DXA Data Research Articles

Modelling future bone mineral density: Simplicity or complexity?

BackgroundOsteoporotic fractures are a major global public health issue, leading to patient suffering and death, and considerable healthcare costs. Bone mineral density (BMD) measurement is important to identify those with osteoporosis and assess their risk of fracture. Both the absolute BMD and the change in BMD over time contribute to fracture risk. Predicting future fracture in individual patients is challenging and impacts clinical decisions such as when to intervene or repeat BMD measurement. Although the importance of BMD change is recognised, an effective way to incorporate this marginal effect into clinical algorithms is lacking. MethodsWe compared two methods using longitudinal DXA data generated from subjects with two or more hip DXA scans on the same machine between 2000 and 2018. A simpler statistical method (ZBM) was used to predict an individual's future BMD based on the mean BMD and the standard deviation of the reference group and their BMD measured in the latest scan. A more complex deep learning (DL)-based method was developed to cope with multidimensional longitudinal data, variables extracted from patients' historical DXA scan(s), as well as features drawn from the ZBM method. Sensitivity analyses of several subgroups was conducted to evaluate the performance of the derived models. Results2948 white adults aged 40–90 years met our study inclusion: 2652 (90 %) females and 296 (10 %) males. Our DL-based models performed significantly better than the ZBM models in women, particularly our Hybrid-DL model. In contrast, the ZBM-based models performed as well or better than DL-based models in men. ConclusionsDeep learning-based and statistical models have potential to forecast future BMD using longitudinal clinical data. These methods have the potential to augment clinical decisions regarding when to repeat BMD testing in the assessment of osteoporosis.

Value of different preoperative bone evaluation methods in predicting intraoperative screw insertion torque: a prospective clinical comparative trial

BACKGROUND CONTEXTEstablishing good screw-bone structural stability is conducive to reducing the risk of postoperative screw loosening. Screw insertion torque is an objective index for evaluating screw-bone structural stability. Therefore, accurate prediction of screw insertion torque can improve the preoperative evaluation of patients, optimize the surgical plan, and improve the surgical effect. At present, the correlation between different bone assessment methods and screw insertion torque is unclear. PURPOSEThe aim of this study was to evaluate the correlation between different bone assessment methods and screw insertion torque and to optimize the predictive performance of screw insertion torque through mathematical modeling combined with different radiology methods. DESIGNProspective cross-sectional study. PATIENT SAMPLESSeventy-seven patients with preoperatively available DXA, CT and MRI data who underwent spinal fixation surgeries between October 2022 and September 2023 and 357 sets of screw data were included in this analysis. OUTCOME MEASURESSpinal, vertebrae-specific and screw trajectory's BMD were measured preoperatively by different imaging modalities. Intraoperative screw insertion torque was measured using an electronic torque wrench. METHODSPearson linear correlation, scatter plots and univariate linear regression were used to evaluate the correlation between different bone evaluation methods and screw insertion torque. Different bone evaluation methods were fitted into the prediction model of screw torque and the related equations were obtained. RESULTSScrew insertion torque had the strongest positive correlation with the volumetric bone mineral density (vBMD) of the screw trajectory (Pedicle screw insertion torque (PSIT): R = 0.618, p<.001; Terminal screw insertion torque (TSIT): R = 0.735, p<.001). A weak negative correlation was found between the screw insertion torque and level specific vertebral bone quality (VBQ) (PSIT: R = -0.178, p=.001; TSIT: R = -0.147, p=.006). We also found that the PSIT was strongly correlated with the TSIT (R = 0.812, p<.001). CONCLUSIONSCompared to other bone quality assessment methods, screw trajectory vBMD may be better predict the magnitude of screw insertion torque. In addition, we further optimized preoperative assessments by constructing a mathematical model to better predict screw insertion torque. In conclusion, clinicians should select appropriate preoperative bone quality assessment methods, identify potential low-torque patients, optimize surgical plans, and ultimately improve screw insertion accuracy and reduce postoperative screw loosening rate.

Periprosthetic fractures are osteoporotic fractures: missed opportunities for osteoporosis diagnosis.

