Risk Of Osteoporotic Fractures Research Articles

Comparison of the pleiotropic effect of atorvastatin and rosuvastatin on postmenopausal changes in bone turnover: A randomized comparative study.

Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin. This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment. There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations. These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.

Predicting osteoporotic fractures post-vertebroplasty: a machine learning approach with a web-based calculator

PurposeThe aim of this study was to develop and validate a machine learning (ML) model for predicting the risk of new osteoporotic vertebral compression fracture (OVCF) in patients who underwent percutaneous vertebroplasty (PVP) and to create a user-friendly web-based calculator for clinical use.MethodsA retrospective analysis of patients undergoing percutaneous vertebroplasty: A retrospective analysis of patients treated with PVP between June 2016 and June 2018 at Liuzhou People's Hospital was performed. The independent variables of the model were screened using Boruta and modelled using 9 algorithms. Model performance was assessed using the area under the receiver operating characteristic curve (ROC_AUC), and clinical utility was assessed by clinical decision curve analysis (DCA). The best models were analysed for interpretability using SHapley Additive exPlanations (SHAP) and the models were deployed visually using a web calculator.ResultsTraining and test groups were split using time. The SVM model performed best in both the training group tenfold cross-validation (CV) and validation group AUC, with an AUC of 0.77. DCA showed that the model was beneficial to patients in both the training and test sets. A network calculator developed based on the SHAP-based SVM model can be used for clinical risk assessment (https://nicolazhang.shinyapps.io/refracture_shap/).ConclusionsThe SVM-based ML model was effective in predicting the risk of new-onset OVCF after PVP, and the network calculator provides a practical tool for clinical decision-making. This study contributes to personalised care in spinal surgery.

Risk of osteoporotic fractures among patients with thyroid cancer: a nationwide population-based study

Risk of osteoporotic fractures among patients with thyroid cancer: a nationwide population-based study

Association of osteoporotic fractures of femoral neck and femoral neck geometric parameters in native Chinese women

BackgroundAlthough it is generally believed that the femoral neck fracture is related to the femoral neck geometric parameters (FNGPs), the association between the risk of osteoporotic fracture of the femoral neck and FNGPs in native Chinese women is still unclear.MethodsA total of 374 female patients (mean age 70.2 ± 9.32 years) with osteoporotic fracture of the femoral neck, and 374 non-fracture control groups were completely matched with the case group according to the age ratio of 1:1. Using DXA bone densitometer to measured eight FNGPs: the outer diameter (OD), cross-sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR), section modulus (SM), cross-sectional moment of inertia (CSMI), and compressive strength index (CSI) at the narrowest point of the femoral neck.ResultsCompared with the control group, the average values of OD (2.9%), ED (4.5%), and BR (26.1%) in the patient group significantly increased (p = 0.015 to < 0.001), while CSA (‒15.3%), CT (‒18.2%), SM (‒10.3%), CSMI (‒6.4%), and CSI (‒10.8%) significantly decreased (all p < 0.001). The prevalence of osteoporosis in the lumbar spine, femoral neck, and total hip was, respectively, 82%, 81%, and 65% in fracture patients. Cox proportional hazard model analysis showed that in the age adjusted model, the fracture hazard ratio (HR) of CSA, CT, BR, SM, and CSI significantly increased (HRs = 1.60‒8.33; 95% CI = 1.08‒16.6; all p < 0.001). In the model adjusted for age and femoral neck BMD, HRs of CT (HRs = 3.90‒8.03; 95% CI = 2.45‒15.1; all p < 0.001) and BR (HRs = 1.62‒2.60; 95% CI = 1.20‒5.44; all p < 0.001) were still significantly increased.ConclusionThese results suggest that the majority of osteoporotic fractures of the femoral neck of native Chinese women occur in patients with osteoporosis. CT thinning or BR increase of FNGPs may be independent predictors of fragility fracture of femoral neck in native Chinese women unrelated to BMD.

