High Risk Of Fracture Research Articles

Facile fabrication of phosphazene-quercetin-alendronate composites as pH-responsive bone-targeted nanomedicine for osteoporosis treatment

Osteoporosis, closely related to age, is characterized by impaired bone mass and bone strength, damage of bone microstructure, resulting in a higher risk of fractures with minimal trauma, especially in the hip and spine. Quercetin (Que), a natural compound, has previously demonstrated its potential anti-osteoporosis effects via promoting bone formation and anti-bone resorption. However, Que is poor water solubility, lack of bone targeting, and requires high concentration to exert its therapeutic effects. In this work, a pH-responsive and bone-targeted nanomedicine HCCP-Que-PEG-ALN (HQPA) was developed via using hexachlorocyclotriphosphazene(HCCP) as the cross-linkage, Que, alendronate (ALN), and amino-polyethylene glycol (NH2-PEG) as other building blocks. We demonstrated that HQPA can form spherical nanoparticles in aqueous solution with average size of 158.3 ± 59.8 nm with high drug loading capacity of Que (31.4 w/w%) and obvious bone-targeting capability. in vitro experimental results indicated that HQPA NPs have dual anti-osteoporosis effects of promoting osteoblasts and inhibiting osteoclasts. Furthermore, HQPA NPs can effectively reduce the bone loss in OVX mice with low toxicity to major organs. We believe that this method should be a general and useful route for fabrication of bone-targeted natural-compounds-based nanomedicines for treatment different bone-related diseases.

Review of recommendations for bisphosphonate treatment interruption-discontinuation

Bisphosphonates are the main medications in the treatment of osteoporosis, which are effective in reducing the risk of fractures in patients with osteoporosis. It is known that after treatment with bisphosphonates, bone mineral density remains quite stable for a certain time, as well as markers of bone metabolism remain reduced, which, along with the side effects of long-term bisphosphonate therapy, determines the possibility of “Drug holidays”. At the same time, during a break in bisphosphonate treatment, the risk of fractures begins to increase, which is a reason to resume therapy.Currently, there is no uniform worldwide data of starting a “drug holidays” on bisphosphonates. The duration of the “drug holidays” also differs in clinical recommendations from different countries. When to conduct a risk assessment of fractures during a “drug holidays”? To answer these questions, we assessed existing clinical recommendations for treatment interruption/discontinuation of bisphosphonates. A literature search was conducted using the following resources: PubMed®, the Cochrane Library, websites of major international osteoporosis associations, and other targeted Internet searches. The main search terms were “Clinical Guideline of Osteoporosis”, “Bisphosphonates”, “Drug holidays in osteoporosis”, “Discontinuation of bisphosphonates”. Тhe search was carried out using articles in Russian and English published between January 1, 2016 and September 15, 2023. 17 clinical guidelines from different countries (Russian, American, European, Asian and Australian) were found and analyzed in which was information about the break in the treatment and withdrawal of bisphosphonates.The majority of clinical recommendations have the same opinion on the issue of starting “drug holidays”: with a moderate risk of fractures, you can take a break from treatment with tableted bisphosphonates after 5 years, after zoledronic acid — after 3 years of therapy. At high and very high risk of fractures, the duration of treatment is 10 and 6 years, respectively. The duration of “drug holidays” vary in the recommendations, but in most cases the decision-making is based not on the duration, but on the assessment of the risk of fractures with their regular reassessment, which includes previous and new low-energy fractures, the emergence of new risk factors, a decrease in BMD, the dynamics of bone markers, re-evalua­tion of FRAX®.

Fractured cervical spine, dissected vertebral artery, and life-threatening stroke: A challenging case report and literature review

IntroductionVertebral artery injury (VAI) following blunt trauma can lead to acute or delayed life-threatening posterior fossa ischemic stroke. Its management raises controversial issues and is still open to debate. Material & methodWe report the case of a 48-year-old male who presented a life-threatening posterior circulation ischemic stroke, secondary to a vertebral artery dissection caused by a cervical spine fracture. This case was successfully managed through intravenous thrombolysis and endovascular thrombectomy followed by antiplatelet therapy and an anterior cervical discectomy and fusion. At the one-year follow-up, the patient had no persisting deficit and was back working as a policeman. ConclusionRapid management of patients with dramatic clinical presentation can lead to full recovery. Implications include a systematic screening of blunt trauma VAI through computed tomography angiography when dealing with high-risk cervical spine fractures; patients harboring both a cervical spine fracture and a VAI must be transferred to a tertiary referral hospital able to deal both with strokes and cervical spine surgery to ensure responsiveness in case of stroke.

