Risk Of Osteoporotic Fractures Research Articles

Cardiovascular Safety of Romosozumab Compared to Commonly Used Anti-osteoporosis Medications in Postmenopausal Osteoporosis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

The aim of this study was to investigate the cardiovascular safety of romosozumab in postmenopausal women with osteoporosis. Romosozumab, a monoclonal antibody targeting sclerostin, has been shown to increase bone mineral density and reduce the risk of osteoporotic fractures. However, in previous studies, romosozumab therapy was identified as a potential risk factor for cardiovascular events, particularly in patients with predisposing cardiovascular disease. A systematic literature search was performed in the Cochrane Library, Embase, PubMed, and Web of Science databases to identify randomized controlled trials (RCTs) comparing the safety and efficacy of romosozumab versus alendronate, teriparatide, denosumab, or placebo in postmenopausal women with osteoporosis. Contrast-based network meta-analysis was performed using a random-effects model. The pooled estimates are presented as risk ratios with 95% confidence intervals. Of the 5282 articles retrieved, 25 RCTs were included in this review (n = 24,942), and 18 randomized controlled trials (n = 16,777) were included in the network meta-analysis. The results indicated no significant differences in cardiovascular mortality rate between romosozumab and placebo. Regarding the risk of major cardiovascular events, no significant differences were found in the direct evidence or the network meta-analysis with placebo as the reference. Romosozumab might be a safe option for treating postmenopausal women with osteoporosis. The cardiovascular concerns associated with this treatment seem less significant than previously suggested, although additional real-world data are required to confirm this conclusion.

Association between antibiotics use and osteoporotic fracture risk: a nationally representative retrospective cohort study

SummaryThis population-based retrospective cohort study aimed to estimate the association between antibiotic exposure and osteoporotic fracture risk. Long-term antibiotic use was associated with the risk of osteoporotic fracture. An increase in the number of antibiotic classes prescribed may also be associated with an increased osteoporotic fracture risk.PurposeThis study aims to examine the association between antibiotic usage and osteoporotic fractures in a large cohort of Korean adults, with a specific focus on the duration of antibiotic exposure and the number of antibiotic classes used.MethodsThis retrospective cohort study from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from January 1, 2002, to December 31, 2019, included 167,370 Korean adults aged 50 years or older (mean [SD] age, 59.3 [7.82] years; 65,425 [39.09%] women). The cumulative antibiotic prescription days and the classes of antibiotics prescribed between 2004 and 2008 were exposure variables, respectively. The main outcome was a newly diagnosed osteoporotic fracture during follow-up. Cox proportional hazard regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident osteoporotic fractures associated with antibiotic exposure.ResultsThe antibiotic user group with 91 days had a higher risk of osteoporotic fracture in comparison to the antibiotic non-user group (aHR, 1.12; 95% CI, 1.03–1.21). Additionally, those who used more than four different antibiotic classes had an elevated risk of osteoporotic fracture compared to the non-user group (aHR, 1.10; 95% CI, 1.02–1.18).ConclusionThis extensive population-based cohort study conducted on a large population has identified an association between the utilization of antibiotics and an elevated risk of osteoporotic fractures. The cumulative days exposed to antibiotics and osteoporotic fractures may be positively associated.

Elevated Fracture Risks in Patients Using Inhaled Corticosteroids: A Korean Nationwide Study.

In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea. From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period. Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia. These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.

Streamlining the Journey of Research Into Clinical Practice: Making Your Patients and Practice Flourish Optimizing Management and Minimizing Risk of Osteoporotic Vertebral Fractures - Perspectives of the AO Spine KF Trauma and Infection Group Key Opinion Leaders.