Higher high-density lipoprotein cholesterol levels increased vertebral osteoporotic fracture, but reduced hip fracture in men based on the National Health Insurance Service-National Health Screening Cohort

Background ContextLipids are currently known to play an important role in bone metabolism. PurposeThis study aimed to investigate the effect of high-density lipoprotein cholesterol (HDL-C) on osteoporotic fractures beyond its beneficial effects on the cardiovascular system. Study Design/SettingThis was a retrospective, observational study that used data from the National Health Insurance Service-Health Screening cohort database. Patient SampleThis study included 318,237 participants who were 50 years or older and with HDL-C levels of 10 to 200 mg/dL. Outcomes MeasuresPhysiologic measure - Diagnosis of osteoporotic fracture during the follow-up period. MethodsThe study participants were categorized into four quartiles according to baseline HDL-C levels. The Cox proportional hazards model was used to assess osteoporotic fracture risk according to HDL-C levels. ResultsAfter full adjustment and with the Q1 group as the reference group, estimates of hazard ratios (HRs; 95% confidence intervals [CIs]) for any osteoporotic fracture in men were 1.03 (0.94–1.12), 1.02 (0.93–1.11), and 1.07 (0.98–1.18) for the Q2, Q3, and Q4 groups, respectively. After classifying osteoporotic fractures according to the body location, the fully adjusted HRs for vertebral and hip fractures in the men's Q4 groups were 1.16 (1.02–1.31) and 0.74 (0.57–0.96), respectively. In women, fully adjusted HRs (95% CIs) of the female Q4 group for any osteoporotic, vertebral, and hip fractures were 1.03 (0.95–1.11), 0.96 (0.86–1.07), and 1.06 (0.80–1.41), respectively. ConclusionIn this study, HDL-C levels were positively associated with vertebral fractures in both men and women but inversely related to hip fractures in men. Therefore, monitoring the lipid profiles of patients with osteoporosis may be beneficial for the prevention of osteoporotic fractures.

TBS correlates with bone density and microstructure at trabecular and cortical bone evaluated by HR-pQCT.

Trabecular bone score (TBS) estimates bone microstructure, which is directly measured by high-resolution peripheral quantitative computed tomography (HRpQCT). We evaluated the correlation between these methods and TBS influence on fracture risk assessed by FRAX. We evaluated 129 individuals (82 women, 43 postmenopausal) 20 to 82.3 years without prevalent clinical or non-clinical morphometric vertebral fractures, using DXA (spine and hip), HR-pQCT at distal radius (R) and tibia (T) and TBS which classifies bone microarchitecture as normal (TBS ≥ 1.350), partially degraded (1.200 < TBS < 1.350), or degraded (TBS ≤ 1.200). Spine and hip BMD and HR-pQCT parameters at cortical bone: area (T), density (R,T) thickness (T) and trabecular bone: density (R,T), number (T) and thickness (R) were significantly better in the 78 individuals with normal TBS (group 1) versus the 51 classified as partially degraded (n = 42) or degraded microarchitecture (n = 9) altogether (group 2). TBS values correlated with age (r = -0.55), positively with spine and hip BMD and all cortical and trabecular bone density and microstructure parameters evaluated, p < 0.05 all tests. Binary logistic regression defined age (p = 0.008) and cortical thickness (p = 0.018) as main influences on TBS, while ANCOVA demonstrated that HR-pQCT data corrected for age were not different between TBS groups 1 and 2. TBS adjustment increased FRAX risk for major osteoporotic fractures and hip fractures. We describe significant association between TBS and both trabecular and cortical bone parameters measured by HR-pQCT, consistent with TBS influence on fracture risk estimation by FRAX, including hip fractures, where cortical bone predominates.

Tuberculosis and osteoporotic fracture risk: development of individualized fracture risk estimation prediction model using a nationwide cohort study.

