Osteoporotic Subjects Research Articles

Impairment of PTX3 expression in osteoblasts: a key element for osteoporosis

Pentraxin 3 (PTX3) is a multifunctional glycoprotein regulating inflammatory response, cell proliferation and migration and deposition and remodelling of the extracellular matrix by a variety of cells. In this study, we investigated the possible role of PTX3 in bone homeostasis. To this end, we compared the expression and function of PTX3 in human osteoblasts of osteoporotic, osteoarthritic patients and young subjects not affected by bone diseases. Immunohistochemical analysis performed on bone head biopsies showed a close association between bone health and the number of osteoblasts expressing PTX3. Noteworthy, the proportion of PTX3-positive osteoblasts resulted to be significantly lower in osteoporotic patients compared with both young patients and osteoarthritic patients of the same age. Ex vivo culture of osteoblasts isolated from the three groups of patients confirmed in vivo observation. Specifically, we observed rare runt-related transcription factor 2 (RUNX2) immunopositive osteoblasts expressing PTX3 in cell cultures derived from osteoporotic patients and western blotting analysis showed 80% reduction of PTX3 in the corresponding culture extracts compared with young and osteoarthritic patients. The treatment of human osteoblast primary cultures derived from young patients with anti-PTX3 antibody dramatically affected osteoblast behaviour. Indeed, they lost the morphological and molecular features typical of mature osteoblasts, acquiring fibroblast-like shape and highly decreasing nuclear factor kappa-B ligand (RANKL) and RUNX2 expression. Also, the inhibition of PTX3 negatively affected osteoblast proliferation and their ability to form cell clusters and microhydroxyapatite crystals. Altogether, these results suggest a central role of PTX3 in bone homeostasis showing its involvement in osteoblast proliferation, differentiation and function.

Quantitative Ultrasound of the Mandible as a Novel Screening Approach for Osteoporosis

This study used an axial transmission quantitative ultrasound (QUS) device to assess mandibular bone strength. The aim of the study was first to establish the precision and repeatability of the axial transmission QUS measurement for a range of mandibular anatomic sites, and second to investigate the ability of the modality to differentiate between osteoporotic subjects and a control group. Three groups of adult Caucasian women were recruited: (1) healthy premenopausal women (n = 26), (2) healthy postmenopausal women (n = 48), and (3) women with osteoporosis (n = 53). Subjects were excluded from groups 1 and 2 if they had any pre-existing bone conditions. Speed of sound (SOS) measurements were taken from the mandible using an OmniSense multisite QUS device. Group 3 had dual-energy X-ray absorptiometry scans of the lumbar spine and femur. The most suitable site on the mandible was determined by repeat SOS measurements in 10 healthy premenopausal subjects, at 5 different sites. The parasymphysis site had the lowest root mean squared coefficient of variation at 0.74%, and was chosen as the most suitable site for mandibular SOS measurements. Group 1 and group 2 had significantly higher mean SOS measurements than the osteoporotic subjects (group 3), with means of 3683 m/s (210), 3514 m/s (221), and 3312 m/s (264), respectively. A 1-way analysis of variance confirmed a statistically significant difference between mean SOS measurements from the 3 groups (p < 0.0001). Axial transmission QUS of the mandible can differentiate between subjects with osteoporosis and a healthy control group, and shows potential for use as a screening tool for osteoporosis.

Osteosarcopenia: where bone, muscle, and fat collide.

