Changes In BMD Research Articles

Association Between CTSK Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density.

The aim of this study was to explore the association between CTSK polymorphisms and the response to alendronate treatment in postmenopausal Chinese women with low bone mineral density. In this study, 460 postmenopausal women from Shanghai were included. All of them were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for a year. Four tag single nucleotide polymorphisms (SNPs) in CTSK gene were genotyped. Bone mineral densities of lumbar spine (L1-L4), femoral neck and total hip were measured at baseline and after 12 months of treatment, respectively. After 1-year of treatment, there was no significant differences in BMI between baseline and follow-up. After alendronate treatment, the BMD of L1-4, femoral neck and total hip all increased significantly (all P < 0.001), with average increases of 4.33 ± 6.42%, 1.85 ± 4.20%, and 2.36 ± 3.79%, respectively. There was no significant difference in BMD at L1-L4, the femoral neck and total hip between different genotype groups at baseline (P>0.05). After 1-year treatment with alendronate, rs12746973 and rs10847 were associated with the % change of BMD at L1-L4 (P=0.038) and % change of BMD at femoral neck (P=0.038), respectively. Furthermore, rs10847 was associated with BMD response at femoral neck (P=0.013). However, the associations were not significant after Bonferroni correction. We concluded that the common variations of CTSK gene were potentially associated with the therapeutic response to alendronate treatment in Chinese women with low bone mineral density. However, further validation is needed.

A longitudinal genome-wide association study of bone mineral density mean and variability in the UK Biobank.

This study aimed to identify the genetic architecture and potential biomarkers of BMD. Our analysis included 141,261 white participants from the UK Biobank with heel BMD phenotype data. We used a genome-wide trajectory analysis tool, TrajGWAS, to conduct a genome-wide association study (GWAS) of BMD. Then, we validated our findings in previously reported BMD genetic associations and performed replication analysis in the Asian participants. Finally, gene-set enrichment analysis (GSEA) of the identified candidate genes was conducted using the FUMA platform. A total of 52 genes associated with BMD trajectory mean were identified, of which the top three significant genes were WNT16 (P = 1.31 × 10-126), FAM3C (P = 4.18 × 10-108), and CPED1 (P = 8.48 × 10-106). In addition, 114 genes associated with BMD within-subject variability were also identified, such as AC092079.1 (P = 2.72 × 10-13) and RGS7 (P = 4.72 × 10-10). The associations for these candidate genes were confirmed in the previous GWASs and replicated successfully in the Asian participants. GSEA results of BMD change identified multiple GO terms related to skeletal development, such as SKELETAL SYSTEM DEVELOPMENT (Padjusted = 2.45 × 10-3) and REGULATION OF OSSIFICATION (Padjusted = 2.45 × 10-3). KEGG enrichment analysis showed that these genes were mainly enriched in WNT SIGNALING PATHWAY. Our findings indicated that the CPED1-WNT16-FAM3C locus plays a significant role in BMD mean trajectories and identified several novel candidate genes contributing to BMD within-subject variability, facilitating the understanding of the genetic architecture of BMD.

#3641 DOES IBANDRONATE OR CALCIUM AND VITAMIN D MAINTAIN OR IMPROVE BONE MICROARCHITECTURE IN THE FIRST YEAR AFTER KIDNEY TRANSPLANTATION?

