Quantitative imaging of ultrasound backscattered signals with information entropy for bone microstructure characterization.

Osteoporosis is a critical problem during aging. Ultrasound signals backscattered from bone contain information associated with microstructures. This study proposed using entropy imaging to collect the information in bone microstructures as a possible solution for ultrasound bone tissue characterization. Bone phantoms with different pounds per cubic foot (PCF) were used for ultrasound scanning by using single-element transducers of 1 (nonfocused) and 3.5 MHz (nonfocused and focused). Clinical measurements were also performed on lumbar vertebrae (L3 spinal segment) in participants with different ages (n = 34) and postmenopausal women with low or moderate-to-high risk of osteoporosis (n = 50; identified using the Osteoporosis Self-Assessment Tool for Taiwan). The signals backscattered from the bone phantoms and subjects were acquired for ultrasound entropy imaging by using sliding window processing. The independent t-test, one-way analysis of variance, Spearman correlation coefficient rs, and the receiver operating characteristic (ROC) curve were used for statistical analysis. The results indicated that ultrasound entropy imaging revealed changes in bone microstructures. Using the 3.5-MHz focused ultrasound, small-window entropy imaging (side length: one pulse length of the transducer) was found to have high performance and sensitivity in detecting variation among the PCFs (rs = - 0.83; p < 0.05). Small-window entropy imaging also performed well in discriminating young and old participants (p < 0.05) and postmenopausal women with low versus moderate-to-high osteoporosis risk (the area under the ROC curve = 0.80; cut-off value = 2.65; accuracy = 86.00%; sensitivity = 71.43%; specificity = 88.37%). Ultrasound small-window entropy imaging has great potential in bone tissue characterization and osteoporosis assessment.

The Effect of Yoga Asana "Vrksasana (Tree Pose)" on Balance in Patients With Postmenopausal Osteoporosis: A Randomized Controlled Trial.

OBJECTIVE: In this study, the effect of the add-on effect of the Tree Pose (Vrksasana) on the balance of patients with postmenopausal osteoporosis was investigated. DESIGN: Thirty-two patients with postmenopausal osteoporosis were randomly assigned to conservative exercise group (30 mins/d for 12 wks) or Tree Pose-added exercise group (30-min conventional exercise + 2-min Tree Pose/d for 12 wks) by Microsoft Excel randomization option. The balance of the patients was evaluated with Berg Balance Scale, Timed Up and Go Test, single-leg standing test, tandem walk test, tandem stance test, and Korebalance static&dynamic balance tests at baseline, sixth week, and third month of the exercise program. RESULTS: There was no statistically significant difference on baseline data between groups. There was a statistically significant difference between the two groups in the sixth-week measurement of single-leg stance (P < 0.05). In the Berg Balance Scale, static balance test, dynamic balance test, and tandem walk test, a statistically significant difference was found among baseline, sixth-week, and 12th week measurements in both the exercise group and the Tree Pose-added exercise group. CONCLUSIONS: Gains in the static and dynamic balance of postmenopausal osteoporotic patients can be obtained by adding "Vrksasana" to conventional exercises.

Olive oil effectively mitigates ovariectomy-induced marrow adiposity assessed by MR spectroscopy in estrogen-deficient rabbits.