An emergency department-based system intervention to improve osteoporosis screening for older adults at high-risk of fracture

Abstract Falls and osteoporosis are risk factors for fragility fractures. Bone mineral density (BMD) assessment is associated with better preventative osteoporosis care, but it is underutilized by those at high fracture risk. We created a novel electronic medical record (EMR) alert-driven protocol to screen patients in the emergency department (ED) for fracture risk and tested its feasibility and effectiveness in generating and completing referrals for outpatient BMD testing after discharge. The EMR alert was configured in two tertiary-care EDs and triggered by the term “fall” in the chief complaint, age (≥65 years for women, ≥70 years for men), and high fall risk (Morse score ≥ 45). The alert electronically notified ED study staff of potentially eligible patients. Participants received osteoporosis screening education and had BMD testing ordered. From November 15, 2020 to December 4, 2021, there were 2608 EMR alerts among 2509 patients. We identified 558 patients at high-risk of fracture who were screened for BMD testing referral. Participants were excluded for: serious illness (N = 141), no documented health insurance to cover BMD testing (N = 97), prior BMD testing/recent osteoporosis care (N = 58), research assistant unavailable to enroll (N = 53), concomitant fracture (N = 43), bedridden status (N = 38), chief complaint of fall documented in error (N = 38), long-term care residence (N = 34), participation refusal (N = 32), or hospitalization (N = 3). Of the 16 participants who had BMD testing ordered, 7 scheduled and 5 completed BMD testing. EMR alerts can help identify subpopulations who may benefit from osteoporosis screening, but there are significant barriers to identifying eligible and willing patients for screening in the ED. In our study targeting an innovative venue for osteoporosis care delivery, only about 1% of patients at high-risk of fracture scheduled BMD testing after an ED visit. Adequate resources during and after an ED visit are needed to ensure that older adults participate in preventative osteoporosis care.

Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength.

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156-0.366]) vs non-diabetic subjects 0.352% [0.269-0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46-30.10] vs non-diabetic subjects 76.24 MPa [26.81-132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p<0.0001), and GSK3B (p=0.0456) were higher, while collagen (COL1A1) was lower in T2D (p=0.0482). AGEs content was associated with SOST and WNT5A (r=0.9231, p<0.0001; r=0.6751, p=0.0322), but inversely correlated with LEF-1 and COL1A1 (r=-0.7500, p=0.0255; r=-0.9762, p=0.0004). SOST was associated with glycemic control and disease duration (r=0.4846, p=0.0043; r=0.7107, p=0.00174), whereas WNT5A and GSK3B were only correlated with glycemic control (r=0.5589, p=0.0037; r=0.4901, p=0.0051). Finally, Young's modulus was negatively correlated with SOST (r=-0.5675, p=0.0011), AXIN2 (r=-0.5523, p=0.0042), and SFRP5 (r=-0.4442, p=0.0437), while positively correlated with LEF-1 (r=0.4116, p=0.0295) and WNT10B (r=0.6697, p=0.0001). These findings suggest that Wnt signaling and AGEs could be the main determinants of bone fragility in T2D.

Bone canonical Wnt signaling is downregulated in type 2 diabetes and associates with higher advanced glycation end-products (AGEs) content and reduced bone strength

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156–0.366]) vs non-diabetic subjects 0.352% [0.269–0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46–30.10] vs non-diabetic subjects 76.24 MPa [26.81–132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p&lt;0.0001), and GSK3B (p=0.0456) were higher, while collagen (COL1A1) was lower in T2D (p=0.0482). AGEs content was associated with SOST and WNT5A (r=0.9231, p&lt;0.0001; r=0.6751, p=0.0322), but inversely correlated with LEF-1 and COL1A1 (r=–0.7500, p=0.0255; r=–0.9762, p=0.0004). SOST was associated with glycemic control and disease duration (r=0.4846, p=0.0043; r=0.7107, p=0.00174), whereas WNT5A and GSK3B were only correlated with glycemic control (r=0.5589, p=0.0037; r=0.4901, p=0.0051). Finally, Young’s modulus was negatively correlated with SOST (r=−0.5675, p=0.0011), AXIN2 (r=−0.5523, p=0.0042), and SFRP5 (r=−0.4442, p=0.0437), while positively correlated with LEF-1 (r=0.4116, p=0.0295) and WNT10B (r=0.6697, p=0.0001). These findings suggest that Wnt signaling and AGEs could be the main determinants of bone fragility in T2D.

