Measures Of Microarchitecture Research Articles

P102 Can EEG spectral analysis distinguish children with narcolepsy from those with idiopathic hypersomnolence and subjective sleepiness?

Abstract Background EEG spectral analysis provides a measurement of sleep micro-architecture and is a more sensitive measure of sleep disruption than conventional sleep macro-architecture. We aimed to examine the use of this technique in distinguishing children with narcolepsy and idiopathic hypersomnolence (IH) from subjectively sleepy children with a negative multiple sleep latency test. Methods Relative power, the absolute power in each frequency band divided by the total absolute power, was calculated for delta power (0.5 Hz–3.9 Hz), theta power (4 Hz–7.9 Hz), alpha power (8 Hz–11.9 Hz), sigma power (12 Hz–13.9 Hz) and beta power (14 Hz–30 Hz). A mean value for each frequency was calculated for each 30 s epoch then averaged for each sleep stage within each child. Results 28 children with Narcolepsy, 11 with IH and 26 with subjective sleepiness were included and individually matched for age and sex with a control child. In N2, Theta power was higher in the Narcolepsy group (median 13.5%, IQR 11.2-15.5) compared to the subjectively sleepy group (11.1%, 9.0-12.8, p<0.05). During N3, Delta power was higher in the subjectively sleepy group (93.3%, 91.9-93.9 vs 83.3%, 65.8-93.9, p<0.001), and Theta power (4.8%, 4.2-6.3 vs 12.6% 4.8-22.5, p<0.001), Alpha power (0.9%, 0.7-1.3 vs 2.8% 0.9-5.8, p<0.001), and Beta power were lower (0.3% 0.3 -0.4 vs 1.1% 0.3-4.2, p<0.05) compared to their controls. Conclusions Differences in sleep micro-architecture could not distinguish between children with narcolepsy and IH but may be able to distinguish children with narcolepsy from subjectively sleepy children.

Prednisolone impairs trabecular bone score changes in adolescents with 21-hydroxylase deficiency.

Individuals with 21-hydroxylase deficiency (21OHD) require lifelong glucocorticoid (GC) therapy, which increases their risk of fragility fractures. However, fractures in GC-treated individuals can occur at normal bone mineral density (BMD) levels, suggesting an alteration in the bone microarchitecture. To evaluate trabecular bone microarchitecture and its changes in adolescents with 21OHD. We enrolled 38 adolescents with 21OHD for whom complete clinical data and baseline and follow-up lumbar spine bone mineral density (LSBMD) measurements were available. The mean duration was 1.5 ± 0.6 years. Trabecular bone score (TBS), an indirect measurement of bone microarchitecture, was analyzed using iNsight™ software version 3.0. Impaired BMD and TBS were defined at Z-scores ≤ -1.5. At baseline, participants (55% female; 68% salt-wasting type; mean age, 15.2 ± 3.8 years; bone age, 17.5 ± 2.8 years; mean GC dose, 18.5 ± 6.5 mg/m2/day) had the prevalence of impaired BMD and TBS of 5% and 18%, respectively. During follow-up, adolescents with 21OHD receiving prednisolone showed a lower annual percentage change in TBS than those who received hydrocortisone (p = 0.028). A stepwise regression analysis showed that body mass index percentile (p < 0.001) and testosterone concentration (p = 0.002) were independent positive predictors of the baseline TBS Z-score, whereas prednisolone use was the only negative predictor of the annual percentage change in TBS (p = 0.002). Adolescents with 21OHD have a high prevalence of impaired bone microarchitecture. Furthermore, prednisolone therapy is associated with impaired bone microarchitecture development, suggesting that hydrocortisone may better preserve bone microarchitecture and should be considered the first-line treatment for this population.

Objective measures of sleep in adults and older adults with and without depression: A systematic review and meta-analysis

Sleep architecture is poorly defined in people with depression, especially in older adults. We investigated differences in sleep macro- and micro-architecture between adults and older adults (>50 years) with and without depression.A systematic review identified 2135 papers through PubMed, Scopus, Web of Science and Embase databases. Two reviewers excluded articles using PRISMA guidelines. Fifteen articles met inclusion criteria. A random effects model meta-analysis was performed. NICE case-control guidelines were used to assess risk of bias.In the fifteen articles, 838 participants underwent objective sleep measurement (406 depression and 432 control). All adults with depression had less total sleep time, delayed sleep onset latency, higher wake after sleep onset, shorter rapid eye movement latency (ROL) and greater rapid eye movement REM density than controls. Two of these studies examined sleep architecture in 62 older adults (31 depression, 31 control). Older adults with depression had more stage 1 sleep, less stage 2 sleep, shorter ROL than older controls with no between-group difference in sleep efficiency, REM sleep or REM density. Six studies had poor case-control selection, which when removed nullified the effects of REM density and REM latency in all adults. Sleep micro-architecture measures could not be meta-analysed due to the limited studies available.Adults with depression had moderately worse sleep initiation and continuity than controls. Alterations to REM sleep were observed in adults with depression, however these effects were not robust. Sleep macro-architecture differences were not consistent in younger adults and older adults with depression, compared to relative controls.

