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Li Xu,1,* Yanping Gong,2,* Qian Zhao,3 Glen M Blake,4 Kai Li,1 Yong Zhang,1 Qianqian Liu,2 Chunlin Li,2 Xiaoguang Cheng1 1Department of Radiology, Beijing Jishuitan Hospital, Beijing, People’s Republic of China; 2Department of Endocrinology, the Second Medical Center, the Chinese People’s Liberation Army General Hospital, National Clinical Research Center for Geriatric Disease, Beijing, 100853, People’s Republic of China; 3International Medical Center, Sichuan University West China Hospital, Chengdu, People’s Republic of China; 4Biomedical Engineering Department, King’s College London, London, UK*These authors contributed equally to this workCorrespondence: Xiaoguang Cheng, Department of Radiology, Beijing Jishuitan Hospital, Beijing, 100035, People’s Republic of China, Email xiao65@263.net Chunlin Li, Department of Endocrinology, the Second Medical Center, the Chinese People’s Liberation Army General Hospital, National Clinical Research Center for Geriatric Disease, Beijing, 100853, People’s Republic of China, Email lichunlin301@163.comPurpose: To investigated the factors that influence BMAC.Patients and Methods: Quantitative computed tomography (QCT) and magnetic resonance imaging (MRI) were applied to measure abdominal fat areas, liver fat content, erector muscle fat content, and BMAC of the L2-4 vertebrae. Sex hormone, adipokine, and inflammatory factor levels were measured on the same day.Results: Although age, erector muscle fat content, estradiol, testosterone, and adiponectin/leptin levels showed correlations with BMAC in the correlation analysis, the equations obtained from the whole population by multivariate analysis were unclear. Patients were stratified according to BMAC quartiles, and differences were found in vBMD, age, estradiol, testosterone, and erector muscle fat content among the four quartiles. Logistic analyses confirmed that age, estradiol/testosterone ratio, and TNF-α had independent effects on BMAC in all quartiles. In addition, height was related to higher BMAC quartiles, and glucose was related to lower BMAC quartiles.Conclusion: Compared to other body fats, BMAC is a unique fat depot. Age, estradiol/testosterone ratio, and TNF-α are all key influencing factors related to BMAC in postmenopausal women. Furthermore, height and glucose levels were related to BMAC in the higher and lower BMAC quartiles, respectively.Keywords: bone marrow adiposity, postmenopausal women, age, adipokines, sex hormones

Unlabelled: The assessment of regional skeletal metabolism using (18)F-fluoride PET ((18)F-PET) requires segmentation of the tissue region of interest (ROI). The aim of this study was to validate a novel approach to define multiple ROIs at the proximal femur similar to those used in dual x-ray absorptiometry. Regions were first drawn on low-dose CT images acquired as a routine part of the PET/CT study and transferred to the (18)F-PET images for the quantitative analysis of bone turnover. Methods: Four healthy postmenopausal women with a mean age of 65.1 y (range, 61.8-70.0 y), and with no history of metabolic bone disorder and not currently being administered treatment affecting skeletal metabolism, underwent dynamic (18)F-PET/CT at the hip with an injected activity of 180 MBq. The ROIs at the proximal femur included femoral shaft, femoral neck, and total hip and were segmented using both a semiautomatic method and manually by 8 experts at manual ROI delineation. The mean of the 8 manually drawn ROIs was considered the gold standard against which the performances of the semiautomatic and manual methods were compared in terms of percentage overlap and percentage difference. The time to draw the ROIs was also compared. Results: The percentage overlaps between the gold standard and the semiautomatic ROIs for total hip, femoral neck, and femoral shaft were 86.1%, 37.8%, and 96.1%, respectively, and the percentage differences were 14.5%, 89.7%, and 4.7%, respectively. In the same order, the percentage overlap between the gold standard and the manual ROIs were 85.2%, 39.1%, and 95.2%, respectively, and the percentage differences were 19.9%, 91.6%, and 12.2%, respectively. The semiautomatic method was approximately 9.5, 2.5, and 67 times faster than the manual method for segmenting total-hip, femoral-neck, and femoral-shaft ROIs, respectively. Conclusion: We have developed and validated a semiautomatic procedure whereby ROIs at the hip are defined using the CT component of an (18)F-PET/CT scan. The percentage overlap and percentage difference results between the semiautomatic method and the manual method for ROI delineation were similar. Two advantages of the semiautomatic method are that it is significantly quicker and eliminates some of the variability associated with operator or reader input. The tube current used for the CT scan was associated with an effective dose 8 times lower than that associated with a typical diagnostic CT scan. These results suggest that it is possible to segment bone ROIs from low-dose CT for later transfer to PET in a single PET/CT procedure without the need for an additional high-resolution CT scan. [ABSTRACT FROM AUTHOR]

Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of metabolic bone diseases and the response of patients to treatment. The advantage of nuclear medicine imaging as a way of measuring the rate of bone remodeling is that either the whole skeleton or discrete regions of interest (ROIs) may be studied depending on whether there is diffuse or localized disease. This article reviews methods of quantifying (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) kinetics based on a standard bone scan examination by measuring the plasma clearance of tracer to the whole skeleton and/or selected ROIs drawn on the bone scan image. Although the measurement of bone plasma clearance requires blood sampling to find the input curve for free (eg, nonprotein bound) (99m)Tc-MDP, we argue that plasma clearance studies give a more physiological approach in a better accord with the underlying changes in bone turnover than conventional measurements of whole-body retention or bone uptake. We describe 3 methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)): (1) the area under the curve (AUC) method based on taking 6 blood samples at 5, 15, 60, 120, 180, and 240 minutes and measuring the plasma concentration of free (99m)Tc-MDP by ultrafiltration using a 30-kDa filter. The AUC method requires a simultaneous measurement of glomerular filtration rate using (51)Cr-EDTA as a cotracer; (2) the modified Brenner method, which measures K(bone) by drawing a soft-tissue ROI over the adductor muscles and plotting the soft tissue counts at 1, 2, 3, and 4 hours against the AUC values at the corresponding time points; (3) the Patlak method based on combining gamma camera measurements of whole-body retention with plasma data and measuring K(bone) from the slope of the Patlak plot fitted to the 2, 3, and 4 hours data points. Unlike the first 2 methods, the Patlak plot can also be used to measure regional values of K(bone) for any chosen ROI. Initial studies have shown good agreement between the 3 methods of measuring K(bone), and highly significant correlations between the change in K(bone) values during treatment and the corresponding changes in serum and urinary measurements of biochemical markers of bone formation and bone resorption. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic performance of post-contrast CT for predicting moderate hepatic steatosis in an older adult cohort undergoing a uniform CT protocol, utilizing hepatic and splenic attenuation values., Materials and Methods: A total of 1676 adults (mean age, 68.4 ± 10.2 years; 1045M/631F) underwent a CT urothelial protocol that included unenhanced, portal venous, and 10-min delayed phases through the liver and spleen. Automated hepatosplenic segmentation for attenuation values (in HU) was performed using a validated deep-learning tool. Unenhanced liver attenuation < 40.0 HU, corresponding to > 15% MRI-based proton density fat, served as the reference standard for moderate steatosis., Results: The prevalence of moderate or severe steatosis was 12.9% (216/1676). The diagnostic performance of portal venous liver HU in predicting moderate hepatic steatosis (AUROC = 0.943) was significantly better than the liver-spleen HU difference (AUROC = 0.814) (p < 0.001). Portal venous phase liver thresholds of 80 and 90 HU had a sensitivity/specificity for moderate steatosis of 85.6%/89.6%, and 94.9%/74.7%, respectively, whereas a liver-spleen difference of -40 HU and -10 HU had a sensitivity/specificity of 43.5%/90.0% and 92.1%/52.5%, respectively. Furthermore, livers with moderate-severe steatosis demonstrated significantly less post-contrast enhancement (mean, 35.7 HU vs 47.3 HU; p < 0.001)., Conclusion: Moderate steatosis can be reliably diagnosed on standard portal venous phase CT using liver attenuation values alone. Consideration of splenic attenuation appears to add little value. Moderate steatosis not only has intrinsically lower pre-contrast liver attenuation values (< 40 HU), but also enhances less, typically resulting in post-contrast liver attenuation values of 80 HU or less., Clinical Relevance Statement: Moderate steatosis can be reliably diagnosed on post-contrast CT using liver attenuation values alone. Livers with at least moderate steatosis enhance less than those with mild or no steatosis, which combines with the lower intrinsic attenuation to improve detection., Key Points: The liver-spleen attenuation difference is frequently utilized in routine practice but appears to have performance limitations. The liver-spleen attenuation difference is less effective than liver attenuation for moderate steatosis. Moderate and severe steatosis can be identified on standard portal venous phase CT using liver attenuation alone., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Quantitative computed tomography (QCT) has important technical advantages for the measurement of bone mineral density, and the technique is well suited for both the diagnosis of osteoporosis and the monitoring of treatment. Its use deserves a wider application than at present. The use of QCT in both research and in the clinic has recently garnered increasing attention. In this review, we update the advances and application of QCT in the study of osteoporosis., Competing Interests: None declared., (Thieme. All rights reserved.)

