BME PhD Preliminary Exam announcement for Joseph Bustamante (J. Wallace, advisor)

Everyone is invited to attend the public presentation beginning at 10:00 AM.

Research Title: Evaluating Bone-Targeted Therapies in a Novel Aged Diabetic Kidney Disease Mouse Model

Date: July 24, 2025

Time: 10:00 AM

Location: SL220A at Purdue in Indianapolis

Committee:

Dr. Joseph M. Wallace III – Major Professor

Dr. Rachel Surowiec

Dr. Matthew Allen

Dr. Corinne Metzger

Abstract: Diabetes mellitus (DM) and chronic kidney disease (CKD) affect ~1/10 and ~1/7 Americans respectively, but among the aged population (65+), a staggering 30% suffer from DM and 34% have CKD. Additionally, having CKD or DM greatly increases the risk of having the other, referred to as diabetic kidney disease (DKD). While each individually has detrimental bone outcomes, aging, CKD, and DM compound to devastate bone mass and strength. Neither of the diseases are treated primarily for bone effects, and bone targeting treatments and appropriate animal models of this combined disease state are lacking. To better understand the complex interactions of aging, bone, and DKD, a model of DKD established in young mice was adapted for aged C57Bl/6J mice. Aged mice have been studied in CKD and Diabetes before, but high attrition in the individual disease states increases the difficulty of a combined model. At termination, 95% of the DKD animals had survived and been successfully induced with detrimental bone effects. This study demonstrated that an advanced stage of DKD in aged animals is reliably achievable without high attrition. Additionally, Raloxifene (RAL), a selective estrogen receptor modulator, PTH, a naturally occurring anabolic, and Romosozumab, a sclerostin antibody anabolic, have shown to be effective treatments for increasing bone mass in aged animals individually and as pairs of RAL and either of the anabolics. Together, it is hypothesized that RAL + ROMO/ PTH will significantly improve the devastated bone of the aged DKD mice.