As the world's population ages, the prevalence of chronic diseases increases. Sarcopenia and osteoporosis are two conditions that are associated with aging, with similar risk factors that include genetics, endocrine function, and mechanical factors. Additionally, bone and muscle closely interact with each other not only anatomically, but also chemically and metabolically. Fat infiltration, a phenomenon observed in age-related bone and muscle loss, is highly prevalent and more severe in sarcopenic and osteoporotic subjects. Clinically, when individuals suffer a combination of both disorders, negative outcomes such as falls, fractures, loss of function, frailty, and mortality increase, thus generating significant personal and socio-economic costs. Therefore, it is suggested that when bone mineral density loss is synchronic with decreased muscle mass, strength, and function, it should be interpreted as a single diagnosis of osteosarcopenia, which may be preventable and treatable. Simple interventions such as resistance training, adequate protein and calcium dietary intake, associated with maintenance of appropriate levels of vitamin D, have a dual positive effect on bone and muscle, reducing falls, fractures, and, consequently, disability. It is essential that fracture prevention approaches-including postfracture management-involve assessment and treatment of both osteoporosis and sarcopenia. This is of particular importance as in older persons the combination of osteopenia/osteoporosis and sarcopenia has been proposed as a subset of frailer individuals at higher risk of institutionalization, falls, and fractures. This review summarizes osteosarcopenia epidemiology, pathophysiology, diagnosis, outcomes, and managementstrategies.

Profile of chronic kidney disease related-mineral bone disorders in newly diagnosed advanced predialysis diabetic kidney disease patients: A hospital based cross-sectional study

AimChronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD population. There are limited data on the pattern of these disturbances in diabetic CKD patients. Therefore, a study was conducted to find out the profile of mineral bone disorders in T2DM patients with pre-dialysis CKD. MethodsIn this cross-sectional design, diabetic patients with newly-diagnosed stage 4 and 5 CKD were evaluated. Serum levels of calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D and total alkaline phosphatase (ALP) were measured in all patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). ResultsA total of 72 eligible patients participated (44 males, 28 females; age 54.2±11.7). Patients with CKD Stage 5 had a lower level of corrected serum calcium and significantly higher level of inorganic phosphorus, total ALP and iPTH as compared to stage 4 patients. Overall, 38.5% were hypocalcemic, 31.43% were hyperphosphatemic. 24.2% of CKD subjects were vitamin D deficient (<10ng/ml) and 41.4% having vitamin D insufficiency (10–20ng/ml). In stage 4, hyperparathyroidism (iPTH>110pg/ml) was detected in nearly 43% of patients. In stage 5, only 32% patients was found to have hyperparathyroidism (iPTH>300pg/ml).There was a good correlation between iPTH and total ALP (r=0.5, p=0.0001) in this cohort. 25 (OH) vitamin D was inversely correlated with ALP (r=−0.39, P=0.001) and showed negative correlation with urine ACR (r=−0.37, P=0.002). As a group, the osteoporotic CKD subjects exhibited higher iPTH (220.1±153.8 vs. 119±108pg/ml, p<0.05) as compared to those who were osteopenic or had normal bone density. There was significant correlation between BMD and iPTH (adjusted r=−0.436; P=0.001). In the multivariate regression model, we found intact PTH to predict BMD even after adjustment of all the confounders. ConclusionThe current study showed that adynamic bone disease is prevalent even in pre-dialysis CKD population. High bone turnover disease may not be the most prevalent type in diabetic CKD. However, it could contribute to the development of osteoporosis in CKD subjects. Serum total ALP can serve as a biochemical marker to identify pattern of bone turnover where intact PTH is not available.

