Increase In Bone Mineral Density Research Articles

Building a Multidisciplinary Care Pathway Supported by a Surgical Approach to Local Bone Formation.

Osteoporosis is the most common disease of bone mineral metabolism. In Spain, it affects approximately 3 million people, of whom 80% are females and 20% are males. Despite the advances that have been made in this field, we continue to witness alarming levels of fragility hip fractures. In 2010, the cost of osteoporosis in the European Union was estimated to be 37,000 million euros, which included the costs for the treatment of incident fractures (66%), pharmacological prevention (5%), and long-term fracture care (29%). A multidisciplinary care pathway supported by a surgical approach to local bone formation is needed. Recently, the International Osteoporosis Foundation (IOF) and the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) included in their treatment guidelines a local osteo-enhancement procedure (LOEP) as a treatment option. In the Ossure™ LOEP technique (AgNovos Healthcare USA, LLC, Rockville, MD), a calcium-based triphasic osteoconductive implant material (AGN1), which has been shown to increase bone mineral density (BMD) and proximal femoral strength, is introduced percutaneously in the femoral neck and intertrochanteric region. Basically, the procedure consists of three percutaneous steps: prepare, clean, and fill the cavity with AGN1. It can be carried out with sedation and local anaesthesia or spinal anaesthesia. This report presents a clinical case and discusses how to select patients who could potentially benefit from this technique.

Parathyroidectomy Improves Bone Density in Women With Primary Hyperparathyroidism and Preoperative Osteopenia.

Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. Referral center. A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. Parathyroidectomy. BMD change between before and 1 year after parathyroidectomy. Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03-0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00-0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01-0.02)], and the forearm [+0.01 (95% CI 0.00-0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain.

Comprehensive Analysis of Phytoestrogens Intervention in Osteoporosis Management: A Systematic Review of Randomized Controlled Trials

Introduction: Osteoporosis is a medical condition characterized by increased bone turnover and decreased bone mass, which leads to bone fractures. Antiresorptive therapy, hormone replacement therapy (HRT), and bisphosphonates are used as first-line therapy related to numerous side effects. The osteoprotective properties of phytoestrogens are well known. This systematic review aims to explore the potential of phytoestrogen in the management of osteoporosis patients based on serum bone biomarker analysis. Methods: The literature search was conducted in six databases. The outcome of interest measures the mean changes in bone mineral density (BMD) and other serum bone biomarkers. Various forms of phytoestrogen intervention were used, including isoflavone extracts with an administered dose (tablets, capsules), genistein extract (tablets), resveratrol, and isolated soy protein (IBS) in powder form, beverages, food and snacks, and soy products. Quality appraisal was done using the Cochrane Risk of Bias Tool 2. Ten articles were included in the systematic review. Results: Seven studies found the mean changes in BMD values were significantly higher than the control group's after phytoestrogen intervention. Phytoestrogens dramatically boost numerous bone formation markers, including calcium, phosphorus, Ca/P ratio, and vitamin D, followed by a drop in BAP and osteocalcin levels. Phytoestrogens dramatically increased numerous bone formation markers, including calcium, phosphorus, Ca/P ratio, and vitamin D, followed by a decrease in BAP and osteocalcin levels. Furthermore, intervention may reduce bone resorption indicators such as CTX, RANKL, AKP, OPG, DPD, and PTH. Conclusion: Phytoestrogen intervention has demonstrated effectiveness in increasing bone mineral density and serum bone biomarkers.

Adherence of denosumab treatment for low bone mineral density in Japanese people living with HIV: a retrospective observational study

BackgroundLong-term care issues, specifically metabolic bone disorders, are a concern for people living with human immunodeficiency virus (PLWH) who undergo life-long antiretroviral therapy (ART). Previous clinical trials with denosumab, an anti-RANKL antibody inhibitor, have revealed its effectiveness in increasing bone mineral density (BMD) in patients with osteoporosis. However, there are limited data on adherence and effectiveness of denosumab treatment for osteoporosis in PLWH. Hence, this study aimed to investigate the adherence and effectiveness of denosumab treatment for osteoporosis in Japanese PLWH.MethodsThis study is a retrospective exploratory analysis of 29 Japanese PLWH who initiated denosumab treatment for osteoporosis, between 2013 and 2021. The study included patients who received at least one dose of denosumab every 6 months. Adherence and persistence were defined as receiving two consecutive injections of denosumab 6 months ± 4 weeks apart and 6 months + 8 weeks apart, respectively. The primary outcome measure of the study was the adherence of denosumab treatment for 24 months. The secondary outcome measures included treatment persistence and BMD. The period after January 2020 was defined as the coronavirus disease 2019 (COVID-19) pandemic period, and its impact on adherence was investigated.ResultsThe treatment adherence rates at 12 and 24 months were 89.7% and 60.7%, respectively. By contrast, the treatment persistence at 12 and 24 months was 100% and 85.7%, respectively. More patients in the group who initiated denosumab treatment after the COVID-19 pandemic reached non-adherence than in the group who initiated denosumab treatment before the pandemic. BMD at the lumbar spine and femoral neck significantly increased compared to that at baseline, with median percentage changes of 8.7% (p < 0.001) and 3.5% (p = 0.001), respectively.ConclusionsThe results showed that patients in the study had a high rate of non-adherence but a lower rate of non-persistence. Additionally, PLWH on ongoing ART experienced increased BMD with denosumab treatment. This study provides an opportunity to improve future strategies for denosumab treatment in the Japanese PLWH.

