Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density, Fracture Risk, and Bone Metabolism in Adults With Osteoporosis/Fractures.

OBJECTIVE: To evaluate the association of serum 25-hydroxyvitamin D (25(OH) D) levels with bone mineral density (BMD), fracture risk, and bone metabolism. METHODS: This multicenter cross-sectional study recruited menopausal females and males greater than or equal to 50 year old with osteoporosis/fractures between September 2016 and September 2021. Assessment included clinical data, 25(OH)D, intact parathyroid hormone (iPTH), procollagen type 1 amino-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks (CTX), lateral thoracolumbar spine x-rays, and BMD. RESULTS: A total of 3003 individuals were stratified by 25(OH) D levels: 720 individuals (24%) <20 ng/mL, 1338 individuals (44.5%) 20 to 29 ng/mL, and 945 individuals (31.5%) ≥30 ng/mL. In unadjusted and multivariable models, BMD T-score, except spine, was significantly and positively associated with 25(OH)D levels. 25(OH) D levels were inversely associated with Fracture Risk Assessment Tool scores. Patients with 25(OH)D <20 ng/mL had significantly higher iPTH and bone turnover markers (P1NP and CTX) than patients with 25(OH)D â‰§20 ng/mL in all models. When analyzing bone-related markers and BMD, total hip and femoral neck BMD T-scores were positively correlated with 25(OH)D concentrations and BMI but negatively correlated with iPTH, P1NP, CTX, and age. In multivariate models with all bone-related markers, only 25(OH)D levels were significantly associated with total hip and femoral neck BMD. CONCLUSION: Vitamin D deficiency is significantly associated with decreased total hip and femoral neck BMD and increased fracture risk as assessed by Fracture Risk Assessment Tool. In those with osteoporosis/fractures, vitamin D is implicated in the causal relationship between bone remodeling and BMD. Assessing vitamin D status is imperative for those at risk for osteoporosis/fractures.

Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: 2022 update.

Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan.

Asia-pacific consensus on osteoporotic fracture prevention in postmenopausal women with low bone mass or osteoporosis but no fragility fractures.

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics.

Vertebral Fractures in Type 2 Diabetes Patients: Utility of Trabecular Bone Score and Relationship With Serum Bone Turnover Biomarkers.

BACKGROUND: Patients with type 2 diabetes (T2D) have an increased risk for vertebral fracture (VF). The aim of this study is to determine the utility of trabecular bone score (TBS) in T2D patients with VF and the relationship of TBS with serum bone turnover biomarkers (SBTBs). METHODOLOGY: Postmenopausal T2D female patients were prospectively enrolled. All patients received: (1) dual-energy X-ray absorptiometry exam for bone mineral density (BMD), T-score, and TBS values; (2) lateral lumbar spine radiographs for VF assessment; and (3) SBTBs: bone specific alkaline phosphatase and Beta-C-Terminal telopeptides. BMD, T-score, TBS, and SBTBs were tested for association with VF. RESULTS: The study included 285 T2D patients (mean age = 61.1 years) and 32 patients had VF (11.2%). TBS had the strongest association with VF in T2D patients (area under curve 0.775). The TBS cutoff values for VF are 1.279 in T-score ≥1 and 1.236 in T-score <-1. In patients without VF, all sites of BMD and TBS are significantly associated with SBTBs, but in patients with VF, no associations are found between SBTBs and all sites of BMD and TBS. CONCLUSIONS: TBS can assess bone quality in the spine. The low TBS cutoff values for T2D patients with VF imply T2D does impair bone quality. Thus, TBS should be incorporated in VF risk assessment in T2D patients. In addition, a dissociated relationship between BMD and TBS with SBTBs represents imbalanced bone turnover rate and results in bone fragility and VF.

Effect of Chemotherapy on Dual-Energy X-ray Absorptiometry (DXA) Body Composition Precision Error in Head and Neck Cancer Patients.