Tuberculosis (TB) is linked to sustained inflammation even after treatment, and fracture risk is higher in TB survivors than in the general population. However, no individualized fracture risk prediction model exists for TB survivors. We aimed to estimate fracture risk, identify fracture-related factors, and develop an individualized risk prediction model for TB survivors. TB survivors (n = 44,453) between 2010 and 2017 and 1:1 age- and sex-matched controls were enrolled. One year after TB diagnosis, the participants were followed-up until the date of fracture, death, or end of the study period (December 2018). Cox proportional hazard regression analyses were performed to compare the fracture risk between TB survivors and controls and to identify fracture-related factors among TB survivors. During median 3.4 (interquartile range, 1.6-5.3) follow-up years, the incident fracture rate was significantly higher in TB survivors than in the matched controls (19.3 vs. 14.6 per 1,000 person-years, p < 0.001). Even after adjusting for potential confounders, TB survivors had a higher risk for all fractures (adjusted hazard ratio 1.27 [95% confidence interval 1.20-1.34]), including hip (1.65 [1.39-1.96]) and vertebral (1.35 [1.25-1.46]) fractures, than matched controls. Fracture-related factors included pulmonary TB, female sex, older age, heavy alcohol consumption, reduced exercise, and a higher Charlson Comorbidity Index (p < 0.05). The individualized fracture risk model showed good discrimination (concordance statistic = 0.678). TB survivors have a higher fracture risk than matched controls. An individualized prediction model may help prevent fractures in TB survivors, especially in high-risk groups.

P164 Fracture risk in axial spondyloarthritis: a retrospective analysis of the use of the Fracture Risk Assessment Tool in a cohort of affected patients

Abstract Background/Aims Fractures are common in axial spondyloarthritis (axSpA) patients. The FRAX (Fracture Risk Assessment Tool) score is a validated tool for the assessment of fracture risk. Unlike axSpA, rheumatoid arthritis (RA) is counted as a risk factor in FRAX. The primary aim was to calculate a FRAX score in a cohort of axSpA patients. In addition, a second FRAX score was determined by ticking the “RA risk” as positive on the second assessment. Methods Data were examined on a cohort of axSpA patients attending the St James’s Hospital Spondylitis service. Bone mineral density was assessed at the neck of femur on the patient’s dual x-ray absorptiometry (DXA). This, plus the individual patient’s risk factors, were added to the FRAX score calculator. The analysis was then repeated with the RA risk box ticked as positive. The effect of such an adjustment (taking account of their diagnosis of axSpA) on the fracture risk status of these patients was made to assess if this resulted in an additional number of patients within the cohort being at risk of fracture. A patient with a 10-year hip fracture risk of &amp;gt; 3% or 10-year major osteoporotic fracture risk of &amp;gt; 20% is high risk. Results Table 1 summarises the characteristics of the cohort. All (100%) of the patients met ASAS axSpA criteria and 85% met Modified New York (mNY) criteria for ankylosing spondylitis. Five patients had known osteoporosis and an additional 9 patients were classified as being at increased fracture risk using the FRAX Tool. A further 7 patients could be classified as being at increased fracture risk when the FRAX was adjusted for the axSpA diagnosis, by ticking the RA risk box as positive. Conclusion Fracture risk is a significant issue in patients with axSpA; however, this risk is frequently under-recognised. The use of the FRAX score improves the detection of those at fracture risk, and its use should be strongly encouraged in all rheumatology clinics managing axSpA patients. When the same weighting is given to axSpA as RA, there is a further increase in the identification of patients at risk of fractures. Disclosure P. Mulkerrin: None. F. O'Shea: None. G. Fitzgerald: None.

Osteoporosis in Parkinson's disease and the role of lean body mass: a cross-sectional study in a Brazilian tertiary center.

