Trabecular Bone Score Reference Values for Children and Adolescents According to Age,Sex, and Ancestry

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n = 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r = 0.47) than for aBMD or BMAD Z-scores (r = 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).     

老年2型糖尿病患者骨密度及临床相关因素分析

目的 了解老年2型糖尿病患者骨密度的变化，初步探讨临床相关因素对骨密度变化的影响。方法 采用双能X线骨密度仪测定65例老年2型糖尿病患者及80例年龄、性别匹配的正常对照者腰椎及髋部骨密度，同时测定前者空腹血糖（FBG）、餐后2h血糖（PBG）、空腹C肽、餐后2hC肽、果糖胺（FA）、糖化血红蛋白（HBAle）、胆固醇（chol）、甘油三酯（TG）。结果 65例糖尿病患者各部位骨密度值均低于正常对照者，但仅腰椎降低有统计学意义（P〈0．05）；糖尿病组30例（45％）合并骨质疏松（OP）。OP与非0P组病程有显著性差异（P〈0．05）。结论 2型糖尿病会导致骨矿密度减低，并与糖尿病病程密切相关。     

DXA-Generated Z-Scores and T-Scores May Differ Substantially and Significantly in Young Adults

Central dual-energy X-ray absorptiometry (DXA) is the gold standard for non-invasive measurement of bone mineral density (BMD). Using this value and subject demographics, DXA software calculates T-scores and Z-scores. Professional society guidelines for the management of osteoporosis are based on T-scores and Z-scores, rather than on the actual BMD value. Although one expects T-scores and Z-scores to be very similar in young men and women for any given BMD measurement, little literature exists on this issue. Our clinical experience shows that some younger adult individuals (premenopausal women and men younger than 50 yr) have larger than expected difference between their DXA T-score and Z-score. This cross-sectional study evaluates the extent of this discordance between Z-scores and T-scores in a sample of 4275 men and women aged 20–49 yr. All subjects were scanned by central DXA using equipment manufactured by GE Lunar, GE, Madison, WI, or Hologic, Inc., Bedford, MA. Significant differences between Z-scores and T-scores were seen within individuals at the lumbar spine, total hip, femoral neck, and trochanter (p value < 0.001) for both DXA systems. Although these differences were less than half a standard deviation (SD) in most instances, the magnitude of difference was substantial at times, being 1 or more SD in up to 11% of cases (range: −1.95 to +1.54 SD). The smallest differences were seen at the total hip and the largest differences were seen at the femoral neck for both technologies. This is in part because there is no single standard Z-score definition, resulting in different methods of calculation across, and even within, DXA manufacturers. Standardization of Z-score definition and method of calculation is indicated. DXA Z-scores should be interpreted with caution in men and women aged 20–50 yr.     

Increased central adiposity is associated with pro-inflammatory immunoglobulin G N-glycans

Background

Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans.

主诉腰痛女性患者骨密度和骨质疏松患病率分析

目的研究主诉腰痛女性患者腰椎和髋部骨密度(BMD)测量的临床意义及骨质疏松(OP)患病率。方法采用扇形束双能X线骨密度仪(DEXA)测量主诉为腰痛的女性患者的腰椎和髋部BMD,并与对照组的BMD比较,同时比较其相应骨质疏松(OP)患病率。结果临床主诉以腰痛为主的女性病人腰椎及髋部BMD比以关节痛或全身痛为主诉者的低,(P＜0.05);主诉腰痛者各骨骼部位的OP检出率明显高于关节痛或全身痛者,且均与正常对照组有显著性差异(P＜0.05)。结论骨质疏松是女性腰痛病人就诊的主要原因之一,腰痛患者OP患病率较高;腰椎BMD测定是诊断骨质疏松症的重要手段。     

Sclerostin-Neutralizing Antibody Treatment Rescues Negative Effects of Rosiglitazone on Mouse Bone Parameters