Abstract Background and Aims Modern immunosuppressive protocols are associated with less loss of bone mass immediately after kidney transplantation, as compared with previous eras. Even so, bone microarchitecture may still be disturbed due to long-standing uremia, leading to bone fragility and fracture susceptibility. Trabecular bone score (TBS) is a new tool to assess trabecular bone microarchitecture based on standard dual energy X-ray absorptiometry (DXA) of lumbar spine images. TBS reflects bone quality rather than quantity. Studies on the effect of common anti-fracture strategies on TBS in kidney transplant recipients (KTR) are scarce. Our aim was to investigate different treatments on bone microarchitecture by TBS in KTR. Method We analyzed TBS changes and potential treatment effects in 179 de novo KTR, 118 of whom had participated in a randomized controlled trial[1] evaluating the effect of ibandronate (active/placebo) on top of calcium and vitamin D in the first year after kidney transplantation. Trial participants were compared to 61 patients transplanted in the same time-period, meeting the same study inclusion criteria, but receiving no specific bone-directed treatment. Correlations between changes in TBS and lumbar spine BMD were investigated. We used ANOVA and ANCOVA with adjustment for baseline TBS values to evaluate the potential effects of calcium and vitamin D with/without concomitant ibandronate on TBS 12 months after transplantation, as compared to no treatment. Results Mean TBS increased in all groups from baseline to 12 months after transplantation (2.1% for ibandronate/calcium/vitamin D, 2.7% for calcium/vitamin D, and 3.4% for no treatment). Adjusting for baseline TBS, there were no significant differences in TBS at 12 months, neither with overall comparison (p = 0.377) nor when comparing the groups pairwise. The correlation between TBS and BMD was weak (r = 0.170, p = 0.02) at baseline, and change in TBS was not significantly correlated with change in lumbar spine BMD in any of the groups. Conclusion In a group of de novo KTR with reasonably well-preserved bone mass, it does not appear that one year of treatment with ibandronate or calcium and vitamin D significantly affects bone quality as measured by TBS. We found surprisingly weak correlation between changes in TBS and BMD over the study period, indicating that these measurements reflect different aspects of bone integrity and metabolism. This study strengthens the view that focus should be on identifying KTR at high risk of fracture at time of transplantation, as these patients could benefit from anti-resorptive therapy.

Quadriceps Performance and Running Biomechanics Influence Femur BMD Changes after ACL Reconstruction in Collegiate Athletes.

Reduced bone mineral density of the distal femur (BMD DF ) can persist long term after anterior cruciate ligament reconstruction (ACLR), even in athletes who return to high levels of competition. These deficits may have implications for the onset and progression of knee osteoarthritis. It is unknown if clinically modifiable factors are associated with losses in BMD DF . This study evaluated the potential influence of knee extensor peak torque (PT), rate of torque development (RTD), as well as peak knee flexion (PKF) angle and peak knee extensor moment (PKEM) during running, on longitudinal changes in BMD DF post-ACLR. After ACLR, 57 Division I collegiate athletes underwent serial whole-body dual-energy x-ray absorptiometry (DXA) scans between 3 and 24 months post-ACLR. Of these, 43 athletes also had isometric knee extensor testing (21 female, 105 observations), and 54 had running analyses (26 female, 141 observations). Linear mixed-effects models, controlling for sex, assessed the influence of surgical limb quadriceps performance (PT and RTD), running mechanics (PKF and PKEM), and time post-ACLR on BMD DF (5% and 15% of femur length). Simple slope analyses were used to explore interactions. Athletes with RTD less than 7.20 (N·m)·kg -1 ·s -1 (mean) at 9.3 months post-ACLR demonstrated significant decreases in 15% BMD DF over time ( P = 0.03). Athletes with PKEM during running less than 0.92 (N·m)·kg -1 (-1 SD below mean) at 9.8 months post-ACLR demonstrated significant decreases in 15% BMD DF over time ( P = 0.02). Significant slopes were not detected at -1 SD below the mean for PT (1.75 (N·m)·kg -1 , P = 0.07) and PKF (31.3°, P = 0.08). Worse quadriceps RTD and running PKEM were associated with a greater loss of BMD DF between 3 and 24 months post-ACLR.

Long-term effect of denosumab on bone microarchitecture as assessed by tissue thickness–adjusted trabecular bone score in postmenopausal women with osteoporosis: results from FREEDOM and its open-label extension

