Kohler, RachelSegvich, Dyann M.Reul, OliviaMetzger, Corinne E.Allen, Matthew R.Wallace, Joseph M.2024-08-052024-08-052024-05-12Kohler R, Segvich DM, Reul O, Metzger CE, Allen MR, Wallace JM. Romosozumab rescues impaired bone mass and strength in a murine model of diabetic kidney disease. Bone Rep. 2024;21:101774. Published 2024 May 12. doi:10.1016/j.bonr.2024.101774https://hdl.handle.net/1805/42616As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address the high-risk skeletal fragility of what is a complex disease state. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mineral density and decrease fracture rates in osteoporotic patients with mild to severe CKD, but its effect on diabetes-weakened bone is unknown. We aimed to test Romo's performance in a model of combined diabetes and CKD. 6-week old male C57BL/6 mice were randomly divided into control (CON) and disease model (STZ-Ad) groups, using a previously established streptozotocin- and adenine-diet-induced model. After 16 weeks of disease induction, both CON and STZ-Ad groups were subdivided into two treatment groups and given weekly subcutaneous injections of 100 μL vehicle (phosphorus buffered saline, PBS) or 10 mg/kg Romo. Mice were euthanized after 4 weeks of treatment via cardiac exsanguination and cervical dislocation. Hindlimb bones and L4 vertebrae were cleaned of soft tissue, wrapped in PBS-soaked gauze and stored at —20C. Right tibiae, femora, and L4s were scanned via microcomputed tomography; tibiae were then tested to failure in 4-pt bending while L4s were compression tested. Romo treatment significantly increased cortical and trabecular bone mass in both STZ-Ad and CON animals. These morphological improvements created corresponding increases in cortical bending strength and trabecular compression strength, with STZ-Ad treated mice surpassing vehicle CON mice in all trabecular mechanics measures. These results suggest that Romo retains its efficacy at increasing bone mass and strength in diabetic kidney disease.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalDiabetesChronic kidney diseaseBone mechanicsAnabolicSclerostin inhibitorArticle