Transepithelial phototherapeutic keratectomy for treatment-resistant recurrent corneal erosion syndrome.

BACKGROUND: To evaluate the efficacy and safety of trans-epithelial phototherapeutic keratectomy (TE-PTK) as a treatment for recurrent corneal erosion syndrome (RCES) in patients with symptoms refractory to conventional treatments. METHODS: All patients who received TE-PTK treatment for RCES had failed 3 or more conventional treatments and were reviewed, and if met criteria, approved by healthcare workers of the British Columbia public health authority (Medical Services Plan (MSP). A retrospective chart review and telephone survey were conducted at the Pacific Laser Eye Centre (PLEC). Exclusion criteria were ocular co-morbidities potentially affecting treatment efficacy. RESULTS: This study included 593 eyes of 555 patients (46.2% male; 50.9 ± 14.2 years old) who underwent TE-PTK. The leading identified causes of RCES were trauma (45.7%) and anterior basement membrane dystrophy (44.2%). The most common pre-PTK interventions were ocular lubricants (90.9%), hypertonic solutions (77.9%), and bandage contact lenses (50.9%). Thirty-six eyes had undergone surgical interventions such as stromal puncture, epithelial debridement, or diamond burr polishing. Post-PTK, 78% of patients did not require any subsequent therapies and 20% required ongoing drops. Six patients (1.1%) reported no symptom improvement and required repeat TE-PTK for ongoing RCES symptoms after initial TE-PTK. All 6 eyes were successfully retreated with TE-PTK (average time to retreatment was 11.3 ± 14.9 months). There was no significant difference in best corrected visual acuity pre- vs. post-operatively. The mean post-operative follow-up was 60.5 months (range: 5-127 months). CONCLUSION: TE-PTK has a good efficacy and safety profile for treatment-resistant RCES. The third-party public health-reviewed nature of this study, the low recurrence rate of RCES, and the low PTK retreatment rate suggest that TE-PTK might be considered for wider use in the management of RCES.

A comparison between IBEX bone health applied to digital radiographs and dual-energy X-ray absorptiometry at the distal-third and ultra-distal regions of the radius.

BACKGROUND: In an ageing population, low impact fragility fractures are becoming increasingly common. However, fracture risk can be reduced where low bone density can be identified at an early stage. In this study we aim to demonstrate that IBEX Bone Health (IBEX BH) can provide a clinically useful prediction from wrist radiographs of aBMD and T-score at the ultra-distal (UD) and distal-third (DT) regions of the radius. METHODS: A 261-participant single-centre, non-randomised, prospective, study was carried out to compare a) IBEX BH, a quantitative digital radiography software device, to b) Dual-energy X-ray Absorptiometry (DXA). A total of 257 participants with wrist digital radiograph (DR), forearm DXA pairs were included in the analysis after exclusions. RESULTS: The adjusted R2 value for IBEX BH outputs to the radial areal bone mineral density (aBMD) produced by a GE Lunar DXA system for the UD region is 0.87 (99% Confidence Interval (CI) [0.84, 0.89]). The adjusted R2 value for IBEX BH outputs to aBMD for the DT region is 0.88 (99% CI [0.85, 0.90]). The Area Under the Receiver Operating Characteristic curve (AUC) for the forearm T-score ≤ - 2.5 risk prediction model at the UD region is 0.95 (99% CI [0.93, 0.98]). The AUC for the forearm T-score ≤ - 2.5 risk prediction model at the DT region is 0.98 (99% CI [0.97, 0.99]). CONCLUSION: From a DR of the wrist, IBEX BH provides a clinically useful i) estimate of aBMD at the two regions of interest on the radius and ii) risk prediction model of forearm T-score ≤ - 2.5 at the UD and DT regions.

Cross-Calibration Study of The Stratos And Hologic QDR 4500A Dual-Energy X-Ray Absorptiometers to Assess Bone Mineral Density And Body Composition.

The objective of the study was to assess the agreement between the Stratos (DMS) and QDR 4500A (Hologic) DXAs in determining whole body and regional aBMD, as well as whole body composition. Fifty-five individuals (46 women: 84%) with a mean age of 41 ± 13.0 years (range: 20 to 64) and a mean BMI of 31.9 ± 10 kg/m² (range: 12.2 to 49.5) were consecutively scanned on the same day using the two devices. Predictive equations for areal bone mineral density (aBMD) and whole body composition (WBC) were derived from linear regression of the data. The two DXAs were highly correlated (p<0.001 for all parameters) with a correlation coefficient (r) ranging from 0.89 to 0.99 for aBMD (r=0.89 for whole body, r=0.92 for radius, r=0.95 for femoral neck, r=0.96 for total hip, and r=0.99 for L1-L4). For WBC, the r value was 0.98 for lean tissue mass (LTM) and 1.0 for fat mass (FM). Paired t-tests indicated a statistically significant bias between the two DXAs for the majority of measurements, requiring the determination of specific cross-calibration equations. Compared to QDR 4500A, Stratos underestimated whole body aBMD and LTM and overestimated neck and hip aBMD and whole body FM. Conversely, no significant bias was demonstrated for mean aBMD at L1-L4 and radius. For whole body aBMD and FM, the concordance between the two DXAs was influenced by BMI. Despite a high concordance between the two DXAs, the systematic bias for aBMD and WBC measurements illustrates the need to define cross-calibration equations to compare data across systems.