Deciphering the complex relationship between type 2 diabetes and fracture risk with both genetic and observational evidence.

The 'diabetic bone paradox' suggested that type 2 diabetes (T2D) patients would have higher areal bone mineral density (BMD) but higher fracture risk than individuals without T2D. In this study, we found that the genetically predicted T2D was associated with higher BMD and lower risk of fracture in both weighted genetic risk score (wGRS) and two-sample Mendelian randomization (MR) analyses. We also identified ten genomic loci shared between T2D and fracture, with the top signal at SNP rs4580892 in the intron of gene RSPO3. And the higher expression in adipose subcutaneous and higher protein level in plasma of RSPO3 were associated with increased risk of T2D, but decreased risk of fracture. In the prospective study, T2D was observed to be associated with higher risk of fracture, but BMI mediated 30.2% of the protective effect. However, when stratified by the T2D-related risk factors for fracture, we observed that the effect of T2D on the risk of fracture decreased when the number of T2D-related risk factors decreased, and the association became non-significant if the T2D patients carried none of the risk factors. In conclusion, the genetically determined T2D might not be associated with higher risk of fracture. And the shared genetic architecture between T2D and fracture suggested a top signal around RSPO3 gene. The observed effect size of T2D on fracture risk decreased if the T2D-related risk factors could be eliminated. Therefore, it is important to manage the complications of T2D to prevent the risk of fracture.

Deciphering the complex relationship between type 2 diabetes and fracture risk with both genetic and observational evidence

The ‘diabetic bone paradox’ suggested that type 2 diabetes (T2D) patients would have higher areal bone mineral density (BMD) but higher fracture risk than individuals without T2D. In this study, we found that the genetically predicted T2D was associated with higher BMD and lower risk of fracture in both weighted genetic risk score (wGRS) and two-sample Mendelian randomization (MR) analyses. We also identified ten genomic loci shared between T2D and fracture, with the top signal at SNP rs4580892 in the intron of gene RSPO3. And the higher expression in adipose subcutaneous and higher protein level in plasma of RSPO3 were associated with increased risk of T2D, but decreased risk of fracture. In the prospective study, T2D was observed to be associated with higher risk of fracture, but BMI mediated 30.2% of the protective effect. However, when stratified by the T2D-related risk factors for fracture, we observed that the effect of T2D on the risk of fracture decreased when the number of T2D-related risk factors decreased, and the association became non-significant if the T2D patients carried none of the risk factors. In conclusion, the genetically determined T2D might not be associated with higher risk of fracture. And the shared genetic architecture between T2D and fracture suggested a top signal around RSPO3 gene. The observed effect size of T2D on fracture risk decreased if the T2D-related risk factors could be eliminated. Therefore, it is important to manage the complications of T2D to prevent the risk of fracture.

Risk of fracture among patients with spinal cord injury: A nationwide cohort study in South Korea

BackgroundClinical concerns about preventing and managing fractures after spinal cord injury (SCI) have been growing. ObjectiveThis study investigates the risk of fractures among SCI patients according to the presence of disability, disease severity, and level of injury. MethodsWe performed a retrospective cohort study using the Korean National Health Insurance Service (KNHIS 2010–2018) database. We included 5190 SCI patients and 1:3 age- and sex-matched control participants. The primary outcome was fracture, and the cohort was followed until December 31, 2019. ResultsSCI patients had a higher fracture risk than the matched controls (adjusted hazard ratio [aHR] 1.33, 95 % CI 1.16–1.54). The risk of fracture was higher in the presence of disability (aHR 1.57, 95 % CI 1.19–2.07), especially among patients with severe disability (aHR 1.65, 95 % CI 1.05–2.60). Higher fracture risks were observed among SCI patients regardless of injury level, but statistical significance was found only with cervical-level injury. When we considered site-specific fractures, vertebral (aHR 1.31, 95 % CI 1.04–1.64) and hip fracture risks (aHR 2.04, 95 % CI 1.39–2.98) were both higher among SCI patients than the controls. SCI patients with disability and cervical-level injury showed the highest hip fracture risk (aHR 3.67, 95 % CI 1.90–7.07). ConclusionsCompared with the controls, SCI patients were at higher risk of any fracture, particularly hip fracture, especially those with disability and cervical-level injury. Clinicians should be aware of the fracture risk among SCI patients to provide proper management.

