Real-world efficacy of a teriparatide biosimilar (RGB-10) compared with reference teriparatide on bone mineral density, trabecular bone score, and bone parameters assessed using quantitative ultrasound, 3D-SHAPER® and high-resolution peripheral computer tomography in postmenopausal women with osteoporosis and very high fracture risk.

A retrospective analysis comparing a teriparatide biosimilar (RGB-10) with reference teriparatide for osteoporosis treatment in postmenopausal women at high fracture risk found them to be therapeutically equivalent. Both provided significant improvements in lumber spine BMD, TBS, and other parameters of bone health, assessed using multiple diagnostic methods. PURPOSE: To compare the therapeutic efficacy of a teriparatide biosimilar (RGB-10) with reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high fracture risk. METHODS: A retrospective analysis of 25 postmenopausal female patients treated for osteoporosis with RGB-10 for 24 months and a matched cohort of 25 patients treated with reference teriparatide. The following outcomes were assessed at baseline, 12 and 24 months: bone mineral density (BMD) at the lumbar spine, femoral neck and total hip using dual-energy x-ray absorptiometry (DXA) and integral, trabecular and cortical volumetric and surface BMD using 3D-SHAPER® imaging, trabecular bone score (TBS), quantitative ultrasound (QUS) measurements, and high-resolution peripheral quantitative computed tomography (HRpQCT) imaging of the radius and tibia. RESULTS: No significant differences were observed between treatment groups in any of the measured parameters of BMD or bone health at baseline as well as in any timepoint when assessed using these various diagnostic methods. Both compounds provided equivalent significant improvements from baseline in measures of osteoporosis and fracture risk. CONCLUSION: The results of the analysis demonstrate the therapeutic equivalence of the teriparatide biosimilar (RGB-10) to reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high risk of fracture.

Bone density and fracture risk factors in ankylosing spondylitis: a meta-analysis.

We included 39 studies in our meta-analysis, finding that patients with ankylosing spondylitis (AS) exhibit decreased bone mineral density (BMD) and an elevated risk of fractures. Additionally, we analyzed the risk factors associated with fractures in these patients. INTRODUCTION: AS is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints, with reduced BMD, osteoporosis, and fractures being common complications. This study aims to systematically consolidate and conduct a meta-analysis of existing research to comprehensively understand decreased bone mineral density, osteoporosis, and fracture risks at various anatomical sites in AS patients. The objective is to provide reliable information for the management of AS patients and to inform clinical decision making. METHODS: We conducted a thorough search in various databases including Embase, PubMed, Cochrane Library, and Web of Science. These studies focused on the risk of and risk factors for decreased BMD, osteopenia, osteoporosis, and fractures at different sites among AS patients such as the lumbar spine and femoral neck. The quality of eligible studies was evaluated. Sensitivity analysis was performed to assess the reliability of our analysis results and understand the effects of individual studies on the heterogeneity across studies. RESULTS: A total of 39 studies were included. Our meta-analysis results revealed significant differences between AS patients and healthy controls. AS patients had significantly lower BMDs at the femoral neck, hip, lumbar vertebra 2 (L2), lumbar vertebra 3 (L3), and lumbar vertebra 4 (L4), but higher BMDs at 1/3 distal radius and ultra distal radius. Risk factors for fractures among AS patients included old age, long course of disease, and low BMD at the lumbar spine. In contrast, factors such as erythrocyte sedimentation rate (ESR), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, gender, and body mass index (BMI) were not risk factors for fractures in AS patients. CONCLUSION: Our study highlights that BMD at the femoral neck is more effective for evaluating AS patients compared with the BMD at the lumbar spine. Additionally, the risk of osteoporosis and fractures in AS patients is higher in younger patients and those at the early stage of this disease.

Forearm bone mineral density predicts screw loosening after lumbar fusion similar to lumbar Hounsfield unit value in patients with lumbar spondylolisthesis.