Parkinson's disease (PD) is the second most common neurodegenerative illness and has the highest increase rate in recent years. There is growing evidence to suggest that PD is linked to higher osteoporosis rates and risk of fractures. This study aims to estimate the prevalence and factors associated with osteoporosis as defined by the National Osteoporosis Foundation (NOF) and World Health Organization in patients with mild to moderate PD. We performed a cross-sectional study at a tertiary public hospital in Fortaleza, Brazil, dating from May 2021 until April 2022. The study sample was comprised of patients with mild to moderate PD who were at least 40 years old and who had the ability to walk and stand unassisted. Bone Mineral Density (BMD) of both the hip (neck of the femur) and the lumbar spine were obtained via properly calibrated Dual Energy X-ray Absorptiometry (DXA) scanning. The FRAX (Fracture Risk Assessment Tool) score was used to determine a person's 10-year risk of major osteoporotic fracture. The Revised European Working Group on Sarcopenia in Older People (EWGSOP 2) was used as a basis to confirm a sarcopenia diagnosis with the following parameters: low muscle strength gauged by handgrip strength and low muscle quantity by DXA. Physical performance was carefully evaluated by using the Short Physical Performance Battery test. Osteoporosis and osteopenia were diagnosed following the NOF guidelines and WHO recommendations. We evaluated 107 patients in total, of whom 45 (42%) were women. The group's mean age was 68 ± 9 years, and the mean disease time span was 9.9 ± 6.0 years and mean motor UPDRS was 43 ± 15. We found that 42.1% and 34.6% of the sample had osteopenia and osteoporosis following NOF criteria, respectively, and 43% and 33.6% following the WHO recommendations. Lower lean appendicular mass was associated to osteopenia and osteoporosis in multinomial logistic regression analysis in both diagnostic criteria. Our findings provide additional evidence for the protective role of lean mass against osteoporosis in patients with PD.

Osteoporotic fracture risk in women with breast cancer treated with aromatase inhibitors: a health insurance claims database study in Japan

ABSTRACT Background Hormone therapy with aromatase inhibitors (AIs) for estrogen receptor-dependent breast cancer may expose patients to an increased osteoporosis risk. This study was performed to estimate fracture risk in women with breast cancer to whom AIs were prescribed in Japan. Methods This retrospective study used data from the Japanese Medical Data Vision database. Women with breast cancer prescribed AIs over a 12-month period were identified and matched to women not prescribed AIs using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared using a cause-specific Cox hazard model. The proportion of women undergoing bone density tests was retrieved. Results For all fractures sites combined, cumulative fracture incidence at ten years was 0.19 [95%CI: 0.16–0.22] in women prescribed AIs and 0.18 [95%CI: 0.15–0.21] without AIs. AI prescription was not associated with any changes in risk (adjusted hazard ratio: 1.08 [95%CI: 0.99–1.17] p = 0.08). Women prescribed AI more frequently underwent bone density testing (31.9% [95% CI: 31.2%; 32.6%] versus 2.2% [95% CI: 2.0%; 2.4%]). Conclusions The anticipated association between AI exposure and osteoporotic fracture risk in Japanese women with breast cancer was not seen clearly.

Early-onset dementia and risk of hip fracture and major osteoporotic fractures.

There is limited knowledge about early-onset dementia (EOD) on fracture risk. Individuals ages 50 to 64 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (2012 to 2019). The association between EOD and fractures and the association between cholinesterase inhibitors for EOD and fractures were evaluated using logistic regression analyses. We identified 13,614 EOD patients and 9,144,560 cognitively healthy individuals. The analysis revealed that EOD was associated with an increased risk of hip fractures (adjusted odds ratio, 95% confidence interval: 8.79, 7.37-10.48), vertebral fractures (1.73, 1.48-2.01), and major osteoporotic fractures (2.05, 1.83-2.30) over 3 years. The use of cholinesterase inhibitors was significantly associated with a reduction in hip fractures among EOD patients (0.28, 0.11-0.69). EOD patients have a higher risk of osteoporotic fractures than cognitively healthy individuals. The use of cholinesterase inhibitors may reduce the risk of hip fracture among EOD patients. It is unknown whether early-onset dementia (EOD) increases the risk of fractures. We identified 13,614 individuals with EOD using a nationwide administrative database. Patients with EOD have a higher risk of hip, vertebral, and major osteoporotic fractures. The use of cholinesterase inhibitors may reduce hip fracture among patients with EOD.