Bone density in youth with prediabetes: results from the National Health and Nutrition Examination Survey, 2005-2006.

Youth with type 2 diabetes might have suboptimal peak bone mass, but it is unknown whether similar effects are evident in youth with prediabetes. Results from this study suggest that diabetes-related effects on peak bone mass likely occur before disease onset, and involve the muscle-bone unit. INTRODUCTION: Type 2 diabetes might adversely influence bone health around the age of peak bone mass, but it is unknown whether diabetes-related effects on areal bone mineral density (aBMD) are evident in youth with prediabetes. We compared age-related trends in aBMD and associations between lean body mass (LBM) and aBMD between children and adolescents with prediabetes vs. normal glucose regulation. METHODS: Cross-sectional analysis of data from the National Health and Nutrition Examination Survey (2005-2006) in youth ages 12-20 years (49% female, 34% black) with prediabetes (n = 267) and normal glucose regulation (n = 1664). Whole body aBMD and LBM were assessed via DXA. LBM index (LBMI) and Z-scores for aBMD and LBMI were computed. RESULTS: Unadjusted between-group comparisons revealed greater mean weight and LBMI Z-scores in youth with prediabetes vs. normal glucose regulation, but similar bone Z-scores between the two groups. While accounting for differences in BMI Z-score, there was a significant interaction between prediabetes status and age with respect to whole body aBMD Z-score (P < 0.05), such that children with prediabetes tended to have increased aBMD but adolescents and young adults with prediabetes tended have lower aBMD. Furthermore, the positive association between LBMI and whole body aBMD was moderated in youth with prediabetes (P < 0.001), who had slightly lower whole body aBMD for a given LBMI (P = 0.068). Lumbar spine bone measures did not differ between the two groups. CONCLUSIONS: Type 2 diabetes-related threats to peak bone mass might occur prior to disease onset, therefore potentially impacting a considerable proportion of US youth.

Comparison of the Lunar Prodigy and Stratos DR Dual-Energy X-Ray Absorptiometers to Assess Regional Bone Mineral Density.

PURPOSE: The first objective of the study was to assess the agreement between the Stratos DR (DMS) and the GE Prodigy (GE) DXAs in determining femoral neck, total hip and lumbar spine aBMD. The second objective was to assess the potential impact of leg positioning (hip flexed at 90° or not) on lumbar spine aBMD. METHODS: Forty-six individuals (n=42 women, 91.3%), with a mean age of 59.7 ± 13 years and mean BMI of 23.8 ± 4.7 kg/m², were scanned consecutively on the same day using the two devices. In a subgroup (n=30), two consecutive Stratos DR scans (with hip flexed at 90° or not) at the lumbar spine were conducted. Predictive equations for hip and lumbar spine aBMD were derived from linear regression of the data. RESULTS: Correlation coefficients for aBMD measured with the two DXAs were characterised by an R² of 0.76 for the femoral neck, 0.89 for the total hip, and 0.86 for the lumbar spine. However, the derived equations for aBMD determination showed an intercept significantly different from 0 for hip aBMD, and a slope significantly different from 1 for lumbar spine aBMD. These results highlight a bias between the two measurements, thus requiring the determination of specific cross-calibration equations for hip and lumbar spine, femoral neck excepted. When compared with values on the Prodigy, mean aBMD on the Stratos DR was higher at the femoral neck (+4.8%, p<0.001) and total hip (+9.6%, p<0.001) and lower at L2-L4 (-8.8%, p<0.001). The coefficient of variation (CV%) for the two consecutive measures at lumbar spine (with different positioning) with the Stratos DR was 2.9%. CONCLUSIONS: The difference in aBMD measured with the two DXAs illustrates the need to define cross-calibration equations when comparing data across systems in order to avoid erroneous conclusions.

Bone mineral density averaged over a region of interest on femur is affected by age-related change of bone geometry.