SummaryIn postmenopausal women with osteoporosis, up to 10 years of denosumab treatment significantly and continuously improved bone microarchitecture assessed by tissue thickness–adjusted trabecular bone score, independently of bone mineral density. Long-term denosumab treatment decreased the number of high fracture-risk patients and shifted more patients to lower fracture-risk categories.PurposeTo investigate the long-term effect of denosumab on bone microarchitecture assessed by tissue thickness–adjusted trabecular bone score (TBSTT) in post-hoc subgroup analysis of FREEDOM and open-label extension (OLE).MethodsPostmenopausal women with lumbar spine (LS) or total hip BMD T-score <−2.5 and ≥−4.0 who completed the FREEDOM DXA substudy and continued in OLE were included. Patients received either denosumab 60 mg subcutaneously every 6 months for 3 years and same-dose open-label denosumab for 7 years (long-term denosumab; n=150) or placebo for 3 years and open-label denosumab for 7 years (crossover denosumab; n=129). BMD and TBSTT were assessed on LS DXA scans at FREEDOM baseline, month 1, and years 1–6, 8, and 10.ResultsIn long-term denosumab group, continued increases from baseline to years 4, 5, 6, 8, and 10 in BMD (11.6%, 13.7%, 15.5%, 18.5%, and 22.4%) and TBSTT (3.2%, 2.9%, 4.1%, 3.6%, and 4.7%) were observed (all P < 0.0001). Long-term denosumab treatment decreased the proportion of patients at high fracture-risk (according to TBSTT and BMD T-score) from baseline up to year 10 (93.7 to 40.4%), resulting in increases in the proportions at medium-risk (6.3 to 53.9%) and low-risk (0 to 5.7%) (P < 0.0001). Similar responses were observed in crossover denosumab group. Changes in BMD and TBSTT were poorly correlated during denosumab treatment.ConclusionIn postmenopausal women with osteoporosis, up to 10 years of denosumab significantly and continuously improved bone microarchitecture assessed by TBSTT, independently of BMD, and shifted more patients to lower fracture-risk categories.Graphical

Abstract P2-02-04: De-escalation of bone-targeted treatment: Does the number of 6-monthly adjuvant zoledronate infusions received affect treatment efficacy for early breast cancer? A sub-study of ABCSG-12

Abstract Background: The results of the Early Breast Cancer Trialist Group (EBCTCG) meta-analysis (Lancet 2015) led to the widespread adoption of bisphosphonates as adjuvant therapy for postmenopausal early-stage breast cancer (EBC). Despite evaluating multiple bisphosphonate agents and regimens, there was no signal of varying efficacy with different agents, routes of administration or dose/dose intensity. We evaluated the question of treatment de-escalation using long-term outcome data from the prospective randomized ABCSG-12 trial. Patients and methods: Between 1999 and 2006, ABCSG-12 accrued 1803 patients with hormone-receptor positive EBC on ovarian function suppression for three years that were randomized to receive 4 mg zoledronic acid 6-monthly or not (and tamoxifen or anastrozole, in a 2:2 factorial design). In the current retrospective study, we evaluated whether the number of zoledronate infusions actually received had an impact on breast cancer-specific and fragility fracture outcomes. Based on the results of the EBCTCG meta-analysis, we hypothesized that amongst patients who receive less infusions than the planned seven zoledronate infusion in this trial, the number of infusions has no differential effect on these outcomes. Time to event endpoints were analyzed with Cox models and Kaplan Meier curves starting from a 3-year landmark. BMD subset analyses were restricted to patients who participated in the BMD sub-study with available BMD data. Results: 725 patients who received at least one zoledronate infusion were included in the time-to-event-analysis. There was no statistically significant difference in disease-free survival (adjusted HR 0.83, 95% CI 0.48–1.44, p=0.51) or overall survival (HR 0.97, 95% 0.30-3.11, p=0.96) in patients who received ≤6 zoledronate infusions (n=170) compared to those who received ≥7 zoledronate infusions (n=555) (adjusted HR 0.83, 95% CI 0.48 – 1.44, p=0.51). Both subgroups show stable lumbar spine and total hip BMD measurements across the five years. Conclusions: Comparable to the metastatic bone disease and fragility fracture settings, there was no evidence observed to indicate that a reduced number of zoledronate infusions is associated with reduced adjuvant efficacy. Further studies to define optimal regimens of adjuvant bone-targeted therapies (prospective evaluation of “how-low-can-you-go”) are required. Table 1: Multivariate Cox Regression: DFS and OS Table 2: BMD and percent change from baseline at the total hip and lumbar spine (L1-L4) over 60 months Citation Format: Ana-Alicia Beltran-Bless, Mark Clemons, Christian Fesl, Dominik Hlauschek, Lidija Soelkner, Gregory R. Pond, Lisa Vandermeer, Richard Greil, Marija Balic, Vesna Bjelic-Radisic, Christian F. Singer, Guenther Steger, Ruth Helfgott, Daniel Egle, Simon P. Gampenrieder, Stephanie Kacerovsky-Strobl, Christoph Suppan, Magdalena Ritter, Gabriel Rinnerthaler, Georg Pfeiler, Hannes Fohler, John Hilton, Michael Gnant. De-escalation of bone-targeted treatment: Does the number of 6-monthly adjuvant zoledronate infusions received affect treatment efficacy for early breast cancer? A sub-study of ABCSG-12 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-04.

