Bone Fracture Rates Research Articles

Поражение костей у взрослых пациентов с болезнью Гоше I типа: распространенность, клинические особенности, костно-суставные осложнения и проблемы инвалидизации

BACKGROUND. Although highly effective enzyme replacement therapy (ERT) for Gaucher disease (GD) is accessible and affordable, orthopedic issues in patients appear often to be the main factor leading to their disability. Bone lesions are essentially observed in 100 % of GD patients. The nature and severity of bone and joint changes, however, are reported to be extremely heterogeneous, whereas their incidence and clinical features have until now remained underresearched. AIM. To assess the incidence and clinical value of bone and joint lesions which complicate the course of GD type 1 with bone involvement. MATERIALS & METHODS. This trial enrolled 267 GD type 1 patients aged 17–85 years (median 38 years), who were followed-up at the National Research Center for Hematology from 2004 to 2024. There were 109 men and 158 women. The analysis focused on the following MRI findings: bone marrow infiltration (BMI), Barnett-Nordin cortical index (BNI), bone deformity, osteolytic and osteonecrotic lesions, as well as orthopedic pathologies progressing to disability. RESULTS. BMI was identified in 213/267 (79.8 %) patients. Erlenmeyer flask-like femoral expansion was observed in 95 % patients (n = 254). The mean BNI was 42.9 % (the normal BNI in adult population exceeds 45 %). Low BNI values were associated with osteolytic lesions, disability, and BMI. No significant association of decreased BNI was seen with osteonecroses. The incidence of osteolytic lesions was 11.2 % (n = 30). New osteolytic lesions were reported neither in ERT nor in substrate reduction therapy recipients. Medullary osteonecrosis was detected in 206/267 (77.15 %) patients, and epiphyseal osteonecrosis was identified in 74/267 (27.72 %) patients. Along with osteonecroses, in contrast to osteolytic manifestations, new lesions (n = 8) were reported to occur under long-term (> 5 years) ERT. The rate of bone fractures was 6.7 % (n = 18). In 18 patients, 64 fractures were observed at various locations. Disability associated with bone and joint complications of GD occurred in 58/267 (21.72 %) patients. After reconstructive surgery, including total articular replacement arthroplasties, 37 patients achieved complete functional recovery. CONCLUSION. Bone changes are essentially observed in all adult patients with GD type 1. However, clinical severity and disability of patients depend on secondary bone and joint complications, among them arthroses resulting from epiphyseal osteonecrosis, pathologic fractures, bone and joint infections. These complications developing on effective ERT were identified in 67/267 patients, which accounted for 25 %.

Efficacy of a single 5mg zoledronic acid infusion in preventing bone loss and fracture in postmenopausal women with breast cancer.

Chemotherapy-induced bone loss (CTIBL) is common among breast cancer patients, requiring comprehensive assessment and intervention. Zoledronic acid, a strong inhibitor of bone resorption, is effective in CTIBL management, though information on dosing and intervals, particularly the efficacy of the 5mg annual dose for osteoporosis in breast cancer patients, is limited. In this 12-month prospective observational study, 85 breast cancer patients were divided into three groups: 17 received no treatment, 17 received tamoxifen, and 51 received anastrozole or letrozole (AI). Post-surgery, patients were administered a single 5mg dose of zoledronic acid and monitored over 12months for changes in bone mineral density (BMD), fracture rates, and biochemical markers. Initially, the AI group was the oldest, averaging 59.1 ± 8.7years. At baseline, no significant differences in variables, except age, were observed. After 12months, BMD increased in all groups following a single zoledronic acid dose, with the smallest increase in the AI group at the lumbar spine: no treatment (2.4% ± 6.1%), tamoxifen (2.6% ± 3.4%), AI (0.6% ± 14.5%) (p = 0.778). CTx and P1NP levels were consistently suppressed up to 12months post-treatment, with smaller reductions in the AI group. There were no significant differences in fracture or bone metastasis rates among groups. A single infusion of 5mg zoledronic acid was effective in increasing bone density in breast cancer patients. However, AI-treated patients showed less improvement in vertebral bone mineral density and biochemical markers. Further long-term studies with larger cohorts are needed.

