Therapeutic advantage of teriparatide in very elderly patients with proximal femoral fractures: a functional and BMD analysis.

BACKGROUND: Teriparatide, a recombinant parathyroid hormone, is pivotal in osteoporosis treatment, particularly in post-surgical recovery for hip fractures. This study investigates its efficacy in functional recovery post-hip fracture surgery in elderly patients, a demographic particularly susceptible to osteoporotic fractures. METHODS: In this retrospective cohort study, 150 elderly patients with proximal femoral fractures undergoing open reduction and internal fixation were enrolled. They were categorized into two groups: receiving 20 µg of daily teriparatide injections for 18 months and receiving standard antiresorptive medications during a 24-month follow-up. Detailed records of patient demographics, Fracture Risk Assessment Tool scores, and comorbidities were kept. Key outcomes, including bone mineral density (BMD) and functional scores (Barthel Index and Visual Analog Scale for hip pain), were evaluated at 3 and 24 months post-surgery. RESULTS: Out of the original cohort, 126 patients (20 men and 106 women with an average age of 85.5 ± 9.3 years) completed the study. The teriparatide group exhibited significant enhancements in both functional scores and BMD when compared to the control group. Notably, functional improvements were less pronounced in male patients compared to female patients. Additionally, the incidence of new fractures was markedly lower in the teriparatide group. CONCLUSION: Administering teriparatide daily for 18 months post-surgery for proximal femoral fractures significantly benefits very elderly patients by improving functionality and bone density, with observed differences in recovery between genders. These results reinforce the efficacy of teriparatide as a potent option for treating osteoporosis-related fractures in the elderly and highlight the importance of considering gender-specific treatment and rehabilitation strategies.

Microdroplets Encapsulated with NFATc1-siRNA and Exosomes-Derived from MSCs Onto 3D Porous PLA Scaffold for Regulating Osteoclastogenesis and Promoting Osteogenesis.

Introduction: Osteoporotic-related fractures remains a significant public health concern, thus imposing substantial burdens on our society. Excessive activation of osteoclastic activity is one of the main contributing factors for osteoporosis-related fractures. While polylactic acid (PLA) is frequently employed as a biodegradable scaffold in tissue engineering, it lacks sufficient biological activity. Microdroplets (MDs) have been explored as an ultrasound-responsive drug delivery method, and mesenchymal stem cell (MSC)-derived exosomes have shown therapeutic effects in diverse preclinical investigations. Thus, this study aimed to develop a novel bioactive hybrid PLA scaffold by integrating MDs-NFATc1-silencing siRNA to target osteoclast formation and MSCs-exosomes (MSC-Exo) to influence osteogenic differentiation (MDs-NFATc1/PLA-Exo). Methods: Human bone marrow-derived mesenchymal stromal cells (hBMSCs) were used for exosome isolation. Transmission electron microscopy (TEM) and confocal laser scanning microscopy were used for exosome and MDs morphological characterization, respectively. The MDs-NFATc1/PLA-Exo scaffold was fabricated through poly(dopamine) and fibrin gel coating. Biocompatibility was assessed using RAW 264.7 macrophages and hBMSCs. Osteoclast formations were examined via TRAP staining. Osteogenic differentiation of hBMSCs and cytokine expression modulation were also investigated. Results: MSC-Exo exhibited a cup-shaped structure and effective internalization into cells, while MDs displayed a spherical morphology with a well-defined core-shell structure. Following ultrasound stimulation, the internalization study demonstrated efficient delivery of bioactive MDs into recipient cells. Biocompatibility studies indicated no cytotoxicity of MDs-NFATc1/PLA-Exo scaffolds in RAW 264.7 macrophages and hBMSCs. Both MDs-NFATc1/PLA and MDs-NFATc1/PLA-Exo treatments significantly reduced osteoclast differentiation and formation. In addition, our results further indicated MDs-NFATc1/PLA-Exo scaffold significantly enhanced osteogenic differentiation of hBMSCs and modulated cytokine expression. Discussion: These findings suggest that the bioactive MDs-NFATc1/PLA-Exo scaffold holds promise as an innovative structure for bone tissue regeneration. By specifically targeting osteoclast formation and promoting osteogenic differentiation, this hybrid scaffold may address key challenges in osteoporosis-related fractures.

