Bone Abstracts

Objective: The purpose of this study was to determine whether osteogenesis imperfecta (OI) patients entering adulthood should continue with bisphosphonate therapy or would benefit from switching to a RANKL blockade therapy. To address this question, we used a mouse model of type III OI.

Methods: Animal studies were performed under IACUC approval. OI (oim/oim) and wild-type (WT) mice were treated from 2–26 weeks with i) saline; ii) alendronate (ALN; 0.21 mg/kg per dose weekly); or iii) ALN from 2–14 weeks followed by 1.5 mg/kg per dose biweekly RANK-Fc from 14–26 weeks (ALN+RANK-Fc). There were 20 mice per group. Fracture number was calculated from high-resolution faxitrons obtained in the anterior–posterior and medial-lateral planes at 14 weeks and sacrifice. Femurs (n=4–10/group) were analyzed by microcomputed tomography (micro-CT) using a Scanco μCT 35 system (Scanco Medical, Basserdorf, Switzerland). A subset of the femora were embedded in poly methyl methacrylate and section at 2 μm for Fourier transform infrared imaging (FTIRI) analysis (n=3–5/group). Nine images of cortical and trabecular bone were taken from each femur using a Perkin Elmer Spotlight Imaging Spectrometer and ISys (Malevern Instruments) software. Results are statistically significant P<0.05 by two-way ANOVA (SigmaStat).

Results: Fractures: at 14 weeks, ALN-treated oim/oim mice had fewer fractures compared to saline. At 26 weeks, both treatment groups had fewer fractures compared to saline. There were no differences between treatment groups at either time-point and no new fractures after 14 weeks in either group.

Micro-CT: there were no differences in cortical bone in any parameters studied. Trabeculae number was increased in oim/oim for both treatment groups compared to saline. ALN+RANK-Fc increased trabeculae number compared to ALN. Trabeculae spacing decreased and bone volume fraction increased in both treated oim/oim groups compared to saline. Changes in the WT mirror oim/oim.

FTIRI: oim/oim trabecular bone: ALN treatment increased mineral:matrix ratio compared to saline and both treatment groups increased collagen maturity compared to saline. oim/oim cortical bone mineral:matrix ratio was increased in ALN compared to ALN+RANK-Fc treatment. WT cortical bone: ALN+RANK-Fc treatment resulted in more perfect crystals compared to saline.

Discussion: Based on our current data, treatment with ALN or ALN+RANK-Fc comparably reduces fracture number, increases bone quantity, and alters bone quality in oim/oim mice. Mechanical testing will be essential in determining the implication of these changes on patient life.

Declaration of interest: A Boskey owns stock in Amgen. Amgen supplied the drugs for this study.