Olink Proteomics for the Identification of Biomarkers for Early Diagnosis of Postmenopausal Osteoporosis.

This investigation aims to employ Olink proteomics in analyzing the distinct serum proteins associated with postmenopausal osteoporosis (PMOP) and identifying prognostic markers for early detection of PMOP via molecular mechanism research on postmenopausal osteoporosis. Postmenopausal women admitted to Beijing Jishuitan Hospital were randomly selected and categorized into three groups based on their dual-energy X-ray absorptiometry (DXA) T-scores: osteoporosis group (n = 24), osteopenia group (n = 20), and normal bone mass group (n = 16). Serum samples from all participants were collected for clinical and bone metabolism marker measurements. Olink proteomics was utilized to identify differentially expressed proteins (DEPs) that are highly associated with postmenopausal osteoporosis. The functional analysis of DEPs was performed using Gene Ontology and Kyto Encyclopedia Genes and Genomes (KEGG). The biological characteristics of these proteins and their correlation with PMOP were subsequently analyzed. ROC curve analysis was performed to identify potential biomarkers with the highest diagnostic accuracy for early stage PMOP. Through Olink proteomics, we identified five DEPs highly associated with PMOP, including two upregulated and three downregulated proteins. TWEAK and CDCP1 markers exhibited the highest area under the curve (0.8188 and 0.8031, respectively). TWEAK and CDCP1 have the potential to serve as biomarkers for early prediction of postmenopausal osteoporosis.

Time-specific impact of trace metals on breast density of adolescent girls in Santiago, Chile.

Whether trace metals modify breast density, the strongest predictor for breast cancer, during critical developmental stages such as puberty remains understudied. Our study prospectively evaluated the association between trace metals at Tanner breast stage B1 (n = 291) and at stages both B1 and B4 (n = 253) and breast density at 2 years post-menarche among Chilean girls from the Growth and Obesity Cohort Study. Dual-energy x-ray absorptiometry assessed the volume of dense breast tissue (absolute fibroglandular volume [FGV]) and percent breast density (%FGV). Urine trace metals included arsenic, barium, cadmium, cobalt, cesium, copper, magnesium, manganese, molybdenum, nickel, lead, antimony, selenium, tin, thallium, vanadium, and zinc. At B1, a doubling of thallium concentration resulted in 13.69 cm3 increase in absolute FGV (ß: 13.69, 95% confidence interval [CI]: 2.81, 24.52), while a doubling of lead concentration resulted in a 7.76 cm3 decrease in absolute FGV (ß: -7.76, 95%CI: -14.71, -0.73). At B4, a doubling of barium concentration was associated with a 10.06 cm3 increase (ß: 10.06, 95% CI: 1.44, 18.60), copper concentration with a 12.29 cm3 increase (ß: 12.29, 95% CI: 2.78, 21.56), lead concentration with a 9.86 cm3 increase (ß: 9.86, 95% CI: 0.73, 18.98), antimony concentration with a 12.97 cm3 increase (ß: 12.97, 95% CI: 1.98, 23.79) and vanadium concentration with a 13.14 cm3 increase in absolute FGV (ß: 13.14, 95% CI: 2.73, 23.58). Trace metals may affect pubertal breast density at varying developmental stages with implications for increased susceptibility for breast cancer.

Variability in performance of genetic-enhanced DXA-BMD prediction models across diverse ethnic and geographic populations: A risk prediction study.

BACKGROUND: Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations. METHODS AND FINDINGS: We developed BMD prediction models for the femoral neck (FNK) and lumbar spine (SPN) using both genetic variants and clinical factors (such as sex, age, height, and weight), within 17,964 British white individuals from UKBB. Models based on regression with least absolute shrinkage and selection operator (LASSO), selected based on the coefficient of determination (R2) from a model selection subset of 5,973 individuals from British white population. These models were tested on 5 UKBB test sets and 12 independent cohorts of diverse ancestries, totaling over 15,000 individuals. Furthermore, we assessed the correlation of predicted BMDs with fragility fractures risk in 10 years in a case-control set of 287,183 European white participants without DXA-BMDs in the UKBB. With single-nucleotide polymorphism (SNP) inclusion thresholds at 5×10-6 and 5×10-7, the prediction models for FNK-BMD and SPN-BMD achieved the highest R2 of 27.70% with a 95% confidence interval (CI) of [27.56%, 27.84%] and 48.28% (95% CI [48.23%, 48.34%]), respectively. Adding genetic factors improved predictions slightly, explaining an additional 2.3% variation for FNK-BMD and 3% for SPN-BMD over clinical factors alone. Survival analysis revealed that the predicted FNK-BMD and SPN-BMD were significantly associated with fragility fracture risk in the European white population (P < 0.001). The hazard ratios (HRs) of the predicted FNK-BMD and SPN-BMD were 0.83 (95% CI [0.79, 0.88], corresponding to a 1.44% difference in 10-year absolute risk) and 0.72 (95% CI [0.68, 0.76], corresponding to a 1.64% difference in 10-year absolute risk), respectively, indicating that for every increase of one standard deviation in BMD, the fracture risk will decrease by 17% and 28%, respectively. However, the model's performance declined in other ethnic groups and independent cohorts. The limitations of this study include differences in clinical factors distribution and the use of only SNPs as genetic factors. CONCLUSIONS: In this study, we observed that combining genetic and clinical factors improves BMD prediction compared to clinical factors alone. Adjusting inclusion thresholds for genetic variants (e.g., 5×10-6 or 5×10-7) rather than solely considering genome-wide association study (GWAS)-significant variants can enhance the model's explanatory power. The study highlights the need for training models on diverse populations to improve predictive performance across various ethnic and geographical groups.