BACKGROUND: Precision error in dual-energy X-ray absorptiometry (DXA) is defined as difference in results due to instrumental and technical factors given no biologic change. The aim of this study is to compare precision error in DXA body composition scans in head and neck cancer patients before and 2 months after chemotherapy. METHODOLOGY: A total of 34 male head and neck cancer patients with normal body mass index (BMI) were prospectively enrolled and all patients received 2 consecutive DXA scans both before and after 2 months of chemotherapy for a total of 4 scans. The precision error of 3 DXA body composition values (lean mass, fat mass, and bone mineral content) was calculated for total body and 5 body regions (arms, legs, trunk, android, and gynoid). Precision errors before and after treatment were compared using generalized estimating equation model. RESULTS: There was no significant change in precision error for the DXA total body composition values following chemotherapy; lean mass (0.33%-0.40%, p = 0.179), total fat mass (1.39%-1.70%, p = 0.259) and total bone mineral content (0.42%-0.56%, p = 0.243). However, there were significant changes in regional precision error; trunk lean mass (1.19%-1.77%, p = 0.014) and android fat mass (2.17%-3.72%, p = 0.046). CONCLUSIONS: For head and neck cancer patients, precision error of DXA total body composition values did not change significantly following chemotherapy; however, there were significant changes in fat mass in the android and lean mass in the trunk. Caution should be exercised when interpreting longitudinal DXA body composition data in those body parts.

Effects of phytoestrogens on the activity and growth of primary breast cancer cells ex vivo.

AIM: To explore the ex vivo effects of phytoestrogens on primary human breast cancer cells. METHODS: Breast cancer cells were obtained from patients who underwent primary breast cancer surgery, which were treated with 10-8 M 17ß-estradiol (E2 ), one of three phytoestrogens (genistein, resveratrol and quercetin, 10-7 M), and a combination of E2 and one of the three phytoestrogens for 48 h. These cells were then extracted for viability and apoptosis assay. The proteins involved in the proliferative and apoptotic pathways were evaluated by western blot analysis. RESULTS: Human breast cancer cell viability was inhibited by all phytoestrogens but induced by E2 with or without phytoestrogen. Apoptotic cells, as well as the proteins involved in apoptotic pathway and estrogen receptor (ER) ß, were significantly increased in the cells treated with phytoestrogen alone. The use of E2 with or without a phytoestrogen revealed completely opposite results. The proteins involved in the proliferative pathway and ER α expression were all increased in the cultures with E2 with or without phytoestrogens. CONCLUSION: In the presence of E2 , these phytoestrogens lose the effects of suppressing breast cancer cells; contrastingly, induce growth stimulatory effects by inhibiting apoptosis and stimulating proliferation in primary breast cancer cells. Thus, the effects of phytoestrogens on breast cancer should be considered as E2 still present in breast cancer tissue.

ROS Promote Ox-LDL-Induced Platelet Activation by Up-Regulating Autophagy Through the Inhibition of the PI3K/AKT/mTOR Pathway.

BACKGROUND/AIMS: Oxidized low-density lipoprotein (oxLDL) promotes unregulated platelet activation in patients with dyslipidemic disorders. Although oxLDL stimulates activating signaling, researchers have not clearly determined how these events drive accelerated thrombosis. Here, we describe the mechanism by which ROS regulate autophagy during ox-LDL-induced platelet activation by modulating the PI3K/AKT/mTOR signaling pathway. METHODS: For in vitro experiments, ox-LDL, the ROS scavenger N-acetylcysteine (NAC), the mTOR inhibitor rapamycin and the autophagy inhibitor 3-MA were used alone or in combination with other compounds to treat platelets. Then, platelet aggregation was evaluated on an aggregometer and platelet adhesion was measured under shear stress. The levels of a platelet activation marker (CD62p) were measured by flow cytometry, reactive oxygen species (ROS) levels were then quantified by measuring DCFH-DA fluorescence intensity via flow cytometry. Nitric oxide (NO) and superoxide (O2·-) levels were determined by the nitric acid deoxidize enzyme method and lucigenin-enhanced chemiluminescence (CL), respectively. Transmission electron microscopy was used to observe the autophagosome formation, immunofluorescence staining was employed to detect LC3 expression and western blotting was used to measure the levels of PI3K/AKT/mTOR pathway- and autophagy-related proteins. RESULTS: Ox-LDL-induced platelets showed a significant increase in platelet aggregation and adhesion, CD62p expression, ROS level and O2·- content, with an elevated LC3II/LC3I ratio and Beclin1 expression, but a dramatic reduction in the levels of p62 and pathway-related proteins (all P < 0.05). However, platelet activation and autophagy were aggravated by the Rapamycin treatment, and decreased following treatment with NAC, 3-MA, or NAC and 3-MA, together with increased activity of the PI3K/AKT/mTOR pathway. Additionally, decreased platelet activation and autophagy were observed in platelets treated with NAC and Rapamycin or Rapamycin and 3-MA compared with platelets treated with Rapamycin alone, suggesting that both NAC and 3-MA reversed the effects of Rapamycin. CONCLUSION: Inhibition of ROS production may reduce autophagy to suppress ox-LDL-induced platelet activation by activating PI3K/AKT/mTOR pathway.