Femur expansion occurs during normal aging in both men and women. Average bone mineral density (BMD) over a region of interest (ROI) on the femur may considerably decrease with age even in healthy people, and therefore, it is inaccurate if used to monitor treatment-induced bone change. INTRODUCTION: Areal bone mineral density (BMD), averaged over a region of interest (ROI) on the femur, is widely used in the diagnosis of osteoporosis, assessment of fracture risk, and monitoring of treatment effectiveness. We studied the effect of age-related change in femur geometry on average BMD. METHODS: The effect of age-related bone geometric change on averaged BMD was investigated by a cross-sectional study. Total 83 healthy subjects were selected for this study. For each subject, QCT of left femur was scanned using clinical scanner. For each standard volume of interest (VOI), integral/cortical/trabecular bone volume, volumetric BMD (vBMD), and bone mass were measured using QCT Pro; the corresponding areal BMD (aBMD) was projected using CTXA-Hip. Both QCT Pro and CTXA-Hip are commercial software. Correlations between bone volume/density/mass and age were studied. RESULTS: In the studied population, there was no association between body weight/BMI (body mass index) and age, correlation between normalized femoral neck width and age was 0.24 (p < 0.05). Both aBMD and integral vBMD decreased with age (after adjusted by BMI, for aBMD, r = - 0.21 to - 0.24, p ≤ 0.05 except at trochanter; for vBMD, r = - 0.20 to - 0.31, p < 0.05); cortical vBMD had no significant change; trabecular vBMD decreased at all VOIs except at trochanter (after adjusted by BMI, r = - 0.22 to 0.32, p ≤ 0.05). Integral volume showed slight increase but only significant at the trochanter after adjusted by body size, cortical volume showed insignificant decrease, and trabecular volume considerably increased with age in all VOIs (after adjusted by body size, r = 0.27-0.40, p < 0.05). Integral, cortical, and trabecular mass had no significant change in all VOIs, except that at the trochanter trabecular mass slightly increased with age (r = 0.31, p < 0.05). CONCLUSIONS: Even though there is no change in bone mass, average BMD may considerably decrease with age due to bone expansion. Comparatively, aBMD is less affected than vBMD.

Bone mineral density at the hip and its relation to fat mass and lean mass in adolescents: the Tromsø Study, Fit Futures.

BACKGROUND: Positive association between body weight and bone mass is well established, and the concept of body mass index (BMI) is associated with higher areal bone mineral density (aBMD) and reduced fracture risk. BMI, that comprises both fat mass (FM) and lean mass (LM) may contribute to peak bone mass achievement in different ways. This study explored the influence of body composition in terms of total body LM and FM on hip aBMD-values in adolescence. METHODS: In 2010/2011, 93% of the region's first-year upper-secondary school students (15-17 years old) in Tromsø, Norway attended the Tromsø Study, Fit Futures. Areal BMD at femoral neck (aBMDFN) and total hip (aBMDTH) (g/cm2), total body LM and FM (g) were measured by dual energy X-ray absorptiometry (DXA). Height and weight were measured, and BMI calculated. Lifestyle variables were collected by self-administered questionnaires and interviews, including questions on time spent on leisure time physical activity. Stratified analyses of covariance and regression models included 395 girls and 363 boys. Crude results were adjusted for age, height, sexual maturation, physical activity levels, vitamin D levels, calcium intake, alcohol consumption and smoking habits. RESULTS: Unadjusted distribution indicated higher aBMD-levels at higher LM-levels in both genders (p < 0.001), but higher aBMD at higher FM-levels were found only in girls (p < 0.018). After multiple adjustments, aBMDFN-levels in girls were associated by 0.053 g/cm2 and 0.032 g/cm2 per standard deviation (SD) change in LM and FM (p < 0.001). Corresponding values in boys were 0.072 and 0.025 (p < 0.001). The high LM groups accounted for the highest aBMD-levels, while aBMD-levels at the LM/FM-combinations indicated different patterns in girls compared to boys. The adjusted odds ratio (95% CI) for low levels of aBMDFN was 6.6 (3.4,13.0) in boys, compared to 2.8 (1.6,4.9) in girls per SD lower LM. CONCLUSIONS: LM and FM should be regarded as strong predictors for bone mass and hence bone strength in adolescents. A gender specific difference indicated that high lean mass is of crucial importance prominently in boys. In adolescents with low lean mass, especially in girls, high fat mass may partially ameliorate the effect of deficient lean mass levels.

Association between bone indices assessed by DXA, HR-pQCT and QCT scans in post-menopausal women.

Quantitative computed tomography (QCT), high-resolution peripheral QCT (HR-pQCT) and dual X-ray absorptiometry (DXA) scans are commonly used when assessing bone mass and structure in patients with osteoporosis. Depending on the imaging technique and measuring site, different information on bone quality is obtained. How well these techniques correlate when assessing central as well as distal skeletal sites has not been carefully assessed to date. One hundred and twenty-five post-menopausal women aged 56-82 (mean 63) years were studied using DXA scans (spine, hip, whole body and forearm), including trabecular bone score (TBS), QCT scans (spine and hip) and HR-pQCT scans (distal radius and tibia). Central site measurements of areal bone mineral density (aBMD) by DXA and volumetric BMD (vBMD) by QCT correlated significantly at the hip (r = 0.74, p < 0.01). Distal site measurements of density at the radius as assessed by DXA and HR-pQCT were also associated (r = 0.74, p < 0.01). Correlations between distal and central site measurements of the hip and of the tibia and radius showed weak to moderate correlation between vBMD by HR-pQCT and QCT (r = -0.27 to 0.54). TBS correlated with QCT at the lumbar spine (r = 0.35) and to trabecular indices of HR-pQCT at the radius and tibia (r = -0.16 to 0.31, p < 0.01). There was moderate to strong agreement between measuring techniques when assessing the same skeletal site. However, when assessing correlations between central and distal sites, the associations were only weak to moderate. Our data suggest that the various techniques measure different characteristics of the bone, and may therefore be used in addition to rather than as a replacment for imaging in clinical practice.

