Osteoporosis-related Fractures Research Articles

Secondary osteoporosis prevention: three-year outcomes from a Fracture Liaison Service in elderly hip fracture patients

BackgroundHip fractures are the most serious fragility fractures due to their associated disability, higher hospitalization costs and high mortality rates. Fracture Liaison Service (FLS) programs have enhanced the management of osteoporosis-related fractures and have shown their clinical effectiveness.AimsTo analyze the effect of the implementation of a FLS model of care over the survival and mortality rates following a hip fracture.MethodsWe conducted a prospective cohort study on patients over 60 years of age who suffered a hip fracture before and after the implementation of the FLS in our center (between January 2016 and December 2019). Patients were followed for three years after the index date. Mortality, complications and refracture rates were compared between the two groups using a Multivariate Cox proportional hazard model.ResultsA total of 1366 patients were included in this study (353 before FLS implementation and 1013 after FLS implementation). Anti-osteoporotic drugs were more frequently prescribed after FLS implementation (79.3% vs 12.5%; p < 0.01) and there was an increase in adherence to treatment (51.7% vs 30.2%; p < 0.01). A total of 413 (40.8%) patients after FLS implementation and 141 (39.9%) individuals before (p = 0.47) died during the three-years follow-up period. A second fracture occurred in 101 (10.0%) patients after FLS implementation and 37 (10.5%) individuals before (p = 0.78). Patients after the implementation of the FLS protocol had a lower all cause one-year mortality [adjusted Hazard Ratio (HR) 0.74 (0.57–0.94)] and a decreased risk of suffering a second osteoporotic fracture [adjusted HR 0.54 (0.39–0.75) in males and adjusted HR 0.46 (0.30–0.71) in females].ConclusionsThe implementation of a FLS protocol was associated with a lower all-cause one-year mortality rate and a higher survivorship in elderly hip fracture patients. However, no three-year mortality rate differences were observed between the two groups. We also found a reduction in the complication and second-fracture rates.

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

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

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

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

Trabecular bone mineral density as measured by thoracic vertebrae predicts incident hip and vertebral fractures: the multi-ethnic study of atherosclerosis.

Osteoporosis affects an enormous number of patients, of all races and both sexes, and its prevalence increases as the population ages. Few studies have evaluated the association between the vertebral trabecular bone mineral density(vBMD) and osteoporosis-related hip fracture in a multiethnic population, and no studies have demonstrated the predictive value of vBMD for fractures. We sought to determine the predictive value of QCT-based trabecular vBMD of thoracic vertebrae derived from coronary artery calcium scan for hip fractures in the Multi-Ethnic Study of Atherosclerosis(MESA), a nationwide multicenter cohort included 6814 people from six medical centers across the USA and assess if low bone density by QCT can predict future fractures. Measures were done using trabecular bone measures, adjusted for individual patients, from three consecutive thoracic vertebrae (BDI Inc, Manhattan Beach CA, USA) from non-contrast cardiac CT scans. Six thousand eight hundred fourteen MESA baseline participants were included with a mean age of 62.2 ± 10.2years, and 52.8% were women. The mean thoracic BMD is 162.6 ± 46.8mg/cm3 (95% CI 161.5, 163.7), and 27.6% of participants (n = 1883) had osteoporosis (T-score 2.5 or lower). Over a median follow-up of 17.4years, Caucasians have a higher rate of vertebral fractures (6.9%), followed by Blacks (4.4%), Hispanics (3.7%), and Chinese (3.0%). Hip fracture patients had a lower baseline vBMD as measured by QCT than the non-hip fracture group by 13.6mg/cm3 [P < 0.001]. The same pattern was seen in the vertebral fracture population, where the mean BMD was substantially lower 18.3mg/cm3 [P < 0.001] than in the non-vertebral fracture population. Notably, the above substantial relationship was unaffected by age, gender, race, BMI, hypertension, current smoking, medication use, or activity. Patients with low trabecular BMD of thoracic vertebrae showed a 1.57-fold greater risk of first hip fracture (HR 1.57, 95% CI 1.38-1.95) and a nearly threefold increased risk of first vertebral fracture (HR 2.93, 95% CI 1.87-4.59) compared to normal BMD patients. There is significant correlation between thoracic trabecular BMD and the incidence of future hip and vertebral fracture. This study demonstrates that thoracic vertebrae BMD, as measured on cardiac CT (QCT), can predict both hip and vertebral fractures without additional radiation, scanning, or patient burden. Osteopenia and osteoporosis are markedly underdiagnosed. Finding occult disease affords the opportunity to treat the millions of people undergoing CT scans every year for other indications.