Literature review with clinical recommendations. To highlight important studies about osteoporotic spinal fractures (OF) that may be integrated into clinical practice based on the assessment of the AO Spine KF Trauma and Infection group key opinion leaders. 4 important studies about OF that may affect current clinical practice of spinal surgeons were selected and reviewed with the aim of providing clinical recommendations to streamline the journey of research into clinical practice. Recommendations were graded as strong or conditional following the GRADE methodology. 4 studies were selected. Article 1: a validation of the Osteoporotic Fracture (OF)-score to treat OF fractures. Conditional recommendation to incorporate the OF score in the management of fractures to improve clinical results. Article 2: a randomized multicenter study comparing romosozumab/alendronate vs alendronate to decrease the incidence of new vertebral fractures. Strong recommendation that the group receiving romosozumab/alendronate had a decreased risk of new OF when compared with the alendronate only group only. Article 3: a systematic literature review of spinal orthoses in the management of. Conditional recommendation to prescribe a spinal orthosis to decrease pain and improve quality of life. Article 4: post-traumatic deformity after OF. A conditional recommendation that middle column injury and pre-injury use of steroids may lead to high risk of post-traumatic deformity after OF. Management of patients with OF is still complex and challenging. This review provides some recommendations that may help surgeons to better manage these patients and improve their clinical practice.

Lipid metabolites are associated with the risk of osteoporotic fractures

We conducted this cross-sectional study to investigate the independent associations between lipid metabolites and osteoporotic fractures among participants aged 40–69 years from the UK Biobank. Serum lipid, lipoprotein levels and nuclear magnetic resonance (NMR) based metabolic biomarkers were measured at the baseline. We conducted multivariable logistic analyses to investigate potential independent associations between concentrations of lipid metabolites and osteoporotic fractures in both men and women. The odds ratios (ORs) for lipid metabolites were calculated based on their lowest tertile. Over a median follow-up period of 15 years, a total of 978 men and 4515 women were diagnosed with osteoporosis, whereas 138 men and 327 women encountered incident fractures. Statistically significant disparities were identified in NMR-based metabolic biomarkers among men and women with incident fractures compared to those without. Out of the 144 distinct lipid metabolites known, 35 exhibited significant associations with incident fractures in patients diagnosed with osteoporosis. Following the adjustment for confounding factors, degree of unsaturation (p = 0.0066) and docosahexaenoic acids (p = 0.0011) in male patients increased the risk of incident fractures. And high level of different metabolites of HDL (p = 0.0153), 3-Hydroxybutyrate (p = 0.0012) and Sphingomyelins (p = 0.0036) decreased the risk of incident fractures in female patients. This outcome indicates that these identified lipid metabolites may potentially have unique roles in independently contributing to the occurrence of osteoporotic fractures.

The reduced cortical bone density in vertebral bodies: risk for osteoporotic fractures? Insights from CT analysis

BackgroundThere is a corresponding increase in the prevalence of osteoporosis and related fractures with the aging population on the rise. Furthermore, osteoporotic vertebral compression fractures (OVCF) may contribute to higher patient mortality rates. It is essential to conduct research on risk factors for OVCF and provide a theoretical basis for preventing such fractures.MethodsWe retrospectively recruited patients who had spine CT for OVCF or back pain. Demographic and CT data were collected. Quantitative computed tomography (QCT) software analyzed the CT data, using subcutaneous fat and paraspinal muscles as reference standards for BMD processing. BMD of cortical and cancellous bones in each patient’s vertebral body was determined.ResultsIn this study, 144 patients were divided into non-OVCF (96) and OVCF (48) groups. Non-OVCF patients had higher cortical BMD of 382.5 ± 52.4 to 444.6 ± 70.1 mg/cm3, with T12 having the lowest BMD (p < 0.001, T12 vs. L2). Cancellous BMD ranged from 128.5 ± 58.4 to 140.9 ± 58.9 mg/cm3, with L3 having the lowest BMD. OVCF patients had lower cortical BMD of 365.0 ± 78.9 to 429.3 ± 156.7 mg/cm3, with a further decrease in T12 BMD. Cancellous BMD ranged from 71.68 ± 52.07 to 123.9 ± 126.2 mg/cm3, with L3 still having the lowest BMD. Fractured vertebrae in OVCF patients (T12, L1, and L2) had lower cortical bone density compared to their corresponding vertebrae without fractures (p < 0.05).ConclusionsT12 had the lowest cortical BMD and L3 had the lowest cancellous BMD in OVCF patients, with T12 also having the highest incidence of osteoporotic fractures. These findings suggest that reduction in cortical BMD has a greater impact on OVCF than reduction in cancellous BMD, along with biomechanical factors.

