Saturated and Unsaturated Bone Marrow Lipids Have Distinct Effects on Bone Density and Fracture Risk in Older Adults

Greater bone marrow adiposity (BMAT) is associated with lower bone mineral density (BMD) and vertebral fractures; less is known about BMAT composition and bone. We studied BMAT composition and bone outcomes in 465 participants from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. BMAT saturation and unsaturation, measured with magnetic resonance spectroscopy, were defined as the ratio of saturated (1.3 ppm peak) or unsaturated (5.3 ppm peak) lipid to total marrow contents, respectively. At baseline and follow-up visits, spine and hip BMD were assessed with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) and vertebral fractures were identified with DXA. Incident clinical fractures were identified through medical records for up to 8.8 years of follow-up. Associations between BMAT composition and BMD, bone loss, and fractures were evaluated in adjusted regression models. At baseline, mean ± standard deviation (SD) participant age was 81.7 ± 4.3 years, mean BMAT unsaturation was 3.5% ± 1.0%, and mean saturation was 46.3% ± 7.2% in the full cohort (47.7% women). Each SD increase in BMAT saturation was associated with lower trabecular BMD: −23.6% (spine) and −13.0% (total hip) (all p < 0.0001). Conversely, BMAT unsaturation (per SD increase) was associated with higher trabecular BMD: +17.5% (spine) and +11.5% (total hip) (all p < 0.001). BMAT saturation (per SD increase) was associated with greater risk for prevalent (odds ratio [OR] 1.46; 95% confidence interval [CI], 1.11–1.92) and incident (OR 1.55; 95% CI, 1.03–2.34) vertebral fracture. BMAT unsaturation (per SD increase) was associated with lower risk for incident vertebral fracture (OR 0.58; 95% CI, 0.38–0.89). In gender stratified analyses, BMAT saturation and unsaturation had opposite associations with incident clinical fracture among men. In general, saturated marrow lipids were associated with worse skeletal outcomes, whereas unsaturated lipids were associated with better outcomes. We recommend that future studies of marrow fat and skeletal health report measurements of saturated and unsaturated marrow lipids, rather than total marrow fat content alone. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Effects of blood contamination on resin-resin bond strength.

OBJECTIVE: Incremental placement and curing of resin composites has been recommended. However, this requires longer operating time, and therefore, increased risk of contamination. The purpose of this study was to evaluate the effects of blood contamination on microtensile bond strengths (microTBS) between resin interfaces and to determine the best decontamination method to re-establish the original resin-resin bond strength. MATERIALS: The top surfaces of 64, 4-mm composite blocks (Z-250, Renew, APX, Pertac II) were untreated as the control, or were treated as follows: blood applied and dried on the surface (Treatment 1), blood applied, rinsed, dried (Treatment 2), blood applied, rinsed, and an adhesive applied (Single Bond, One-Step, Clearfil SE, Prompt L-Pop) (Treatment 3). Fresh composite was applied and light-cured in 2-mm increments. After 24 h storage in water, the specimens were sectioned into 0.7-mm thick slabs, trimmed to a cross-sectional area of 1 mm(2), and loaded to failure at a crosshead speed of 1 mm/min using an Instron universal testing machine. Data were analyzed using two-way ANOVA and Fisher's PLSD test (p<0.05). RESULTS: Control values ranged from 45.1 MPa for Pertac II to 71.5 MPa for APX. Untreated blood contamination resulted in resin-resin bond strengths of only 1.0-13.1 MPa. Rinsing raised bond strengths to over 40 MPa for each material. Use of an adhesive further increased bond strengths except for Pertac II. SIGNIFICANCE: Rinsing blood from contaminated surfaces increases the resin-resin bond strength significantly and the application of an appropriate adhesive increases the bond strength to control levels.     