Different Statin Dosages and Their Effects on Osteoporosis

The aim of the study was to investigate the effect of different doses of statins on the progression of osteoporosis during a 36-month follow-up period. The study included 98 postmenopausal women diagnosed with osteoporosis and the presence of atherosclerosis of lower limb arteries. Patients were divided into 2 groups: women who received statins as part of atherosclerosis treatment (group 1, n=53) and those who did not receive statin therapy for hyperlipidemia (group 2, n=45). After 36 months of follow-up, patients were divided into two groups — with unfavorable (n=42) and favorable (n=56) course of osteoporosis. Progression of osteoporosis was considered unfavorable if during the follow-up period the patients had low traumatic fractures of large bones and/or progressive decrease in bone mineral density (BMD). Depending on the statin dose taken, patients were divided into groups: 1) those taking atorvastatin 20 mg or rosuvastatin 10 mg; 2) those taking atorvastatin 40 mg or rosuvastatin 20 mg. The results revealed a significant association between statin therapy and a favorable course of osteoporosis (OR=0.316, 95% C.I. =0.137-0.727, p=0.003). The use of higher doses of statins (atorvastatin 40 mg or rosuvastatin 20 mg) was associated with the development of low traumatic fractures of large bones and/or progressive decrease in MPC during 36 months of follow-up (OR=3.0, 95% C.I.=1.119-8.040, p=0.030). On the other hand, the use of lower doses of statins (20 mg atorvastatin or 10 mg rosuvastatin) was associated with a favorable course of osteoporosis (OR=0.047, 95% C.I.=0.010-0.212, p=0.030). The dose of statin taken was also moderately negatively correlated with IPC (r=−0.45; p=0.005). Thus, the use of statins for a long period (36 months) in low doses (atorvastatin 20 mg or rosuvastatin 10 mg) is an effective and safe method of treating cardiovascular comorbidities represented by atherosclerosis of lower limb vessels and osteoporosis in postmenopausal women and is characterized by a reduced risk of osteoporosis-related large bone fractures.

Osteoporosis and cement usage in total hip arthroplasty.

Cement usage in total hip arthroplasty (THA) is increasingly common. However, osteoporosis-related fracture risk in cemented vs uncemented THA patients is poorly characterized. We aim to analyze the usage of metabolic bone care and osteoporosis fracture risk in cemented vs uncemented THA patients using FRAX and radiographic bone measurements. Chart review on 250 THA patients was performed retrospectively. Demographics, FRAX scores, hip radiograph measurements, osteoporosis diagnosis, treatment and screening were compared between cemented and uncemented THA patients. Logistic regression model was used to analyze factors influencing cement usage. Cemented THA patients have significantly higher osteoporosis-related fracture risk as measured by FRAX major (20% vs 13%) and FRAX hip (8% vs 5%). There is no significant difference in osteoporosis treatment, vitamin D / calcium supplementation, or metabolic bone disease screening based on patients' cement status. Female sex and rheumatoid arthritis status significantly predict cement usage, but FRAX scores do not predict cement usage. Additionally, 50% (10/20) of patients with Dorr C classification were uncemented. Although some patients undergoing THA with high osteoporosis-related fracture risk were identified and cemented, some risk factors including poor proximal femur shape (by Dorr classification) and poor bone quality (as measured by FRAX score) were potentially overlooked. Cemented patients had an increased risk for fractures but did not receive appropriately increased osteoporosis screening or treatment. III.

Augmentation techniques for the treatment of osteoporosis-associated fractures of the extremities

The current demographic development is leading to an increasing number of cases of osteoporosis-related fractures. Affected individuals are typically part of avulnerable, predominantly geriatric patient group with limited physical resources. Additionally, the pathophysiological characteristics of osteoporotic bones with reduced bone quality and quantity, pose asignificant challenge to the osteosynthesis techniques used. Achieving rapid postoperative mobilization and stable weight-bearing osteosynthesis to prevent postoperative medical complications are the main goals of the surgical management. In recent years augmentation techniques have gained in importance in the treatment of osteoporosis-related fractures by significantly enhancing the stability of osteosyntheses and reducing mechanical complication rates. The main options available are polymethyl methacrylate (PMMA) augmentation and various bioresorbable bone substitute materials with different properties. Implant augmentations can be applied at various locations in the extremity bones and standardized procedures are now available, such as for the proximal humerus and femur. When used correctly, low complication rates and promising clinical outcomes are observed. This article aims to provide an overview of available techniques and applications based on the current literature. Guidelines and substantial scientific evidence are still limited.

