Anti-osteoporotic Therapy Research Articles

High-resolution peripheral quantitative computed tomography: research or clinical practice?

High-resolution peripheral quantitative CT (HR-pQCT) is a low-dose three-dimensional imaging technique, originally developed for in vivo assessment of bone microarchitecture at the distal radius and tibia in osteoporosis. HR-pQCT has the ability to discriminate trabecular and cortical bone compartments, providing densitometric and structural parameters. At present, HR-pQCT is mostly used in research settings, despite evidence showing that it may be a valuable tool in osteoporosis and other diseases. This review summarizes the main applications of HR-pQCT and addresses the limitations that currently prevent its integration into routine clinical practice. In particular, the focus is on the use of HR-pQCT in primary and secondary osteoporosis, chronic kidney disease (CKD), endocrine disorders affecting bone, and rare diseases. A section on novel potential applications of HR-pQCT is also present, including assessment of rheumatic diseases, knee osteoarthritis, distal radius/scaphoid fractures, vascular calcifications, effect of medications, and skeletal muscle. The reviewed literature seems to suggest that a more widespread implementation of HR-pQCT in clinical practice would offer notable opportunities. For instance, HR-pQCT can improve the prediction of incident fractures beyond areal bone mineral density provided by dual-energy X-ray absorptiometry. In addition, HR-pQCT may be used for the monitoring of anti-osteoporotic therapy or for the assessment of mineral and bone disorder associated with CKD. Nevertheless, several obstacles currently prevent a broader use of HR-pQCT and would need to be targeted, such as the small number of installed machines worldwide, the uncertain cost-effectiveness, the need for improved reproducibility, and the limited availability of reference normative data sets.

Establishment of a novel risk prediction model for recompression of augmented vertebrae at the thoracolumbar junction and modified puncture technique for prevention: a multicenter retrospective study.

Recompression of augmented vertebrae (RCAV) is often seen after percutaneous kyphoplasty (PKP), especially at the thoracolumbar junction. The authors aimed to develop and validate a risk prediction model (nomogram) for RCAV and to evaluate the efficacy of a modified puncture technique for RCAV prevention after PKP for thoracolumbar osteoporotic vertebral fractures (OVFs). Patients who underwent PKP for single thoracolumbar OVFs (T10-L2) between January 2016 and October 2020 were reviewed and followed up for at least 2 years. All patients were randomly divided into a training group (70%) and a validation group (30%). Relevant potential data affecting recompression were collected. Predictors were screened by using binary logistic regression analysis to construct the nomogram. Calibration and receiver operating characteristic curves were used to evaluate the consistency of the prediction models. Finally, the efficacy of the modified puncture technique for prevention of RCAV in OVF patients with a preoperative intravertebral cleft (IVC) was further demonstrated through binary logistic regression analysis. Overall, 394 patients were included and 116 of them (29.4%) sustained RCAV. The independent risk factors included decreased bone mineral density, lower level of serum 25-hydroxy vitamin D3, larger C7-S1 sagittal vertical axis (SVA), preoperative IVC, and solid-lump cement distribution. The area under the curve (AUC) of the prediction model was 0.824 in the training group and 0.875 in the validation group patients. The calibration curve indicated the predictive power of this nomogram, with the preoperative IVC having the highest prediction accuracy (AUC 0.705). The modified puncture technique significantly reduced the incidence of RCAV by enhancing bone cement distribution into a sufficiently diffused distribution in OVF patients with preoperative IVC. The nomogram prediction model had satisfactory accuracy and clinical utility for identification of patients at low and high risk of postoperative RCAV. Patients at high risk of postoperative RCAV might benefit from the target puncture technique and vitamin D supplementation as well as effective antiosteoporotic therapies.

Bone collagen quality in lumbar fusion patients: the association between volumetric bone mineral density and advanced glycation endproducts.