BACKGROUND: Polyphenols in extra virgin olive oil (EVOO) have been found to reduce the expression of PPARγ2, inhibit adipocyte differentiation, and enhance the formation of osteoblasts from bone marrow stem cells. However, the underlying mechanisms of their action remain unknown. PURPOSE: To determine the sequential effects of EVOO on marrow fat expansion induced by estrogen deprivation using 3.0-T proton magnetic resonance (MR) spectroscopy in an ovariectomy (OVX) rabbit model of postmenopausal bone loss over a six-month period. MATERIAL AND METHODS: A total of 45 female New Zealand rabbits were equally divided into sham-operation, OVX controls, and OVX treated with EVOO for six months. Marrow fat fraction was measured by MR spectroscopy at baseline conditions, and three and six months postoperatively, respectively. Serum bone biomarkers, lumbar and femoral bone mineral density, microtomographic parameters, biomechanical properties, and quantitative parameters of marrow adipocytes were studied. RESULTS: OVX was associated with marrow adiposity in a time-dependent manner, accompanied with increased bone turnover and impaired bone mass and trabecular microarchitecture. In OVX rabbits, EVOO markedly alleviated trabecular bone loss and reduced the accumulation of lipid droplets including adipocyte size, density, and areas of fat deposits in the bone marrow. EVOO prevented such changes in terms of both marrow adiposity and bone remodeling. CONCLUSION: Early EVOO treatment may exert beneficial effects on bone by modulating marrow adiposity, which would support their protective effect against bone pathologies.

Circulating MicroRNA Expression, Vitamin D, and Hypercortisolism as Predictors of Osteoporosis in Elderly Postmenopausal Women.

BACKGROUND: MicroRNAs (miRNA) identified as critical molecular regulators for bone development, function, and modeling/remodeling process and could be predictable for osteoporotic fractures in postmenopausal elderly women. AIM: The potential diagnostic role of circulating miRNAs, miR-148a and miR-122-5p, in the pathogenesis of osteoporosis and its association with bone markers, hypercortisolism, and vitamin D deficiency were explored in postmenopausal elderly women with osteoporosis. METHODS: A total of 120 elderly women aged 50-80 years old were recruited in this study, of which only 100 eligible women with amenorrhea of at least 12 consecutive months or surgical menopause participated in this study. Based upon bone mineral density (BMD) measurements, the participants were classified according into two groups: normal (n = 45; T score of ≥-1.0) and osteoporosis (n = 55; T score: ≤-2.5). Circulating miRNAs, miR-148a and miR-122-5p, were estimated by real-time RT-PCR analysis. In addition, bone markers, hypercortisolism, and vitamin D deficiency were colorimetrically and ELISA immune assay estimated. The potential role of miR-148a, miR-122-5p, cortisol, and vitamin D in the diagnosis of osteoporosis was predicted using the analysis of the respective area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The expressed level of miR-148a significantly increased and miR-122-5p significantly decreased in the serum of osteoporotic patients compared to healthy controls. In addition, a significant increase in the levels of cortisol, s-BAP, and CTx and significant decrease in the levels of T-BMD, the levels of OC, and s-Ca were also identified. All parameters significantly correlated with fracture risk parameters; BMD, and T score lumbar spine (L2-L4). Thus, the data showed AUC cut off values (miR-148a; 0.876, miR-122-5p; 0.761) were best evaluated for clinical diagnosis of patients with osteoporosis and that AUC cut off values of 0.748 for cortisol and 0.635 for vitamin D were the best cut off values, respectively, reported for the prediction of osteoporosis clinical diagnosis. CONCLUSION: In this study, expressed miRNAs miR-148a and miR-122-5p and changes in the levels of both cortisol and vitamin D status are significantly associated with bone loss or osteoporosis. Thus, circulation miRNAs alone or in combination with cortisol and vitamin D status might be considered predictable biomarkers in the diagnosis or the pathogenesis of osteoporosis in elderly postmenopausal women; however, more studies are recommended.

Osteocytes and Estrogen Deficiency.

PURPOSE OF REVIEW: Postmenopausal osteoporosis reduces circulating estrogen levels, which leads to osteoclast resorption, bone loss, and fracture. This review addresses emerging evidence that osteoporosis is not simply a disease of bone loss but that mechanosensitive osteocytes that regulate both osteoclasts and osteoblasts are also impacted by estrogen deficiency. RECENT FINDINGS: At the onset of estrogen deficiency, the osteocyte mechanical environment is altered, which coincides with temporal changes in bone tissue composition. The osteocyte microenvironment is also altered, apoptosis is more prevalent, and hypermineralization occurs. The mechanobiological responses of osteocytes are impaired under estrogen deficiency, which exacerbates osteocyte paracrine regulation of osteoclasts. Recent research reveals changes in osteocytes during estrogen deficiency that may play a critical role in the etiology of the disease. A paradigm change for osteoporosis therapy requires an advanced understanding of such changes to establish the efficacy of osteocyte-targeted therapies to inhibit resorption and secondary mineralization.