Associations between Macronutrients Intake and Bone Mineral Density: A Longitudinal Analysis of the Health Workers Cohort Study Participants

ObjectiveThis study aimed to evaluate the association between macronutrient intake and bone mineral density (BMD) using non-substitution and substitution statistical approaches. DesignLongitudinal analysis. Settings and Participants1,317 adults in the Health Worker Cohort Study in Mexico. MeasurementsThese participants were assessed at baseline (2004–2006) and follow-up (2010–2012). Dietary intakes were assessed using validated food frequency questionnaires. BMD at the different sites was performed by dual-energy X-ray absorptiometry (DXA). Hybrid-mixed effects regression models were performed to evaluate the associations of interest. ResultsCross-sectional associations were found between fiber intake and higher total hip and femoral neck BMD in women and longitudinal associations with loss of femoral neck BMD in men. An increase in 5% energy intake from carbohydrate was associated with a BMD loss at several site in women and total hip and femoral neck in men. In both sexes, an increase in 5% energy intake of animal protein or fat was associated with a site-specific BMD gain after six years. Substitution analysis showed that the energy intake replacement from fat or carbohydrate by protein had an increase in BMD at different sites in women; while in men, it was only significant when replacing carbohydrate. Substitution of protein or fat by carbohydrates was associated with lower BMD in women, and only protein replacement by carbohydrates in men. ConclusionOur findings suggest that carbohydrate intake was associated with loss of BMD, while animal protein and fat intake was associated with gain of BMD among the Mexican population. Macronutrient substitutions resulted in significant associations; however, additional studies are needed to confirm these findings.

The effects of abaloparatide on hip geometry and biomechanical properties in Japanese osteoporotic patients assessed using DXA-based hip structural analysis: results of the Japanese phase 3 ACTIVE-J trial

SummaryDaily subcutaneous injection of 80 μg abaloparatide increased bone mineral density in Japanese patients with osteoporosis at high fracture risk in the ACTIVE-J trial. Dual-energy X-ray absorptiometry–based hip structural analysis from ACTIVE-J data showed improved hip geometry and biomechanical properties with abaloparatide compared with placebo.PurposeAbaloparatide (ABL) increased bone mineral density (BMD) in Japanese patients with osteoporosis at high fracture risk in the ACTIVE-J trial. To evaluate the effect of ABL on hip geometry and biomechanical properties, hip structural analysis (HSA) was performed using ACTIVE-J trial data.MethodsHip dual-energy X-ray absorptiometry scans from postmenopausal women and men (ABL, n = 128; placebo, n = 65) at baseline and up to week 78 were analyzed to extract bone geometric parameters at the narrow neck (NN), intertrochanteric region (IT), and proximal femoral shaft (FS). Computed tomography (CT)-based BMD and HSA indices were compared between baseline and week 78.ResultsABL treatment showed increased mean percent change from baseline to week 78 in cortical thickness at the NN (5.3%), IT (5.3%), and FS (2.9%); cross-sectional area at the NN (5.0%), IT (5.0%), and FS (2.6%); cross-sectional moment of inertia at the NN (7.6%), IT (5.1%), and FS (2.5%); section modulus at the NN (7.4%), IT (5.4%), and FS (2.4%); and decreased mean percent change in buckling ratio (BR) at the IT (− 5.0%). ABL treatment showed increased mean percent change in total volumetric BMD (vBMD; 2.7%) and trabecular vBMD (3.2%) at the total hip and decreased mean percent change in BR at femoral neck (− 4.1%) at week 78 vs baseline. All the changes noted here were significant vs placebo (P < 0.050 using t-test).ConclusionA 78-week treatment with ABL showed improvement in HSA parameters associated with hip geometry and biomechanical properties vs placebo.Trial registrationJAPIC CTI-173575

Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review

Bone fragility is a complication of type 2 diabetes mellitus (T2DM) that has been identified in recent decades. Trabecular bone score (TBS) appears to be more accurate than bone mineral density (BMD) in diabetic bone disease, particularly in menopausal women with T2DM, to independently capture the fracture risk. Our purpose was to provide the most recent overview on TBS-associated clinical data in T2DM. The core of this narrative review is based on original studies (PubMed-indexed journals, full-length, English articles). The sample-based analysis (n = 11, N = 4653) confirmed the use of TBS in T2DM particularly in females (females/males ratio of 1.9), with ages varying between 35 and 91 (mean 65.34) years. With concern to the study design, apart from the transversal studies, two others were prospective, while another two were case-control. These early-post-pandemic data included studies of various sample sizes, such as: males and females (N of 245, 361, 511, and 2294), only women (N of 80, 96, 104, 243, 493, and 887), and only men (N = 169). Overall, this 21-month study on published data confirmed the prior profile of BMD-TBS in T2DM, while the issue of whether checking the fracture risk is mandatory in adults with uncontrolled T2DM remains to be proven or whether, on the other hand, a reduced TBS might function as a surrogate marker of complicated/uncontrolled T2DM. The interventional approach with bisphosphonates for treating T2DM-associated osteoporosis remains a standard one (n = 2). One control study on 4 mg zoledronic acid showed after 1 year a statistically significant increase of lumbar BMD in both diabetic and non-diabetic groups (+3.6%, p = 0.01 and +6.2%, p = 0.01, respectively). Further studies will pinpoint additive benefits on glucose status of anti-osteoporotic drugs or will confirm if certain glucose-lowering regimes are supplementarily beneficial for fracture risk reduction. The novelty of this literature research: these insights showed once again that the patients with T2DM often have a lower TBS than those without diabetes or with normal glucose levels. Therefore, the decline in TBS may reflect an early stage of bone health impairment in T2DM. The novelty of the TBS as a handy, non-invasive method that proved to be an index of bone microarchitecture confirms its practicality as an easily applicable tool for assessing bone fragility in T2DM.

Meta-Analysis on the Association Between DPP-4 Inhibitors and Bone Mineral Density and Osteoporosis

Background Type 2 Diabetes Mellitus (T2DM) frequently coexists with osteoporosis and reduced bone mineral density (BMD). Dipeptidyl peptidase-4 inhibitors (DPP-4i), a class of antihyperglycemic agents, are commonly employed in T2DM treatment. However, the influence of DPP-4i on bone health remains unclear and debated. This meta-analysis is conducted to explore the relationship between the use of DPP-4i and changes in BMD, as well as the prevalence of osteoporosis among T2DM patients.Methods We conducted a comprehensive search in PubMed, Embase, and Cochrane Library and Web of Science databases for relevant studies published up until June 2023. Studies included in the meta-analysis were those investigating T2DM patients under DPP-4i treatment, and examining the effects on BMD and osteoporosis. Random-effects models and fixed-effect models were utilized to compute the pooled effects. Heterogeneity among the included studies was evaluated using I² statistics.Results This meta-analysis incorporated a total of 10 studies, encompassing a combined population of 214,541 individuals. The results from this meta-analysis indicated an increase in BMD following DPP-4i usage (SMD 0.15, 95 % confidence interval 0.03-0.26). Additionally, the risk of osteoporosis was significantly reduced (OR 0.90, 95 % confidence interval 0.86-0.94) with very low heterogeneity, recorded at 0 % and 53.0 % respectively. No publication bias was detected in the funnel plot, and sensitivity analyses affirmed the stability of the study's conclusions.Conclusion Our results offer valuable insights into the positive impact of DPP-4i on bone health in T2DM patients, contributing to informed clinical decision-making. These findings may inform the development of more comprehensive T2DM management strategies that account for bone health.

Efficacy and safety of alendronic acid in the treatment of osteoporosis in children

Objectivesto describe the efficacy and safety of the off-label use of alendronate in the treatment of osteoporosis in children and adolescents. Methoda retrospective study (2008-2014) of all patients under 18 years who were dispensed alendronate for this indication. The criteria for initiating treatment were: bone mineral density with a Z-score < -2.5 SD, a past history of bone fractures without a previous traumatism, and persistent pain. The variables collected were: demographic, treatment-related, clinical. and safety data. The treatment was considered to be effective when there was an increase in bone mineral density up to a Z-score > -2.5 SD. Resultsa total of 12 patients, 8 of them male, with a mean age of 11 years (± 3 SD), were treated with alendronate. After a mean time of treatment of 2.15 years (± 1.2 SD), there was an increase in bone mineral density in all patients, 9 of which achieved a Z-score > -2.5 SD, so the drug was considered effective in 75% of cases. No patient had bone fractures or expressed adverse effects during treatment. Conclusionsalendronate increased bone mineral density and was well tolerated in all patients, therefore it could be considered as a therapeutic option in the treatment of osteoporosis in children.