Determinants of microstructural, dimensional and bone mineral changes postpartum in Swedish women.

During lactation, areal (a) and volumetric (v) bone mineral density (BMD) are known to temporarily decrease. Factors that affect skeletal changes postpartum are not fully elucidated. The aim was to study determinants of the previously observed changes in aBMD at lumbar spine, and cortical vBMD, microstructure and dimensions at ultra-distal tibia postpartum. Women (25-40 years) were studied longitudinally at 2 weeks (baseline) and 4 months (n 81), 12 months (n 79) and 18 months (n 58) postpartum. At each visit, blood samples were collected, body weight and height were measured and information about lactation habits, oestrogen contraceptives and physical activity was obtained. Ca intake was measured using 4-d food diaries at 4 months postpartum. Serum 25-hydroxyvitamin D (25OHD) was analysed by liquid chromatography-tandem MS. Skeletal changes were assessed with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Mean baseline BMI was 24·8 (sd 3·1) kg/m2. Median (quartiles 1-3) duration of total lactation was 8·1 (6·8-10·4) months. Longer duration of full lactation was associated with larger decreases of lumbar spine aBMD and tibia vBMD and microstructure. Higher baseline body weight was associated with smaller decreases in tibia vBMD and microstructure. Higher Ca intake was associated with smaller decreases in tibia cortical vBMD and thickness. Higher baseline 25OHD was only associated with larger decreases in lumbar spine aBMD. In conclusion, lactation and body weight were the main determinants of skeletal changes during the first 18 months postpartum. Ca intake and serum concentrations of 25OHD appear to have different associations with cortical and trabecular bone.

Inverse Correlation at the Hip Between Areal Bone Mineral Density Measured by Dual-Energy X-ray Absorptiometry and Cortical Volumetric Bone Mineral Density Measured by Quantitative Computed Tomography.

Quantitative computed tomography (QCT) is considered to measure true volumetric bone mineral density (vBMD; mg/cm3) and enables differentiation between cortical and trabecular bone. We aimed to determine the value of QCT by correlating areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) with vBMD when using a fixed threshold to delineate cortical from trabecular bone. In a cross-sectional study, 98 postmenopausal women had their hip scanned by DXA and by QCT. At the total hip and the trabecular bone compartment, aBMD correlated significantly with vBMD (r=0.74 and r=0.63; p<0.01, respectively). A significant inverse correlation was found between aBMD and cortical vBMD (r=-0.57; p<0.01). Total hip volume by QCT did not change with aBMD. However, increased aBMD was associated with a decreased trabecular bone volume (r=-0.36; p<0.01) and an increased cortical volume (r=0.69; p<0.01). Changing the threshold used to delineate cortical from trabecular bone from default 350 mg/cm3 to either 300 or 400 mg/cm3 did not affect integral vBMD (p=89) but had marked effects on estimated vBMD at the cortical (p<0.001) and trabecular compartments (p<0.001). Furthermore, increasing the threshold decreased cortical thickness (p<0.001), whereas the strength parameter in terms of buckling ratio increased (p<0.001). Our results show good agreement between aBMD and integral vBMD. However, using a fixed threshold to differentiate cortical from trabecular bone causes an apparent increase in cortical volume with a decrease in cortical density as aBMD increases. This may be caused by the classification of a larger part of the transition zone as cortical bone with increased aBMD.

Essential function of the N-termini tails of the proteasome for the gating mechanism revealed by molecular dynamics simulations.

Proteasome is involved in the degradation of proteins. Proteasome activators bind to the proteasome core particle (CP) and facilitate opening a gate of the CP, where Tyr8 and Asp9 in the N-termini tails of the CP form the ordered open gate. In a double mutant (Tyr8Gly/Asp9Gly), the N-termini tails are disordered and the stabilized open-gate conformation cannot be formed. To understand the gating mechanism of the CP for the translocation of the substrate, four different molecular dynamics simulations were carried out: ordered- and Tyr8Gly/Asp9Gly disordered-gate models of the CP complexed with an ATP-independent PA26 and ordered- and disordered-gate models of the CP complexed with an ATP-dependent PAN-like activator. The free-energies of the translocation of a polypeptide substrate moving through the gate were estimated. In the ordered-gate models, the substrate in the activator was more stable than that in the CP. The conformational entropy of the N-termini tails of the CP was larger when the substrate was in the activator than in the CP. In the disordered-gate models, the substrate in the activator was more destabilized than in the ordered-gate models. The mutated N-termini tails became randomized and their increased conformational entropy could no longer increase further even when the substrate was in the activator, meaning the randomized N-termini tails had lost the ability to stabilize the substrate in the activator. Thus, it was concluded that the dynamics of the N-termini tails entropically play a key role in the translocation of the substrate.

