Spatial patterns of sediment contamination and their influence on benthic infaunal communities in a highly tidal and industrial estuary in Atlantic Canada.

Sediment contamination can be elevated in ports, harbours, and estuaries with legacies of exploitation, negatively impacting infaunal invertebrate communities. Saint John Harbour (45.25° N, 66.05° W), New Brunswick, Canada, is an active harbour with strong tides and a long history of human activity. To examine spatial patterns of sediment contamination, samples were collected between 2011 and 2021 from subtidal sites near potential contaminant sources. Invertebrate data from the same samples were used to investigate potential effects on biological communities. Contaminant concentrations in the inner parts of the harbour were elevated compared to reference sites, but generally did not reach levels comparable to other highly contaminated harbours in the region. Effects on invertebrates were detectable, particularly at sites with higher contamination, although physical factors (depth, sediment grain size) were more important. Dynamic tidal conditions in the harbour may reduce the accumulation of contaminants in subtidal sediments and their impacts on infaunal communities.

Degree of leukochimerism with calf age in Angus-crossbred twin sets.

Twinning in cattle is infrequent and usually undesired. It can result in an increased occurrence of abortion and dystocia, reduced calf survival and a high likelihood of freemartinism in mixed-sex twins. Twin gestations are also commonly associated with the formation of placental vascular anastomoses (PVA) between twins. Through PVA they share blood, hormones (leading to freemartinism in mixed sex twins) and hematopoietic stem cells, which are the progenitors of white blood cells. The sharing of stem cells between twins can result in leukochimeric twin sets. These are twins that have white blood cells derived from both self and the co-twin owing to the fetal migration of hematopoietic stem cells from the extraembryonic mesoderm of the yolk sac to final sites like bone marrow and thymus. This study examined the degree to which this leukochimerism changes with age. DNA was extracted from hair bulbs containing mesenchymal dermal papilla to determine the individual's true genotype and blood samples were obtained at six time points from 1 week to 8 months of age to assess leukochimerism. Samples were genotyped using a medium density SNP chip, and quantitative estimates of allele frequency were determined using SNPs for which members of a twin set had alternative homozygous genotypes. The results indicate statistically significant changes in the proportion of self and co-twin with age and suggest that by 2-4 months of age the genotypic mix in white blood cells represents the hematopoetic stem cell population resident in the individual (i.e. permanently found in thymus and bone marrow).

Temporal and Spatial Trends in Benthic Infauna and Potential Drivers, in a Highly Tidal Estuary in Atlantic Canada.

Infaunal invertebrate communities of coastal marine sediments are often impacted by human activities, particularly in harbours and estuaries. However, while many studies have attempted to identify the key factors affecting benthic infauna, few have done so for highly energetic tidal estuaries. Samples were collected over a decade (2011-2020) from a series of reference sites in Saint John Harbour (45.25° N, 66.05° W), a highly tidal estuary in the Bay of Fundy, Canada. These data were used to examine spatial and temporal trends in infaunal invertebrate communities and sediment properties and to determine the extent to which the biological patterns were driven by measured physical and chemical variables. There were substantial differences among sites in infaunal invertebrate abundance (median ranging from 688 to 13,700 individuals per square meter), infaunal species richness (median ranging from 8 to 22), and Shannon diversity (median ranging from 1.26 to 2.34); multivariate analysis also revealed variation in species composition among sites. Sediment contaminant concentrations also varied among sites, but differences tended to be smaller (e.g. median chromium concentrations ranging from 21.6 to 27.6 mg/kg). Sample contaminant concentrations were all below probable effect levels, and almost all below threshold effect levels (Canadian interim sediment quality guidelines), but relationships with biological data were still detectable. However, physical variables (depth, sediment characteristics) were better predictors of biological variables and community composition. These results confirm the importance of physical factors in shaping infaunal communities in soft-sediment habitats in tidally influenced coastal waters. Supplementary Information: The online version contains supplementary material available at 10.1007/s12237-023-01222-w.