Anabolic Bone Stimulus Requires a Pre-Exercise Meal and 45-Minute Walking Impulse of Suprathreshold Speed-Enhanced Momentum to Prevent or Mitigate Postmenopausal Osteoporosis within Circadian Constraints.

Osteoporosis currently afflicts 8 million postmenopausal women in the US, increasing the risk of bone fractures and morbidity, and reducing overall quality of life. We sought to define moderate exercise protocols that can prevent postmenopausal osteoporosis. Our previous findings singled out higher walking speed and pre-exercise meals as necessary for suppression of bone resorption and increasing of markers of bone formation. Since both studies were amenable to alternate biomechanical, nutritional, and circadian interpretations, we sought to determine the relative importance of higher speed, momentum, speed-enhanced load, duration of impulse, and meal timing on osteogenic response. We hypothesized that: (1) 20 min of exercise one hour after eating is sufficient to suppress bone resorption as much as a 40-min impulse and that two 20 min exercise bouts separated by 7 h would double the anabolic effect; (2) early morning exercise performed after eating will be as effective as mid-day exercise for anabolic outcome; and (3) the 08:00 h 40-min. exercise uphill would be as osteogenic as the 40-min exercise downhill. Healthy postmenopausal women, 8 each, were assigned to a no-exercise condition (SED) or to 40- or 20-min exercise bouts, spaced 7 h apart, for walking uphill (40 Up and 20 Up) or downhill (40 Down and 20 Down) to produce differences in biomechanical variables. Exercise was initiated at 08:00 h one hour after eating in 40-min groups, and also 7 h later, two hours after the midday meal, in 20-min groups. Measurements were made of CICP (c-terminal peptide of type I collagen), osteocalcin (OC), and bone-specific alkaline phosphatase (BALP), markers of bone formation, and of the bone resorptive marker CTX (c-terminal telopeptide of type 1 collagen). The osteogenic ratios CICP/CTX, OC/CTX, and BALP/CTX were calculated. Only the 40-min downhill exercise of suprathreshold speed-enhanced momentum, increased the three osteogenic ratios, demonstrating the necessity of a 40-min, and inadequacy of a 20-min, exercise impulse. The failure of anabolic outcome in 40-min uphill exercise was attributed to a sustained elevation of PTH concentration, as its high morning elevation enhances the CTX circadian rhythm. We conclude that postmenopausal osteoporosis can be prevented or mitigated in sedentary women by 45 min of morning exercise of suprathreshold speed-enhanced increased momentum performed shortly after a meal while walking on level ground, or by 40-min downhill, but not 40-min uphill, exercise to avoid circadian PTH oversecretion. The principal stimulus for the anabolic effect is exercise, but the prerequisite for a pre-exercise meal demonstrates the requirement for nutrient facilitation.

Tributyltin protects against ovariectomy-induced trabecular bone loss in C57BL/6J mice with an attenuated effect in high fat fed mice.