Efficacy of anti-osteoporosis treatment for men with osteoporosis: a meta-analysis.

Osteoporosis and fracture are important healthcare problems for men worldwide, which are relevant to severe disability and mortality. This meta-analysis aimed to assess the effectiveness of pharmacological therapy in men with osteoporosis, and to provide evidence-based hints for clinical practice. PubMed, Embase, Web of Science were searched from inception to July 31, 2022. Pooled standardized mean difference (SMD) and relative risk (RR) were calculated. Heterogeneity between included studies and publication bias were detected. Twenty clinical studies were enrolled in this meta-analysis. The pooled SMD for mean percentage differences of change from baseline in lumbar spine BMD between the treatment group and the control group was 4.95 (95% CI 2.48, 7.42, I2 = 99%, p < 0.0001). For mean percentage differences of change in femoral neck BMD, the overall SMD was 3.08 (95% CI 0.95, 5.20, I2 = 99%, p = 0.0045). For a change in total hip BMD, the overall SMD was 1.06 (95% CI 0.50, 1.63, I2 = 82%, p = 0.0002). The overall RR for incident vertebral fractures was 0.50 (95% CI 0.37, 0.68, I2 = 5%, p = 0.3971). The pooled RR for nonvertebral fractures and clinical fracture were 0.74 (95% CI 0.41, 1.33, I2 = 28%, p = 0.3139) and 0.81 (95% CI 0.54, 1.21, I2 = 0%, p = 0.2992). Findings in this meta-analysis indicate that pharmacological treatment increases lumbar spine, femoral neck, total hip BMD, and decreases incident vertebral fractures in men with osteoporosis.

Z-scores of bone turnover markers calculated from new established sex- and age-specific reference curves are associated to future change in BMD in children and adolescents.

Z-scores of bone turnover markers calculated from new established sex- and age-specific reference curves are associated to future change in BMD in children and adolescents.

Denosumab's Therapeutic Effect for Future Osteosarcopenia Therapy : A Systematic Review and Meta-Analysis.

Osteosarcopenia, a combination of osteopenia/osteoporosis and sarcopenia, is a common condition among older adults. While numerous studies and meta-analyses have been conducted on the treatment of osteoporosis, the pharmacological treatment of osteosarcopenia still lacks evidence. Denosumab, a human monoclonal antibody, has shown encouraging results for the treatment of osteosarcopenia. Our systematic review and meta-analysis aimed to investigate the potential dual role of denosumab as an anti-resorptive agent and for other beneficial muscle-related effects in patients with osteosarcopenia, and to evaluate whether denosumab can be a treatment of choice compared to bisphosphonate. Relevant literature was collated from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Google Scholar databases. The primary outcome was denosumab's effect on lumbar spine bone mineral density (LS BMD), handgrip strength, and gait speed change. The secondary outcome was the effect of denosumab on appendicular lean mass (ALM). The outcomes were presented as mean difference (MD). A random effects model was used in the analysis to represent the population. The risk of bias was assessed using funnel plots. Out of the 3,074 studies found, four full-text studies met the inclusion criteria, including 264 and 244 participants in the intervention and control groups, respectively. Regarding a primary outcome, our meta-analysis showed that denosumab showed no significant differences in LS BMD and gait speed changes compared to other agents-MD=0.37, 95% confidence interval (CI), -0.35 to 0.79; p=0.09 and MD=0.11; 95% CI, -0.18 to 0.40; p=0.46, respectively. Denosumab had a significant effect on handgrip strength change compared to standard agents-MD=5.16; 95% CI, 1.38 to 18.94; p=0.007, based on the random effects model. Denosumab was better than bisphosphonate and placebo in improving muscle strength (handgrip strength). Therefore, denosumab may be favored in individuals with osteosarcopenia to improve muscular performance and reduce fall risk.

Exercise effects on glucocorticoid-induced bone loss in adults: a systematic review and meta-analysis.