Moderate static magnetic field promotes fracture healing and regulates iron metabolism in mice

BackgroundFractures are the most common orthopedic diseases. It is known that static magnetic fields (SMFs) can contribute to the maintenance of bone health. However, the effect and mechanism of SMFs on fracture is still unclear. This study is aim to investigate the effect of moderate static magnetic fields (MMFs) on bone structure and metabolism during fracture healing.MethodsEight-week-old male C57BL/6J mice were subjected to a unilateral open transverse tibial fracture, and following treatment under geomagnetic field (GMF) or MMF. The micro-computed tomography (Micro-CT) and three-point bending were employed to evaluate the microarchitecture and mechanical properties. Endochondral ossification and bone remodeling were evaluated by bone histomorphometric and serum biochemical assay. In addition, the atomic absorption spectroscopy and ELISA were utilized to examine the influence of MMF exposure on iron metabolism in mice.ResultsMMF exposure increased bone mineral density (BMD), bone volume per tissue volume (BV/TV), mechanical properties, and proportion of mineralized bone matrix of the callus during fracture healing. MMF exposure reduced the proportion of cartilage in the callus area during fracture healing. Meanwhile, MMF exposure increased the number of osteoblasts in callus on the 14th day, and reduced the number of osteoclasts on the 28th day of fracture healing. Furthermore, MMF exposure increased PINP and OCN levels, and reduced the TRAP-5b and β-CTX levels in serum. It was also observed that MMF exposure reduced the iron content in the liver and callus, as well as serum ferritin levels while elevating the serum hepcidin concentration.ConclusionsMMF exposure could accelerate fracture healing via promote the endochondral ossification and bone formation while regulating systemic iron metabolism during fracture healing. This study suggests that MMF may have the potential to become a form of physical therapy for fractures.

Coronary artery calcification is associated with smaller increases in femoral neck bone mineral density with anti-resorptive therapy

Abstract Introduction Patients with osteoporosis are at high cardiovascular risk, partly due to vascular calcification, such as in the coronary vessels. It is uncertain if the presence of coronary artery calcification (CAC) effects bone mineral density (BMD) response to anti-resorptive treatment – first line therapy for osteoporosis. We therefore assessed changes in BMD following initiation of anti-resorptive treatment for osteoporosis in patients with and without evidence of CAC. Methods Individuals dispensed at least one prescription for an anti-resorptive medication (bisphosphonates or denosumab) at Monash Health between 2009-2022 were identified. Unique record numbers for these individuals were then cross-matched against the cardiac CT imaging service at Monash Heart (HREC#73603). CAC was detected using a 320-slice CT coronary angiogram (CTCA). We included only those patients having a baseline BMD measurement within two years of CTCA. The annualised percentage change in femoral neck BMD was calculated and adjusted for age, sex, height, weight, and number of years on anti-resorptive treatment. Results 106 individuals were identified of which 85 (women=70 [85%], median age=73 years [interquartile range 64-79 years]) had a follow-up BMD measurement including 19 with, and 66 without, evidence of CAC. Those with CAC were older (76 years versus 64 years, p&amp;lt;0.001). There were 70 bisphosphonate users and 15 denosumab users. Individuals with evidence of CAC experienced, on average, a 1.2% lower increase [(0.345% (0.343 to 0.348) versus -0.881% (-0.883 to -0.879), mean difference -1.226% (-1.493 to -0.959; p&amp;lt;0.05)] in annualised femoral neck BMD with anti-resorptive therapy after adjusting for important clinical risk factors. Interpretation These preliminary data suggests that CTCA-determined CAC may negatively impact femoral neck BMD increases with anti-resorptive therapy. This is perhaps consistent with existing and evolving hypotheses of dysregulatory processes driving ectopic calcium deposition, which we surmise would partially counter the effects of anti-resorptive therapy and potentially manifest as CAC. Thus, of particular interest will be the comparison of cardiovascular outcomes of patients with known CAC with and without anti-resorptive therapy, with the hypothesis that anti-resorptive therapy may potentially have cardioprotective effects in context of CAC. Analysis of the full cohort is underway.Table 1

