Effects of daily probiotic supplementation with Lactobacillus acidophilus on calcium status, bone metabolism biomarkers, and bone mineral density in postmenopausal women: a controlled and randomized clinical study.

Background: Menopause poses significant health risks for women, particularly an increased vulnerability to fractures associated with osteoporosis. Dietary interventions have emerged as promising strategies, focusing on mitigating the risk of osteoporosis rather than solely addressing the established disease. This 12-week randomized controlled trial aimed to analyze the effects of consuming Lactobacillus acidophilus probiotics on calcium levels, biomarkers of bone metabolism, and bone mineral density (BMD) profiles in postmenopausal women. Methods: Fifty-five participants were randomly assigned to receive either a placebo (n = 25) or the probiotic L. acidophilus UALa-01™ (n = 30) daily via oral intervention. Throughout the study, evaluations included body composition, blood biochemical parameters, serum calcium levels, and biomarkers of bone metabolism. Additionally, Dual-energy X-ray absorptiometry was used to measure BMD profiles. Results: The findings delineated that the probiotic group experienced a decrease in serum calcium levels compared to their initial levels. However, hair calcium levels and biomarkers related to bone metabolism showed no notable changes within this group. Consumption of probiotic L. acidophilus also seemed to prevent fluctuations in bone turnover markers. Moreover, there were no significant alterations in BMD levels at the lumbar spine, left femur, and total body in the probiotic group. Additionally, probiotic intake led to favorable outcomes by significantly reducing both body fat and visceral fat during the intervention period. Conversely, an adverse effect of consuming probiotic L. acidophilus was observed with a significant increase in glucose concentration. Conclusion: In conclusion, the consumption of L. acidophilus probiotics daily for 12 weeks among postmenopausal women does not affect the profile of BMD, but it may help in stabilizing bone turnover. It is important to note that most measured parameters were within the normal range for this population. However, it is worth noting that 3 months of probiotic supplementation could potentially disrupt calcium and glucose status in postmenopausal women.

Towards visceral fat estimation at population scale: correlation of visceral adipose tissue assessment using three-dimensional cross-sectional imaging with BIA, DXA, and single-slice CT.

Background: In terms of assessing obesity-associated risk, quantification of visceral adipose tissue (VAT) has become increasingly important in risk assessment for cardiovascular and metabolic diseases. However, differences exist in the accuracy of various modalities, with a lack of up-to-date comparison with three-dimensional whole volume assessment. Aims: Using CT or MRI three-dimensional whole volume VAT as a reference, we evaluated the correlation of various commonly used modalities and techniques namely body impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA) as well as single slice CT to establish how these methods compare. Methods: We designed the study in two parts. First, we performed an intra-individual comparison of the 4558 participants from the UK Biobank cohorts with matching data of MRI abdominal body composition, DXA with VAT estimation, and BIA. Second, we evaluated 174 CT scans from the publicly available dataset to assess the correlation of the commonly used single-slice technique compared to three-dimensional VAT volume. Results: Across the UK Biobank cohort, the DXA-derived VAT measurement correlated better (R2 0.94, p<0.0001) than BIA (R2 0.49, p<0.0001) with reference three-dimensional volume on MRI. However, DXA-derived VAT correlation was worse for participants with a BMI of < 20 (R2 = 0.62, p=0.0013). A commonly used single slice method on CT demonstrated a modest correlation (R2 between 0.51 - 0.64), with best values at L3- and L4 (R2 L3 = 0.63, p<0.0001; L4 = 0.64, p<0.0001) compared to reference three-dimensional volume. Combining multiple slices yielded a better correlation, with a strong correlation when L2-L3 levels were combined (R2 = 0.92, p<0.0001). Conclusion: When deployed at scale, DXA-derived VAT volume measurement shows excellent correlation with three-dimensional volume on MRI based on the UK Biobank cohort. Whereas a single slice CT technique demonstrated moderate correlation with three-dimensional volume on CT, with a stronger correlation achieved when multiple levels were combined.

Evaluation of bone density and skeletal muscle mass after sleeve gastrectomy using computed tomography method.