A survey of transplant providers regarding attitudes, barriers, and facilitators to living donor liver transplantation in the United States.

INTRODUCTION: A successful living donor liver transplant (LDLT) is the culmination of a multifaceted process coordinated among key stakeholders. METHODS: We conducted an electronic survey of US liver transplant (LT) centers (August 26, 2021-October 10, 2021) regarding attitudes, barriers, and facilitators of LDLT to learn how to expand LDLT safely and effectively in preparation for the American Society of Transplantation Living Donor Liver Transplant Consensus Conference. RESULTS: Responses were received from staff at 58 programs (40.1% of US LT centers). There is interest in broadening LDLT (100% of LDLT centers, 66.7% of non-LDLT centers) with high level of agreement that LDLT mitigates donor shortage (93.3% of respondents) and that it should be offered to all suitable candidates (87.5% of respondents), though LDLT was less often endorsed as the best first option (29.5% of respondents). Key barriers at non-LDLT centers were institutional factors and surgical expertise, whereas those at LDLT centers focused on waitlist candidate and donor factors. Heterogeneity in candidate selection for LDLT, candidate reluctance to pursue LDLT, high donor exclusion rate, and disparities in access were important barriers. CONCLUSION: Findings from this study may help guide current and future expansion of LDLT more efficiently in the US. These efforts require clear and cohesive messaging regarding LDLT benefits, engagement of the public community, and dedicated resources to equitably increase LDLT access.

Stakeholders' perspectives on transplant metrics: the 2022 Scientific Registry of Transplant Recipients' consensus conference.

In July 2022, the Scientific Registry of Transplant Recipients (SRTR) hosted an innovative, multistakeholder consensus conference to identify information and metrics desired by stakeholders in the transplantation system, including patients, living donors, caregivers, deceased donor family members, transplant professionals, organ procurement organization professionals, payers, and regulators. Crucially, patients, caregivers, living donors, and deceased donor family members were included in all aspects of this conference, including serving on the planning committee, participating in preconference focus groups and learning sessions, speaking at the conference, moderating conference sessions and breakout groups, and shaping the conclusions. Patients constituted 24% of the meeting participants. In this report, we document the proceedings and enumerate 160 recommendations, 10 of which have been highly prioritized. SRTR will use the recommendations to develop new presentations of information and metrics requested by stakeholders to support informed decision-making.

Inactivation of Salmonella in nonintact beef during low-temperature sous vide cooking.

Sous vide cooking is a method of food preparation in which food is vacuum sealed and cooked in a water bath that is set to a precise temperature and circulated by a sous vide device. Due to ease of use and affordability, this cooking method has grown increasingly popular in food service kitchens and domestic settings. However, low-temperature, long holding time sous vide cooking recommendations from manufacturers and chefs in popular press raise food safety concerns - specifically those for the preparation of nonintact beef products. The objective of this experiment was to address these concerns by validating a 5 log reduction of Salmonella spp. in sous vide cooked, nonintact beef steaks. Beef semitendinosus sliced into 2.54 cm steaks were internally inoculated to 7 log with Salmonella Typhimurium, Enteritidis, and Heidelberg via a needle inoculation pin pad. Steaks were individually vacuum sealed, and sous vide cooked at 46.1, 51.6, and 54.4°C. The minimum time measured for a 5 log reduction at 51.6 and 54.4°C was 150 and 64.5 min, respectively (P < 0.01). Additionally, a 7.28 log final reduction was achieved at 51.6°C after 322.5 min (P < 0.01). However, 46.1°C was only able to achieve a final reduction of 2.01 log (P < 0.01) after a holding time of 420 min. The results of this experiment validate in sous vide cooked products the time and temperature combinations provided in the USDA-FSIS Appendix A guidance for a 5 log reduction of Salmonella spp. in meat products. Moreover, more research is needed with other relevant foodborne pathogens to determine if sous vide cooking below Appendix A recommendations could lead to unsafe products.