Periprosthetic fractures (PPFx) cause morbidity, mortality, and cost. This study's purpose was to describe osteoporosis-related data available at the time of PPFx. The electronic medical record (EMR) of PPFx patients seen over 4years in a university orthopedic practice were reviewed. Demographic data and osteoporosis relevant parameters were collected. Prior DXA studies were reviewed, and L1 Hounsfield unit (HU) measurements were performed on CT scans obtained within 2years before PPFx. Clinical osteoporosis was defined as prior diagnosis, prescribed osteoporosis treatment, T-score ≤ - 2.5, HU ≤ 100, or prior fracture. Records of 156 PPFx patients (115 F/41M), mean (SD) age 75.4 (11.9), were reviewed. Almost all 153/156 (98%) of these fractures were femoral. Falls caused 139 (89%); 12 (8%) were spontaneous. Mean time post-arthroplasty was 7.9 (6.3) years. Prior fragility fracture(s) occurred in 72 (46%); 14 were PPFx. Osteoporosis was previously diagnosed in 45 (29%) and medications prescribed in 41 (26%). Prior to PPFx, DXA data were available in 62, mean (SD) lowest T-score was - 1.9 (0.9) and was ≤ - 2.5 in 19. CT data were available in 46; mean (SD) L1 HU was 79.0 (29.4) and was ≤ 100 in 35. Based on existing data, clinical osteoporosis could have been diagnosed in 104 (67%) at the time of PPFx. Periprosthetic fractures are osteoporosis-related. They occur in older adults, often female, and result from falls; BMD, when assessed, is low. Data available at the time of PPFx often allows osteoporosis diagnosis; this should prompt evaluation and pharmacologic treatment consideration.

Fat-free mass predictive equation using bioelectrical impedance and maturity offset in adolescent athletes: Development and cross-validation

ObjectivesThis is a cross-sectional study, aimed to develop and cross-validate a fat-free mass (FFM) predictive equation using single-frequency bioelectrical impedance (BIA), considering the predicted age at peak height velocity (PHV) as a variable. Additionally, the study aims to test the FFM-BIA obtained using a previous predictive equation that used skeletal maturity as a variable. MethodThe participants (n = 169 male adolescent athletes) were randomly divided into two groups: development of a new predictive equation (n = 113), and cross-validation (n = 56). The concordance test between the FFM values obtained by Koury et al. predictive equation and DXA data was determined (n = 169). Bioelectrical data was obtained using a single-frequency analyzer. ResultsAmong the models tested, the new predictive equation has resistance index (height2/resistance) and predictive age at PHV as variables and presented R2 = 0.918. The frequency of maturity status using skeletal maturity and PHV diagnosis was inadequate (Kappa = 0.4257; 95%CI = 0.298–0.553). Bland-Altman plots and concordance correlation coefficient showed substantial concordance between the FFM-DXA values (48.8 ± 11.2 kg) and the new predictive equation (CCC = 0.960). The results showed that the new equation performed better than the equation developed by Koury et al. (CCC = 0.901). ConclusionsOur results show that it is feasible to predict FFM in male adolescent athletes using predictive age at PHV, with moderate concordance. The calculation of FFM using more economical and less complex variables is viable and should be further explored.

Sarcopenia and poor nutritional status in older adults

Background & aimsThe association between sarcopenia and malnutrition has been poorly studied in the older population. The purpose of this study is to address the association between sarcopenia, according to different validated definitions, and nutritional status in a large population of community-dwelling older adults. MethodsObservational, cross-sectional study of the Geriatric Frailty Clinic (GFC) for Assessment of Frailty and Prevention of Disability, held by the “Gérontopôle” of the Toulouse University Hospital. Patients aged above 65 years who benefitted from a Dual X-ray Densitometry (DXA) during their assessment at the GFC from June 5th 2013 to January 28th 2020 were included. Sarcopenia was defined according to proposed validated definitions. The Mini Nutritional Assessment (MNA) was used to stratify nutritional status, and identify patients with a poor nutritional status (at risk of malnutrition or malnourished, MNA <24). Multiple logistic regression analyses were performed between MNA and each sarcopenia definition adjusted for confounders. ResultsAmong the 938 patients with DXA data, a total of 809 (86.2%) subjects were included in the analysis (mean age 81.8 ± 6.9 years, 527 females (65.1%)). Prevalence of sarcopenia ranged from 12.6% to 44.9%, according to various definitions. Overall 244 (30.2%) of the patients had a poor nutritional status (MNA-score <24), Baumgartner and Newman definitions of sarcopenia were both associated with low MNA-scores (OR=4.69, CI 3.15-6.98 and OR=2.30, CI 1.55-3.14, respectively), EWGSOP2 “confirmed sarcopenia” definition was also associated with low MNA-scores (OR=3.68, CI 2.30-5.89), as well as for the lean mass definition according EWGSOP2 cut-off (OR 5.22 CI 3.52-7.73). Both FNIH and EWGSOP2 “probable sarcopenia” definitions were not associated with the risk of malnutrition. ConclusionsIn this study, the prevalence of sarcopenia ranged from 12.6 to 44.9% according to various definitions. A score of MNA under 24, was associated with almost all of the sarcopenia definitions. This study reinforces the concept that malnutrition and sarcopenia are strictly related. When facing malnutrition in daily clinical practice, body composition should be assessed and the proposed nutritional intervention should be tailored by these results in order to prevent the onset of late-life disability.