The sole determination of volumetric bone mineral density (vBMD) is insufficient to evaluate overall bone integrity. The accumulation of advanced glycation endproducts (AGEs) stiffens and embrittles collagen fibers. Despite the important role of AGEs in bone aging, the relationship between AGEs and vBMD is poorly understood. We hypothesized that an accumulation of AGEs, a marker of impaired bone quality, is related to decreased vBMD. Prospectively collected data of 127 patients undergoing lumbar fusion were analyzed. Quantitative computed tomography (QCT) measurements were performed at the lumbar spine. Intraoperative bone biopsies were obtained and analyzed with confocal fluorescence microscopy for fluorescent AGEs, both trabecular and cortical. Spearman's correlation coefficients were calculated to examine relationships between vBMD and fAGEs, stratified by sex. Multivariable linear regression analysis with adjustments for age, sex, body mass index (BMI), race, diabetes mellitus and HbA1c was used to investigate associations between vBMD and fAGEs. One-hundred and twenty-seven patients (51.2% female, 61.2years, BMI of 28.7kg/m2) with 107 bone biopsies were included in the final analysis, excluding patients on anti-osteoporotic drug therapy. In the univariate analysis, cortical fAGEs increased with decreasing vBMD at (r = -0.301; p = 0.030), but only in men. In the multivariable analysis, trabecular fAGEs increased with decreasing vBMD after adjusting for age, sex, BMI, race, diabetes mellitus and HbA1c (β = 0.99;95%CI=(0.994,1.000); p = 0.04). QCT-derived vBMD measurements were found to be inversely associated with trabecular fAGEs. Our results enhance the understanding of bone integrity by suggesting that spine surgery patients with decreased bone quantity may also have poorer bone quality.

Artículo traducido] Perfil clínico-epidemiológico del paciente atendido en una unidad multidisciplinar de fractura de cadera de un hospital de primer nivel en el noroeste de España

IntroductionHip fractures constitute a capital public health issue associated with aging and frailty because of its impact on both quality of life and morbidity and mortality in older people. Fracture liaison services (FLS) have been proposed as tools to minimize this emergent problem. Material and methodsA prospective observational study was conducted with 101 patients treated for hip fracture by the FLS of a regional hospital between October 2019 and June 2021 (20 months). Epidemiological, clinical, surgical, and management variables were collected during admission and up to 30 days after discharge. ResultsMean age of patients was 87.6 ± 6.1 years and 77.2% were female. Some degree of cognitive impairment was detected at admission in 71.3% of patients using the Pfeiffer questionnaire, and 13.9% were nursing home residents, and 76.24% could walk independently before the fracture. Fractures were more commonly pertrochanteric (45.5%). Patients were receiving antiosteoporotic therapy in 10.9% of cases. The median surgical delay from admission was 26 h (RIC 15–46 h), the median length of stay was 6 days (RIC 3–9 days) and in-hospital mortality was 10.9%, and 19.8% at 30 days, with a readmission rate of 5%. DiscussionPatients treated in our FLS at the beginning of its activity were similar to the general picture in our country in terms of age, sex, type of fracture, and proportion of patients treated surgically. A high mortality rate was observed, and low rates of pharmacological secondary prevention were followed at discharge. Clinical results of FLS implementation in regional hospitals should be assessed prospectively in order to decide their suitability.

Evaluation of Usage of a Fracture Risk Assessment by FRAX Tool in Adults With Type 2 Diabetes Mellitus.

