The fracture behavior of bone is critically important for evaluating its mechanical competence and ability to resist fractures. Fracture toughness is an intrinsic material property that quantifies a material's ability to withstand crack propagation under controlled conditions. However, properly conducting fracture toughness testing requires the access to calibrated mechanical load frames and the destructive testing of bone samples, and therefore fracture toughness tests are clinically impractical. Impact microindentation mimicks certain aspects of fracture toughness measurements, but its relationship with fracture toughness remains unknown. In this study, we aimed to compare measurements of notched fracture toughness and impact microindentation in fresh and boiled bovine bone. Skeletally mature bovine bone specimens (n = 48) were prepared, and half of them were boiled to denature the organic matrix, while the other half remained preserved in frozen conditions. All samples underwent a notched fracture toughness test to determine their resistance to crack initiation (KIC) and an impact microindentation test using the OsteoProbe to obtain the Bone Material Strength index (BMSi). Boiling the bone samples increased the denatured collagen content, while mineral density and porosity remained unaffected. The boiled bones also showed significant reduction in both KIC (P < .0001) and the average BMSi (P < .0001), leading to impaired resistance of bone to crack propagation. Remarkably, the average BMSi exhibited a high correlation with KIC (r = 0.86; P < .001). A ranked order difference analysis confirmed the excellent agreement between the 2 measures. This study provides the first evidence that impact microindentation could serve as a surrogate measure for bone fracture behavior. The potential of impact microindentation to assess bone fracture resistance with minimal sample disruption could offer valuable insights into bone health without the need for cumbersome testing equipment and sample destruction.
Although the eyes are the main site of metastatic calcification in patients with chronic kidney disease (CKD), corneal and conjunctival calcification (CCC) is poorly evaluated in this population. Whether CCC correlates with coronary artery calcification remains unknown since studies so far have relied on methods with low sensitivity. Our objective was to test the relationship between CCC and coronary calcification based on tomography. This was a cross-sectional study that included patients on maintenance dialysis. Clinical, demographic, and biochemical data (calcium, phosphorus, parathormone, alkaline phosphatase, and 25(OH)-vitamin D) were recorded. Hyperparathyroidism was defined as parathyroid hormone (PTH) > 300 pg/mL. CCC was evaluated by anterior segment optical coherence tomography (AS-OCT), and coronary calcium scores (Agatston method) were assessed by computed tomography. We compared no/mild with moderate/severe CCC. Twenty-nine patients were included (49.6 ± 15.0 years, 62.1% female, on hemodialysis for 5.7 [2.7–9.4] years, 17.2% with diabetes mellitus, 75.9% with hyperparathyroidism). CCC was found in 82.7% of patients, with median scores of 9 (3, 14.5), ranging from 0 to 16. CCC was classified as absent/mild, moderate, and severe in 27.6%, 20.7%, and 51.7%, respectively. Coronary calcification was found in 44.8% of patients, with median scores of 11 (0, 464), varying from 0 and 6456. We found no significant correlation between coronary calcium scores and CCC (r = 0.203, p = 0.282). Hyperphosphatemia was more frequent in patients with moderate/severe CCC than in those with absent/mild CCC. We concluded that CCC was frequent in patients with CKD on dialysis and did not correlate with coronary calcium scores. Hyperphosphatemia appears to contribute to CCC. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Chronic kidney disease (CKD)–mineral bone disorder (CKD-MBD) leads to fractures and cardiovascular disease. Observational studies suggest beneficial effects of dietary fiber on both bone and cardiovascular outcomes, but the effect of fiber on CKD-MBD is unknown. To determine the effect of fiber on CKD-MBD, we fed the Cy/+ rat with progressive CKD a casein-based diet of 0.7% phosphate with 10% inulin (fermentable fiber) or cellulose (non-fermentable fiber) from 22 weeks to either 30 or 32 weeks of age (~30% and ~15% of normal kidney function; CKD 4 and 5). We assessed CKD-MBD end points of biochemistry, bone quantity and quality, cardiovascular health, and cecal microbiota and serum gut-derived uremic toxins. Results were analyzed by two-way analysis of variance (ANOVA) to evaluate the main effects of CKD stage and inulin, and their interaction. The results showed that in CKD animals, inulin did not alter kidney function but reduced the increase from stage 4 to 5 in serum levels of phosphate and parathyroid hormone, but not fibroblast growth factor-23 (FGF23). Bone turnover and cortical bone parameters were similarly improved but mechanical properties were not altered. Inulin slowed progression of aorta and cardiac calcification, left ventricular mass index, and fibrosis. To understand the mechanism, we assessed intestinal microbiota and found changes in alpha and beta diversity and significant changes in several taxa with inulin, together with a reduction in circulating gut derived uremic toxins such as indoxyl sulfate and short-chain fatty acids. In conclusion, the addition of the fermentable fiber inulin to the diet of CKD rats led to a slowed progression of CKD-MBD without affecting kidney function, likely mediated by changes in the gut microbiota composition and lowered gut-derived uremic toxins. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
Nguyen HD, Lortie A, Mbous Nguimbus L, et al. Osteoclast microRNA profiling in rheumatoid arthritis to capture the erosive factor. JBMR Plus. 2023;7:e10776. https://doi.org/10.1002/jbm4.10776
In the originally published version of the article, the author's names were inadvertently transposed. The correct author list appears below. The online version of this article has been corrected accordingly.
We apologize for this error.
Hoang Dong Nguyen,1 Audrey Lortie,2 Léopold Mbous Nguimbus,2 Javier Marrugo,2 Hugues Allard-Chamard,2 Luigi Bouchard,1,3 Gilles Boire,2 Michelle S Scott,1 and Sophie Roux 2.
1Department of Biochemistry and Functional Genomics, University of Sherbrooke and Research Centre of the Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie – Centre Hospitalier Universitaire de Sherbrooke (CIUSSSE-CHUS), Sherbrooke, Canada.
2Division of Rheumatology, Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke and Research Centre of the Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie – Centre Hospitalier Universitaire de Sherbrooke (CIUSSSE-CHUS), Sherbrooke, Canada.
3Department of Medical Biology, CIUSS du Saguenay-Lac-Saint-Jean Hôpital Universitaire de Chicoutimi, Saguenay, Canada.
Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting bone tissue and leading to increased fracture risk in men and women, independent of bone mineral density (BMD). Thus, bone material quality (i.e., properties that contribute to bone toughness but are not attributed to bone mass or quantity) is suggested to contribute to higher fracture risk in diabetic patients and has been shown to be altered. Fracture toughness properties are assumed to decline with aging and age-related disease, while toughness of human T2DM bone is mostly determined from compression testing of trabecular bone. In this case-control study, we determined fracture resistance in T2DM cortical bone tissue from male individuals in combination with a multiscale approach to assess bone material quality indices. All cortical bone samples stem from male nonosteoporotic individuals and show no significant differences in microstructure in both groups, control and T2DM. Bone material quality analyses reveal that both control and T2DM groups exhibit no significant differences in bone matrix composition assessed with Raman spectroscopy, in BMD distribution determined with quantitative back-scattered electron imaging, and in nanoscale local biomechanical properties assessed via nanoindentation. Finally, notched three-point bending tests revealed that the fracture resistance (measured from the total, elastic, and plastic J-integral) does not significantly differ in T2DM and control group, when both groups exhibit no significant differences in bone microstructure and material quality. This supports recent studies suggesting that not all T2DM patients are affected by a higher fracture risk but that individual risk profiles contribute to fracture susceptibility, which should spur further research on improving bone material quality assessment in vivo and identifying risk factors that increase bone fragility in T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.