ASSOCIATIONS BETWEEN TRABECULAR BONE SCORE AND VERTEBRAL FRACTURES ACCORDING TO SPINE T-SCORES

Trabecular bone score (TBS) has been shown to be significantly related to vertebral fractures. The study aimed to evaluate the associations between TBS and vertebral fractures according to BMD T-scores. Areal BMD at the lumbar spine (L1-L4) was assessed in 957 women aged 45 years and older from Seoul National University Bundang Hospital from February 2015 to 2016 using dual x-ray absorptiometry (DXA) scan and TBS was further analyzed using iNsight software (Med-Imaps, Pessac, France). Vertebral fractures were identified on lateral X-ray films of the spine. Mean age was 66.4 ± 10.5 years and vertebral fractures were observed in 93 (9.7%) subjects. Twenty-four percent of fractures were occurred in normal BMD, 44.1% in osteopenia and 32.3% in osteoporotic ranges. According to the TBS levels, 7.5% fractures were happened in higher TBS levels (>1.350), 55.9% in middle TBS (1.201–1.350), and 37.8% in lower TBS levels (≤1.200). Adjusted odds of lumbar spine T score for fractures was 0.40 (95% CI 0.32–0.51, p<0.001). Odds of each increase of 1 SD in TBS was 0.75 (95% CI 0.57–0.98, P <0.05). Adjusted ORs for lumbar spine T-score were only significant in osteoporotic or osteopenic subjects, whereas adjusted ORs for 1SD increases in TBS was only significant in women with normal T-scores. In conclusion, both lumbar spine T-score and TBS were significantly associated with vertebral fractures. However, lumbar spine T-score predicts fractures well in women with osteopenia or osteoporosis, but TBS levels are better predictable in subjects with normal BMD.

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene

A growing understanding of the bone remodeling process suggests that inflammation significantly contributes to the pathogenesis of osteoporosis. T cells and various cytokines contribute majorly to the estrogen deficiency-induced bone loss. Recent studies have identified the IL-12 cytokine family as consisting of pro-inflammatory IL-12 and IL-23 and the anti-inflammatory IL-27 and IL-35 cytokines. IL-27 exerts protective effects in autoimmune diseases like experimental autoimmune encephalomyelitis; however, its role in the pathogenesis of osteoporosis remains to be determined. In this report, we study the effect of IL-27 supplementation on ovariectomized estrogen-deficient mice on various immune and skeletal parameters. IL-27 treatment in ovariectomized mice suppressed Th17 cell differentiation by inhibiting transcription factor RORγt. Supplementation of IL-27 activates Egr-2 to induce IL-10 producing Tr1 cells. IL-27 treatment prevented the loss of trabecular micro-architecture and preserved cortical bone parameters. IL-27 also inhibited osteoblast apoptosis through increased Egr-2 expression, which induces anti-apoptotic factors like MCL-1. IL-27 suppressed osteoclastogenesis in an Egr-2-dependent manner that up-regulates Id2, the repressor of the receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis. Additionally, these results were corroborated in female osteoporotic subjects where we found decreased serum IL-27 levels along with reduced Egr-2 expression. Our study forms a strong basis for using humanized IL-27 toward the treatment of post-menopausal osteoporosis.

Imminent fracture risk.

The clinical significance of osteoporosis is in the occurrence of fractures and re-fractures. The main risk factor of sustaining a fracture is a previous one, but a recent fracture is a better fracture risk factor than fracture history. The role of the recency of fracture has been shown for both vertebral and non-vertebral fracture risk. This imminent risk is explained by both bone-related factors (underlying osteoporosis) and fall-related factors (including those related to postfracture care). Such a short-term increased risk has been shown also in patients initiating corticosteroids and in frail osteoporotic subjects with central nervous system (CNS) diseases or drugs targeting CNS, and thus a high risk of falls. Patients with an imminent (i.e. 2years) risk of fracture or refracture should be identified in priority in order to receive an immediate treatment and a program of fall prevention.

Prevalence of Concomitant Bone and Muscle Wasting in Elderly Women from the SarcoPhAge Cohort: Preliminary Results.