Fragility fractures are increasingly recognized as a complication of type 2 diabetes mellitus (T2DM). The FRAX-Port® is a calculation tool that assesses the 10-year risk of either major and hip fracture, integrating several clinical risk factors, including T2DM. We aimed to evaluate the fracture risk in adults with T2DM and determine the rate of patients at high risk for fracture under anti-osteoporotic therapy. We developed a cross-sectional study, including a convenience sample of adults with T2DM, followed in our tertiary center between 2019 and 2022. Fracture risk was evaluated according to FRAX-Port®. One hundred adults were included, 54% male, with a mean age of 68.4±9.2 years. Respecting fracture risk factors, 17% had a previous fragility fracture, 12% had a history of hip fracture in their parents, 9% had active alcohol consumption, and 4% had active smoking. Additionally, 17% presented secondary osteoporosis, being the most frequent cause of systemic corticosteroid exposure (10%). Regarding diabetes-specific risk factors, 94% had a diabetes duration longer than five years; HbA1c greater than 7% in 70%; 42% had diabetic retinopathy, 33% had diabetic chronic kidney disease, 18% had peripheral neuropathy, and 7% had autonomic neuropathy; 83% were on insulin, 2% on canagliflozin and 1% on pioglitazone. According to the FRAX-Port®, the median probability of major fracture was 6.8% (IQR 6.9), and hip fracture was 2.4% (IQR 3.9). Fracture risk was high, intermediate, and low at 41%, 15%, and 44%, respectively. Lastly, 56% of participants should undergo bone densitometry and 45% had a formal recommendation to begin an anti-osteoporotic treatment. However, only 6% were under anti-osteoporotic therapy: bisphosphonates (5%) and denosumab (1%). More than a third of T2DM patients evaluated had a high fracture risk. We found that FRAX-Port® is an easy-to-apply tool, which helps in the decision to perform densitometry or to institute anti-osteoporotic therapy. Given the increasing prevalence of T2DM and the associated risk of falls, this study highlights the need to recognize the fracture risk in these patients, usually a forgotten complication during the screening of risk factors for adverse events in adults with T2DM.

The problem is the prescription of drug therapy to reduce the risk of fractures and its solution

The older people with osteoporosis, especially those with low-energy fractures, are the most vulnerable group of geriatric patients. They are shown the appointment of anti-osteoporotic therapy, which should be effective and safe. Unfortunately, the real prescription of medical treatment of osteoporosis in the world barely reaches 20%. This is due not only to low adherence to therapy by elderly patients, but also to financial and economic difficulties in obtaining drugs. For most patients, drug therapy for osteoporosis is quite expensive, especially given its long-term, often lifelong, course of action. However, new opportunities have now emerged to provide certain anti-osteoporotic drugs not only to patients in the preferential category, but also without disabilities. This will not only increase the number of patients receiving treatment for osteoporosis, but also reduce the risk of fractures, both primary and recurrent, the risk of falls, injuries and premature death among the elderly population. The article presents modern possibilities of providing medicines to patients with osteoporosis and its complications in the form of pathological fractures using clinical and statistical groups (CSG) as new methods of payment for inpatient and hospital-replacing care in the Russian Federation.

Efficacy of zoledronate, denosumab or teriparatide in postmenopausal women with type 2 diabetes mellitus at high risk of fragility fractures: protocol of an open, blinded endpoint randomized controlled pilot trial.

People with type 2 diabetes (T2D) are at high risk of fragility fractures; however, there are no randomized controlled trials evaluating the efficacy of anti-osteoporosis drugs as a primary pre-specified endpoint in T2D. To compare the efficacy of anti-osteoporotic drugs in postmenopausal women with T2D. Prospective, randomized, open, blinded endpoint clinical pilot trial. Postmenopausal women (⩾50 years) with T2D (duration ⩾5 years), HbA1c 7-10%, eGFR ⩾45 mL/min/1.73 m2 and prior vertebral (clinical/morphometric), hip, radius, humeral fragility fracture or bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ⩽-2.5 and high FRAX score will be eligible for inclusion. Subjects with secondary causes of osteoporosis, prior exposure to bone-active therapies or history of use of glucocorticoids/pioglitazone/thiazides/canagliflozin will be excluded. Finally, eligible subjects will undergo estimation of serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone turnover markers (BTMs) (total procollagen type I N-propeptide, β-CTX) along with trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of non-dominant hand and leg. After a 2-week run in phase, they will be randomized in a 1:1:1:1 ratio to receive yearly zoledronate, or biannually denosumab or daily teriparatide (in addition to standard of care, i.e., calcium 1000 mg/day and cholecalciferol 1000 IU/day) or only standard of care (control). The primary endpoints will be change in areal BMD and frequency of incident fractures at 18 months. The secondary endpoints will be change in HR-pQCT parameters, TBS and BTMs at 18 months. Adverse events will be recorded for all randomized participants. The study has been approved by the Institute Ethics Committee. Written informed consent will be obtained from each participant. The trial is expected to provide information regarding optimal anti-osteoporotic therapy in people with T2D and bone fragility. Prospectively registered in Clinical Trial Registry of India (CTRI/2022/02/039978).