Cost-effectiveness of romosozumab for the treatment of postmenopausal women with osteoporosis at high risk of fracture in Belgium

SummaryThis study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium.PurposeThis study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021.MethodsA Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed.ResultsRomosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis.ConclusionSequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

The role of the primary care physician in identifying patients at high risk of fractures in real clinical practice

BACKGROUND: The FRAX calculator is an accessible method for identifying patients at high risk of fracture. However, data on its practical use in primary health care settings are limited.&#x0D; AIM: To evaluate the correctness of calculating the 10-year fracture probability according to FRAX by primary care physicians and then analyze the impact of the results on patient routing.&#x0D; MATERIALS AND METHODS: The base of the study was the city polyclinic No. 25 of the Nevsky district of Saint Petersburg. The study included men and women aged 40 years and older.&#x0D; During 2017–2020, polyclinic doctors assessed the risk of fracture using the FRAX calculator for 11,013 people. A group of patients with significant differences (30% or more) in the obtained value of the risk of major osteoporotic fractures from the average was identified. A 10-year probability of fractures was recalculated for these patients.&#x0D; RESULTS: Major osteoporotic fracture risk scores were compared before and after recalculation. In most cases of patients (83%), the risk category did not change after recalculation. In 15% of patients changed to a higher risk. In the total group (11,013 people), errors in FRAX calculation led to an underestimation of high fracture risk in 41 patients (0.4%).&#x0D; CONCLUSIONS: The study showed that primary care physicians use the FRAX calculator correctly. The proportion of incorrect fracture risk calculations was low. Nevertheless, training of primary care physicians in the calculation and interpretation of the FRAX score is essential.

Decomposing and simplifying the Fracture Risk Assessment Tool-a module from the Taiwan-specific calculator.

The Fracture Risk Assessment Tool (FRAX®) is a widely utilized country-specific calculator for identifying individuals with high fracture risk; its score is calculated from 12 variables, but its formulation is not publicly disclosed. We aimed to decompose and simplify the FRAX® by utilizing a nationwide community survey database as a reference module for creating a local assessment tool for osteoporotic fracture community screening in any country. Participants (n = 16384; predominantly women (75%); mean age = 64.8years) were enrolled from the Taiwan OsteoPorosis Survey, a nationwide cross-sectional community survey collected from 2008 to 2011. We identified 11 clinical risk factors from the health questionnaires. BMD was assessed via dual-energy X-ray absorptiometry in a mobile DXA vehicle, and 10-year fracture risk scores, including major osteoporotic fracture (MOF) and hip fracture (HF) risk scores, were calculated using the FRAX®. The mean femoral neck BMD was 0.7 ± 0.1g/cm2, the T-score was -1.9 ± 1.2, the MOF was 8.9 ± 7.1%, and the HF was 3.2 ± 4.7%. Following FRAX® decomposition with multiple linear regression, the adjusted R2 values were 0.9206 for MOF and 0.9376 for HF when BMD was included and 0.9538 for MOF and 0.9554 for HF when BMD was excluded. The FRAX® demonstrated better prediction for women and younger individuals than for men and elderly individuals after sex and age stratification analysis. Excluding femoral neck BMD, age, sex, and previous fractures emerged as 3 primary clinical risk factors for simplified FRAX® according to the decision tree analysis in this study population. The adjusted R2 values for the simplified country-specific FRAX® incorporating 3 premier clinical risk factors were 0.8210 for MOF and 0.8528 for HF. After decomposition, the newly simplified module provides a straightforward formulation for estimating 10-year fracture risk, even without femoral neck BMD, making it suitable for community or clinical osteoporotic fracture risk screening.

The role of the psychological attributes of parents and children, and fracture history in upper extremity fractures in school-age and adolescents: A case-control study.