Estimation of Absolute and Relative Body Fat Content Using Noninvasive Surrogates: Can DXA Be Bypassed?

Dual-energy x-ray absorptiometry (DXA) scanning is used for objective determination of body composition, but instrumentation is expensive and not generally available in customary clinical practice. Anthropometric surrogates are often substituted as anticipated correlates of absolute and relative body fat content in the clinical management of obesity and its associated medical risks. DXA and anthropometric data from a cohort of 9230 randomly selected American subjects, available through the ongoing National Health and Nutrition Examination Survey, was used to evaluate combinations of surrogates (age, height, total weight, waist circumference) as predictors of DXA-determined absolute and relative body fat content. Multiple regression analysis yielded linear combinations of the 4 surrogates that were closely predictive of DXA-determined absolute fat content (R2 =0.93 and 0.96 for male and female subjects). Accuracy of the new algorithm was improved over customary surrogate-based predictors such as body mass index. However prediction of relative body fat was less robust (R2 less than0.75), probably due to the nonlinear relation between degree of obesity (based on body mass index) and relative body fat. The paradigm was validated using an independent cohort from the National Health and Nutrition Examination Survey, as well as two independent external subject groups. The described regression-based algorithm is likely to be a sufficiently accurate predictor of absolute body fat (but not relative body fat) to substitute for DXA scanning in many clinical situations. Further work is needed to assess algorithm validity for subgroups of individuals with "atypical" body construction.

Bone mineral density and fractures in patients with rheumatoid arthritis: the DXA-HIP project.

RA is a chronic disabling disease affecting 0.5-1% of adults worldwide. People with RA have a greater prevalence of multimorbidity, particularly osteoporosis and associated fractures. Recent studies suggest that fracture risk is related to both non-RA and RA factors, whose importance is heterogeneous across studies. This study seeks to compare baseline demographic and DXA data across three cohorts: healthy controls, RA patients and a non-RA cohort with major risk factors and/or prior major osteoporotic fracture (MOF). This is a cross-sectional study using data collected from three DXA centres in the west of Ireland from January 2000 to November 2018. Data were available for 30 503 subjects who met our inclusion criteria: 9539 (31.3%) healthy controls, 1797 (5.9%) with RA and 19 167 (62.8%) others. Although age, BMI and BMD were similar between healthy controls, the RA cohort and the other cohort, 289 (16.1%) RA patients and 5419 (28.3%) of the non-RA cohort had prior MOF. In the RA and non-RA cohorts, patients with previous MOF were significantly older and had significantly lower BMD at the femoral neck, total hip and spine. Although age, BMI and BMD were similar between a healthy control cohort and RA patients and others with major fracture risk factors, those with a previous MOF were older and had significantly lower BMD at all three measured skeletal sites. Further studies are needed to address the importance of these and other factors for identifying those RA patients most likely to experience fractures.

#5440 BONE TURNOVER MARKERS AND BONE MINERAL DENSITY 1 YEAR AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Alterations of bone metabolism are a hallmark of chronic kidney disease (CKD) patients and do not completely ameliorate after kidney transplantation. In the setting of a secondary analysis of a RCT, we evaluated changes of bone turnover biomarkers (BTM) and their associations with changes of bone mineral density (BMD) as assessed by DXA. Method Sixty-six Kidney Transplant (KTx) recipients were enrolled between 2014-2017. In these patients, at baseline (T0) and 12 months (T12) we measured BTM (Figure 1). The prevalence of vitamin K deficiency was assessed based on undercarboxylated-BGP (uc-BGP) cut-off: &amp;gt; = 4.5 ng/ml, whilst dephosphorylated-ucMGP (dp-ucMGP) we considered a cut-off &amp;gt;500 pmol/L levels. DXA data were assessed at lumbar spine, femoral neck, total hip, one-third and ultradistal radius both baseline and after one year, evaluating the changes in areal BMD (aBMD). Results were expressed as mean ±SD or median and inter-quartile range, as appropriate. Correlations were investigated by Spearman's analysis. Results The mean age of enrolled patients was 51± 13 years, 34% were female. BMI was on average 27.8 ± 5.5 kg/m2. 24 patients (39.3%) were pre-emptive and 37 (60.7%) on dialysis and 19% of patients had a history of fracture. In Figure 1 the trend of BTM 1 year after KTx. We highlighted a significant reduction of PTH, CTX, P1NP, and VKDPs. This latter while improving but was not completely restored. Table 1 shows the correlations between the percentage variation of BTM and percentage variation of BMD at several sites evaluated. Conclusion In the first-year post-transplant, along with the improvement of renal function, PTH values were reduced as well those of CTX and P1NP. Moreover, we observed an inverse correlation between BTM and BMD, the reduction of bone turnover expressed by the trend of BTM translates into an improvement of BMD.