Circulating MicroRNA as a Potential Biomarker for Skeletal Disease in Primary Hyperparathyroidism: A Case-control Study.

OBJECTIVE: The goal of this study was to characterize the microRNA (miRNA) expression signatures in patients with Primary hyperparathyroidism (PHPT) and identify miRNA biomarkers of bone homeostasis. BACKGROUND: PHPT is associated with increased bone turnover and decreased bone mass. miRNA are markers of bone remodeling. METHODS: We performed a prospective case-control study of postmenopausal females with PHPT and control subjects matched for race, age, and bone mineral density (BMD). We collected clinical and biochemical data, assessed BMD by dual-energy x-ray absorptiometry, and measured 27 serum miRNAs related to bone remodeling. We used linear regression to assess the correlation between miRNA levels, conventional biochemical markers, and BMD. RESULTS: A total of 135 subjects were evaluated, including 49 with PHPT (discovery group), 47 control patients without PHPT, and an independent validation cohort of 39 PHPT patients. Of 27 miRNAs evaluated, 9 (miR-335-5p, miR-130b-3p, miR-125b-5p, miR-23a-3p, miR-152-3p, miR-582-5p, miR-144-5p, miR-320a, and miR-19b-3p) were differentially expressed in PHPT compared with matched control subjects. All 9 differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and 8 of the 9 correlated with calcium levels. No differentially expressed miRNAs were consistently correlated with markers of BMD. Subjects with PHPT segregate from controls based on the signature of these 9 miRNAs on principle component analysis. CONCLUSIONS: These data suggest that PHPT is characterized by a unique miRNA signature that is distinct from postmenopausal and idiopathic osteoporosis. Levels of specific miRNAs significantly correlate with PTH, suggesting that bone remodeling in PHPT may be mediated in part by PTH-induced changes in miRNA.

Osteoporosis and Fragility Fractures in Patients With Cirrhosis Evaluated for Liver Transplantation: Identification of High-Risk Patients Based on Computed Tomography at Evaluation.

INTRODUCTION: Osteoporosis in candidates for liver transplantation (LT) is often underdiagnosed despite the important consequences of morbidity. METHODS: We included 376 patients with cirrhosis evaluated for LT with available computed tomography (CT) scans. Prevalent vertebral fractures (VFs) were identified on CT reconstructions, and bone density was assessed by measuring CT attenuation of the L1 vertebra (L1-CT). RESULTS: We identified 139 VFs in 55 patients (14.6%). Logistic regression models showed that low L1-CT was the only independent determinant of VF. DISCUSSION: In patients with cirrhosis evaluated for LT, CT scans identified persons with severe osteoporosis without additional costs.

Long-term effects of aromatase inhibitor withdrawal on bone mineral density in early breast cancer patients: 10-year follow-up results of the BREX study.

PURPOSE: We aimed to provide long-term bone mineral density (BMD) data on early breast cancer patients of the BREX (Breast Cancer and Exercise) study. The effects of exercise and adjuvant endocrine treatment 10 years after randomization were analyzed, with special emphasis on aromatase inhibitor (AI) therapy discontinuation at 5 years. METHODS: The BREX study randomized 573 pre- and postmenopausal breast cancer patients into a 1-year supervised exercise program or a control group. 372 patients were included into the current follow-up analysis. BMD (g/cm2) was measured by dual-energy X-ray absorptiometry at lumbar spine (LS), left femoral neck (FN), and the total hip. Separate groups were displayed according to baseline menopausal status, and whether the patient had discontinued AI therapy at 5 years or not. RESULTS: The BMD change from 5 to 10 years did not significantly differ between the two randomized arms. AI discontinuation at 5 years had statistically significant BMD effects. The FN BMD continued to decrease in patients who discontinued AI therapy during the first 5-year off-treatment, but the decrease was three-fold less than in patients without AI withdrawal (- 1.4% v. - 3.8%). The LS BMD increased (+ 2.6%) in patients with AI withdrawal during the first 5 years following treatment discontinuation, while a BMD decrease (-1.3%) was seen in patients without AI withdrawal. CONCLUSION: This study is to our knowledge the first to quantify the long-term impact of AI withdrawal on BMD. Bone loss associated with AI therapy seems partially reversible after stopping treatment. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov/ (Identifier Number NCT00639210).