Diabetes mellitus and metabolic syndrome are closely linked with visceral body composition, but clinical assessment is limited to external measurements and laboratory values including hemoglobin A1c (HbA1c). Modern deep learning and AI algorithms allow automated extraction of biomarkers for organ size, density, and body composition from routine computed tomography (CT) exams. Comparing visceral CT biomarkers across groups with differing glycemic control revealed significant, progressive CT biomarker changes with increasing HbA1c. For example, in the unenhanced female cohort, mean changes between normal and poorly-controlled diabetes showed: 53% increase in visceral adipose tissue area, 22% increase in kidney volume, 24% increase in liver volume, 6% decrease in liver density (hepatic steatosis), 16% increase in skeletal muscle area, and 21% decrease in skeletal muscle density (myosteatosis) (all p < 0.001). The multisystem changes of metabolic syndrome can be objectively and retrospectively measured using automated CT biomarkers, with implications for diabetes, metabolic syndrome, and GLP-1 agonists., (© 2024. The Author(s).)

Objective: To determine which bones and which grades had the highest inter-rater variability when employing the Tanner-Whitehouse (T-W) method., Materials and Methods: Twenty-four radiologists were recruited and trained in the T-W classification of skeletal development. The consistency and skill of the radiologists in determining bone development status were assessed using 20 pediatric hand radiographs of children aged 1 to 18 years old. Four radiologists had a poor concordance rate and were excluded. The remaining 20 radiologists undertook a repeat reading of the radiographs, and their results were analyzed by comparing them with the mean assessment of two senior experts as the reference standard. Concordance rate, scoring, and Kendall's W were calculated to evaluate accuracy and consistency., Results: Both the radius, ulna, and short finger (RUS) system (Kendall's W = 0.833) and the carpal (C) system (Kendall's W = 0.944) had excellent consistency, with the RUS system outperforming the C system in terms of scores. The repeatability analysis showed that the second rating test, performed after 2 months of further bone age assessment (BAA) practice, was more consistent and accurate than the first. The capitate had the lowest average concordance rate and scoring, as well as the lowest overall concordance rate for its D classification. Moreover, the G classifications of the seven carpal bones all had a concordance rate less than 0.6. The bones with lower Kendall's W were likewise those with lower scores and concordance rates., Conclusion: The D grade of the capitate showed the highest variation, and the use of the Tanner-Whitehouse 3rd edition (T-W3) to determine bone age (BA) was frequently inconsistent. A more comprehensive description with a focus on inaccuracy bones or ratings and a modification to the T-W3 approach would significantly advance BAA., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objective: We analyzed quantitative computed tomography (CT) and chemical shift-encoded magnetic resonance imaging (MRI) data from a Chinese cohort to investigate the effects of BMI and aging on different adipose tissue (AT) depots., Methods: In 400 healthy, community-dwelling individuals aged 22 to 83 years, we used MRI to quantify proton density fat fraction (PDFF) of the lumbar spine (L2-L4) bone marrow AT (BMAT), the psoas major and erector spinae (ES) muscles, and the liver. Abdominal total AT, visceral AT (VAT), and subcutaneous AT (SAT) areas were measured at the L2-L3 level using quantitative CT. Partial correlation analysis was used to evaluate the relationship of each AT variable with age and BMI. Multiple linear regression analysis was performed in which each AT variable was evaluated in turn as a function of age and the other five independent AT measurements., Results: Of the 168 men, 29% had normal BMI (<24.0 kg/m 2 ), 47% had overweight (24.0-27.9 kg/m 2 ), and 24% had obesity (≥ 28.0 kg/m 2 ). In the 232 women, the percentages were 46%, 32%, and 22%, respectively. Strong or very strong correlations with BMI were found for total AT, VAT, and SAT in both sexes. BMAT and ES PDFF was strongly correlated with age in women and moderately correlated in men. In both sexes, BMAT PDFF correlated only with age and not with any of the other AT depots. Psoas PDFF correlated only with ES PDFF and not with age or the other AT depots. Liver PDFF correlated with BMI and VAT and weakly with SAT in men. VAT and SAT correlated with age and each other in both sexes., Conclusions: Age and BMI are both associated with adiposity, but their effects differ depending on the type of AT., (© 2024 The Obesity Society.)