Living donor liver transplantation: A multi-disciplinary collaboration towards growth, consensus, and a change in culture.

INTRODUCTION: Living donor liver transplantation (LDLT) reduces liver transplant waitlist mortality and provides excellent long-term outcomes for persons with end stage liver disease. Yet, utilization of LDLT has been limited in the United States (US). METHODS: In October 2021, the American Society of Transplantation held a consensus conference to identify important barriers to broader expansion of LDLT in the US, including data gaps, and make recommendations for impactful and feasible mitigation strategies to overcome these barriers. Domains addressed encompassed the entirety of the LDLT process. Representation from international centers and living donor kidney transplantation were included for their perspective/experience in addition to members across disciplines within the US liver transplantation community. A modified Delphi approach was employed as the consensus methodology. RESULTS: The predominant theme permeating discussion and polling results centered on culture; the beliefs and behaviors of a group of people perpetuated over time. CONCLUSIONS: Creating a culture of support for LDLT in the US is key for expansion and includes engagement and education of stakeholders across the spectrum of the process of LDLT. A shift from awareness of LDLT to acknowledgement of benefit of LDLT is the primary goal. Propagation of the maxim "LDLT is the best option" is pivotal.

Variation in adult living donor liver transplantation in the United States: Identifying opportunities for increased utilization.

In the United States, living donor liver transplantation (LDLT) is limited to transplant centers with specific experience. However, the impact of recipient characteristics on procedure selection (LDLT vs. deceased donor liver transplant [DDLT]) within these centers has not been described. Transplant registry data for centers that performed ≥1 LDLT in 2002-2019 were analyzed using hierarchal regression modeling to quantify the impact of patient and center factors on the adjusted odds ratio (aOR) of LDLT (vs DDLT). Among 73,681 adult recipients, only 4% underwent LDLT, varying from <1% to >60% of total liver transplants. After risk adjustment, the likelihood of receiving an LDLT rose by 73% in recent years (aOR 1.73 for 2014-2019 vs. 2002-2007) but remained lower for older adults, men, racial and ethnic minorities, and obese patients. LDLT was less commonly used in patients with hepatocellular carcinoma or alcoholic cirrhosis, and more frequently in those with hepatitis C and with lower severity of illness (Model for End-Stage Liver Disease (MELD) score < 15). Patients with public insurance, lower educational achievement, and residence in the Northwest and Southeast had decreased access. While some differences in access to LDLT reflect clinical factors, further exploration into disparities in LDLT utilization based on center practice and socioeconomic determinants of health is needed.

Climate, currents and species traits contribute to early stages of marine species redistribution.

Anthropogenic climate change is causing a rapid redistribution of life on Earth, particularly in the ocean, with profound implications for humans. Yet warming-driven range shifts are known to be influenced by a variety of factors whose combined effects are still little understood. Here, we use scientist-verified out-of-range observations from a national citizen-science initiative to assess the combined effect of long-term warming, climate extremes (i.e., heatwaves and cold spells), ocean currents, and species traits on early stages of marine range extensions in two warming 'hotspot' regions of southern Australia. We find effects of warming to be contingent upon complex interactions with the strength of ocean currents and their mutual directional agreement, as well as species traits. Our study represents the most comprehensive account to date of factors driving early stages of marine species redistributions, providing important evidence for the assessment of the vulnerability of marine species distributions to climate change.

Utilizing Social Media to Identify Potential Living Donors: Learning from US Living Donor Programs.

Purpose of Review: Living donor transplantation provides the best possible recipient outcomes in solid organ transplantation. Yet, identifying potential living donors can be a laborious and resource intensive task that heavily relies on the recipient's means and social network. Social media has evolved to become a key tool in helping to bring recipients and potential living donors together given its ease of utilization, widespread access, and improved recipient's comfort with public solicitation. However, in the USA, formal guidelines to direct the use of social media in this context are lacking. Recent Findings: To better inform the landscape and opportunities utilizing social media in living donation, the OPTN Living Donor Committee surveyed US transplant programs to explore programs' experiences and challenges when helping patients use social media to identify potential living donors (September 2019). A large majority of survey participants (N = 125/174, 72%) indicated that their program provided education to use social media to identify potential living donors and most programs tracking referral source confirmed an increase utilization over time. The use of social media was compounded with program and recipient's challenges including concerns about privacy, inadequate technology access, and knowledge gaps. In this review, we discuss the results of this national survey and recent literature, and provide suggestions to inform program practices and guidance provided to patients wishing to use social media to identify potential living donors. Summary: Transplant programs should become competent in the use of social media for potential living donor identification to empower patients interested in using this tool. Social media education should be provided to all patients regardless of voiced interest and, when appropriate, revisited at multiple time points. Programs should consider developing a "team of experts" that can provide focused education and support to patients embarking in social media living donor campaigns. Care should be taken to avoid exacerbating disparities in access to living donor transplantation. Effective and timely guidance to patients in the use of social media could enhance the identification of potential living donors. Supplementary Information: The online version contains supplementary material available at 10.1007/s40472-022-00382-1.

Total-Body 18F-FDG PET/CT in Autoimmune Inflammatory Arthritis at Ultra-Low Dose: Initial Observations.

Autoimmune inflammatory arthritides (AIA), such as psoriatic arthritis and rheumatoid arthritis, are chronic systemic conditions that affect multiple joints of the body. Recently, total-body (TB) PET/CT scanners exhibiting superior technical characteristics (total-body coverage, geometric sensitivity) that could benefit AIA evaluation, compared with conventional PET/CT systems, have become available. The objectives of this work were to assess the performance of an ultra-low-dose, 18F-FDG TB PET/CT acquisition protocol for evaluating systemic joint involvement in AIA and to report the association of TB PET/CT measures with joint-by-joint rheumatologic examination and standardized rheumatologic outcome measures. Methods: Thirty participants (24 with AIA and 6 with osteoarthritis) were prospectively enrolled in this single-center, observational study. All participants underwent a TB PET/CT scan for 20 min starting at 40 min after intravenous injection of 78.1 ± 4.7 MBq of 18F-FDG. Qualitative and quantitative evaluation of 18F-FDG uptake and joint involvement were performed from the resulting images and compared with the rheumatologic assessments. Results: TB PET/CT enabled the visualization of 18F-FDG uptake at joints of the entire body, including those of the hands and feet, in a single bed position, and in the same phase of radiotracer uptake. A range of pathologies consistent with AIA (and non-AIA in the osteoarthritis group) were visualized, and the feasibility of extracting PET measures from joints examined by rheumatologic assessments was demonstrated. Of 1,997 evaluable joints, there was concordance between TB PET qualitative assessments and joint-by-joint rheumatologic evaluation in the AIA and non-AIA cohorts for 69.9% and 91.1% joints, respectively, and an additional 20.1% and 8.8% joints, respectively, deemed negative on rheumatologic examination showed PET positivity. On the other hand, 10.0% and 0% joints in the AIA and non-AIA cohorts, respectively, were positive on rheumatologic evaluation but negative on TB PET. Quantitative measures from TB PET in the AIA cohort demonstrated a moderate-to-strong correlation (Spearman ρ = 0.53-0.70, P < 0.05) with the rheumatologic outcome measures. Conclusion: Systemic joint evaluation in AIA (and non-AIA) is feasible with a TB PET/CT system and an ultra-low-dose protocol. Our results provide the foundation for future larger studies to evaluate the possible improvements in AIA joint assessment via the TB PET/CT technology.

Blanching Defects at the Pressure Points: Observations from Dynamic Total-Body PET/CT Studies.

Total-body PET/CT allows simultaneous acquisition of all the body parts in a single bed position during the radiotracer uptake phase. Dynamic imaging protocols employing total-body PET could demonstrate findings that may not have been previously visualized or described using conventional PET/CT scanners. We examined the characteristics of blanching defects, areas of markedly reduced (partial defect) or absent (complete defect) radiotracer uptake seen at the skin/subcutaneous tissues opposite the bony prominences at pressure points. Methods: In this observational study, 77 participants underwent dynamic total-body PET/CT imaging using 18F-FDG (Group 1, N = 47, 60-min dynamic, arms-down, divided into 3 subgroups according to the injected dose) or 18F-fluciclovine (Group 2, N = 30, 25-min dynamic, arms above the head). 40 out of 47 participants in Group 1 were re-imaged at 90 min after being allowed off the scanning table. Blanching defects, partial or complete, were characterized opposite the bony prominences at 7 pressure points (the skull, scapula, and calcaneus bilaterally, as well as the sacrum). Association of the blanching defects with different clinical and technical characteristics were analyzed using uni- and multi-variate analyses. Results: A total of 124 blanching defects were seen in 68 out of 77 (88%) participants at one or more pressure points. Blanching defects were higher, on average, in Group 2 participants (3.5±1.7) compared to Group 1 (2.1±1.4; P <0.001), but it did not vary within Group 1 for different 18F-FDG dose subgroups. All defects resumed normal pattern on delayed static (90-min) images except for 14 partial defects. No complete blanching defects were seen on the 90-min images. By multivariate analysis, arm positioning above the head was associated with skull defects; scapular and sacral defects were significantly more encountered in men and with lower BMI, while calcaneal defects could not be associated to any factor. Conclusion: Blanching defects opposite the bony pressure points are common on dynamic total-body PET/CT images using different radiopharmaceuticals and injection doses. Their appearance should not be immediately interpreted as an abnormality. The current findings warrant further exploration in a prospective setting and may be utilized to study various mechano-pathologic conditions, such as pressure ulcers.

Safeguarding marine life: conservation of biodiversity and ecosystems.

Marine ecosystems and their associated biodiversity sustain life on Earth and hold intrinsic value. Critical marine ecosystem services include maintenance of global oxygen and carbon cycles, production of food and energy, and sustenance of human wellbeing. However marine ecosystems are swiftly being degraded due to the unsustainable use of marine environments and a rapidly changing climate. The fundamental challenge for the future is therefore to safeguard marine ecosystem biodiversity, function, and adaptive capacity whilst continuing to provide vital resources for the global population. Here, we use foresighting/hindcasting to consider two plausible futures towards 2030: a business-as-usual trajectory (i.e. continuation of current trends), and a more sustainable but technically achievable future in line with the UN Sustainable Development Goals. We identify key drivers that differentiate these alternative futures and use these to develop an action pathway towards the desirable, more sustainable future. Key to achieving the more sustainable future will be establishing integrative (i.e. across jurisdictions and sectors), adaptive management that supports equitable and sustainable stewardship of marine environments. Conserving marine ecosystems will require recalibrating our social, financial, and industrial relationships with the marine environment. While a sustainable future requires long-term planning and commitment beyond 2030, immediate action is needed to avoid tipping points and avert trajectories of ecosystem decline. By acting now to optimise management and protection of marine ecosystems, building upon existing technologies, and conserving the remaining biodiversity, we can create the best opportunity for a sustainable future in 2030 and beyond.

Distributions of Microdamage Are Altered Between Trabecular Rods and Plates in Cancellous Bone From Men With Type 2 Diabetes Mellitus.

Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fracture despite exhibiting normal to high bone mineral density (BMD). Conditions arising from T2DM, such as reduced bone turnover and alterations in microarchitecture, may contribute to skeletal fragility by influencing bone morphology and microdamage accumulation. The objectives of this study were (i) to characterize the effect of T2DM on microdamage quantity and morphology in cancellous bone, and (ii) relate the accumulation of microdamage to the cancellous microarchitecture. Cancellous specimens from the femoral neck were collected during total hip arthroplasty (T2DM: n = 22, age = 65 ± 9 years, glycated hemoglobin [HbA1c] = 7.00% ± 0.98%; non-diabetic [non-DM]: n = 25, age = 61 ± 8 years, HbA1c = 5.50% ± 0.4%), compressed to 3% strain, stained with lead uranyl acetate to isolate microdamage, and scanned with micro-computed tomography (µCT). Individual trabeculae segmentation was used to isolate rod-like and plate-like trabeculae and their orientations with respect to the loading axis. The T2DM group trended toward a greater BV/TV (+27%, p = 0.07) and had a more plate-like trabecular architecture (+8% BVplates , p = 0.046) versus non-DM specimens. Rods were more damaged relative to their volume compared to plates in the non-DM group (DVrods /BVrods versus DVplates /BVplates : +49%, p < 0.0001), but this difference was absent in T2DM specimens. Longitudinal rods were more damaged in the non-DM group (DVlongitudinal rods /BVlongitudinal rods : +73% non-DM versus T2DM, p = 0.027). Total damage accumulation (DV/BV) and morphology (DS/DV) did not differ in T2DM versus non-DM specimens. These results provide evidence that cancellous microarchitecture does not explain fracture risk in T2DM, pointing to alterations in material matrix properties. In particular, cancellous bone from men with T2DM may have an attenuated ability to mitigate microdamage accumulation through sacrificial rods. © 2022 American Society for Bone and Mineral Research (ASBMR).

Poleward bound: adapting to climate-driven species redistribution.

One of the most pronounced effects of climate change on the world's oceans is the (generally) poleward movement of species and fishery stocks in response to increasing water temperatures. In some regions, such redistributions are already causing dramatic shifts in marine socioecological systems, profoundly altering ecosystem structure and function, challenging domestic and international fisheries, and impacting on human communities. Such effects are expected to become increasingly widespread as waters continue to warm and species ranges continue to shift. Actions taken over the coming decade (2021-2030) can help us adapt to species redistributions and minimise negative impacts on ecosystems and human communities, achieving a more sustainable future in the face of ecosystem change. We describe key drivers related to climate-driven species redistributions that are likely to have a high impact and influence on whether a sustainable future is achievable by 2030. We posit two different futures-a 'business as usual' future and a technically achievable and more sustainable future, aligned with the Sustainable Development Goals. We then identify concrete actions that provide a pathway towards the more sustainable 2030 and that acknowledge and include Indigenous perspectives. Achieving this sustainable future will depend on improved monitoring and detection, and on adaptive, cooperative management to proactively respond to the challenge of species redistribution. We synthesise examples of such actions as the basis of a strategic approach to tackle this global-scale challenge for the benefit of humanity and ecosystems. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-021-09641-3.

Radioembolization Dosimetry with Total-Body 90Y PET.