The distribution of breast density in women aged 18 years and older.

PURPOSE: Age and body mass index (BMI) are critical considerations when assessing individual breast cancer risk, particularly for women with dense breasts. However, age- and BMI-standardized estimates of breast density are not available for screen-aged women, and little is known about the distribution of breast density in women aged < 40. This cross-sectional study uses three different modalities: optical breast spectroscopy (OBS), dual-energy X-ray absorptiometry (DXA), and mammography, to describe the distributions of breast density across categories of age and BMI. METHODS: Breast density measures were estimated for 1,961 Australian women aged 18-97 years using OBS (%water and %water + %collagen). Of these, 935 women had DXA measures (percent and absolute fibroglandular dense volume, %FGV and FGV, respectively) and 354 had conventional mammographic measures (percent and absolute dense area). The distributions for each breast density measure were described across categories of age and BMI. RESULTS: The mean age was 38 years (standard deviation = 15). Median breast density measures decreased with age and BMI for all three modalities, except for DXA-FGV, which increased with BMI and decreased after age 30. The variation in breast density measures was largest for younger women and decreased with increasing age and BMI. CONCLUSION: This unique study describes the distribution of breast density measures for women aged 18-97 using alternative and conventional modalities of measurement. While this study is the largest of its kind, larger sample sizes are needed to provide clinically useful age-standardized measures to identify women with high breast density for their age or BMI.

Osteoporotic Precise Screening Using Chest Radiography and Artificial Neural Network: The OPSCAN Randomized Controlled Trial.

Background Diagnosing osteoporosis is challenging due to its often asymptomatic presentation, which highlights the importance of providing screening for high-risk populations. Purpose To evaluate the effectiveness of dual-energy x-ray absorptiometry (DXA) screening in high-risk patients with osteoporosis identified by an artificial intelligence (AI) model using chest radiographs. Materials and Methods This randomized controlled trial conducted at an academic medical center included participants 40 years of age or older who had undergone chest radiography between January and December 2022 without a history of DXA examination. High-risk participants identified with the AI-enabled chest radiographs were randomly allocated to either a screening group, which was offered fully reimbursed DXA examinations between January and June 2023, or a control group, which received usual care, defined as DXA examination by a physician or patient on their own initiative without AI intervention. A logistic regression was used to test the difference in the primary outcome, new-onset osteoporosis, between the screening and control groups. Results Of the 40 658 enrolled participants, 4912 (12.1%) were identified by the AI model as high risk, with 2456 assigned to the screening group (mean age, 71.8 years ± 11.5 [SD]; 1909 female) and 2456 assigned to the control group (mean age, 72.1 years ± 11.8; 1872 female). A total of 315 of 2456 (12.8%) participants in the screening group underwent fully reimbursed DXA, and 237 of 315 (75.2%) were identified with new-onset osteoporosis. After including DXA results by means of usual care in both screening and control groups, the screening group exhibited higher rates of osteoporosis detection (272 of 2456 [11.1%] vs 27 of 2456 [1.1%]; odds ratio [OR], 11.2 [95% CI: 7.5, 16.7]; P < .001) compared with the control group. The ORs of osteoporosis diagnosis were increased in screening group participants who did not meet formalized criteria for DXA compared with those who did (OR, 23.2 [95% CI: 10.2, 53.1] vs OR, 8.0 [95% CI: 5.0, 12.6]; interactive P = .03). Conclusion Providing DXA screening to a high-risk group identified with AI-enabled chest radiographs can effectively diagnose more patients with osteoporosis. Clinical trial registration no. NCT05721157 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Smith and Rothenberg in this issue.

Bone mineral density in young adults 5 to 11 years after adolescent metabolic and bariatric surgery for severe obesity compared to peers.

OBJECTIVE: Metabolic and bariatric surgery (MBS) is associated with decreased bone mineral density (BMD) in adults. The long-term impact of MBS during adolescence on BMD is unknown. We report bone health status 5 to 11 years after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) from the Teen-LABS study cohort. METHODS: Between 2016 and 2022, BMD was measured by dual energy x-ray absorptiometry (DXA) in 106 young adults who had undergone MBS as adolescents. Volumetric BMD by peripheral quantitative computed tomography was measured on a subset. Ninety-one controls who had not undergone MBS were recruited for comparison. RESULTS: In cases (RYGB: mean age 26.8 ± 1.9 years, mean BMI 42.1 ± 9.9 kg/m2, VSG: mean age 25.1 ± 2.1 years, mean BMI 37.1 ± 8.4 kg/m2), compared to controls (mean age 26.5 ± 2.7 years, mean BMI 40.2 ± 8.7 kg/m2) (age p < 0.001, BMI p = 0.02), adjusted mean DXA-BMD (g/cm2) of the RYGB (n = 58) and VSG (n = 48) groups were lower at the hip (-10.0% and -6.3%), femoral neck (-9.6% and -5.7%) and ultra-distal radius (-7.9% and -7.0%; all p < 0.001), respectively. DXA-BMD did not differ between RYGB and VSG groups. Trabecular volumetric BMD at the radius and tibia were lower in the RYGB (-30% and -26%) and VSG (-15% and -14%) groups compared to the control group (p < 0.001). Greater time since MBS was associated with lower BMD Z-scores at the hip (p = 0.05) and femoral neck (p = 0.045). Percent change in body mass index (BMI) from baseline or in the first year after MBS were not associated with bone measures at a median of 9.3 years post MBS. CONCLUSION: BMD, especially of the hip and femoral neck, was lower in young adults who underwent MBS during adolescence compared to matched peers who had not undergone MBS. BMD Z-scores of the femoral neck were inversely associated with time since MBS but were not associated with BMI change.