Clinical Efficacy of Zoledronic Acid on Fracture Reduction in Youth with Primary and Secondary Skeletal Fragility.

Prior studies have demonstrated the safety and efficacy of zoledronic acid (ZA) to increase bone mineral density (BMD) in children. By contrast, the efficacy of ZA on fractures in the pediatric population remains uncertain. To investigate the effect of ZA on fracture rate in a clinical cohort of children and young adults with skeletal fragility. Retrospective cohort study. Academic medical center. 102 individuals (65 males; 39 with primary and 63 with secondary skeletal fragility) ages 0-21 years old treated with ZA for skeletal fragility between 2010 and 2017. ZA was prescribed at discretion of the treating clinician using a standardized protocol. The primary outcome was change in annualized fracture rate. Secondary outcomes included long bone and spine fracture rates. Areal BMD was analyzed in a subset of individuals with dual energy X-ray absorptiometry (DXA) scans. The overall median fracture rate decreased from 0.6 (IQR: 0.3-1.1) to 0 (IQR: 0-0.4) fractures per year, p<0.001, over a median treatment duration of 1.8 (IQR:0.6-3.0) years. Significant reductions in fracture rate were observed in both primary [1.0 (IQR: 0.6-1.5) to 0.3 (IQR: 0-0.6)] and secondary [0.5 (IQR: 0.1-0.8) to 0 (IQR: 0-0.3)] forms of skeletal fragility, p<0.001 for both. Significant reductions in fracture rate persisted when limited to long bone or long bone plus spine fractures. ZA treatment as a component of clinical care was associated with significant declines in fracture rate in this cohort of children and young adults with skeletal fragility.

Effects of Metabolic Dysfunction-Associated Steatotic Liver Disease on Bone Density and Fragility Fractures: Associations and Mechanisms.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has profound adverse effects on bone health and homeostasis. MASLD appears to be associated with changes in bone mineral density (BMD) and fracture rate. However, the data are ambiguous and conflicting. Although several studies have shown that children and adolescents with MASLD have decreased BMD, the data on the prevalence of fragility fractures among children are scarce. In adults, increasing evidence suggests that MASLD decreases BMD and increases the risk of fragility fractures, which appears to be due to deterioration of bone architecture in addition to a decrease in BMD. Effects of MASLD on bone health may also be age- and race-specific. MASLD does not seem to increase fracture risk in children and adolescents but increases the risk of fractures in elderly men, especially those of Asian origin. From a mechanistic perspective, bone remodeling is a continuous process between osteoblasts (bone-forming) and osteoclasts (bone-resorbing), with any imbalance resulting in metabolic bone disease. In individuals with MASLD, loss of anabolic insulin receptor signaling (insulin resistance) in osteoblasts and increased receptor activator of nuclear factor κB (RANK)/RANK ligand signaling in osteoclasts (proinflammatory cytokines) swings the pendulum toward accelerated bone loss. These processes are further complicated by the concomitant presence of obesity, type 2 diabetes mellitus, or sarcopenia in individuals with MASLD. This study reviews the current literature associated with the effects of MASLD on BMD and fragility fractures in children/adolescents and adults. This review also discusses the pathomechanisms that link MASLD with changes in BMD and fragility fractures.

Significant Interaction between Melatonin and Titanium Bone Implants: Available Evidence and Future Research Directions.

The trend in the incidence rate of bone fractures has been upward and as a result, the burden associated with orthopedic fractures has increased significantly. Titanium (Ti) implants are considered a preferred method of managing long bone fractures. However, no benefit comes without some downside, and using Ti implants is associated with several complications. In this respect, it was observed that in bones, Ti can disrupt the bone healing process by disturbing the balance of osteoclast and osteoblast activation and also increasing the production of inflammatory cytokines. Melatonin is a widely-acting molecule that possesses strong anti-oxidant features. This molecule reinforces mineral density and improves bone formation processes. In this review, we focused on the protective effect of melatonin in mitigating the Ti-related complications.