Due to their pronounced anti-inflammatory and immunosuppressive effects, glucocorticoids (GCs) are widely used in inflammatory conditions and organ transplants. Unfortunately, GC-induced osteoporosis is one of the most common causes of secondary osteoporosis. The aim of the present systematic review and meta-analysis was to determine the effect of exercise added to GC therapy on BMD at the lumbar spine or femoral neck in people on GC therapy. A systematic literature search of five electronic databases included controlled trials with a duration of >6 months and at least two study arms [glucocorticoids (GCs) and GCs and exercise (GC + EX)] were conducted up to 20 September 2022. Studies involving other pharmaceutical therapies with relevant effects on bone metabolism were excluded. We applied the inverse heterogeneity model. Outcome measures were standardized mean differences (SMDs) with 95% CIs for BMD changes at the lumbar spine (LS) and femoral neck (FN). We identified three eligible trials with a total of 62 participants. In summary, the GC + EX intervention indicated statistically significantly higher SMDs for LS-BMD [SMD 1.50 (95% CI 0.23, 2.77)] but not for FN-BMD [0.64 (95% CI -0.89, 2.17)] compared with GC treatment alone. We observed substantial heterogeneity (LS-BMD I 2 = 71%, FN-BMD I 2 = 78%) between the study results. Although more well-designed exercise studies are needed to address the issue of exercise effects on GC-induced osteoporosis (GIOP) in more detail, upcoming guidelines should pay more attention to the aspect of exercise for bone strengthening in GIOP. PROSPERO: CRD42022308155.

Discontinuation of denosumab in men with prostate cancer.

Patients with prostate cancer receiving androgen deprivation therapy (ADT) are treated with denosumab (DMAB) to prevent fractures and preserve bone mass. We wanted to investigate the change in BMD in men with non-metastatic prostate cancer discontinuing DMAB. We conducted a retrospective cohort study based on medical records from patients referred to the Department of Endocrinology from the Department of Urology, Aarhus University Hospital between June 1, 2018, and June 1, 2021. We retrieved information on biochemistry and DXA performed 0-6months after the last DMAB injection and a second DXA performed approximately 12months after the first. In case of a BMD T-score ≤ - 1 at the lumbar spine or total hip at the first DXA, the patients were treated with zoledronate. The primary endpoint was change in lumbar spine BMD. We included 50 patients with non-metastatic prostate cancer. The mean DMAB treatment duration was 5 ± 0.1years. Among the patients treated with zoledronate (n = 9), BMD was maintained at the spine and femoral neck after a mean of 16months. We found a significant decrease in BMD; - 4.9 ± 4.2%, - 1.9 ± 3.5%, and - 2.4 ± 3.6% at the spine, total hip, and femoral neck between the first and second DXA in the patients not treated with zoledronate (n = 24) (p ≤ 0.01 for all). One patient who did not receive ZOL sustained multiple fragility vertebral fractures after DMAB discontinuation. In men with non-metastatic prostate cancer, discontinuation of DMAB after stopping ADT led to an average bone loss of 2-5%. Zoledronate prevented bone loss in men with osteopenia.

Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis.

Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis. The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis. A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed via sensitivity and subgroup analyses. Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.

Effects of Teriparatide on Bone Mineral Density and Prevention of Fragility Fractures in Saudi Arabian Subjects with Osteoporosis: A Two-Year Clinical Study from a Single Center.

A prospective study was conducted. Setting. This study took place at King Fahd Hospital of the University, Imam AbdulRahman Bin Faisal University, Dammam, Saudi Arabia. Primary and Secondary Outcomes. The study aimed to evaluate changes in BMD and prevention of fragility fractures. We followed up 439 patients who were prescribed teriparatide at the King Fahd Hospital of the University, AlKhobar, and 415 (94.5%) patients completed a 24-month teriparatide course. The data gathered before starting medication were age, sex, previous therapy, history of fractures, and other diseases like diabetes mellitus, hypertension, and cardiac disease. At the time of the final assessment after 24 months, a history of fractures if any during the treatment was collected and a DXA scan was done. A total of 415 patients were followed up for 2 years. Three hundred and sixty-five patients (87.9%) were females, and the rest were males. The average age was 68.21 ± 17.6 years. Two hundred and forty-eight patients (59.8%) were treatment naïve, and 167 (40.2%) were on treatment for osteoporosis. Twenty patients (4.8%) sustained fracture on treatment. The pretreatment DXA showed that the mean hip T-score was -3.1 ± 0.79, and after completion of the treatment, it was -1.5 ± 0.62 (P < 0.001), while the T-score of the lumbar spine was 4.4 ± 0.86 versus -3.2 ± 0.87 (P < 0.001). Seventeen (4.09%) had fractures while on teriparatide treatment. The mean significant gain (MSG) for BMD for the hip was 0.095 g/cm2, and for the lumbar spine, it was was 0.109 g/cm2 with P < 0.001 at 95% CI. Our study shows that 94.5% completed the treatment duration, and there was an increase in the BMD. The decrease in T-scores of the lumbar spine and hip was significant so was the reduction in the number of fractures.