Longitudinal changes in body fat and metabolic complications in young people with perinatally acquired HIV.

BACKGROUND: The role of body fat on metabolic complications remains poorly understood in young people living with perinatally acquired HIV (YPHIV). OBJECTIVE: Our objective was to assess the association of changes in adiposity over 2 years with metabolic outcomes in YPHIV. METHODS: The PHACS Adolescent Master Protocol (AMP) study enrolled YPHIV from 2007 to 2009 across 15 US sites, including Puerto Rico. We included YPHIV aged 7-19 years with body composition data assessed by whole-body dual-energy X-ray absorptiometry (DXA) at baseline and 2 years later. Metabolic outcomes included homeostatic model assessment of insulin resistance (HOMA-IR) and non-high-density lipoprotein cholesterol (non-HDL-C). We fitted linear regression models to assess the association of increase in body fat over 2 years with metabolic outcomes at years 2 and 3. RESULTS: In all, 232 participants had a second DXA and either HOMA-IR or non-HDL-C measured at year 2. Participant characteristics at the first DXA were: age 12 years (9-14) [median (Q1-Q3)], 69% Black, and median CD4 count 714 cells/µL; 70% with HIV RNA <400 copies/mL. In adjusted analyses for every 1% increase in body fat from baseline to year 2, HOMA-IR was higher by 1.03-fold at year 3 (95% CI: 1.00, 1.05). We observed that for every 1% increase in body fat from baseline to year 2, non-HDL-C was 0.72 mg/dL higher at year 2 (95% CI: -0.04-1.49) and 0.81 mg/dL higher at year 3 (95% CI: -0.05-1.66). CONCLUSIONS: Increases in adiposity over time may lead to downstream decreased insulin sensitivity and dyslipidaemia in YPHIV.

Body composition parameters in systemic sclerosis-a systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to summarize current evidence regarding body composition (BC) in SSc in order to gain new insights and improve clinical care in the context of the nutritional status of SSc patients. METHODS: The databases Web of Science, PubMed, Scopus and Cochrane Library were searched on 4 January 2023. Studies were included if they provided data regarding BC obtained by dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) in patients with SSc and healthy controls (HC). The study design criteria for inclusion were cohort and observational studies. The risk of bias assessment was performed using the Newcastle-Ottawa scale. For meta-analysis, mean difference with a 95% confidence interval was obtained and all results were depicted as forest plots. RESULTS: The number of retrieved publications was 593, of which nine were included in a random-effects meta-analysis totalling 489 SSc patients and 404 HC. Overall, significantly lower body mass index, lean mass (LM), fat mass (FM) and phase angle values were found in SSc patients when compared with HC. Furthermore, FM and LM were significantly lower in SSc patients when the DXA method was applied, whereas the same parameters were comparable between two groups of participants when BIA was applied. CONCLUSION: Altered BC is characteristic of SSc patients indicating the need for regular nutritional status assessment in order to improve the quality of life and clinical care of patients with SSc.

Sarcopenia assessed by DXA and hand-grip dynamometer: a potential marker of damage, disability and myokines imbalance in inflammatory myopathies.

OBJECTIVES: To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM). METHODS: Forty adult IM patients with a disease duration ≥12 months, low or no disease activity for ≥6 months, were prospectively enrolled. Thirty healthy age and sex-matched volunteers were enrolled as controls. Whole-body DXA and hand-grip dynamometer were used to measure muscle mass, grip strength and diagnose sarcopenia (EWGSOP2 criteria). Relationships between the results of strength in 12 muscles, functional tests, patient-reported disability, IMACS damage score, and history of the disease were assessed. The serum levels of potential molecular actors in the damage were measured. RESULTS: DXA and grip strength measurements took ≤20 min. Both muscle mass and grip strength were decreased in IM patients vs volunteers (-10% and -30%, respectively) with a dispersion that varied widely (interquartile range -24.3% to +7.8% and -51.3% to -18.9%, respectively). Muscle mass and grip strength were non-redundantly correlated (r up to 0.6, P = 0.0001) with strength in 14 muscles (manual muscle test and hand-held dynamometer), functions (of limbs, respiratory and deglutition muscles), patient-reported disability, damage (extension and severity in muscular and extra-muscular domains) and blood levels of several myokines. Seven IM patients (17.5%) were sarcopenic. They had the worst damage, impaired functions, disability and history of severe myopathy. Decreased irisin and osteonectin levels were associated with sarcopenia (area under the curve 0.71 and 0.80, respectively). CONCLUSION: DXA and hand-grip dynamometer are useful tools to assess damage in IM. Irisin and osteonectin may play a role in IM damage pathogenesis.