Preoperative bone density assessment is necessary to predict screw loosening. The forearm BMD is a useful predictor of BMD-related complications after lumbar operation. Our results show that the forearm BMD is as effective a predictor of screw loosening as the lumbar average HU value. Measurement of the forearm BMD may be a useful adjunct in predicting screw loosening following lumbar fusion. PURPOSE: To determine the relationship between forearm bone mineral density (BMD) and the risk of pedicle screw loosening in patients with lumbar spondylolisthesis. METHODS: We retrospectively evaluated 270 patients who underwent posterior lumbar interbody fusion for lumbar spondylolisthesis. The patients were divided into two groups on the basis of the with or without loose screws: the loosening group and the non-loosening group. The patient's gender, age, BMI, smoking and diabetes histories, and the operative segment were recorded as the basic information. The Hounsfield unit (HU) value for the BMD of the L1-4 lumbar was measured using computed tomography. The patient's distal one-third of the length of the radius and ulna of the non-dominant forearm was chosen as the site for dual-energy X-ray (DXA) bone density testing. RESULTS: The rate of screw loosening was 13% at a minimum 12 months follow-up. Average forearm BMD (0.461 ± 0.1 vs 0.577 ± 0.1, p < 0.001) and mean HU value (L1-4) (121.1 ± 27.3 vs 155.6 ± 32.2, p < 0.001) were lower in the screw loosening group than those in the non-loosening group. In multivariate logistic regression analysis, the forearm BMD (OR 0.840; 95%CI 0.797-0.886) and HU value (L1-4) (OR 0.952; 95%CI 0.935-0.969) were independent risk factor for screw loosening. The area under the curve (AUC) for the forearm BMD and HU value for prediction of pedicle screw loosening was 0.802 and 0.811. The forearm BMD cut-off for predicting pedicle screw loosening was 0.543 (sensitivity, 0.800; specificity, 0.864). CONCLUSIONS: The forearm BMD was an independent risk factor for loosening of the lumbar pedicle screws. The forearm BMD was a valid predictor of pedicle screw loosening in patients undergoing lumbar fusion, as was the CT HU value.

The joint effects of physical activity and sleep duration on risk of osteoporosis in Taiwanese adult population: The Taiwan Biobank Study.

Most studies investigating the association between physical activity and osteoporosis prevention only focused on specific types of physical activity. This study's evidence regarding the combined effects or interaction of sleep duration and physical activity. The findings emphasize the role of sleep duration and physical activity in association with osteoporosis. PURPOSE: The associations between physical activity, sleep duration, and prevalent osteoporosis in Taiwanese adults were studied in this cross-sectional study. METHODS: The Taiwan Biobank enrolled a community-based cohort of ~ 120,000 volunteers (as of April 30, 2020) between 30 and 76 years of age with no history of cancer. Amongst, bone mineral density (BMD) measures by dual-energy X-ray absorptiometry (DXA) were available in 22,402 participants. After excluding individuals who had no complete data of BMI (n = 23), MET score (n = 207), T-score (n = 8,826), and sleep duration (n = 16), 13,330 subjects were included as the primary cohort. Univariate and multivariable regression analyses were performed to determine the associations between the presence of osteoporosis, physical activity level, sleep duration, and other variables. RESULTS: The results showed that after adjustment, subjects with physical activity < 20 METs/week and ≥ 20 METs/week (aOR = 1.017 and 0.767, respectively) were associated with risk of osteoporosis than those with zero MET. The odds of osteoporosis were not significantly lower in subjects who slept for ≥ 8 h/day (aOR = 0.934,p=0.266). In addition, compared to short sleepers with no physical activity, adults with increased physical activity ≥ 20 METs/week and sleep ≥ 8 h/day had a significantly lowest likelihood of osteoporosis (aOR = 0.702). Those with medium physical activity (< 20 METs/week) plus average sleep duration (6.5-8 h/day) did not have significant higher odds of osteoporosis (aOR = 1.129,p=0.151). CONCLUSION: The findings emphasize the joint role of sleep duration and physical activity in association with osteoporosis. Adults with high physical activity plus high sleep hours have the highest BMD and lowest risk of osteoporosis.

The relationship between bone strain index, bone mass, microarchitecture and mechanical behavior in human vertebrae: an ex vivo study.