Bone Mineral Density Derived from Cardiac CT Scans: Using Contrast Enhanced Scans for Opportunistic Screening

Purpose: Osteoporosis is under-diagnosed and often co-exists with other diseases. Very low bone mineral density (BMD) indicates risk of osteoporosis and opportunistic screening for low BMD in CT-scans has been suggested. In a non-contrast enhanced thoracic CT scan, the scan-field-of-view includes vertebrae enabling BMD estimation. However, many CT scans are obtained by administration of contrast material. If the impact of contrast enhancement on BMD measurements could be quantified, considerably more patients are eligible for screening. Methods: This study investigated the impact of intravenous contrast on thoracic BMD measurements in cardiac CT scans pre- and post-contrast, including different contrast trigger levels of 130 and 180 Hounsfield units (HU). BMD was measured using quantitative CT with asynchronous calibration. Results: In 195 participants undergoing cardiac CT (mean age 57±9 years, 37 % females) contrast increased mean thoracic BMD from 116±33 mg/cm3 (non-enhanced CT) to 130±38 mg/cm3 (contrast-enhanced CT) (p<0.001). Using clinical cut-off values for very low (<80 mg/cm3) and low BMD (<120 mg/cm3) showed that 24 % (47/195 participants) were misclassified when BMD was measured on contrast-enhanced CT-scans. Of the misclassified patients, 6 % (12/195 participants) were categorized as having low BMD despite having very low BMD on the non-enhanced images. Contrast-CT using a higher contrast trigger level showed a significant increase in BMD compared to the lower trigger level (119±32 vs. 135±40 mg/cm3, p<0.01). Conclusion: For patients undergoing cardiac CT, using contrast-enhanced images to assess BMD entails substantial overestimation. Contrast protocol trigger levels also affect BMD measurements. Adjusting for these factors is needed before contrast-enhanced images can be used clinically. Mini abstract: Osteoporosis is under-diagnosed. Contrast-enhanced CT made to examine other diseases might be utilized simultaneously for bone mineral density (BMD) screening. These scans, however, likely entails overestimation of BMD due to the effect of contrast. Adjusting for this effect is needed before contrast-enhanced images can be implemented clinically for BMD screening.

Quality improvement initiative to increase bone mineral density screening with DEXA scans among patients receiving aromatase inhibitors or androgen deprivation therapy at an urban safety-net hospital.

468 Background: Patients on aromatase inhibitors (AI) or androgen deprivation therapy (ADT) are at increased risk for osteopenia and osteoporosis. Guidelines recommend baseline and regular bone mineral density (BMD) assessment with dual-energy x-ray absorptiometry (DEXA) scans for these patients. Baseline data for BMD assessment for patients on either AI or ADT at our institution was reviewed and interventions were subsequently developed to improve screening rates. Methods: A retrospective chart review was performed for patients seen in the medical oncology clinic at Denver Health from 2018 through the first 2 quarters of 2020. Patients had a diagnosis of breast cancer or prostate cancer and were prescribed AI or ADT. The review evaluated whether DEXA scans had been ordered for this population. In September 2020, interventions were implemented including: an electronic reminder for ordering providers, education for pharmacists, and education for all nurses who worked in the clinic and the infusion center. Primary care providers who work outside of the oncology clinic were also contacted. An alert in Denver Health’s electronic medical software (EPIC) was launched successfully in September 2020. The alert reminded all providers ordering AI or ADT that a DEXA scan should be performed. The data for DEXA scan monitoring post-intervention was then tracked and measured through the second quarter of 2022. Results: A total of 282 patients were prescribed AI or ADT during the initial retrospective study, out of which 88 had baseline DEXA scans performed, accounting for 31.2% of the patients. After the intervention was implemented in 2020, the rate of DEXA scans performed increased to 44.2% in 2020, 59.4% in 2021 and 54.1% in 2022. The main barriers to the completion of DEXA scans were issues with transportation, multiple appointments leading to patient confusion and time constraints, and health literacy. Conclusions: Although BMD screening remains a very important part of cancer treatment and survivorship, it remains underutilized. In addition to the EPIC alert that was implemented, we are optimistic that continued education and reminders for all clinical staff will help ensure that the utilization of DEXA scans for BMD screening for patient on AI or ADT continues to increase. Community outreach is being planned to provide education about the importance of bone health.