Risk factors for poor bone quality include estrogen loss at menopause, a high fat diet and exposures to drugs/chemicals that activate peroxisome proliferator activated receptor gamma (PPARγ). We previously reported that the PPARγ and retinoid X receptor dual ligand, tributyltin (TBT), repressed periosteal bone formation but enhanced trabecular bone formation in vivo. Here, we examined the interaction of diet, ovariectomy (OVX) and TBT exposure on bone structure. C57BL/6J mice underwent either sham surgery or OVX at 10 weeks of age. At 12 weeks of age, they were placed on a low (10% kcal) or high (45% kcal) fat, sucrose-matched diet and treated with vehicle or TBT (1 or 5 mg/kg) for 14 weeks. OVX increased body weight gain in mice on either diet. TBT enhanced body weight gain in intact mice fed a high fat diet, but decreased weight gain in OVX mice. Elemental tin concentrations increased dose-dependently in bone. TBT had marginal effects on cortical and trabecular bone in intact mice fed either diet. OVX caused a reduction in cortical and trabecular bone, regardless of diet. In high fat fed OVX mice, TBT further reduced cortical thickness, bone area and total area. Interestingly, TBT protected against OVX-induced trabecular bone loss in low fat fed mice. The protective effect of TBT was nullified by the high fat. These results show that TBT protects against trabecular bone loss, even in the presence of a strongly resorptive environment, at an even lower level of exposure than we showed repressed homeostatic resorption.

Assessment of the effect of estradiol on biochemical bone turnover markers among postmenopausal women.

INTRODUCTION: Estrogen deficiency found in postmenopausal women may lead to disturbances in the balance of bone metabolism. Study of the influence of estradiol on markers of bone turnover may help to understand the mechanisms of bone metabolism and to monitor osteoporosis therapy in postmenopausal women at high risk of fractures. The aim of the study was evaluation of the effect of estradiol on the basic markers of bone turnover in postmenopausal women. MATERIAL AND METHODS: The study was conducted in a group of 92 postmenopausal women, divided into two groups: Gr-1 with low estradiol levels ≤ 10 pg/ml and Gr-2 with reference estradiol levels ≥ 25 pg/ml). Basic markers of bone turnover were examined: Ctx (C-terminal cross-linked telopeptide of type I collagen alpha chain) and OC (osteocalcin); pro-resorptive cytokines: IL-6 and TNF-α; vitamin 25(OH)D3 and lipid profile. Women was also analyzed according to demographic and clinical data. RESULTS: A positive relationship was found between estradiol and the main bone formation marker - OC (p = 0.041, r = 0.213) and IL-6, TNF-α (p = 0.007, r = 0.281 and p = 0.018, r = 0.246, respectivly, but only in the group with a reference hormone level. Moreover, the main markers of bone turnover: Ctx and OC showed a mutual positive correlation (p = 0.013; r = 0.257) in women with reference estradiol levels. Relationships between markers of bone remodeling, pro-resorptive cytokines and vitamin D3 depending on the level of estradiol showed no statistically significant correlation. CONCLUSIONS: The study showed that only in women with the reference estradiol level (≥ 25 pg/ml) were the bone formation and resorption processes balanced.

Development of selective bispecific Wnt mimetics for bone loss and repair.

The Wnt signaling pathway is intricately connected with bone mass regulation in humans and rodent models. We designed an antibody-based platform that generates potent and selective Wnt mimetics. Using this platform, we engineer bi-specific Wnt mimetics that target Frizzled and low-density lipoprotein receptor-related proteins and evaluate their effects on bone accrual in murine models. These synthetic Wnt agonists induce rapid and robust bone building effects, and correct bone mass deficiency and bone defects in various disease models, including osteoporosis, aging, and long bone fracture. Furthermore, when these Wnt agonists are combined with antiresorptive bisphosphonates or anti-sclerostin antibody therapies, additional bone accrual/maintenance effects are observed compared to monotherapy, which could benefit individuals with severe and/or acute bone-building deficiencies. Our data support the continued development of Wnt mimetics for the treatment of diseases of low bone mineral density, including osteoporosis.

A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways.

Bromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F-actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL-stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

Effectiveness of Pilates and Yoga to improve bone density in adult women: A systematic review and meta-analysis.