Dp-ucMGP as a Biomarker in Sarcopenia.

Sarcopenia is linked with an increased risk of falls, osteoporosis and mortality and is an increasing problem for healthcare systems. No satisfying biomarkers for sarcopenia diagnosis exist, connecting bone, fat and muscle. Matrix-GLA-protein (MGP) is an adipokine that regulates bone metabolism and is associated with decreased muscle strength. Associations of dp-ucMGP were analyzed in the BioPersMed cohort (58 ± 9 years), including 1022 asymptomatic subjects at moderate cardiovascular risk. Serum measurements of dp-ucMGP in 760 persons were performed with the InaKtif MGP Kit with the IDS-iSYS Multi-Discipline Automated System. DXA data (792 persons) measured with the Lunar iDXA system and physical performance data (786 persons) were available. Dp-ucMGP plasma levels correlate with sarcopenia parameters like gait speed (ρ = −0.192, p < 0.001), appendicular skeletal muscle mass (ρ = 0.102, p = 0.005) and appendicular skeletal muscle mass index (ρ = 0.112, p = 0.001). They are lower in persons with sarcopenia (p < 0.001) and higher in persons with reduced physical performance (p = 0.019). Persons in the lowest dp-ucMGP quartile have the highest risk for reduced muscle mass, decreasing with each quartile, whereas persons in the highest quartile have the highest risk of reduced muscle strength. Dp-ucMGP might be a good biomarker candidate in sarcopenia characterization.

RF12 | PSUN80 A Novel DXA Algorithm to Aid in the Diagnosis of Familial Partial Lipodystrophy

Abstract Familial partial lipodystrophy (FPLD) is a rare and heterogenous disease without gold-standard diagnostic criteria. The heterogeneity applies to fat distribution, symptomatology, metabolic complications, and genetic etiology. Disease heterogeneity has contributed to the lack of standardized diagnostic criteria, an obstacle to understanding both the natural history of the disease and response to therapies. We have assessed whether DXA data can aid in disease diagnosis. DXA scans quantify fat and lean mass in the whole body, arms, legs, and trunk. An increased ratio of fat percentage in the trunk to the legs (termed "trunk-leg ratio", TLR) has been proposed as an objective method to detect FPLD. Using large sets of DXA data from control subjects, along with data from FPLD subjects, we sought to improve upon TLR. We hypothesized that TLR might change as a function of overall adiposity (total body fat, TF). Females were studied first because of the high female: male ratio of disease prevalence observed in FPLD. In 2713 control females with DXA measurements within the UKBiobank (UKB), TLR increased linearly as a function of TF until a TF of ∼36% and then the TLR plateaued with higher TF. We analyzed published DXA data of FPLD subjects from the USA (n=55).1 FPLD subjects had higher TLRs than controls at each level of adiposity. Due to the non-linear relationship between total adiposity and TLR, two linear fits were generated to best discriminate controls from FPLD subjects for a given adiposity. For females with body fat &amp;lt;36%, the algorithm predicts FPLD if TLR &amp;gt;TF*0.0311+0.232. For females with body fat ≥36%, the algorithm predicts FPLD if TLR &amp;gt;1.353. After training on this UKB data set, we tested the algorithm on independent data sets of control females from NHANES (n=2347) and FPLD subjects (n=37, from the NIH). The algorithm had a sensitivity of 92–97% and a specificity of 99.3%. This degree of specificity is still not sufficient for implementation of rare disease screening in the general population, but could be useful in a population with increased pre-test probability of having FPLD such as non-obese individuals with Type 2 diabetes and/or hypertriglyceridemia. Because race and ethnicity are possible modifiers of body fat distribution, we examined the relationship between TF and TLR across ethnic and racial groups in NHANES. Mexican-Americans (n=659), Hispanic-other (n=81), White (n=871), Black (n=612), and other/biracial (n=124) subjects from NHANES had a similar relationship between adiposity and TLR. Therefore, the same DXA criteria can be applied across these ethnicities. In summary, the relationship between adiposity and TLR may be used to aid in the diagnosis of FPLD in females. Reference Meral R, et al. Diabetes Care. 2018;41,2255–2258. Presentation: Saturday, June 11, 2022 1:06 p.m. - 1:11 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Bone marrow transplantation as a therapy for autosomal dominant osteopetrosis type 2 in mice.