Geometry and bone mineral density determinants of femoral neck strength changes following exercise

Physical exercise induces spatially heterogeneous adaptation in bone. However, it remains unclear where the changes in BMD and geometry have the greatest impact on femoral neck strength. The aim of this study was to determine the principal BMD-and-geometry changes induced by exercise that have the greatest effect on femoral neck strength. Pre- and post-exercise 3D-DXA images of the proximal femur were collected of male participants from the LIFTMOR-M exercise intervention trial. Meshes with element-by-element correspondence were generated by morphing a template mesh to each bone to calculate changes in BMD and geometry. Finite element (FE) models predicted femoral neck strength changes under single-leg stance and sideways fall load. Partial least squares regression (PLSR) models were developed with BMD-only, geometry-only, and BMD-and-geometry changes to determine the principal modes that explained the greatest variation in neck strength changes. The PLSR models explained over 90% of the strength variation with 3 PLS components using BMD-only (R2 > 0.92, RMSE < 0.06 N) and 8 PLS components with geometry-only (R2 > 0.93, RMSE < 0.06 N). Changes in the superior neck and distal cortex were most important during single-leg stance while the superior neck, medial head, and lateral trochanter were most important during a sideways fall. Local changes in femoral neck and head geometry could differentiate the exercise groups from the control group. Exercise interventions may target BMD changes in the superior neck, inferior neck, and greater trochanter for improved femoral neck strength in single-leg stance and sideways fall.

One-year supplementation with Lactobacillus reuteri ATCC PTA 6475 counteracts a degradation of gut microbiota in older women with low bone mineral density

Recent studies have shown that probiotic supplementation has beneficial effects on bone metabolism. In a randomized controlled trial (RCT) we demonstrated that supplementation of Lactobacillus reuteri ATCC PTA 6475 reduced bone loss in older women with low bone mineral density. To investigate the mechanisms underlying the effect of L. reuteri ATCC PTA 6475 on bone metabolism, 20 women with the highest changes (good responders) and the lowest changes (poor responders) in tibia total volumetric BMD after one-year supplementation were selected from our previous RCT. In the current study we characterized the gut microbiome composition and function as well as serum metabolome in good responders and poor responders to the probiotic treatment as a secondary analysis. Although there were no significant differences in the microbial composition at high taxonomic levels, gene richness of the gut microbiota was significantly higher (P < 0.01 by the Wilcoxon rank-sum test) and inflammatory state was improved (P < 0.05 by the Wilcoxon signed-rank test) in the good responders at the end of the 12-month daily supplementation. Moreover, detrimental changes including the enrichment of E. coli (adjusted P < 0.05 by DESeq2) and its biofilm formation (P < 0.05 by GSA) observed in the poor responders were alleviated in the good responders by the treatment. Our results indicate that L. reuteri ATCC PTA 6475 supplementation has the potential to prevent a deterioration of the gut microbiota and inflammatory status in elderly women with low bone mineral density, which might have beneficial effects on bone metabolism.

Cortex or cancellous-which is early for the decrease of bone content for vertebral body in health?