BACKGROUND: The ageing population brings about the appearance of age-related health disorders, such as osteoporosis or osteopenia. These disorders are associated with fragility fractures. The impact is greater among postmenopausal women due to an acceleration of bone mineral density (BMD) loss. OBJECTIVE: To estimate the effectiveness of Pilates or Yoga on BMD in adult women. METHODS: Five electronics databases were searched up to April 2021. Randomized controlled trials (RCTs), non-RCTs and pre-post studies were included. The main outcome was BMD. Risk of bias was evaluated using the Cochrane risk of bias tool. A random effects model was used to pool data from primary studies. Subgroup analyses based on the type of exercise were conducted. RESULTS: Eleven studies including 591 participants aged between 45 and 78 years were included. The mean length of the interventions ranged from 12 to 32 weeks, and two studies were performed for a period of at least one year. The pooled effect size for the effect of the intervention (Pilates/Yoga) vs the control group was 0.07 (95% Confidence interval [CI]: -0.05 to 0.19; I2 = 0.0%), and 0.10 (95% CI: 0.01 to 0.18; I2 = 18.4%) for the secondary analysis of the pre-post intervention. CONCLUSIONS: Despite of the non-significant results, the BMD maintenance in the postmenopausal population, when BMD detrimental is expected, could be understood as a positive result added to the beneficial impact of Pilates-Yoga in multiple fracture risk factors, including but not limited to, strength and balance.

The effect of whole-body vibration exercise on postmenopausal women with osteoporosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Osteoporosis (OP) is an age-related disease characterized by reduced bone mass and increased bone fragility. It is more common in older people and postmenopausal women. As a new type of exercise training for OP, whole-body vibration (WBV) exercise has been proved to have a good effect on postmenopausal women with OP. It can increase bone density and improve strength and balance in postmenopausal population, which has certain clinical value, but lacks evidence-based medicine evidence. This study aims to systematically study the effectiveness of WBV exercise on postmenopausal women with OP. METHODS: The English databases (PubMed, Embase, Web of Science, The Cochrane Library) and Chinese databases (China National Knowledge Network, Wanfang, Weipu, China Biomedical Database) were searched by computer. From the establishment of the database to February 2021, the randomized controlled clinical studies on WBV exercise on postmenopausal women with OP were conducted. The quality of the included studies was independently extracted by 2 researchers and literature quality was evaluated. Meta-analysis of the included studies was performed using RevMan5.3 software. RESULTS: In this study, the efficacy and safety of WBV exercise on postmenopausal women with OP were evaluated by lumbar spine bone density, femoral neck bone density, pain, incidence of falls, incidence of fractures, and quality of life scale score, etc. CONCLUSION: This study will provide reliable evidences for the clinical application of WBV exercise on postmenopausal women with OP. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/WPYT9.

Faster Lumbar Spine Bone Loss in Midlife Predicts Subsequent Fracture Independent of Starting Bone Mineral Density.

CONTEXT: Bone mineral density (BMD) decreases rapidly during menopause transition (MT), and continues to decline in postmenopause. OBJECTIVE: This work aims to examine whether faster BMD loss during the combined MT and early postmenopause is associated with incident fracture, independent of starting BMD, before the MT. METHODS: The Study of Women's Health Across the Nation, a longitudinal cohort study, included 451 women, initially premenopausal or early perimenopausal, and those transitioned to postmenopause. Main outcome measures included time to first fracture after early postmenopause. RESULTS: In Cox proportional hazards regression, adjusted for age, body mass index, race/ethnicity, study site, use of vitamin D and calcium supplements, and use of bone-detrimental or -beneficial medications, each SD decrement in lumbar spine (LS) BMD before MT was associated with a 78% increment in fracture hazard (P = .007). Each 1% per year faster decline in LS BMD was related to a 56% greater fracture hazard (P = .04). Rate of LS BMD decline predicted future fracture, independent of starting BMD. Women with a starting LS BMD below the sample median, and an LS BMD decline rate faster than the sample median had a 2.7-fold greater fracture hazard (P = .03). At the femoral neck, neither starting BMD nor rate of BMD decline was associated with fracture. CONCLUSION: At the LS, starting BMD before the MT and rate of decline during the combined MT and early postmenopause are independent risk factors for fracture. Women with a below-median starting LS BMD and a faster-than-median LS BMD decline have the greatest fracture risk.