Recent studies suggest that bone and muscle wasting are closely interconnected. The aim was of this study is to assess the prevalence of osteoporosis in a population of women diagnosed with sarcopenia. Participants, setting and design: We analyzed cross-sectional data of women, aged 65 years and above, for whom bone mineral density was available at the time of inclusion in the SarcoPhAge (Sarcopenia and Physical impairment with advancing Age) cohort, an ongoing prospective study with the aim to assess consequences of sarcopenia. Muscle strength was evaluated with a hydraulic hand-dynamometer, appendicular lean mass and bone mineral density by Dual-Energy X-Ray Absorptiometry and physical performance by the Short Physical Performance Battery test (SPPB). Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People definition, i.e. a low muscle mass plus either low muscle strength or low physical performance. A bone mineral density T-score equal to or below -2.5SD at the lumbar spine, at the total hip or at the femoral neck was used to define osteoporosis (World Health Organization definition). A total of 126 women aged 74.38±6.32 years were included. Among them, 26 were assessed with sarcopenia (20.6%) and 34 (27.0%) with osteoporosis. There were more osteoporotic women among sarcopenic subjects (46.1%) than among non-sarcopenic subjects (22.0%) (p-value=0.011). A significant lower appendicular lean mass index was observed in osteoporotic women (p-value=0.025). We also observed, in osteoporotic subjects, a lower muscle strength (p-value=0.023). Numerical values of bone mineral density were lower in the sarcopenic population but the differences did not reach the level of statistical significance. Our study demonstrated that muscle mass and strength are lower in patients with osteoporosis. Prospective changes in bone and muscle mass will be investigated during the follow-up of our cohort.

Evaluation of Corelation between Salivary Calcium, Alkaline Phosphatase and Osteoporosis- A Prospective, Comparative and Observational Study

Fixed and/or removable prosthodontics caters to the restorative needs of the largest count of geriatric patients whose rehabilitative procedures depend on the quality and quantity of available bone. The common diagnostic parameters for quantifying bone may involve an invasive blood examination, an expensive bone densitometry procedure or a urine analysis. Sialometry involving the basic biochemistry of saliva analysis may be proposed as an alternative to the conventional investigative protocol and its usefulness may be attributed owing to its non invasive and simpler procedure. The aim of this study was to compare the salivary calcium and alkaline phosphatase among osteoporotic, osteopenic and normal edentulous subjects. A prospective, comparative and observational study was carried out on 80 selected edentulous subjects (40 males and 40 females) aged 55-75 years (30 osteoporotic, 30 osteopenic and 20 control). A sample of saliva was taken for the study. Salivary calcium was measured by Arsenazo reaction; and alkaline phosphatase by the International Federation of Clinical Chemistry (IFCC) method. Statistical analysis was done by unpaired t-test. A comparison was made in the levels of salivary calcium and alkaline phosphatase with that of osteoporosis and osteopenia. The mean salivary calcium and alkaline phosphatase levels were found to be significantly higher in the osteoporotic and osteopenic edentulous subjects as compared to the control group. Salivary calcium and alkaline phosphatase are increased significantly in case of osteoporosis and osteopenia. Hence, screening of salivary samples of patients may be an effective indicator for the detection of underlying disorders of bone metabolism.

Psoralen Inhibited Apoptosis of Osteoporotic Osteoblasts by Modulating IRE1-ASK1-JNK Pathway.

Osteoporosis is a common disease causing fracture in older populations. Abnormal apoptosis of osteoblasts contributes to the genesis of osteoporosis. Inhibiting apoptosis of osteoblasts provides a promising strategy to prevent osteoporosis. The proliferation of osteoblasts isolated from osteoporotic patients or healthy subjects was determined by MTT assay. Apoptosis was determined by Annexin V/PI assay. Protein expression was measured by western blot. The proliferation of osteoblasts isolated from osteoporotic patients was inhibited and the apoptosis level of these cells was higher than the osteoblasts from healthy subjects. Incubation with psoralen or estradiol significantly enhanced the proliferation and decreased the apoptosis level of osteoporotic osteoblasts. Western blot demonstrated that psoralen or estradiol treatment downregulated the expression of IRE1, p-ASK, p-JNK, and Bax. Meanwhile, expression of Bcl-2 was upregulated. Pretreatment by IRE1 agonist tunicamycin or JNK agonist anisomycin attenuated the effect of psoralen on osteoporotic osteoblasts. Psoralen inhibited apoptosis of osteoporotic osteoblasts by regulating IRE1-ASK1-JNK pathway.

