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Introduction: Patients with chronic kidney disease (CKD) are at an alarming risk of fracture compared to age and sex-matched non-CKD individuals. Clinical and preclinical data highlight two key factors in CKD-induced skeletal fragility: cortical porosity and reduced matrix-level properties including bone hydration. Thus, strategies are needed to address these concerns to improve mechanical properties and ultimately lower fracture risk in CKD. We sought to evaluate the singular and combined effects of mechanical and pharmacological interventions on modulating porosity, bone hydration, and mechanical properties in CKD. Methods: Sixteen-week-old male C57BL/6J mice underwent a 10-week CKD induction period via a 0.2 % adenine-laced casein-based diet (n = 48) or remained as non-CKD littermate controls (Con, n = 48). Following disease induction (26 weeks of age), n = 7 CKD and n = 7 Con were sacrificed (baseline cohort) to confirm a steady-state CKD state was achieved prior to the initiation of treatment. At 27 weeks of age, all remaining mice underwent right tibial loading to a maximum tensile strain of 2050 μƐ 3× a week for five weeks with the contralateral limb as a non-loaded control. Half of the mice (equal number CKD and Con) received subcutaneous injections of 0.5 mg/kg raloxifene (RAL) 5× a week, and the other half remained untreated (UN). Mice were sacrificed at 31 weeks of age. Serum biochemistries were performed, and bi-lateral tibiae were assessed for microarchitecture, whole bone and tissue level mechanical properties, and composition including bone hydration. Results: Regardless of intervention, BUN and PTH were higher in CKD animals throughout the study. In CKD, the combined effects of loading and RAL were quantified as lower cortical porosity and improved mechanical, material, and compositional properties, including higher matrix-bound water. Loading was generally responsible for positive impacts in cortical geometry and structural mechanical properties, while RAL treatment improved some trabecular outcomes and material-level mechanical properties and was responsible for improvements in several compositional parameters. While control animals responded positively to loading, their bones were less impacted by the RAL treatment, showing no deformation, toughness, or bound water improvements which were all evident in CKD. Serum PTH levels were negatively correlated with matrix-bound water. Discussion: An effective treatment program to improve fracture risk in CKD ideally focuses on the cortical bone and considers both cortical porosity and matrix properties. Loading-induced bone formation and mechanical improvements were observed across groups, and in the CKD cohort, this included lower cortical porosity. This study highlights that RAL treatment superimposed on active bone formation may be ideal for reducing skeletal complications in CKD by forming new bone with enhanced matrix properties.
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Correlation between reference point indentation and mechanical properties of 3D-printed polymers
Reference point indentation (RPI) is a novel experimental technique designed to evaluate bone quality. This study utilizes two RPI instruments, BioDent and Osteoprobe, to investigate the mechanical responses of several 3D-printed polymers. We correlated the mechanical properties from a tensile test with the RPI parameters obtained from the BioDent and OsteoProbe. In addition, we tested the same polymers five years later (Age 5). The results show that for Age 0 polymers, the elastic modulus is highly correlated with average unloading slope (r = 0.87), first unloading slope (r = 0.85), bone material strength index (BMSi) (r = 0.85), average loading slope (r = 0.82), first indentation distance (r = 0.79), and total indentation distance (r = 0.76). The ultimate stress correlates significantly with first unloading slope (r = 0.85), average unloading slope (r = 0.83), BMSi (r = 0.81), first indentation distance (r = 0.73), average loading slope (r = 0.71), and total indentation distance (r = 0.70). The elongation has no significant correlation with the RPI parameters except with the average creep indentation distance (r = 0.60). For Age 5 polymers, correlations between mechanical properties and RPI parameters are low. This study illustrates the potential of RPI to assess the mechanical properties of polymers nondestructively with simple sample requirements. Furthermore, for the first time, 3D-printed polymers and aged polymers are investigated with RPI.
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- Award ID(s):
- 1926353
- PAR ID:
- 10537624
- Publisher / Repository:
- AIP Publishing
- Date Published:
- Journal Name:
- Review of Scientific Instruments
- Volume:
- 94
- Issue:
- 8
- ISSN:
- 0034-6748
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1063/5.0149701