#495 Effect of Vit D supplementation on bone mineral density in haemodialysis patients. A comparative study

Abstract Background and Aims Low serum 25(OH) vit D levels are usually observed in haemodialysis patients. In this population, vit D deficiency is associated with secondary hyperparathyroidism (SHPT) and low bone mineral density (BMD). Although, vit D supplements are routinely prescribed in haemodialysis patients, their exact role in preventing bone loss hasn't been studied thoroughly. The primary aim of this study was to estimate the effect of cholecalciferol (vit D3) use on BMD changes of haemodialysis patients. Secondary aim was to evaluate how parathyroid hormone (PTH), phosphorus and calcium levels are affected by vit D3 supplementation. Method Twelve (12) haemodialysis patients with low levels of serum vit D were included. All of them had their bone density measured with Dual - Energy X-Ray Absorptionmetry (DXA). The study population was then divided in two groups. Half of them (6 patients) received oral cholecarciferol (study group) and the rest continued with their standard treatment (control group). Initial dose of cholecalciferol was 25000 iu weekly and titrated upwards until 25 (OH) vit D levels were reaching 20 ng/ml. Then, cholecarciferol was continued in maintenance dose to keep vit D levels between 20 and 40 ng/ml. Thirty (30) months later, DXA was repeated in all patients. BMD in total hip region was evaluated. During the study period, phosphorus, calcium and PTH levels were measured monthly while 25 (OH) vit D levels were measured every three months. Results Patients’ mean age was 61.9 (±8.8) years. There were no differences in age, initial BMD, PTH or vit D levels between the two groups. Overall, initial mean vit D value was 8.5 ng/ml. At the end of the study, vit D levels had increased to 23.6 ng/ml in the study group while remaining unchanged in the control group. At the beginning of the study, mean BMD in the whole population was 0.742 gr/cm3 and it decreased by 0.042 gr/cm3 after 30 months. No differences in BMD change were observed between the two groups (ΔBMD was −0.057 versus -0.029 gr/cm3 in the study and control group respectively, p = 0.12). PTH levels were reduced in the study group and increased in the control group but the observed difference was not significant (p = 0.11). Phosphorus and calcium levels were not affected by vit D supplementation. Of note, three fractures were observed in the study group and one in the control group during the study period. Conclusion Vit D3 supplementation didn't seem to affect the rate of bone loss in haemodialysis patients, at least in the doses received and levels of 25 (OH) achieved above. Its exact effect in PTH levels as well as in the rate of bone fractures needs to be verified by larger studies.

Facial Trauma Affects the Radiological Diagnosis of Nasal Bone Fractures.

Timely and accurate diagnosis of nasal bone fractures (NBFs) is crucial for preserving the cosmetic and functional aspects of the nose. This study aims to identify factors influencing radiographic and computed tomography (CT) diagnosis of NBF in patients with nasal trauma. Two hundred six patients with acute nasal trauma underwent both conventional radiography and facial bone CT. An experienced otorhinolaryngologist independently interpreted images. Results were categorized into "Concordance" or "Discrepancy" groups, with demographic and clinical data compared. The study classified 167 patients into "Concordance" and 39 into "Discrepancy" groups based on radiography and CT interpretations. The "discrepancy group" showed higher rates of previous nasal bone fractures (P=0.044), rhinoplasty history (P=0.044), and concomitant facial bone fractures (P=0.001). Adjusted odds ratios revealed significant associations between discrepancies and a history of nasal bone fracture (OR=5.197, 95% CI 1.165-23.171), rhinoplasty (OR=6.114, 95% CI 1.393-26.847), and concomitant facial bone fractures (OR=3.765, 95% CI 1.663-8.523). This study highlights the impact of facial trauma, including rhinoplasty, on the radiological diagnosis of NBF. Consequently, in the presence of signs of concurrent facial trauma, previous nasal trauma, or rhinoplasty history, a prompt CT scan and comprehensive evaluation are recommended for accurate diagnosis and timely treatment, ultimately improving the patient's prognosis.