HRQoL Evaluation of Pediatric Osteogenesis Imperfecta with Zoledronic Acid Therapy

Background: Zoledronic acid as bisphosphonates could increase bone mineral density (BMD), which in osteogenesis imperfecta will reduce clinical manifestations. Pediatric patients with osteogenesis imperfecta given zoledronic acid therapy should improve their quality of life.Methods: A retrospective analytic study was conducted on 16 pediatric osteogenesis imperfecta patients who had received intravenous zoledronic acid. Interview using PedsQL 4.0 regarding the condition before and after therapy assessed the quality of life. A paired t-test was used to assess the contrast in each aspect of PedsQL 4.0. Results were expressed as an adjusted odds ratio with a 95% confidence interval. P-value &lt;0.05 is considered statistically significant.Results: A significant increase was found in the child report of social performance (+12.083, p=0.023), and proxy report of physical performance, social performance, and total score of the proxy report (+14.844, p=0.006; +10.625, p=0.010; +10.364, p=0.006). An insignificant increase was found in the child report of physical performance, school performance, and total score of the child report (+8.833, p=0.148; +5.000, p=0.359; +7.065, p=0.115), and proxy report of emotional performance and school performance (+2.500, p=0.669; +6.250, p=0.167). An insignificant decrease was found in child reports of emotional performance (-2.500, p=0.669).Conclusion: After receiving bisphosphonate therapy, pediatric patients with osteogenesis imperfecta experienced an increased quality of life in most aspects within every perception. Physical and social aspects experienced the greatest improvement. Emotional is the aspect that experienced the lowest increase in the child's perception and decreased parent perception of the value of quality of life after bisphosphonate therapy.

Antiresorptive Versus Anabolic Therapy in Managing Osteoporosis in People with Type 1 and Type 2 Diabetes.

Diabetes is characterized by hyperglycemia, but the two main types, type 1 diabetes (T1D) and type 2 diabetes (T2D), have distinct pathophysiology and epidemiological profiles. Individuals with T1D and T2D have an increased risk of fractures, particularly of the hip, upper arm, ankle, and nonvertebral sites. The risk of fractures is higher in T1D compared to T2D. The diagnosis of osteoporosis in individuals with T1D and T2D follows similar criteria as in the general population, but treatment thresholds may differ. Antiresorptive therapies, the first-line treatment for osteoporosis, are effective in individuals with T2D. Observational studies and post hoc analyses of previous trials have indicated that antiresorptive drugs, such as bisphosphonates and selective estrogen receptor modulators, are equally effective in reducing fracture risk and increasing bone mineral density (BMD) in individuals with and without T2D. Denosumab has shown similar effects on vertebral fracture risk but increases the risk of nonvertebral fractures. Considering the low bone turnover observed in T1D and T2D, anabolic therapies, which promote bone formation and resorption, have emerged as a potential treatment option for bone fragility in this population. Data from observational studies and post hoc analyses of previous trials also showed similar results in increasing BMD and reducing the risk of fractures in people with or without T2D. However, no evidence suggests that anabolic therapy has greater efficacy than antiresorptive drugs. In conclusion, there is an increased risk of fractures in T1D and T2D. Reductions in BMD cannot solely explain the relationship between T1D and T2D and fractures. Bone microarchitecture and other factors play a role. Antiresorptive and anabolic therapies have shown efficacy in reducing fracture risk in individuals with T2D, but the evidence is more robust for antiresorptive drugs. Evidence in T1D is scant. Further research is needed to fully understand the underlying mechanisms and optimize management strategies for bone fragility in T1D and T2D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Adrenomedullin has no effect on segmental bone defect healing but increases bone mineral density in rat model.

This study aimed to investigate the effect of adrenomedullin on the healing of the segmental bone defect in a rat model. Thirty-six Wistar rats were randomly divided into 6 groups based on follow-up periods and administered a dose of adrenomedullin hormone. In each group, bilaterally, a 2-mm bone defect was created at the diaphysis of the radius. Sodium chloride solution was administered to sham groups 3 times a week for 4 and 8 weeks intraperitoneally. Adrenomedullin was administered to the study groups 3 times a week: 15 μg-4 weeks, 15 μg-8 weeks, 30 μg-4 weeks, and 30 μg-8 weeks, respectively. After euthanasia, the segmental defects were evaluated by histomorphometric [new bone area (NBA)] and microtomographic [bone volume (BV), bone surface (BS), and bone mineral density (BMD)] analyses. Although the 4- and 8-week 15 μg administered study groups had higher NBA values than the other study and control groups, the histomorphometric analysis did not reveal any statistical difference between the control and study groups regarding NBA (P > .05). In microtomographic analysis, BV was higher in the 15 μg 4-week group than 30 μg 4-week group (296.9 vs. 208.5, P=.003), and BS was lower in the 30 μg 4-week group than in the 4-week control group (695.5 vs. 1334.7, P=.005), but overall, no significant difference was found between the control and study groups (P > .05). Despite these minor differences in histomorphometric and microtomographic criteria indicating new bone formation, the BMD values of the 15 μg 8-week study group showed a significant increase compared with the control group (P=.001, respectively). Adrenomedullin positively affected BMD at 15 μg, but this study could not show healing in the segmental defect site at different dose regimens. Further studies are needed to assess its effects on bone tissue trauma.