Introduction: Sleeve gastrectomy is the most common surgical procedure to reduce weight and treat metabolic complications in patients with moderate-to-severe obesity; however, it affects the musculoskeletal system. Dual-energy X-ray absorptiometry (DXA), which is commonly used to measure bone mineral density (BMD), may be affected by excess fat tissue around the bones, interrupting BMD measurement. Due to the strong correlation between DXA and the Hounsfield units (HU) obtained from computed tomography (CT) scans, BMD assessment using clinical abdominal CT scans has been useful. To date, there has been no report of detailed CT evaluation in patients with severe obesity after sleeve gastrectomy. Objective: This study investigated the effect of sleeve gastrectomy in severely obese patients on bone and psoas muscle density, and cross-sectional area using retrospective clinical CT scans. Methods: This was a retrospective observational study that included 86 patients (35 males and 51 females) who underwent sleeve gastrectomy between March 2012 and May 2019. Patients' clinical data (age at the time of surgery, sex, body weight, body mass index (BMI), comorbidities, and preoperative and postoperative blood test results, HU of the lumbar spine and psoas muscle and psoas muscle mass index (PMI)) were evaluated. Results: The mean age at the time of surgery was 43 years, and the body weight and BMI significantly reduced (p < 0.01) after surgery. The mean hemoglobin A1c level showed significant improvement in males and females. Serum calcium and phosphorus levels remained unchanged before and after surgery. In CT analysis, HU of the lumbar spine and psoas muscle showed no significant decrease, but PMI showed a significant decrease (p < 0.01). Conclusions: Sleeve gastrectomy could dramatically improve anthropometric measures without causing changes in serum calcium and phosphorus levels. Preoperative and postoperative abdominal CT revealed no significant difference in the bone and psoas muscle density, and the psoas muscle mass was significantly decreased after sleeve gastrectomy.

A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis.

Background & Aims: Efruxifermin has shown clinical efficacy in patients with non-alcoholic steatohepatitis (NASH) and F1-F3 fibrosis. The primary objective of the BALANCED Cohort C was to assess the safety and tolerability of efruxifermin in patients with compensated NASH cirrhosis. Methods: Patients with NASH and stage 4 fibrosis (n = 30) were randomized 2:1 to receive efruxifermin 50 mg (n = 20) or placebo (n = 10) once-weekly for 16 weeks. The primary endpoint was safety and tolerability of efruxifermin. Secondary and exploratory endpoints included evaluation of non-invasive markers of liver injury and fibrosis, glucose and lipid metabolism, and changes in histology in a subset of patients who consented to end-of-study liver biopsy. Results: Efruxifermin was safe and well-tolerated; most adverse events (AEs) were grade 1 (n = 7, 23.3%) or grade 2 (n = 19, 63.3%). The most frequent AEs were gastrointestinal, including transient, mild to moderate diarrhea, and/or nausea. Significant improvements were noted in key markers of liver injury (alanine aminotransferase) and glucose and lipid metabolism. Sixteen-week treatment with efruxifermin was associated with significant reductions in non-invasive markers of fibrosis including Pro-C3 (least squares mean change from baseline [LSMCFB] -9 µg/L efruxifermin vs. -3.4 µg/L placebo; p = 0.0130) and ELF score (-0.4 efruxifermin vs. +0.4 placebo; p = 0.0036), with a trend towards reduced liver stiffness (LSMCFB -5.7 kPa efruxifermin vs. -1.1 kPa placebo; n.s.). Of 12 efruxifermin-treated patients with liver biopsy after 16 weeks, 4 (33%) achieved fibrosis improvement of at least one stage without worsening of NASH, while an additional 3 (25%) achieved resolution of NASH, compared to 0 of 5 placebo-treated patients. Conclusions: Efruxifermin appeared safe and well-tolerated with encouraging improvements in markers of liver injury, fibrosis, and glucose and lipid metabolism following 16 weeks of treatment, warranting confirmation in larger and longer term studies. Lay summary: Cirrhosis resulting from non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease, represents a major unmet medical need. Currently there are no approved drugs for the treatment of NASH. This proof-of-concept randomized, double-blind clinical trial demonstrated the potential therapeutic benefit of efruxifermin treatment compared to placebo in patients with cirrhosis due to NASH. Clinical Trial Number: NCT03976401.

Exercise volume load in women with breast cancer: Study protocol for the ABRACE randomized clinical trial.