Deep learning in the radiologic diagnosis of osteoporosis: a literature review.

Osteoporosis is a systemic bone disease characterized by low bone mass, damaged bone microstructure, increased bone fragility, and susceptibility to fractures. With the rapid development of artificial intelligence, a series of studies have reported deep learning applications in the screening and diagnosis of osteoporosis. The aim of this review was to summary the application of deep learning methods in the radiologic diagnosis of osteoporosis. We conducted a two-step literature search using the PubMed and Web of Science databases. In this review, we focused on routine radiologic methods, such as X-ray, computed tomography, and magnetic resonance imaging, used to opportunistically screen for osteoporosis. A total of 40 studies were included in this review. These studies were divided into three categories: osteoporosis screening (n = 20), bone mineral density prediction (n = 13), and osteoporotic fracture risk prediction and detection (n = 7). Deep learning has demonstrated a remarkable capacity for osteoporosis screening. However, clinical commercialization of a diagnostic model for osteoporosis remains a challenge.

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.

Optimal dual calcium and cholecalciderol dosages for osteoporotic fracture risk patients

Background: Vitamin D is crucial for musculoskeletal health, promoting calcium absorption, osteoid tissue mineralization, and muscle function. Insufficient levels can lead to bone dystrophy, muscle weakness, and osteoporotic fractures. Aims: This research investigates the correlation between bone mineral density and osteoporotic fracture risk, including positive and negative influences, and aims to determine the optimal vitamin D level. Methods: This retrospective observational study examined 206 Jordanian rehabilitation and rheumatology clinic patients from September to November 2021. The participants were post-menopausal women and men over 60. The Age-adjusted Charlson Co-Morbidity Index and Functionality Grade system was used to assess participants' co-morbidity burden and functionality. DEXA scans assessed participants' proximal femoral hip and anteroposterior spine. Participants were divided into two Vit D groups: those below 30 ng/ml and those above 30. Results were compared using a Chi Square test. The study examined correlations, total variations, and Vit D prediction quality using logistic regression analyses. SPSS 23.0 was used for statistical analysis with a 5% significance level. Results: A binary logistic regression model was employed to simulate the correlation between the vitamin D levels of patients and their bone mineral density. The model indicated a 61.39% likelihood of having a fH_BMD (femoral head bone mineral density) equal to or greater than 0.755 g/cm2 when the vitamin D level is at its optimal value of 27.25 ng/ml. The model indicated a 27.25% likelihood of a fHOPF risk-free tool with a value of ≥3% when the optimal vitamin D level is 27.25 ng/ml. The model indicated a 17.74% likelihood of experiencing a significant osteoporotic fracture within the next 10 years. Conclusion: The findings of our study demonstrated a direct correlation between elevated levels of vitamin D and improved bone mineral quality indices that were examined. The serum 25-OH Cholecalciferol levels are more likely to have a beneficial effect on bone health status.

THE FOCUS ON INCREASED RISK OF FRACTURES IN THEIR PROLONGED USE

Proton pump inhibitors are the most effective drugs for the treatment of acid-dependent diseases. For a long time, proton pump inhibitors have been considered to be completely safe drugs both for short-term and long-term use. A number of modern clinical studies note that when prescribing proton pump inhibitors in high doses for a long time, the possibility of side effects should be taken into account. The purpose of the review is to study the effect of prolonged use of proton pump inhibitors on the condition of bone tissue and the risk of osteoporotic fractures. Materials and methods. A search was conducted in the PubMed and Scopus information databases for publications on the safety of using proton pump inhibitors, including sources published before December 1, 2023, with an emphasis on the influence of proton pump inhibitors on bone tissue and the possible risk of fractures. Results. According to numerous studies, prolonged use of proton pump inhibitors is associated with an increased risk of fractures of the hip, vertebrae and the wrist. An increased risk of fractures may be associated with hypergastrinemia and hypochlorhydria (due to inhibition of acid secretion by proton pump inhibitors), and electrolyte disorders (hypocalcemia). Conclusions. All the pros and cons of prescribing proton pump inhibitors in patients with a history of fractures associated with osteoporosis should be carefully considered. In the curation of comorbid/multimorbid patients, proton pump inhibitors should be used if medically required for as short duration as possible and at the minimum effective dose to relieve symptoms.