Bone Density Screening, Treatment and Fracture Rates in Allogeneic Hematopoietic Cell Transplant Patients

Bone Density Screening, Treatment and Fracture Rates in Allogeneic Hematopoietic Cell Transplant Patients

National Trends and Clinical Outcomes after Scooter Injury in the US: 2016 to 2020.

In recent years, the adoption of electric scooters has been accompanied by a surge of scooter-related injuries in the US, raising concerns for their severity and associated healthcare costs. This study aimed to assess temporal trends and outcomes of scooter-related hospital admissions compared with bicycle-related hospitalizations. This was a retrospective cohort study using the 2016 to 2020 National Inpatient Sample for patients younger than 65 years who were hospitalized after bicycle- and scooter-related injuries. The Trauma Mortality Prediction Model was used to quantify injury severity. The primary outcomes of interest were temporal trends of micromobility injuries. In-hospital mortality, rates of long bone fracture, traumatic brain injury, paralysis, length of stay, hospitalization costs, and nonhome discharge were secondarily assessed. Among 92,815 patients included in the study, 6,125 (6.6%) had scooter-related injuries. Compared with patients with bicycle-related injuries, patients with scooter-related injuries were more commonly younger than 18 years (26.7% vs 16.4%, p < 0.001) and frequently underwent major operations (55.8% vs 48.1%, p < 0.001). After risk adjustment, scooter-related injuries were associated with greater risks of long bone fracture (adjusted odds ratio 1.40, 95% CI 1.15 to 1.70) and paralysis (adjusted odds ratio 2.06, 95% CI 1.16 to 3.69) compared with bicycle-related injuries. Additionally, patients with bicycle- or scooter-related injuries had comparable index hospitalization durations of stay and costs. The prevalence and severity of scooter-related injuries have significantly increased in the US, thereby attributing to a substantial cost burden on the healthcare system. Multidisciplinary efforts to inform safety policies and enact targeted interventions are warranted to reduce scooter-related injuries.

THU452 Polyostotic Fibrous Dysplasia Complicated By Aneurysmal Bone Cyst In A Patient With McCune-Albright Syndrome

Abstract Disclosure: E. Milazzo: None. K.L. Hermayer: None. Introduction: McCune-Albright Syndrome (MAS) is a rare mosaic disorder with GNAS mutations, encoding the alpha-subunit of the Gs G-coupled protein receptor, activating it, and inappropriately producing cAMP. The hyperfunctioning endocrinopathies associated with MAS are due to signaling through the TSH, LH, FSH, GHRH, and ACTH receptors. MAS clinical presentation occurs with café-au-lait skin macules, precocious puberty, and fibrous dysplasia (FD) of the bone. FD is a benign tumor that leads to increased rates of bone fractures and if it causes facial deformities, can be complicated with orbital neuropathies. An aneurysmal bone cyst (ABC) is a blood-filled cyst that can be a primary or secondary lesion due to co-existing lesions. ABC is a rare complication of FD. We report a rare case of ABC in a MAS patient who presented with acute visual disturbance and enlargement of the forehead and was successfully treated with surgery. Clinical Case: A 20-year-old female diagnosed with MAS at the age of 2 who had precocious puberty by the 3rd year of life and developed polyostotic FD in the right arm, left femur, cranial, and skull bones with multiple long bone fractures by the age of 5-6 and required numerous orthopedic surgeries. She presented with the characteristic café-au-lait skin macules on the back and right arm. In 2018, a slow decline of left eye vision required left cranial decompression of the optic nerve, with pathology showing fibrous tissue compatible with FD. In 2021, she complained of acute right forehead enlargement, compressing her right eye with blurry vision. An MRI showed FD involving the facial and skull bones with a new expansible lesion in the right frontal bone with internal layering fluid, exerting a mild mass effect on the frontal lobe and extending superiorly to the orbit with inferior displacement of the globe. These findings were consistent with an ABC. Right frontal craniectomy and cranioplasty were performed in 12/2021, with pathology showing a fibrous pseudocyst wall with associated lymphoplasmacytic inflammation and evidence of prior hemorrhage with Ki-67 in the cyst wall at 15%. Lab work showed chronic alkaline phosphatase elevation at 567IU/L (42-106IU/L), normal calcium at 9.2mg/dl (8.4-10.3mg/dl), phosphate at 3.3mg/dl (3.3-5.1mg/dl), and PTH at 26pg/ml (15-65mg/dl), with Vitamin D insufficiency at 25.1ng/ml (30-100ng/ml). Endocrinology workup was negative for thyroid, adrenal, gonadotrophic, and GH dysfunction. 5 months post-surgery, the patient demonstrated complete recovery, and MRI showed no recurrence of the ABC. Conclusion: ABC is a benign solitary tumor generally arising from the metaphysis of long bones and rarely involves the cranium. ABC associated with FD has only been reported in a few cases. The treatment is surgical excision, with radiation and cryotherapy used in nonorbital cases. Presentation: Thursday, June 15, 2023

A retrospective comparative study of maxillofacial injury patterns caused by electric scooters and bicycles.

The emergence of shared stand-up electric scooters has led to an increase in their usage and, subsequently, an increase in the incidence of maxillofacial trauma. This study aimed to investigate the trauma pattern associated with the use of stand-up electric scooters compared with that related to the use of bicycles, which was a popular mode of personal mobility before the emergence of stand-up electric scooters. This study investigated the medical records of patients who visited Wonju Christian Hospital for maxillofacial trauma due to the use of stand-up electric scooter and bicycles between November 1, 2017 and October 31, 2022. Maxillofacial trauma was analyzed based on medical records, including those in the evaluation results of teeth, maxillofacial bones, and soft tissues. Crown fractures and tooth avulsions were observed more frequently with the use of stand-up electric scooters than with the use of bicycles. In contrast, crown-root fractures, tooth subluxation, and extrusive luxation were more commonly observed in bicycle riders. Additionally, the proportion of root fractures was similar between the two groups. However, no vertical root fractures were observed in patients who rode bicycles. The maxillofacial bone fracture rates between the two groups were similar, although the fracture patterns were different. The number of patients using stand-up electric scooters is increasing, and they are likely to have a worse prognosis compared with those using existing personal mobility devices.

Renal protection and safety of sodium-glucose cotransporter-2 inhibitors in chronic kidney disease.

Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose cotransporter 2 inhibitors), a class of anti-diabetic medications, is shown to reduce cardiovascular and renal events. This systematic review and meta-analysis aimed to assess whether SGLT2i could become a new treatment strategy for CKD for its renal protection and safety. Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3. Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group. SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.

Pioglitazone reduces cardiovascular events and dementia but increases bone fracture in elderly patients with type 2 diabetes mellitus: a national cohort study.

The prevalence of type 2 diabetes (T2DM) in elderly people has expanded rapidly. Considering cognitive impairment and being prone to hypoglycemia of the elder, the pros and cons of oral hypoglycemic agents (OHA) should be reassessed in this population. Pioglitazone might be appropriate for elderly DM patients because of its insulin-sensitizing effect and low risk of hypoglycemia. By using Taiwan's National Health Insurance Research Database, 191,937 types 2 diabetes patients aged ≥65 years under treatment between 2005 and 2013 were identified and further divided into two groups according to whether they received pioglitazone (pioglitazone group) or other OHAs (non-pioglitazone group) in the 3 months preceding their first outpatient visit date after 65 years of age, with a diagnosis of T2DM. Propensity score stabilization weight (PSSW) was used to balance the baseline characteristics. In results, the pioglitazone group (n = 17,388) exhibited a lower rate (per person-years) of major advanced cardiovascular events MACCE (2.76% vs. 3.03%, hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.87-0.95), new- diagnosis dementia (1.32% vs. 1.46%, HR: 0.91, 95% CI: 0.84-0.98) but a higher rate of new-diagnosis bone fractures (5.37% vs. 4.47%, HR: 1.24, 95% CI: 1.19-1.28) than the non-pioglitazone group (n = 174,549). In conclusion, using pioglitazone may reduce the risks of MACCE and dementia but increases the probability of bone fractures in the elderly DM population.

Metformin promotes osteogenic differentiation and prevents hyperglycaemia-induced osteoporosis by suppressing PPARγ expression.

Metformin can prevent hyperglycaemia-induced osteoporosis and decrease the bone fracture rate, but the mechanism has not been fully elucidated. To reveal the mechanism by which metformin affects hyperglycaemia-induced osteoporosis, we treat a mouse osteoporosis cell model with metformin and find that osteoblast mineralization increases and PPARγ expression decreases. Single-cell mRNA sequencing analysis show that PPARγ is highly expressed in the bone tissue of osteoporosis patients, which highlights the role of PPARγ in osteoporosis. Furthermore, we find that PPARγ is the effector through which metformin prevents osteoporosis. We further examine the mechanism of PPARγ regulation and reveal that metformin regulates PPARγ expression through the AMPK pathway and that PPARγ affects osteoblasts through the endoplasmic reticulum stress (ERS) pathway. Moreover, we verify the association between the effect of metformin on bone metabolism and the expression of PPARγ in high-fat diet-induced diabetic rats. Thus, we identify and functionally validate that metformin prevents hyperglycaemia-induced osteoporosis by regulating the AMPK-PPARγ-ERS axis.

Comparison of Bisphosphonates Versus Teriparatide in Therapy of the Glucocorticoid-Induced Osteoporosis (GIOP): A Meta-Analysis of Randomized Controlled Trials.

Osteoporosis (OP) is characterized as decreased bone mineral density (BMD) and increased risk of bone fracture. Secondary OP resulting from excess endogenous or exogenous glucocorticoid is defined as glucocorticoid-induced osteoporosis (GIOP). Current therapeutic strategies for GIOP are similar to menopausal osteoporosis, including calcium and vitamin D supplementation, bisphosphonates, and parathyroid hormone (PTH) analogues (teriparatide). Previously, several published meta-analyses compared anti-osteoporotic agents for the menopausal or aging-dependent OP. However, the physiopathologic bone metabolism of GIOP is different. In this study, we investigated the efficacy of BMD enhancement, bone fracture rate and safety of bisphosphonates versus teriparatide in the therapy of GIOP. We searched databases including PubMed, Embase, and the Cochrane Library until Jan 2023, and selected ten random clinical trials (RCT)s that compared the efficacy and/or safety of bisphosphonate versus teriparatide for GIOP patients. Teriparatide therapy increased lumber spinal BMD by 3.96% (95% CI 3.01-4.9%, p<0.00001), 1.23% (95% CI 0.36-2.1%, p=0.006) at total hip, and 1.45% (95% CI 0.31-2.58%, p=0.01) at femoral neck, respectively, compared to bisphosphonates at 18-month therapy for GIOP. Teriparatide also reduced bone fracture especially in vertebral bone (p=0.0001, RR 6.27, 95% CI 2.44-16.07), and increased bone formation and resorption marker levels. There was no difference in the incidence of adverse effects in bisphosphonate and teriparatide groups. Teriparatide showed better performance over bisphosphonate in BMD enhancement, bone fracture reduction, and bone remodeling improvement, without increasing the incidence of adverse effects.

Macrophage-Targeted Dextran Sulfate-Dexamethasone Conjugate Micelles for Effective Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic immune disease that causes joint affection and even disability. Activated macrophages play an important role in the pathogenesis and progression of RA by producing pro-inflammatory factors. The use of dexamethasone (DXM) is effective in relieving the intractable pain and inflammatory progression of RA. However, long-term use of DXM is strongly associated with increased rates of diabetes, osteoporosis, bone fractures, and mortality, which hinders its clinical use. In this study, the dextran sulfate-cisaconitic anhydride-dexamethasone (DXM@DS-cad-DXM) micelles were prepared to treat RA by selectively recognizing scavenger receptor (SR) on the activated macrophages. The potent targeting property of DXM@DS-cad-DXM micelles to SR was by fluorescence microscope. Additionally, the effective accumulation and powerful anti-inflammatory activity of DXM@DS-cad-DXM micelles were observed in the inflamed joints of adjuvant-induced arthritis (AIA) rats after intravenous administration. Overall, DXM@DS-cad-DXM micelles are a potentially effective nanomedicine for targeted therapy of RA.

Maintaining bone health by estrogen therapy in patients with advanced prostate cancer: a narrative review.

The purpose of androgen deprivation therapy (ADT) in prostate cancer (PCa), using luteinizing hormone-releasing hormone agonists (LHRHa) or gonadotrophin-releasing hormone antagonists, is to suppress the levels of testosterone. Since testosterone is the precursor of estradiol (E2), one of the major undesired effects of ADT is the concomitant loss of E2, causing among others an increased bone turnover and bone loss and an increased risk of osteoporosis and fractures. Therefore, the guidelines for ADT indicate to combine ADT routinely with bone-sparing agents such as bisphosphonates, denosumab or selective estrogen receptor modulators. However, these compounds may have side effects and some require inconvenient parenteral administration. Co-treatment with estrogens is an alternative approach to prevent bone loss and at the same time, to avoid other side effects caused by the loss of estrogens, which is the topic explored in the present narrative review. Estrogens investigated in PCa patients include parenteral or transdermal E2, diethylstilbestrol (DES), and ethinylestradiol (EE) as monotherapy, or high-dose estetrol (HDE4) combined with ADT. Cardiovascular adverse events have been reported with parenteral E2, DES and EE. Encouraging effects on bone parameters have been obtained with transdermal E2 (tE2) and HDE4, in the tE2 development program (PATCH study), and in the LHRHa/HDE4 co-treatment study (PCombi), respectively. Confirmation of the beneficial effects of estrogen therapy with tE2 or HDE4 on bone health in patients with advanced PCa is needed, with special emphasis on bone mass and fracture rate.

Protective effect of isoflavone enriched soy β-conglycinin on osteoporosis in ovariectomized rats.

Research shows that the consumption of soybean foods can reduce the incidence rate of bone fractures in women after menopause. The aim of this study was to investigate the effects of different complex of soy β-conglycinin (7S) and isoflavones (7S-ISO) on osteoporosis in ovariectomized rats. All treatments were administrated intragastrically to the groups every afternoon for 3 months. The treatments were administrated at 1mL·(100 g)-1 , the animals were given 50 mg·kg-1 ·d-1 ISO, and the concentration of protein was about 2wt. %. The bone mineral density (BMD) and the bone biomechanics results of left tibia' maximum load in the 7S-ISO group is significantly higher than in the ovariectomized group and the 7S group (p < .05). Otherwise, the serum tartrate-resistant acid phosphatase (s-TRACP), serum osteocalcin (s-BGP), and serum estradiol (s-E2 ) levels in 7S-ISO were all significantly different from the OVX, OVX + casein, and the OVX + 7S group (p < .05). The serum calcium (s-Ca) level was not significantly different among all the groups. 7S-ISO may exhibit moderate estrogenic activities and as compared to 7S and ISO in osteoporosis (OP) of ovariectomized rats. PRACTICAL APPLICATIONS: The effects of soy proteins on the health of females have always been a concern. It has been extensively reported soy 7S globulin (7S) as a type of trimer glycoprotein can depress blood fats. The aim of this study was to investigate the effects of different complex of soy β-conglycinin and isoflavones (ISO), the main storage proteins and polyphenols in soy, on osteoporosis in ovariectomized rats.