The 1994 WHO criterion of a T-score ≤ -2.5 for densitometric osteoporosis was chosen because it results in a prevalence commensurate with the observed lifetime risk of fragility fractures in Caucasian women aged ≥ 50 years. Due to the much lower risk of fragility fracture among East Asians, the application of the conventional WHO criterion to East Asians leads to an over inflated prevalence of osteoporosis, particularly for spine osteoporosis. According to statistical modeling and when a local BMD reference is used, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.7 for Hong Kong Chinese women. Using radiographic osteoporotic vertebral fracture as a surrogate clinical endpoint, we empirically demonstrated that a femoral neck T-score of -2.77 for Chinese women was equivalent to -2.60 for Italian women, a spine T-score of -3.75 for Chinese women was equivalent to -2.44 for Italian women, and for Chinese men a femoral neck T-score of -2.77 corresponded to spine T-score of -3.37. For older Chinese men, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.2. With the BMD reference published by IKi et al. applied, T-score of femoral neck, total hip, and spine of -2.75, -3.0, and -3.9 for Japanese women will be more in line with the WHO osteoporosis definition. The revised definition of osteoporosis cutpoint T-scores for East Asians will allow a more meaningful international comparison of disease burden., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Objective: Bone loss in people with HIV (PWH) is poorly understood. Switching tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) has yielded bone mineral density (BMD) increases. PETRAM (NCT#:03405012) investigated whether BMD and bone turnover changes correlate., Design: Open-label, randomized controlled trial., Setting: Single-site, outpatient, secondary care., Participants: Nonosteoporotic, virologically suppressed, cis-male PWH taking TDF/emtricitabine (FTC)/rilpivirine (RPV) for more than 24 weeks., Intervention: Continuing TDF/FTC/RPV versus switching to TAF/FTC/RPV (1 : 1 randomization)., Main Outcome Measures: :[ 18 F]NaF-PET/CT for bone turnover (standardized uptake values, SUV mean ) and dual-energy x-ray absorptiometry for lumbar spine and total hip BMD., Results: Thirty-two men, median age 51 years, 76% white, median duration TDF/FTC/RPV 49 months, were randomized between 31 August 2018 and 09 March 2020. Sixteen TAF:11 TDF were analyzed. Baseline-final scan range was 23-103 (median 55) weeks. LS-SUV mean decreased for both groups (TAF -7.9% [95% confidence interval -14.4, -1.5], TDF -5.3% [-12.1,1.5], P  = 0.57). TH-SUV mean showed minimal changes (TAF +0.3% [-12.2,12.8], TDF +2.9% [-11.1,16.9], P  = 0.77). LS-BMD changes were slightly more favorable with TAF but failed to reach significance (TAF +1.7% [0.3,3.1], TDF -0.3 [-1.8,1.2], P  = 0.06). Bone turnover markers decreased more with TAF ([CTX -35.3% [-45.7, -24.9], P1NP -17.6% [-26.2, -8.5]) than TDF (-11.6% [-28.8, +5.6] and -6.9% [-19.2, +5.4] respectively); statistical significance was only observed for CTX ( P  = 0.02, P1NP, P  = 0.17)., Conclusion: Contrary to our hypothesis, lumbar spine and total hip regional bone formation (SUV mean ) and BMD did not differ postswitch to TAF. However, improved LS-BMD and CTX echo other TAF-switch studies. The lack of difference in SUV mean may be due to inadequate power., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The 2013 ISCD consensus recommended a Caucasian female reference database for T-score calculation in men, which says "A uniform Caucasian (non-race adjusted) female reference database should be used to calculate T-scores for men of all ethnic groups." However, this statement was recommended for the US population, and no position was taken with respect to BMD reference data or ethnicity matching outside of the USA. In East Asia, currently, a Japanese BMD reference database is universally adopted in Japan for clinical DXA diagnosis, while both local BMD and Caucasian BMD reference databases are in use in Mainland China, South Korea, Taiwan, and Singapore. In this article, we argue that an ethnicity- and gender-specific BMD database should be used for T-score calculations for East Asians, and we list the justifications why we advocate so. Use of a Caucasian BMD reference database leads to systematically lower T-scores for East Asians and an overestimation of the prevalence of osteoporosis. Using a female BMD reference database to calculate T-scores for male patients leads to higher T-score values and an underestimation of the prevalence of osteoporosis. Epidemiological evidence does not support using a female BMD reference database to calculate T-scores for men. We also note that BMD reference databases collected in Asia should be critically evaluated for their quality., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background: Uptake to anastrozole for breast cancer prevention is low, partly due to women's concerns about side effects including gains in weight and specifically gains in body fat. Previous evidence does not link anastrozole with gains in weight, but there is a lack of data on any effects on body composition i.e. changes in fat and fat free mass. Here we assess association of anastrozole with body composition changes in a prospective sub-study from the second international breast intervention trial (IBIS-II)., Methods: Participants had DXA scans at baseline and for five years of anastrozole/placebo and beyond (between March 2004 and September 2017. Primary outcomes were changes in body weight, body fat and fat free mass at 9-18 months. A linear model was used to estimate the size of a differential effect in these outcomes by randomised treatment allocation adjusted for baseline value and time since last scan, age, 10-year breast cancer risk, smoking and HRT status., Results: 203 postmenopausal women were recruited (n = 95 anastrozole, n = 108 placebo), mean age 58 years (SD = 5.4), BMI 28.0 kg/m 2 (SD = 5.5). There was no evidence of a strong association between anastrozole or placebo and endpoints at 9-18 months; effect size (95 %CI) for anastrozole minus placebo for body weight (per/kg) -0.11 (-1.29-1.08); body fat 0.11 (-0.75-0.96) and fat free mass -0.30 (-0.79-0.19)., Conclusions: There is unlikely to be a clinically significant change to body composition with anastrozole for breast cancer prevention., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Purpose: Predictors of 'imminent' risk of second hip fracture are unknown. The aims of the study were to explore strength of hip areal bone mineral density (aBMD), and muscle area and density for predicting second hip fracture at different time intervals., Methods: Data of the Chinese Second Hip Fracture Evaluation were analyzed, a longitudinal study to evaluate the risk of second hip fracture (of the contralateral hip) by using CT images obtained immediately after first hip fracture. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur at the contralateral unfractured side. Patients were followed up for a median time of 4.5 years. Separate Cox models were used to predict second hip fracture risk at different time intervals after first event adjusted for age, sex, BMI and diabetes., Results: The mean age of subjects with imminent (within 1st or 2nd year) second hip fracture was 79.80 ± 5.16 and 81.56 ± 3.64 years. In the 1st year after the first hip fracture, femoral neck (FN) aBMD predicted second hip fracture (HR 5.88; 95 % CI, 1.32-26.09). In the remaining years of follow-up after 2nd year, muscle density predicted second hip fracture (G.MaxM HR 2.13; 95 % CI, 1.25-3.65,G.Med/MinM HR 2.10; 95 % CI, 1.32-3.34)., Conclusions: Our results show that femoral neck aBMD is an important predictor for second hip fracture within the first year and therefore suggest supports the importance concept of early and rapid-acting bone-active drugs to increase hip BMD. In addition, the importance of muscle density predicting second hip fracture after the second year suggest post hip fracture rehabilitation and exercise programs could also be important to reduce muscle fatty infiltration., Competing Interests: KE is a part time employee of Clario, Inc.. Other authors declare no conflict of interest., (© 2023 Published by Elsevier Inc.)

BACKGROUND. Precontrast CT is an established means of evaluating for hepatic steatosis; postcontrast CT has historically been limited for this purpose. OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance of portal venous phase postcontrast CT in detecting at least moderate hepatic steatosis using liver and spleen attenuation measurements determined by an automated artificial intelligence (AI) tool. METHODS. This retrospective study included 2917 patients (1381 men, 1536 women; mean age, 56.8 years) who underwent a CT examination that included at least two series through the liver. Examinations were obtained from an AI vendor's data lake of data from 24 centers in one U.S. health care network and 29 centers in one Israeli health care network. An automated deep learning tool extracted liver and spleen attenuation measurements. The reference for at least moderate steatosis was precontrast liver attenuation of less than 40 HU (i.e., estimated liver fat > 15%). A radiologist manually reviewed examinations with outlier AI results to confirm portal venous timing and identify issues impacting attenuation measurements. RESULTS. After outlier review, analysis included 2777 patients with portal venous phase images. Prevalence of at least moderate steatosis was 13.9% (387/2777). Patients without and with at least moderate steatosis, respectively, had mean postcontrast liver attenuation of 104.5 ± 18.1 (SD) HU and 67.1 ± 18.6 HU ( p < .001); a mean difference in postcontrast attenuation between the liver and the spleen (hereafter, postcontrast liver-spleen attenuation difference) of -7.6 ± 16.4 (SD) HU and -31.8 ± 20.3 HU ( p < .001); and mean liver enhancement of 49.3 ± 15.9 (SD) HU versus 38.6 ± 13.6 HU ( p < .001). Diagnostic performance for the detection of at least moderate steatosis was higher for postcontrast liver attenuation (AUC = 0.938) than for the postcontrast liver-spleen attenuation difference (AUC = 0.832) ( p < .001). For detection of at least moderate steatosis, postcontrast liver attenuation had sensitivity and specificity of 77.8% and 93.2%, respectively, at less than 80 HU and 90.5% and 78.4%, respectively, at less than 90 HU; the postcontrast liver-spleen attenuation difference had sensitivity and specificity of 71.4% and 79.3%, respectively, at less than -20 HU and 87.0% and 62.1%, respectively, at less than -10 HU. CONCLUSION. Postcontrast liver attenuation outperformed the postcontrast liver-spleen attenuation difference for detecting at least moderate steatosis in a heterogeneous patient sample, as evaluated using an automated AI tool. Splenic attenuation likely is not needed to assess for at least moderate steatosis on postcontrast images. CLINICAL IMPACT. The technique could promote early detection of clinically significant nonalcoholic fatty liver disease through individualized or large-scale opportunistic evaluation.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1090/coif). YXJW serves as the Editor-in-Chief of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare.