Background: An increased number of breast cancer patients are challenged by acute and persistent treatment side effects. Oncology guidelines have been establishing physical exercise to counteract several treatment-related toxicities throughout cancer care. However, evidence regarding the optimal dose-response, feasibility, and the minimal resistance exercise volume and/or intensity remains unclear. The ABRACE Study will assess the impact of different resistance training volumes (i.e., single or multiple sets) combined with aerobic exercise on physical and psychological outcomes of breast cancer patients undergoing primary treatment. Methods: This study is a randomized, controlled, three-armed parallel trial. A total of 84 participants, aged ≥18 years, with breast cancer stages I-III, initiating adjuvant or neoadjuvant chemotherapy (≤50% of sessions completed) will be randomized to multiple sets resistance training plus aerobic training group, single set resistance training plus aerobic training group or control group. Neuromuscular and cancer-related fatigue (primary outcomes), muscle strength, muscle thickness, muscle quality by echo intensity, body composition, cardiorespiratory capacity, functional performance, upper-body endurance and quality of life will be measured before and after the 12-week intervention. Our analysis will follow the intention-to-treat approach and per-protocol criteria, with additional sub-group analysis. Discussion: Findings support prescribing exercise during chemotherapy for breast cancer and elucidate the potential role of different resistance training volumes as a management strategy for physical and psychological impairments in women with early-stage breast cancer. Our main hypothesis is for superiority in physical and psychological outcomes for both training groups compared to the control group, with no difference between single or multiple sets groups. Trial registration: Clinical trials NCT03314168.

Assessment of DXA derived bone quality indexes and bone geometry parameters in early breast cancer patients: A single center cross-sectional study.

Background: Bone mineral density (BMD) lacks sensitivity in individual fracture risk assessment in early breast cancer (EBC) patients treated with aromatase inhibitors (AIs). New dual-energy X-ray absorptiometry (DXA) based risk factors are needed. Methods: Trabecular bone score (TBS), bone strain index (BSI) and DXA parameters of bone geometry were evaluated in postmenopausal women diagnosed with EBC. The aim was to explore their association with morphometric vertebral fractures (VFs). Subjects were categorized in 3 groups in order to evaluate the impact of AIs and denosumab on bone geometry: AI-naive, AI-treated minus (AIDen-) or plus (AIDen+) denosumab. Results: A total of 610 EBC patients entered the study: 305 were AI-naive, 187 AIDen-, and 118 AIDen+. In the AI-naive group, the presence of VFs was associated with lower total hip BMD and T-score and higher femoral BSI. As regards as bone geometry parameters, AI-naive fractured patients reported a significant increase in femoral narrow neck (NN) endocortical width, femoral NN subperiosteal width, intertrochanteric buckling ratio (BR), intertrochanteric endocortical width, femoral shaft (FS) BR and endocortical width, as compared to non-fractured patients. Intertrochanteric BR and intertrochanteric cortical thickness significantly increased in the presence of VFs in AIDen- patients, not in AIDen+ ones. An increase in cross-sectional area and cross-sectional moment of inertia, both intertrochanteric and at FS, significantly correlated with VFs only in AIDen+. No association with VFs was found for either lumbar BSI or TBS in all groups. Conclusions: Bone geometry parameters are variably associated with VFs in EBC patients, either AI-naive or AI treated in combination with denosumab. These data suggest a tailored choice of fracture risk parameters in the 3 subgroups of EBC patients.

Factors associated with poor sleep quality in midlife Singaporean women: The Integrated Women's Health program (IWHP).