Autosomal dominant osteopetrosis type II (ADO2) is a heritable bone disease of impaired osteoclastic bone resorption caused by missense mutations in the chloride channel 7 (CLCN7) gene. Clinical features of ADO2 include fractures, osteomyelitis of jaw, vision loss, and in severe cases, bone marrow failure. Currently, there is no effective therapy for ADO2, and patients usually receive symptomatic treatments. Theoretically, bone marrow transplantation (BMT), which is commonly used in recessive osteopetrosis, could be used to treat ADO2, although the frequency of complications related to BMT is quite high. We created an ADO2 knock-in (p.G213R mutation) mouse model on the 129 genetic background, and their phenotypes mimic the human disease of ADO2. To test whether BMT could restore osteoclast function and rescue the bone phenotypes in ADO2 mice, we transplanted bone marrow cells from 6-8 weeks old male WT donor mice into recipient female ADO2 mice. Also, to determine whether age at the time of transplant may play a role in transplant success, we performed BMT in young (12-week-old) and old (9-month-old) ADO2 mice. Our data indicate that ADO2 mice transplanted with WT marrow achieved more than 90% engraftment up to 6 months post-transplantation at both young and old ages. The in-vivo DXA data revealed that young ADO2 mice transplanted with WT marrow had significantly lower whole body and spine areal bone mineral density (aBMD) at month 6 post-transplantation compared to the ADO2 control mice. The old ADO2 mice also displayed significantly lower whole body, femur, and spine aBMD at months 4 and 5 post-transplantation compared to the age-matched control mice. The in-vivo micro-CT data showed that ADO2 experimental mice transplanted with WT marrow had significantly lower BV/TV at months 2 and 4 post-transplantation compared to the ADO2 control mice at a young age. In contrast, ADO2 control and experimental mice displayed similar BV/TV values for all post-transplantation time points at old age. In addition, serum CTX was significantly higher at month 2 post-transplantation in both young and old ADO2 experimental mice compared to the ADO2 control mice. Serum P1NP levels in young ADO2 experimental mice were significantly higher at baseline and month 2 post-transplantation compared to the ADO2 control mice. These data suggest that BMT may provide, at least, some beneficial effect at both young and adult ages.

Peculiarities of the structural and functional state of bone tissue in children during the second growth spurt

Background. Bone health is relevant for patients of all age groups. Special attention is paid to childhood and adolescence, since it is during this period that bone mass is actively accumulated, which depends on the structural and functional state of the bone tissue of an adult. The purpose of this study was to determine the features of the structural and functional state of bone tissue in children during the second growth spurt based on the analysis of markers of bone modeling, the level of 25(OH)D and the indicators of ultrasound densitometry and DXA. Materials and methods. 205 children aged 9–17 years were examined. They divided into three groups depending on the presence and intensity of growth spurts. Examination included: general clinical examination with an assessment of the levels of physical and sexual development, determine of the levels of 25(OH)D, glycosaminoglycans, chondroitin sulfates and alkaline phosphatase, ultrasound densitometry and DXA. Results. 83.9 % of children had vitamin D deficiency, 16.1 % of children had insufficiency. A decrease in BMD according to UD data was diagnosed in 48.0 % (n = 24) of children with growth spurt, in 60.87 % (n = 28) of children with intense growth spurt, and in 39.45% (n = 43) of children without growth spurt. According to DXA data, BMD reduction was confirmed in 56.25 % (n=18) of 32 examined children: children with growth spurt — 38.9 % (n=7), children with intense growth spurt— 50.0% (n = 9), children without growth spurt — 11.1 % (n = 2). The level of chondroitin sulfates in children with growth spurt and intense growth spurt is significantly higher than in children without growth spurt, which indicates the instability of metabolic processes. At the same time, the level of total glycosaminoglycans is significantly lower in the group of children with growth spurt and intense growth spurt than in the group of children without growth spurt, which indicates the intensity of metabolic processes in children of these groups. Conclusions. 100 % of children had insufficiency and deficiency of vitamin D. A decrease in BMD is more often diagnosed in children during an intense growth spurt and does not have a reliable relationship with the level of vitamin D, in contrast to children without a growth spurt. Children with growth spurts and intense growth spurts had an imbalance in the level of chondroitin sulfates and glycosaminoglycans, which indicates the instability and activity of bone tissue growth processes.