Zoledronic Acid Accelerates Bone Healing in Carpal Navicular Fracture via Silencing Long Non-coding RNA Growth Arrest Specificity 5 to Modulate MicroRNA-29a-3p Expression.

Carpal navicular fractures are the most common carpal fractures. This study intends to explore the specific mechanism of Zoledronic Acid (ZA) in carpal navicular fracture healing via long non-coding RNA (lncRNA) growth arrest specificity 5 (GAS5) to mediate microRNA (miR)-29a-3p.A fractured rat model was constructed. Two weeks later, a subcutaneous injection of systemic ZA was implemented, and an injection of plasmid vectors interfered with GAS5 or miR-29a-3p expression was performed on the fracture site. Osteocalcin (OCN) and bone morphogenetic protein-2 (BMP-2) were determined, as well as serum levels of alkaline phosphatase (ALP), osteopontin (OPN) and osteoprotegerin (OPG) and bone mineral density. MC3T3-E1 cells were transfected with plasmid vectors interfering with GAS5 or miR-29a-3p, and cell proliferation and apoptosis were analyzed. GAS5 and miR-29a-3p expression in fractured rats was tested, together with their binding relationship.ZA promoted OCN and BMP-2 expression, increased bone mineral density and serum levels of ALP, OPN and OPG in fractured rats. GAS5 was upregulated and miR-29a-3p was down-regulated in fractured rats. Downregulation of GAS5 or upregulation of miR-29a-3p further promoted bone healing in fractured rats. GAS5 targets miR-29a-3p, and down-regulation of miR-29a-3p can reverse the effect of down-regulation of GAS5 on bone healing in fractured rats. ZA promoted the proliferation of MC3T3-E1 cells and inhibited apoptosis by regulating the GAS5/miR-29a-3p axis.ZA regulates miR-29a-3p expression by down-regulating GAS5 to promote carpal navicular fracture healing, promote MC3T3-E1 cell proliferation, and inhibit cell apoptosis.

Reducing Fracture Risk in Postmenopausal Osteoporosis: a Review of Effective and Safe Pharmacological Therapy Providing Adherence to Treatment

INTRODUCTION. Postmenopausal osteoporosis (PMO) accounts for up to 85 % of all cases of osteoporosis, complications of which — pathological fractures — lead to a decrease in quality of life and functionality, pain, severe psycho-emotional disorders, loss of ability to self-care, disability and an increased risk of death. Timely prescribed pathogenetic therapy for osteoporosis, including in patients undergoing medical rehabilitation, helps reduce the risk of developing osteoporotic fractures and prevent complications associated with them. MAIN CONTENT OF THE REVIEW. The literature review analyzes 5 domestic and 47 foreign literary sources, on the basis of which a description of modern methods of treating PMO is made in order to reduce the risk of developing pathological fractures. Poor patient adherence to osteoporosis therapy is associated with low effectiveness of PMО treatment and an increased financial burden on the healthcare system — increased hospitalization rates and treatment costs. The infrequent dosing frequency and good tolerability of therapy help to increase adherence to oral supplements. CONCLUSION. The review focused on the effectiveness and safety of the oral bisphosphonate ibandronic acid 150 mg once a month, the administration of which to women with PMO demonstrated good tolerability, ease of use and high efficiency, both in reducing the risk of fractures and in increasing bone mineral density, including long-term treatment periods — 5 years.