The developing juvenile talus: Radiographic identification of distinct ontogenetic phases and structural trajectories.

Trabecular bone architecture in the developing skeleton is a widely researched area of bone biomechanics; however, despite its significance in weight-bearing locomotion, the developing talus has received limited examination. This study investigates the talus with the purpose of identifying ontogenetic phases and developmental patterns that contribute to the growing understanding of the developing juvenile skeleton. Colour gradient mapping and radiographic absorptiometry were utilised to investigate 62 human tali from 38 individuals, ranging in age-at-death from 28 weeks intrauterine to 20 years of age. The perinatal talus exhibited a rudimentary pattern comparable to the structural organisation observed within the late adolescent talus. This early internal organisation is hypothesised to be related to the vascular pattern of the talus. After 2 years of age, the talus demonstrated refinement, where radiographic trajectories progressively developed into patterns consistent with adult trabecular organisation, which are linked to the forces associated with the bipedal gait, suggesting a strong influence of biomechanical forces on the development of the talus.

Characteristics of bone mineral density in patients with functional hypothalamic amenorrhoea and its association with reproductive hormones and body composition.

OBJECTIVE: Bone mineral density (BMD) is typically reduced in patients with female athlete triad (FAT) and anorexia nervosa (AN). However, bone health in most patients with functional hypothalamic amenorrhoea (FHA), who may not suffer from severe energy deficiency, has not received adequate attention in clinical practice. This study aimed to investigate BMD and its association with clinical and endocrine features in individuals with FHA and to provide clinical evidence for improving bone loss and preventing osteoporosis in FHA. DESIGN: To assess the bone status of patients with FHA and investigate its association with various clinical and endocrinological characteristics. PATIENTS: We retrospectively analysed 80 patients with FHA who attended the Obstetrics and Gynecology Hospital of Fudan University from January 2022 to March 2023. MEASUREMENTS: The levels of reproductive hormones, including luteinising hormone (LH), follicle-stimulating hormone, oestradiol (E2 ) and total testosterone (TT), were examined at the time of initial diagnosis, and a body composition analyser was used to measure body fat percentage (BF%), lean body mass (LBM) and segmental muscle/fat. Dual-emission X-ray absorptiometry was used to measure lumbar spine BMD and femoral neck BMD in patients with FHA, and the Z score was calculated. RESULTS: The study cohort consisted of 80 female patients with FHA. The average age of the patients was 24.64 ± 6.02 years, and their body mass index (BMI) was 19.47 ± 2.86 kg/m2 . The duration of weight loss was 12 (6, 24) months, while the duration of oligo/amenorrhoea was 12 (4.5, 24) months. The mean degree of weight loss was 18.39 ± 9.53%. Low BMD were present in 15% of patients with FHA at the lumbar spine and/or femoral neck; 12.5% and 10% had low bone mass at the lumbar spine and femoral neck, respectively. The low bone mass group experienced a longer period of weight loss than the normal group [24 (16.5, 60) vs. 12 (4.5, 24) months, p = .037]. In addition, the abnormal group had a lower BMR (basal metabolic rate, BMR) [1158 ± 85 vs. 1231 ± 91 kcal/day, p = .011] and lower bone mineral content [2.15 ± 0.26 vs. 2.43 ± 0.31 kg, p = .009] than the normal group. Both LBMD and femoral neck BMD (Fn BMD) were positively correlated with BMI, BF%, LBM, and regional muscle/fat mass (all p < .05). There was also a positive correlation between LBMD and basal LH levels (p = .009) and waist-to-hip ratio (p = .034), whereas Fn BMD was positively correlated with TT levels (p = .029). Multiple linear regression analysis showed that LBM was positively associated with LBMD (ß = .007, 95% confidence interval [CI] = 0.004-0.009, p < .001), while trunk muscle mass was positively associated with Fn BMD (ß = .046, 95% CI = 0.013-0.080, p = .008). CONCLUSION: Fifteen percent of the patients with FHA exhibited low bone mass, a condition associated with prolonged weight loss. The basal LH and TT levels showed positive correlations with LBMD and Fn BMD, respectively. Meanwhile, BMR levels, BMI, BF%, and muscle mass were all positively correlated with LBMD and Fn BMD. Clinically, we should be attentive to suboptimal bone health in patients with FHA and take early screening, diagnosis and intervention measures, especially appropriate muscle mass gain, to prevent the onset of osteoporosis and fragility fractures in the long term.

Bone health in women with premature ovarian insufficiency/early menopause: a 23-year longitudinal analysis.