A participatory process to design an app to improve adherence to anti-osteoporotic therapies: A development and usability study.

The aim of the study was to develop an app to improve patients' adherence to therapy for osteoporosis and to test its usability. In Phase I, the app functions needed to improve medication adherence were identified through a focus group with six patients with osteoporosis and a joint interview with two bone specialists. The app prototype was then developed (Phase II) and refined after its feasibility testing (Phase III) for 13-25 days by eight patients. Finally, the app underwent usability testing (Phase IV) for 6 months by nine other patients. The mHealth App Usability Questionnaire (MAUQ) was used to collect the assessment of the app by the 17 patients. The final version of the app provided information on osteoporosis, allowed patients to contact the bone specialist for an additional consultation, and generated a reminder for taking medications accompanied by feedback on adherence. The assessment of the app was positive but evaluations differed between the feasibility and usability testing, with the former displaying a significantly (p ≤ .05) better assessment across all MAUQ items. In this study, we tested an app for improving adherence to medical therapies in patients with osteoporosis. The usability testing revealed a lower "patient-centered" performance of the app as compared to that observed during the feasibility phase. Future developments of the study include increasing the testing cohort and adding a technical support during the usability testing.

Anabolic Peptide-Enriched Stealth Nanoliposomes for Effective Anti-Osteoporotic Therapy.

The objective of the present work was to develop PTH (1-34)-loaded stealth nanoliposomes (PTH-LPs) by employing the use of the Quality by Design (QbD) approach. Risk identification was carried out using the Ishikawa fishbone diagram. PTH-LPs were optimized using Box Behnken Design, a type of response surface methodology to examine the effect of independent variables on dependent variables such as particle size and percentage entrapment efficiency (%EE). Design space was generated for PTH-LPs to reduce interbatch variability during the formulation development process. Furthermore, a cytotoxicity assay, cell proliferation assay, calcium calorimetric assay, mineralized nodule formation, and cellular uptake assay were carried out on MG-63 osteoblast-like cells. The results obtained from these procedures demonstrated that lipid concentration had a significant positive impact on particle size and %EE, whereas cholesterol concentration showed a reduction in %EE. The particle size and %EE of optimized formulation were found to be 147.76 ± 2.14 nm and 69.18 ± 3.62%, respectively. Optimized PTH-LPs showed the sustained release profile of the drug. In vitro cell evaluation studies showed PTH-LPs have good biocompatibility with MG-63 cells. The cell proliferation study revealed that PTH-LPs induced osteoblast differentiation which improved the formation of mineralized nodules in MG-63 cells. The outcome of the present study conclusively demonstrated the potential of the QbD concept to build quality in PTH-LPs with improved osteoanabolic therapy in osteoporosis.

Fracture in Patients with Normal Bone Mineral Density: An Evaluation of the American Orthopaedic Association's Own the Bone Registry.