Age-associated risk of sarcopenia, falls and fractures: results of Ukrainian cohort study

Background. It is well-known that sarcopenia increases the risk of falls and fractures, and therefore, requires correction to improve the quality of life of elderly people. This research purposed to study the age-related changes in the sarcopenia risk, falls, and fractures in Ukrainian women in the late reproductive and postmenopausal periods. Materials and methods. We examined 573 females aged from 40 to 89 years old. The subjects were grouped by age decades and presence of high sarcopenia risk (HSR). The SARC-F questionnaire measured the sarcopenia risk, and the risk of falls using the Desmond Fall Risk Questionnaire, the 10-year probability of major osteoporotic and hip fractures was assessed by FRAX, and daily activity — according to the IADL scale. Also, we performed the hand grip strength and five-repetition sit-to-stand tests. Results. The frequency of HSR increased with age from 1.5 % in the 40–49-year-old group to 73.7 % in subjects over 80, as well as fracture and fall risks (p &lt; 0.00001 for both indices) related to decreasing independence in the subject’s everyday life. Also, we revealed age-dependent loss of muscle strength according to the hand grip and the five-repetition sit-to-stand tests. After the adjustment of the subjects by age we found that the females with HSR had a higher risk of falls, a lower level of independence, and increased frequency and risk of osteoporotic fractures. Conclusions. Women with HSR have a higher risk of falls, fractures, and more limitations in daily living activities independently from age and body mass index. These findings request comprehensive management of older women with attention to various parameters for the increase of independence and quality of life.

Metabolic dysfunction-associated fatty liver disease and osteoporosis: the mechanisms and roles of adiposity.

Nonalcoholic fatty liver disease (NAFLD) has recently been renamed metabolic dysfunction-associated fatty liver disease (MAFLD) by international consensus. Both MAFLD and osteoporosis are highly prevalent metabolic diseases. Recent evidence indicates that NAFLD increases the risk of low bone mineral density and osteoporosis, likely mediated by obesity. NAFLD has a close association with obesity and other metabolic disorders. Although obesity was previously thought to protect against bone loss, it now heightens osteoporotic fracture risk. This overview summarizes current clinical correlations between obesity, NAFLD, and osteoporosis, with a focus on recent insights into potential mechanisms interconnecting these three conditions. This study reviewed the scientific literature on the relationship between obesity, nonalcoholic fatty liver disease, and osteoporosis as well as the scientific literature that reveals the underlying pathophysiologic mechanisms between the three. Emerging evidence suggests obesity plays a key role in mediating the relationship between NAFLD and osteoporosis. Accumulating laboratory evidence supports plausible pathophysiological links between obesity, NAFLD, and osteoporosis, including inflammatory pathways, insulin resistance, gut microbiota dysbiosis, bone marrow adiposity, and alterations in insulin-like growth factor-1 signaling. Adiposity has important associations with NAFLD and osteoporosis, the underlying pathophysiologic mechanisms between the three may provide new therapeutic targets for this complex patient population.

Association of obesity with osteoporotic fracture risk in individuals with bone metabolism-related conditions: a cross sectional analysis.

This study aimed to investigate the individual and composite associations of different indices of obesity on osteoporotic fractures at three different sites among individuals affected by conditions influencing bone metabolism. Participants were included from the National Health and Nutrition Examination Survey (NHANES), a national cross-sectional survey. BMI and WC were used separately and in combination to evaluate the presence of obesity. Obesity was defined as BMI ≥ 30 kg/m2, WC ≥ 88 cm in females, and WC ≥ 102 cm in males. Associations between obesity and osteoporotic fractures were assessed using multivariable logistic regression and OR curves. Associations modified by age, sex, race, and alcohol consumption were also evaluated. A total of 5377 participants were included in this study. In multivariable logistic regression analyses, we found that BMI, WC, BMI defining obesity, and WC defining obesity were negatively associated with hip fracture (all p < 0.05). However, harmful associations between WC and BMI defining obesity and spine fracture were found (all p < 0.05). OR curves revealed that BMI and WC had a linear relationship with hip and spine fractures (all P for non-linearity >0.05). Further analyses showed that the highest WC quartile was harmfully associated with a higher risk of spine fractures (p < 0.05). Obese participants diagnosed by both BMI and WC were less likely to have hip fractures but more likely to have spine fractures (all P for trend <0.05). A significant interaction between age (Ref: age < 50 years) and BMI and WC was detected for hip fractures (all P for interaction <0.05). In people with conditions influencing bone metabolism, obesity diagnosed by BMI and WC was associated with a lower risk of hip fracture, while obesity diagnosed by BMI and the highest WC quartile were associated with a higher risk of spine fracture.