To obtain the cortex and cancellous parameter of the vertebral bone of healthy subjects using QCT. To explore which is earlier or faster for bone loss with age. 733 physical examiners underwent chest low-dose CT examination were recruited, from April 1, 2021 to October 1, 2021. QCT sequence was used to obtain the bone mineral density of T12-L2 vertebral body without additional radiation. The mass and area of vertebral cortex and cancellous at the central level of L2 vertebral body were measured. The age -related characteristics of vertebral cortex and cancellous between male and female was analyzed and compared. The vBMD of T12-L2 vertebral body decreased with age. Significant differences were found in volumetric bone mineral density (vBMD) of T12-L2 vertebral body. For female, significant differences were found in bone content involving cortical mass, cancellous mass, cortical area, cancellous area, cortical mass/cancellous mass and cortical area/cancellous area in different age groups, respectively. The cortical mass decreased with age in female. The cancellous mass of female increased and then decreased with peak at 31-40 y. The cortical area of female decreased gradually before 71 y. The cancellous area of female increased and then decreased with peak at 51-60 y. The values of mass ratio and area ratio in female showed a slowly downward trend with age. Significant differences of bone content between non-menopausal and menopausal women were found except the cancellous mass. For male, no significant differences were found in all parameters of bone content. The changes of vertebral BMD, bone content of cortex and cancellous have different characteristics in different age. The change of cortex in female maybe earlier and faster than that of cancellous, especially in menopausal women.

형태와 빈도에 따른 저강도 운동이 근감소증 비만 고령여성의 신체조성 변화에 관한 연구

The purpose of this study is to investigate any changes in body composition, such as muscle mass, %fat, and bone density, in exercise intervention according to the frequency of low-intensity aerobic exercise and resistance exercise for 16 weeks.BRThe subjects of the study were women aged over 75 yrs older living in Jin-gu, Busan, who were selected for sarcopenia by diagnosis of sarcopenia (ASM/weight, % ; 25.6% or less) and obesity (% fat, % ; 30% or over), Through drawing lots, a total of 104 people participated in the experiment, 29 people were eliminated from the pre-test measurement. And 29 people were excluded from the exercise intervention. The participants were randomly assigned into 5 groups; low intensity aerobic exercise 3 times per week group (n=10, 75.6±3.5 yrs), low intensity aerobic exercise 5 times per week group (n=8, 74.2±3.9 yrs), low intensity resistance exercise 3 times per week group (n=10, 75.4±3.7 yrs), low intensity resistance exercise 5 times per week group(n=8, 75.6±4.1 yrs) and a control group (n=10, 77.7±3.8 years).BRFor the statistical analysis, such as One-Way ANOVA, t-test, and Two-Way Repeated measures ANOVA was calculated using SPSS Version 22.0. To verify mean differences between the 5 groups, two-way repeated measures ANOVA was used.BRAs a result of the study, the interaction effect of the group and time period of %fat was shown (p＜.05), As a result of post-verification, A5-G and R5-G were higher than CG. In the change in the main effect of the time period within the group, there was a significant decrease in A5-G (p＜.001) and R5-G (p＜.01). And in the change in LBM, there were no interaction effects and main effects. And the interaction effect was not shown in the change in Total BMD, but a significant decrease was shown in R3-G (p＜.01) and CG (p＜.05) in the change in the main effect.BRBased on the research results, The interaction effect of aerobic exercise and resistance exercise 5 times a week was shown in the body fat rate change according to the low intensity form and frequency of exercise for 16 weeks in elderly women with muscle fat and bone density. However, through this study, there is a significant decrease in bone density in older women in the control group and aerobic exercise and resistance exercise group conducted three times a week, so it seems to play a role in suppressing fat and bone density due to aging.

Changes in the composition of gut and vaginal microbiota in patients with postmenopausal osteoporosis.