Fractures often occur in patients with normal dual x-ray absorptiometry (DXA)-measured bone mineral density (BMD). DXA does not consider clinical fracture risk factors or bone quality. We hypothesized that patients with normal BMD who sustain a fracture have other characteristics suggesting abnormal bone and an elevated fracture risk requiring additional bone health evaluation and potential anti-osteoporotic treatment. A total of 7,219 patients who were ≥50 years of age, had sustained a fracture from July 2016 to July 2021, and had DXA data in the American Orthopaedic Association's Own the Bone (AOA OTB) registry were included in this study. The index and prior fracture site data were obtained. BMD status was classified by the World Health Organization T-score criteria. The Fracture Risk Assessment Tool (FRAX) scores with and without BMD were calculated in patients with normal BMD. An elevated risk was defined as a major osteoporotic fracture risk of ≥20% or a hip fracture risk of ≥3%. The mean patient age (and standard deviation) was 70.8 ± 9.71 years, 84% of patients were female, and 92% of patients were Caucasian. Normal BMD was present in 8.6% of patients. The index fracture was a major osteoporotic fracture in 68.6% of patients with normal BMD and 75.6% of patients with osteoporosis. The most common site for index and prior fractures other than major osteoporotic fractures was the foot and ankle; of patients with normal BMD, 13.9% had this as the most common index site and 17.4% had this as the most common prior site. The FRAX risk calculated without BMD was elevated in 72.9% of patients with normal BMD, and the FRAX risk calculated with BMD was elevated in 12.0% of patients. Most patients with a fracture and normal BMD met indications, including a prior fracture or elevated FRAX risk, for anti-osteoporotic therapies. Most patients were Caucasian and therefore potentially had a higher baseline fracture risk. The FRAX risk calculated without BMD was elevated more often than the FRAX risk with BMD, implying that clinical risk factors, which highlight multiple opportunities for non-pharmacologic secondary fracture prevention, should be considered along with DXA. Fractures other than major osteoporotic fractures were more common in patients with normal BMD, suggesting that minor fractures in adults who are ≥50 years of age should be considered sentinel events warranting further evaluation. Surgeons must recognize that other important risk factors apart from BMD may help to guide further bone health evaluation. Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

The Association of Postoperative Osteoporosis Therapy With Periprosthetic Fracture Risk in Patients Undergoing Arthroplasty for Femoral Neck Fractures

BackgroundDisplaced femoral neck fractures in older adults are generally treated with hip arthroplasty. One concern following hip arthroplasty is the risk for periprosthetic fractures (PPFs). Most patients who have hip fractures are candidates for antiosteoporotic therapy, but the impact of this treatment on PPFs is unknown. Therefore, the primary objective of this study was to evaluate whether patients treated with antiosteoporotic medical therapy had lower odds of PPFs following arthroplasty for hip fracture. MethodsPatients at least 65 years old who underwent hip arthroplasty for femoral neck fractures from 2010 to 2020 were identified in a national database. Patients were stratified based on whether they initiated antiosteoporotic therapy within 1 year of hip arthroplasty. Minimum follow-up was 1 year, and maximum follow-up was 10.6 years. The primary endpoint was cumulative incidence of PPF as determined using Kaplan–Meier and Cox proportional hazards regression analyses. Overall, 2,026 patients who underwent arthroplasty for femoral neck fracture received antiosteoporotic medications within 1 year following surgery (mean follow up 4.8 years; range 1.0 to 10.6 years) and 33,639 patients did not (mean follow up 4.1 years; range 1.1 to 10.3 years). ResultsThe 10-year cumulative incidence of PPF for patients treated for osteoporosis was 3.88% compared to 5.92% for those who were untreated (P < .001). Adjusting for covariates, patients who received osteoporosis treatment had a significantly lower risk for PPF than those who were untreated (hazard ratio (HR): 0.663; 95% confidence interval (CI): 0.465-0.861; P = .038). ConclusionThe present study suggests that osteoporosis treatment is associated with lower incidence of PPF following hip arthroplasty for femoral neck fractures. Treatment of osteoporosis should be initiated in eligible patients who sustain a femoral neck fracture, especially those who undergo hip arthroplasty.

Clinical–epidemiological profile of the patient attended in a Fracture Liaison Service (FLS) of a regional hospital in north-west of Spain