Real world clinical outcomes when discontinuing denosumab or bisphosphonates in patients with surgically managed osteoporotic vertebral compression fractures: a population-based cohort study

BACKGROUND CONTEXTOsteoporotic vertebral compression fractures (OVCFs) are common fragility fractures. Patients who undergo surgical treatment for their initial OVCFs warrant particular attention because there is an elevated risk of subsequent vertebral fractures and other types of fragility fractures. However, the optimal osteoporosis treatment for this specific patient group is less investigated. PURPOSEThis study compares the risk of subsequent osteoporotic fractures and mortality rate for patients who are initiated with denosumab and bisphosphonates and determines the effect of adherence to treatment. STUDY DESIGNRetrospective nationwide cohort study PATIENT SAMPLEA total of 2,858 patients who had surgically-managed osteoporotic vertebral compression fractures. OUTCOME MEASURESThe risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. METHODSThis is a retrospective nationwide cohort study that uses the National Health Insurance Research Database. Patients aged ≥50 years who were admitted for surgical interventions for OVCF between 2012 and 2016 and subsequently received denosumab or bisphosphonates for one year were included. Patients were stratified according to their antiosteoporosis medications and adherence to treatment. A multivariable, time-varying Cox proportional hazards model was used to determine the risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. RESULTSA total of 2,858 patients were included in this study: 1,123 patients in the denosumab group and 1,735 patients in the bisphosphonates group. Compared to persistent denosumab users, the nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent bisphosphonate users had a greater risk of osteoporotic fractures, with respective hazard ratios of 1.64 (95% confidence interval [CI], 1.16–2.32), 1.74 (95% CI, 1.25–2.42) and 1.53 (95% CI, 1.14–2.06). If osteoporotic fractures were divided into nonvertebral and vertebral fractures, none of the groups exhibited an increased risk of vertebral fractures compared to persistent denosumab users, with an HR of 1.00 (95% CI: 0.54–1.88) for nonpersistent denosumab users, 1.64 (95% CI: 0.96–2.81) for persistent bisphosphonate users and 1.52 (95% CI: 0.95–2.43) for nonpersistent bisphosphonate users. However, there was a significantly greater risk of nonvertebral fracture, with respective hazard ratios of 2.04 (95% CI, 1.33–3.11), 1.80 (95% CI, 1.18–2.76) and 1.56 (95% CI, 1.06–2.27) for nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent users. Noteworthy, nonpersistent denosumab users exhibited a significantly greater risk of mortality than persistent denosumab users, with a hazard ratio of 3.12 (95% CI, 2.22–4.38). CONCLUSIONSIn terms of patients with OVCFs who require hospitalization and surgical intervention, those who receive ongoing denosumab treatment exhibit less risk of developing subsequent osteoporotic fractures than those who receive bisphosphonates or nonpersistent denosumab treatment. However, discontinuation of denosumab is associated with a significantly increased risk of subsequent fractures and mortality. Therefore, adherence to the treatment is crucial for patients who are initiated with denosumab.

Significant decrease of osteoporosis and osteoporotic fractures in rheumatoid arthritis within a period of 24 years: experiences of a single centre

ObjectivesRheumatoid arthritis (RA) is associated with an increased risk for osteoporosis and osteoporotic fractures. Since the treatment of RA has improved significantly in recent years, we can expect RA-associated osteoporosis...

Hydroxychloroquine and risk of osteoporosis in patients with rheumatoid arthritis: A population-based retrospective study of 6408 patients.