STUDY QUESTION: What is the frequency of, and predictors for, osteoporosis, fractures, and osteoporosis management (investigation, treatment) in women with premature ovarian insufficiency (POI; menopause <40 years) and early menopause (EM; menopause 40-44years)? SUMMARY ANSWER: Over the 23-year follow-up duration, at a mean age of 68 years, women with POI/EM had higher osteoporosis/fracture risk and prevalence, higher osteoporosis screening and anti-osteoporosis medication use compared to women with usual age menopause; increasing age was predictive of increased risk of osteoporosis/fracture and menopause hormone therapy (MHT) prior to or at study entry (aged 45-50 years) was protective. WHAT IS KNOWN ALREADY: Women with POI/EM have increased risk of osteoporosis and fractures with limited data regarding risk factors for reduced bone density and fractures. Clinical guidelines recommend screening with dual X-ray absorptiometry (DXA) and treatment with MHT for most women with POI/EM to reduce osteoporosis and fracture risk; however, studies indicate gaps in osteoporosis knowledge, guideline uptake, and management adherence by clinicians and women. STUDY DESIGN, SIZE, DURATION: The Australian Longitudinal Study on Women's Health is a prospective longitudinal study of Australian women. This study uses the cohort of women born between 1946 and 1951, surveyed nine times between 1996 and 2019. Data from the Australian administrative health records, including hospital admissions data (fractures, osteoporosis), Medicare Benefits Schedule (DXA), and the Pharmaceutical Benefits Scheme (PBS; MHT, anti-osteoporosis medication, available only from 2002) were linked to survey data. PARTICIPANTS/MATERIALS, SETTING, METHODS: Survey respondents with self-reported age of menopause were included. POI/EM was defined as menopause <45 years. T-test or chi-square were used for comparisons at baseline (P < 0.05 indicates significance). Generalized estimating equations for panel data explored predictors for the longitudinal outcomes of osteoporosis, fractures, DXA rates, MHT use, and anti-osteoporosis medication (in women with osteoporosis/fracture, from Survey 4 onwards only). Univariable regression was performed, and variables retained where P < 0.2, to form the multivariable model, and bootstrapping with 100 repetitions at 95% sampling of the original dataset to ensure robustness of results. MAIN RESULTS AND THE ROLE OF CHANCE: Eight thousand six hundred and three women were included: 610 (7.1%) with POI/EM. Mean (SD) baseline age was 47.6 (1.45) years in the entire cohort and mean (SD) age of menopause was 38.2 (7.95) and 51.3 (3.04) years in women with POI/EM and usual age menopause, respectively (P < 0.001). Over the 23 years, of women with POI/EM, 303 (49.7%) had osteoporosis/fractures, 421 (69.0%) had DXA screening, 474 ever used MHT (77.7%), and 116 (39.1%) of those with osteoporosis/fractures used anti-osteoporosis medication. Of women with usual age menopause, 2929 (36.6%) had osteoporosis/fractures, 4920 (61.6%) had DXA screening, 4014 (50.2%) used MHT, and 964 (33.0%) of those with osteoporosis/fractures used anti-osteoporosis medication. Compared to women with menopause at age ≥45 years and after adjusting for other risk factors, women with POI/EM had increased risk of osteoporosis (odds ratio [OR] 1.37; 95% CI 1.07-1.77), fractures (OR 1.45; 1.15-1.81), DXA testing (OR 1.64; 1.42-1.90), MHT use (OR 6.87; 5.68-8.30), and anti-osteoporosis medication use (OR 1.50; 1.14-1.98). In women with POI/EM women, increasing age was associated with greater risk of osteoporosis/fracture (OR 1.09; 1.08-1.11), and MHT prior to or at study entry (aged 45-50 years), was protective (OR 0.65, 0.45-0.96). In women with POI/EM, age (OR 1.11; 1.10-1.12), fractures (OR 1.80, 1.38-2.34), current smoking (OR 0.60; 0.43-0.86), and inner (OR 0.68; 0.53-0.88) or outer regional (OR 0.63; 0.46-0.87) residential location were associated with DXA screening. In women with POI/EM, increasing age (OR 1.02; 1.01-1.02), and currently consuming alcohol (OR 1.17; 1.06-1.28), was associated with having ever used MHT. In the 299 women with POI/EM and osteoporosis/fractures, only 39.1% ever received treatment with an anti-osteoporosis medication. Increasing age (OR 1.07; 1.04-1.09) and lower BMI (OR 0.95; 0.92-0.98) were associated with greater likelihood of treatment with anti-osteoporosis medication. LIMITATIONS, REASONS FOR CAUTION: Survey data including age of menopause were self-reported by participants; fracture questions were not included in the 2001 survey, and location or level of trauma of self-reported fractures was not asked. Additional risk/protective factors such as vitamin D status, calcium intake, and exercise were not able to be included. Due to sample size, POI and EM were combined for all analyses, and we were unable to differentiate between causes of POI/EM. PBS data were only available from 2004, and hospital admissions data were state-based, with all of Australia were only available from 2007. WIDER IMPLICATIONS OF THE FINDINGS: This study supports previous literature indicating increased risk of osteoporosis and fractures in women with POI, and adds evidence for women with POI/EM, where there was a relative paucity of data. This is the first study to analyse a variety of clinical and demographic risk factors for osteoporosis and fractures in women with POI/EM, as well as analysing investigation and treatment rates. In these women, using MHT prior to or at study entry, aged 45-50 years, was protective for osteoporosis/fractures; however, having ever used MHT was not, highlighting the importance of early treatment with MHT in these women to preserve bone strength. Although women with POI/EM and osteoporosis or fractures were more likely to use anti-osteoporosis medications than those with usual age menopause, overall treatment rates are low at <40%, demonstrating a significant treatment gap that should be addressed to reduce future fracture risk. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Australian NHMRC Centre of Research Excellence Women's Health in Reproductive Life (CRE-WHIRL, project number APP1171592). A.R.J. is the recipient of a National Health and Medical Research Council post-graduate research scholarship (grant number 1169192). P.R.E. is supported by a National Health and Medical Research Council grant 1197958. P.R.E. reports grants paid to their institution from Amgen, Sanofi, and Alexion, honoraria from Amgen paid to their institution, and honoraria from Alexion and Kyowa-Kirin. TRIAL REGISTRATION NUMBER: N/A.