Peak Bone Mass Formation: Modern View of the Problem.

Peak bone mass is the amount of bone tissue that is formed when a stable skeletal state is achieved at a young age. To date, there are no established peak bone mass standards nor clear data on the age at which peak bone mass occurs. At the same time, the level of peak bone mass at a young age is an important predictor of the onset of primary osteoporosis. The purpose of this review is to analyze the results of studies of levels of peak bone mass in general, the age of its onset, as well as factors influencing its formation. Factors such as hormonal levels, body composition, physical activity, nutrition, heredity, smoking, lifestyle, prenatal predictors, intestinal microbiota, and vitamin and micronutrient status were considered, and a comprehensive scheme of the influence of these factors on the level of peak bone mass was created. Determining the standards and timing of the formation of peak bone mass, and the factors affecting it, will help in the development of measures to prevent its shortage and the consequent prevention of osteoporosis and concomitant diseases.

A cross-calibration study using a novel dual X-ray absorptiometry system for bone mineral density measurements with the European Spine Phantom.

Background: For bone health assessment, dual-energy X-ray absorptiometry (DEXA) is recommended to measure bone mineral content and areal bone mineral density (aBMD) in the lumbar spine. However, intermachine differences were not taken into account when developing these recommendations. According to the International Society of Clinical Densitometry (ISCD), phantom-based cross-calibration is adequate after replacing the DEXA system from a different manufacturer. For different DEXA equipment, individual calibration equations were found to be necessary to fit the observed values with the given densities. Methods: The BMD European Spine Phantom (ESP) measurements (L1, L2, and L3) were assessed on 3 machines. We used the Welch test in the one-way analysis of variance (ANOVA) with a post-hoc Tamhane T2 test, linear regressions, and Bland-Altman analysis to assess the consistency of measurements and establish cross-calibration equations. Results: The coefficients of variation (CV)% of the phantom BMD values measured using the 3 systems were less than 3.0%. The 3 DEXA systems were highly correlated with BMD in the lumbar spine, with correlation values ranging from 0.933 to 0.984 (P<0.0001). The cross-calibration regression models of the ESP measurements yielded the highest prediction accuracies with the lowest prediction errors (the standard error of the estimate ranged from 0.004 to 0.008 g/cm2; P<0.0001). After the regression equations were applied, the differences in BMD values among the 3 systems were negligible. In addition, the Bland-Altman plot showed that almost all data points were within the 95% limits of agreement. Conclusions: A strong agreement for BMD measurement was established between the 3 DEXA systems. Cross-calibration equations for the lumbar spine BMD values need to be applied to transform the Hologic Discovery A or GE Lunar iDXA measurements into SONIALVISION SMIT measurements to comply with the ISCD standards for patient continuity of care in assessment during clinical diagnosis.

Bone Geometry, Density, Microstructure, and Biomechanical Properties in the Distal Tibia in Patients With Primary Hypertrophic Osteoarthropathy Assessed by Second-Generation High-Resolution Peripheral Quantitative Computed Tomography.

Periosteosis refers to pathological woven bone formation beneath the cortical bone of the long bones. It is an imaging hallmark of primary hypertrophic osteoarthropathy (PHO) and also considered as one of the major diagnostic criteria of PHO patients. Up to date, detailed information on bone quality changes in long bones of PHO patients is still missing. This study aimed to evaluate bone microarchitecture and bone strength in PHO patients by using high-resolution peripheral quantitative computed tomography (HR-pQCT). The study comprised 20 male PHO patients with the average age of 27.0 years and 20 age- and sex-matched healthy controls. The areal bone mineral density (aBMD) was assessed at the lumbar spine (L1 -L4 ) and hip (total hip and femoral neck) by dual-energy X-ray absorptiometry (DXA). Bone geometry, volumetric bone mineral density (vBMD), and microstructure parameters at the distal tibia were evaluated by using HR-pQCT. Bone strength was evaluated by finite element analysis (FEA) based on HR-pQCT screening at distal tibia. Urinary prostaglandin E2 (PGE2 ), serum phosphatase (ALP), beta-C-telopeptides of type I collagen (ß-CTX), soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG), and neuronal calcitonin gene-related peptide (CGRP) were investigated. As compared with healthy controls, PHO patients had larger bone cross-sectional areas; lower total, trabecular, and cortical vBMD; compromised bone microstructures with more porous cortices, thinned trabeculae, reduced trabecular connectivity, and relatively more significant resorption of rod-like trabeculae at distal tibia. The apparent Young's modulus was significantly lower in PHO patients. The concentration of PGE2 , biomarkers of bone resorption (ß-CTX and sRANKL/OPG ratio), and the neuropeptide CGRP were higher in PHO patients versus healthy controls. PGE2 level correlated negatively with vBMD and estimated bone strength and positively with bone geometry at distal tibia. The present HR-pQCT study is the first one illustrating the microarchitecture and bone strength features in long bones. © 2021 American Society for Bone and Mineral Research (ASBMR).