Pre-existing osteoporosis and serum vitamin D levels in patients with distal radius fractures: are we missing something?

IntroductionGiven the significant therapeutic gap for osteoporosis, this study aims to investigate the most common osteoporosis-related fracture. The analysis will also consider patients’ serum vitamin D levels and the indications for basic osteoporosis diagnostic tests and osteoporosis therapy prior to fracture.Materials and methodsThis prospective clinical trial included patients with distal radius fractures who underwent surgery at our hospital between 1 April 2021 and 7 April 2022. Blood samples were taken from all participants and existing risk factors for osteoporosis were recorded. In addition, the indication for a guideline-based osteoporosis diagnosis was assessed and the risk of another future fracture with FRAX® was calculated. This information was used to decide whether there was an indication for specific osteoporosis therapy.ResultsA diagnosis gap of 53% and a treatment gap of 84% were identified among the 102 patients investigated. The patients’ ages ranged from 46 to 91 years, with an average vitamin D level of 57 nmol/l, which was below the recommended level of 75 nmol/l. It was noted on a monthly basis that the vitamin D level (without substitution) never exceeded the recommended value of 75 nmol/l in any month. Three-quarters of patients had indications for a baseline osteoporosis diagnosis, yet less than 50% received one. According to FRAX® data, 57% of patients had indications for specific osteoporosis treatment before experiencing the fracture.ConclusionEven without a previous distal radius fracture, many patients are in need of osteoporosis diagnosis or treatment. Our research suggests that patients with distal radius fractures should have their vitamin D levels checked via a blood test and be evaluated for osteoporosis. As endogenous vitamin D levels are often inadequate, year-round vitamin D supplementation should be considered for the prevention of osteomalacia and as a basis for the treatment of osteoporosis.German clinical trial register IDDRKS00028085.

Blood cadmium is associated with increased fracture risk in never-smokers - results from a case-control study using data from the Malmö Diet and Cancer cohort

BackgroundSeveral studies have shown associations between cadmium (Cd) exposure and an increased risk of fractures. However, the size of the risk is still unclear and proper adjustment for smoking is a challenge. The aim of this study was to quantify the association between dietary cadmium measured in blood and fracture risk in the general Swedish population through a large population-based case-control study in never-smokers. MethodsThe study included 2113 incident cases with osteoporosis-related fractures and the same number of age- and sex-matched controls in never-smokers from the Swedish population-based Malmö Diet and Cancer study cohort. Cd in blood (B-Cd) was analyzed at baseline (1991–1996). Incident osteoporosis-related fractures (of the hip, distal radius, and proximal humerus) up to the year 2014 were identified using the National Patient Register. Associations between B-Cd and fractures were analyzed using logistic regression. ResultsMedian B-Cd was 0.22 μg/L (P25 = 0.16, P75 = 0.31) among 2103 cases and 0.21 (P25 = 0.15, P75 = 0.30) among 2105 controls. The risk of fracture was significantly increased (OR 1.58; 95 % confidence interval 1.08–2.31, per μg/L of B-Cd), after adjustment for age, sex, BMI, physical activity, and fiber consumption. In analyses by cadmium quartiles, the OR increased monotonically and was significant in the highest quartile of B-Cd (for B-Cd > 0.31 versus B-Cd < 0.15 μg/L; OR 1.21; 95 % confidence interval 1.01–1.45). ConclusionEven modestly increased blood cadmium in never-smokers is associated with increased risk of incident osteoporosis-related fractures.

Proportion of Hidden Vertebral Fractures Among Egyptian Males With Fragility Hip Fractures in the Emergency Room of Ain Shams University Hospitals.