Calcitonin receptor gene polymorphisms at codon 447 in patients with osteoporosis and chronic periodontitis in South Indian population - An observational study.

Context:Chronic periodontitis and osteoporosis are multifactorial diseases which share common risk factors. Interactions between genetic and other factors determine the likely hood of osteoporotic fractures and chronic periodontitis. Calcitonin receptor (CTR) gene polymorphism is one of the important factors which contribute to the development of osteoporosis and chronic periodontitis.Aims:This study highlights the association of CTR gene polymorphisms at codon 447 in patients with osteoporosis and chronic periodontitis and healthy controls in south Indian population.Settings and Design:The study was designed as a case–control retrospective, observational clinical trial which was conducted to assess the role of CTR gene polymorphism in patients with osteoporosis and periodontitis as well as in healthy controls.Materials and Methods:A total of 50 subjects were taken into the study comprising of 20 healthy and 30 osteoporotic subjects with chronic periodontitis between the age group of 30–55 years. Within the limitations of our study, only 50 subjects were taken in the study due to the strict sampling method (Patients who were just diagnosed with osteoporosis and periodontitis and hence not taking any medication). 2 ml of blood sample was collected in ethylenediamine tetra acetic acid containing vials, and polymerase chain reaction was run to identify CTR gene polymorphism.Statistical Analysis Used:Statistical analysis was done by student t-test. Pertaining to C > T allele pattern there was a significant difference between the test and control group.Results:A significant difference was observed between the test and control group in relation to the C > T allele pattern. Patients showing TT genotype distribution had greater periodontal destruction and lower bone-mineral density compared to CT genotype distribution followed by CC genotype distribution indicating TT homozygotes are more prone to the development of osteoporosis with increased risk of fracture and loss of alveolar bone. Males and females showed equal susceptibility to osteoporosis and chronic periodontitis.Conclusions:CTR polymorphism at codon 447 may be associated with osteoporosis and chronic periodontitis

Effect of combined treatment with focused mechano-acoustic vibration and pharmacological therapy on bone mineral density and muscle strength in post-menopausal women.

Osteoporosis is a systemic disease of the skeleton characterized by a reduction in bone mass and alterations in microarchitecture accompanied by increase in fracture risk, with a relevant decline in quality of life and important social, economic, and health implications, representing one of the most common causes of disability and a major financial item of health cost in many Countries. The best therapy for osteoporosis is prevention, consisting in measures to avoid or slow the onset of the disease. Treatment includes measures aimed at osteoporotic individuals, with or without previous fractures and a high risk of a first or additional fracture. We enrolled thirty post-menopausal osteoporotic women, allocated in the first group underwent a 6-month personalized drug therapy and focused mechanoacoustic vibration (2 sessions per week, each lasting 15 minutes); women allocated in the second group underwent only 6-month personalized drug therapy. Patients were evaluated performing dual-energy X-ray absorptiometry (DXA) and isokinetic machine evaluation, and administration of Tinetti scale and ECOS-16 questionnaire. Show improvement of bone mineral density (BMD) and T-score at the lumbar spine and femoral neck, handgrip strength and isokinetic strength of the knee estensors, balance and gait, and quality of life. Hence, the combined treatment with focused mechano-acoustic vibration and pharmacological therapy has a beneficial effect on BMD and T-score as well as on the muscle strength and quality of life of osteoporotic subjects.