Evaluating the impact of COVID-19 on DXA waiting lists and osteoporosis prescription trends in England 2019-2023.

This study uses NHS waiting times and osteoporosis medication community prescription datasets to assess the impact of COVID-19 on DXA waits and osteoporosis medication patterns in England. Results show significant increases in DXA waiting list times and variation in prescription rates. Investment is needed to improve waiting list times. PURPOSE: This study investigates the impact of COVID-19 on DXA scan waiting lists, service recovery and osteoporosis medication prescriptions in the NHS following the March 2020 national lockdowns and staff redeployment. METHODS: Data from March 2019 to June 2023, including NHS digital diagnostics waiting times (DM01) and osteoporosis medication prescriptions from the English Prescribing Dataset (EPD), were analysed. This encompassed total waiting list data across England's seven regions and prescribing patterns for various osteoporosis medications. Analyses included total activity figures and regression analysis to estimate expected activity without COVID-19, using R for all data analysis. RESULTS: In England, DXA waiting lists have grown significantly, with the yearly mean waiting list length increasing from 31,851 in 2019 to 65,757 in 2023. The percentage of patients waiting over 6 weeks for DXA scans rose from 0.9% in 2019 to 40% in 2020, and those waiting over 13 weeks increased from 0.1% in 2019 to 16.7% in 2020. Prescription trends varied, with increases in denosumab, ibandronic acid and risedronate sodium and decreases in alendronic acid, raloxifene hydrochloride and teriparatide. A notable overall prescription decrease occurred in the second quarter of 2020. CONCLUSION: COVID-19 has significantly increased DXA scan waiting lists with ongoing recovery challenges. There is a noticeable disparity in DXA service access across England. Osteoporosis care, indicated by medication prescriptions, also declined during the pandemic. Addressing these issues requires focused investment and effort to improve DXA scan waiting times and overall access to osteoporosis care in England.

Associations between new obesity indices and abnormal bone density in type 2 diabetes mellitus patients.

The clinical data analysis found that, compared with the traditional obesity index, the waist-weight ratio (WWR) has more advantages in predicting abnormal bone mineral density in subjects with type 2 diabetes. WWR may serve as a new predictive indicator for osteoporosis in T2DM patients. PURPOSE: This study was designed to explore the correlation between obesity-related indices and bone mineral density (BMD) and its influencing factors in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 528 patients with type 2 diabetes were recruited. Glucose tolerance, insulin stimulation, and blood biochemical tests were conducted on all participants. All subjects underwent dual-energy X-ray bone density testing and were grouped based on the bone density results. RESULTS: Compared with those in the normal BMD group, the waist-to-body weight ratio (WWR) and weight-adjusted-waist index (WWI) in the osteopenia and osteoporosis groups were significantly greater, while body mass index (BMI) was significantly lower (P < 0.05). The logistic regression results showed that the WWR, WWI, and BMI were independently correlated with abnormal BMD in T2DM patients (P < 0.05). WWR and the WWI were negatively correlated with the T-value of bone density in various parts of the body, while BMI was positively correlated with the T-value of bone density (P < 0.05). The area under the working characteristic curve (AUC) for T2DM patients with abnormal bone mass predicted by the WWR [0.806, 95% CI = (0.770-0.843), P < 0.001] was greater than that for patients with other obesity indicators, such as the WWI and BMI. CONCLUSION: We found a positive correlation between the WWR and bone density in T2DM patients. Compared with other obesity indicators, such as BMI and WWI, the WWR has a stronger discriminative ability for T2DM patients with abnormal bone density. Therefore, more attention should be given to the WWR in T2DM patients.