This study aims to investigate the influence of parents and children's psychological attributes and previous fracture history on upper extremity fractures in school-aged and adolescent children. Between January 2022 and January 2023, a total of 194 participants consisting of 97 cases with upper extremity fractures (23 males, 74 females; median age: 10 years; range, 6 to 16 years) and 97 age-matched controls suffering from growing pains (47 males, 50 females; median age: 10 years; range, 6 to 16 years) were included in this case-control study. Both cases and controls were of school-age or over. The parents of the children were interviewed face-to-face using psychological scales including the Adult Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS), the Autism-Spectrum Quotient (AQ), the Short Form of the Conners' Parent Rating Scale-Revised (CPRS-R:S), and the Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07). The results derived from these scales and the demographics of the participants were evaluated in terms of their association with the risk of upper extremity fractures. A household income below the official minimum monthly wage (MMW) and a previous fracture history showed a higher risk for upper extremity fractures (odds ratio [OR]=2.38, 95% confidence interval [CI]: 1.07-5.26 and OR=24.93, 95% CI: 3.27-189.98, respectively). In the univariate analyses, elevated scores on the hyperactivity subscale of CPRS-R:S (CPRS-R:SHS) were associated with a higher fracture risk (OR=1.14, 95% CI: 1.05-1.24). Furthermore, both a household income below MMW, a previous fracture history, and higher CPRS-R:S-HS scores were found as independent risk factors for upper extremity fractures in the multivariate regression analysis (OR=2.78, 95% CI: 1.13-6.86, OR=21.79, 95% CI: 2.73-174.03), and OR=1.11, 95% CI: 1.02-1.22, respectively). Our study results highlight the importance of known risk factors for upper extremity fractures such as lower monthly wage and the presence of previous fractures. The psychological states of parents and children should be evaluated together.

Construction and verification of risk prediction model of osteoporotic fractures in patients with osteoporosis in China.

To explore the influencing factors of osteoporotic fractures (OPF) in patients with osteoporosis, construct a prediction model, and verify the model internally and externally, so as to provide reference for early screening and intervention of OPF in patients with osteoporosis. Osteoporosis patients in the First Affiliated Hospital of Soochow University were selected, and the medical records of patients were consulted through the Hospital Information System (HIS) and the data management platform of osteoporosis patients, so as to screen patients who met the criteria for admission and discharge and collect data. SPSS 26.0 software was used for single factor analysis to screen statistically significant variables (p < 0.05). The influencing factors of OPF were determined by multivariate analysis, and a binary Logistic regression model was established according to the results of multivariate analysis. Hosmer-Lemeshow (H-L) goodness of fit and receiver operating characteristic curve (ROC) were used to test the model's efficiency, and Stata 16.0 software was used to verify the Bootstrap model, draw the model calibration curve, clinical applicability curve and nomogram. In this study, the data of modeling set and verification set were 1,435 and 580, respectively. There were 493 (34.4%) cases with OPF and 942 (65.6%) cases without OPF in the modeling set. There were 204 (35.2%) cases with OPF and 376 (64.8%) cases without OPF. The variables with statistically significant differences in univariate analysis are Age, BMI, History of falls, Usage of glucocorticoid, ALP, Serum Calcium, BMD of lumbar, BMD of feminist neck, T value of feminist neck, BMD of total hip and T value of total hip. The area under ROC curve of the risk prediction model constructed this time is 0.817 [95%CI (0.794 ~ 0.839)], which shows that the model has a good discrimination in predicting the occurrence of OPF. The optimal threshold of the model is 0.373, the specificity is 0.741, the sensitivity is 0.746, and the AUC values of the modeling set and the verification set are 0.8165 and 0.8646, respectively. The results of Hosmer and Lemeshow test are modeling set: (χ2 = 6.551, p = 0.586); validation set: [(χ2 = 8.075, p = 0.426)]. The calibration curve of the model shows that the reference line of the fitted curve and the calibration curve is highly coincident, and the model has a good calibration degree for predicting the occurrence of fractures. The net benefit value of the risk model of osteoporosis patients complicated with OPF is high, which shows that the model is effective. In this study, a OPF risk prediction model is established and its prediction efficiency is verified, which can help identify the high fracture risk subgroup of osteoporosis patients in order to choose stronger intervention measures and management.

Clinical Characteristics and Outcomes of Limb Fractures in Saudi Children.