The aim of this study was to determine whether the Bone Strain Index (BSI), a recent DXA-based bone index, is related to bone mechanical behavior, microarchitecture and finally, to determine whether BSI improves the prediction of bone strength and the predictive role of BMD in clinical practice. PURPOSE: Bone Strain Index (BSI) is a new DXA-based bone index that represents the finite element analysis of the bone deformation under load. The current study aimed to assess whether the BSI is associated with 3D microarchitecture and the mechanical behavior of human lumbar vertebrae. METHODS: Lumbar vertebrae (L3) were harvested fresh from 31 human donors. The anteroposterior BMC (g) and aBMD (g/cm2) of the vertebral body were measured using DXA, and then the BSI was automatically derived. The trabecular bone volume (Tb.BV/TV), trabecular thickness (Tb.Th), degree of anisotropy (DA), and structure model index (SMI) were measured using µCT with a 35-µm isotropic voxel size. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies under displacement control to assess failure load and stiffness. RESULTS: The BSI was significantly correlated with failure load and stiffness (r = -0.60 and -0.59; p < 0.0001), aBMD and BMC (r = -0.93 and -0.86; p < 0.0001); Tb.BV/TV and SMI (r = -0.58 and 0.51; p = 0.001 and 0.004 respectively). After adjustment for aBMD, the association between BSI and stiffness, BSI and SMI remained significant (r = -0.51; p = 0.004 and r = -0.39; p = 0.03 respectively, partial correlations) and the relation between BSI and failure load was close to significance (r = -0.35; p = 0.06). CONCLUSION: The BSI was significantly correlated with the microarchitecture and mechanical behavior of L3 vertebrae, and these associations remained statistically significant regardless of aBMD.

Trabecular bone mineral density as measured by thoracic vertebrae predicts incident hip and vertebral fractures: the multi-ethnic study of atherosclerosis.

We evaluated the relationship of bone mineral density (BMD) by computed tomography (CT), to predict fractures in a multi-ethnic population. We demonstrated that vertebral and hip fractures were more likely in those patients with low BMD. This is one of the first studies to demonstrate that CT BMD derived from thoracic vertebrae can predict future hip and vertebral fractures. PURPOSE/INTRODUCTION: Osteoporosis affects an enormous number of patients, of all races and both sexes, and its prevalence increases as the population ages. Few studies have evaluated the association between the vertebral trabecular bone mineral density(vBMD) and osteoporosis-related hip fracture in a multiethnic population, and no studies have demonstrated the predictive value of vBMD for fractures. METHOD: We sought to determine the predictive value of QCT-based trabecular vBMD of thoracic vertebrae derived from coronary artery calcium scan for hip fractures in the Multi-Ethnic Study of Atherosclerosis(MESA), a nationwide multicenter cohort included 6814 people from six medical centers across the USA and assess if low bone density by QCT can predict future fractures. Measures were done using trabecular bone measures, adjusted for individual patients, from three consecutive thoracic vertebrae (BDI Inc, Manhattan Beach CA, USA) from non-contrast cardiac CT scans. RESULTS: Six thousand eight hundred fourteen MESA baseline participants were included with a mean age of 62.2 ± 10.2 years, and 52.8% were women. The mean thoracic BMD is 162.6 ± 46.8 mg/cm3 (95% CI 161.5, 163.7), and 27.6% of participants (n = 1883) had osteoporosis (T-score 2.5 or lower). Over a median follow-up of 17.4 years, Caucasians have a higher rate of vertebral fractures (6.9%), followed by Blacks (4.4%), Hispanics (3.7%), and Chinese (3.0%). Hip fracture patients had a lower baseline vBMD as measured by QCT than the non-hip fracture group by 13.6 mg/cm3 [P < 0.001]. The same pattern was seen in the vertebral fracture population, where the mean BMD was substantially lower 18.3 mg/cm3 [P < 0.001] than in the non-vertebral fracture population. Notably, the above substantial relationship was unaffected by age, gender, race, BMI, hypertension, current smoking, medication use, or activity. Patients with low trabecular BMD of thoracic vertebrae showed a 1.57-fold greater risk of first hip fracture (HR 1.57, 95% CI 1.38-1.95) and a nearly threefold increased risk of first vertebral fracture (HR 2.93, 95% CI 1.87-4.59) compared to normal BMD patients. CONCLUSION: There is significant correlation between thoracic trabecular BMD and the incidence of future hip and vertebral fracture. This study demonstrates that thoracic vertebrae BMD, as measured on cardiac CT (QCT), can predict both hip and vertebral fractures without additional radiation, scanning, or patient burden. Osteopenia and osteoporosis are markedly underdiagnosed. Finding occult disease affords the opportunity to treat the millions of people undergoing CT scans every year for other indications.

Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE: We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS: Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS: The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION: Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Evaluation of bone mineral density (BMD) and trabecular bone score (TBS) in pheochromocytoma and paraganglioma; a multi-centric case-control study from India.

Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) due to excess sympathetic system stimulation. Our study revealed low BMD and TBS (trabecular bone score) in cases compared to matched controls. Plasma-free nor-metanephrine and hypertension duration found to be most consistent predictive factors. PURPOSE: Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) and increased fracture risks. Sympathetic nervous system stimulation has been shown to increase bone resorption and decrease bone formation via ß2 receptors. Chronic inflammation and increased cytokine production add to more bone loss. TBS (trabecular bone score) is an established surrogate marker for bone histomorphometry. BMD and TBS data in pheochromocytoma and PPGL are scarce. The aim was to assess the BMD and TBS in pheochromocytoma and PPGL and look for clinical and biochemical predictors. METHODS: This case-control study had sample size of 58 (29 cases and controls each). BMI-, age-, and sex-matched controls were taken for comparison. Both cases and controls had undergone DXA scan and BMD {Z-scores and bone mineral concentration (BMC) in g/cm2} and TBS were analyzed. Detailed clinical histories and relevant biochemistry values were noted. RESULTS: The mean age of our case population was 29.5 ± 9.4 years with a mean age of HTN onset at 26.86 ± 6.6 years. Lumbar spine BMC (0.86 ± 0.14 vs 0.96 ± 0.15; p = 0.036), femoral neck Z-score (- 1.23 ± 1.07 vs - 0.75 ± 0.97; p = 0.003), and whole body BMC (0.91 ± 0.14 vs 1.07 ± 0.11; p = 0.000) were significantly low in cases compared to controls. Similarly, TBS was significantly lower in cases compared to controls (1.306 ± 0.113 vs 1.376 ± 0.083; p = 0.001). CONCLUSION: This study establishes both low bone mass and poor bone quality in an Indian pheochromocytoma and PPGL patient's cohort. Plasma-free nor-metanephrine and duration of hypertension were found to be most consistent predictive factors in multivariate regression analysis.

Utility of MRI-based vertebral bone quality scores and CT-based Hounsfield unit values in vertebral bone mineral density assessment for patients with diffuse idiopathic skeletal hyperostosis.

This study investigated bone mineral density assessment for patients with DISH. DXA-based T-scores overestimated bone quality, while MRI-based VBQ scores and CT-based HU values provided accurate assessments, particularly for advanced degenerative cases. This enhances accurate evaluation of BMD, crucial for clinical decision-making. PURPOSE: To investigate the diagnostic effectiveness of DXA, MRI, and CT in assessing bone mineral density (BMD) for diffuse idiopathic skeletal hyperostosis (DISH) patients. METHODS: Retrospective analysis of 105 DISH patients and 116 age-matched controls with lumbar spinal stenosis was conducted. BMD was evaluated using DXA-based T-scores, MRI-based vertebral bone quality (VBQ) scores, and CT-based Hounsfield unit (HU) values. Patients were categorized into three BMD subgroups. Lumbar osteophyte categories were determined by Mata score. Demographics, clinical data, T-scores, VBQ scores, and HU values were collected. Receiver operating characteristic (ROC) analysis identified VBQ and HU thresholds for diagnosing normal BMD using DXA in controls. Correlations between VBQ, HU, and lumbar T-score were analyzed. RESULTS: Age, gender, and BMI showed no significant differences between DISH and control groups. DISH patients had higher T-score (L1-4), the lowest T-score, and Mata scores. VBQ and HU did not significantly differ between groups. In controls, VBQ and HU effectively diagnosed normal BMD (AUC = 0.857 and 0.910, respectively) with cutoffs of 3.0 for VBQ and 104.3 for HU. DISH had higher normal BMD prevalence using T-scores (69.5% vs. 58.6%, P < 0.05), but no significant differences using VBQ (57.1% vs. 56.2%, P > 0.05) and HU (58.1% vs. 57.8%, P > 0.05). Correlations revealed moderate correlations between HU and T-scores (L1-4) in DISH (r = 0.642, P < 0.001) and strong in controls (r = 0.846, P < 0.001). Moderate negative correlations were observed between VBQ and T-scores (L1-4) in DISH (r = - 0.450, P < 0.001) and strong in controls (r = - 0.813, P < 0.001). CONCLUSION: DXA-based T-scores may overestimate BMD in DISH. VBQ scores and HU values could effectively complement BMD assessment, particularly in DISH patients or those with advanced lumbar degeneration.