Psoas muscle cross sectional area relates to bone density and microarchitecture in candidates for spine fusion surgery

Prior studies demonstrate that muscle and bone health are integrally related, and both independently impact orthopedic surgery outcomes. However, relationships between bone density, in vivo microarchitecture, and muscle area have not been previously investigated in orthopedic surgery patients. This study assessed associations between psoas cross sectional area (CSA), bone mineral density (BMD), and microstructure in a cohort undergoing spine fusion. Pre-operatively, bilateral psoas CSA was measured on axial lumbar spine CT in the L3-L4 disc space. To adjust for body size, Psoas Muscle Index (PMI) was calculated (CSA divided by the square of patient height). High resolution peripheral quantitative CT (HR-pQCT, XtremeCT2) assessed volumetric BMD (vBMD), cortical (Ct) and trabecular (Tb) microarchitecture at the distal radius and tibia. Areal BMD (aBMD) was measured by DXA at the lumbar spine (LS), total hip (TH), femoral neck (FN), and the 1/3 radius (1/3R). Pearson correlations related psoas CSA and bone imaging parameters before and after correcting for height and weight. Among 88 patients included, mean age was 63 ± 12 years, BMI was 28 ± 7 kg/m2, 47 (53 %) were female. Larger psoas CSA was associated with higher vBMD, greater Ct thickness and better Tb microarchitecture (higher Tb number and lower Tb separation) at the tibia and radius. Larger psoas CSA was also associated with greater aBMD at TH and FN bilaterally and 1/3R (r 0.33 to 0.61; p < 0.002 for all comparisons). Psoas CSA was not associated with aBMD at the LS. Similar results were observed when relating PMI, and adjusting for age, height and weight to HR-pQCT and DXA measurements. Investigation of subgroups by sex demonstrated that relationships were similar magnitude among women but not the men. Patients who underwent primary compared to revision spine surgery had similar associations. Our results demonstrate a link between psoas muscle size and peripheral bone microarchitecture among patients undergoing posterior lumbar spinal fusion. Given the importance of both muscle and skeletal integrity to the success of spine surgery, further study regarding the associations between measurements of psoas muscle, bone microarchitecture, and surgical outcomes is warranted.

Short-term risk of fracture is increased by deficits in cortical and trabecular bone microarchitecture independent of DXA BMD and FRAX: Bone Microarchitecture International Consortium (BoMIC) prospective cohorts.

Identifying individuals at risk for short-term fracture is essential to offer prompt beneficial treatment, especially since many fractures occur in those without osteoporosis by DXA-aBMD. We evaluated whether deficits in bone microarchitecture and density predict short-term fracture risk independent of the clinical predictors, DXA-BMD and FRAX. We combined data from eight cohorts to conduct a prospective study of bone microarchitecture at the distal radius and tibia (by HR-pQCT) and 2-year incidence of fracture (non-traumatic and traumatic) in 7327 individuals (4824 women, 2503 men, mean 69 ± 9years). We estimated sex-specific hazard ratios (HR) for associations between bone measures and 2-year fracture incidence, adjusted for age, cohort, height, and weight, and then additionally adjusted for FN aBMD or FRAX for major osteoporotic fracture. Only 7% of study participants had FN T-score ≤ -2.5, whereas 53% had T-scores between -1.0 and -2.5 and 37% had T-scores ≥-1.0. Two-year cumulative fracture incidence was 4% (296/7327). Each SD decrease in radius cortical bone measures increased fracture risk by 38%-76% for women and men. After additional adjustment for FN-aBMD, risks remained increased by 28%-61%. Radius trabecular measures were also associated with 2-year fracture risk independently of FN-aBMD in women (HRs range: 1.21 per SD for trabecular separation to 1.55 for total vBMD). Decreased failure load (FL) was associated with increased fracture risk in both women and men (FN-aBMD ranges of adjusted HR = 1.47-2.42). Tibia measurement results were similar to radius results. Findings were also similar when models were adjusted for FRAX. In older adults, FL and HR-pQCT measures of cortical and trabecular bone microarchitecture and density with strong associations to short-term fractures improved fracture prediction beyond aBMD and FRAX. Thus, HR-pQCT may be a useful adjunct to traditional assessment of short-term fracture risk in older adults, including those with T-scores above the osteoporosis range.