Objective: To examine factors associated with poor sleep quality in community-dwelling midlife women. Methods: Healthy women (aged 45-69 years) of Chinese, Malay and Indian ethnicities attending well-women clinics at the National University Hospital, Singapore, completed the Pittsburgh Sleep Quality Index (PSQI). A PQSI score >5 denoted poor sleep quality. The women filled out validated questionnaires covering menopausal and genito-urinary symptoms, and mental health. Physical performance was measured. Bone mineral density and visceral adiposity were assessed by dual energy X-ray absorptiometry. Binary logistic regression analyses assessed independent factors for poor sleep. Results: Poor sleep quality was reported in 38.2% of women (n = 1094, mean age: 56.4 ± 6.2 years). Indian women had higher sleep disturbance scores than Chinese women (mean ± SD: 1.33 ± 0.58 vs 1.17 ± 0.49). Malays experienced more daytime dysfunction (0.54 ± 0.60 vs 0.33 ± 0.55) and had a higher overall PSQI score (6.00 ± 3.31 vs 5.02 ± 2.97) than the Chinese. A low education level (aOR: 1.76, 95% CI: 1.01-3.05), feelings of irritability (2.67, 1.56-4.60) and vaginal dryness (1.62, 1.03-2.54) were associated with poor sleep quality in the adjusted multivariable model. Women with moderate to severe disability were ∼3 times (2.99, 1.20-7.44) more likely to experience less than ideal sleep quality, while urinary incontinence (1.53, 1.08-2.17) and breast cancer history (2.77, 1.36-5.64) were also associates of poor sleep quality. Conclusion: Self-reports of education level, irritability, vaginal dryness, disability, urinary incontinence, and breast cancer history were independently related to poor sleep. Ethnic differences suggest the need for targeted interventions among the ethnic groups.

Impact of simple equation for estimating appendicular skeletal muscle mass in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

Background: Sarcopenia, which is evaluated based on appendicular skeletal muscle mass (ASM) using dual-energy X-ray absorptiometry and bioelectrical impedance analysis, is a prognostic predictor for adverse outcomes in patients with coronary artery disease (CAD). However, a simple equation for estimating ASM is yet to be validated in clinical practice. Methods: We enrolled 2211 patients with CAD who underwent percutaneous coronary intervention at our hospital between 2010 and 2017. The mean age was 68 years and 81.5 % were men. Patients were divided into 2 groups based on each ASM index (ASMI): low; male < 7.3 and female < 5.0 and high; male ≥ 7.3 and female ≥ 5.0. ASM was calculated using the following equation: 0.193 × bodyweight + 0.107 × height - 4.157 × gender - 0.037 × age - 2.631. Primary endpoints were major adverse cardiac events (MACE, which includes cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure), and all-cause mortality. Results: During the median follow-up period of 4.8 years, cumulative incidence of events were significantly higher in the low ASMI group. Cox proportional hazards model revealed that the low ASMI group had a significantly higher risk of primary endpoints than the high ASMI group (all-cause mortality; hazard ratio (HR): 2.13, 95 % confidence interval [CI]: 1.40-3.22, p < 0.001 and 4-point MACE; HR: 1.72, 95 % CI: 1.12-2.62, p = 0.01). Similar trends were observed after stratification by age of 65 years. Conclusion: Low ASMI, evaluated using the aforementioned equation, is an independent predictor of MACE and all-cause mortality in patients with CAD.

Physical activity is inversely associated with hepatic fibro-inflammation: A population-based cohort study using UK Biobank data.

Background & Aims: Physical activity (PA) is recommended in the management of non-alcoholic fatty liver disease (NAFLD) given its beneficial effects on liver fat and cardiometabolic risk. Using data from the UK Biobank population-cohort, this study examined associations between habitual PA and hepatic fibro-inflammation. Methods: A total of 840 men and women aged 55-70 years were included in this cross-sectional study. Hepatic fibro-inflammation (iron-corrected T1 [cT1]) and liver fat were measured using MRI, whilst body fat was measured using dual-energy X-ray absorptiometry. PA was measured using accelerometry. Generalised linear models examined associations between PA (light [LPA], moderate [MPA], vigorous [VPA], moderate-to-vigorous [MVPA] and mean acceleration) and hepatic cT1. Models were fitted for the whole sample and separately for upper and lower median groups for body and liver fat. Models were adjusted for sociodemographic and lifestyle variables. Results: In the full sample, LPA (-0.08 ms [-0.12 to -0.03]), MPA, (-0.13 ms [-0.21 to -0.05]), VPA (-1.16 ms [-1.81 to -0.51]), MVPA (-0.14 ms [-0.21 to -0.06]) and mean acceleration (-0.67 ms [-1.05 to-0.28]) were inversely associated with hepatic cT1. With the sample split by median liver or body fat, only VPA was inversely associated with hepatic cT1 in the upper median groups for body (-2.68 ms [-4.24 to -1.13]) and liver fat (-2.33 [-3.73 to -0.93]). PA was unrelated to hepatic cT1 in the lower median groups. Conclusions: Within a population-based cohort, device-measured PA is inversely associated with hepatic fibro-inflammation. This relationship is strongest with VPA and is greater in people with higher levels of body and liver fat. Lay summary: This study has shown that people who regularly perform greater amounts of physical activity have a reduced level of inflammation and fibrosis in their liver. This beneficial relationship is particularly strong when more intense physical activity is undertaken (i.e., vigorous-intensity), and is most visible in individuals with higher levels of liver fat and body fat.