A comparison of different exercise intensities for improving bone mineral density in postmenopausal women with osteoporosis: A systematic review and meta-analysis.

Objective: This study aimed to compare the effects of moderate- and high-intensity resistance and impact training (MiRIT and HiRIT, respectively) on changes in bone mineral density (BMD) in postmenopausal women with osteoporosis. Methods: Randomized controlled trials that compared the intervention effects of MiRIT and HiRIT were used as selection criteria to assess study patients with osteoporosis or an osteoporotic condition. Database searches were conducted on August 25, 2022, using CENTRAL, PubMed, CINAHL Web of Science, EMBASE, and MEDLINE. A risk of bias assessment was performed using Revised Cochrane risk of bias tool for the assessment of randomized controlled trials. Point estimates and 95 % confidence intervals of change in BMD derived using dual-energy X-ray absorptiometry were collected as outcomes, and a meta-analysis was performed using the amount of change in BMD before and after the intervention. Adverse event data were also collected. Results: The search yielded six studies (391 patients, mean age 53-65 years) that met the inclusion criteria. The intervention duration ranged from 24 weeks to 13 months. Compared with the MiRIT group, the HiRIT group showed significantly improved BMD of the lumbar spine (standardized mean difference 2.37 [0.10-4.65]). However, a high degree of heterogeneity was observed for three studies (154 patients, I2 = 98 %). Almost all studies reported minimal adverse events. The certainty of evidence was extremely low because of the risk of bias, inconsistency among studies, and imprecision in terms of sample size. Conclusion: Postmenopausal women with osteoporosis may achieve more significantly improved lumbar spine BMD with HiRIT than with MiRIT.

Bone accrual and structural changes over one year in youth with cystic fibrosis.

Background: Pediatric bone accrual governs peak bone mass and strength. Longitudinal studies of bone health in youth with cystic fibrosis (CF) may provide insight into CF-related bone disease (CFBD), a prevalent co-morbidity in adults with CF. Methods: This one-year longitudinal study of youth with pancreatic insufficient CF, enrolled in a nutrition intervention study [n = 62 (36 M/26F)] 1) examined dual-energy x-ray absorptiometry (DXA)-defined lumbar spine (LS) and total body less head (TBLH) bone accrual and 2) compared their changes in peripheral quantitative computed tomography (pQCT) cortical and trabecular tibial bone density and geometry to those of a healthy reference group [n = 143 (68 M/75F)].Main outcome measures were 1) DXA: lumbar spine areal bone mineral density (LSaBMD) and total body less head bone mineral content (TBLH-BMC), sex- and pubertal status-specific, height velocity (HV)-adjusted or HV and lean body mass velocity (HV-LBMV)-adjusted annualized velocity-Z scores and 2) pQCT: age, sex, pubertal status and, when appropriate, tibial length adjusted Z-scores for bone architecture measures.DXA velocity-Z were compared to expected mean of 0 and correlations with clinical parameters (age, BMI-Z and FEV1%-predicted) tested. Within-subject comparisons of HV-adjusted and LBMV-HV-adjusted DXA velocity-Z were conducted in CF.pQCT Z-scores were compared between the two groups over one year using longitudinal models. Longitudinal relationships between measures of bone health and clinical parameters (age, BMI-Z and FEV1%-predicted) were examined in individuals with CF. Results: DXA velocity-Z were higher than normal in females (p < 0.05) but not males with CF. HV-adjusted and LBMV-HV-adjusted velocity-Z did not differ for LSaBMD or TBLH-BMC.In males with CF, both HV-adjusted and LBMV-HV-adjusted LSaBMD velocity-Z scores correlated negatively with age (HV rho: -0.35; p = 0.045 and LBMV-HV rho: -0.47; p = 0.0046). In males with CF BMI-Z correlated positively with HV-adjusted LSaBMD velocity-Z (rho: 0.37; p = 0.034), but this relationship did not persist for LBMV-HV (rho: 0.14; p = 0.42). In females with CF, no correlations between LSaBMD velocity-Z scores and age or BMI-Z were found (all p > 0.05). No correlations between LSaBMD velocity-Z scores and FEV1%-predicted were seen in either sex (all p > 0.12). TBLH-BMC velocity Z-scores were not correlated with clinical parameters in either sex (all p > 0.1).At baseline, multiple pQCT parameters were lower in CF (p < 0.05). pQCT Z-scores did not differ between baseline and one-year in either CF or reference group. In a longitudinal model comparing pQCT-Z changes in CF and reference, multiple pQCT-Z outcomes remained lower in CF, but the changes in parameters did not differ in CF vs reference (all p > 0.26). Lower pQCT outcomes in CF were largely restricted to males (CF group*female sex interaction beta coefficients > 0). In this combined longitudinal model, of both CF and reference, BMI-Z was positively associated with pQCT-Z parameters(p < 0.001).Multiple pQCT-Z outcomes positively correlated with both BMI-Z and FEV1%-predicted in males with CF, and with FEV1%-predicted in females with CF (p < 0.05). Age was negatively associated with section modulus (p = 0.001) in males and with cortical density-Z in females (p < 0.001). Conclusions: With improved longevity, bone health in CF is of increasing importance. On average, bone accrual was preserved in youth with CF, and while deficits in bone geometry and strength were found, these deficits did not worsen over the one-year study. Lower LS bone accrual with increasing age suggests emerging adulthood is a period of vulnerability in CF while the role of LBM in bone health is underscored by the lack of relationship between LBMV-adjusted accrual and BMI. These findings may be useful in targeting screening practices and interventions.

