ANTI-OSTEOPORTOTIC DRUG IBANDRONATE AFFECTS CALLUS FORMATION AND MECHANICAL PROPERTIES DURING FRACTURE REPAIR IN OVARIECTOMIZED RATS

Abstract

Introduction: Patients who are prescribed bisphosphonates are still at risk to endure a fracture from weak and brittle bones. The question is what pharmacologic strategy should be taken to accelerate fracture healing when the patient is currently taking a bisphosphonate. Ibandronate, was tested in an osteoporotic rat model to determine how it modified the callus healing and resistance to torsion after a transverse fracture was produced in a femur.

Materials and Methods: 36 female rats were divided into 3 groups; ovariectomized (OVX) placebo control, non-OVX control and Ibandronate. Prior to the osteotomy, the Ibandronate treatment group was injected with the drug over 21 days healing. Each sample was scanned by the SCANCO uCT 80 to measure volume of the callus and quality of the trabeculae in the proximal femur. Instron testing recorded the modulus of rigidity and torque until failure. Yield point and toughness were also calculated.

Results: uCT images taken over the fracture gap showed that the Ibandronate rats had greater bone volume fraction of woven callus by ANOVA compared to control groups (p< 0.05). Significant in total callus volume for Ibandronate, were shown to be 32% larger than the non-OVX control group and 45% larger than the placebo group. Ibandronate also increased BMD of woven bone in the callus by 14%. Ibandronate showed the highest polar moment of inertia as well.

The torsion testing in Ibandronate had 51% greater toughness than placebo and 69% greater than the non-OVX group. Ibandronate increased trabecular number significantly over the placebo and was not significantly different from the non-OVX group. Trabecular separation was less in Ibandronate compared to the placebo group. Volume in the trabecular neck increased by 35% for the Ibandronate over the placebo.

Discussion: Ibandronate had an anabolic effect to produce more callus tissue at the fracture site, most likely by suppressing osteoclast remodelling activity. A large callus with more bone would increase fracture stability and reduce risk of non union. This is supported by a larger polar moment of inertia. Ibandronate had greater resistance to torsion, which could indicate better healing. However increased rigidity would not entirely benefit the healing unless the bone could handle load plastically. The toughness results showed that Ibandronate can absorb more energy than the control groups before refracturing. Continued treatment with this drug after a fracture could form a larger callus with greater mechanical toughness while also treating the disease of osteoporosis in other fracture risk sites of the body.