Aromatase deficiency in a tall man: Case report of two novel mutations and review of literature.

Aromatase (CYP19A1) is the only enzyme known to catalyse the conversion of androgen to estrogen. Aromatase deficiency occurs due to mutation in CYP19A1gene which has an autosomal recessive inheritance pattern. It leads to decrease in estrogen synthesis and delayed epiphyseal closure, eunuchoid habitus and osteopenia. We are presenting here, a 24 years old male, with history of progressive increase in height and knock knees. X-ray showed open wrist and knee epiphysis. The serum testosterone level was normal and serum estradiol level was undetectable. Semen analysis showed azoospermia. Clinical exome sequencing gave two novel mutations in CYP19A1. The first variant was a novel single nucleotide deletion of thiamine at 570th base of the cDNA (c.570delT) of CYP19A1 gene. The second variant detected was again a novel one in the same gene in Exon 5 corresponding 344th base of the cDNA (c344G>A) resulting in a missense mutation of 115th arginine to glutamine in the protein. Sanger sequencing showed that the later mutation was inherited from the father. The patient was started on oral estradiol valerate for epiphyseal closure to prevent further increase in height. Only 15 mutations have been reported in the aromatase gene in males till date, our report of these novel mutations will be an add-on to the literature.

Impact of romosozumab on serum calcium concentration and factors predicting the fluctuations in calcium concentration upon romosozumab administration: A multicenter retrospective study.

Objectives: As romosozumab has both bone anabolic and antiresorptive effects, it is not clear which patient groups are more likely to have decreased calcium concentrations when treated with romosozumab. The aim of this study was to investigate the impact of romosozumab treatment on serum calcium concentration in patients with osteoporosis with a high risk of fractures and identify factors that might be associated with, or even predict, a fluctuation in calcium concentration upon romosozumab administration. Materials and methods: In total, 47 patients were included in this retrospective study. We performed a Wilcoxon signed-rank test to identify differences in the calcium concentration before and 1 month after romosozumab initiation. Associations between baseline variables and changes in serum calcium concentration were investigated with a multiple-linear regression model using a forward-backward stepwise procedure. Results: Romosozumab administration reduced the serum calcium concentration by an average of 3.1 % after 1 month. No patient complained of symptoms of hypocalcemia during the first month after treatment. Univariate regression analysis showed that age and calcium concentration were significantly associated with the decrease in serum calcium concentrations by romosozumab administration. In addition, stepwise regression analysis identified age and calcium concentrations as independent factors associated with the decrease in calcium concentration by romosozumab. Conclusion: Romosozumab administration caused a modest but significant decrease in serum calcium concentration. Older age and higher baseline calcium concentrations were associated with a greater decrease in calcium concentrations by romosozumab administration. Although the likelihood of severe hypocalcemia from romosozumab administration may be low, physicians prescribing romosozumab to patients with osteoporosis should be aware of the symptoms of hypocalcemia and promptly evaluate calcium levels if patients complain of these symptoms.

Associations between paraspinal muscles fatty infiltration and lumbar vertebral bone mineral density - An investigation by fast kVp switching dual-energy CT and QCT.

Purpose: To investigate the relationship between paraspinal muscles fat content and lumbar bone mineral density (BMD). Methods: A total of 119 participants were enrolled in our study (60 males, age: 50.88 ± 17.79 years, BMI: 22.80 ± 3.80 kg·m-2; 59 females, age: 49.41 ± 17.69 years, BMI: 22.22 ± 3.12 kg·m-2). Fat content of paraspinal muscles (erector spinae (ES), multifidus (MS), and psoas (PS)) were measured at (ES L1/2-L4/5; MS L2/3-L5/S1; PS L2/3-L5/S1) levels using dual-energy computed tomography (DECT). Quantitative computed tomography (QCT) was used to assess BMD of L1 and L2. Linear regression analysis was used to assess the relationship between BMD of the lumbar spine and paraspinal muscles fat content with age, sex, and BMI. The variance inflation factor (VIF) was used to detect the degree of multicollinearity among the variables. P < .05 was considered to indicate a statistically significant difference. Results: The paraspinal muscles fat content had a fairly significant inverse association with lumbar BMD after controlling for age, sex, and BMI (adjusted R 2 = 0.584-0.630, all P < .05). Conclusion: Paraspinal muscles fat content was negatively associated with BMD.Paraspinal muscles fatty infiltration may be considered as a potential marker to identify BMD loss.