Background Fragility fractures are linked to significant costs for society as well as significant pain and suffering, disability, and even death. It is well-recognized that osteoporosis-related fragility fractures raise the risk of subsequent fragility fractures. One of the most frequent osteoporotic fractures brought on by low bone mineral density and other risk factors is vertebral fractures. Considering that most vertebral fractures are asymptomatic and not clinically identified, proactive screening could stop additional impairment. Objective The current study aims to determine the prevalence and risk factors of hidden vertebral fractures in Egyptian males who have fragility hip fractures. Patients and methods A cross-sectional case-control study examining the correlation of risk factors between cases (fragility hip fracture and vertebral fractures) and a control group (fragility hip fracture without vertebral fracture) was carried out from September 2020 to September 2021 on patients visiting the orthopedic emergency department of a university hospital in Cairo, Egypt. Males who presented to the emergency room (ER) with fragility hip fractures and were 40 years of age or older met our inclusion criteria. For every patient who presented with a fragility hip fracture, standard lateral and anteroposterior radiographs of the dorso-lumbar spine were taken. Results A total of 43,935 patients visited the orthopedic emergency room (ER) throughout the study period; 13,034 of those patients were men, accounting for 29.7% of all orthopedic ER visits. Our inclusion criteria for fragility hip fractures were met by 132 male participants. The screening lumbosacral plain X-rays identified 27 (20.5%) of the 132 patients as having concomitant vertebral fractures in addition to the fragility hip fractures. Concomitant hidden vertebral fractures among Egyptian males with other fragility fractures, particularly fragility hip fractures, are predicted by the number of co-morbid diseases, hypertension, and continuous use of steroids and anti-epileptics. Conclusion Most fragility fractures are avoidable. Because one fragility fracture increases the likelihood of others, early detection is crucial. To prevent complications and mortality, it is important to identify and manage individuals who have a fragility hip fracture as they frequently have concurrent hidden vertebral fractures. Predictive risk factors for fragility vertebral fractures include hypertension, the number of concomitant illnesses, and chronic drugs (anti-epileptics and steroids).

Higher-intensity ultrasound accelerates fracture healing via mechanosensitive ion channel Piezo1.

Osteoporosis-related fractures are a major public health problem. Mechanobiological stimulation utilizing low-intensity pulsed ultrasound (LIPUS) is the most widely accepted modality for accelerating fracture healing. However, recent evidence has demonstrated the ineffectiveness of LIPUS, and the biophysical mechanisms of ultrasound-induced bone formation also remain elusive. Here, we demonstrate that ultrasound at a higher intensity than LIPUS effectively accelerates fracture healing in a mouse osteoporotic fracture model. Higher-intensity ultrasound promoted chondrogenesis and hypertrophic differentiation of chondrocytes in the fracture callus. Higher-intensity ultrasound also increased osteoblasts and newly formed bone in the callus, resulting in accelerated endochondral ossification during fracture healing. In addition, we found that accelerated fracture healing by ultrasound exposure was attenuated when the mechanosensitive ion channel Piezo1 was inhibited by GsMTx4. Ultrasound-induced new bone formation in the callus was attenuated in fractured mice treated with GsMTx4. Similar results were also confirmed in a 3D osteocyte-osteoblast co-culture system, where osteocytic Piezo1 knockdown attenuated the expression of osteoblastic genes after ultrasound exposure. Together these results demonstrate that higher-intensity ultrasound than clinically used LIPUS can accelerate endochondral ossification after fractures. Furthermore, our results suggest that mechanotransduction via Piezo1 mediates ultrasound-stimulated fracture healing and bone formation.

Musculoskeletal and Psychological Rehabilitation.

Although it has long been believed that stress has a detrimental effect on health and the risk of disease, little research has been done on the precise mechanisms by which this happens. The literature produced by past workers suggests many possibly intersecting mechanistic pathways that might be useful for future fundamental and clinical study. Exercise has been thoroughly researched as a non-pharmacologic strategy to increase bone mass. Many evidence-based treatment recommendations for patients suffering from osteoporosis-related fractures, potential courses of care, and rehabilitation concur that multidisciplinary therapy would be the most beneficial. Older and recent articles about musculoskeletal and psychological rehabilitation in the management of osteoporosis published in prominent and reputed journals are reviewed. Important and interesting information from some of the cross-references is also included. Opinions and impressions from the experience of treating osteoporosis are added while describing various aspects of psychological and physical rehabilitation. The recent evidence, reviewed here, also indicates the possibility of cross-effects between osteoporosis and psychological issues. A multi-factorial and personalised strategy should be explored for improved outcomes in patients under psychological stress, particularly those at increased risk of osteoporosis development. Reviewing current publications, the objectives of rehabilitation are evolving based on the disease's stage. For example, during the initial stage of a vertebral body collapse, the patient is treated with bracing, physical therapy, education, local and systemic analgesics, and a brief period of bed rest. The need to mobilise the patient carefully and safely along with a mix of medical care, dietary supplements, rehabilitation, and instructions to facilitate daily living activities, are endorsed to manage post-fracture osteoporosis. This chapter is not to make treatment advice, but rather to outline potential connections between psychological stress and low bone density and to emphasise potential multi-system consequences of pharmaceutical therapies. The goal is to enhance activities of daily living, which will increase safety, minimise falls, and maintain bone mass. Osteoporosis and fragility fractures can be prevented and managed with regular medical check-ups, daily exercise and yoga, a healthy diet, fall prevention measures,recreational groupactivities, supportive medications, control ofcomorbidities, use of assistivedevices, and customised rehabilitation programmes.