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.

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.

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.

Risk of Fracture in Patients with Myasthenia Gravis: A Nationwide Cohort Study in Korea.

Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junctions, resulting in muscle weakness and fatigue. Muscle weakness, restricted mobility, and frequent use of corticosteroids in patients with MG may predispose them to a higher risk of fractures. However, studies on the impact of MG on bone health and the associated fracture risk are scarce. Utilizing claim database of the Korean National Health Insurance Service collected between 2002 and 2020, we compared the risk of major osteoporotic fracture between 23 118 patients with MG and 115 590 individuals as an age- and sex-matched control group using multivariable Cox proportional hazard models. Over a median follow-up duration of 5.58years, the MG group (mean age 53.7years; 55% women) had higher risk of major osteoporotic fracture compared to controls (incidence rate 13.59 versus 9.74 per 10 000 person-years), which remained independent of age, sex, comorbidities, drug use including anti-osteoporotic agents, and previous fracture history (adjusted hazard ratio [aHR] 1.19, p < 0.001; subdistributed HR 1.14, p < 0.001 adjusted for mortality as competing risk). Subgroup analyses showed a greater association between MG and major osteoporotic fracture risk in younger (age 50 or younger) than older individuals (aHR 1.34 vs. 1.17) and in men compared to women (aHR 1.32 vs. 1.15; p for interaction <0.05 for all). An imminent divergence of the fracture risk curve between MG and controls was observed for vertebral fracture while there was time delay for non-vertebral sites, showing site-specific association. Factors associated with higher fracture risk in patients with MG were older age, female gender, high dose glucocorticoid use (> 7.5mg/day), immunosuppressant use, and previous history of fracture. In summary, patients with MG had higher risk of major osteoporotic fracture compared to controls, which calls further preventive actions in this patient group.

A clinical study on the risk and safety profiles of NSAIDs used for osteoporotic fractures in Chinese patients with rheumatoid arthritis

Purpose: To investigate the risk and safety profile of non-steroidal anti-inflammatory drugs (NSAIDs) for osteoporotic fractures in patients with rheumatoid arthritis (RA). &#x0D; Methods: 298 RA patients admitted to The First People's Hospital of Huzhou, Huzhou, China from August 2020 to September 2022, were investigated. Patients were assigned to groups based on drugs used viz: control group received anti-rheumatic drugs other than NSAIDs; corticosteroid group received dexamethasone, disease-modifying anti-rheumatic drugs (DMARDs) groups received sulfasalazine, NSAID group received either diclofenac or ibuprofen etc. Each group of patients received the respective treatment frequently for at least 3 years. The primary outcome in this study was the incidence of osteoporotic fracture resulting from fragile bone and deterioration of bone mass. &#x0D; Results: The incidence of osteoporotic fracture was highest in NSAID group (11.58 %) when compared to 5.44, 4.96, and 2.36 % in the corticosteroid, DMARD and control groups, respectively (p &lt; 0.05). This shows that users of NSAIDs had a 5-fold higher risk of osteoporotic fracture than patients in control group (OR = 1.26 (95 % CI: 1.22 - 1.81)) and 2-fold possibility of osteoporotic fracture when compared to corticosteroid users ((OR = 1.46 (95 % CI: 1.57 - 2.32)) and DMARD users (1.83 (95 % CI: 1.26 - 1.67)). &#x0D; Conclusion: Rheumatoid arthritis patients on NSAIDs such as celecoxib, diclofenac, ibuprofen, indomethacin, and oxaprozin are at risk of developing osteoporotic fracture. Therefore, NSAIDs must be used with proper counseling in RA patients to minimize the risk of osteoporotic fracture. In future, the study duration will need to be extended to determine the long-term effects and potential changes in bone properties.