Obesity, a growing pandemic, is a risk factor for many cancers and causes increased bone marrow adipose tissue (BMAT). in vitro studies and obese animal models suggest that BMAT contributes to cancer progression, but there is a lack of preclinical models to directly test BMAT's role in cancer. Overactivation of peroxisome-proliferator-activated receptor-γ (PPARγ) can skew bone formation and resorption rates, resulting in increased BMAT and trabecular bone loss. Thiazolidinediones (eg, rosiglitazone) are anti-diabetic therapies that promote adipogenesis through PPARγ activation. We investigated if rosiglitazone increases BMAT in an immunocompromised model, commonly used in cancer research, and if these effects could be reversed by co-administering a bone anabolic agent (sclerostin-neutralizing antibody [Scl-Ab]), which has been shown to inhibit adipogenesis, using DXA, μCT, OsO4 μCT, and dynamic histomorphometry. Four weeks of rosiglitazone in female SCID Beige mice (cohort 1) significantly decreased trabecular bone volume (BV/TV) by about one-half, through increased osteoclast and suppressed osteoblast activity, and significantly increased BMAT. In cohort 2, mice were administered rosiglitazone ± Scl-Ab for 4 weeks, and then rosiglitazone was discontinued and Scl-Ab or vehicle were continued for 6 weeks. Scl-Ab significantly increased bone parameters (eg, BV/TV, N.Ob/B.Pm, and MS/BS) in both groups. Scl-Ab also overcame many negative effects of rosiglitazone (eg, effects on trabecular bone parameters, increased mineralization lag time [MLT], and decreased bone formation rate [BFR]). Interestingly, Scl-Ab significantly decreased rosiglitazone-induced BMAT in the femur, mostly due to a reduction in adipocyte size, but had a much weaker effect on tibial BMAT. These data suggest targeting sclerostin can prevent rosiglitazone-induced bone loss and reduce BM adiposity, in some, but not all BMAT locations. Collectively, our data demonstrate that rosiglitazone increases BMAT in SCID Beige mice, but concomitant changes in bone may confound its use to specifically determine BMAT's role in tumor models. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Bone Radiomics Score Derived From DXA Hip Images Enhances Hip Fracture Prediction in Older Women

Dual-energy X-ray absorptiometry (DXA)-based bone mineral density testing is standard to diagnose osteoporosis to detect individuals at high risk of fracture. A radiomics approach to extract quantifiable texture features from DXA hip images may improve hip fracture prediction without additional costs. Here, we investigated whether bone radiomics scores from DXA hip images could improve hip fracture prediction in a community-based cohort of older women. The derivation set (143 women who sustained hip fracture [mean age 73 years, time to fracture median 2.1 years] versus 290 age-matched women [mean age 73 years] who did not sustain hip fracture during follow-up [median 5.5 years]) were split into the train set (75%) and the test set (25% hold-out set). Among various models using 14 selected features out of 300 texture features mined from DXA hip images in the train set, random forest model was selected as the best model to build a bone radiomics score (range 0 to 100) based on the performance in the test set. In a community-based cohort (2029 women, mean age 71 years) as the clinical validation set, the bone radiomics score was calculated using a model fitted in the train set. A total of 34 participants (1.7%) sustained hip fracture during median follow-up of 5.4 years (mean bone radiomics score 40 ± 16 versus 28 ± 12 in non-fractured, p < 0.001). A one-point bone radiomics score increment was associated with a 4% elevated risk of incident hip fracture (adjusted hazard ratio [aHR] = 1.04, p = 0.001) after adjustment for age, body mass index (BMI), previous history of fracture, and femoral neck T-score, with improved model fit when added to covariates (likelihood ratio chi-square 10.74, p = 0.001). The association between bone radiomics score with incident hip fracture remained robust (aHR = 1.06, p < 0.001) after adjustment for FRAX hip fracture probability. Bone radiomics scores estimated from texture features of DXA hip images have the potential to improve hip fracture prediction. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures,Falls, and Mortality,Independent of Prior Falls,FRAX, and BMD: Findings from the Women's Health Initiative (WHI)

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX^®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height²) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height² (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height² was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height² and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height², depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height² and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

