Bone marrow adipose tissue expansion and bone loss in experimental chronic kidney disease is independent of altered bone marrow stromal cell lineage determination.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Chronic kidney disease-mineral bone disorder is the irreversible loss of kidney function leading to altered mineral homeostasis and bone loss, commonly referred to as renal osteodystrophy. Bone marrow adipose tissue (BMAT) accumulates in clinical CKD and animal models of this disease, but the mechanism(s) responsible are unclear. This study sought to determine the relationship between BMAT distribution and bone structure and to establish whether disease progression directly affected: 1) the commitment of bone marrow mesenchymal stromal cells (BMSCs) to osteoblastic (OPC) and adipogenic (APC) precursor cells, and 2) the differentiation of BMSCs to mature adipocytes and osteoblasts. Eight-week-old male C57BL/6J mice received a diet supplemented with 0.2% adenine for ≤5 weeks to induce CKD. Control mice received the same diet without adenine. Serum biochemistries were quantified using a biochemistry analyzer and plasma hormone levels by ELISA. Bone phenotypes were evaluated by µCT. The same bones were decalcified and stained with 1% osmium tetroxide and BMAT quantified using µCT. Precursor cell populations in bone marrow were quantified by flow cytometry. The development of CKD during the early stages of the disease was confirmed by elevated serum concentrations of blood urea nitrogen and creatinine from 3-weeks' induction. After 5-weeks' induction, trabecular bone microarchitectu

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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