Risk factors associated with osteoporosis and fracture in psoriatic arthritis.

Background:Although there are few studies mentioned there may be some relationship between psoriatic arthritis (PsA) and osteoporosis, clinical data in real world still need to be clarified in China. The aim of this study was to assess the areal and volumetric bone mineral density (BMD), frequency of fracture, and risk factors in patients with PsA.Methods:A total of one hundred PsA patients who visited Peking University First Hospital and one hundred age- and sex-matched healthy controls with DXA data were enrolled in the study. Patients with clinical fractures confirmed by X-ray during follow-up were also recorded. Clinical characteristics of the patients were recorded and compared between the abnormal BMD group and the normal BMD group, as well as between the fracture and non-fracture groups. Risk factors for fracture and low BMD were analyzed.Results:Mean BMD at the total hip and femoral neck was significantly lower in PsA patients than that in healthy controls (0.809 ± 0.193 vs. 0.901 ± 0.152 g/cm2, P = 0.041; 0.780 ± 0.146 vs. 0.865 ± 0.166 g/cm2, P = 0.037, respectively). Moreover, lumbar spine BMD was negatively correlated with psoriasis duration, swollen joint count and DAS28-CRP (r = –0.503, –0.580, –0.438; P < 0.05). Total hip BMD and femoral neck BMD were negatively correlated with HAQ (r = –0.521, –0.335; P < 0.05). Fractures occurred in 29 patients during the follow-up period. Logistic regression analysis showed that older age (OR 1.132 [95%CI: 1.026–1.248), P < 0.05], higher HAQ score (OR 1.493, 95%CI: 1.214–1.836, P < 0.01), higher disease activity index for psoriatic arthritis (OR 1.033, 95% CI: 1.002–1.679, P < 0.05) and hip joint involvement (OR 6.401, 95% CI: 4.012–44.180, P < 0.05) were risk factors for fracture in the multivariate model.Conclusions:Increased risks of osteoporosis and fracture were found in PsA patients compared to healthy controls. Besides age, high disease activity and hip joint involvement were risk factors for decreased BMD and fracture.

Adiposity and mortality in Korean adults: a population-based prospective cohort study

The Asia-Pacific obesity classification recommends using lower BMI cutoffs in Asians compared with those in Western populations. However, the supporting evidence is scarce and little is known about the exact shape of the relations between adiposity and mortality in Asians. We investigated the relations of BMI (in kg/m2), waist circumference, and predicted body fat mass with mortality using a population-based prospective cohort of Korean men and women. This analysis included 44,060 Korea National Health and Nutrition Examination Survey 2007-2014 participants who agreed to mortality follow-up through 31 December, 2016. At baseline, height, weight, and waist circumference were measured. Using DXA data, we derived predicted body fat and fat-free mass. Cox proportional hazards models were used to estimate HRs and 95% CIs for the associations with mortality, adjusting for potential confounders. We tested for nonlinearity using the likelihood ratio test comparing nonlinear restricted cubic spline models with linear models. During ≤9.5 y of follow-up, 1682 deaths were identified. The relations of BMI with all-cause and cardiovascular mortality were J-shaped with the nadir at BMI=25.0-29.9 (P-nonlinearity<0.001). Among participants without a history of cancer or cardiovascular disease, waist circumference (≥95 compared with 75.0-79.9 cm: HR: 2.10; 95% CI: 1.54, 2.86) and predicted body fat mass (highest compared with lowest sextiles: 2.55; 95% CI: 1.60, 4.06) were positively associated with all-cause mortality (all P-nonlinearity≤0.03), as well as cancer and cardiovascular mortality. The highest mortality was observed among participants who had both high predicted fat mass and low fat-free mass. Our data suggest a strong positive association between adiposity and mortality in a population without pre-existing disease. We observed the lowest mortality at BMI=25.0-29.9, suggesting that the current cutoff for overweight (BMI ≥23) may require re-evaluation and that BMI alone may not be a useful measure for indicating adiposity in Asians.