Older women with a first hip fracture exhibit heightened susceptibility and incidence of second fracture and potentially severe consequences. This prospective study was to compare the predictive power of qualitative and quantitative muscle parameters for a second hip fracture in older women with a first hip fracture. A total of 206 subjects were recruited from the longitudinal Chinese Second Hip Fracture Evaluation study. Hip computed tomography (CT) scans were obtained immediately after the first fracture. Muscle fat infiltration was assessed according to the Goutallier classification qualitatively. Quantitative parameters included cross-sectional area and density of gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) muscles. CT X-ray absorptiometry was used to measure the areal bone mineral density (aBMD) of the contralateral femur. Cox proportional hazards models were used to compute hazard ratios (HR) of second hip fracture risk. The mean age of subjects was 74.9 (±9.5) years at baseline. After 4.5 years, 35 had a second hip fracture, 153 without a second hip fracture, and 18 died. Except for the combined G.MinM Goutallier grade 3 and 4 groups before adjustment for covariates (HR = 5.83; 95% confidence interval [CI] 1.49-22.83), there were no significant HRs for qualitative classification to predict a second hip fracture. Among quantitative metrics, after adjustment for covariates, G.Med/MinM density was significant in the original (HR = 1.44; CI 1.02-2.04) and competing risk analyses (HR = 1.46; CI 1.02-2.07). After additional adjustment for femoral neck (FN) aBMD, G.Med/MinM density remained borderline significant for predicting a second hip fracture in competing risk analysis (HR = 1.43; CI 0.99-2.06; p  = 0.057). Our study revealed that Goutallier classification was less effective than quantitative muscle metrics for predicting hip second fracture in this elderly female cohort. After adjustment for FN aBMD, G.Med/MinM density is a borderline independent predictor of second hip fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

We review the rationale, methodology, and clinical utility of quantitative [ 18 F] sodium fluoride ([ 18 F]NaF) positron emission tomography-computed tomography (PET-CT) imaging to measure bone metabolic flux (K i , also known as bone plasma clearance), a measurement indicative of the local rate of bone formation at the chosen region of interest. We review the bone remodelling cycle and explain what aspects of bone remodelling are addressed by [ 18 F]NaF PET-CT. We explain how the technique works, what measurements are involved, and what makes [ 18 F]NaF PET-CT a useful tool for the study of bone remodelling. We discuss how these measurements can be simplified without loss of accuracy to make the technique more accessible. Finally, we briefly review some key clinical applications and discuss the potential for future developments. We hope that the simplified method described here will assist in promoting the wider use of the technique., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Puri, Frost, Moore, Choudhury, Vinjamuri, Mahajan, Fynbo, Vrist, Theil, Kairemo, Wong, Zaidi, Revheim, Werner, Alavi, Cook and Blake.)

Background: Mortality following hip fracture is high and incompletely understood. We hypothesize that hip musculature size and quality are related to mortality following hip fracture. This study aims to investigate the associations of hip muscle area and density from hip CT with death following hip fracture as well as assess the dependence of this association on time after hip fracture., Methods: In this secondary analysis of the prospectively collected CT images and data from the Chinese Second Hip Fracture Evaluation, 459 patients were enrolled between May 2015 and June 2016 and followed up for a median of 4.5 years. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur. The Goutallier classification (GC) was used for qualitatively assessing muscle fat infiltration. Separate Cox models were used to predict mortality risk adjusted for covariates., Results: At the end of the follow-up, 85 patients were lost, 81 patients (64% women) had died, and 293 (71% women) survived. The mean age of non-surviving patients at death (82.0 ± 8.1 years) was higher than that of the surviving patients (74.4 ± 9.9 years). The Parker Mobility Score and the American Society of Anesthesiologists scores of the patients that died were respectively lower and higher compared to the surviving patients. Hip fracture patients received different surgical procedures, and no significant difference in the percentage of hip arthroplasty was observed between the dead and the surviving patients (P = 0.11). The cumulative survival was significantly lower for patients with low G.MaxM area and density and low G.Med/MinM density, independent of age and clinical risk scores. The GC grades were not associated with the mortality after hip fracture. Muscle density of both G.MaxM (adj. HR 1.83; 95% CI, 1.06-3.17) and G.Med/MinM (adj. HR 1.98; 95% CI, 1.14-3.46) was associated with mortality in the 1st year after hip fracture. G.MaxM area (adj. HR 2.11; 95% CI, 1.08-4.14) was associated with mortality in the 2nd and later years after hip fracture., Conclusion: Our results for the first time show that hip muscle size and density are associated with mortality in older hip fracture patients, independent of age and clinical risk scores. This is an important finding to better understand the factors contributing to the high mortality in older hip fracture patients and to develop better future risk prediction scores that include muscle parameters., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Introduction: Lumbar intervertebral disc degeneration (LDD) and osteoporosis (OP) are age-related conditions that induce low back pain and have an impact on quality of life. The relationship between LDD and changes in bone mineral density (BMD) is, however, contentious and ever-changing. The purpose of this study is to investigate the relationship between lumbar vertebral volumetric BMD (vBMD) and LDD in an urban population of young and middle-aged community-dwelling Chinese adults., Materials and Methods: 719 participants were recruited from among the subjects enrolled in a 10-year longitudinal study of degeneration of the spine and knee being conducted at the Beijing Jishuitan Hospital. The severity of LDD was graded using the five-grade Pfirrmann classification, and lumbar vertebral vBMD was measured using quantitative computed tomography (QCT). The relationship between the grade of intervertebral disc degeneration and lumbar vertebral vBMD was analyzed, and multiple linear regression was performed to adjust for covariates., Results: The mean lumbar vBMD decreased as the grade of LDD increased (171.5 g/cm 3 , 147.8 g/cm 3 , and 124.3 g/cm 3 , respectively; P < 0.001). After adjusting for age, a higher LDD stage was associated with a lower mean L2-L4 vBMD, although a statistically significant correlation was observed only in men (standardized coefficient β = - 0.656, P = 0.004). In men, there was a negative correlation between single-vertebra vBMD and degeneration of adjacent intervertebral discs, particularly those involving the L3 vertebra (L2-3 disc: β = - 0.333, P < 0.001, L3-4 disc: β = - 0.398, P < 0.001), as well as the mean grade of the L2-4 discs (β = - 0.448, P < 0.001). However, the L5-S1 disc had a smaller correlation with age than others, and no statistically significant associations with lumbar vBMD were observed in either men (β = - 0.024, P = 0.729) or women (β = - 0.057, P = 0.396)., Conclusion: Our study found that the degree of LDD was negatively associated with lumbar trabecular vBMD, although (excepting the L5-S1 disc), the relationship was statistically significant only in men., (© 2023. The Japanese Society Bone and Mineral Research.)