Patients with rheumatoid arthritis (RA) are at a higher risk of osteoporotic fractures. Studies have shown that patients with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE) experienced an increase in bone mineral density (BMD) after receiving hydroxychloroquine (HCQ) treatment, indicating a potential protective effect against osteoporosis. Therefore, this study is to examine the relationship between HCQ usage and the risk of osteoporosis in patients diagnosed with RA. The retrospective cohort study used data from Taiwan's National Health Insurance Research Database (NHIRD) covering the period from January 2010 to December 2018, which included 14 050 newly diagnosed RA patients, subsequently divided into two groups: HCQ users and non-users. Propensity score matching (PSM) based on sex, age, urbanization, insured unit type, insured area, and comorbidities was conducted to match the groups. The primary outcome assessed was the evaluation of the risk of osteoporosis by employing a multivariable Cox proportional hazard regression model to calculate the adjusted hazard ratio (aHR). After PSM, a total of 6408 RA patients were included in the analysis (3204 HCQ users and 3204 non-users). There was no significantly higher risk of osteoporosis in HCQ users compared with non-users, aHR = 0.99 (95% CI: 0.82-1.196). Additionally, different durations of HCQ usage demonstrated a neutral effect on the risk of osteoporosis [HCQ <90 days, aHR = 0.88 (95% CI: 0.585-1.324); HCQ 90-180 days, aHR = 0.941 (95% CI: 0.625-1.418); HCQ >180 days, aHR = 1.019 (95% CI: 0.832-1.249)]. The study indicates that there is no significant association between the use of HCQ and the risk of osteoporosis in patients with RA.

Enhanced osteogenic differentiation for osteoporosis treatment through controlled icariin release in the bone cavity via extracorporeal shock wave

Controlling drug release from the bone cavity through physical stimulation remains a challenge because the unique shielding properties of the bone structure make it difficult for many physical stimuli to be effective in skeletal disorders. Herein, we designed a type of high-loading nanocomposites self-assembled from Icariin (ICA), Ca2+, and Zoledronic acid (ZOL), which could respond to extracorporeal shock wave (ESW) to control drug release in the bone cavity and govern osteoblast-adipocyte lineage commitment to prevent osteoporotic fracture. The nanocomposites contain more than 70 % of the payloads and exhibit excellent function in bone marrow targeting. When shocked with ESW, the payloads including ICA, Ca2+, and ZOL, can be released in the bone marrow. ICA can inhibit the formation of adipocyte lineages and promote the formation of osteoblast lineages by inhibiting the transcription of peroxisome proliferators-activated receptor γ (PPARγ) and fatty acid-binding protein 4 (FABP4), ESW, and Ca2+ further increase osteoblast activity meanwhile, and ZOL acts as an inhibitor of osteoclasts, leading to an overall anabolism. In vivo, the treatment contributed to a significant increase in bone anabolism, including bone-related parameters, bone strength, and bone resilience, ultimately greatly reducing the risk of osteoporotic fracture. This study demonstrated the high feasibility of combining the bone-penetrating ESW-responsive drug-controlled release system with the regulation of osteoblast-adipocyte lineage commitment for osteoporotic fracture prevention.

Role of sclerostin deletion in bisphosphonate-induced osteonecrosis of the jaw

PurposeBone resorption inhibitors, such as bisphosphonates (BP) and denosumab, are frequently used for the management of osteoporosis. Although both drugs reduce the risk of osteoporotic fractures, they are associated with a serious side effect known as medication-related osteonecrosis of the jaw (MRONJ). Sclerostin antibodies (romosozumab) increase bone formation and decrease the risk of osteoporotic fractures: however, their anti-resorptive effect increases ONJ. Thus, this study aimed to elucidate the role of sclerostin deletion in the development of MRONJ. MethodsSclerostin knockout (SostΔ26/Δ26) mice were used to confirm the development of ONJ by performing tooth extractions. To confirm the role of sclerostin deficiency in a more ONJ-prone situation, we used the BP-induced ONJ model in combination with severe periodontitis to evaluate the development of ONJ and bone formation in wild-type (WT) and SostΔ26/Δ26 mice. Wound healing assay using gingival fibroblasts with or without sclerostin stimulation and tooth extraction socket healing were evaluated in the WT and SostΔ26/Δ26 mice. ResultsONJ was not detected in the extraction socket of SostΔ26/Δ26 mice. Moreover, the incidence of ONJ was significantly lower in the SostΔ26/Δ26 mice treated with BP compared to that of the WT mice. Osteogenic proteins, osteocalcin, and runt-related transcription factor 2, were expressed in the bone surface in SostΔ26/Δ26 mice. Recombinant sclerostin inhibited gingival fibroblast migration. The wound healing rate of the extraction socket was faster in SostΔ26/Δ26 mice than in WT mice. ConclusionSclerostin deficiency did not cause ONJ and reduced the risk of developing BP-induced ONJ. Enhanced bone formation and wound healing were observed in the tooth extraction socket. The use of romosozumab (anti-sclerostin antibody) has proven to be safe for surgical procedures of the jaw.

