Combining dietary fiber inulin with parathyroid hormone–lowering therapy improves bone remodeling and mechanics in a rat model of Chronic Kidney Disease–Mineral Bone Disorder

INTRODUCTION: Chronic kidney disease (CKD) has devastating effects on the skeletal system resulting in an increased fracture risk. CKD results in the buildup of metabolites in the blood (often referred to as uremic toxins), and several uremic toxins have been linked to adverse skeletal outcomes. We have shown that dietary fiber inulin reduced uremic toxins and had a positive effect on bone. Here, we determine if combining inulin with parathyroid hormone (PTH) lowering therapies could improve skeletal properties beyond either therapy alone. METHODS: An animal model of CKD-Mineral Bone Disorder (CKD-MBD) (Cy/+ rats) was treated with or without inulin in the presence or absence of the PTH-suppressing agents (KP-2326, an analogue of the calcimimetic etelcalcetide, or 2% calcium). Key outcome measures included bone architecture, bone remodeling, mechanical properties and serum biomarkers. RESULTS: Dietary inulin groups had lower circulating levels of the uremic toxin p-cresol sulfate and higher circulating butyrate indicating diet-induced differences in gut-derived metabolites. Combining inulin with KP-2326 resulted in lower cortical bone porosity than in untreated animals and lower trabecular bone turnover (relative to untreated animals) than either treatment alone. Combining inulin with KP-2326 led to improved mechanical properties. Combining inulin with calcium treatment suppressed bone turnover below healthy control levels. CONCLUSIONS: The improvement in bone remodeling and mechanical properties speaks favorably for combining dietary fiber intervention with calcimimetics for reducing the skeletal deterioration in CKD with hyperparathyroidism.