Development of new adjusted equations to estimate the skeletal muscle mass stratified by nutritional status for patients with rheumatoid arthritis: a methodological study

Abstract Our objective was to adjust and validate predictive equations for appendicular skeletal muscle mass (ASM) in patients with Rheumatoid Arthritis (RA). Whole-body DXA data in 90 RA patients were used for measurement of ASM (kg). The prediction equation anthropometric for muscle mass proposed by Lee et al was used to generate estimates of ASM. Appendicular skeletal muscle mass index (ASMI, kg/m2) was calculated. Frequency analysis, Paired student's t-test, Linear regression, Pearson correlation, Intraclass correlation coefficients, and Bland-Altman scatter were performed. The statistical significance considered was p&lt;0.05. Lee’s equation was overestimated by 30% when compared with ASMI by DXA. When stratified by nutritional status, Lee’s equation overestimated the ASMI by 30% in overweight patients and by 50% in obese patients when compared with DXA (p&lt;0.05). These adjusted equations estimated values for ASMI were closer to those obtained by DXA than those estimated by the original Lee’s equation (p&lt;0.05). This greater concordance was confirmed by the observed interclass correlation coefficients and by Bland-Altman scatter graphs. In conclusion, the prediction of muscle mass in RA patients may be performed with equations that consider the nutritional status of patients.

Frequency of normal bone measurement in postmenopausal women with fracture: a registry-based cohort study.

Some fractures occur in women with normal BMD. We hypothesized that adding trabecular bone score (TBS) to DXA would (1) demonstrate that few women with fracture have normal bone, i.e., normal BMD T-score and TBS and (2) increase the percentage of women with fracture that have abnormal bone defined as a BMD T-score ≤ - 2.5 or low TBS. The public healthcare system in Manitoba, Canada, makes it possible to link clinical DXA data to population databases. This study included all women age 50+ with a first DXA from February 1999 to March 2018 with valid BMD, TBS, and fracture data. Bone status was defined as Normal = BMD T-score of the spine, femoral neck, and total femur ≥ - 1.0 AND TBS > 1.31; Abnormal = BMD T-score ≤ - 2.5 OR TBS < 1.23; and borderline = all others. Analyses were stratified by age decade. Among women with prior (n = 4649) or incident (n = 2547) fracture, bone status assessed by both BMD and TBS was normal in only 6% and 4%, respectively. In women with prior or incident hip fracture, normal bone was present in < 1%. The prevalence of normal bone declined (p trend < 0.001) with age as expected. BMD T-score osteoporosis was present in 40% with any prior and 46% with any incident fracture. BMD T-score osteoporosis was present in 65% and 60% with prior and incident hip fracture, respectively. Including TBS with BMD increased the percentage of women with abnormal bone to 61% and 68% for any prior or incident fracture and to 80% and 81% for prior or incident hip fracture, respectively (all p < 0.001). Including TBS with BMD increases identification of abnormal bone in women with fracture compared with BMD alone. Normal bone is present in < 6% of women with any fracture and < 1% of those with hip fracture. What is thought to be normal bone in women with fracture is rarely normal.

The problem of mismatches between CT scan and DXA results

Background. It is reported that radiodensity measured in Hounsfield units becomes more and more popular in bone property assessment, however also mismatch with DXA results is observed.Purpose. The aim of this study is to evaluate the relationships between the results of DXA and CT with a focus on explanations for observed discrepancies.Material and methods. This is a cross-sectional study; forty patients were enrolled, all patients underwent DXA and CT. A bone mineral density BMD (g/cm2 ) was calculated for each vertebra of a lumbar spine (L1-L4 inclusive), neck, upper neck, shaft, Wards triangle and trochanter of hip. Bone radiodensity in HU was taken from each vertebral body in the sagittal, axial and coronal planes. A total vertebra body radiodensity including cortical bone and radiodensity of only cancellous bone were calculated. To assess a potential impact on DXA and CT data agreement a mean radiodensity and square of the right and left vertebral pedicles and facet joints were measured for each vertebra.Results. A strong correlation between BMD measured using DXA and CT data was estimated with a multiply r accounting for 0,84169, p&lt;0,0001, however the most contributing parameters were those calculated for facet joints. It has been detected that both radiodensity of only a cancellous bone and total have a weak correlation with matching BMD measurements of a proximal femur.Conclusion. The results of DXA could be strongly influenced by hypertrophic changes of facet joints. Both CT and DXA measurements taken from a lumbar spine may have a mismatch with figures taken from hip.