Coffee Drinking and the Odds of Osteopenia and Osteoporosis in Middle-Aged and Older Americans: A Cross-Sectional Study in NHANES 2005-2014.

The study investigates the association of coffee consumption and odds of osteoporosis/osteopenia among individuals older than 50 years in the United States. In NHANES 2005-2014, drinking ≤ 2 cups(16 oz) of coffee per day can reduce the risk of osteoporosis/osteopenia at the femoral neck and lumbar spine in US adults. Previous epidemiological studies revealed that daily coffee intake reduced the incidence of a cluster of metabolic diseases, however, the link between coffee consumption and prevalence of osteoporosis/osteopenia still remain inconclusive and awaits further confirmation. Based on data collection from 2005 to 2014 survey cycles, National Health and Nutrition Examination Survey (NHANES), a sample size of 8789 participants aged 50 and above completing two nonconsecutive 24-h dietary recalls were eventually enrolled for analysis. Associations between coffee intake and BMD were assessed. A lower odds of having femoral neck osteopenia/osteoporosis (FOO) was observed in participants with moderate intake of coffee (≤ 2 cups per day), rather than other beverages (OR 0.83; 95% CI, 0.72-0.95; p = 0.01). Moreover, significant associations existed between daily caffeine intake and both FOO and lumbar-spine osteopenia/osteoporosis (LOO). Even after adjusting for decaffeinated coffee, tea, sugar-sweetened beverages (SSBs), and coffee consumption, osteopenia and osteoporosis the odds remained lower at both femoral and neck levels. Our data suggest moderate habitual coffee intake (≤ 2 cups coffee/day) would have protective effects against osteoporosis/osteopenia of femoral neck and spine, among US adults over the age of 50.

Secular Trends in Peak Bone Mineral Density: The National Health and Nutrition Examination Survey 1999-2018.

Peak bone mineral density (BMD) is one of the most important factors influencing the development of osteoporosis. It was predicted that a 10% increase in peak BMD will delay the onset of osteoporosis by 13 years. However, changes in peak BMD over time are unknown. This study aimed to investigate secular trends in peak BMD among young adults in the United States. Based on the National Health and Nutrition Examination Survey from 1999-2018, 3,975 males aged 19-28 years and 2370 females aged 31-40 years were our target population for estimating peak lumbar spine BMD. BMD was measured by dual-energy X-ray absorptiometry. Generalized linear models adjusted for multiple covariates were used to examine the secular trends in peak BMD in males and females, respectively. Secular trends for peak lumbar spine BMD from 1999-2000 to 2017-2018 were not statistically significant in males or females (all Plinear and Pquadratic > 0.05). Similar results were observed in race/ethnicity subgroups (all Plinear and Pquadratic > 0.05). However, in stratified analyses by obesity category, peak lumbar spine BMD in obese males and females increased from 1999-2000 to 2009-2010 and then decreased until 2017-2018, while peak lumbar spine BMD in non-obese females decreased from 1999-2000 to 2005-2006 and then increased until 2017-2018 (all Pquadratic < 0.05). Peak lumbar spine BMD was greater in obese males and females than in non-obese males and females up to 2009-2010, but not from 2011-2012 onwards. Overall, there were no significant secular trends in peak lumbar spine BMD. However, secular trends differed between obese and non-obese groups.

The Relationship Between Scoliosis, Spinal Bone Density, and Truncal Muscle Strength in Familial Dysautonomia Patients.

This combined retrospective and prospective study aimed to investigate the relationship between scoliosis, spinal bone mineral density (BMD), and truncal muscle strength in patients with familial dysautonomia (FD). A total of 79 FD patients (40 male, 39 female) aged 5-44 years were included. The severity of scoliosis, lumbar spine BMD (Z-score), and truncal muscle strength were assessed. Correlations were analyzed using Pearson's correlation coefficient. Inverse correlations were observed between scoliosis severity and BMD (r = - 0.328, p = 0.001), as indicated by increasingly negative Z-score values with worsening osteoporosis. There were also inverse correlations between scoliosis and truncal muscle strength (r = - 0.595, p < 0.001). The correlation between scoliosis and age was notable up to 22 years (r = 0.421, p = 0.01), but not in the older age group (22-44 years). Our study identified inverse correlations between osteoporosis and scoliosis, as well as between scoliosis and truncal muscle strength, in FD patients. These findings suggest that there may be a relationship between bone density, muscle strength, and the severity of spinal curvature in this population. While our results highlight the potential importance of early diagnosis and management of osteoporosis, and possibly the benefits of physical therapy to strengthen truncal muscles, further research is needed to determine the direct impact of these interventions on preventing the progression of scoliosis and its associated complications in FD patients. A long-term longitudinal study could provide more insights into these relationships and inform treatment strategies for FD patients.

Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study.

Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.

GC-MS analysis of 4-hydroxyproline: elevated proline hydroxylation in metformin-associated lactic acidosis and metformin-treated Becker muscular dystrophy patients.

Metformin (N,N-dimethylbiguanide), an inhibitor of gluconeogenesis and insulin sensitizer, is widely used for the treatment of type 2 diabetes. In some patients with renal insufficiency, metformin can accumulate and cause lactic acidosis, known as metformin-associated lactic acidosis (MALA, defined as lactate ≥ 5 mM, pH < 7.35, and metformin concentration > 38.7 µM). Here, we report on the post-translational modification (PTM) of proline (Pro) to 4-hydroxyproline (OH-Pro) in metformin-associated lactic acidosis and in metformin-treated patients with Becker muscular dystrophy (BMD). Pro and OH-Pro were measured simultaneously by gas chromatography-mass spectrometry before, during, and after renal replacement therapy in a patient admitted to the intensive care unit (ICU) because of MALA. At admission to the ICU, plasma metformin concentration was 175 µM, with a corresponding lactate concentration of 20 mM and a blood pH of 7.1. Throughout ICU admission, the Pro concentration was lower compared to healthy controls. Renal excretion of OH-Pro was initially high and decreased over time. Moreover, during the first 12 h of ICU admission, OH-Pro seems to be renally secreted while thereafter, it was reabsorbed. Our results suggest that MALA is associated with hyper-hydroxyprolinuria due to elevated PTM of Pro to OH-Pro by prolyl-hydroxylase and/or inhibition of OH-Pro metabolism in the kidneys. In BMD patients, metformin, at the therapeutic dose of 3 × 500 mg per day for 6 weeks, increased the urinary excretion of OH-Pro suggesting elevation of Pro hydroxylation to OH-Pro. Our study suggests that metformin induces specifically the expression/activity of prolyl-hydroxylase in metformin intoxication and BMD.

Lessons for future clinical trials in adults with Becker muscular dystrophy: Disease progression detected by muscle magnetic resonance imaging, clinical and patient-reported outcome measures.

BACKGROUND AND PURPOSE: Because Becker muscular dystrophy (BMD) is a heterogeneous disease and only few studies have evaluated adult patients, it is currently still unclear which outcome measures should be used in future clinical trials. METHODS: Muscle magnetic resonance imaging, patient-reported outcome measures and a wide range of clinical outcome measures, including motor function, muscle strength and timed-function tests, were evaluated in 21 adults with BMD at baseline and at 9 and 18 months of follow-up. RESULTS: Proton density fat fraction increased significantly in 10/17 thigh muscles after 9 months, and in all thigh and lower leg muscles after 18 months. The 32-item Motor Function Measurement (MFM-32) scale (-1.3%, p = 0.017), North Star Ambulatory Assessment (-1.3 points, p = 0.010) and patient-reported activity limitations scale (-0.3 logits, p = 0.018) deteriorated significantly after 9 months. The 6-min walk distance (-28.7 m, p = 0.042), 10-m walking test (-0.1 m/s, p = 0.032), time to climb four stairs test (-0.03 m/s, p = 0.028) and Biodex peak torque measurements of quadriceps (-4.6 N m, p = 0.014) and hamstrings (-5.0 N m, p = 0.019) additionally deteriorated significantly after 18 months. At this timepoint, domain 1 of the MFM-32 was the only clinical outcome measure with a large sensitivity to change (standardized response mean 1.15). DISCUSSION: It is concluded that proton density fat fraction imaging of entire thigh muscles is a sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, already after 9 months of follow-up. Finally, significant changes are reported in a wide range of clinical and patient-reported outcome measures, of which the MFM-32 appeared to be the most sensitive to change in adults with BMD.