Purpose: This study aimed to investigate the increase in bone marrow adipose tissue (BMAT) in overweight and obese women with polycystic ovary syndrome (PCOS) and its relationship with hyperandrogenism, obesity, and metabolic disorders., Methods: The study included 87 overweight or obese women with PCOS (mean age 29 ± 4 years), as well as 87 age-matched controls recruited from a separate population study. All PCOS patients were measured for anthropometric features, abdominal adipose tissue areas, BMAT, biochemistry, and sex hormones. BMAT was compared between the PCOS patients and controls. In PCOS patients, subgroup comparisons of BMAT and its associations with body adiposity indices, biochemistry, and sex hormones were analyzed. The odds ratios (ORs) of elevated BMAT (defined as BMAT ≥ 38%) were calculated., Results: On average BMAT was increased by 5.6% ( ± 11.3%) in PCOS patients compared to controls. BMAT were significantly higher in the upper tertiles of total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). BMAT was not correlated with abdominal adiposity indices or biochemistry except for LDL-C (r = 0.253-0.263, p = 0.014-0.018). LDL-C was not significantly different between the normal and abnormal androgen PCOS subgroups ( p = 0.10-0.887). LDL-C, follicle stimulating hormone (FSH), and total testosterone (TT) were risk factors for elevated BMAT, with ORs of 1.899 ( p = 0.038-0.040), 1.369 ( p = 0.030-0.042), and 1.002 ( p = 0.040-0.044) for each unit increase, respectively., Conclusion: BMAT was increased in overweight and obese PCOS patients, but the increase in BMAT was not associated with the hyperandrogenism related obesity or metabolic disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Min, Li, Blake, Zhao, Ruan and Cheng.)

Studies of skeletal metabolism using measurements of bone metabolic flux (K i ) obtained with [ 18 F] sodium fluoride ([ 18 F]NaF) positron emission tomography (PET) scans have been used in clinical research for the last 30 years. The technique has proven useful as an imaging biomarker in trials of novel drug treatments for osteoporosis and investigating other metabolic bone diseases, including chronic kidney disease mineral and bone disorder. It has also been shown to be valuable in metastatic bone disease in breast cancer patients and may have potential in other cancer types, such as prostate cancer, to assess early bone fracture risk. However, these studies have usually required a 60-min dynamic PET scan and measurement of the arterial input function (AIF), making them difficult to translate into the clinic for diagnostic purposes. We have previously proposed a simplified method that estimates the K i value at an imaging site from a short (4-min) static scan and venous blood samples. A key advantage of this method is that, by acquiring a series of static scans, values of K i can be quickly measured at multiple sites using a single injection of the tracer. To date, the widespread use of [ 18 F]NaF PET has been limited by the need to measure the AIF required for the mathematical modeling of tracer kinetics to derive K i and other kinetic parameters. In this report, we review different methods of measuring the AIF, including direct arterial sampling, the use of a semi-population input function (SP-AIF), and image-derived input function, the latter two requiring only two or three venous blood samples obtained between 30 and 60 min after injection. We provide an SP-AIF model and a spreadsheet for calculating K i values using the static scan method that others can use to study bone metabolism in metabolic and metastatic bone diseases without requiring invasive arterial blood sampling. The method shortens scan times, simplifies procedures, and reduces the cost of multicenter trials without losing accuracy or precision., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: To investigate the age and gender differences in vertebral bone marrow adipose tissue (BMAT) and volumetric bone mineral density (vBMD)., Method: A total of 427 healthy adults, including 175 males (41 %) and 252 females (59 %) with an age range of 21-82 years, underwent MRI and quantitative CT examinations of the lumbar spine (L2-L4), and the corresponding BMAT and vBMD values were measured. The age-related progressions of BMAT and vBMD in men and women were evaluated and compared., Results: In males, vertebral BMAT rose gradually throughout life, while in females, BMAT increased sharply between 41 and 60 years of age. In participants aged < 40 years, BMAT was greater in males compared to females (p ≤ 0.01), while after the age of 60, BMAT was higher in females (p < 0.05). In males, vBMD decreased gradually with age, while in females, there was a sharp decrease in vBMD after the age of 40 years. At age of 31-40 years, vBMD was higher in females (P < 0.002), while at age > 60 years, vBMD was higher in males (61-70 years, P < 0.01; > 70 years, P = 0.02)., Conclusions: We found significant age and gender differences in lumbar BMAT and vBMD. These findings will help to improve our understanding of the interaction between bone marrow fat content and bone mineral density in the ageing process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT)., Methods: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women)., Results: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm 3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (β, -24.00; 95% CI, -28.54 to -19.46 mg/cm 3 ). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years., Conclusions: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures., Key Points: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: This study evaluated the prevalence of vertebral fractures (VF) in middle-aged and elderly Chinese men and women and explored the differences in lumbar spine volumetric bone mineral density (vBMD) derived from quantitative CT (QCT) between those with a grade 1 vertebral fracture and non-fractured individuals., Materials and Methods: 3,457 participants were enrolled in the China Action on Spine and Hip Status (CASH) study and had upper abdominal CT examinations. Vertebral fractures were identified by Genant's semi-quantitative method from lateral CT scout views or CT sagittal views. L1-3 vBMD was measured by Mindways QCT Pro v5.0 software. The characteristics of different fracture severity groups were compared using one-way ANOVA, independent-samples t-tests, and Kruskal-Wallis H-tests., Results: 1267 males (aged 62.77 ± 9.20 years) and 2170 females (aged 61.41 ± 9.01 years) were included in the analysis. In men, the prevalence of VF increased from 14.7% at age&lt;50 years to 23.2% at age ≥70 years, and in women from 5.1% at age&lt;50 years to 33.0% at age ≥70 years. Differences in mean age and vBMD were found between the different fracture grade groups. After age stratification, vBMD differences in men aged &lt; 50 years old disappeared (p = 0.162) but remained in the older age bands. There was no significant difference in mean vBMD between those with multiple mild fractures and those with a single mild fracture., Conclusion: In women, the prevalence of VF increased rapidly after age 50, while it grew more slowly in men. In general, with the exception of men &lt;50 years old, participants with a grade 1 VF had lower vBMD than non-fractured individuals. The majority of women younger than 50 with a grade 1 VF had normal bone mass. We recommend that a vertebral height reduction ratio of &lt;25% be diagnosed as a deformity rather than a fracture in people under the age of 50. The presence of multiple mild fractured vertebrae does not imply lower BMD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Yu, Li, Wang, Huang, Geng, Zhang, Duanmu, Blake and Cheng.)

Objective: Although sarcopenia and osteoporosis are inter-related conditions that are common with advancing age, few studies have explored relationships between muscle quality and bone mineral density (BMD). We investigated age- and sex-specific paraspinal muscle fat infiltration (MFI), muscle cross-sectional area (CSA), and spine volumetric BMD (vBMD) in healthy Chinese adults., Methods: 605 healthy adults aged 20-59 years (340 women, mean age 39.2 years; 265 men, mean age 38.8 years) had axial T 2 WI MRI imaging of the lumbar spine and CSA (cm 2 ) and MFI (%) were measured in the psoas and multifidus and erector spinae (MF-ES) muscles (L3-L4). MFI measurements were calibrated against a region of interest in an adjacent area of subcutaneous pure fat. L2-L4 vBMD was measured by quantitative CT. Age- and sex-specific subgroups were compared using the Mann-Whitney test. Multiple regression was used to test independent associations of MFI and CSA with vBMD., Results: Females had lower CSA and higher MFI than males in both the psoas and MF-ES muscles ( p < 0.001). In females and males, MF-ES MFI increased with age ( p < 0.001) and in females age-related increases were observed for the psoas muscles ( p < 0.05). Greater fat infiltration of the MS-ES muscle unit was associated with lower vBMD in both sexes ( p < 0.001) but not with CSA. Following adjustment for demographic variables and CSA, MS-ES MFI remained predictive of vBMD (β = -0.408 to -0.157, p < 0.001)., Conclusion: We have demonstrated that, independent of CSA and demographic variables, MFI of the MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes., Advances in Knowledge: This is the first study to demonstrate that, independent of muscle size and demographic variables, MFI of the paraspinal MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes.