Children's bones are at high risk of fracture as they grow. The clinical characteristics of fractures in children differ from those in adults. Studying fractures in healthy children is critical for identifying cases of fragility fractures. The aim of this study was to assess the clinical characteristics of limb fractures as well as clinical indicators of fracture healing outcomes in healthy Saudi children seen in an emergency room. A retrospective review of the treatment course of all pediatric fractures and related factors treated at King Abdullah Specialist Children's Hospital (KASCH) in Riyadh between 2016 and 2018 was conducted. Children with a primary bone disorder or chronic comorbidities known to affect bone health were excluded. The study included 143patients(mean age ±SD =8.23 + 3.76 years), and 71% (n= 102) were males. Motor vehicle accidents (MVAs) were the most common mechanism of injury, accounting for 50 (35%) cases, followed by fall injuries, sports injuries, and pedestrian accidents at 45 (31.4%), 16 (11.2%), and 13 (9.1%), respectively. A total of 178 fractures were reported, with the femur (n= 75, 42.1%) being the most common of the reported fracture sites, followed by the forearm (n= 44, 24.7%). The most common type of fracture was transverse fracture (n= 96, 54% of patients). Vitamin D levels were measured in 53/143 cases. Of these, vitamin D deficiency was found in 38 (71.7%) patients. The average time for fracture healing was 32.9 ± 30.2 weeks. The mechanisms of injury, including MVAs and sports injuries, as well as femur and forearm fractures, were clinical factors that were independently associated with a longer duration of fracture healing time (p< 0.001), but age, gender, and vitamin D status were not associated with that outcome. MVAs andfall injurieswere the most common causes of fracture in our patients. MVAs and sports injurieswere associated with prolonged healing time. Large prospective, multicenter, or field studies may be required to further explore clinical characteristics, outcomes, and environmental factors.

Age-dependent FRAX-based assessment and intervention thresholds for therapeutic decision making in osteoporosis in the Malaysian population.

We aimed to examine the role of age-dependent intervention thresholds (ITs) applied to the Fracture Risk Assessment (FRAX) tool in therapeutic decision making for osteoporosis in the Malaysian population. Data were collated from 1380 treatment-naïve postmenopausal women aged 40-85 years who underwent bone mineral density (BMD) measurements for clinical reasons. Age-dependent ITs, for both major osteoporotic fracture (MOF) and hip fracture (HF), were calculated considering a woman with a BMI of 25 kg/m2, aged between 40 and 85years, with a prior fragility fracture, sans other clinical risk factors. Those with fracture probabilities equal to or above upper assessment thresholds (UATs) were considered to have high fracture risk. Those below the lower assessment thresholds (LATs) were considered to have low fracture risk. The ITs of MOF and HF ranged from 0.7 to 18% and 0.2 to 8%, between 40 and 85years. The LATs of MOF ranged from 0.3 to 11%, while those of HF ranged from 0.1 to 5.2%. The UATs of MOF and HF were 0.8 to 21.6% and 0.2 to 9.6%, respectively. In this study, 24.8% women were in the high-risk category while 30.4% were in the low-risk category. Of the 44.8% (n=618) in the intermediate risk group, after recalculation of fracture risk with BMD input, 38.3% (237/618) were above the ITs while the rest (n=381, 61.7%) were below the ITs. Judged by the Youden Index, 11.5% MOF probability which was associated with a sensitivity of 0.62 and specificity of 0.83 and 4.0% HF probability associated with a sensitivity of 0.63 and a specificity 0.82 were found to be the most appropriate fixed ITs in this analysis. Less than half of the study population (44.8%) required BMD for osteoporosis management when age-specific assessment thresholds were applied. Therefore, in more than half, therapeutic decisions can be made without BMD based on these assessment thresholds.

Long-term treatment with bisphosphonates in clinical practice: advantages, main problems and risks

Bisphosphonates are the main class of drugs for treatment osteoporosis (OP) and other diseases with increased bone resorption, as bisphosphonates are very effective in reducing risk of fracture. The problem of maintaining the effectiveness and possible loss of effect of bisphosphonates, as well as their safety during long-term use, remains actual Long-them therapy with bisphosphonates and it’s effects has been discussed over the past 20 years, as the risk of osteoporotic fracture may stay hight in patients with presence of irreducible risk factors (continous use of glucocorticoids etc.) despite ongoing antiosteoporotic therapy. Real clinical practice demonstrates very low patient adherence to treatment with bisphosphonates. However, observational studies have showed that treatment with bisphosphonates for more than 10 years without initiating a drug holiday can be effective for patients at high risk of fracture. Moreover, the longer therapy with bisphosphonates is continued and the later the“drug holiday”is initiated, the lower the risks of fractures of the proximal femur and clinical vertebral fractures. However, the duration of continuous bisphosphonate therapy for each patient remains at the decision of the physician and is determined individually in each case, based on the risk-benefit ratio, taking into account the patient’s risk factors for fractures and comorbid diseases.

