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. Results. Fracture analyses revealed that OVX+IBN significantly reduced yield displacement (vs SHAM/OVX) and resilience, and increased stiffness (vs SHAM). OVX+IBN elevated tibial trabecular parameters and also increased cortical cross-sectional area and second moment of area around minor axis, and diminished ellipticity proximally. Conclusion. These data indicate that combined ovariectomy and bisphosphonate generates cortical changes linked with greater bone brittleness and modified fracture characteristics, which may provide a basis in mice for interrogating the mechanisms and genetics of atypical fracture aetiology. Cite this article: Bone Joint Open 2020;1-9:512–519

Aims. Post-operative migration of cemented acetabular components as measured by radiostereometric analysis (RSA) has a strong predictive power for late, aseptic loosening. Also, radiolucent lines predict late loosening. Migration has been reduced by systemic bisphosphonate treatment in randomised trials of hip and knee arthroplasty. Used as a local treatment, a higher local dose of bisphosphonate can be achieved without systemic exposure. We wished to see if this principle could be applied usefully in total hip arthroplasty (THA). Patients and Methods. In this randomised placebo-controlled, double-blinded trial with 60 participants, we compressed gauze soaked in bisphosphonate solution (ibandronate) or saline against the acetabular bone bed immediately before cementing the acetabular component. RSA, classification of radiolucent lines, the Harris Hip Score (HHS) and the Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) were carried out at three-, six-, 12-, and 24-month follow-up. Results. Migration of the cemented acetabular component relative to the pelvis was reduced by movement almost half in the ibandronate group, when measured as maximum total point or as movement of the femoral head (p = 0.001 and 0.004, respectively). Radiolucent lines after one year were classified as absent, partial or complete, and correlated with treatment (rho 0.37; p = 0.004). Only three of 30 patients in the ibandronate group had complete lines, compared with 13 of 28 in the placebo group (p = 0.002). There were no significant effects on HHS or WOMAC score. Conclusion. Considering the power of RSA to predict loosening of cemented acetabular components, and the likelihood that radiolucent lines indicate risk of loosening, these data suggest that local treatment with a bisphosphonate can reduce the risk of late aseptic loosening. Cite this article: Bone Joint J 2017;99-B:317–24

During revision total hip replacement using morcellised compacted bone allograft, 16 patients were randomised to receive a graft which had been rinsed in either an ibandronate solution or in saline. Patients were assessed by dual energy x-ray absorptiometry after operation and at 3, 6, 12 and 24 months. A region of interest between the tip of the femoral stem and the distal plastic plug was chosen to measure the changes in bone density over time. The study was double-blinded. In all the control patients the bone density decreased during the first three months and then remained constant at this lower level. A large proportion of the mass of the bone graft was lost. In contrast, all patients with grafts treated with bisphosphonate showed a slight increase in bone density. The difference between the groups was highly significant at all points in time. We conclude that rinsing the graft in a bisphosphonate solution prevents its resorption and may therefore reduce the risk of mechanical failure. The treatment is simple, inexpensive, and appears virtually free of risk