Prevalence and Risk Factors of Osteoporosis in Chinese Postmenopausal Women Awaiting Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) complications associated with low bone quality are challenging for orthopaedic surgeons to treat, but little is known about bone quality in Chinese postmenopausal women awaiting TKA. This study investigated the incidence of osteoporosis (OP) and explored the preoperative risk factors for OP in this population. METHODS: We retrospectively reviewed the data of Chinese postmenopausal women who were indicated for TKA between May 2017 and June 2020. The bone mineral density (BMD) of the hip and lumbar spine and multiple preoperative parameters were collected and analyzed. Binary logistic regression analysis was performed to identify independent risk factors for OP in this population. RESULTS: A total of 204 postmenopausal women with advanced knee OA were included in the study (age: 69.7±8.5 years; body mass index [BMI]: 25.5±4.0 kg/m2). The OP prevalence among all participants was 59.8%, and the patients aged 60-80 years had a significantly lower BMD than did the age/ethnicity-adjusted population. An age ≥60 years, a BMI<25, and the presence of a varus knee deformity were independent risk factors for preoperative OP in the postmenopausal women awaiting TKA. CONCLUSION: The prevalence of OP in Chinese postmenopausal women awaiting TKA is higher than that in the age/ethnicity-adjusted normal population. An age ≥60 years, a BMI<25, and the presence of a varus knee deformity are independent risk factors that can be used to predict preoperative OP in this population.

Genotypic Analyses of the Sclerostin rs851056 and Dickkopf rs1569198 Polymorphisms in Mexican-Mestizo Postmenopausal Osteoporosis: A Case-Control Study.

Background: The Wnt/ß catenin pathway promotes bone mineralization stimulating proliferation, differentiation, and survival of osteoblasts; it also inhibits osteoclast differentiation and osteocyte activity. Sclerostin (SOST) and Dickkopf 1 (DKK1) are Wnt/ß catenin pathway inhibitors. Genetic variability in the expression of SOST and DKK1 might be involved in the development of postmenopausal osteoporosis (OP). Aim: To determine whether the SOST rs851056 and DKK1 rs1569198 polymorphisms are associated with OP in Mexican-Mestizo postmenopausal women. Materials and Methods: Two hundred and eighty Mexican-Mestizo postmenopausal women were assessed for their bone mineral density by dual-energy X-ray absorptiometry (DXA). Patients were classified as OP or non-OP. Genomic DNA was extracted from peripheral blood leukocytes. Genetic polymorphisms were analyzed by quantitative polymerase chain reaction using TaqMan probes. Results: The frequency of OP was 40% among the study population. Osteoporotic patients were older (p < 0.001), had a higher frequency of smoking (p = 0.01), and lower body mass index (p < 0.001) compared with the non-osteoporotic patients. The genotypic frequencies of the rs851056 locus of the SOST gene were GG 19%, GC 45%, and CC 35%, whereas the genotypic frequencies of the rs1569198 locus of the DKK1 gene were GG 15%, GA 40%, and AA 44%. In relation to rs851056 locus of the SOST gene, no differences were observed between the OP and non-OP cohorts in the frequencies of the GC polymorphism (48.7% vs. 43.1%). Similarly, analyses of the DKK1 rs1569198 does not demonstrate differences in the GA genotypic frequencies between the OP and non-OP cohorts (42.5% vs. 38.9%). Conclusion: Polymorphisms SOST rs851056 and DKK1 rs1569198 polymorphisms are not associated with OP in Mexican-Mestizo postmenopausal women.