Guidelines for the management of traumatic dental injuries. III. Primary teeth

Abstract –  Trauma to the primary dentition present special problems and the management is often different as compared with permanent teeth. An appropriate emergency treatment plan is important for a good prognosis. Guidelines are useful for delivering the best care possible in an efficient manner. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialties were included in the group. In cases in which the data did not appear conclusive, recommendations were based on the consensus opinion of the IADT board members. The guidelines represent the current best evidence based on literature research and professional opinion. In this third article out of three, the IADT Guidelines for the management of traumatic injuries in the primary dentition, are presented.     

The incidence of a first major osteoporotic fracture in Iceland and implications for FRAX

Summary

Based on an extensive cohort study over 25 years, the present study supports the assumption that major osteoporotic fractures can be reasonably predicted from hip fracture rates.

Introduction

The construct for FRAX models depends on algorithms to adjust for double counting of fracture outcomes in some models and in others, to estimate the incidence of a major fracture from hip fracture rates. The aim of the present study was to test the validity of these algorithms in a large prospective cohort.

Methods

The incidence of hip, clinical spine, distal forearm, and humerus fracture was determined in the prospective and ongoing population-based Reykjavik Study with follow up of 257,001 person-years. The incidence of a first major fracture was compared with the correction factors used in FRAX to adjust the incidence of several fracture outcomes for double counting. In addition, the incidence of a major osteoporotic fracture estimated from the Icelandic hip fracture rates was compared with the Malmo ratios used in FRAX.

Results

The adjustments necessary to account for multiple fracture outcomes were similar to those previously derived from Sweden. Additionally, incidence of a first major osteoporotic fracture was similar to that derived for FRAX models.

Conclusion

The findings of the present study support the algorithms used in FRAX to estimate the incidence of a first major fracture and the predictive value of hip fracture for other major fractures.     

Shape matters in protein mobility within membranes

The lateral mobility of proteins within cell membranes is usually thought to be dependent on their size and modulated by local heterogeneities of the membrane. Experiments using single-particle tracking on reconstituted membranes demonstrate that protein diffusion is significantly influenced by the interplay of membrane curvature, membrane tension, and protein shape. We find that the curvature-coupled voltage-gated potassium channel (KvAP) undergoes a significant increase in protein mobility under tension, whereas the mobility of the curvature-neutral water channel aquaporin 0 (AQP0) is insensitive to it. Such observations are well explained in terms of an effective friction coefficient of the protein induced by the local membrane deformation.Brownian motion plays an essential role in biological processes. Since the pioneering experiments of Perrin (1), the observation of diffusing objects has emerged as a mean to extract the rheological properties of the surrounding medium or the probe particle size. The theoretical investigation of diffusion of proteins within membranes has been studied widely going back to P. G. Saffman and M. Delbrück (SD). They investigated the hydrodynamic drag acting on a membrane inclusion when the membrane is described as a 2D fluid sheet of viscosity embedded within a less viscous fluid of viscosity η (2). In this theory, the diffusion coefficient D₀ in the limit of a large viscosity contrast between the membrane and bulk fluid is given by:The length is the length scale over which flow is generated within the bilayer by the inclusion, k_BT is the thermal energy, and γ is Euler’s constant. This model predicts a logarithmic dependence of D₀ on the protein radius a_p, which has been confirmed for some in vitro experiments on membranes containing transmembrane proteins (see ref. 3 and references therein). In contrast, the experiments of Gambin et al. (4) showed significant deviations from the SD theory.A possible origin for the discrepancy observed by Gambin et al. (4) is the significant local membrane deformation due to the interaction between the inclusion and the lipid bilayer (5). Naji et al. suggested in ref. 6 that inclusions experience additional dissipation, either due to internal flows within the membrane or to additional fluid flows produced by the deformed membrane. This work triggered a number of theoretical studies investigating the coupling of inclusion proteins with the membrane that had been pioneered by the Seifert’s group (see ref. 7 and references therein). Such studies have systematically gone beyond the SD model by including additional effects (8–12). So far, a thorough verification of these ideas has not been attempted. To investigate the effect of the protein–lipid coupling on the protein mobility, we study its dependence on membrane tension, because this parameter affects the local membrane deformation.In this work, we compare the mobility of two transmembrane proteins with the same lateral size, aquaporin 0 (AQP0) and a voltage-gated potassium channel (KvAP), reconstituted in giant unilamellar vesicles (GUVs). Whereas AQP0 does not deform locally the bilayer, KvAP locally bends the membrane (13). Using single-particle tracking (SPT), we demonstrate that the curvature-coupled protein KvAP undergoes a significant increase in mobility under tension, whereas the mobility of the curvature-neutral water channel AQP0 is insensitive to it. This difference, which goes beyond the SD model, is explained by an approach that includes the interplay between membrane deformation and friction with the surrounding medium and within the bilayer. This is compelling evidence that the Brownian motion of a shaping-membrane protein is not simply dependent on the inclusion size but also related to the lateral extension of the deformed membrane patch, which depends on tension.     