BackgroundPostmenopausal osteoporosis (PMO) is influenced by estrogen metabolism and immune response, which are modulated by several factors including the microbiome and inflammation. Therefore, there is increasing interest in understanding the role of microbiota in PMO.ObjectivesTo investigate variations in gut microbiota (GM) and vaginal microbiota (VM) in postmenopausal women with osteoporosis.MethodsA total of 132 postmenopausal women were recruited for the study and divided into osteoporosis (n = 34), osteopenia (n = 47), and control (n = 51) groups based on their T score. The serum levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, and lipopolysaccharide-binding protein were determined via enzyme-linked immunosorbent assay. Additionally, 16S rRNA gene V3-V4 region sequencing was performed to investigate the GM and VM of the participants.ResultsSignificant differences were observed in the microbial compositions of fecal and vaginal samples between groups (p < 0.05). It was noted that for GM, Romboutsia, unclassified_Mollicutes, and Weissella spp. were enriched in the control group, whereas the abundances of Fusicatenibacter, Lachnoclostridium, and Megamonas spp. were higher in the osteoporosis group than in the other groups. Additionally, for VM, Lactobacillus was enriched in the control group, whereas the abundances of Peptoniphilus, Propionimicrobium, and Gallicola spp. were higher in the osteoporosis group than in the other groups. The predicted functional capacities of GM and VM were different in the various groups. We also found that the serum level of IL-10 in the osteoporosis group was significantly lower than that in the control group and osteopenia group, while TNF-α was significantly higher in the osteoporosis group than that in the control group (p < 0.05).ConclusionThe results show that changes in BMD in postmenopausal women are associated with the changes in GM and VM; however, changes in GM are more closely correlated with PMO than VM.

Efficacy of generic teriparatide and alendronate in Chinese postmenopausal women with osteoporosis: a prospective study

SummaryThe efficacy of generic teriparatide in improving BMD at lumbar spine in patients with osteoporosis was similar to that of alendronate. It provided a new choice for osteoporosis treatment in Chinese population.IntroductionTo determine whether the efficacy of generic teriparatide is noninferior to alendronate for Chinese postmenopausal women with osteoporosis.MethodsEligible patients were randomly assigned (2:1) in a 48-week, open-label design to receive 20 µg sc daily teriparatide or 70 mg oral weekly alendronate. Primary outcome was percentage change in BMD at the lumbar spine from baseline to 48 weeks and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint.ResultsThree hundred ninety-one and 196 participants were randomly assigned to the teriparatide or alendronate group, of whom 379 and 194 receiving at least one dose of teriparatide and alendronate treatment were eligible for the efficacy analysis. Teriparatide was non-inferior to alendronate for BMD change at lumbar spine (treatment difference: 0.7%, 95% CI: − 0.3 to 1.7%), which excluded the predefined non-inferiority margin of − 1.5%. However, teriparatide was not statistically superior to alendronate in improving BMD at lumbar spine (P = 0.169). At 48 weeks, changes in BMD at total hip were − 1.0% and 2.2% in teriparatide and alendronate group, respectively (P < 0.001). The incidence of new fracture showed no statistical difference between groups (P = 0.128). Serum P1NP and β-CTX levels significantly increased in the teriparatide group and markedly decreased in alendronate group (all P < 0.001 vs baseline). The adverse events (AEs) and serious AEs were more common in the teriparatide group than in the alendronate group, which were mainly teriparatide-related hypercalcemia, elevated alkaline phosphatase or parathyroid hormone, dizziness, and arthralgia.ConclusionsTeriparatide was not inferior to alendronate in increasing BMD at lumbar spine in Chinese postmenopausal women, and they achieved these effects through different mechanisms.

Genetic Polymorphisms of Nuclear Factor-κB Family Affect the Bone Mineral Density Response to Zoledronic Acid Therapy in Postmenopausal Chinese Women.

The aim of this study was to explore the allelic association between genetic polymorphisms of the NF-κB pathway and the variance of clinical effects of zoledronic in postmenopausal Chinese women with osteoporosis. In the study, 110 Chinese postmenopausal women with osteoporosis were recruited. Every patient received zoledronic once a year. BMD was measured at baseline and after one year of treatment. The 13 tagger SNPs of five genes in the NF-κB pathway were genotyped. In the study, 101 subjects completed the one-year follow-up. The ITCTG and DTCTG haplotypes, which are constituted of rs28362491, rs3774937, rs230521, rs230510 and rs4648068 of the NF-κB1 gene, were associated with improvement in BMD at L1-4 and femoral neck (p < 0.001, p = 0.008, respectively). The CGC haplotype, which is constituted of rs7119750, rs2306365 and rs11820062 of the RELA gene, was associated with improvement in BMD at total hip (p < 0.001). After Bonferroni correction, haplotypes ITCTG and CGC still showed significant association with the % change of BMD at L1-4 and total hip. Therefore, NF-κB1 and RELA gene were significantly associated with bone response to the treatment of zoledronic in postmenopausal Chinese women with osteoporosis.