Change in kyphosis does not affect the risk of falling in postmenopausal osteopenic and osteoporotic women.

OBJECTIVES: To examine the influence of the annual change in kyphosis on the risk of falling in postmenopausal osteopenic and osteoporotic women. METHODS: This prospective observational study included 498 postmenopausal Greek women over the age of 50, suffering from either osteoporosis or osteopenia. Data on age, height, weight, and self-reported falls were collected. Additionally, we evaluated the degree of the kyphosis angle, the balance, the mobility, the functionality and the handgrip strength on both hands of each subject using the Debrunner kyphometer, the Berg Balance Scale, the Timed-Up-and-Go test, the 30 Seconds Sit-to-Stand test and the Jamar Hydraulic Hand Dynamometer, respectively. All the above data were recorded at the baseline visit and the 12-month follow-up visit for each participant. RESULTS: All examined variables presented a statistically significant change at the 12-month follow-up visit. Nevertheless, the annual change in kyphosis did not show any association with the risk of falling. CONCLUSION: No association was shown between the annual change in kyphosis and the risk of falling in postmenopausal osteopenic and osteoporotic women, nor bears any substantial prognostic value for future falls.

Mechanism of dexmedetomidine regulating osteogenesis-angiogenesis coupling through the miR-361-5p/VEGFA axis in postmenopausal osteoporosis.

AIMS: Postmenopausal osteoporosis (PMOP) is a growing health problem affecting many postmenopausal women. This study intended to identify the role of dexmedetomidine (Dex) in osteoporosis (OP). MAIN METHODS: Microarray analysis was performed for the gene expression profiles of PMOP patients and postmenopausal healthy volunteers, and the most differentially expressed microRNA (miR)-361-5p was verified in clinic, and its diagnostic value in PMOP patients was analyzed. After establishment of OP model by ovariectomy, Dex treatment and overexpression of miR-361-5p or vascular endothelial growth factor A (VEGFA) were performed in OP rats or isolated bone marrow mesenchymal stem cells (BMSCs). Bone mineral density (BMD) related indexes and levels of osteogenesis-angiogenesis related genes were measured. The apoptosis and osteogenic differentiation of BMSCs were detected. After human umbilical vein endothelial cells (HUVECs) and BMSCs were cocultured, the angiogenesis of BMSCs was detected by Matrigel-based angiogenesis experiment. KEY FINDINGS: miR-361-5p was highly expressed in PMOP patients and OP rats, with good diagnostic effect on PMOP. After Dex treatment, the expressions of miR-361-5p, VEGFA, BMD related indexes were increased in OP rats. In BMSCs, level of osteogenesis-angiogenesis related genes were increased after adding Dex, and the apoptosis was decreased after coculture of HUVECs and BMSCs. miR-361-5p could target VEGFA. After miR-361-5p overexpression + Dex treatment, the indexes related to osteogenesis and angiogenesis in OP rats and BMSCs were decreased, which were reversed after further overexpressing VEGFA. SIGNIFICANCE: Dex can enhance VEGFA by inhibiting miR-361-5p, and then promote osteogenesis-angiogenesis, thus providing potential targets for PMOP treatment.

Comparison of the Characteristics of Back Pain in Women with Postmenopausal Osteoporosis with and without Vertebral Compression Fracture: A Retrospective Study at a Single Osteoporosis Center in Poland.