Background: Radiographic absorptiometry (RA) is one of the earliest methods of bone densitometry and has been used to measure the phalanges and metacarpals where soft tissue attenuation is minimal. The aim of this study was to determine whether the technique can be adapted to correct for soft tissue attenuation and measure areal bone mineral density (aBMD) in the forearm., Methods: A total of 51 patients referred for a clinical spine and hip dual-energy X-ray absorptiometry (DXA) examination and 8 young and middle-aged volunteers were recruited to this study. The first 29 participants (20 women, 9 men, aged 61±14 years) served as the training cohort, and the remaining 30 (20 women, 10 men, aged 55±16 years) comprised the validation cohort. All participants underwent a DXA scan of their non-dominant forearm, and a digital X-ray image of the same arm was acquired with a step phantom. Identical regions of interest (ROIs) in the radius and ulna at the one-third radius site were measured on the X-ray and DXA images, and a soft tissue ROI was measured on X-ray images between the radius and ulna. The X-ray measurements in the training cohort were expressed as equivalent step phantom thickness (Eq. SPT) and used to estimate forearm aBMD using a linear equation calibrated against the DXA scans. Estimates of forearm aBMD made from the digital X-ray images acquired in the validation cohort were compared with the results of the DXA scans., Results: Digital X-ray estimates of radius and ulna aBMD at the one-third radius site in the validation cohort showed a good correlation with GE-Lunar iDXA scanner measurements (r=0.795; P<0.001). The Bland-Altman plot had a mean bias of -0.002 g/cm 2 and 95% limits of agreement of -0.185 to +0.181 g/cm 2 ., Conclusions: Digital X-ray estimates of proximal forearm aBMD corrected for soft tissue attenuation correlated with DXA measurements with correlation coefficients comparable to those seen for other peripheral bone densitometry technologies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-842/coif). Klaus Engelke is a part-time employee of BioClinica, Inc. The other authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Patients with a first hip fracture are at high risk of fracturing their other hip. Despite this, preventive therapy is often not given. Because little is known about specific risk factors of a second hip fracture, we investigated the association with areal bone mineral density (aBMD), muscle size, and density. We also investigated whether muscle parameters predict the risk of a contralateral fracture independently of aBMD., Methods: Three groups were included, one without hip fracture (a subcohort of the China Action on Spine and Hip Status study), one with a first, and one with a second hip fracture. Subjects with fractures were recruited from the longitudinal Chinese Second Hip Fracture Evaluation (CSHFE). Computed tomography scans of CSHFE patients, which were obtained immediately following their first fracture, were used to measure cross-sectional area and density of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) muscles. Computed tomography X-ray absorptiometry was used to measure aBMD of the contralateral femur. Median follow-up time to second fracture was 4.5 years. Cox proportional hazards models were used to compute hazard ratios (HR) of second hip fracture risk in subjects with a first hip fracture. Multivariate logistic regressions were used to compare odds ratios (OR) for the risk of a first and second hip fracture., Results: Three hundred and one participants (68.4 ± 6.1 years, 64% female) without and 302 participants (74.6 ± 9.9 years, 71% female) with a first hip fracture were included in the analysis. Among the latter, 45 (79.2 ± 7.1 years) sustained a second hip fracture. ORs for first hip fracture were significant for aBMD and muscle size and density. ORs for a second fracture were smaller by a factor of 3 to 4 and no longer significant for femoral neck (FN) aBMD. HRs for predicting second hip fracture confirmed the results. G.Med/MinM density (HR, 1.68; CI, 1.20-2.35) and intertrochanter aBMD (HR, 1.62; CI, 1.13-2.31) were the most significant. FN aBMD was not significant. G.Med/MinM density remained significant for predicting second hip fracture after adjustment for FN (HR, 1.66; Cl, 1.18-2.30) or total hip aBMD (HR, 1.50; 95% Cl, 1.04-2.15)., Conclusions: Density of the G.Med/MinM muscle is an aBMD independent predictor of the risk of second hip fracture. Intertrochanteric aBMD is a better predictor of second hip fracture than FN and total hip aBMD. These results may trigger a paradigm shift in the assessment of second hip fracture risk and prevention strategies., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

BACKGROUND. Calibrated CT fat fraction (FF CT ) measurements derived from un-enhanced abdominal CT reliably reflect liver fat content, allowing large-scale population-level investigations of steatosis prevalence and associations. OBJECTIVE. The purpose of this study was to compare the prevalence of hepatic steatosis, as assessed by calibrated CT measurements, between population-based Chinese and U.S. cohorts, and to investigate in these populations the relationship of steatosis with age, sex, and body mass index (BMI). METHODS. This retrospective study included 3176 adults (1985 women and 1191 men) from seven Chinese provinces and 8748 adults (4834 women and 3914 men) from a single U.S. medical center, all drawn from previous studies. All participants were at least 40 years old and had undergone unenhanced abdominal CT in previous studies. Liver fat content measurements on CT were cross-calibrated to MRI proton density fat fraction measurements using phantoms and expressed as adjusted FF CT measurements. Mild, moderate, and severe steatosis were defined as adjusted FF CT of 5.0-14.9%, 15.0-24.9%, and 25.0% or more, respectively. The two cohorts were compared. RESULTS. In the Chinese and U.S. cohorts, the median adjusted FF CT for women was 4.7% and 4.8%, respectively, and that for men was 5.8% and 6.2%, respectively. In the Chinese and U.S. cohorts, steatosis prevalence for women was 46.3% and 48.7%, respectively, whereas that for men was 58.9% and 61.9%, respectively. Severe steatosis prevalence was 0.9% and 1.8% for women and 0.2% and 2.6% for men in the Chinese and U.S. cohorts, respectively. Adjusted FF CT did not vary across age decades among women or men in the Chinese cohort, although it increased across age decades among women and men in the U.S. cohort. Adjusted FF CT and BMI exhibited weak correlation ( r = 0.312-0.431). Among participants with normal BMI, 36.8% and 38.5% of those in the Chinese and U.S. cohorts, respectively, had mild steatosis, and 3.0% and 1.5% of those in the Chinese and U.S. cohorts, respectively, had moderate or severe steatosis. Among U.S. participants with a BMI of 40.0 or greater, 17.7% had normal liver content. CONCLUSION. Steatosis and severe steatosis had higher prevalence in the U.S. cohort than in the Chinese cohort in both women and men. BMI did not reliably predict steatosis. CLINICAL IMPACT. The findings provide new information on the dependence of hepatic steatosis on age, sex, and BMI.

Objectives: White fat contributes to body weight (BW) but accumulates very little [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) in the fasting state. As a result, higher standardised uptake values normalised to BW (SUV) are observed in non-fatty tissue in obese patients compared to those in non-obese patients. Therefore, SUV normalised to lean body mass (SUL) that makes tumour uptake values less dependent on patients' body habitus is considered more appropriate. This study aimed to assess ten mathematical equations to predict lean body mass (LBM) by comparison with dual-energy X-ray absorptiometry (DXA) as the reference method., Methods: DXA-based LBM was compared with ten equation-based estimates of LBM in terms of the slope, bias and 95% limits of agreement (LOA) of Bland-Altman plots, and Pearson correlation coefficients (r). Data from 747 men and 811 women aged 60-65 years were included., Results: Gallagher's equation was optimal in males (slope = 0.13, bias = -2.4 kg, LOA = 12.8 kg and r = 0.900) while Janmahasatian's equation was optimal in females (slope = 0.14, bias = -0.9 kg, LOA = 10.7 kg and r = 0.876). Janmahasatian's equation performed slightly better than Gallagher's in the pooled male and female data (slope = 0.00, bias = -1.6 kg, LOA = 12.3 kg and r = 0.959)., Conclusions: The Gallagher and Janmahasatian equations were optimal and almost indistinguishable in predicting LBM in subjects aged 60-65 years., Advances in Knowledge: Determination of the optimum equation for predicting lean body mass to improve the calculation of SUL for [ 18 F]FDG PET quantification.