The Accuracy of Incident Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches

Vertebral fractures are clinically important sequelae of a wide array of pediatric diseases. In this study, we examined the accuracy of case-finding strategies for detecting incident vertebral fractures (IVF) over 2 years in glucocorticoid-treated children (n = 343) with leukemia, rheumatic disorders, or nephrotic syndrome. Two clinical situations were addressed: the prevalent vertebral fracture (PVF) scenario (when baseline PVF status was known), which assessed the utility of PVF and low lumbar spine bone mineral density (LS BMD; Z-score <−1.4), and the non-PVF scenario (when PVF status was unknown), which evaluated low LS BMD and back pain. LS BMD was measured by dual-energy X-ray absorptiometry, vertebral fractures were quantified on spine radiographs using the modified Genant semiquantitative method, and back pain was assessed by patient report. Forty-four patients (12.8%) had IVF. In the PVF scenario, both low LS BMD and PVF were significant predictors of IVF. Using PVF to determine which patients should have radiographs, 11% would undergo radiography (95% confidence interval [CI] 8–15) with 46% of IVF (95% CI 30–61) detected. Sensitivity would be higher with a strategy of PVF or low LS BMD at baseline (73%; 95% CI 57–85) but would require radiographs in 37% of children (95% CI 32–42). In the non-PVF scenario, the strategy of low LS BMD and back pain produced the highest specificity of any non-PVF model at 87% (95% CI 83–91), the greatest overall accuracy at 82% (95% CI 78–86), and the lowest radiography rate at 17% (95% CI 14–22). Low LS BMD or back pain in the non-PVF scenario produced the highest sensitivity at 82% (95% CI 67–92), but required radiographs in 65% (95% CI 60–70). These results provide guidance for targeting spine radiography in children at risk for IVF. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Patient Outcomes in the Years After a DXA-BMD Treatment Monitoring Test: Improved Medication Adherence in Some,But Too Little Too Late

The role of mid-treatment monitoring dual-energy X-ray absorptiometry–bone mineral density (DXA-BMD) for bisphosphonate-treated patients with osteoporosis remains unsettled. A common reason for such monitoring is to encourage ongoing medication adherence. We sought to determine if a DXA-BMD treatment monitoring test was associated with improved medication adherence and whether improved adherence after a DXA-BMD treatment monitoring test was associated with subsequent reduction in fracture rates. Using linked administrative databases within Manitoba, Canada, we performed a retrospective cohort study of women starting and continuing antiresorptive therapy in whom a mid-treatment DXA-BMD monitoring test was performed. From the provincial pharmacy database, we estimated medication adherence by calculating annual medication possession ratio (MPR) and determining the change in MPR with respect to change (stable/decrease) in the DXA-BMD monitoring test, in addition to fracture rates before and after the test. The cohort comprised 3418 women, 90.7% treated with oral bisphosphonate, with pharmacy data for the 3 years before and after the mid-treatment DXA-BMD. Median (interquartile range) MPR was 0.84 (0.49–0.99) in the year before DXA-BMD and 0.84 (0.48–0.99) in the year after DXA-BMD (p = 0.37). Among those whose DXA-BMD declined, MPR in the prior year was 0.54 (0.04–0.92) but improved to 0.70 (0.31–0.92) in the year after DXA-BMD (p < 0.001). Among those whose DXA-BMD monitoring test was stable/improved, the fracture rate before the monitoring DXA-BMD was 10.1 per 1000 person-years and in those whose DXA-BMD monitoring test showed a decrease, the rate was 23.7 per 1000 person-years (p < 0.001). Despite improved adherence in those with DXA-BMD decline, the post DXA-BMD fracture rate was 22.4 per 1000 person-years versus 12.9 per 1000 person-years in those who had stable DXA-BMD (p < 0.001). A mid-treatment DXA-BMD reassessment strategy may be useful to focus attention upon adherence, but for optimal fracture outcomes, treatment adherence should be specifically addressed at the commencement of therapy. © 2021 American Society for Bone and Mineral Research (ASBMR).