Correlation of quality of life with risk factors for first-incident hip fracture in postmenopausal women.

AIM: The aim of this study was to identify the correlation between health-related quality of life (HRQOL) and risk factors of first-incidence hip fracture in postmenopausal women. METHODS: This case-control study included 99 postmenopausal women with first-incident hip fracture and 101 women without hip fracture who were matched according to age. Evaluation consisted of clinical factors, 36-item Short-Form Health Survey (SF-36) and dual-energy X-ray absorptiometry for bone mineral density of hip and spine. RESULTS: The mean age of patients with an accidental first-incident hip fracture was 78.0 years. Patients with hip fractures had significantly lower scores for SF-36 domains at enrollment and 4-month follow up compared with the controls. Mental health also deteriorated significantly 4 months after hip fracture. Aside from lower HRQOL, clinical factors, including increased body height, no experience with estrogen therapy, rheumatoid arthritis, use of walking aids, less weight-bearing exercise, and diuretics use, were significant risk factors for hip fracture in univariate analysis. After multivariate adjustment, only the use of walking aids and decreased physical component summary were independent risk factors of hip fracture. Besides aging, use of walking aids, weight-bearing exercise, and psychological medication were the main factors affecting HRQOL when considering their relationship with hip fractures. CONCLUSION: The occurrence of first-incidence hip fracture is highly associated with HRQOL. Aside from aging, clinical factors affecting HRQOL correlated with hip fracture incidence. Thus, in elderly women, exercise or physical therapy to improve physical function and mental support is crucial and should be considered the most important factors for first-incidence hip fracture prevention.

Role of HMGB1 in regulation of STAT3 expression in CD4(+) T cells from patients with aGVHD after allogeneic hematopoietic stem cell transplantation.

Treg/Th17 balance plays a critical role in maintaining immune homeostasis of acute graft-versus-host disease (aGVHD) patients. STAT3 is an important factor involved in the instability of Treg and the promotion of Th17. HMGB1 is a cytokine mediator of inflammation and an important chromatin protein regulating gene transcription. In this study, we found that the expressions of HMGB1 and STAT3 were higher in CD4(+) T cells of patients with aGVHD compared with those without aGVHD, and the HMGB1 expression was positively correlated with the STAT3 expression. Simultaneously, their expressions were positively correlated with the severity of the aGVHD. We also demonstrated that HMGB1 could regulate the expression of STAT3 by modulation of its DNA methylation in CD4(+) T cells, moreover downregulated HMGB1 in aGVHD CD4(+) T cells could change the ratio of Treg/Th17. These data strongly suggest that HMGB1 plays a crucial role in the regulation of Treg/Th17 and progression of aGVHD.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway.

The high mobility group 1B protein (HMGB1) mediates chronic inflammatory responses in endothelial cells, which play a critical role in atherosclerosis. However, the underlying mechanism is unknown. The goal of our study was to identify the effects of HMGB1 on the RAGE-induced inflammatory response in endothelial cells and test the possible involvement of the endoplasmic reticulum stress pathway. Our results showed that incubation of endothelial cells with HMGB1 (0.01-1 µg/ml) for 24h induced a dose-dependent activation of endoplasmic reticulum stress transducers, as assessed by PERK and IRE1 protein expression. Moreover, HMGB1 also promoted nuclear translocation of ATF6. HMGB1-mediated ICAM-1 and P-selectin production was dramatically suppressed by PERK siRNA or IRE1 siRNA. However, non-targeting siRNA had no such effects. HMGB1-induced increases in ICAM-1 and P-selectin expression were also inhibited by a specific eIF2α inhibitor (salubrinal) and a specific JNK inhibitor (SP600125). Importantly, a blocking antibody specifically targeted against RAGE (anti-RAGE antibody) decreased ICAM-1, P-selectin and endoplasmic reticulum stress molecule (PERK, eIF2α, IRE1 and JNK) protein expression levels. Collectively, these novel findings suggest that HMGB1 promotes an inflammatory response by inducing the expression of ICAM-1 and P-selectin via RAGE-mediated stimulation of the endoplasmic reticulum stress pathway.

Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study.

BACKGROUND: Invasive fungal infection (IFI) is common in neutropenic patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is a broad-spectrum triazole antifungal drug with efficacy in prevention of IFI; however, it has not been previously studied as prophylaxis in a Chinese population. METHODS: This multicenter, randomized study in China enrolled AML and MDS patients with persistent chemotherapy-induced neutropenia. Prophylaxis with posaconazole or fluconazole was administered for a maximum of 12 weeks, or until patients recovered from neutropenia and achieved complete remission or an IFI occurred. The primary endpoint was incidence of proven, probable, or possible IFI during treatment. Clinical failure rate, all-cause mortality and time to first systemic antifungal treatment were secondary endpoints. RESULTS: Patients were randomized to receive posaconazole (n = 129) or fluconazole (n = 123); 117 patients in each group were included in the statistical analysis. The incidence of proven, probable or possible IFI was 9.4% (11/117) and 22.2% (26/117) in the posaconazole and fluconazole groups, respectively (p = 0.0114). The clinical failure rate was numerically lower in the posaconazole group (37/117 (31.6%; 95%CI: 23.3 - 40.9)) than in the fluconazole group (49/117 (41.88%; 95% CI: 32.8 - 51.4)) (p = 0.168). Patients receiving posaconazole had a later onset of first systematic antifungal treatment than those receiving fluconazole (p = 0.0139). The most common important adverse events were liver function abnormalities (11 patients (8.8%) on posaconazole and 6 (5.0%) on fluconazole (p = 0.221)). CONCLUSIONS: Posaconazole demonstrates efficacy as prophylaxis against IFI in high-risk neutropenic Chinese patients and is well tolerated during long-term use (ClinicalTrials. gov number, NCT00811928).

Regulation of the cell cycle and P13K/AKT/mTOR signaling pathway by phthalates in normal human breast cells.

OBJECTIVE: To investigate the impact of phthalates, including Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP), in breast carcinogenesis. MATERIALS AND METHODS: MCF-10A normal breast cells were treated with phthalates (100 nM) and 17ß-estradiol (E2, 10 nM), which were co-cultured with fibroblasts from normal mammary tissue adjacent to estrogen receptor positive primary breast cancers. Cell viability was determined using a 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell cycles were analyzed using flow cytometry. The proteins involving cell cycles and P13K/AKT/mTOR signaling pathway were then evaluated by Western blot analysis. RESULTS: MCF-10A co-cultured cells treated with E2, BBP, DBP, and DEHP exhibited a significant increase in cell viability using MTT assay. The expressions of P13K, p-AKT, and p-mTOR, as well as PDK1 expression, were significantly higher in MCF-10A cells treated with E2 and phthalates. E2, BBP, DBP, and DEHP significantly increased cell percentages in the S and G2/M phases. The significantly higher expression of cyclin D/CDK4, cyclin E/CDK2, cyclin A/CDK2, cyclin A/CDK1, and cyclin B/CDK1 in MCF-10A co-cultured cells were induced by E2 and these three phthalates. CONCLUSION: These results provide consistent data regarding the potential role of phthalates exposure in the stimulating proliferation of normal breast cells, enhancing cell viability, and driving P13K/AKT/mTOR signaling pathway and cell cycle progression. These findings strongly support the hypothesis that phthalates may play a crucial role in breast tumorigenesis.

The no-observed-adverse-effect level of phthalates promotes proliferation and cell cycle progression in normal human breast cells.