Background and Purpose: Although it is widely recognized that hip BMD is reduced in patients with hip fracture, the differences in geometrical parameters such as cortical volume and thickness between subjects with and without hip fracture are less well known., Materials and Methods: Five hundred and sixty two community-dwelling elderly women with hip CT scans were included in this cross-sectional study, of whom 236 had an acute hip fracture. 326 age matched women without hip fracture served as controls. MIAF-Femur software was used for the measurement of the intact contralateral femur in patients with hip fracture and the left femur of the controls. Integral and cortical volumes (Vols) of the total hip (TH), femoral head (FH), femoral neck (FN), trochanter (TR) and intertrochanter (IT) were analyzed. In the FH and FN the volumes were further subdivided into superior anterior (SA) and posterior (SP) as well as inferior anterior (IA) and posterior (IP) quadrants. Cortical thickness (CortThick) was determined for all sub volumes of interest (VOIs) listed above., Results: The average age of the control and fracture groups was 71.7 and 72.0 years, respectively. The fracture patients had significantly lower CortThick and Vol of all VOIs except for TRVol. In the fracture patients, cortical thickness and volume at the FN were significantly lower in all quadrants except for cortical volume of quadrant SA (p= 0.635). Hip fracture patients had smaller integral FN volume and cross-sectional area (CSA) before and after adjustment of age, height and weight. With respect to hip fracture discrimination, cortical volume performed poorer than cortical thickness across the whole proximal femur. The ratio of Cort/TrabMass (RCTM), a measure of the internal distribution of bone, performed better than cortical thickness in discriminating hip fracture risk. The highest area under curve (AUC) value of 0.805 was obtained for the model that included THCortThick, FHVol, THRCTM and FNCSA., Conclusion: There were substantial differences in total and cortical volume as well as cortical thickness between fractured and unfractured women across the proximal femur. A combination of geometric variables resulted in similar discrimination power for hip fracture risk as aBMD., Competing Interests: KE is a part-time employee of BioClinica, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Yang, Liu, Ge, Zhu, Su, Cheng, Wu, Blake and Engelke.)

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., Competing Interests: KE is a part-time employee of BioClinica, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhao, Zha, Ran, Su, Yang, Shuang, Liu, Xu, Blake, Cheng, Engelke and Vlug.)

We describe a multicenter study using the European Spine Phantom (ESP) to compare the accuracy, linearity and precision of QCT measurements of spine vBMD between different brands of scanner, different models of the same brand and identical units of the same model. Ten scans of the same ESP with repositioning were performed on forty CT scanners from five manufacturers in different hospitals across China, all calibrated with the Mindways QCT system. The three ESP vertebral bodies simulating low (L1), medium (L2) and high (L3) vBMD and their average (L1-3 vBMD) were compared with phantom values. Linearity was assessed using the standard error of the estimate derived from linear regression. Precision errors were expressed as the standard deviation of the ten measurements on each scanner. Median (IQR) vBMD over all forty CT scanners compared with phantom values were: L1: 52.2 (49.9-56.4) vs 51.0; L2: 104.4 (101.2-108.6) vs 102.2; L3: 201.4 (195.0-204.9) vs 200.4; L1-3: 119.3 (116.6-123.2) vs 117.9 mg/cm 3 . Statistically significant differences in L1-3 vBMD were found between different brands (p= 0.005) and between different models of the same brand and identical units of the same model (both p< 0.001). Cross-calibration using linear regression gave a good fit for all forty systems with a median standard error of the estimate of 1.7 mg/cm 3 . The median precision error for L1-3 vBMD was 0.61 mg/cm 3 . Statistically significant differences in spine vBMD measurements between different scanners reinforce the importance of cross-calibration in multi-center studies. Cross-calibration can be reliably performed using linear regression equations., (Copyright © 2021 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

This report describes the significance of the kinetic parameters (k-values) obtained from the analysis of dynamic positron emission tomography (PET) scans using the Hawkins model describing the pharmacokinetics of sodium fluoride ([ 18 F]NaF) to understand bone physiology. Dynamic [ 18 F]NaF PET scans may be useful as an imaging biomarker in early phase clinical trials of novel drugs in development by permitting early detection of treatment-response signals that may help avoid late-stage attrition.

[ 18 F]NaF PET measurements of bone metabolic flux (K i ) are conventionally obtained with 60-min dynamic scans analysed using the Hawkins model. However, long scan times make this method expensive and uncomfortable for subjects. Therefore, we evaluated and compared measurements of K i with shorter scan times analysed with fixed values of the Hawkins model rate constants. The scans were acquired in a trial in 30 postmenopausal women, half treated with teriparatide (TPT) and half untreated. Sixty-minute PET-CT scans of both hips were acquired at baseline and week 12 after injection with 180 MBq [ 18 F]NaF. Scans were analysed using the Hawkins model by fitting bone time-activity curves at seven volumes of interest (VOIs) with a semi-population arterial input function. The model was re-run with fixed rate-constants for dynamic scan times from 0-12 min increasing in 4-min steps up to 0-60 min. Using the Hawkins model with fixed rate-constants, K i measurements with statistical power equivalent or superior to conventionally analysed 60-min dynamic scans were obtained with scan times as short as 12 min.

BACKGROUND. Hepatic attenuation at unenhanced CT is linearly correlated with the MRI proton density fat fraction (PDFF). Liver fat quantification at contrast-enhanced CT is more challenging. OBJECTIVE. The purpose of this article is to evaluate liver steatosis categorization on contrast-enhanced CT using a fully automated deep learning volumetric hepatosplenic segmentation algorithm and unenhanced CT as the reference standard. METHODS. A fully automated volumetric hepatosplenic segmentation algorithm using 3D convolutional neural networks was applied to unenhanced and contrast-enhanced series from a sample of 1204 healthy adults (mean age, 45.2 years; 726 women, 478 men) undergoing CT evaluation for renal donation. The mean volumetric attenuation was computed from all designated liver and spleen voxels. PDFF was estimated from unenhanced CT attenuation and served as the reference standard. Contrast-enhanced attenuations were evaluated for detecting PDFF thresholds of 5% (mild steatosis, 10% and 15% (moderate steatosis); PDFF less than 5% was considered normal. RESULTS. Using unenhanced CT as reference, estimated PDFF was ≥ 5% (mild steatosis), ≥ 10%, and ≥ 15% (moderate steatosis) in 50.1% ( n = 603), 12.5% ( n = 151) and 4.8% ( n = 58) of patients, respectively. ROC AUC values for predicting PDFF thresholds of 5%, 10%, and 15% using contrast-enhanced liver attenuation were 0.669, 0.854, and 0.962, respectively, and using contrast-enhanced liver-spleen attenuation difference were 0.662, 0.866, and 0.986, respectively. A total of 96.8% (90/93) of patients with contrast-enhanced liver attenuation less than 90 HU had steatosis (PDFF ≥ 5%); this threshold of less than 90 HU achieved sensitivity of 75.9% and specificity of 95.7% for moderate steatosis (PDFF ≥ 15%). Liver attenuation less than 100 HU achieved sensitivity of 34.0% and specificity of 94.2% for any steatosis (PDFF ≥ 5%). A total of 93.8% (30/32) of patients with contrast-enhanced liver-spleen attenuation difference 10 HU or less had moderate steatosis (PDFF ≥ 15%); a liver-spleen difference less than 5 HU achieved sensitivity of 91.4% and specificity of 95.0% for moderate steatosis. Liver-spleen difference less than 10 HU achieved sensitivity of 29.5% and specificity of 95.5% for any steatosis (PDFF ≥ 5%). CONCLUSION. Contrast-enhanced volumetric hepatosplenic attenuation derived using a fully automated deep learning CT tool may allow objective categoric assessment of hepatic steatosis. Accuracy was better for moderate than mild steatosis. Further confirmation using different scanning protocols and vendors is warranted. CLINICAL IMPACT. If these results are confirmed in independent patient samples, this automated approach could prove useful for both individualized and population-based steatosis assessment.