Association of serum leptin with bone mineral density in postmenopausal osteoporotic females

Objective: Present study was designed to find out whether leptin is a predictor of bone mass density (BMD) in premenopausal women (PMW) and postmenopausal osteoporotic women (PMOPW) or it has no association with BMD.Methods: One hundred and ninety two women (98 PMOPW and 94 PMW) were recruited for this study. The control group was BMI matched with osteoporotic subjects. BMD assessment was done on calcaneus by peripheral ultrasound bone densitometry and T scores were determined. Serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA).Results: Serum leptin and BMD values were significantly different in both groups (leptin, 18.56 ± 8.65 ng/ml versus 21.64 ± 9.80 ng/ml, p = 0.02) and (BMD, −0.70 ± 0.19 versus −3.17 ± 0.59, p = 0.000), respectively. In PMOPW serum leptin and BMD were considerably correlated with weight (lep, r = 0.53, p = <0.001; BMD, r = −0.21, p = 0.02), BMI (lep, r = 0.52, p = <0.001; BMD, r = −0.27, p = 0.005), waist circumference (lep, r = 0.61, p = <0.001; BMD, r = 0.18, p = 0.04), hip circumference (lep, r = 0.58, p = <0.001).Multivariate linear stepwise regression analysis showed that weight and BMI in PMW and PMOPW were independent predictors of BMD. Serum leptin level was not found to be the predictor of BMD in both groups.Conclusion: The present results indicate that body weight and BMI have an impact on BMD while serum leptin is not associated with BMD in PMW and PMOPW.

Trabecular bone characterization using circular parametric models

Abstract Texture analysis of radiographic bone X-ray images presents a major challenge for pattern recognition and medical applications. Classifying such textures from osteoporotic and healthy subjects is a difficult task. In this paper, we propose a new approach combining wavelet decomposition and parametric circular models to capture the statistical behavior of phase coefficients. We demonstrate that, unlike the magnitude components, the wavelet phase coefficients convey local and structural information across scales and orientations which are of great interest for the study of trabecular bone texture. To assess how well the proposed circular models fit phase coefficients, the statistical test of Kuiper and graphical analysis Quantile–Quantile plots were used. The Support Vector Machine (SVM) and the Neural Network (NN) classifiers were used to evaluate the efficiency of the proposed models to classify two populations composed of osteoporotic patients and control subjects. Using Gabor filters and the Wrapped Cauchy model, an Area Under Curve (AUC) rate of 96.45% was achieved with the SVM classifier. To compare the performance of the proposed parametric approach to other non-parametric texture analysis techniques, the Receiver Operating Characteristic (ROC) analysis was performed. Results have proven that the proposed approach provides the best performance in terms of ROC curves.

Osteoclastogenic capacity of peripheral blood mononuclear cells is not different between women with and without osteoporosis

IntroductionPeripheral Blood Mononuclear Cells (PBMCs) have been extensively used as a culture model to generate osteoclasts in vitro. The aim of this study was to assess the osteoclastogenic potential of PBMCs derived from post-menopausal women with longstanding osteoporosis and compare this with PBMCs from healthy controls. Material and methodsWe selected from the population-based Rotterdam Study 82 participants of which 43 were diagnosed with osteoporosis (T-score below −2.5 at the lumbar spine) and the presence of at least 1 fracture and 29 healthy controls (T-score above 1; no fracture). PBMCs were differentiated into osteoclasts, and both differentiation capacity and activity were measured. Total RNA was obtained to assess gene expression of osteoclast markers. Deoxypyridinoline (DPD) was measured in plasma as a marker for bone resorption, in vivo. ResultsNeither the number of osteoclasts nor cathepsin K (CTSK) and dendritic cell-specific transmembrane protein (TM7SF4) gene expression was significantly different between both groups. There was also no significant difference in resorption pit area and plasma DPD levels. Stratification by fracture type into a group with vertebral, non-vertebral and both vertebral and non-vertebral fractures showed no difference in osteoclast formation or osteoclastic bone resorption. However, plasma DPD, but not the RNA expression markers, was significantly lower in the group of subjects with vertebral fracture group and those with vertebral and non-vertebral fractures compared to the healthy controls. No differences in osteoclastogenesis, osteoclastic resorption and plasma DPD levels were detected also after exclusion of past or present users of bisphosphonates and glucocorticoids. Stratification into high and low DPD levels showed higher osteoclastogenesis and more osteoclastic bone resorption in the high DPD group compared to the low DPD levels within the group of osteoporotic subjects. ConclusionThis study showed no difference in PBMC osteoclastogenic capacity and activity between women with and without osteoporosis and at least one previous fracture, who were on average 29.5years after menopause, suggesting that there is no difference in circulating osteoclast precursors. Although we cannot exclude that circulating precursors may behave differently at the bone site, it is possible that long after menopause a more stable phase of bone turnover is reached compared to earlier after the start of menopause in which differences in circulating osteoclast precursors and osteoclastogenic potential are more prominent.