OBJECTIVE: The data on the association between phthalates and breast cancer risk remains inconsistent. This study aimed to explore the possible mechanism of low-dose exposures of phthalates, including Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP), on breast tumorigenesis. METHODS AND METHODS: MCF-10A normal breast cells were treated with phthalates (10 and 100 nM) and 17ß-estradiol (E2, 10 nM), which were co-cultured with fibroblasts from normal mammary tissue. Cell viability, cycle, and apoptosis were detected by MTT assay, flow cytometry, and TUNEL assay respectively. The expression levels of related proteins were determined by Western blot. RESULTS: Like E2, both 10 nM and 100 nM phthalates exerted significantly higher cell viability, lower apoptosis, and increased cell numbers in the S and G2/M phases with up-regulation of cyclin D/CDK4, cyclin E/CDK2, cyclin A/CDK2, cyclin A/CDK1, and cyclin B/CDK1, compared with the control group. Significant increase in PDK1, P13K, p-AKT, p-mTOR, and BCL-2 expression and a decrease in Bax protein, cytochrome C, caspase 8, and caspase 3 levels were noted in cells treated with 10 nM and 100 nM phthalates and E2, compared with the control group and MCF-10A cells co-cultured with fibroblasts. The effects of the three phthalates were noted to be dose-dependent. CONCLUSIONS: The results indicate that phthalates at a level below its no-observed-adverse-effect concentration, as defined by the current standards, still induce cell cycle progression and proliferation as well as inhibit apoptosis of normal breast cells. Thus, the possibility of breast tumorigenesis through chronic phthalate exposure should be considered.

Impact of bisphosphonates and comorbidities on initial hip fracture prognosis.

The aim of this study is to investigate the impact of bisphosphonate treatment on the prognosis of patients with initial hip fracture. Patients aged fifty years and older with initial hip fracture were identified from the Taiwan National Health Insurance Research Database between 2002 and 2011. A multi-state model was established to evaluate the transition between "first to second hip fracture", "first hip fracture to death", and "second hip fracture to death". Transition probability and cumulative hazards were used to compare the prognosis of initial hip fracture in a bisphosphonate treated cohort versus non-treated cohort. In addition, Deyo-Charlson comorbidities, both vertebral and non-vertebral fractures, and cataracts were also included for analysis. After 10-year follow-up, there is decreased cumulative transition probability for both second hip fracture and mortality after both first and second hip fracture in the bisphosphonate treated cohort. Multivariable, transition-specific time-dependent Cox model revealed that bisphosphonate treatment significantly reduced risk for second hip fracture in the first 5 years of the treatment (HR 0.88; 95% CI 0.79-0.99; P: 0.034), first hip fracture mortality (HR 0.88; 95% CI 0.83-0.93; P < 0.001), and second hip fracture mortality in the first 2 years of the treatment (HR 0.78; 95% CI 0.65-0.95; P = 0.011). Female sex, both vertebral and non-vertebral fractures, cataracts, dementia in the first 2 years, and DM with complication were all significantly associated with risk of a second hip fracture. Cerebrovascular disease and hemiplegia comorbidities had less risk of a second hip fracture. The risk of mortality after both first and second hip fracture was significantly associated with congestive heart failure, renal disease, myocardial infarction, and moderate to severe liver disease. Our study demonstrated that bisphosphonate treatment and strict management of comorbidities after the initial hip fracture significantly decrease the risk for a second hip fracture and mortality.

The Effectiveness of a Group Kickboxing Training Program on Sarcopenia and Osteoporosis Parameters in Community-Dwelling Adults Aged 50-85 Years.