Flavonoid extract from propolis alleviates periodontitis by boosting periodontium regeneration and inflammation resolution via regulating TLR4/MyD88/NF-κB and RANK/NF-κB pathway

Ethnopharmacological relevanceIn traditional Chinese medicine, propolis has been used for treating oral diseases for centuries, widely. Flavonoid extract is the main active ingredient in propolis, which has attracted extensive attention in recent years. Aim of the studyThe objective and novelty of the current study aims to identify the mechanism of total flavonoid extract of propolis (TFP) for the treatment of periodontitis, and evaluate the therapeutic effect of TFP-loaded liquid crystal hydrogel (TFP-LLC) in rats with periodontitis. MethodsIn this study, we used lipopolysaccharide-stimulated periodontal ligament stem cells (PDLSCs) to construct in vitro inflammation model, and investigated the anti-inflammatory effect of TFP by expression levels of inflammatory factors. Osteogenic differentiation was assessed using alkaline phosphatase activity and alizarin red staining. Meanwhile, the expression of toll like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor-kappa B (NF-κB), receptor activator of NF-κB (RANK) etc, were quantitated to investigate the therapeutic mechanism of TFP. Finally, we constructed TFP-LLC using a self-emulsification method and administered it to rats with periodontitis via periodontal pocket injection to evaluate the therapeutic effects. The therapeutic index, microcomputed tomography (Micro-CT), H&E staining, TRAP staining, and Masson staining were used for this evaluation. ResultsTFP reduced the expression of TLR4, MyD88, NF-κB and inflammatory factor in lipopolysaccharide-stimulated PDLSCs. Meanwhile, TFP simultaneously regulating alkaline phosphatase, RANK, runt-associated transcription factor-2 and matrix metalloproteinase production to accelerate osteogenic differentiation and collagen secretion. In addition, TFP-LLC can stably anchor to the periodontal lesion site and sustainably release TFP. After four weeks of treatment with TFP-LLC, we observed a decrease in the levels of NF-κB and interleukin-1β (IL-1β) in the periodontal tissues of rats, as well as a significant reduction in inflammation in HE staining. Similarly, Micro CT results showed that TFP-LLC could significantly inhibit alveolar bone resorption, increase bone mineral density (BMD) and reduce trabecular bone space (Tb.Sp) in rats with periodontitis. ConclusionCollectively, we have firstly verified the therapeutic effects and mechanisms of TFP in PDLSCs for periodontitis treatment. Our results indicate that TFP perform anti-inflammatory and tissue repair activities through TLR4/MyD88/NF-κB and RANK/NF-κB pathways in PDLSCs. Meanwhile, for the first time, we employed LLC delivery system to load TFP for periodontitis treatment. The results showed that TFP-LLC could be effectively retained in the periodontal pocket and exerted a crucial role in inflammation resolution and periodontal tissue regeneration.

FRI690 Should Treatment For Osteoporosis Be Started In Patients With Primary Hyperparathyroidism Within The First Year After Parathyroidectomy?

Abstract Disclosure: K. Swe: None. A. Chiu: None. E. Pelley: None. Osteoporosis is one of the indications for parathyroidectomy in patients with primary hyperparathyroidism. Studies show the improvement of bone mineral density (BMD) in the lumbar spine and hip within the first year after parathyroidectomy. Therefore, the decision to treat osteoporosis has usually been delayed until a follow-up bone densitometry scan (DXA) at least one year after parathyroidectomy. To study the BMD changes with or without osteoporosis treatment till first follow-up DXA after parathyroidectomy, we retrospectively reviewed a prospective database of patients undergoing parathyroidectomy for primary hyperparathyroidism between 2010 to 2017 at our institution. We included both male and female patients between the ages 50 to 80, with a history of fragility fracture and/ or T score less than -2.4, and normal renal function. We excluded patients with persistent hyperparathyroidism post-surgery, osteoporosis medication within 3 years before surgery, and DXA performed outside of our facility. Patients who received osteoporosis medication between surgery and the first follow-up DXA were compared to those who underwent surgery alone. We compared the changes in BMD at the total hip and lumbar spine (L1-L4) between baseline and the first follow-up DXA for the two groups. Data was evaluated using a student’s t-test. A total of 386 patients underwent parathyroidectomy during the study period of which 92 patients met the inclusion criteria. Among them, 28 patients were treated after surgery and 64 patients had parathyroidectomy alone. The mean duration to treatment initiation after surgery was approximately 4 months (SD +/- 3 months), and the mean duration until the first follow-up DXA after the surgery was 17 months (SD +/- 8 months). There was no difference in the change of BMD at the total hip between two groups. Both increased by 0.01 g/cm2 (p=0.74). However, there was a greater increase in BMD at the lumber spine for those treated (0.047 g/cm2 increase) compared to surgery alone (0.019 g/cm2 increase) (p=0.02). We concluded that initiation of osteoporosis treatment within the first year after parathyroidectomy led to similar BMD outcomes at the total hip, but the treatment group experienced greater gains in BMD at the lumbar spine compared to parathyroidectomy alone, in patients with primary hyperparathyroidism and osteoporosis. Presentation: Friday, June 16, 2023