Updated reference values for BMD and lean mass measured by DXA in Thai children.

INTRODUCTION: This study established normative references for total body less head (TBLH) BMD, lumbar spine (L1-L4) BMD, and both total and appendicular lean mass (LM) in Thai children and adolescents (aged 5-18 years) using DXA. This work expands upon 2014 normative data for Thai children, which included L2-L4 BMD, total body BMD (head included), and total LM. MATERIALS AND METHODS: We reanalyzed total body and lumbar spine DXA scans (Lunar Prodigy Pro, GE Healthcare; enCORE version 7.53) from 174 boys and 193 girls, using upgraded software (enCORE version 17SP2) for TBLH BMD, L1-L4 BMD, and LM analysis. The "enhanced" mode was applied for TBLH BMD and LM. Adjustments for total and appendicular LM were made relative to squared height (m2) to account for body size variability. RESULTS: Normative data stratified by sex and Tanner stage were generated for TBLH BMD, L1-L4 BMD, and LM indices. Weight and Tanner stage significantly determined BMD and LM. Adolescent girls exhibited higher LSBMD values due to earlier pubertal onset. Boys showed higher LM indices with more rapid gains during growth spurts. CONCLUSION: This study provides updated normative reference values for BMD (TBLH and L1-L4) and LM (total and appendicular) in Thai children and adolescents, measured via DXA. These references will enhance the assessment of low bone mass and LM deficits in Thai pediatric populations, particularly in those with chronic illnesses.

Effects of whole-body vibration on bone mineral density in postmenopausal women: an overview of systematic reviews.

OBJECTIVE: The aim of this study is to evaluate the findings of existing systematic reviews (SRs) and provide scientific evidence on the efficacy and safety of whole-body vibration (WBV) in improving bone mineral density (BMD) in postmenopausal women, to provide recommendations and guidance for future high-quality clinical research and SRs. METHODS: We conducted searches in six databases (SinoMed, CNKI, Cochrane Library, Embase, PubMed, Web of Science) from the inception of the databases until July 31, 2023. The language was limited to Chinese or English. The methodological quality, risk of bias, and evidence grade of outcomes were evaluated using AMSTAR-2, ROBIS, and GRADE, respectively. Additionally, the degree of overlap in randomized controlled trials (RCTs) among the SRs was calculated using corrected covered area (CCA). Furthermore, we performed quantitative synthesis or descriptive analysis of the relevant data. All relevant operations were independently conducted by two individuals. RESULTS: A total of 15 SRs were included in the analysis, out of which three were qualitative descriptions and 12 were meta-analyses. According to AMSTAR-2, only two SRs were rated as low or moderate, while the remaining 13 SRs were rated as critically low quality. The ROBIS assessment indicated that seven SRs had a low risk of bias, while 8 SRs had a high risk of bias. The overall findings suggest that WBV does not have a significant advantage in improving BMD in postmenopausal women. Furthermore, the CCA results revealed a high overlap in RCTs across five outcomes among the 15 SRs. Only five SRs reported specific adverse reactions/events experienced by participants after WBV interventions, and none of the SRs reported any severe adverse events. CONCLUSION: The existing evidence cannot establish definitive advantages of WBV in improving BMD in postmenopausal women. Therefore, we do not recommend the use of WBV for improving BMD in postmenopausal women. However, WBV may have potential value in maintaining BMD in postmenopausal women, further research is needed to confirm these findings.

Factors associated with low bone mineral density in Turner syndrome: a multicenter prospective observational study.

Turner syndrome (TS) is associated with a high risk of fracture due to low bone mineral density (BMD). While hypogonadism is known to play a role in decreasing BMD, other factors have not been studied well. Focusing on diet, exercise, and bone metabolism markers, the present, multicentric, prospective, observational study aimed to identify factors contributing to decreased BMD in TS. In total, 48 patients with TS aged between 5 and 49 years comprising a pre-pubertal group (n = 9), a cyclical menstruation group (n = 6), and a hormone replacement therapy (HRT) group (n = 33) were enrolled. The cyclical menstruation group and the HRT group were referred to collectively as the post-pubertal group. The bone mineral apparent density (BMAD) Z-score was higher in the pre-pubertal group than in the post-pubertal group (-0.3 SD vs. -1.8 SD; p = 0.014). Within the post-pubertal group, the median BMAD Z-score was -0.2 SD in the cyclical menstruation group and -2.3 SD in the HRT group (p = 0.016). Spearman's rank correlation revealed no correlation between the BMAD Z-score and bone metabolism markers. No significant relationship was observed between the BMAD Z-score and either the vitamin D sufficiency rate or the step sufficiency rate. A negative correlation was found between BMAD Z-score and serum sclerostin in the pre-pubertal group and serum FSH in the post-pubertal group. In conclusion, the present study found no relationship between the vertebral BMAD Z-score and diet or exercise habits in TS, indicating that estrogen deficiency is the chief reason for low BMD in TS.