Biologics: Teriparatide and Newer Anabolics.

The landscape of osteoporosis management has evolved significantly over the years, witnessing a paradigm shift from conventional therapies to the emergence of biologic agents. This chapter delves into the intricate mechanisms, potential applications, and future directions of biologic interventions in osteoporosis care. Biologic agents, with their targeted approach to bone health, have revolutionized the field by offering precision-driven strategies that address the underlying mechanisms of bone fragility. This chapter explores the mechanisms of action of various biologics, including Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) inhibitors, monoclonal antibodies targeting sclerostin, parathyroid hormone (PTH) analogues, and cathepsin K inhibitors. It discusses their potential benefits, limitations, and safety considerations, while shedding light on the promise of combination therapies that merge biologic agents with traditional approaches. Furthermore, the chapter delves into the potential applications of biologic agents in specific patient populations, the role of biomarkers in predicting treatment responses, and the influence of emerging biological targets. It also explores the advancements in novel targets and drug delivery systems that aim to enhance treatment convenience and effectiveness. By tailoring treatments based on patient characteristics and exploring novel therapeutic targets, the chapter envisions a future of precision medicine in osteoporosis care. As research continues to evolve, the chapter anticipates a transformative impact on bone health outcomes, fracture prevention, and overall quality of life for individuals at risk of osteoporosis-related fractures. Through comprehensive insights into the mechanisms, applications, and future directions of biologic agents, this chapter offers a holistic perspective on the evolving landscape of osteoporosis management.

Study of acute toxicity of a new drug “AOS” for the treatment of osteoporosis.

Background. Osteoporosis is one of the most common diseases, which, along with myocardial infarction, stroke, cancer, and sudden death, occupies a leading place in the structure of morbidity and mortality of the population. Postmenopausal women are most vulnerable and are approximately 4 times more likely to be affected than men (80 % of all patients), and osteoporosis-related fractures are responsible for a significant increase in morbidity, disability, and mortality, especially in the elderly.Objective. To study the acute toxicity of the new drug “Antiosteoporosis drug” (patent No. 02-04-16643/15-0 dated February 26, 2015) with a single intragastric administration to mature outbred rats of both sexes.Design and methods. The study was conducted on outbred rats of both sexes according to protocol OECD 420, GOST 32296-2013. The development of a toxic effect was concluded based on behavioral tests, clinical examinations, changes in body weight, the results of pathomorphological examination of organ tissue and biochemical parameters of blood and urine.Results. According to the results of the study, the tested drug was classified according to the active substance into category 5 according to the GHS classification (2000&lt;LD50 (i/g)&lt;5000 mg/kg). An assessment of the dynamics of body weight in experimental animals showed that a single intragastric administration of the test drug had no effect on this indicator. The study of individual behavior as part of the main study on the 14th day after a single intragastric administration of the test drug showed that a single intragastric administration of the test drug at a dose of 2000 mg/kg did not have a delayed effect on the general condition and indicative research activity of experimental animals. Autopsy and pathological examination of animals on the 15th day after a single intragastric administration of the test drug did not reveal the presence of any residual effects associated with the administration of the test drug. The tested drug did not have a local irritant effect on the injection site — the gastrointestinal tract. In all tests, the degree of change in indicators caused by the test drug was the same: there were no statistically significant differences in the recorded parameters between the test drug and the control group.

Pathodynamics.

Osteoporosis and osteoporosis-related fractures in the aging population are becoming a health care problem and a burden on health service resources available. Osteoporosis is a systemic skeletal disorder that results from an imbalance in bone remodeling, leading to a reduction in bone strength with microarchitectural disruption and skeletal fragility, increasing fracture susceptibility. Osteoporosis is considered a well-known metabolic bone disorder. Although its prevalence is more commonly seen in women than men, it is eventually seen in both genders. In the elderly population, there is an increase in disability and mortality due to osteoporotic fractures.

