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Bone & Joint Open
Vol. 2, Issue 6 | Pages 414 - 421
1 Jun 2021
Kim SK Nguyen C Avins AL Abrams GD

Aims. The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury. Methods. Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies. Results. There was a total of 2,214 cases of ACL and PCL injury and 519,869 controls within the two cohorts, with three loci demonstrating a genome-wide significant association in the meta-analysis: INHBA, AEBP2, and LOC101927869. Of the eight candidate genes previously studied in the literature, six were present in the current dataset, and only COL3A1 (rs1800255) showed a significant association (p = 0.006). Conclusion. Genetic markers in three novel loci in this study and one previously-studied candidate gene were identified as potential risk factors for ACL and PCL injury and deserve further validation and investigation of molecular mechanisms. Cite this article: Bone Jt Open 2021;2(6):414–421


Bone & Joint Open
Vol. 4, Issue 3 | Pages 182 - 187
14 Mar 2023
Sheridan GA Hanlon M Welch-Phillips A Spratt K Hagan R O'Byrne JM Kenny PJ Kurmis AP Masri BA Garbuz DS Hurson CJ

Aims

Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings.

Methods

A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. ‘Controls’ were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size.


Bone & Joint Open
Vol. 1, Issue 9 | Pages 512 - 519
1 Sep 2020
Monzem S Ballester RY Javaheri B Poulet B Sônego DA Pitsillides AA Souza RL

Aims

The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones.

Methods

Three groups (seven per group) of 12-week-old mice were: 1) ovariectomized and 20 weeks thereafter treated weekly for 24 weeks with 100 μm/kg subcutaneous ibandronate (OVX+IBN); 2) ovariectomized (OVX); or 3) sham-operated (SHAM). Quantitative fracture analysis generated biomechanical properties for the femoral neck. Tibiae were microCT scanned and trabecular (proximal metaphysis) and cortical parameters along almost its whole length measured.