Markers of bone metabolism are associated in all-cause mortality in heart failure with reduced ejection fraction

Abstract Background In patients with heart failure an increased risk of fracture-related mortality has been reported. A growing body of evidence suggests that, heart failure (HF) itself may be related to disturbances in bone metabolism, but the exact mechanism remains unclear. In patients with HF previous studies indicated a loss of renal function and alterations in bone micro-architecture, but the clinical relevance remains unclear. Purpose We aimed to evaluate the association between markers of bone metabolism with mortality and pro-brain natriuretic peptide (proBNP) in patients with HF with reduced ejection fraction (HFrEF). Methods We analysed participants of a prospective cohort study of patients referred to coronary angiography (CA). The baseline examination was performed at a tertiary care centre in Germany. Indications for CA were based on clinical routine. For the current analysis only patients with HFrEF were included. Patients were selected based on echocardiographic left ventricular (LV)-EF≤40%, symptoms of heart failure and elevated proBNP concentrations, as recommended by current clinical guidelines. We estimated the risk associated with parathyroid hormone (PTH), osteocalcin (OC), beta-crosslaps (βCL) and alkaline phosphatase (AP) and all-cause mortality using Cox proportional hazard models. Adjustments for demographic and clinical characteristics from the index hospital presentation were used as covariates. We included all individuals who had complete data for all variables in the study in our primary analysis. Additionally, we used linear regression analysis to investigate the correlation between proBNP and its association with PTH, OC, βCL and AP. Results A total of 297 participants (63.9±9.9 years; 17.9% females) were included in the analysis. Median follow-up was 10 years. Median LV-EF was 35%, median New York Heart Association functional class was 2 (IQR=1–3), mean pulmonary capillary wedge pressure was 15.3±7.4 mmHg and median proBNP levels of 2282 (IQR 1875–3758) ng/ml. Participants had in 42.3% multi-vessel atherosclerotic CAD (with stenosis of ≥50% considered diagnostic) with 66.4% had a previous myocardial infarction. In multivariate cox proportionate hazard models OC, βCL and AP were statistically significant associated with an increased risk for all-cause mortality (hazard ratio (HR)=1.6 [95% CI 1.2–2.2], HR=1.8 [95% CI 1.1–2.9] and HR=2.1 [95% CI 1.5–2.9], respectively). In multivariate analysis proBNP was associated with PTH (β-coefficient = 0.076; P≤0.001), AP (β-coefficient = 0.125; P=0.001) and βCL (β-coefficient = 0.062; P=0.046), but not with osteocalcin (β-coefficient = −0.055; P=0.145). Conclusion In patients with HFrEF markers of bone metabolism were significantly associated with mortality and proBNP concentrations. Future studies should focus on different aspects of bone metabolism, fracture rates and fracture related mortality in patients with different stages of heart failure. Funding Acknowledgement Type of funding sources: None.

Identification of Diagnostic Genes and Effective Drugs Associated with Osteoporosis Treatment by Single-Cell RNA-Seq Analysis and Network Pharmacology.

Background Osteoporosis is a common bone metabolic disease with increased bone fragility and fracture rate. Effective diagnosis and treatment of osteoporosis still need to be explored due to the increasing incidence of disease. Methods Single-cell RNA-seq was acquired from GSE147287 dataset. Osteoporosis-related genes were obtained from chEMBL. Cell subpopulations were identified and characterized by scRNA-seq, t-SNE, clusterProfiler, and other computational methods. “limma” R packages were used to identify all differentially expressed genes. A diagnosis model was build using rms R packages. Key drugs were determined by proteins-proteins interaction and molecular docking. Results Firstly, 15,577 cells were obtained, and 12 cell subpopulations were identified by clustering, among which 6 cell subpopulations belong to CD45+ BM-MSCs and the other subpopulations were CD45-BM-MSCs. CD45- BM-MSCs_6 and CD45+ BM-MSCs_5 were consider as key subpopulations. Furthermore, we found 7 genes were correlated with above two subpopulations, and F9 gene had highest AUC. Finally, five compounds were identified, among which DB03742 bound well to F9 protein. Conclusions This work discovered that 7 genes were correlated with CD45-BM-MSCs_6 and CD45+ BM-MSCs_5 subpopulations in osteoporosis, among which F9 gene had better research value. Moreover, compound DB03742 was a potential inhibitor of F9 protein.