An update on methods for assessing bone quality and health in Cystic fibrosis.

With increasing life expectancy in people with Cystic fibrosis (CF), the focus of clinical care has shifted to management and prevention of non-pulmonary comorbidities. CF related bone disease, defined by low bone mineral density (BMD), is prevalent across all age groups and acknowledges the increased fractures rates that negatively impact lung function and quality of life. Dual energy X-ray absorptiometry (DXA) measurement of bone mineral content (BMC) and "areal" BMD (aBMD) is recommended for identifying and monitoring bone health in children and adults due to its low cost, low radiation exposure, and widespread availability. Recent studies in children and adolescents with chronic illness focus on adjustment of BMC and aBMD measurements for height due to the effects of short stature and delayed maturation on bone size. Expanded reference databases for alternate imaging sites such as the ultradistal radius and hip present opportunities for research and long-term monitoring. As the two-dimensional nature of DXA imposes limitations, we highlight other imaging modalities including peripheral quantitative computed tomography QCT (pQCT), magnetic resonance imaging, and quantitative ultrasound (QUS). These tools, while primarily used in a research setting, can impart information on true volumetric bone density and bone microarchitecture as well as contribute to fracture assessment and prediction. Due to the high morbidity and mortality associated with vertebral and hip fracture, we will present on vertebral fracture assessment (VFA) in both children and adults as well as applied analyses including hip structural analysis (HSA), trabecular bone score (TBS), and fracture risk assessment (FRAX) for high risk groups. Questions remain on the future clinical applicability and accessibility of these assessment and prediction tools, longitudinal monitoring through adolescence and adulthood, and how outcome measures may guide bone modifying therapies.

Discriminating value of HR-pQCT for fractures in women with similar FRAX scores: A substudy of the FRISBEE cohort.

Areal bone mineral density (aBMD) has a low sensitivity to identify women at high fracture risk. The FRAX algorithm, by combining several clinical risk factors, might improve fracture prediction compared to aBMD alone. Several micro-architectural and biomechanical parameters which can be measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) are associated with fracture risk. HR-pQCT in combination or not with finite element analysis (FEA) may be used to improve bone strength prediction. Our aim was to assess whether HR-pQCT measurements (densities, cortical and trabecular microarchitecture, biomechanical proprieties assessed by FEA) had an added value in predicting fractures in a subgroup of women belonging to the Belgian FRISBEE cohort. One hundred nineteen women who sustained a fracture (aged 60 to 85 years) during the initial follow-up of our cohort had a radius and tibia examination by HR-pQCT and were compared with controls matched for their FRAX score at baseline. We found that low distal radius total (OR = 1.41 [1.07-1.86] per SD, p < 0.05) and trabecular densities (OR = 1.45 [1.10-1.90], p < 0.01), trabecular number (OR = 1.32 [1.01-1.72], p < 0.05), intra individual distribution of separation (OR = 0.73 [0.54-0.99], p < 0.05) as several FEA parameters were significantly associated with fractures. At the distal tibia, impaired cortical density (OR = 1.32 [1.03-1.70] per SD, p < 0.05) and thickness (OR = 1.29 [1.01-1.63], p < 0.05) and apparent modulus (OR = 1.30 [1.01-1.66], p < 0.05) were significantly correlated with fractures. A low ultra distal radial aBMD (UDR) measured at the time of HR-pQCT was significantly associated with fractures (OR = 1.67 [1.22-2.28], p < 0.01). Women from both groups were followed further after the realization of the HR-pQCT and 46 new fractures were registered. In this second part of the study, low UDR aBMD (OR = 1.66 [1.18-2.35], p < 0.01), total (OR = 1.48 [1.08-2.03], p < 0.05), cortical (OR = 1.40 [1.04-1.87], p < 0.05) and trabecular (OR = 1.37 [1.01-1.85], p < 0.05) densities or apparent modulus (OR = 1.49 [1.07-2.05], p < 0.05) at the radius were associated with a significant increase of fracture risk. At the tibia, only the cortical density was significantly associated with the fracture risk (OR = 1.34 [1.02-2.76], p < 0.05). These results confirm the interest of HR-pQCT measurements for the evaluation of fracture risk, also in women matched for their baseline FRAX score. They also highlight that UDR aBMD contains pertinent information.