Biological sex variation in bone mineral density in the cranium and femur

ObjectivesSex and age trends in bone mineral density (BMD) play an important role in the estimation of age-at-death (AAD) of unidentified human remains. Current methodologies lack the ability to precisely estimate age in older individuals. In this study, BMD of the cranium and femur measured by DXA were examined to establish their applicability for age estimation in older adults. BMD as measured by DXA, is most commonly used clinically for prediction of osteoporotic fracture risk. We hypothesized that weight-bearing and non-weight-bearing bones, the femur and cranium, respectively, would provide valuable insights for aging. MethodsThe sample consists of 32 sets of excised cranial fragments from the Regional Forensic Center, Johnson City, Tennessee and 41 associated crania and femora from the North Carolina Office of the Chief Medical Examiner. All crania and femora were scanned using a Hologic (R) DXA scanner and data were analyzed using Student t-tests, Loess regression, and ANOVA. ResultsStudent t-tests indicate a significant relationship between the sexes and cranial BMD and a significant relationship between age cohorts and femoral neck BMD. The Loess regression showed different aging patterns in the cranium for females and males older than 55. And the ANOVA showed changes in femoral neck after age 55. ConclusionsThese results indicate age and sex dependent changes in BMD especially for individuals over the age of 55, which offers improvement from current aging methods for older individuals. Further research using a larger sample size could improve the predictive capabilities of the model.

Development of Novel Methods to Define Deficits in Appendicular Lean Mass Relative to Fat Mass.

BackgroundRecent studies suggest that adjustment of measures of lean mass for adiposity improves associations with physical function. Our objective was to develop and test a method to adjust appendicular lean mass for adiposity.MethodsWhole-body DXA data in 14,850 adults in the National Health and Nutrition Examination Survey were used to generate sex-, and race-specific standard deviation scores (Z-Scores relative to age and T-scores relative to 25 year-olds) for appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2). Correlations between ALMI and FMI Z- and T-Scores were assessed within demographic categories. Fat-adjusted ALMI (ALMIFMI) scores were determined using residual methods. Sarcopenia was defined as a T-Score <-2.0 and low lean for age as a Z-Score <-1.0. Correlations with physical function were assessed in an at-risk population.ResultsPositive associations between ALMI and FMI Z- and T-Scores were significant (R >0.50; p<0.001) within all demographic categories. The impact of a unit greater FMI Z-score on ALMI Z-score was less in the elderly, men, white subjects, and among individuals with lower FMI (all tests for interaction p<0.001). There was fair agreement between ALMI and ALMIFMI estimates of sarcopenia and low lean for age [Kappa: 0.46, 0.52, respectively (p<0.0001)]. Elderly subjects were likely to be re-classified as sarcopenic while young subjects were likely to be re-classified as normal using ALMIFMI. ALMIFMI T-scores resulted in approximately twice the number of subjects defined as sarcopenic, compared with ALMI T-Scores. (1299 v. 534). Among rheumatoid arthritis patients, ALMIFMI Z-scores correlated with physical function (Health Assessment Questionnaire: rho = -0.22, p = 0.04; Short Physical Performance Battery: rho = 0.27, p = 0.01); however, the ALMI Z-Score did not.ConclusionsAdjustment of ALMI for the confounding association with FMI impacts the definition of lean mass deficits. These methods provide a practical tool for investigators and clinicians based on population-based reference data.

Proportion of osteoporotic women remaining at risk for fracture despite adherence to oral bisphosphonates

BackgroundAdherence to oral bisphosphonates is often low, but even adherent patients may remain at elevated fracture risk. The goal of this study was to estimate the proportion of bisphosphonate-adherent women remaining at high risk of fracture. MethodsA retrospective cohort of women aged 50years and older, adherent to oral bisphosphonates for at least two years was identified, and data were extracted from a multi-system health information exchange. Adherence was defined as having a dispensed medication possession ratio≥0.8. The primary outcome was clinical occurrence of: low trauma fracture (months 7–36), persistent T-score≤−2.5 (months 13–36), decrease in bone mineral density (BMD) at any skeletal site≥5%, or the composite of any one of these outcomes. ResultsOf 7435 adherent women, 3110 had either pre- or post-adherent DXA data. In the full cohort, 7% had an incident osteoporotic fracture. In 601 women having both pre- and post-adherent DXA to evaluate BMD change, 6% had fractures, 22% had a post-treatment T-score≤−2.5, and 16% had BMD decrease by ≥5%. The composite outcomes occurred in 35%. Incident fracture was predicted by age, previous fracture, and a variety of co-morbidities, but not by race, glucocorticoid treatment or type of bisphosphonate. ConclusionDespite bisphosphonate adherence, 7% had incident osteoporotic fractures and 35% had either fracture, decreases in BMD, or persistent osteoporotic BMD, representing a substantial proportion of treated patients in clinical practices remaining at risk for future fractures. Further studies are required to determine the best achievable goals for osteoporosis therapy, and which patients would benefit from alternate therapies.