Non-osteoporotic fractures are associated with increased risk of subsequent major osteoporotic fractures

SummaryWe studied the association between non-osteoporotic fractures and future major osteoporotic fractures, using UK health records. Non-osteoporotic fractures were found to increase the risk of major osteoporotic fractures, although to a lesser extent than osteoporotic fractures. This highlights the importance of considering all previous fractures in assessing future fracture risk.PurposePrevious studies demonstrated that osteoporotic fractures—minor and major—increase the risk for future major osteoporotic fractures; we test whether non-osteoporotic fractures are also associated with such increased risk.MethodsThe study is a retrospective cohort study using UK primary care electronic health records. Exposure groups were defined according to fracture location prior to the year 2011 (index date): major, minor, and non-osteoporotic. The outcome of incident major osteoporotic fractures following the index date was compared between the exposure groups and the general population.ResultsThe general study population included 1,951,388 patients. The exposure groups included 39,931 patients with a prior major osteoporotic fracture, 19,397 with a prior minor osteoporotic fracture, and 50,115 patients with a prior non-osteoporotic fracture. The standardized Incidence Rate Ratio for future major osteoporotic fractures was 2.73 (95% confidence interval: 2.64–2.82), 2.43 (2.32–2.54), and 1.83 (1.74–1.92), respectively.ConclusionNon-osteoporotic fractures are significantly associated with increased risk for future major osteoporotic fractures relative to the general population, yet to a lesser extent compared to major and minor osteoporotic fractures.

Performance of the Brazilian Fracture Assessment Risk Tool (FRAX) model and the age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines on fracture prediction in community-dwelling older adults: the São Paulo Ageing and Health (SPAH) Study.

To determine the performances of FRAX and age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines with and without bone mineral density (BMD) regarding fracture prediction in community-dwelling elderly Brazilians. Seven hundred and five older adults (447 women; 258 men) were followed for 4.3 ± 0.8years. FRAX risk for hip and major osteoporotic fractures with and without BMD was calculated at baseline. The bivariate analysis investigated the associations between the absolute probability of fracture (FRAX), as well as the age-dependent intervention thresholds (NOGG), and the incidence of vertebral fracture (VF), non-vertebral fracture (NVF), and major osteoporotic fractures (MOF), segregated by sex. Age-adjusted Poisson's multiple regression and ROC curves were constructed to determine FRAX and NOGG's accuracies as fracture predictors. Fractures occurred in 22% of women and 15% of men. FRAX with and without BMD was higher in women with all types of fractures (p < 0.001). Only NOGG risk classification without BMD was associated with NVF (p = 0.047) and MOF (p = 0.024). FRAX was associated with NVF in the multiple regression, regardless of BMD. ROC curves of FRAX with and without BMD had AUCs of 0.74, 0.64, and 0.61 for NVF, VF, and MOF, respectively. The most accurate risk cutoffs for FRAX were 8% for MOF and 3% for hip fractures. No statistically significant associations were found in men. FRAX predicted NVF more accurately than VF or MOF in elderlies, regardless of BMD. These results reiterate that FRAX may be used without BMD, even considering that Brazilian elderlies have known higher fracture risk.

Predicting the probability of osteoporotic fracture risk in men versus women: do we need specific reference interventional thresholds for men?

BackgroundGender differences in the diagnosis and treatment of osteoporosis is a relatively common phenomenon, particularly amongst those patients under 80 years of age presenting with fragility fractures. The clinical implications of these findings are that strategies, which tend to focus on osteoporosis management in women, should also pay enough attention to osteoporosis in men. However, there have been questions whether there is a gender difference when setting intervention thresholds for osteoporosis management. This work was carried out aiming to determine the fracture probabilities calculated by FRAX at which therapeutic intervention in older men and women can be considered.ResultsAssessment of fracture risk probability thresholds in men revealed that for hip fractures, ROC was 0.754 (95% CI: 0.69–0.817). The sensitivity was 80.5% for threshold probabilities of 2.5%. For the major osteoporosis fracture, ROC was 0.828 (95% CI: 0.694–0.963). The sensitivity was 87.5% for threshold probabilities of 10%. Assessment of fracture risk probability threshold in women ROC was 0.760 (95% CI: 0.691–0.83). The sensitivity was 76.1% for threshold probabilities of 3%. For major osteoporosis fracture, ROC was 0.848 (95% CI: 0.784–0.912). The sensitivity was 87.3% for threshold probabilities of 15%.ConclusionOperational aspects of osteoporosis management should consider gender specific fracture thresholds. Interventional thresholds were found to be different in men compared to women. This helps to optimise fracture prevention in older men.