Study of a new bone-targeting titanium implant-bone interface.

New strategies involving bone-targeting titanium (Ti) implant–bone interface are required to enhance bone regeneration and osseointegration for orthopedic and dental implants, especially in osteoporotic subjects. In this study, a new dual-controlled, local, bone-targeting delivery system was successfully constructed by loading tetracycline-grafted simvastatin (SV)-loaded polymeric micelles in titania nanotube (TNT) arrays, and a bone-targeting Ti implant–bone interface was also successfully constructed by implanting the delivery system in vivo. The biological effects were evaluated both in vitro and in vivo. The results showed that Ti surfaces with TNT–bone-targeting micelles could promote cytoskeletal spreading, early adhesion, alkaline phosphatase activity, and extracellular osteocalcin concentrations of rat osteoblasts, with concomitant enhanced protein expression of bone morphogenetic protein (BMP)-2. A single-wall bone-defect implant model was established in normal and ovariectomized rats as postmenopausal osteoporosis models. Microcomputed tomography imaging and BMP-2 expression in vivo demonstrated that the implant with a TNT-targeting micelle surface was able to promote bone regeneration and osseointegration in both animal models. Therefore, beneficial biological effects were demonstrated both in vitro and in vivo, which indicated that the bone-targeting effects of micelles greatly enhance the bioavailability of SV on the implant–bone interface, and the provision of SV-loaded targeting micelles alone exhibits the potential for extensive application in improving local bone regeneration and osseointegration, especially in osteoporotic subjects.

Fractional Brownian Motion and Rao Geodesic Distance for Bone X-Ray Image Characterization.

Osteoporosis diagnosis has attracted particular attention in recent decades. Textured images from the microarchitecture of osteoporotic and healthy subjects show a high degree of similarity, increasing the difficulty of classifying such textures. Thus, the evaluation of osteoporosis from the bone X-ray images presents a major challenge for pattern recognition and medical applications. The purpose of this paper is to use the fractional Brownian motion (fBm) model and the probability density function of its increments to compute a similarity measure with the Rao geodesic distance to classify trabecular bone X-ray images. When evaluated on synthetic fBm images (test vectors) with the well-known Hurst parameter H, the proposed method met our expectations in which a good classification of the synthetic images was achieved. A clinical study was conducted on textured bone X-ray images from two different female populations of osteoporotic patients (fracture cases) and control subjects. Using the proposed method, an area under curve rate of 97% was achieved.

Computers in providing nutrition education to osteoporotic patients: An Ardent need

With a frightening increase in the prevalence of non-communicable diseases and their high therapeutic cost it becomes indispensable that the vast pool of existing knowledge be made available to the ultimate beneficiaries with the help of most widely accepted modern technological tool i.e. via computers as they have played an excellent role in growth and development knowledge assessment tool comprised of questions on different aspects (general facts, prevalence, etiology, clinical manifestation, role of diet and exercise in the management of the disease) was framed after reviewing the literature extensively. The maximum attainable scores were then distributed into three categories (good, average and fair). The knowledge assessment tools so developed were tested for its reliability by selecting 10 disease subjects purposively and the tool was found highly reliable (r=0.94). With the use of this system there was a significant increase in the knowledge of the users in males as well as in females of the disease group with a total per cent improvement of 82.98 in osteoporotic subjects. The mean pre test scores was 9.7±3.29 and the mean post test scores were 17.75±2.57. All the patients were falling in the fair range of knowledge and they were all shifted to the category of good after the exposure of the developed system. Hence, it can be concluded that software has definitely played a crucial role in improving the knowledge level of the users.

Systemic Administration of Allogeneic Mesenchymal Stem Cells Does Not Halt Osteoporotic Bone Loss in Ovariectomized Rats

Mesenchymal stem cells (MSCs) have innate ability to self-renew and immunosuppressive functions, and differentiate into various cell types. They have become a promising cell source for treating many diseases, particular for bone regeneration. Osteoporosis is a common metabolic bone disorder with elevated systemic inflammation which in turn triggers enhanced bone loss. We hypothesize that systemic infusion of MSCs may suppress the elevated inflammation in the osteoporotic subjects and slow down bone loss. The current project was to address the following two questions: (1) Will a single dose systemic administration of allogenic MSCs have any effect on osteoporotic bone loss? (2) Will multiple administration of allogenic MSCs from single or multiple donors have similar effect on osteoporotic bone loss? 18 ovariectomized (OVX) rats were assigned into 3 groups: the PBS control group, MSCs group 1 (receiving 2x106 GFP-MSCs at Day 10, 46, 91 from the same donor following OVX) and MSCs group 2 (receiving 2x106 GFP-MSCs from three different donors at Day 10, 46, 91). Examinations included Micro-CT, serum analysis, mechanical testing, immunofluorescence staining and bone histomorphometry analysis. Results showed that BV/TV at Day 90, 135, BMD of TV and trabecular number at Day 135 in the PBS group were significantly higher than those in the MSCs group 2, whereas trabecular spacing at Day 90, 135 was significantly smaller than that in MSCs group 2. Mechanical testing data didn’t show significant difference among the three groups. In addition, the ELISA assay showed that level of Rantes in serum in MSCs group 2 was significantly higher than that of the PBS group, whereas IL-6 and IL-10 were significantly lower than those of the PBS group. Bone histomorphometry analysis showed that Oc.S/BS and Oc.N/BS in the PBS group were significant lower than those in MSCs group 2; Ob.S/BS and Ob.N/BS did not show significant difference among the three groups. The current study demonstrated that systemic administration of allogenic MSCs had no obvious effect on osteoporotic bone loss in OVX rats when using the cells from the same donor; and repeated injection of allogeneic MSCs from different donors might promote bone loss in OVX rats. These findings indicate that despite allogenic MSCs systemic infusion is safe, their administration alone may not be an effective mean for preventing osteoporotic bone loss.

IL-18BP is decreased in osteoporotic women: Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation.

IL-18BP is a natural antagonist of pro-inflammatory IL-18 cytokine linked to autoimmune disorders like rheumatoid arthritis. However, its role in post menopausal osteoporosis is still unknown. In this study, we investigated the role of IL-18BP on murine osteoblasts, its effect on osteoblasts-CD4+ T cells and osteoblasts-CD11b+ macrophage co-culture. mIL-18BPd enhances osteoblast differentiation and inhibits the activation of NLRP3 inflammasome and caspase-1 which process IL-18 to its active form. Using estrogen deficient mice, we also determined the effect of mIL-18BP on various immune and skeletal parameters. Ovariectomized mice treated with mIL-18BPd exhibited decrease in Th17/Treg ratio and pro-inflammatory cytokines. mIL-18BPd treatment restored trabecular microarchitecture, preserved cortical bone parameters likely attributed to an increased number of bone lining cells and reduced osteoclastogenesis. Importantly, these results were corroborated in female osteoporotic subjects where decreased serum IL-18BP levels and enhanced serum IL-18 levels were observed. Our study forms a strong basis for using humanized IL-18BP towards the treatment of postmenopausal osteoporosis.