Abdominal aortic calcification on lateral spine images captured during bone density testing and late-life dementia risk in older women: A prospective cohort study.

Background: Dementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority. Methods: In prospective study of 958 ambulant community-dwelling older women (≥70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E (APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records. Findings: At baseline women were 75.0 ± 2.6 years, 44.7% had low AAC, 36.4% had moderate AAC and 18.9% had extensive AAC. Over 14.5- years, 150 (15.7%) women had a late-life dementia hospitalisation (n = 132) and/or death (n = 58). Compared to those with low AAC, women with moderate and extensive AAC were more likely to suffer late-life dementia hospitalisations (9.3%, 15.5%, 18.3%, respectively) and deaths (2.8%, 8.3%, 9.4%, respectively). After adjustment for cardiovascular risk factors and APOE, women with moderate and extensive AAC had twice the relative hazards of late-life dementia (moderate, aHR 2.03 95%CI 1.38-2.97; extensive, aHR 2.10 95%CI 1.33-3.32), compared to women with low AAC. Interpretation: In community-dwelling older women, those with more advanced AAC had higher risk of late-life dementia, independent of cardiovascular risk factors and APOE genotype. Given the widespread use of bone density testing, simultaneously capturing AAC information may be a novel, non-invasive, scalable approach to identify older women at risk of late-life dementia. Funding: Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, National Health and Medical Research Council of Australia.

Serum Resistin Levels and Related Genetic Variants Are Associated With Bone Mineral Density in Postmenopausal Women.

Background: Osteoporosis is a multifactorial disorder and a number of genetic variants or loci responsible for bone mineral density (BMD) have been identified. Resistin, a novel adipokine has diverse role in human body including its function in bone remodeling. The objective of this study was to see the association of serum resistin levels and related genetic variants (rs3931020, rs13144478) with BMD in postmenopausal females. Methods: This comparative analytical study was conducted on postmenopausal osteoporotic (n=101), osteopenic (n=77) and non-osteoporotic (n=74) females. For comparison and correlational analysis, Kruskal-Wallis test and Spearman's rho correlation were used respectively. Hardy-Weinberg equilibrium (HWE) was calculated by using Chi-square test (χ2). Results: There was significant difference in the serum levels of resistin (p <0.001), among the three groups. Significant negative correlation of resistin was observed with BMD at various sites. Serum resistin levels were significantly low in the rs3931020 AA homozygous genotype (p = 0.010), and significantly high in the rs13144478 AT heterozygous genotype (p = 0.020), BMD at all sites except left femoral neck was significantly high in rs3931020 AA genotype, while BMD at lumbar spine, left hip and total BMD were significantly low in the rs13144478 TT homozygotes. Conclusion: High serum resistin levels are associated with low BMD and single nucleotide variation in rs3931020 and rs13144478 may lead to high serum resistin levels and low bone mineral density. Resistin can serve as a new genetic marker, potential therapeutic target and predictor of osteoporosis.

Identification of bone metabolism disorders in patients with Alström and Bardet-Biedl syndromes based on markers of bone turnover and mandibular atrophy.