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture. © 2014 American Society for Bone and Mineral Research.     

Mediation Analysis of Aortic Stiffness and Renal Microvascular Function

Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular–microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72–92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=−2.28±0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, −1.35 to −0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, −2.22 to −0.40; 95% confidence interval of indirect effect including renal vascular resistance, −2.51 to −0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.     

Nocturnal nasal obstruction is frequent and reduces sleep quality in patients with obstructive sleep apnea

The prevalence and consequences of nasal obstruction in untreated obstructive sleep apnea patients are not known. The study objectives were to investigate the frequency of subjective and objective nasal obstruction in untreated sleep apnea patients and the associations with sleep and quality of life. Patients in the Icelandic Sleep Apnea Cohort were subjected to a type 3 sleep study, answered questionnaires and had their nasal dimensions measured by acoustic rhinometry. In total, 810 patients participated (including 153 females), aged 54.5 ± 10.6 years [mean ± standard deviation (SD)] with an apnea/hypopnea index 44.7 ± 20.7 h^?1. Nocturnal nasal obstruction (greater than or equal to three times per week) was reported by 35% of the patients. These patients had smaller nasal dimensions measured by the minimum cross‐sectional area within the smaller nasal valve (0.42 ± 0.17 versus 0.45 ± 0.16 cm², P = 0.013), reported more daytime sleepiness (Epworth Sleepiness Scale score 12.5 ± 4.9 versus 10.8 ± 5.0; P < 0.001) and slightly lower mental quality of life than patients without nocturnal nasal obstruction. Nocturnal nasal obstruction is reported in one‐third of the sleep apnea patients and they are more likely to suffer from daytime sleepiness and slightly reduced quality of life than other sleep apnea patients.     

Late right ventricular performance after mitral valve repair assessed by exercise echocardiography

Objectives

The aim of the study was to evaluate the right ventricular (RV) performance during exercise in patients who underwent mitral valve repair for chronic mitral valve insufficiency relative to healthy individuals and to assess exercise capacity using a semisupine ergometer.

Methods

We studied 56 patients who underwent mitral valve repair for degenerative posterior mitral leaflet prolapse between 2005 and 2014 and a control group of 13 healthy individuals. Clinical data were collected prospectively, and echocardiographic measurements of RV function were obtained at rest and at peak exercise.

Results

One-third of the study patients had RV systolic dysfunction as indicated by tricuspid annular plane excursion (TAPSE) at rest. Resting TAPSE was lower in the study group (16.7?±?3.3 mm) than in the control group (24.4?±?4.3 mm), p?<?0.001. TAPSE increased in both groups during exercise and exercise was shown to have a significant main effect on TAPSE F(1, 52)?=?80, p?<?0.001. TAPSE increased more in the control group and an interaction was detected between the participant groups (study group vs. control group) and exercise, F(1, 52)?=?24, p?<?0.001. In the study group, Poor postoperative RV function was associated with preoperative left ventricular dilatation but was not correlated with impaired maximum exercise capacity.

Conclusions

Despite the excellent clinical outcome during rest and exercise after mitral valve repair, our results suggest patients that have undergone mitral valve repair due to posterior leaflet prolapse have significantly reduced RV function at rest and during exercise compared to healthy controls at long-term follow-up, as measured by TAPSE.