Quantification of bone microarchitecture using photon-counting CT at different radiation doses: A comparison with µCT

PurposeAccurate measurements of trabecular bone microarchitecture are required for a proper assessment of bone fragility. Photon-counting detector CT (PCD-CT) has different technical properties than conventional CT, resulting in higher resolution and thereby potentially enabling in-vivo measurement of trabecular microarchitecture. The purpose of this study was to quantify trabecular bone microarchitectural parameters with PCD-CT at varying radiation doses and compare this to µCT as gold standard. MethodBoth distal radii, distal tibiae, femoral heads, and two vertebrae were dissected from one human. All specimens were scanned ex-vivo on a PCD-CT system (slice increment 0.1 mm; pixel size 0.1042–0.127 mm) and a µCT system (isotropic voxel size 49–68.4 µm). The radiation doses of the PCD-CT scans were varied from 2.5 to 120 mGy based on the volume CT dose index (CTDIvol32). For the PCD-CT scans, contrast-to-noise ratio and trabecular sharpness were calculated and compared between radiation doses. µCT and PCD-CT scans were registered. The trabecular bone was then segmented from all PCD-CT and µCT scans and split into cubes with 6-mm edge length. For each cube, bone volume over total volume, trabecular thickness, trabecular number, and trabecular heterogeneity were calculated and compared between corresponding PCD-CT and µCT cubes. ResultsWith increasing dose, contrast-to-noise ratio and trabecular sharpness values increased for the PCD-CT images. Already at the lowest dose, high correlations between the trabecular microarchitectural parameters between µCT and PCD-CT were found (R2 = 0.55–0.95), which improved with increasing radiation dose (R2 = 0.76–0.96 at 20 mGy). ConclusionsPCD-CT can be used to quantify trabecular bone microarchitecture, with accuracy comparable to µCT and at clinically relevant radiation doses.

Disease Activity and Bone Microarchitectural Phenotype in Patients With Axial Spondyloarthritis

Background: Axial spondyloarthritis (AxSpA) is a chronic rheumatic disease characterized by spine inflammation, abnormal bone growth, and paradoxically osteoporosis and vertebral fractures. The pathogenesis of skeletal deficits in this disease is poorly understood. Purpose: We sought to evaluate volumetric bone mineral density (vBMD) and bone microarchitecture in patients with AxSpA and to identify disease-related factors associated with skeletal abnormalities. Methods: We enrolled patients between 2018 and 2021 as part of a 2-year prospective study at a single institution investigating skeletal health and the skeletal effects of interleukin-17 (IL-17) treatment. Patients with AxSpA who met Assessment in SpondyloArthritis International Society (ASAS) classification criteria by X-ray or had evidence of active inflammation on magnetic resonance imaging suggestive of sacroiliitis were referred to the study by their rheumatologists. We excluded those with a history of fragility fracture, multiple myeloma, Cushing’s disease, primary hyperparathyroidism, osteomalacia, untreated vitamin D deficiency, secondary osteoporosis, or other systemic rheumatic diseases, as well as use of oral steroids for 2 or more weeks in the 6 months prior or current use of hormone replacement therapy, current oral bisphosphonate, past or current intravenous bisphosphonate, teriparatide, or denosumab therapies. A total of 1606 patients were screened for eligibility. Of these, 30 participants were enrolled (mean age 43 years, 50% male). Patients with AxSpA had dual-energy X-ray absorptiometry (DXA) measurements of areal BMD (aBMD) and high-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of vBMD microarchitecture and failure load by finite element analysis. Standardized disease assessment tools used included the Bath Ankylosing Spondylitis Disease Activity (BASDAI), Metrology Index (BASMI), and Functional Index (BASFI). Results: In the 30 included patients, mean DXA and HR-pQCT Z-scores were within 1 standard deviation (SD) of normal for all indices, except for total vBMD in males (–1.2 SD below mean). Mean symptom duration was 11.7 years and mean scores for BASDAI, BASFI, and BASMI were 4.6, 3.6, and 2.7, respectively (range 1–10, 10 = severe limitation). Longer disease duration was associated with more severe skeletal deficits at the hip and tibia—specifically, lower hip aBMD, lower meta- and inner-trabecular vBMD, lower trabecular number, and higher trabecular separation and heterogeneity. Conclusion: This study of 30 patients with AxSpA found that abnormalities in bone density and microarchitecture at weightbearing sites were associated with longer disease duration. Because of its small sample size, larger studies are needed to better characterize the pathogenic disease factors that govern skeletal damage in AxSpA.

Association between sleep microarchitecture and cognition in obstructive sleep apnea.

Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication. Participants with suspected OSA (n = 1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit-Symbol Coding, DSC). Associations between cognitive scores and stage 2 non-rapid eye movement (NREM) sleep spindle density, power, frequency and %-fast (12-16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP), and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition. All spindle characteristics were lower in participants with moderate and severe OSA (p ≤ .001, vs. no/mild OSA) and positively associated with MoCA, RAVLT, and DSC scores (false discovery rate corrected p-value, q ≤ 0.026), except spindle power which was not associated with RAVLT (q = 0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p ≤ .001) but neither ORPNREM (q ≥ 0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q ≥ 0.166). In mediation analyses, spindle density and EEGNP (p ≥ .048) mediated moderate-to-severe OSA's negative effect on MoCA scores while ORPNREM, spindle power, and %-fast spindles mediated OSA's negative effect on DSC scores (p ≤ .018). Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.

Bone health in young adults with type 1 diabetes and progressive eGFR decline

BackgroundType 1 Diabetes (T1D) is associated with increased risk of fractures, worsened by presence of microvascular complications. This study’s objective is to determine the impact of progressive decline in estimated glomerular filtration rate (eGFR) on bone biomarkers and bone microarchitecture in youth with T1D.MethodsSlopes of eGFR were calculated using measures obtained at four timepoints from adolescence to young adulthood. Participants were identified as eGFR decliners if eGFR decreased ≥ 3ml/min/1.73m2/year. Bone health was assessed in young adulthood by high resolution peripheral quantitative computed tomography (HRpQCT Xtreme CTII) and bone biomarkers; osteocalcin, procollagen 1 intact n-terminal pro-peptide (P1NP), c-terminal telopeptide (CTX), and bone specific alkaline phosphatase. The relationship between diabetes duration, glycated hemoglobin, body mass index (BMI) and vitamin D level on bone biomarkers and microarchitecture was evaluated. Linear regression analysis was used for the statistical analysis in this study.ResultsNinety-nine study participants were studied with longitudinal evaluation of eGFR over 7.4 ± 1.0 years with mean age of 14.7 ± 1.7 years at baseline. Cross sectional evaluation of bone was performed at 21.3 ± 2.1 years. 44% participants had eGFR decline and showed 5% higher cortical porosity diameter than non-decliners (p = 0.035). Greater diabetes duration was associated with higher trabecular separation (p = 0.004) and lower trabecular number (p = 0.01). Higher level of 25 hydroxy-vitamin D was associated with lower trabecular separation (p = 0.01). Elevated glycated hemoglobin (p = 0.0008) and BMI (p = 0.009), were associated with lower markers of bone formation.ConclusionMild increase in cortical porosity diameter was found in youth with T1D and eGFR decline, however, overall measures of bone microarchitecture on HR-pQCT were similar between both groups and there were no statistically significant changes in bone biomarkers. Hence, skeletal impairments were limited in youth with different eGFR trajectories near peak bone mass. Longitudinal HR-pQCT studies are needed to further understand the impact of eGFR decline on bone microarchitecture. Optimal glycemic control, normal BMI and vitamin D status were supported by this study as important markers for good bone health.

Effect of abdominal tissue thickness on trabecular bone score and fracture risk in adults with diabetes: the Manitoba BMD registry.

Individuals with type 2 diabetes have lower trabecular bone score (TBS) and increased fracture risk despite higher bone mineral density. However, measures of trabecular microarchitecture from high-resolution peripheral computed tomography are not lower in type 2 diabetes. We hypothesized that confounding effects of abdominal tissue thickness may explain this discrepancy, since central obesity is a risk factor for diabetes and also artifactually lowers TBS. This hypothesis was tested in individuals aged 40years and older from a large DXA registry, stratified by sex and diabetes status. When DXA-measured abdominal tissue thickness was not included as a covariate, men without diabetes had lower TBS than women without diabetes (mean difference -0.074, P < .001). TBS was lower in women with versus without diabetes (mean difference -0.037, P < .001), and men with versus without diabetes (mean difference -0.007, P = .042). When adjusted for tissue thickness these findings reversed, TBS became greater in men versus women without diabetes (mean difference +0.053, P < .001), in women with versus without diabetes (mean difference +0.008, P < .001), and in men with versus without diabetes (mean difference +0.014, P < .001). During mean 8.7years observation, incident major osteoporotic fractures were seen in 7048 (9.6%). Adjusted for multiple covariates except tissue thickness, TBS predicted fracture in all subgroups with no significant diabetes interaction. When further adjusted for tissue thickness, HR per SD lower TBS remained significant and even increased slightly. In conclusion, TBS predicts fractures independent of other clinical risk factors in both women and men, with and without diabetes. Excess abdominal tissue thickness in men and individuals with type 2 diabetes may artifactually lower TBS using the current algorithm, which reverses after accounting for tissue thickness. This supports ongoing efforts to update the TBS algorithm to directly account for the effects of abdominal tissue thickness for improved fracture risk prediction.

Super-resolution of clinical CT: Revealing microarchitecture in whole bone clinical CT image data

Osteoporotic fractures, prevalent in the elderly, pose a significant health and economic burden. Current methods for predicting fracture risk, primarily relying on bone mineral density, provide only modest accuracy. If better spatial resolution of trabecular bone in a clinical scan were available, a more complete assessment of fracture risk would be obtained using microarchitectural measures of bone (i.e. trabecular thickness, trabecular spacing, bone volume fraction, etc.). However, increased resolution comes at the cost of increased radiation or can only be applied at small volumes of distal skeletal locations. This study explores super-resolution (SR) technology to enhance clinical CT scans of proximal femurs and better reveal the trabecular microarchitecture of bone. Using a deep-learning-based (i.e. subset of artificial intelligence) SR approach, low-resolution clinical CT images were upscaled to higher resolution and compared to corresponding MicroCT-derived images. SR-derived 2-dimensional microarchitectural measurements, such as degree of anisotropy, bone volume fraction, trabecular spacing, and trabecular thickness were within 16 % error compared to MicroCT data, whereas connectivity density exhibited larger error (as high as 1094 %). SR-derived 3-dimensional microarchitectural metrics exhibited errors <18 %. This work showcases the potential of SR technology to enhance clinical bone imaging and holds promise for improving fracture risk assessments and osteoporosis detection. Further research, including larger datasets and refined techniques, can advance SR's clinical utility, enabling comprehensive microstructural assessment across whole bones, thereby improving fracture risk predictions and patient-specific treatment strategies.

Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. The mean age of the patients was 45.5 ± 9.3years with a lag of 8.3 ± 7.2years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Six-minute, in vivo MRI quantification of proximal femur trabecular bone 3D microstructure.

Assessment of proximal femur trabecular bone microstructure in vivo by magnetic resonance imaging has recently been validated for acquiring information independent of bone mineral density in osteoporotic patients. However, the requisite signal-to-noise ratio (SNR) and resolution for interrogation of the trabecular microstructure at this anatomical location prolongs the scan duration and renders the imaging protocol clinically infeasible. Parallel imaging and compressed sensing (PICS) techniques can reduce the scan duration of the imaging protocol without substantially compromising image quality. The present work investigates the limits of acceleration for a commonly used PICS technique, ℓ1-ESPIRiT, for the purpose of quantifying measures of trabecular bone microarchitecture. Based on a desired error tolerance, a six-minute, prospectively accelerated variant of the imaging protocol was developed and assessed for intersession reproducibility and agreement with the longer reference scan. To investigate the limits of acceleration for MRI-based trabecular bone quantification by parallel imaging and compressed sensing reconstruction, and to develop a prototypical imaging protocol for assessing the proximal femur microstructure in a clinically practical scan time. Healthy participants (n=11) were scanned by a 3D balanced steady-state free precession (bSSFP) sequence satisfying the Nyquist criterion with a scan duration of about 18min. The raw data were retrospectively undersampled and reconstructed to mimic various acceleration factors ranging from 2 to 6. Trabecular volumes-of-interest in four major femoral regions (greater trochanter, intertrochanteric region, femoral neck, and femoral head) were analyzed and six relevant measures of trabecular bone microarchitecture (bone volume fraction, surface-to-curve ratio, erosion index, elastic modulus, trabecular thickness, plates-to-rods ratio) were obtained for images of all accelerations. To assess agreement, median percent error and intraclass correlation coefficients (ICCs) were computed using the fully-sampled data as reference. Based on this analysis, a prospectively 3-fold accelerated sequence with a duration of about 6min was developed and the analysis was repeated. A prospective acceleration factor of 3 demonstrated comparable performance in reproducibility and absolute agreement to the fully-sampled scan. The median CoV over all image-derived metrics was generally <6% and ICCs >0.70. Also, measurements from prospectively 3-fold accelerated scans demonstrated in general median percent errors of <7% and ICCs >0.70. The present work proposes a method to make in vivo quantitative assessment of proximal femur trabecular microstructure with a clinically practical scan duration of about 6min.

Hyperbaric oxygen therapy exerts anti-osteoporotic effects in obese and lean D-galactose-induced aged rats.

Obesity accelerates the aging processes, resulting in an aggravation of aging-induced osteoporosis. We investigated the anti-osteoporotic effect of hyperbaric oxygen therapy (HBOT) in obese- and lean-aged rats through measurement of cellular senescence, hypoxia, inflammation, antioxidants, and bone microarchitecture. Obese and lean male Wistar rats were injected with 150 mg/kg/day of D-galactose for 8 weeks to induce aging. Then, all rats were randomly given either sham or HBOT for 14 days. Metabolic parameters were determined. Expression by bone mRNA for cellular senescence, hypoxia, inflammation, antioxidative capacity, and bone remodeling were examined. Micro-computed tomography and atomic absorption spectroscopy were performed to evaluate bone microarchitecture and bone mineral profiles, respectively. We found that HBOT restored the alterations in the mRNA expression level of p16, p21, HIF-1α, TNF-α, IL-6, RANKL, RANK, NFATc1, DC-STAMP, Osx, ALP, and Col1a1 in the bone in obese-and lean- aging rats. In obese-aging rats, HBOT increased the level of expression of Sirt1 and CuZnSOD mRNA and diminished the expression level of HIF-2α and ctsk mRNA to the same levels as the control group. However, HBOT failed to alter catalase and OCN mRNA expression in obese-aged rats. HBOT partially improved the bone microarchitecture in obese-aged rats, but completely restored it in lean-aged rats. Interestingly, HBOT protected against obesity-induced demineralization in obese-aged rats. In summary, HBOT exerts an anti-osteoporotic effect in lean-aged rats and prevents some, but not all the negative effects of obese-aged conditions on bone health. Therefore, HBOT is considered as a potential therapy for aging-induced osteoporosis, regardless of obese status.

Deficits in volumetric bone mineral density, bone microarchitecture, and estimated bone strength in women with atypical anorexia nervosa compared to healthy controls.

Anorexia nervosa is associated with low bone mineral density (BMD) and deficits in bone microarchitecture and strength. Low BMD is common in atypical anorexia nervosa, in which criteria for anorexia nervosa are met except for low weight. We investigated whether women with atypical anorexia nervosa have deficits in bone microarchitecture and estimated strength at the peripheral skeleton. Measures of BMD and microarchitecture were obtained in 28 women with atypical anorexia nervosa and 27 controls, aged 21-46 years. Mean tibial volumetric BMD, cortical thickness, and failure load were lower, and radial trabecular number and separation impaired, in atypical anorexia nervosa versus controls (p < .05). Adjustingfor weight, deficits in tibial cortical bone variables persisted (p < .05). Women with atypical anorexia nervosa and amenorrhea had lower volumetric BMD and deficits in microarchitecture and failure load versus those with eumenorrhea and controls. Those with a history of overweight/obesity or fracture had deficits in bone microarchitecture versus controls. Tibial deficits were particularly marked. Less lean mass and longer disease duration were associated with deficits in high-resolution peripheral quantitative computed tomography (HR-pQCT) variables in atypical anorexia nervosa. Women with atypical anorexia nervosa have lower volumetric BMD and deficits in bone microarchitecture and strength at the peripheral skeleton versus controls, independent of weight, and particularly at the tibia. Women with atypical anorexia nervosa and amenorrhea, less lean mass, longer disease duration, history of overweight/obesity, or fracture history may be at higher risk. This is salient as deficits in HR-pQCT variables are associated with increased fracture risk. Atypical anorexia nervosa is a psychiatric disorder in which psychological criteria for anorexia nervosa are met despite weight being in the normal range. We demonstrate that despite weight in the normal range, women with atypical anorexia nervosa have impaired bone density, structure, and strength compared to healthy controls. Whether this translates to an increased risk of incident fracture in this population requires further investigation.

Associations of Lean Mass, Muscular Strength, and Physical Function with Trabecular Bone Score in Older Adults

Introduction/Background: Trabecular bone score (TBS) is an indirect measurement of bone quality and microarchitecture determined from dual-energy X-ray absorptiometry (DXA) imaging of the lumbar spine. TBS predicts fracture risk independent of bone mass/density, suggesting this assessment of bone quality adds value to the understanding of patients’ bone health. While lean mass and muscular strength have been associated with higher bone density and lower fracture risk among older adults, the literature is limited regarding the relationship of lean mass and strength with TBS. The purpose of this study was to determine associations of DXA-determined total body and trunk lean mass, maximal muscular strength, and gait speed as a measure of physical function, with TBS in 141 older adults (65-84 yr, 72.5 +/- 5.1 yr, 74% women). Methodology: Assessments included lumbar spine (L1-L4) bone density and total body and trunk lean mass by DXA, lower body (leg press) and upper body (seated row) strength by one repetition maximum tests, hand grip strength, and usual gait speed. TBS was derived from the lumbar spine DXA scan. Multivariable linear regression determined the contribution of proposed predictors to TBS. Results: After adjusting for age, sex, and lumbar spine bone density, upper body strength significantly predicted TBS (unadjusted/adjusted R2= 0.16/ 0.11, β coefficient =0.378, p=0.005), while total body lean mass index showed a trend in the expected direction (β coefficient =0.243, p=0.053). Gait speed and grip strength were not associated with TBS (p>0.05). Conclusion: Maximum strength of primarily back muscles measured as the seated row appears important to bone quality as measured by TBS, independent of bone density. Additional research on exercise training targeting back strength is needed to determine its clinical utility in preventing vertebral fractures among older adults.

Peripheral cortical bone density predicts vertebral bone mineral properties in spine fusion surgery patients.

Spine fusion surgery is one of the most common orthopedic procedures, with over 400,000 performed annually to correct deformities and pain. However, complications occur in approximately one third of cases. While many of these complications may be related to poor bone quality, it is difficult to detect bone abnormalities prior to surgery. Areal BMD (aBMD) assessed by DXA may be artifactually high in patients with spine pathology, leading to missed diagnosis of deficits. In this study, we related preoperative imaging characteristics of both central and peripheral sites to direct measurements of bone quality in vertebral biopsies. We hypothesized that pre-operative imaging outcomes would relate to vertebral bone mineralization and collagen properties. Pre-operative assessments included DXA measurements of aBMD of the spine, hip, and forearm, central quantitative computed tomography (QCT) of volumetric BMD (vBMD) at the lumbar spine, and high resolution peripheral quantitative computed tomography (HRpQCT; Xtreme CT2) measurements of vBMD and microarchitecture at the distal radius and tibia. Bone samples were collected intraoperatively from the lumbar vertebrae and analyzed using Fourier-transform Infrared (FTIR) spectroscopy. Bone samples were obtained from 23 postmenopausal women (mean age 67±7years, BMI 28±8kg/m2). We found that patients with more mature bone by FTIR, measured as lower acid phosphate content and carbonate to phosphate ratio, and greater collagen maturity and mineral maturity/crystallinity (MMC), had greater cortical vBMD at the tibia and greater aBMD at the lumbar spine and one-third radius. Our data suggests that bone quality at peripheral sites may predict bone quality at the spine. As bone quality at the spine is challenging to assess prior to surgery, there is a great need for additional screening tools. Pre-operative peripheral bone imaging may provide important insight into vertebral bone quality and may foster identification of patients with bone quality deficits.

Abstract P3-03-26: Osteopenia and osteoporosis in women with breast cancer in Taiwan: single center retrospective data

Abstract Purpose: Osteopenia and osteoporosis are commonly encounter in elder women. One third of women elder than fifty years suffer a fracture second to osteoporosis around the world. Standard treatments for breast cancer such as chemotherapy or hormonal therapy may increase the risk of both osteopenia and osteoporosis. Premenopausal women treated with standard adjuvant chemotherapy frequently develop ovarian failure, or early menopause, which is associated with accelerated bone loss. Trabecular bone score (TBS), an index extracted by DXA that provides an indirect measurement of bone axial microarchitecture. In addition to the BMD, TBS are warranted to improve the prediction of fracture risk at the individual level. However, due to regulations of National Health Insurance in Taiwan, data are limited on the incidence of osteopenia and osteoporosis in women with breast cancer in Taiwan. In this study, we investigated the proportion of osteopenia and osteoporosis in women with breast cancer in Taiwan. Materials and Methods: There were enrolled 201 female who diagnosed with breast cancer between May 2019 and December 2020 in this retrospective study. Patients with bone metastasis (n=11) and double cancer(n=3) were excluded. All patients received dual energy X-ray absorptiometry (DXA) at least once, including bone mineral density (BMD), T-score (spine and total hip) and trabecular bone score (TBS) data. The data were retrospectively analyzed baseline age, BMD, breast cancer type, aromatase inhibitors (AIs) usage status by Kruskal-Wallis test. Results: Basing on the lowest T-score from measurements at the spine or total hip, 58.8% (n=110) of osteopenia (-2.5≤T←1) and 27.8%(n=52) of osteoporosis (T←2.5) were identified in women with breast cancer (figure1). Statistics significance was noted in patients’ age and BMI between three groups. There was no difference in bone mineral density according to breast cancer subtype. (table 1) Patients who ever use aromatase inhibitors (n=90) had lower BMD (T=-2.14) and trabecular bone score (TBS=1.3) than non-AI group (n=97, T=-1.84, TBS=1.34). (figure 2) (table 2) Conclusions: According to Taiwan’s NHI sampling data from 1999 to 2001, the averaged prevalence of osteoporosis in those aged ≥50 years was 11.35% for women. Breast cancer survivors are at higher risk for osteopenia and osteoporosis compared to cancer-free women in Taiwan. Aromatase inhibitors (AIs) group had lower BMD and TBS (p&amp;lt; 0.05). In our study, forty percent of TNBC patients diagnosed osteoporosis, which is compatible with increased bone loss due to chemotherapy-induced ovarian failure. Therefore, clinicians should be aware not only of AI-associated bone loss but also of patients who ever accepted long-term chemotherapy. A normal range for TBS values in postmenopausal women has been proposed: a TBS of ≥1.350 is considered normal; a TBS between 1.20 and 1.35 is considered consistent with partially degraded microarchitecture, and a TBS of ≤ 1.200 defines degraded microarchitecture. In our study, mean TBS in women with breast cancer (n=187) is 1.32. Further research is needed to determine the validity of cut-points for guiding treatment decisions. Figure 1. Inclusion/exclusion criteria and flow chart Figure 1. Inclusion/exclusion criteria and flow chart Table 1 Figure 2. Aromatase inhibitors group had lower BMD and Trabecular bone score Figure 2. Aromatase inhibitors group had lower BMD and Trabecular bone score Citation Format: Chia-Hua Liu, Chih-Chiang Hung, I-Chen Tsai. Osteopenia and osteoporosis in women with breast cancer in Taiwan: single center retrospective data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-26.