Objectives: Causative variants in genes responsible for Alström syndrome (ALMS) and Bardet-Biedl syndrome (BBS) cause damage to primary cilia associated with correct functioning of cell signaling pathways in many tissues. Despite differences in genetic background, both syndromes affect multiple organs and numerous clinical manifestations are common including obesity, retinal degeneration, insulin resistance, type 2 diabetes and many others. The aim of the study was to evaluate bone metabolism abnormalities and their relation to metabolic disorders based on bone turnover markers and presence of mandibular atrophy in patients with ALMS and BBS syndromes. Material and methods: In 18 patients (11 with ALMS and 7 with BBS aged 5-29) and in 42 age-matched (p < 0.05) healthy subjects, the following markers of bone turnover were assessed: serum osteocalcin (OC), osteoprotegerin (OPG), s-RANKL and urinary deoxypyridinoline - DPD. In addition, a severity of alveolar atrophy using dental panoramic radiograms was evaluated. Results: Lower serum OC (p = 0.0004) and urinary DPD levels (p = 0.0056) were observed in the study group compared to controls. In ALMS and BBS patients, serum OC and urinary DPD values negatively correlated with the HOMA-IR index, while a positive correlation between the OC and 25-OHD levels and a negative correlation between s-RANKL and fasting glucose concentrations were found. A significant difference in the incidence of low-grade mandibular atrophy between patients with ALMS and BBS and controls (p < 0.0001) was observed. Conclusions: The identification of bone metabolism disorders in patients with ALMS and BBS syndromes indicates the necessity to provide them with appropriate diagnosis and treatment of these abnormalities.

A Pilot Study to Assess Opportunistic Use of CT-Scan for Osteoporosis Screening in Chronic Pancreatitis.

Objectives: CT scans are commonly performed in patients with chronic pancreatitis (CP). Osteopathy and fractures are recognized in CP but no osteoporosis screening guidelines are recommended. "Opportunistic" CT scan-derived bone density thresholds are assessed for identifying osteoporosis in CP. Methods: Retrospective pilot cohort study. CP subjects who had CT scans and dual-energy x-ray absorptiometry (DXA) within 1 year were included. CT-derived bone density was measured at the L1 level. Pearson's correlation was performed between age and CT-derived bone density in Hounsfield unit (HU). Univariate analysis using HU to identify osteoporosis was performed at various thresholds of bone density. The discriminatory ability of the model was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC). Several HU thresholds were tested. Results: Twenty-seven CP subjects were included, of whom 11 had normal bone density, 12 osteopenia, and four osteoporosis on DXA. The mean age was 59.9 years (SD 13.0). There was a negative correlation of age with HU (r = -0.519, p = 0.006). CT-derived bone density predicted DXA-based osteoporosis in the univariable analysis (Odds Ratio (OR) = 0.97 95% Confidence Interval (CI) 0.94-1.00, p = 0.03). HU thresholds were tested. A threshold of 106 HU maximized the accuracy (AUC of 0.870). Conclusions: CT scan may be repurposed for "opportunistic" screening to rule out osteoporosis in CP. A larger study is warranted to confirm these results.

Spontaneous reshaping of vertebral fractures in an adolescent with osteogenesis imperfecta.

Background: Vertebral compression fractures (VFs) are a common and severe finding in patients with osteoporosis. In children, VFs have the unique potential to reshape and regain their original configuration. Spontaneous vertebral body reshaping (i.e., medication-unassisted) has been reported in secondary osteoporosis. Here we describe a previously unreported spontaneous vertebral reshaping in an adolescent with osteogenesis imperfecta (OI) with multiple vertebral fractures. Case report: A 17-year-old female was diagnosed with OI type I at 5 years of age caused by a novel frameshift variant in COL1A1 (NM_000088.4: c.540delC; p.Met181TrpfsTer84). Due to parental reservations about medication, she had never received bisphosphonate or any other bone active therapy. A lateral spine X-ray demonstrated transparent bones and no VF. However, previous spine X-rays taken at age of 6 years at an external institution showed VFs in T5-7 (Genant semiquantitative method grade I-II). The two lateral spine x-rays, taken 11 years apart, demonstrate that substantial spontaneous vertebral reshaping occurred without bone active therapy during puberty. Discussion: Vertebral reshaping is explained by the stabilization of bone mineral density (BMD) and the remaining growth capacity the children. We hypothesize that spontaneous reshaping may occur in milder forms of OI, and that puberty may be a key mediator of the phenomenon. In all children with OI and vertebral fractures, we nevertheless recommend bisphosphonate therapy since it improves bone mass, BMD, vertebral shape, physical activity and reduces fracture rates.

Attention deficit hyperactivity disorder medications and bone mineral density of adults in the United States.