BACKGROUND The incidence of unspecific back pain and osteoporotic vertebral compression fractures increases significantly with age. Considering the difficulties in the diagnosis of spontaneous osteoporotic vertebral fractures, this retrospective study aimed to compare the characteristics of back pain in women with postmenopausal osteoporosis with and without vertebral compression fractures. MATERIAL AND METHODS This study enrolled 334 women with postmenopausal osteoporosis; 150 had vertebral fractures, and 184 had no vertebral fractures. Densitometric vertebral fracture assessment and bone mineral density measurements in the central skeleton were performed for each patient. The participants completed a survey about features of their back pain. RESULTS Patients with vertebral fractures had more severe back pain based on the numeric rating scale: 6.14 vs. 4.33 (P<0.001, odds ratio [OR]=1.43, 95% confidence interval [CI]: 1.29-1.59). Among these individuals, back pain caused reduction in normal activity during the day (P<0.001, OR=4.68, 95% CI: 2.86-7.68), and pain occurred more often (P<0.001, OR=1.77, 95% CI: 1.47-2.13), lasted longer (P<0.001, OR=2.01, 95% CI: 1.65-2.46), predominantly occurred in the lumbar spine (P<0.001, OR=4.70, 95% CI: 1.96-11.29), and intensified during normal everyday activities (P<0.001). Based on these results, a new survey was created. It demonstrated a sensitivity of 70.67% and a specificity of 67.37% in predicting a current compression fracture. CONCLUSIONS Patients with vertebral compression fractures experience higher pain intensity and exhibit specific features of back pain. The new survey can be considered a supportive tool in assessing the possibility of vertebral compression fractures.

Plasma periostin as a biomarker of osteoporosis in postmenopausal women with type 2 diabetes.

INTRODUCTION: Periostin, as an emerging biomarker, is involved in multiple steps in bone metabolism. This study aimed to investigate the correlation between periostin levels and bone mineral density as well as bone turnover markers in postmenopausal women with type 2 diabetes (T2DM). MATERIALS AND METHODS: This study was a cross-sectional study that included 164 postmenopausal women with T2DM as study subjects and 32 age-matched nondiabetic postmenopausal women with normal bone mineral density (BMD) as healthy control subjects. A total of 164 subjects with T2DM were then divided into three groups according to BMD: the normal BMD group (n = 29), the osteopenia group (n = 70), and the osteoporosis group (n = 65). The clinical data of all subjects along with the relevant biochemical parameter data were collected. Plasma periostin was detected using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma periostin levels were significantly increased in T2DM patients with normal BMD compared with healthy controls (p < 0.05). In the diabetic group, plasma periostin levels were significantly elevated with decreased BMD, were positively correlated with osteocalcin levels (r = 0.162, p = 0.039) and were inversely associated with femoral neck BMD (r = - 0.308, p < 0.001) and total femur BMD (r = - 0.295, p < 0.001). In the case of chronic complications, periostin levels were slightly increased in individuals with complications of diabetic retinopathy, diabetic nephropathy and fracture (p > 0.05). CONCLUSIONS: The current study demonstrated that plasma periostin levels were significantly associated with BMD in patients with T2DM, and periostin might act as a novel biochemical marker of osteoporosis in postmenopausal women with type 2 diabetes.

Exosomal miR-186 derived from BMSCs promote osteogenesis through hippo signaling pathway in postmenopausal osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMO) that results from estrogen withdrawal is the most common primary osteoporosis among older women. However, little is known about the mechanism of PMO, and effective treatment of PMO is limited. METHODS: We used real-time polymerase chain reaction (qPCR), Western blotting, and RNA pull down to investigate the relationship between miR-186 and MOB Kinase Activator 1A (Mob1). Also, we investigated the effect of exosome in osteogenesis using alkaline phosphatase (ALP) staining. And hematoxylin eosin (HE) staining was used to verify the osteogenesis in PMO model. RESULTS: Exosomal miR-186 plays an important role in bone formation. The results of miRNA-seq and q-PCR showed that miR-186 was upregulated in a PMO + Exo treatment group. Results of RNA-pull down and luciferase reporter assays verified interactions between miR-186 and Mob1. We also verified the Hippo signaling pathway plays an important role in osteogenesis. CONCLUSIONS: We concluded that exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) can transfer miR-186 to promote osteogenesis in ovariectomy (OVX) rats through the Hippo signaling pathway.