METHODS
  We measured bone mineral geometry (and subsequent adaptation) at the medial collateral ligament (MCL) origin, using micro-computed tomography (muCT). Groups of normal control, 6 and 14 wk anterior cruciate ligament transected (ACLX), and 6 wk ACLX-BP (risedronate) dosed rabbits were evaluated. Samples were then processed histologically, and the results of mineral adaptation and progression of osteoarthritis (OA) compared to joint laxity values obtained from previous biomechanical testing of the MCL-complex.
  
  
  RESULTS
  muCT defined the MCL origin as a symmetrical, metaphyseal depression that contained soft-tissue elements, including fibrocartilage and ligament--as seen in subsequent histological sections. In contrast, the insertions from ACLX animals lost significant bone mineral, with an MCL-insertion volume 1.2 times that of normal controls at 6 wk ACLX, which further increased to 2.3 times that of normal controls at 14 wk ACLX. Significant differences were also measured between 6 and 14 wk ACLX and age-matched normal controls in volume of cortical bone containing the MCL insertion. However, there were no significant differences in the percentage of cortical bone to underlying trabecular bone at the MCL insertion. When comparing muCT mineral adaptation at the MCL-enthesis with historical MCL-complex laxity data, the values for laxity after ACLX increased proportionately as bone mineral at the insertion was lost, and subsequent use of the BP risedronate reduced both mineral loss and MCL-complex laxity.
  
  
  CONCLUSIONS
  Compared to the untreated ACLX condition, administering bisphosphonate immediately after loss of the ACL conserved bone mineral at the MCL enthesis, suggesting the potential to therapeutically influence joint-complex laxity and OA progression.
authors.affiliation: McCaig Centre for Joint Injury & Arthritis Research, Biomedical Peptide-Conjunction Laboratory, Department of Chemical and Materials Engineering, University of Calgary, Calgary, AB, Canada. mdoschak@ualberta.ca
authors.forename: M R
authors.initials: MR
authors.lastname: Doschak
authors.forename: J M
authors.initials: JM
authors.lastname: LaMothe
authors.forename: D M L
authors.initials: DM
authors.lastname: Cooper
authors.forename: B
authors.initials: B
authors.lastname: Hallgrimsson
authors.forename: D A
authors.initials: DA
authors.lastname: Hanley
authors.forename: R C
authors.initials: RC
authors.lastname: Bray
authors.forename: R F
authors.initials: RF
authors.lastname: Zernicke
mesh_terms: D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology; D004164:Diphosphonates / Q000627:therapeutic use*; D005269:Femur / Q000378:metabolism*; D006614:Hindlimb; D008903:Minerals / Q000378:metabolism*; D023421:Models, Animal; D011817:Rabbits; D014056:Tomography, X-Ray
chemical_list: D004164:Diphosphonates; D008903:Minerals