IntroductionHip fractures constitute a capital public health issue associated with aging and frailty because of its impact on both quality of life and morbidity and mortality in older people. Fracture Liaison Services (FLS) have been proposed as tools to minimize this emergent problem. Material and methodsA prospective observational study was conducted with 101 patients treated for hip fracture by the FLS of a regional hospital between October 2019 and June 2021 (20 months). Epidemiological, clinical, surgical and management variables were collected during admission and up to 30 days after discharge. ResultsMean age of patients was 87.6±6.1 years and 77.2% were female. Some degree of cognitive impairment was detected at admission in 71.3% of patients using the Pfeiffer questionnaire, and 13.9% were nursing home residents, and 76.24% could walk independently before the fracture. Fractures were more commonly pertrochanteric (45.5%). Patients were receiving antiosteoporotic therapy in 10.9% of cases. The median surgical delay from admission was 26h (RIC 15–46h), the median length of stay was 6 days (RIC 3–9 days) and in-hospital mortality was 10.9%, and 19.8% at 30 days, with a readmission rate of 5%. DiscussionPatients treated in our FLS at the beginning of its activity were similar to the general picture in our country in terms of age, sex, type of fracture, and proportion of patients treated surgically. A high mortality rate was observed, and low rates of pharmacological secondary prevention were followed at discharge. Clinical results of FLS implementation in regional hospitals should be assessed prospectively in order to decide their suitability.

Dual Targeting Anti-Osteoporotic Therapy Through Potential Nanotherapeutic Approaches

Osteoporosis is characterised by a major public health burden, particularly taking into account the ageing global population. Therapeutic modalities for osteoporosis are categorised on the basis of their effect on bone remodeling: antiresorptive agents and anabolic agents. Anabolic drugs are favoured as they promote the formation of new bone, whereas antiresorptive drugs terminate the further deterioration of bone. Non-specific delivery of anabolic agents results in prolonged kidney exposure causing malignant hypercalcemia, whereas antiresorptive agents and bisphosphonates may produce osteonecrosis of the jaw. Several clinical trials have been reported for combinational therapy of anabolic agents and antiresorptive agents for osteoporosis. However, none of them have proven their cumulative effectiveness in the treatment of disease. The present work emphasizes on dual-targeting drug delivery approach comprising of bone anabolic and antiresorptive agents that would deliver the therapeutic agents to both the zones of bone simultaneously. The anticipated pioneering delivery approach will intensify the explicit interaction between the therapeutic agent and bone surfaces separately without developing severe adverse effects and improve the osteoporotic therapy effectively compared to non-targeted drug delivery.

Pharmacological management, and potentially inappropriate prescriptions in patients with osteoporosis

Background The treatment of osteoporosis involves medications that reduce the risk of fractures, but some medications can decrease bone density. The aim of this study was to identify the treatments, comorbidities, and prescriptions related to reducing bone mineral density in patients with osteoporosis. Research design and methods A cross-sectional study that identified patterns of anti-osteoporotic drug prescriptions for outpatient use and potentially inappropriate prescriptions for patients with osteoporosis based on the drug-dispensing database (Audifarma SA) of 8.5 million people affiliated with the Colombian Health System and six health insurance companies. All patients ≥65 years with a diagnosis of osteoporosis were included. A multivariate analysis was performed to identify variables related to potentially inappropriate prescriptions for ≥3 months (glucocorticoids, proton pump inhibitors, among others). Results A total of 16,362 patients with osteoporosis were identified. They had a median age of 74.4 years, and 47.9% received anti-osteoporotic therapy, especially diphosphonates (41.6%), and 86.5% received calcium and/or vitamin D supplement. 41.6% of those who had a history of bone fractures were prescribed anti-osteoporotic drugs. Potentially inappropriate prescriptions, especially glucocorticoids at doses greater than 5mg prednisolone equivalent (4.4%), were found in 41.4% of cases for ≥3 months and were more common in older patients (OR:1.31;CI95%:1.18-1.46) and those with a history of fractures (OR:1.14;CI95%:1.04-1.25) or with cardiovascular (OR:2.23;CI95%:2.07-2.40), digestive (OR:3.09;CI95%:2.80-3.41), neurological (OR:1.49;CI95%:1.34-1.64), psychiatric (OR:2.71;CI95%:2.42-3.03) or neoplastic comorbidities (OR:1.94;CI95%:1.59-2.36). In addition, synthetic (OR:3.62;CI95%:3.21-4.07) and biological rheumatic disease-modifying drugs (OR:2.14;CI95%:1.15-4.01) also increased the likelihood of having potentially inappropriate prescriptions. Conclusions A significant proportion of patients with osteoporosis are not treated according to clinical practice guidelines. Potentially inappropriate prescriptions were common, especially in older patients, with certain comorbidities, and those receiving comedication with antirheumatic drugs.