Background: Sarcopenia and osteoporosis are important health issues faced by older people. These are often associated with each other and share common risk factors and pathologic mechanisms. In the recently revised consensus of the European Working Group on Sarcopenia in Older People, low muscle strength has been defined as the first characteristic of sarcopenia rather than a loss in muscle mass, and walking speed has been stated as an indicator of the severity of sarcopenia. It is believed that these markers of muscle function can be potentially reversed via exercise-based interventions. The purpose of this study was to evaluate the effects of kickboxing exercise training on the parameters of sarcopenia and osteoporosis in community-dwelling adults. Methods: In total, one hundred eligible subjects were randomized into an intervention group (n = 50) with 76% women and control group (n = 50) with 86% women. Both the intervention and control groups were provided with classroom lectures and personal consultations pertaining to sarcopenia and osteoporosis, whereas a 12-week kickboxing exercise training was arranged only for the intervention group. All anthropometric, physical performance, body composition, and bone mineral density measurements along with participant completed questionnaires were conducted before and after the training period. Results: After 12 weeks, 41 participants in the intervention group and 34 participants in the control group completed the final assessments. There was no difference between the intervention and control groups in terms of basic demographic data. The BMI (+1.14%) of the control group increased significantly during the study period. The waist circumference (-6.54%), waist-to-height ratio (-6.57%), waist-to-hip ratio (-4.36%), total body fat (-1.09%), and visceral fat area (-4.6%) decreased significantly in the intervention group. Handgrip strength (+5.46%) and gait speed (+5.71%) improved significantly in the intervention group. The lean body mass increased by 0.35% in the intervention group and by 0.9% in the control group. The femoral neck bone mineral density (-1.45%) and T score (-3.72%) of the control group decreased significantly. The intervention group had more improvement in the status of sarcopenia (OR 1.91) and osteoporosis over the control group. Finally, the intervention group had less deterioration in the status of sarcopenia (OR 0.2) and osteoporosis (OR 0.86) compared with the control group. Conclusion: Our study demonstrated that a 12-week kickboxing exercise training program is effective for improving sarcopenic parameters of muscle strength and function, but not muscle mass in adults, aged 50-85 years. Furthermore, markers of osteoporosis also showed improvement. These findings suggest that a 12-week kickboxing program is effective for muscle and bone health among community-dwelling older individuals.

Association between P1NP and bone strength in postmenopausal women treated with teriparatide.

OBJECTIVE: To evaluate the association between P1NP and bone strength in postmenopausal women treated with teriparatide. MATERIALS AND METHODS: This prospective study enrolled 248 postmenopausal women with severe osteoporosis treated with teriparatide. Procollagen type 1 N-terminal propeptide (P1NP) were assessed at baseline, 3, 6, and 12 months. Lumbar spine (LS), femoral neck (FN), and total hip (TH) bone mineral density (BMD) and LS trabecular bone score (TBS) were measured by Dual-energy x-ray absorptiometry at baseline and 12 months. RESULTS: With teriparatide use, P1NP levels increase and peaked at 6 months. Significant increase in LS and hip BMD and LS TBS were also noted. The percentage change or absolute change >10 µg/L in PINP at 3 months was only related to changes in LS BMD at 12 months. With a median baseline P1NP level was 65.5 ng/mL, we found no correlation between P1NP and LS and hip BMD nor LS TBS. There was no association between LS TBS and axial BMD. After treatment, there was also no significance between the changes in TBS and axial BMD. Over the study period, 83.9% of the 248 participants were persistent with teriparatide at 3 months, 77.8% at 6 months, and 67.3% women at 12 months. CONCLUSION: P1NP levels may provide a signal of osteoporosis risk but is not related to bone strength. Early changes in P1NP may offer information regarding subsequent BMD response so standardized monitoring of P1NP levels at baseline and at 3 months should be considered during osteoporosis therapy. As an additional benefit, serum level monitoring during treatment may also improve medication persistence.

Utilizing nomograms to predict prevalent vertebral fracture risk: An analysis of dysmobility syndrome in a community-dwelling population.