Hyperglycemia Is Not Associated With Higher Volumetric BMD in a Chinese Health Check-up Cohort.

Background and Purpose: Type 2 diabetes mellitus patients have an increased fracture risk despite having higher areal bone mineral density (aBMD) measured by DXA. This apparent paradox might be explained by the overestimation of BMD by DXA due to the higher fat mass in type 2 diabetes mellitus patients. Volumetric BMD (vBMD) as assessed by quantitative CT (QCT) is not influenced by fat mass. We assessed the association of vBMD and fasting plasma glucose in a large cohort of Chinese subjects and compared the vBMD in healthy and diabetic subjects. In addition, we compared the relation between aBMD, vBMD, glucose and fat mass in a subset of this cohort. Materials and Methods: 10309 participants from the China Biobank project underwent QCT based on chest low dose CT to compute vBMD of L1 and L2 vertebrae and FPG measurements between 2018 and 2019. Among them, 1037 subjects also had spine DXA scans. Data was analyzed using linear regression models. Results: In the total cohort (5889 men and 4420 women, mean age 53 years, range 30-96), there was no significant association between vBMD and FPG after adjustment for age (women: p=0.774; men: p=0.149). 291 women and 606 men fitted the diagnostic criteria of diabetes. Both women and men with diabetes had lower vBMD compared to non-diabetic subjects, but this became non-significant after adjusting for age in the total cohort (women: p=0.817; men: p=0.288) and after propensity score matching based on age (women: p=0.678; men: p=0.135). In the DXA subcohort, aBMD was significantly higher in men with diabetes after adjusting for age and this difference disappeared after further adjusting for total fat area (p=0.064). Conclusion: We did not find any effect of fasting plasma glucose or diabetes on the volumetric BMD measured with QCT after adjustment for age. Therefore, vBMD measured with QCT might be a more reliable measurement to diagnose osteoporosis and assess fracture risk than aBMD measured with DXA in diabetic patients.

The quantitative ultrasound method for assessing low bone mass in women with anorexia nervosa.

This study investigated the potential role of quantitative ultrasound (QUS) to assess low bone mass in anorexia nervosa patients (AN). Bone parameters from QUS and DXA were positively correlated and significantly reduced in AN compared with controls, suggesting that QUS is a pertinent technique to assess low bone mass in these patients. PURPOSE: The aim of this study was to investigate the potential role of an alternative technique, quantitative ultrasound (QUS), to assess low bone mass in patients with anorexia nervosa (AN). METHODS: Two hundred seven young women (134 patients with AN and 73 healthy controls) with ages ranging from 14.4 to 38.4 years participated in this observational cross-sectional study. Bone mass was concomitantly evaluated by DXA to determine areal bone mineral density (aBMD; g/cm2) at hip, lumbar spine, and radius and by QUS to determine broadband ultrasound attenuation (BUA; dB/MHz) at the heel. RESULTS: BUA (66.5 ± 4.6 dB/MHz vs 61.0 ± 5.0 dB/MHz) and aBMD at the hip (0.916 ± 0.013 g/cm2 vs 0.806 ± 0.010 g/cm2), lumbar spine (0.966 ± 0.012 g/cm2 vs 0.886 ± 0.010 g/cm2), and radius (0.545 ± 0.005 g/cm2 vs 0.526 ± 0.04 g/cm2) were significantly decreased (p < 0.01) in patients with AN compared with controls. When patient and control data were pooled, BUA was significantly correlated with aBMD at the hip (r = 0.60, p < 0.001), lumbar spine (r = 0.48, p < 0.001), and radius (r = 0.40, p<0.001). In patients with AN, BUA and aBMD were mainly and positively correlated with weight, lean tissue mass, body mass index (BMI), and minimal BMI life and negatively with the duration of both disease and amenorrhea. Better concordance between the two techniques was obtained when absolute BUA and aBMD values were used according to the WHO T score classification. CONCLUSION: BUA measurement at the heel by QUS appears to be a pertinent nonionizing technique to assess low bone mass in patients with AN.