Transarterial radioembolization (TARE) is a locoregional radiopharmaceutical therapy based on the delivery of radioactive 90Y microspheres to liver tumors. The importance of personalized dosimetry to make TARE safer and more effective has been demonstrated in recent clinical studies, stressing the need for quantification of the dose-response relationship to ultimately optimize the administered activity before treatment and image it after treatment. 90Y dosimetric studies are challenging because of the lack of accurate and precise methods but are best realized with PET combined with Monte Carlo simulations and other image modalities to calculate a segmental dose distribution. The aim of this study was to assess the suitability of imaging 90Y PET patients with the total-body PET/CT uEXPLORER and to investigate possible improvements in TARE 90Y PET-based dosimetry. The uEXPLORER is the first commercially available ultra-high-resolution (171 cps/kBq) total-body digital PET/CT device with a 194-cm axial PET field of view that enables the whole body to be scanned at a single bed position. Methods: Two PET/CT scanners were evaluated in this study: the Biograph mCT and the total-body uEXPLORER. Images of a National Electrical Manufacturers Association (NEMA) image-quality phantom and 2 patients were reconstructed using our standard clinical oncology protocol. A late portal phase contrast-enhanced CT scan was used to contour the liver segments and create corresponding volumes of interest. To calculate the absorbed dose, Monte Carlo simulations were performed using Geant4 Application for Tomographic Emission (GATE). The absorbed dose and dose-volume histograms were calculated for all 6 spheres (diameters ranging from 10 to 37 mm) of the NEMA phantom, the liver segments, and the entire liver. Differences between the phantom doses and an analytic ground truth were quantified through the root mean squared error. Results: The uEXPLORER showed a higher signal-to-noise ratio at 10- and 13-mm diameters, consistent with its high spatial resolution and system sensitivity. The total liver-absorbed dose showed excellent agreement between the uEXPLORER and the mCT for both patients, with differences lower than 0.2%. Larger differences of up to 60% were observed when comparing the liver segment doses. All dose-volume histograms were in good agreement, with narrower tails for the uEXPLORER in all segments, indicating lower image noise. Conclusion: This patient study is compelling for the use of total-body 90Y PET for liver dosimetry. The uEXPLORER scanner showed a better signal-to-noise ratio than mCT, especially in lower-count regions of interest, which is expected to improve dose quantification and tumor dosimetry.

Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus.

The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters microscale bone tissue composition. We used Fourier-transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of postmenopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n = 35, age = 65 ± 7 years, HbA1c = 5.8 ± 0.3%), impaired glucose tolerance (IGT; n = 26, age = 64 ± 5 years, HbA1c = 6.0 ± 0.4%), and overt T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.13 ± 0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (-10%) in T2DM versus NGT groups (p < 0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM versus NGT and IGT groups (-14% and -14%, respectively) and in trabecular NGT and IGT versus T2DM groups (-11% and -10%, respectively) (all p < 0.05). The distributions of crystallinity were wider in cortical NGT versus T2DM groups (+16%) and in trabecular NGT versus T2DM groups (+14%) (all p < 0.05). Additionally, bone turnover was lower in T2DM versus NGT groups (P1NP: -25%, CTx: -30%, ucOC: -24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, although the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue-level mechanical properties and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans. © 2020 American Society for Bone and Mineral Research (ASBMR).

Effects of Diabetes on Bone Material Properties.

PURPOSE OF REVIEW: Individuals with type 1 and type 2 diabetes mellitus (T1DM, T2DM) have an increased risk of bone fracture compared to non-diabetic controls that is not explained by differences in BMD, BMI, or falls. Thus, bone tissue fracture resistance may be reduced in individuals with DM. The purpose of this review is to summarize work that analyzes the effects of T1DM and T2DM on bone tissue compositional and mechanical properties. RECENT FINDINGS: Studies of clinical T2DM specimens revealed increased mineralization and advanced glycation endproduct (AGE) concentrations and significant relationships between mechanical performance and composition of cancellous bone. Specifically, in femoral cancellous tissue, compressive stiffness and strength increased with mineral content; and post-yield properties decreased with AGE concentration. In addition, cortical resistance to in vivo indentation (bone material strength index) was lower in patients with T2DM vs. age-matched non-diabetic controls, and this resistance decreased with worsening glycemic control. Recent studies on patients with T1DM and history of a prior fragility fracture found greater mineral content and concentrations of AGEs in iliac trabecular bone and correspondingly stiffer, harder bone at the nanosacle. Recent observational data showed greater AGE and mineral content in surgically retrieved bone from patients with T2DM vs. non-DM controls, consistent with reduced bone remodeling. Limited data on human T1DM bone tissue also showed higher mineral and AGE content in patients with prior fragility fractures compared to non-DM and non-fracture controls.

Chronic kidney disease and aging differentially diminish bone material and microarchitecture in C57Bl/6 mice.

Chronic kidney disease (CKD) is a common disease of aging and increases fracture risk over advanced age alone. Aging and CKD differently impair bone turnover and mineralization. We thus hypothesize that the loss of bone quality would be greatest with the combination of advanced age and CKD. We evaluated bone from young adult (6 mo.), middle-age (18 mo.), and old (24 mo.) male C57Bl/6 mice three months following either 5/6th nephrectomy, to induce CKD, or Sham procedures. CKD exacerbated losses of cortical and trabecular microarchitecture associated with aging. Aging and CKD each resulted in thinner, more porous cortices and fewer and thinner trabeculae. Bone material quality was also reduced with CKD, and these changes to bone material were distinct from those due to age. Aging reduced whole-bone flexural strength and modulus, micrometer-scale nanoindentation modulus, and nanometer-scale tissue and collagen strain (small-angle x-ray scattering [SAXS]. By contrast, CKD reduced work to fracture and variation in bone tissue modulus and composition (Raman spectroscopy), and increased percent collagen strain. The increased collagen strain burden was associated with loss of toughness in CKD. In addition, osteocyte lacunae became smaller, sparser, and more disordered with age for Sham mice, yet these age-related changes were not clearly observed in CKD. However, for CKD, larger lacunae positively correlated with increased serum phosphate levels, suggesting that osteocytes play a role in systemic mineral homeostasis. This work demonstrates that CKD reduces bone quality, including microarchitecture and bone material properties, and that loss of bone quality with age is compounded by CKD. These findings may help reconcile why bone mass does not consistently predict fracture in the CKD population, as well as why older individuals with CKD are at high risk of fragility.

Altered Tissue Composition, Microarchitecture, and Mechanical Performance in Cancellous Bone From Men With Type 2 Diabetes Mellitus.

People with type 2 diabetes mellitus (T2DM) have normal-to-high BMDs, but, counterintuitively, have greater fracture risks than people without T2DM, even after accounting for potential confounders like BMI and falls. Therefore, T2DM may alter aspects of bone quality, including material properties or microarchitecture, that increase fragility independently of bone mass. Our objective was to elucidate the factors that influence fragility in T2DM by comparing the material properties, microarchitecture, and mechanical performance of cancellous bone in a clinical population of men with and without T2DM. Cancellous specimens from the femoral neck were collected during total hip arthroplasty (T2DM: n = 31, age = 65 ± 8 years, HbA1c = 7.1 ± 0.9%; non-DM: n = 34, age = 62 ± 9 years, HbA1c = 5.5 ± 0.4%). The T2DM specimens had greater concentrations of the advanced glycation endproduct pentosidine (+ 36%, P < 0.05) and sugars bound to the collagen matrix (+ 42%, P < 0.05) than the non-DM specimens. The T2DM specimens trended toward a greater bone volume fraction (BV/TV) (+ 24%, NS, P = 0.13) and had greater mineral content (+ 7%, P < 0.05) than the non-DM specimens. Regression modeling of the mechanical outcomes revealed competing effects of T2DM on bone mechanical behavior. The trend of higher BV/TV values and the greater mineral content observed in the T2DM specimens increased strength, whereas the greater values of pentosidine in the T2DM group decreased postyield strain and toughness. The long-term medical management and presence of osteoarthritis in these patients may influence these outcomes. Nevertheless, our data indicate a beneficial effect of T2DM on cancellous microarchitecture, but a deleterious effect of T2DM on the collagen matrix. These data suggest that high concentrations of advanced glycation endproducts can increase fragility by reducing the ability of bone to absorb energy before failure, especially for the subset of T2DM patients with low BV/TV. © 2019 American Society for Bone and Mineral Research.