Increased risk of hip and major osteoporotic fractures in 8463 patients who have undergone stem cell transplantation, a Swedish population-based study

SummaryIn this retrospective cohort study of adult stem cell transplanted patients (n = 8463), a significant increased risk of both MOF and hip fractures was seen compared with the Swedish population and occurred in mean more than 2 years after stem cell transplantation.PurposeTo explore the risk for osteoporotic fracture in patients who have undergone hematopoietic stem cell transplantation (HSCT) compared with the Swedish population.MethodsThe risk of osteoporotic fractures was determined in a retrospective population cohort study of adult (≥ 18 years) Swedish patients (n = 8463), who were transplanted with HSCT 1997–2016 and compared with all adults living in Sweden during the same period.ResultsIn the total study group (n = 8463), 90 hip fractures (1.1% both in males and females) and 361 major osteoporotic fractures (MOF) (3.2% in men and 6.0% in women) were identified. In the total study population, the ratio of observed and expected number of hip fracture for women was 1.99 (95% CI 1.39–2.75) and for men 2.54 (95% CI 1.91–3.31). The corresponding ratio for MOF in women was 1.36 (CI 1.18–1.56) and for men 1.61 (CI 1.37–1.88). From 2005 onwards, when differentiation in the registry between allo- and auto-HSCT was possible, the observed number of hip fracture and MOF in allo-HSCT (n = 1865) were significantly increased (observed/expected hip fracture 5.24 (95% CI 3.28–7.93) and observed/expected MOF 2.08 (95% CI 1.63–2.62)). Fractures occurred in mean 2.7 (hip) and 2.5 (MOF) years after allo-HSCT. Graft-versus-host disease (GVHD) was not associated with an increased risk of fracture.ConclusionPatients who underwent HSCT had an increased risk of both hip and major osteoporotic fracture compared with the Swedish population and occurred in 4.3% of patients. GVHD was not statistically significantly associated with fracture risk.

Low-dose glucocorticoid increase the risk of fracture in postmenopausal women with low bone mass: a retrospective cohort study.

The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated. 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up. The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94]). Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass.

Development and validation of a predictive model for vertebral fracture risk in osteoporosis patients.

This study aimed to develop and validate a predictive model for osteoporotic vertebral fractures (OVFs) risk by integrating demographic, bone mineral density (BMD), CT imaging, and deep learning radiomics features from CT images. A total of 169 osteoporosis-diagnosed patients from three hospitals were randomly split into OVFs (n = 77) and Non-OVFs (n = 92) groups for training (n = 135) and test (n = 34). Demographic data, BMD, and CT imaging details were collected. Deep transfer learning (DTL) using ResNet-50 and radiomics features were fused, with the best model chosen via logistic regression. Cox proportional hazards models identified clinical factors. Three models were constructed: clinical, radiomics-DTL, and fusion (clinical-radiomics-DTL). Performance was assessed using AUC, C-index, Kaplan-Meier, and calibration curves. The best model was depicted as a nomogram, and clinical utility was evaluated using decision curve analysis (DCA). BMD, CT values of paravertebral muscles (PVM), and paravertebral muscles' cross-sectional area (CSA) significantly differed between OVFs and Non-OVFs groups (P < 0.05). No significant differences were found between training and test cohort. Multivariate Cox models identified BMD, CT values of PVM, and CSAPS reduction as independent OVFs risk factors (P < 0.05). The fusion model exhibited the highest predictive performance (C-index: 0.839 in training, 0.795 in test). DCA confirmed the nomogram's utility in OVFs risk prediction. This study presents a robust predictive model for OVFs risk, integrating BMD, CT data, and radiomics-DTL features, offering high sensitivity and specificity. The model's visualizations can inform OVFs prevention and treatment strategies.