Effects of high-intensity training on fatty infiltration in paraspinal muscles in elderly males with osteosarcopenia - the randomized controlled FrOST study.

BACKGROUND: Osteosarcopenia is a common geriatric syndrome with an increasing prevalence with age, leading to secondary diseases and complex consequences such as falls and fractures, as well as higher mortality and frailty rates. There is a great need for prevention and treatment strategies. METHODS: In this analysis, we used magnetic resonance imaging (MRI) data from the randomised controlled FrOST trial, which enrolled community-dwelling osteosarcopenic men aged > 72 years randomly allocated to 16 months of twice-weekly high-intensity resistance training (HIRT) or a non-training control group. MR Dixon imaging was used to quantify the effects of HIRT on muscle fat infiltration in the paraspinal muscles, determined as changes in muscle tissue, fat faction and intermuscular adipose tissue (IMAT) in the erector spinae and psoas major muscles. Intention-to-treat analysis with multiple imputation was used to analyse the data set. RESULTS: After 16 months of intervention, 15 men from the HIRT and 16 men from the CG were included in the MRI analysis. In summary, no positive effects on the fat infiltration of the erector spinae and psoas major muscles were observed. CONCLUSIONS: The previously reported positive effects on lumbar spine bone mineral density (BMD) suggest that mechanotransduction induces tropic effects on bone, but that fat infiltration of the erector spinae and psoas major muscles are either irreversible or, for some unknown reason, resistant to exercise. Because of the beneficial effects on spinal BMD, HIRT is still recommended in osteosarcopenic older men, but further research is needed to confirm appropriate age-specific training exercises for the paraspinal muscles. The potential of different MRI sequences to quantify degenerative and metabolic changes in various muscle groups must be better characterized. TRIAL REGISTRATIONS: FrOST was approved by the University Ethics Committee of the Friedrich-Alexander University of Erlangen-Nürnberg (number 67_15b and 4464b) and the Federal Office for Radiation Projection (BfS, number Z 5-2,246,212 - 2017-002). Furthermore, it fully complies with the Declaration of Helsinki and is registered at ClinicalTrials.gov: NCT03453463 (05/03/2018). JAMA 310:2191-2194, 2013.

Bone mineral density differences between femurs of scoliotic patients undergoing quantitative computed tomography analysis.

PURPOSE: Scoliosis is a cause of loading imbalance between the lower limbs, which can result in BMD differences between the two femurs. We investigated the discrepancy in BMD values assessed by quantitative computed tomography (QCT) between femurs in patients with and without scoliosis, also assessing if this difference can be related to spine convexity. METHODS: Abdominal CT examinations were retrospectively reviewed. An ''asynchronous'' calibration of CT images was performed to obtain BMD values from QCT. Scoliosis was evaluated on the antero-posterior CT localizer to calculate the Cobb angle. Differences between aBMD and vBMD of femurs were assessed in both scoliotic and non-scoliotic subjects. RESULTS: Final study cohort consisted of 263 subjects, 225 of them without scoliosis (85.6%) and 38 with scoliosis (14.4%). No significant differences were found in the general population without scoliosis, except for vBMD at the neck. Comparison of femurs in scoliotic patients showed statistically significant differences at neck aBMD -0.028 g/cm2, p = 0.004), total femur aBMD (--0.032 g/cm2, p = 0.008) and total femur vBMD (--8.9 mg/cm3, p = 0.011), with lower BMD values on the convexity side. In 10 cases (26%) a change in the final T-score diagnosis was observed. CONCLUSION: QCT analysis demonstrated a difference in both areal and volumetric BMD between the two femurs of scoliotic patients, in relation to the side of the scoliotic curve. If these data will be confirmed by larger studies, bilateral femoral DXA acquisition may be proposed for these patients.