Long term trends in the incidence of distal radius fractures in Sindhudurg, west coast of Maharashtra Retrospective analysis of 1776 distal radius fractures (1989 to 1999), hospital based study

The over all incidences related to age, gender with secular trends and seasonal variation in the catchment area of Sindhudurg, are reported in this study. This study included all the patients of distal radius fractures treated by the author at Government. hospital Kudal, Sindhudurg between 1989 to 1999. A retrospective analysis was done extracting the data from Government hospital OPD registers, indoor case papers, cross-checked with operation theatre, radiology files. Overall 1776 distal radius fractures conferred of which 692(39.0%) were women. The annual incidence was 1.41 for 1989 and 2.58 for 1999 per 10,000 inhabitants. There was an exponential increase in incidence of adolescents of 11 to 20 years [26(22.1%) in 1989 and 56(25.4%) in 1999] and between 51 to 70 years age group [37(31.4%) in 1989 and 82(37.2%) in 1999] in both genders. After 71 years there was gradual decline in incidence in both men and women. Low velocity injuries due to indoor and outdoor falling was the most common mechanism of injury in 1340(75.5%). Associated ulnar styloid fracture was seen in 912(51.3%). Surgical intervention was done in 522(57.2%) with ulnar styloid fracture and in 186(21.5%) with intact ulnar styloid.The annualincidence of distal radius fracture is consistently increasing over a decade time, much more so in adolescents. Men and women between 51 to 70 years had a higher risk of fracture than other groups. Low energy injuries were most predominant.

Risk Factors for Bone Fractures in Patients With Comorbid Pathology

Patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), leading to macrophage activation, impaired microvascular function, changes in muscle contraction and fibrosis development. In addition, these proinflammatory cytokines promote bone resorption, thereby increasing the incidence of bone fractures. The aim of the study is to evaluate the effect of tumor necrosis factor-alpha receptor types 1 and 2 (TNF-α-SR1 and TNF-α-SR2) on fracture probability in individuals with osteoporosis who have concurrent chronic heart failure (HF) and type 2 diabetes mellitus (T2DM). The study was conducted on 178 women aged 50 to 65 years. Among these women, 48 were in group 1 and had both heart failure and type 2 diabetes. Group 2 included 93 patients with osteoporosis and heart failure and group 3 included 37 women with osteoporosis, heart failure and type 2 diabetes. Thirty-five postmenopausal women without any clinical and instrumental signs of cardiovascular pathology or osteoporosis were selected as the control group. The levels of TNF-α-SR1 and TNF-α-SR2 receptors in patient groups 1-3 were significantly higher (p&lt;0.01) than in the control group, as were their concentrations. In addition, it was found that the levels of both receptors were significantly higher in group 3 than in patients in groups 1 and 2. To evaluate the levels of TNF-α-SR1 and TNF-α-SR2, the data were divided into four quartiles (Q1-Q4) based on the increase in the concentrations of these markers. For TNF-α-SR2, an increasing risk gradient was observed, with the odds ratio (OR) for osteoporosis events increasing from 1.4 to 12.83, but the risk was statistically significant only for Q3-Q4. For Q4 TNF-α-SR1 levels, a significant increase in the risk of an adverse osteoporosis outcome at 36 months was also found (OR=5.25, p=0.038). In addition, the use of loop diuretics was found to be a predictor of high risk of osteoporotic fractures in patients with chronic HF (JR=6.29, 95% CI=1.45-17.26, p=0.015). Postmenopausal women with chronic HF and elevated levels of soluble TNF-α-SR1 and TNF-α-SR2 receptors are at higher risk for osteoporosis and adverse disease progression. In addition, the use of loop diuretics in these individuals is associated with an increased risk of osteoporotic fractures.

Evidence-Based Guideline for the management of osteoporosis in men.

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and itsassociated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, andinterventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.