The role of echinacoside-based cross-linker nanoparticles in the treatment of osteoporosis.

Background: Current drugs for treating osteoporosis may lead to toxic side effects. Echinacoside (ECH) is a natural small molecule drug. This study examined and compared the therapeutic effects of cross-linker (CL)-ECH and ECH-free nanoparticles on osteoporosis. Methods: Echinocandin-based CL-ECH nanoparticles were prepared, and the nanoparticle size and drug loading were optimized and characterized by adjusting the ratio. The antioxidant effect of CL-ECH nanoparticles on bone marrow-derived macrophages (BMDMs) was analyzed using flow cytometry, immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR). Bone marrow stromal cells (BMSCs)-based detection of bone-producing effects was conducted using alkaline phosphatase (ALP), Alizarin Red S (ARS) and qRT-PCR. TRAP, phalloidin staining, and qRT-PCR was performed to detect osteogenesis-inhibiting effect on BMDMs. CL-ECH nanoparticles were applied to treat an ovariectomized (OVX) mouse model at low doses. Results: Compared to ECH, CL-ECH nanoparticles suppressed oxidative stress in BMDMs by promoting NRF-2 nuclear translocation, which inhibited the production of both reactive oxygen species (ROS) and osteoclast production through downregulating NF-κB expression, with limited effect on the osteogenesis of BMSCs. In vivo studies showed that low-dose CL-ECH nanoparticles markedly improved bone trabecular loss compared to ECH administration in the treatment of osteoporosis. Conclusions: The current discoveries provided a solid theoretical foundation for the development of a new generation of anti-bone resorption drugs and antiosteoporosis drugs.

Influence of Various Strontium Formulations (Ranelate, Citrate, and Chloride) on Bone Mineral Density, Morphology, and Microarchitecture: A Comparative Study in an Ovariectomized Female Mouse Model of Osteoporosis.

Osteoporosis stands out as a prevalent skeletal ailment, prompting exploration into potential treatments, including dietary strontium ion supplements. This study assessed the efficacy of supplementation of three strontium forms-strontium citrate (SrC), strontium ranelate (SrR), and strontium chloride (SrCl)-for enhancing bone structure in 50 female SWISS mice, aged seven weeks. In total, 40 mice underwent ovariectomy, while 10 underwent sham ovariectomy. Ovariectomized (OVX) mice were randomly assigned to the following groups: OVX (no supplementation), OVX + SrR, OVX + SrC, and OVX + SrCl, at concentrations equivalent to the molar amount of strontium. After 16 weeks, micro-CT examined trabeculae and cortical bones, and whole-bone strontium content was determined. Results confirm strontium administration increased bone tissue mineral density (TMD) and Sr content, with SrC exhibiting the weakest effect. Femur morphometry showed limited Sr impact, especially in the OVX + SrC group. This research highlights strontium's potential in bone health, emphasizing variations in efficacy among its forms.

The association between body mass index and osteoporosis in a Taiwanese population: a cross-sectional and longitudinal study.

This study investigates the correlation between body mass index (BMI) and osteoporosis utilizing data from the Taiwan Biobank. Initially, a comprehensive analysis of 119,009 participants enrolled from 2008 to 2019 was conducted to assess the association between BMI and osteoporosis prevalence. Subsequently, a longitudinal cohort of 24,507 participants, initially free from osteoporosis, underwent regular follow-ups every 2-4 years to analyze the risk of osteoporosis development, which was a subset of the main cohort. Participants were categorized into four BMI groups: underweight (BMI < 18.5 kg/m2), normal weight (18.5 kg/m2 ≤ BMI < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 27 kg/m2), and obese groups (BMI ≥ 27 kg/m2). A T-score ≤ - 2.5 standard deviations below that of a young adult was defined as osteoporosis. Overall, 556 (14.1%), 5332 (9.1%), 2600 (8.1%) and 1620 (6.7%) of the participants in the underweight, normal weight, overweight and obese groups, respectively, had osteoporosis. A higher prevalence of osteoporosis was noted in the underweight group compared with the normal weight group (odds ratio [OR], 2.20; 95% confidence interval [95% CI], 1.99 to 2.43; p value < 0.001) in multivariable binary logistic regression analysis. Furthermore, in the longitudinal cohort during a mean follow-up of 47 months, incident osteoporosis was found in 61 (9%), 881 (7.2%), 401 (5.8%) and 213 (4.6%) participants in the underweight, normal weight, overweight and obese groups, respectively. Multivariable Cox proportional hazards analysis revealed that the risk of incident osteoporosis was higher in the underweight group than in the normal weight group (hazard ratio [HR], 1.63; 95% CI 1.26 to 2.12; p value < 0.001). Our results suggest that BMI is associated with both the prevalence and the incidence of osteoporosis. In addition, underweight is an independent risk factor for developing osteoporosis. These findings highlight the importance of maintaining normal weight for optimal bone health.

A Study on Intelligent Optical Bone Densitometry.

Osteoporosis is a prevalent chronic disease worldwide, particularly affecting the aging population. The gold standard diagnostic tool for osteoporosis is Dual-energy X-ray Absorptiometry (DXA). However, the expensive cost of the DXA machine and the need for skilled professionals to operate it restrict its accessibility to the general public. This paper builds upon previous research and proposes a novel approach for rapidly screening bone density. The method involves utilizing near-infrared light to capture local body information within the human body. Deep learning techniques are employed to analyze the obtained data and extract meaningful insights related to bone density. Our initial prediction, utilizing multi-linear regression, demonstrated a strong correlation (r = 0.98, p-value = 0.003**) with the measured Bone Mineral Density (BMD) obtained from Dual-energy X-ray Absorptiometry (DXA). This indicates a highly significant relationship between the predicted values and the actual BMD measurements. A deep learning-based algorithm is applied to analyze the underlying information further to predict bone density at the wrist, hip, and spine. The prediction of bone densities in the hip and spine holds significant importance due to their status as gold-standard sites for assessing an individual's bone density. Our prediction rate had an error margin below 10% for the wrist and below 20% for the hip and spine bone density.

A novel model of locking plate and locking spongious screw: a biomechanical in vitro comparison study with classical locking plate.

BACKGROUND: Locking plates are commonly used for the fixation of comminuted, periprosthetic and osteoporotic bone fractures. These plates are secured to the bone with screws, creating a stable connection with fixed angle between the plate and the screws. In this biomechanical in vitro study, our aim is to evaluate and compare the novel locking plate-locking spongious screw model with FDA approved classical locking plate. METHODS: Sawbone PCF-15 osteoporotic bone model was utilized to simulate osteoporotic bone conditions. Two screws were used to attach both the classical locking plate and the novel locking plate-locking spongious screw model to these bone models. The attachment strength of the screws to the bone blocks was measured by pull-out tests. RESULTS: Novel locking plate-locking spongious screw model exhibited an 84.38% stronger attachment to the osteoporotic bone model compared to the current locking plate model. CONCLUSIONS: In conclusion, one of the important problems in the locking plates which is the high Pull-out risk of the locking spongious screws can been resolved with our proposed new model and has a chance of having a better purchase especially in osteoporotic bones.

Causal relationship between circulating inflammatory factors and osteoporosis: a bidirectional Mendelian randomization study.

OBJECTIVE: Osteoporosis (OP), a persistent metabolic bone disorder linked with inflammation, has an undetermined cause. In our research, we employed bidirectional Mendelian randomization (MR) to investigate the interplay between OP and inflammation agents. MATERIALS AND METHODS: We performed two-way pooled-level MR analyses to characterize the causal relationship between 41 circulating inflammatory modulators and OP. Genetic variation data for the 41 regulatory factors associated with inflammation were obtained from genome-wide association studies (GWASs) of human cytokines. Bone mineral density (BMD) was utilized as a phenotype for OP in our approach. The BMD dataset, sourced from the GEFOS consortium, a large GWAS meta-analysis study and UK Biobank, was classified based on varied sections [whole body (TB), lumbar spine (LS), femoral neck (FN), forearm (FA), and heel] and age brackets (0-15 years, 15-30 years, 30-45 years, 45-60 years, and above 60 years). Primary MR analyses were executed using the inverse variance weighting (IVW) method, and sensitivity analyses were performed using the MR-Egger, weighted median, simple model, and weighted model. Cochran's Q test was utilized to evaluate the existence of heterogeneity. We used MR-Egger regression and MR multiplicity of residuals and outliers (MR-PRESSO) to assess pleiotropy. RESULTS: After false discovery rate (FDR) correction, elevated levels of circulating interleukin-8 (IL-8) [ß = 0.072 (0.031-0.114), p < 0.01], macrophage inflammatory protein-1b (MIP-1ß) [ß = 0.008 (0.003-0.013), p < 0.01; ß = 0.026 (0.009-0.042), p < 0.01], and cutaneous T-cell attracting chemokine (CTACK) [ß = 0.037 (0.017-0.056), p < 0.01] was associated with a reduced risk of OP. Reduced levels of hepatocyte growth factor (HGF), IL-1ra, IL-10, macrophage colony-stimulating factor (MCSF), and MIP-1α were associated with a reduced risk of OP [ß = -0.030 (-0.047 - -0.013), p < 0.01; ß = -0.025 (-0.041 - -0.010), p < 0.01; ß = -0.018 (-0.029 - -0.007), p < 0.01; ß = -0.060 (-0.097 - -0.024), p < 0.01; ß = -0.118 (-0.190 - -0.047), p < 0.01]. We observed a significant causal correlation between FN-BMD and MCP-3 (FDR < 0.05). The occurrence of OP may also lead to elevated levels of MCP3 [ß = -0.466 (-0.714 - -0.217), p < 0.01]. The reliability of the results was confirmed by sensitivity analyses. CONCLUSIONS: This study demonstrated the pathogenic role of circulating inflammatory modulators in OP using bidirectional MR analysis. This further deepens the understanding of OP pathogenesis and provides new ideas for therapeutic intervention in OP.

Influence of anti-sclerostin monoclonal antibody in the repair of post-extraction sockets of ovariectomized rats.

OBJECTIVE: This study assessed the impact of an anti-sclerostin monoclonal antibody (Scl-Ab)-based osteoporosis drug on the post-extraction alveolar repair of ovariectomized rats. DESIGN: Fifteen female rats were randomly distributed into three groups: CTR (healthy animals), OST (osteoporosis induced by ovariectomy), and OST+Scl-Ab (osteoporosis induction followed by Scl-Ab treatment). Ovariectomy or sham surgery was performed 30 days before baseline, and Scl-Ab or a vehicle was administered accordingly in the groups. After seven days, all rats underwent the first lower molar extraction and were euthanized 15 days later. Computed microtomography, histological analysis, and collagen content measurement were performed on post-extraction sockets and intact mandibular and maxillary bone areas. RESULTS: Microtomographic analyses of the sockets and mandibles did not reveal significant differences between groups on bone morphometric parameters (p > 0.05), while maxillary bone analyses resulted in better maintenance of bone architecture in OST+Scl-Ab, compared to OST (p < 0.05). Descriptive histological analysis and polarization microscopy indicated better post-extraction socket repair characteristics and collagen content in OST+Scl-Ab compared to OST (p < 0.05). CONCLUSIONS: Scl-Ab-based medication did not accelerate alveolar bone formation but exhibited better post-extraction repair characteristics, and collagen content compared to ovariectomized animals only.

Moderate salt restriction in primary aldosteronism improves bone metabolism through attenuation of urinary calcium and phosphate losses.

Accumulating evidence links osteoporosis and dietary salt consumption. Primary aldosteronism (PA) is a model disease with increased dietary salt intake and constitutes an independent risk factor for osteoporosis. We, thus, assessed whether a short-term moderate reduction in salt intake in PA results in detectable osteoanabolic effects. Forty-one patients with PA on stable mineralocorticoid receptor antagonist therapy were subjected to a 12-week salt restriction. Serum and urinary electrolytes, markers of bone turnover, and a 15 steroids plasma profile were registered. After 12 weeks, urinary calcium and phosphate decreased, while plasma testosterone, serum phosphate, and bone alkaline phosphatase (BAP) all increased significantly. Longitudinal changes in BAP were independently correlated with changes in serum phosphate, parathyroid hormone, and urinary calcium in multivariate analysis. Salt restriction in PA limits urinary calcium and phosphate losses and may confer favorable osteoanabolic effects. Our findings suggest that salt restriction should be considered in patients with PA to improve bone health.

Osteoporotic quality of life, self-efficacy, and fracture protection behaviors in postmenopausal women.

It is important for postmenopausal women to acquire bone health protective behaviors to protect them from fractures. For this reason, it is necessary to evaluate bone health during menopause and to inform women. PURPOSE: This study was conducted to examine osteoporotic fracture protection behaviors, quality of life, and self-efficacy in postmenopausal women. METHODS: In the study, the data were evaluated with the socio-demographic data form, Osteoporotic Fracture Protection Scale, Osteoporosis Self-Efficacy-Efficacy Scale, European Osteoporosis Foundation Quality of Life Questionnaire-41, which includes introductory information on socio-demographic characteristics. RESULTS: It was determined that the postmenopausal women included in our study were between the ages of 45-92; more than half of them had chronic diseases; their average BMI was 29; and their DEXA score was - 3.00 ± 0.41. Among the people included in our study, those with a history of fractures had lower self-efficacy scores. It was determined that the fracture prevention scale scores of the participants were above the average, and the average of the osteoporosis-related quality of life score was high. In addition, it was determined that there was a strong positive correlation between self-efficacy and fracture prevention scale. CONCLUSION: It is important to determine behaviors to prevent osteoporotic fractures in postmenopausal women, to raise the necessary awareness and to inform patients about the precautions to be taken. It is thought that it will increase patients' quality of life by increasing their disease-related self-efficacy. Therefore, there is a need for research on providing education to op patients and examining the results.

Development and experimental validation of an energy metabolism-related gene signature for diagnosing of osteoporosis.

Osteoporosis is usually caused by excessive bone resorption and energy metabolism plays a critical role in the development of osteoporosis. However, little is known about the role of energy metabolism-related genes in osteoporosis. This study aimed to explore the important energy metabolism-related genes involved in the development of osteoporosis and develop a diagnosis signature for osteoporosis. The GSE56814, GSE62402, and GSE7158 datasets were downloaded from the NCBI Gene Expression Omnibus. The intersection of differentially expressed genes between high and low levels of body mineral density (BMD) and genes related to energy metabolism were screened as differentially expressed energy metabolism genes (DE-EMGs). Subsequently, a DE-EMG-based diagnostic model was constructed and differential expression of genes in the model was validated by RT-qPCR. Furthermore, a receiver operating characteristic curve and nomogram model were constructed to evaluate the predictive ability of the diagnostic model. Finally, the immune cell types in the merged samples and networks associated with the selected optimal DE-EMGs were constructed. A total of 72 overlapped genes were selected as DE-EMGs, and a five DE-EMG based diagnostic model consisting B4GALT4, ADH4, ACAD11, B4GALT2, and PPP1R3C was established. The areas under the curve of the five genes in the merged training dataset and B4GALT2 in the validation dataset were 0.784 and 0.790, respectively. Moreover, good prognostic prediction ability was observed using the nomogram model (C index = 0.9201; P = 5.507e-14). Significant differences were observed in five immune cell types between the high- and low-BMD groups. These included central memory, effector memory, and activated CD8 T cells, as well as regulatory T cells and activated B cells. A network related to DE-EMGs was constructed, including hsa-miR-23b-3p, DANCR, 17 small-molecule drugs, and two Kyoto Encyclopedia of Genes and Genomes pathways, including metabolic pathways and pyruvate metabolism. Our findings highlighted the important roles of DE-EMGs in the development of osteoporosis. Furthermore, the DANCR/hsa-miR-23b-3p/B4GALT4 axis might provide novel molecular insights into the process of osteoporosis development.

Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high). OBJECTIVES: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively. SEARCH METHODS: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023. SELECTION CRITERIA: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study. MAIN RESULTS: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies. AUTHORS' CONCLUSIONS: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

Bone evaluation study-2: update on the epidemiology of osteoporosis in Germany.

Osteoporosis is the most common bone disorder. Our data gives an estimate of around 5.87 million cases of osteoporosis in the general German population in 2018. Only 30% of insured individuals who suffered an osteoporotic fracture and/or had a confirmed diagnosis of osteoporosis, received an appropriate prescription. PURPOSE: Osteoporosis is the most common bone disorder. It particularly affects elderly people and increases the risk of atraumatic fractures. The aim of this study was to estimate the prevalence of osteoporosis in the general German population aged ≥ 50 years and to collect data on the frequency of prescription of osteoporosis-specific medication in order to assess the treatment gap. METHODS: Retrospective analysis of anonymized data of individuals aged ≥ 50 years insured under statutory healthcare schemes from the database of the Institute for Applied Health Research Berlin (InGef) for 2018 (study population). Insured individuals with osteoporosis were identified based on osteoporosis diagnoses, osteoporosis-specific prescriptions, or osteoporotic fractures. Thus, we estimated the prevalence of osteoporosis in the general German population aged ≥ 50 years. The prevalence of diagnoses, fractures, and prescriptions was determined for the study population and stratified by age and gender. RESULTS: Within the study population of 1,599,299 insured individuals, a prevalence of osteoporosis of 15.9% was determined. This estimated approximately 5.87 million cases of osteoporosis for the general German population. 81.6% of the cases were women. Osteoporosis-specific prescriptions were received by 30.0% of the insured individuals in the study population who had been diagnosed with osteoporosis and/or suffered an osteoporotic fracture. CONCLUSIONS: Germany has a high prevalence of osteoporosis. Only a small portion of individuals who may require osteoporosis-specific treatment actually receive it.

Impact of osteoporosis and Cement-Augmented fusion on adjacent spinal levels Post-Fusion Surgery: Patient-Specific finite element analysis.

Cement-augmentation is a technique commonly used during posterior lumbar instrumented fusion (PLIF) to reinforce compromised osteoporotic vertebral bone, minimize the risk of loosening screws, enhance stability, and improve overall surgical outcomes. In this study, we introduce a novel segmented vertebral body regional modeling approach to investigate the effects of osteoporosis and cement-augmented lumbar fusion on disc biomechanics at spinal levels adjacent to the fused vertebrae. Using our previously validated personalized-poroelastic-osteoligamentous FE model of the spine, fusion was simulated at L4-L5, and the biomechanics of adjacent levels were studied for 30 patients (non-osteoporotic patients (N = 15), osteoporotic patients (N = 15)). PLIF models, with and without cement-augmentation, were developed and compared after an 8 h-rest period (200 N), following a 16 h-cyclic compressive loading of 500-1000 N (40 and 20 min, respectively). Movement in different directions (flexion/ extension/ lateral bending/ axial rotation) was simulated using 10Nm moment before and after cyclic loading. The material mapping algorithm was validated by comparing the results of voxel-based and parametric models. The FE cement-augmented models, subject to daily activity loading, demonstrated significant differences in disc height loss and fluid loss as compared to non-cemented models. The calculated axial stress and fiber strain values were also significantly higher for these models. This work demonstrates that although osteoporosis does not significantly alter the time-dependent characteristics of adjacent IVDs post-surgery, cement-augmentation increases the risk of adjacent segment disease (ASD) incidence. A holistic understanding of the trade-offs and long-term complex interplay between structural reinforcement modalities, including cement augmentation, and altered biomechanics warrants further investigation.

The association of FRAX with predictors of falls in the assessment of postmenopausal osteoporosis in Turkey: the fracture study of Turkey (FRACT study).

Although FRAX is used for fracture risk evaluation, this tool does not include balance and fall risk. The association between the predictors of falls and high FRAX scores we found in this study suggests that risk indicators for falls may add substantial value to FRAX by improving fracture risk prediction. PURPOSE: This observational, descriptive, and cross-sectional study aimed to assess the fall risk predictors and explore their association with FRAX in Turkish patients with postmenopausal osteoporosis. METHODS: Two hundred and nine (209) women with postmenopausal osteoporosis referred to the Fracture Liaison Service (FLS) at Istanbul University-Cerrahpasa were enrolled in the FRACT study (The Fracture Study of Turkey). Clinical risk factors were assessed using the FRAX tool. Tandem stance, Tandem walking, Timed up and go (TUG), and Chair stand tests were performed to assess balance and fall risk. RESULTS: Among patients with a mean age of 67.6 (± 9.7) years, 66 patients (31.6%) had osteoporosis without fractures and 143 patients (68.4%) had fragility fractures. The proportion of patients with poor performance of fall prediction tests was significantly higher in patients with a fragility fracture than those with osteoporosis alone. There was an inverse relationship between dynamic balance tests and the reported number of prior falls in the past year. FRAX score was higher in patients with impaired Tandem stance, Tandem walking, and TUG tests (p = 0.008, p = 0.035, p = 0.001, respectively). CONCLUSION: Assessment of fall risk predictors should be one of the major pillars in the physical evaluation of osteoporotic patients in the FLS setting. FRAX is a useful tool to determine the fracture risk of patients with both static and dynamic balance impairments. Combining balance assessment with FRAX may be an important step to optimize osteoporosis risk assessment.

Manejo de la osteoporosis en el paciente con enfermedad renal crónica (Estudio ERCOS): un desafío en la asistencia nefrológica / Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care

La valoración del riesgo de fractura del paciente con enfermedad renal crónica (ERC) ha sido incluida en el complejo Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) en guías nefrológicas internacionales y nacionales, sugiriéndose por primera vez la evaluación de la densidad mineral ósea (DMO) si los resultados pueden condicionar la toma de decisiones terapéuticas. Sin embargo, existe muy poca información en práctica clínica real en esta población. El objetivo principal del estudio ERC-Osteoporosis (ERCOS) es describir el perfil de los pacientes con ERC G3-5D con osteoporosis (OP) y/o fracturas por fragilidad atendidos en consultas especializadas de nefrología, reumatología y medicina interna en España. Participaron 15 centros y se incluyeron 162 pacientes (siendo en su mayoría mujeres [71,2%] posmenopáusicas [98,3%]) con una mediana de edad de 77 años. La mediana del filtrado glomerular estimado (FGe) fue de 36ml/min/1,73m2 y el 38% de pacientes incluidos estaban en diálisis. Destacamos la elevada frecuencia de fracturas por fragilidad prevalentes ([37,7%), principalmente vertebrales [52,5%] y de cadera 24,6%]), el antecedente desproporcionado de pacientes con enfermedad glomerular en comparación con series puramente nefrológicas (corticoides) y el infratratamiento para la prevención de fracturas, fundamentalmente en consultas nefrológicas. Este estudio supone una inmediata llamada a la acción con la difusión de las nuevas guías clínicas, más proactivas, y subraya la necesidad de homogeneizar el enfoque asistencial/terapéutico multidisciplinar coordinado de estos pacientes de un modo eficiente para evitar las actuales discrepancias y el nihilismo terapéutico. (AU)

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD) complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results will impact treatment decisions. However, there is very little information on actual clinical practice in this population. The main objective of the ERC-Osteoporosis (ERCOS) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36ml/min/1.73m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures ([37.7%], mainly vertebral [52.5%] and hip [24.6%]), the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and efficient multidisciplinary care/therapeutic approach to these patients to avoid current discrepancies and therapeutic nihilism. (AU)

Lineamientos para la prevención y el tratamiento de la osteoporosis inducida por glucocorticoides en pediatría / Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis in pediatrics

Objetivo. Proporcionar un marco para profesionales de la salud que tratan a pacientes pediátricos bajo terapia con glucocorticoides (GC) y desarrollar recomendaciones para la prevención y el tratamiento de la osteoporosis inducida por GC en la población pediátrica. Métodos. Un panel de expertos en enfermedades óseas y pediátricas generó una serie de preguntas PICO que abordan aspectos relacionados con la prevención y el tratamiento de osteoporosis en pacientes bajo tratamiento con GC. Siguiendo la metodología GRADE, se realizó una revisión sistemática de la literatura, se resumieron las estimaciones del efecto y se calificó la calidad de la evidencia. Luego se procedió a la votación y a la formulación de las recomendaciones. Resultados. Se desarrollaron 7 recomendaciones y 6 principios generales para osteoporosis inducida por GC en población pediátrica. Conclusión. Estas recomendaciones proporcionan orientación para los médicos que deben tomar decisiones en pacientes pediátricos bajo tratamiento con GC.

Objective. To provide a framework for healthcare professionals managing pediatric patients who are on active glucocorticoid (GC) therapy and to develop recommendations for the prevention and treatment of GC-induced osteoporosis in the pediatric population. Methods. A panel of experts on bone and pediatric diseases developed a series of PICO questions that address issues related to the prevention and treatment of osteoporosis in patients on GC therapy. In accordance with the GRADE approach, we conducted a systematic review of the literature, summarized effect estimations, and classified the quality of the evidence. Then, voting and the formulation of recommendations followed. Results. Seven recommendations and six general principles were developed for GC-induced osteoporosis in the pediatric population. Conclusion. These recommendations provide guidance for clinicians who must make decisions concerning pediatric patients undergoing treatment with GC.