BACKGROUND: To determine a reliable method to predict prevalent vertebral fractures (VF) by assessing the association between dysmobility syndrome (DS) and VF in a community-dwelling population. METHODS: This cross-sectional study enrolled 518 participants from fracture-prevention educational activities held in multiple communities in Taiwan. Assessments included questionnaires, fracture risk assessment tool (FRAX), bone mineral density (BMD) and body composition using dual-energy x-ray absorptiometry (DXA), lateral thoracolumbar spine x-rays (specifically T8-S1), grip strength (GS), walking speed, and fall history. RESULTS: DS was noted in 257 participants (49.6%) and VF was identified in 196 participants (37.8%). A higher prevalence of VF was noted in those with DS. The prevalence of VF was significantly associated with age, gender, FRAX both with and without BMD, osteoporosis, low GS, and DS. In multivariate models accounting for age and sex, the c-index was greater in those with low GS plus osteoporosis as compared to DS alone. Low GS, osteoporosis, and pre-BMD FRAX all had similar c-indexes. Pre-BMD FRAX plus low GS and osteoporosis was superior in predicting VF compared to pre-BMD FRAX plus low GS or osteoporosis alone. Besides the inclusion of age and gender, the nomogram with pre-BMD FRAX major osteoporosis fracture probability (MOF) plus low GS had improved correlation between the estimated and actual VF probability than those with pre-BMD FRAX MOF plus osteoporosis. CONCLUSIONS: The constructed nomogram containing pre-BMD FRAX MOF plus low GS may be considered as a first-line prevalent VF screening method. Those with high-risk scores should subsequently undergo vertebral radiography and/or BMD.

Inflammation Status and Body Composition Predict Two-Year Mortality of Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma under Provision of Recommended Energy Intake during Concurrent Chemoradiotherapy.

Only few prospective cohort trials have evaluated the risk factors for the 2-year mortality rate between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC): oral cavity cancer with adjuvant concurrent chemoradiotherapy (CCRT) (OCC) and non-oral cavity cancer with primary CCRT (NOCC), under the recommended calorie intake and investigated the interplay among calorie supply, nutrition-inflammation biomarkers (NIBs), and total body composition change (TBC), as assessed using dual-energy X-ray absorptiometry (DXA). Patients with LAHNSCC who consumed at least 25 kcal/kg/day during CCRT were prospectively recruited. Clinicopathological variables, blood NIBs, CCRT-related factors, and TBC data before and after treatment were collected. Factor analysis was performed to reduce the number of anthropometric and DXA-derived measurements. Cox proportional hazards models were used for analysis. We enrolled 123 patients with LAHNSCC (69 with OCC and 54 with NOCC). The mean daily calorie intake correlated with the treatment interval changes in total body muscle and fat. Patients consuming ≥30 kcal/kg/day had lower pretreatment levels but exhibited fewer treatment interval changes in anthropometric and DXA measurements than patients consuming <30 kcal/kg/day. In the multivariate analysis of the 2-year mortality rate, the prognostic influence of the recommended calorie intake could not be confirmed, but different risk factors (performance status, pretreatment platelet-to-lymphocyte ratio, and treatment interval body muscle changes in patients with OCC; age, pretreatment neutrophil-to-lymphocyte ratio, and body fat storage in patients with NOCC) showed independent effects. Therefore, the inflammation status and body composition, but not the recommended calorie supply, contribute to the 2-year mortality rate for patients with LAHNSCC receiving CCRT.

The alteration of placental-derived soluble MHC class I chain-related protein A and B during pregnancy.

OBJECTIVE: According to a novel mechanism for fetal evasion from maternal immune attack via the engagement and down-regulation of the maternal natural killer cell receptor NKG2D by soluble MHC class I chain-related proteins (sMIC) A and B derived from placenta, we aimed to measure whether the sMICA/B level altered during pregnancy. DESIGN AND SETTING: Healthy women undergoing routine antepartum examination at Kee-Lung Chang Gung Memorial Hospital from December 2006 to December 2007 were prospectively registered for this study. SAMPLES: We collected 337 serum specimens and 10 amniotic fluid samples from 300 normal pregnant women for sMICA/B analysis. METHODS: Capture ELISA procedures were used to determine sMICA/B concentration in serum and amniotic fluid specimens. MAIN OUTCOME MEASURES: We hypothesized that the sMICA/B level would increase in proportion to the gestational age to protect the fetus from maternal immune rejection in the normal pregnancy. Results. The serum sMICA/B level rose gradually with the progression of gestation and decreased after the second trimester, with the lowest level appearing before delivery. In addition, we found that levels of soluble MICA/B were extremely low in amniotic fluid. CONCLUSIONS: We suggest that, as delivery approaches, the reduced production of soluble MICA/B by the aged placenta may be playing a role in parturition. Furthermore, we suggest that the effect of soluble MICA/B on natural killer cells of pregnant women is limited to the maternal placental surface, but not transferred through the placenta into the amniotic cavity.