Cortical porosity development and progression is mitigated after etelcalcetide treatment in an animal model of chronic kidney disease

Swallow, Elizabeth A.<sup>1</sup>; Metzger, Corinne E.<sup>1</sup>; Newman, Christopher L.<sup>2</sup>; Chen, Neal X.<sup>3</sup>; Moe, Sharon M.<sup>3,4</sup>; Allen, Matthew R.<sup>1,3,4</sup>

Affiliations

¹Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, United States

²Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States

³Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States

⁴Roudebush Veterans Administration Medical Center, Indianapolis, IN, United States

Abstract and keywords

Purpose: Chronic kidney disease (CKD) leads to increased bone fragility and risk of fracture. Cortical deteriorations, including cortical porosity, are key factors in fracture susceptibility in CKD. Since secondary hyperparathyroidism is common in CKD individuals and contributes to cortical deterioration, we hypothesized that reducing parathyroid hormone (PTH) may modulate CKD-induced cortical porosity. The goal of this pilot study was to assess the effects of lowering PTH, via the preclinical analogue of the FDA-approved calcimimetic etelcalcetide (KP-2326), on the development and progression of cortical pores in the setting of CKD.

Methods: Male Cy/+ Sprague Dawley rats with clinical biochemistries consistent with CKD (N = 8) were assigned to the study. At 30–32 weeks of age, cortical bone was assessed via In vivo μCT and blood collected for biochemistries to create baseline measures. Calcimimetic treatment with KP-2326 (KP) was then administered 3× weekly for 2–4 weeks. Cortical bone and biochemical parameters were repeated at study endpoint (33–37 wks of age). A group of age- and cohort-matched CKD rats (N = 4) were utilized as untreated controls.

Results: Untreated CKD rats had significantly increased cortical porosity over time, while porosity in KP-treated CKD rats was not significantly changed over time. Individual pore analysis revealed that pore area was significantly higher for expanding pores in untreated CKD rats compared to KP-treated CKD rats. Mechanical properties of KP-treated animal femora were similar to historical values of age-matched CKD animals and lower than those of age-matched non-diseased animals.

Conclusion: Our pilot preclinical study demonstrates that etelcalcetide treatment can mitigate the progression of cortical bone changes in an animal model of CKD through suppression of pre-existing cortical pore expansion and limiting the size of new pore development. While stabilization of porosity is beneficial it remains likely that infilling of porosity will be needed to positively affect mechanical properties of bones in the setting of CKD.

Keywords: Renal osteodystrophy; MicroCT; Etelcalcetide; CKD-MBD; Pore dynamics

Links

DOI: 10.1016/j.bone.2022.116340

PubMed: 35085840

WoS: 000773553100011

History

Received: 2021-11-23

Revised: 2022-01-05

Accepted: 2022-01-19

Online: 2022-01-24

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Cited By (1)

Year	Entry
2023	Newman CL, Surowiec RK, Swallow EA, Metzger CE, Kim J, Tomaschke AA, Chen NX, Allen MR, Wallace JM, Moe SM, Wu Y-C, Niziolek PJ. Assessing cortical bone porosity with MRI in an animal model of chronic kidney disease. Bone. August 2023;173:116808.