Sarcopenia definitions and their association with injurious falls in older Swedish women from the Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone fractures (SUPERB) study.

Associations between different sarcopenia definitions and the risk of injurious falls were investigated in 75-80-year-old women in the Swedish SUPERB cohort. Only sarcopenia according to the Sarcopenia Definitions and Outcomes Consortium (SDOC) definition was associated with incident injurious falls with and without fractures in older women. PURPOSE: To investigate the association between three commonly used sarcopenia definitions and the risk of injurious falls in a population of older Swedish women. METHODS: A total of 2,883 75-80-year-old women with complete data on relevant sarcopenia definitions from the Swedish SUPERB cohort were studied. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC: low handgrip strength and gait speed), revised European Working Group on Sarcopenia in Older People (EWGSOP2: low appendicular lean mass index (ALMI, dual-energy X-ray absorptiometry (DXA)-derived), appendicular lean mass (kg)/height (m2), hand grip strength (kg), or low chair stand time (s)), and Asian Working Group for Sarcopenia (AWGS: low ALMI and hand grip strength (kg) or low gait speed (m/s)). Questionnaires captured the occurrence of falls in the past 12 months. Incident injurious falls were identified using national registers. Cox regression (hazard ratios (HR) and 95% confidence intervals (CI)) analyses were performed without adjustment and after adjustment for age, body mass index, previous falls, and the Charlson comorbidity index. RESULTS: During a median (IQR) follow-up time of 7.06 (6.2-7.9) years, there were 491 injurious falls without fracture and 962 injurious falls when also including falls resulting in a fracture. Sarcopenia according to EWGSOP2 and AWGS was not associated with an increased risk of injurious falls. Individuals with sarcopenia defined by SDOC had a higher risk of injurious falls with and without fracture (HR 2.11; 95% CI, 1.63-2.73 and HR, 2.16; 95% CI, 1.55-3.02, respectively). CONCLUSION: Sarcopenia definitions confined to muscle function and strength such as SDOC, rather than including DXA-determined ALMI (EWGSOP2 and AWGS), are associated with incident injurious falls with and without fractures in older women.

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

Joint replacement surgery is common in older adults, leading to increasing periprosthetic fracture (PPFx) occurrence. We reviewed all PPFx seen over a 4-year period at an academic hospital. Clinical osteoporosis could be diagnosed based on existing data in 104 (67%) at the time of PPFx. Periprosthetic fractures are generally osteoporosis-related. PURPOSE: Periprosthetic fractures (PPFx) cause morbidity, mortality, and cost. This study's purpose was to describe osteoporosis-related data available at the time of PPFx. METHODS: The electronic medical record (EMR) of PPFx patients seen over 4 years 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 2 years before PPFx. Clinical osteoporosis was defined as prior diagnosis, prescribed osteoporosis treatment, T-score ≤ - 2.5, HU ≤ 100, or prior fracture. RESULTS: Records of 156 PPFx patients (115 F/41 M), 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. CONCLUSION: 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.

Total knee arthroplasty and periprosthetic distal femoral fracture: looking beyond the osteoporosis to previous osteoporotic fracture.

Osteoporosis increases the risk of periprosthetic distal femoral fractures after TKA, especially in patients with a history of osteoporotic fractures. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized by the patients following primary TKA. PURPOSE: Osteoporosis is a risk factor for fractures, including those of the hip, vertebrae, and distal radius; however, the association between osteoporosis and periprosthetic fractures after total knee arthroplasty (TKA) has not been much investigated. Therefore, we aimed to investigate the association of the presence of systemic osteoporosis with periprosthetic fractures after TKA. METHODS: This study included 34 patients with periprosthetic fractures following primary TKA and 106 controls matched for age and sex. Bone mineral density was evaluated at the femoral neck, total hip, and lumbar spine using dual X-ray absorptiometry. Medical records were reviewed for age; sex; body mass index; smoking; rheumatoid arthritis, endocrine diseases, and cardiovascular diseases; history of glucocorticoid use; medication for osteoporosis; and history of previous osteoporotic fracture. In addition, anterior femoral notching after TKA was evaluated. Univariable and multivariable logistic regression analysis were used to determine factors associated with periprosthetic fracture. RESULTS: The prevalence of osteoporosis in the fracture group was higher than that in the control group (61.8% vs. 40.6%, p=0.045). The rate of medication for osteoporosis was significantly low in the fracture group (47.6 % vs 76.7%, p=0.026). History of previous osteoporotic fracture (odds ratio [OR], 9.1; p=0.015) and osteoporosis (OR, 3.6; p=0.013) were significant risk factors for periprosthetic fractures after TKA. Medication for osteoporosis could decrease the risk of periprosthetic fracture (OR 0.3; p=0.020). CONCLUSION: Osteoporosis is a major risk factor for periprosthetic distal femoral fractures after TKA. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized to the patients following primary TKA, especially in patients with a history of osteoporotic fracture. LEVEL OF EVIDENCE: Prognostic study, level III.