Nanoemulsified Genistein and Vitamin D Mediated Epigenetic Regulation to Inhibit Osteoporosis.

The imbalance in the bone remodeling process with more bone resorption by osteoclasts compared to bone formation by osteoblasts results in a metabolic bone disorder known as osteoporosis. This condition reduces the bone mineral density and increases the risk of fractures due to low bone mass and disrupted bone microarchitecture. Osteoclastogenesis increases when the receptor activator NFκB ligand (RANKL) on the osteoblast surface binds to the receptor activator NFκB (RANK) on the osteoclast surface and the function of the decoy receptor of RANKL, osteoprotegrin, is compromised due to external stimuli such as heparin and lipopolysaccharides. The RANK/RANKL axis promotes the nuclear factor kappa B (NFκB) expression, which in turn increases the histone methyltransferase activity of EzH2 and EzH1 for the epigenetic regulation of osteoclastogenesis-related genes. Genistein counteracts NFκB-induced osteoclastogenesis and downstream signaling through the direct regulation of histone methyltransferase, EzH2 and EzH1, transcription. However, genistein possesses limitations like low bioavailability, low water solubility, high estrogen activity, and thyroid side effects, which obstruct its therapeutic usage. Here, the nanoemulsified formulation of genistein with vitamin D was utilized to circumvent the limitations of genistein so that it can be utilized for therapeutic purposes in osteoporosis management. The nanoemulsification of genistein and vitamin D was performed through the spontaneous emulsification using Tween 80 and medium chain triglyceride oil as an organic phase. The physiologically stable and biocompatible combination of the genistein and vitamin D nanoemulsion (GVNE) exhibited the controlled release pattern of genistein with Korsmeyer-Peppas and Higuchi models under different pH conditions (7.4, 6.5, and 1.2). The GVNE potentially enhanced the therapeutic efficacy under in vitro osteoporosis models and helped restore disease parameters like alkaline phosphatase activity, tartrate-resistant acid phosphatase activity, and the formation of multinuclear giant cells. Molecularly, the GVNE overturned the LPS-induced osteoclastogenesis by downregulation of NFκB expression along with its binding on EzH2 and EzH1 promoters. GVNE effects on the osteoporosis model established it as an efficient antiosteoporotic therapy. This nanonutraceutical-based formulation provides an epigenetic regulation of osteoporosis management and opens new avenues for alternate epigenetic therapies for osteoporosis.

2. The association between lumbar bone mineral density and advanced glycation end products derived from confocal fluorescence microscopy: a prospective investigation of bone biopsies in patients undergoing lumbar spinal fusion surgery

2. The association between lumbar bone mineral density and advanced glycation end products derived from confocal fluorescence microscopy: a prospective investigation of bone biopsies in patients undergoing lumbar spinal fusion surgery

1. The association between advanced glycation end products derived from confocal fluorescence microscopy of bone biopsies and dermal ultrasound echogenicity in patients undergoing lumbar spinal fusion surgery

1. The association between advanced glycation end products derived from confocal fluorescence microscopy of bone biopsies and dermal ultrasound echogenicity in patients undergoing lumbar spinal fusion surgery

Anti-osteoporotic treatment and COVID-19 risk: is there an association?