Intake and growth histories modulate bone morphology, microarchitecture, and mineralization in juvenile green turtles (Chelonia mydas)

Abstract Compensatory growth (CG) is accelerated growth that occurs when food availability increases after food restriction. This rapid growth may be associated with sublethal consequences. In this study, we investigated the effects of food restriction and subsequent realimentation and CG on bone structure in juvenile green turtles (Chelonia mydas). Turtles were fed ad libitum food for 12 weeks (AL), restricted food for 12 weeks (R), or restricted food for 5 weeks followed by ad libitum food for 7 weeks (R-AL). R-AL turtles demonstrated partial CG via enhanced food conversion efficiency (FCE) upon realimentation. After the 12th week, gross morphology (GM), microarchitecture, and mineralization of the right humerus of each turtle were analyzed. Many GM measurements (including proximal and maximal bone lengths, bone widths, and shaft thickness), most measurements of bone microarchitecture (excluding cortical and trabecular thickness and trabecular separation), and all mineralization measurements were labile in response to intake. We examined the possibility that changes in nutrient allocation to bone structure during realimentation facilitated CG in previously food-restricted turtles. Restoration of bone lengths was prioritized over restoration of bone widths during CG. Furthermore, restoration of trabecular number, connectivity density, and bone volume fraction was prioritized over restoration of cortical bone volume fraction. Finally, diaphyseal bone mineralization was partially restored, whereas no restoration of epiphyseal bone mineralization occurred during CG. Shifts in nutrient allocation away from certain bone attributes during food restriction that were not rectified when food availability increased probably provided an energy surplus that enhanced the conversion of food to growth and thus powered the CG response. Our study revealed how resource allocation to various bone attributes is prioritized as nutritional conditions change during development. These “priority rules” may have detrimental consequences later in life, indicating that conservation of green turtle foraging grounds should be given high priority.

Exploring the role of sleep in Alzheimer’s disease: The AlfaSleep project

AbstractBackgroundSleep disruption is prevalent in the aging population and increasingly recognized as a risk factor and an early sign of Alzheimer’s disease (AD). Emerging data suggest that dysregulated orexin signaling may play a role in this association. The AlfaSleep study aims to characterize sleep patterns with objective measurements, and determine CSF orexin‐A levels in cognitively unimpaired middle‐aged adults at increased risk of AD.MethodTwo‐hundred cognitively unimpaired middle‐aged adults from the prospective observational ALFA+ study have been invited to participate in this study based on their cerebrospinal fluid (CSF) biomarker profile at the ALFA+ study baseline (100 in the AD continuum and 100 control, non‐altered biomarkers). ALFA+ participants are followed‐up every three years (and currently are undergoing the first follow‐up visit) with neuropsychological testing, blood and CSF sampling, and MRI and PET (with FDG, amyloid and tau tracers) acquisition. Participants included in the AlfaSleep study are additionally characterized with actigraphy (Actiwatch2®, Philips Respironics during two weeks), a nasal flow monitoring device (RUSleeping RTS®, Philips Respironics during one night) and CSF orexin‐A measurements. Furthermore, a subset (n = 90) will undergo overnight polysomnography at the Hospital Clinic Sleep Unit (Figure 1). Sleep‐related outcomes include total sleep time, sleep latency, sleep efficiency, sleep fragmentation, apnea‐hypopnea index and sleep microarchitecture measures (e.g. spectral power analyses). These data, as well as CSF orexin‐A levels will be compared across participants with different AD biomarkers profiles and correlated with cognitive performance, neuroimaging and fluid biomarkers data.ResultTo date, 134 participants (mean age 64.4 years, 67% female) have been included in the AlfaSleep study. Of these, 50 (37.9%) reported poor sleep quality (PSQI&gt;5), 45.5% are APOE‐ε4 carriers and 35.8% had abnormal CSF amyloid levels, as measured at the ALFA+ baseline visit (see Table 1 for a detailed description).ConclusionDue to its multimodal approach, and the profile of the study population (cognitively unimpaired middle‐aged adults in the AD continuum), the present project will make relevant contributions to understand the role of sleep disruption as a risk factor and early clinical manifestation of AD. Preliminary results will be presented at the conference.