Introduction: Several medications used to treat attention deficit hyperactivity disorder (ADHD) have been associated with diminished bone mineral density (BMD) in children. The objective of this study was to determine if evidence exists for a similar association among adults. Materials and methods: A retrospective cross-sectional analysis was conducted using data collected by the National Health Nutrition Examination Survey 2013-2018. Data from 7961 individuals aged 18 to 50, 79 of whom were taking medications to treat ADHD. Dual-energy X-ray absorptiometry scans provided measure of body composition. Linear regression models were used to examine associations between ADHD medication use and body composition. Results: Stimulant ADHD medication usage was found to be associated with decreased BMD in both the skull (-6.6%; 95% CI 5.9-7.2) (P < 0.05) and thoracic spine (-6.0%; 95% CI 5.1-7.0) (P < 0.05). No difference in BMD was seen in any other skeletal region based on stimulant ADHD medication use (P > 0.05). We found no evidence to suggest that duration of use affected the observed decreases in BMD, P > 0.05. Conclusion: This study using a nationally representative sample assessed whether stimulant medication use in adults with ADHD was associated with decreased BMD. The overall results are inconclusive. Further study is needed to better evaluate if ADHD and/or stimulant medication use is independently associated with bone health.

The Mediating Role of Endocrine Factors in the Positive Relationship Between Fat Mass and Bone Mineral Content in Children Aged 9-11 Years: The Physical Activity and Nutrition in Children Study.

Introduction: We aimed to investigate whether the relationship between fat mass and bone mineral content (BMC) is mediated by insulin, leptin, adiponectin, dehydroepiandrosterone sulphate, testosterone and estradiol in children aged 9-11 years. Materials and Methods: We utilised cross-sectional data from the Physical Activity and Nutrition in Children study (n = 230 to 396; 112 to 203 girls). Fat mass and BMC were assessed with dual-energy X-ray absorptiometry. Endocrine factors were assessed from fasted blood samples. We applied the novel 4-way decomposition method to analyse associations between fat mass, endocrine factors, and BMC. Results: Fat mass was positively associated with BMC in girls (ß = 0.007 to 0.015, 95% confidence interval (CI) 0.005 to 0.020) and boys (ß = 0.009 to 0.015, 95% CI 0.005 to 0.019). The relationship between fat mass and BMC was mediated by free leptin index in girls (ß = -0.025, 95% CI -0.039 to -0.010) and boys (ß = -0.014, 95% CI -0.027 to -0.001). The relationship between fat mass and BMC was partially explained by mediated interaction between fat mass and free leptin index in boys (ß = -0.009, 95% CI -0.013 to -0.004) and by interaction between fat mass and adiponectin in girls (ß = -0.003, 95% CI -0.006 to -0.000). Conclusion: At greater levels of adiponectin and free leptin index, the fat mass and BMC relationship becomes less positive in girls and boys respectively. The positive association between fat mass with BMC was largely not explained by the endocrine factors we assessed. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT01803776], identifier NCT01803776.

Contemporary kidney transplantation has a limited impact on bone microarchitecture.

Bone microarchitecture is an important component of bone quality and disturbances may reduce bone strength and resistance to trauma. Kidney transplant recipients have an excess risk of fractures, and bone loss affecting both trabecular and cortical bone compartments have been demonstrated after kidney transplantation. The primary aim of this study was to investigate the impact of kidney transplantation on trabecular and cortical bone microarchitecture, assessed by histomorphometry and micro computed tomography (µCT). Iliac crest bone biopsies, analyzed by bone histomorphometry and µCT, were performed at time of kidney transplantation and 12 months post-transplantation in an unselected cohort of 30 patients. Biochemical markers of mineral metabolism and bone turnover were measured at both time-points. At 12 months post-transplantation, bone turnover was low in 5 (17%) and normal in 25 (83%) patients. By histomorphometry, bone remodeling normalized, with decreases in eroded perimeters (4.0 to 2.1%, p = 0.02) and number of patients with marrow fibrosis (41 to 0%, p < 0.001). By µCT, trabecular thickness (134 to 125 µM, p = 0.003) decreased slightly. Other parameters of bone volume and microarchitecture, including cortical thickness (729 to 713 µm, p = 0.73) and porosity (10.2 to 9.5%, p = 0.15), remained stable. We conclude that kidney transplantation with current immunosuppressive protocols has a limited impact on bone microarchitecture.