Introduction. Despite the recent ASBMR, AACE, Endocrine Society, ECTS&amp;NOF guidelines for osteoporosis management in the era of COVID-19 the impact of antiosteoporotic drugs on disease risk and severity is insufficiently studied. The purpose of this study was to assess the COVID-19 risk for the patients receiving the parenteral bisphosphonate or Denosumab treatment, and the severity of its course in patients with systemic osteoporosis. Materials and methods. We performed the phone survey and studied the results of 195 patients (92 % women; mean age – 62.7±10.8 years) with systemic osteoporosis depending on the current use of parenteral antiresorptive drugs (Zoledronic, Ibandronic acids, or Denosumab, n = 125) and compared the results with data of the patients with osteoporosis who did not use any anti-osteoporotic drugs previously (n = 70). Results. The group of patients with COVID-19 included 32.9 % of patients who did not receive previously any anti-osteoporotic treatment and 33.3 % of osteoporotic patients treated with parenteral antiresorptive drugs. The share of the patients taking the Zoledronic acid who fell ill with COVID-19 was 29.2 %, the share of those taking the Ibandronic acid was 34.4%, and the share of those taking Denosumab was 42.9 %. We did not reveal any significant differences in the COVID-19 frequency and severity depending on the presence and type of parenteral anti-osteoporotic therapy. Additionally, there were no differences depending on the patients' age, gender, obesity, and other osteoporosis risk factors. The risk of COVID-19 in the patients with systemic osteoporosis did not differ depending on antiresorptive drug use, amounting (odds ratio (OR) 95 % CI) 1.1 (0.6-2.0), or on the use of the definite anti-osteoporotic drug (for the Zoledronic acid – 0.9 (0.4-2.0), the Ibandronic acid – 1.1 (0.5-2.3), and for the Denosumab – 1.6 (0.5-5.2). Conclusions. Parenteral anti-osteoporotic drugs (Zoledronic acid, Ibandronic acid, or Denosumab) do not have any influence on COVID-19 frequency and severity and can be recommended for the continuation of the treatment of patients with osteoporosis.

The Impact of Seropositivity on Systemic Bone Loss in Rheumatoid Arthritis-A 3-Year Interim Analysis of a Longitudinal Observational Cohort Study.

ObjectiveTo explore the impact of seropositivity on systemic bone loss in rheumatoid arthritis (RA).MethodsWe conducted an interim analysis of the RA registry. Patients were examined with dual-energy X-ray absorptiometry at baseline and again 3 years later. Participants were grouped into seropositive (SPRA) and seronegative (SNRA) based on the presence or absence of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (ACPA). After matching (1:2) for age and sex, SNRA and SPRA patients were divided into groups A and B. Each matched group (A or B) was further subdivided according to the number of antibodies present (0, group I; 1, group II; 2, group III). Multiple ordinary least squares regression was used with the dependent variables to develop a model to predict bone mineral density (BMD) change.ResultsA total of 477 participants who completed a 3-year observation period were included. After matching, 312 participants were enrolled (group A, 104; group B, 208). Three years later, group B had significant BMD reduction in the femoral neck (FN) (p < 0.001), total hip (TH) (p = 0.001), and first through fourth lumbar vertebrae (L1–4) (p = 0.006), while group A had bone loss only at FN (p = 0.002). Groups I, II, and III included 104, 52, and 156 participants, respectively. Compared to baseline, BMD decreased significantly at FN (p = 0.002) in group I, FN (p < 0.001) in group II, and FN (p < 0.001), TH (p = 0.002), and L1–4 (p = 0.016) in group III. In terms of regression-adjusted percent change in BMD, more significantly negative changes were found at all measured sites in group B (p < 0.001, all) and at TH and L1–4 within groups I-III (p for trend < 0.001 and < 0.001, respectively). Regardless of antibodies, anti-osteoporotic therapy can preserve bone density in RA patients.ConclusionAfter 3 years, SPRA patients lost more bone density than SNRA patients. More attention should be paid to SPRA patients, especially those with double-positive antibodies, including a vigorous evaluation of BMD and fracture risk. Anti-osteoporotic therapy can prevent BMD loss irrespective of autoantibodies.

Protocolo del uso diagnóstico de los biomarcadores del metabolismo óseo

The bioavailability of biochemical bone turnover markers (BTM) (formation and resorption) that can be measured quickly and at a relatively low cost are an advantage in the evaluation and treatment of patients with metabolic bone diseases, especially osteoporosis. BTM provide a dynamic evaluation of the bone system which could potentially complement the static measurement of bone mineral density. However, it is necessary to know their limitations and use them in an appropriate clinical context. Currently, the clinical use of BTM is to monitor the efficacy of antiosteoporotic therapy. BTM could potentially have other functions, such as the prediction of treatment response and control of compliance with and appropriate use of the treatment.