[18F]NaF PET imaging is a useful tool for measuring regional bone metabolism. However, due to tracer in urine, [18F]NaF PET images of the hip reconstructed using filtered back projection (FBP) frequently show streaking artifacts in slices through the bladder leading to noisy time-activity curves unsuitable for quantification. This study compares differences between quantitative outcomes at the hip derived from images reconstructed using the FBP and ordered-subset expectation maximization (OSEM) methods. Dynamic [18F]NaF PET data at the hip for four postmenopausal women were reconstructed using FBP and nine variations of the OSEM algorithm (all combinations of 1, 5, 15 iterations and 10, 15, 21 subsets). Seven volumes of interest were placed in the hip. Bone metabolism was measured using standardized uptake values, Patlak analysis (Ki-PAT) and Hawkins model Ki-4k. Percentage differences between the standardized uptake values and Ki values from FBP and OSEM images were assessed. OSEM images appeared visually smoother and without the streaking artifacts seen with FBP. However, due to loss of counts, they failed to recover the quantitative values in VOIs close to the bladder, including the femoral head and femoral neck. This was consistent for all quantification methods. Volumes of interest farther from the bladder or larger and receiving greater counts showed good convergence with 5 iterations and 21 subsets. For VOIs close to the bladder, including the femoral neck and femoral head, 15 iterations and 10, 15 or 21 subsets were not enough to obtain OSEM images suitable for measuring bone metabolism and showed no improvement compared to FBP., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Little is known about the effect of lumbar intervertebral disc herniation (LDH) on lumbar bone mineral density (BMD), and few previous studies have used quantitative computed tomography (QCT) to assess whether the staging of LDH correlates with lumbar vertebral trabecular volumetric bone mineral density (Trab.vBMD). To explore the relationship between lumbar Trab.vBMD and LDH, seven hundred and fifty-four healthy participants aged 20-60 years were enrolled in the study from an ongoing study on the degeneration of the spine and knee between June 2014 and 2017. QCT was used to measure L2-4 Trab.vBMD and lumbar spine magnetic resonance images (MRI) were performed to assess the incidence of disc herniation. After 9 exclusions, a total of 322 men and 423 women remained. The men and women were divided into younger (age 20-39 years) and older (age 40-60 years) groups and further into those without LDH, with a single LDH segment, and with ≥2 segments. Covariance analysis was used to adjust for the effects of age, BMI, waistline, and hipline on the relationship between Trab.vBMD and LDH. Forty-one younger men (25.0%) and 59 older men (37.3%) had at least one LDH segment. Amongst the women, the numbers were 46 (22.5%) and 80 (36.4%), respectively. Although there were differences in the characteristics data between men and women, the difference in Trab.vBMD between those without LDH and those with single and ≥2 segments was not statistically significant ( p > 0.05). These results remained not statistically significant after further adjusting for covariates ( p > 0.05). No associations between lumbar disc herniation and vertebral trabecular volumetric bone mineral density were observed in either men or women.

Objectives: There is increasing evidence that muscle volume and mass are poor predictors of muscle strength and physical performance. Other assessments of muscle quality such as skeletal muscle density measured by computed tomography (CT) may be more important. The aim of this study was to explore associations of muscle size and density with handgrip strength (HGS) and the Timed Up and Go test (TUG). We also hypothesized that the strength of these associations would depend on the specific muscle of muscle group, namely trunk, hip, and mid-thigh muscles., Design: Cross-sectional study., Setting and Participants: University hospital; 316 volunteers aged 59 to 85 years., Methods: HGS, TUG, and quantitative CT imaging of the lumber, hip, and mid-thigh were performed in volunteers. From the CT images, cross-sectional area and attenuation were determined for the gluteus muscle, trunk muscle at vertebrae L2 level, and mid-thigh muscle., Results: In men and women, associations of muscle area with TUG were insignificant after adjustment for age, height, and weight. Associations with HGS were only significant in men for the gluteus maximus and the mid-thigh but slopes were rather low (β < 0.20). Associations between muscle density and TUG/HGS were more pronounced, in particular for HGS. After adjustment, associations with TUG were significant in women for the gluteus maximus and trunk muscle even (β -0.06, P .001 and β -0.07, P .031, respectively)., Conclusions and Implications: Muscle density is more strongly associated with muscle strength than muscle size andin women muscle density was also more strongly associated than muscle size with physical performance. Therefore, muscle density may represent a more clinically meaningful surrogate of muscle performance than muscle size. Muscle density measurements of trunk and gluteus muscles can be easily obtained from routine CT scan and, therefore, may become an important measurement to diagnose and screen for sarcopenia., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L 1 -L 2 ) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm 3 ) than men (176.6 mg/cm 3 ) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm 3 ) than men (92.1 mg/cm 3 ) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).., (© 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Background: Although abdominal adiposity is associated with an altered cardiometabolic risk profile, the specific contribution of abdominal adipose tissue distribution remains not fully understood. Computed tomography (CT) is a well-established and precise method to measure abdominal adipose tissue distribution. The present study investigated abdominal adiposity assessed by CT in a large-scale Chinese population., Method: A total of 59,429 adults who underwent a low dose chest CT for lung cancer screening at one of 13 health checkup centers throughout China were evaluated. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured at the center of the 2nd lumbar vertebra with Mindways quantitative CT software using the existing CT dataset without any additional radiation exposure. The ratio of visceral to total adipose tissue (TAT) areas (VAT/TAT ratio) was calculated and expressed as a percentage. Anthropometric indices including body mass index (BMI) and waist circumference were also obtained., Results: BMI, waist circumference, VAT area, SAT area, and the VAT/TAT ratio were 25.0 ± 3.0 kg/m 2 , 90 ± 8 cm, 194 ± 77 cm 2 , 85 ± 41 cm 2 , and 69.5 ± 9.1%, respectively, in men and 23.3 ± 3.1 kg/m 2 , 79 ± 8 cm, 120 ± 57 cm 2 , 123 ± 53 cm 2 , and 48.9 ± 9.7% in women. With increasing age, VAT area and the VAT/TAT ratio increased in both sexes whereas SAT area decreased in men (P < 0.001 for all). After adjustment for BMI and waist circumference, older individuals showed higher VAT area and higher VAT/TAT ratio than younger subjects (P < 0.001 for all). Adjusted VAT areas in participants aged 75 or older was 45 cm 2 (95% confidence interval [CI]: 41 cm 2 , 50 cm 2 ) higher in men and 43 cm 2 (95% CI: 37 cm 2 , 49 cm 2 ) higher in women compared with participants aged 31-44 years. Additionally, differences in VAT area across age groups increased as BMI or waist circumference increased. VAT and SAT areas, but not the VAT/TAT ratio, were positively associated with BMI and waist circumference in every age group., Conclusion: In a nationwide study conducted in China, distributions of CT-derived measures of visceral and subcutaneous adiposity were found to vary significantly between sex and age groups. Our study also revealed that the proportion of VAT (an important driver of cardiometabolic risk) could not be predicted from BMI in a Chinese population., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)