Site-activatable targeting of macromolecular alendronate for accelerated fracture healing

ABSTRACTSustainable social activity is a major goal in an aging society, although this is limited by loss of athleticism, with osteoporosis-related fractures being the most common cause of long-term behavioral restrictions in older people. Therefore, the development of therapeutics that shorten the duration of fracture therapy is essential to improve the quality of life and social activity of older individuals. In this study, we developed a polyethylene glycol-modified alendronate (PEG-ALN) that can efficiently deliver the active ingredient (ALN) to fracture sites. PEG-ALN released ALN in response to an acidic pH and was systemically administered to mice in a fracture model. PEG-ALN exhibited selective accumulation at the fracture site and significantly accelerated bone healing compared to free ALN. This study highlights the utility of a simple polymer modification of ALN as a systemically injectable medicine for patients with bone fractures.

Fusion of electronic health records and radiographic images for a multimodal deep learning prediction model of atypical femur fractures

Atypical femur fractures (AFF) represent a very rare type of fracture that can be difficult to discriminate radiologically from normal femur fractures (NFF). AFFs are associated with drugs that are administered to prevent osteoporosis-related fragility fractures, which are highly prevalent in the elderly population. Given that these fractures are rare and the radiologic changes are subtle currently only 7% of AFFs are correctly identified, which hinders adequate treatment for most patients with AFF. Deep learning models could be trained to classify automatically a fracture as AFF or NFF, thereby assisting radiologists in detecting these rare fractures. Historically, for this classification task, only imaging data have been used, using convolutional neural networks (CNN) or vision transformers applied to radiographs. However, to mimic situations in which all available data are used to arrive at a diagnosis, we adopted an approach of deep learning that is based on the integration of image data and tabular data (from electronic health records) for 159 patients with AFF and 914 patients with NFF. We hypothesized that the combinatorial data, compiled from all the radiology departments of 72 hospitals in Sweden and the Swedish National Patient Register, would improve classification accuracy, as compared to using only one modality. At the patient level, the area under the ROC curve (AUC) increased from 0.966 to 0.987 when using the integrated set of imaging data and seven pre-selected variables, as compared to only using imaging data. More importantly, the sensitivity increased from 0.796 to 0.903. We found a greater impact of data fusion when only a randomly selected subset of available images was used to make the image and tabular data more balanced for each patient. The AUC then increased from 0.949 to 0.984, and the sensitivity increased from 0.727 to 0.849.These AUC improvements are not large, mainly because of the already excellent performance of the CNN (AUC of 0.966) when only images are used. However, the improvement is clinically highly relevant considering the importance of accuracy in medical diagnostics. We expect an even greater effect when imaging data from a clinical workflow, comprising a more diverse set of diagnostic images, are used.

Male Osteoporosis and Frailty.

It is estimated that 50% women and 20% of men over the age of 50 years will have an osteoporosis-related fracture in their remaining life. Although, Osteoporosis is generally thought to be a disease affecting females, more than a third of hip fractures occur in males due to reduced bone strength. Along with Osteoporosis, the other pathological process which occurs simultaneously is Sarcopenia. It is defined as age-related atrophy of skeletal muscle mass that reduces muscle strength, function, and quality of life. This chapter discusses the various aspects of the disease process in the males including its classification, clinical features, diagnosis and treatment.

Understanding Osteoporosis: Human Bone Density, Genetic Mechanisms, Gut Microbiota, and Future Prospects.

Osteoporosis is a systemic condition of the skeleton that leads to diminished bone mass, a breakdown in the bone tissue's microscopic architecture, and an elevated risk of breaking a bone. The elderly and women particularly after menopause are disproportionately affected, and the condition generally stays undiagnosed until a broken bone causes severe pain and immobility. Causes of osteoporosis include low bone mass, more than normal bone loss, changes in hormone levels (decreased estrogen or testosterone), certain diseases and therapies, and lifestyle factors like smoking and inactivity. The spine, hip, and forearm are particularly vulnerable to osteoporosis-related fractures. The purpose of this article is to present a thorough understanding of osteoporosis, including the disease's connection to bone density in humans, and the major part played by genetic pathways and gut flora. The causes of osteoporosis, the effects of aging on bone density, and why some groups experience a higher incidence of the disease than others are investigated. The paper also includes animal and human experiments investigating the link between gut flora and osteoporosis. Finally, it looks to the future and speculates on possible developments in osteoporosis prevention and therapy.

Daidzein alleviates osteoporosis by promoting osteogenesis and angiogenesis coupling.

Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target. Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis. Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs. This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason.