Fracture Risk In Patients Research Articles

Fracture Incidence in Graves' Disease: A Population-Based Study.

Background: Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods: A total of 2134 patients with incident GD and 21,261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to 10 years of age, sex- and county-matched controls per patient were selected from databases from the National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR = 2.83 [CI 1.05-7.64]. The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions: There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.

Long-Term Use of Immunosuppressive Agents Increased the Risk of Fractures in Patients with Autoimmune Diseases: An 18-Year Population-Based Cohort Study.

The risk of fractures is higher in patients with autoimmune diseases, but it is not clear whether the use of immunosuppressive agents can further increase this risk. To investigate this issue, a retrospective study was conducted using data from Taiwan's National Health Insurance Research Database. Patients diagnosed with autoimmune diseases between 2000 and 2014, including psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, were included in the study. A control group of patients without autoimmune diseases was selected from the same database during the same period. Patients with autoimmune diseases were divided into two sub-cohorts based on their use of immunosuppressive agents. This study found the risk of fractures was 1.14 times higher in patients with autoimmune diseases than in those without. Moreover, we found that patients in the immunosuppressant sub-cohort had a higher risk of fractures compared to those in the non-immunosuppressant sub-cohort. The adjusted sub-distribution hazard ratio for shoulder fractures was 1.27 (95% CI = 1.01-1.58), for spine fractures was 1.43 (95% CI = 1.26-1.62), for wrist fractures was 0.95 (95% CI = 0.75-1.22), and for hip fractures was 1.67 (95% CI = 1.38-2.03). In conclusion, the long-term use of immunosuppressive agents in patients with autoimmune diseases may increase the risk of fractures.

SAT232 Patients With Chronic Hypoparathyroidism Have Higher Risk Of Vertebral Fracture And Lower Risk Of Femoral Fracture Compared To Controls

Abstract Disclosure: S. Bjornsdottir: None. W. Kamal: None. B.L. Langdahl: None. T. Spelman: None. B.L. Clarke: None. O. Kampe: None. Context: Previous studies have shown that patients with hypoparathyroidism (hypoPT) have reduced bone remodeling, with consequent increases in bone density, and abnormalities in microarchitecture and bone strength. It is still not clear whether there is an increased risk of fractures in patients with hypoPT. Objective: The aim of this study was to evaluate the risk of fractures in patients with hypoPT in Sweden. Patients: The Swedish National Patient Register, the Swedish Prescribed Drug Register and the Total Population Register were used to identify 1982 patients with chronic hypoPT (duration ≥ 12 months), and 19820 controls matched by age, sex and county of residency between 1997-2018. The 10th revision of the International Classification of Diseases (ICD) was used to identify fractures. Results: Patients with hypoPT did not have higher risk of any fracture compared to controls (HR 0.96; 95% CI 0.86-1.08). However, patients with hypoPT had a slightly higher risk of vertebral fractures (HR 1.33; 95% CI 1.01-1.75), p= 0.047 and a lower risk of femoral fractures (HR 0.60; 95% CI 0.45-0.82), p= 0.001. There was no significant difference in the risk of fractures of the forearm, p= 0.177, proximal humerus, p= 0.096 or pelvis, p= 0.446. There was no difference in the risk of any fracture between females and males with hypoPT (p for interaction= 0.511). Patients with surgical hypoPT had a significantly higher risk of any fracture compared with patients with non-surgical hypoPT (p for interaction= 0.006). Conclusion: The risk of any fracture was not increased in patients with hypoPT. However, the risk of vertebral fracture was increased, and the risk of femoral fracture was lower than for matched controls. No difference was found in fracture risk between females and males. Patients with surgical hypoPT had a higher fracture risk compared to patients with non-surgical hypoPT. Presentation: Saturday, June 17, 2023

FRACTURE RISK AND OBSTRUCTIVE SLEEP APNOEA

Obstructive Sleep Apnoea (OSA) with hypoxemia, oxidative stress, low-grade inflammation and multiple hormonal metabolic changes affect the bone metabolism. This leads to an increased fracture risk in patients with OSA. Purpose: The aim of the study was to explore the connection between fracture risk and newly-diagnosed OSA. Materials/methods: 130 patients with newly diagnosed OSA and 67 controls without OSA were included in the study. Anthropometric, laboratory, instrumental and study tests and fracture risk assessment under the FRAX program were performed. Results: There isn’t a statistical difference in the age and gender in the OSA group compared to the controls (p>0.05). A statistically significant difference between the OSA group and the control group was found with regard to the body mass index (BMI), visceral fat mass ratio (VFR), neck circumference, Epworth sleepiness scale (ESS), Vitamin D levels, beta-crosslaps and osteocalcin (р<0.0001 for all). Reduction of bone mineral density (BMD) was found in patients with OSA. On average, three risk factors for fracture were found in patients with OSA compared to an absence or only one risk factor in the control group (р<0.0001). Conclusion: Patients with OSA are at an increased fracture risk due to disturbed bone metabolism. They have lower Vitamin D levels, reduction of BMD and 3 risk factors for high FR. This requiresan assessment of fracture risk and its eventual reduction in patients with OSA.

Effect of fracture risk in inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

BackgroundThe fracture risk of patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids is controversial. And some large-scale randomized controlled trials have not solved this problem. The purpose of our systematic review and meta-analysis including 44 RCTs is to reveal the effect of inhaled corticosteroids on the fracture risk of COPD patients.MethodsTwo reviewers independently retrieved randomized controlled trials of inhaled corticosteroids or combinations of inhaled corticosteroids in the treatment of COPD from PubMed, Embase, Medline, Cochrane Library, and Web of Science. The primary outcome was a fracture event. This study was registered at PROSPERO (CRD42022366778).ResultsForty-four RCTs were performed in 87,594 patients. Inhaled therapy containing ICSs (RR, 1.19; 95%CI, 1.04–1.37; P = 0.010), especially ICS/LABA (RR, 1.30; 95%CI, 1.10–1.53; P = 0.002) and triple therapy (RR, 1.49; 95%CI, 1.03–2.17; P = 0.04) were significantly associated with the increased risk of fracture in COPD patients when compared with inhaled therapy without ICSs. Subgroup analyses showed that treatment duration ≥ 12 months (RR, 1.19; 95%CI, 1.04–1.38; P = 0.01), budesonide therapy (RR, 1.64; 95%CI., 1.07–2.51; P = 0.02), fluticasone furoate therapy (RR, 1.37; 95%CI, 1.05–1.78; P = 0.02), mean age of study participants ≥ 65 (RR, 1.27; 95%CI, 1.01–1.61; P = 0.04), and GOLD stage III(RR, 1.18; 95%CI, 1.00–1.38; P = 0.04) were significantly associated with an increased risk of fracture. In addition, budesonide ≥ 320 ug bid via MDI (RR, 1.75; 95%CI, 1.07–2.87; P = 0.03) was significantly associated with the increased risk of fracture.ConclusionInhalation therapy with ICSs, especially ICS/LABA or triple therapy, increased the risk of fracture in patients with COPD compared with inhaled therapy without ICS. Treatment duration, mean age of participants, GOLD stage, drug dosage form, and drug dose participated in this association. Moreover, different inhalation devices of the same drug also had differences in risk of fracture.

Adjusting FRAX Estimates of Fracture Probability Based on a Positive Vertebral Fracture Assessment

FRAX is the most widely used and validated fracture risk prediction tool worldwide. Vertebral fractures, which are an indicator of subsequent osteoporotic fractures, can be identified using dual-energy x-ray absorptiometry (DXA) vertebral fracture assessment (VFA). To assess the calibration of FRAX and develop a simple method for improving FRAX-predicted fracture probability in the presence of VFA-identified fracture. This prognostic study analyzed the DXA and VFA results of all individuals who underwent a VFA between March 31, 2010, and March 31, 2018, who were included in the Manitoba Bone Mineral Density Registry. These individuals were randomly assigned to either the development cohort or validation cohort. A modified algorithm-based qualitative approach was used by expert readers to code VFAs as positive (≥1 vertebral fractures detected) or negative (0 vertebral fracture detected). Statistical analysis was conducted from August 7, 2022, to May 22, 2023. FRAX scores for major osteoporotic fracture (MOF) and hip fracture were calculated with or without VFA results. Incident fractures and death were ascertained using linked population-based health care provincial data. Cumulative incidence curves for MOF and hip fracture were constructed, including competing mortality, to predict the 10-year observed risk of fracture. The observed probability was compared with FRAX-predicted fracture probability with and without VFA results and recalibrated FRAX from derived multipliers. The full cohort of 11 766 individuals was randomly allocated to the development cohort (n = 7854; 7349 females [93.6%]; mean [SD] age, 75.7 [6.8] years) or the validation cohort (n = 3912; 3713 females [94.9%]; mean [SD] age, 75.5 [6.9] years). Over a mean (SD) observation time of 3.8 (2.3) years, with the longest observation at 7.5 years, FRAX was well calibrated in subgroups with negative VFA results. For individuals without a prior clinical fracture but with a positive VFA result, the 10-year FRAX-predicted MOF probability was 16.3% (95% CI, 15.7%-16.8%) without VFA information and 23.4% (95% CI, 22.7%-24.1%) with VFA information. The observed 10-year probabilities were 26.9% (95% CI, 26.0%-27.8%) and 11.2% (95% CI, 10.3%-12.1%), respectively, resulting in recalibration multipliers of 1.15 (95% CI, 0.87-1.43) for MOF and 1.31 (95% CI, 0.75-1.87) for hip fracture. For individuals with a prior clinical fracture and a positive VFA result, the 10-year FRAX-predicted probabilities were 25.0% (95% CI, 24.2%-25.7%) for MOF and 9.3% (95% CI, 8.7%-10.0%) for hip fracture. The observed 10-year probabilities were 38.1% (95% CI, 37.0%-39.1%) for MOF and 16.4% (95% CI, 15.4%-17.4%) for hip fracture, resulting in a recalibration multiplier of 1.53 (95% CI, 1.10-1.96) for MOF and 1.76 (95% CI, 1.17-2.35) for hip fracture. Good calibration (>0.90) was confirmed using the derived multipliers in the validation cohort. Results of this prognostic study suggest that FRAX underestimated fracture risk in patients with VFA-identified fractures. Simple multipliers could recover FRAX calibration in individuals with VFA-identified fractures.

Zoledronic Acid Prevents Bone Resorption Caused by the Combination of Radium-223, Abiraterone Acetate, and Prednisone in an Intratibial Prostate Cancer Mouse Model.

An increased risk of non-pathological fractures in patients with prostate cancer and bone metastases has been associated with combination treatment with radium-223, abiraterone, and prednisone/prednisolone in the absence of bone-protecting agents. Here, we investigated possible mechanisms leading to this outcome using an intratibial LNCaP model mimicking prostate cancer bone metastases. Male NOD.scid mice were inoculated intratibially with LNCaP prostate cancer cells and treated with vehicle, radium-223, abiraterone, prednisone, zoledronic acid, or their combinations for 28 days. Serum TRACP 5b and PSA levels were measured. Bone structure, quality, and formation rate of non-tumor-bearing and tumor-bearing tibiae were analyzed by microCT, 3-point bending assay, and dynamic histomorphometry, respectively. Radium-223 incorporation into bone was also measured. Radium-223/abiraterone/prednisone combination treatment induced a transient increase in bone resorption indicated by elevated TRACP 5b levels, which was inhibited by concurrent treatment with zoledronic acid. Furthermore, radium-223/abiraterone/prednisone combination reduced periosteal and trabecular new bone formation and the number of osteoblasts, but bone structure or biomechanical quality were not affected. The abiraterone/prednisone treatment decreased radium-223 incorporation into tumor-bearing bone, possibly explaining the lack of additional antitumor efficacy. In conclusion, radium-223/abiraterone/prednisone combination increased bone resorption, which may have been one of the mechanisms leading to an increased fracture risk in patients with mCRPC.

Diabetes mellitus and bone mineral density on fracture risk in patients with allergic rhinitis and asthma

Diabetes mellitus and bone mineral density on fracture risk in patients with allergic rhinitis and asthma

Fracture Risk in Patients with Hypoparathyroidism.

To summarize the recently published scientific evidence on fracture risk in hypoparathyroidism. Hypoparathyroidism is characterized by a low bone turnover and a high bone mineral density. Data on fracture risk are sparse and due to the rarity of the disease, available studies have only been able to include relatively few patients. Risk of non-vertebral fractures does not seem to be affected to any major degree, although epidemiological studies suggest a decreased risk of fractures at the humerus in postsurgical hypoparathyroidism, whereas an increased risk of fractures at the upper arm has been shown in non-surgical hypoparathyroidism. Several, but not all, studies have also pointed towards an increased risk of vertebral fractures, especially in non-surgical hypoparathyroidism. Fractures at the appendicular skeleton do not seem to be of specific concern in hypoparathyroidism, but emerging data suggest an increased risk of vertebral fractures, which needs to be clarified further in upcoming studies.

The associations of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as add-on to metformin with fracture risk in patients with type 2 diabetes mellitus.

To investigate whether sodium-glucose cotransporter-2 (SGLT2) inhibitor use as compared to dipeptidyl peptidase-4 (DPP-4) inhibitor use as add-on to metformin is associated with the risk of any fracture or major osteoporotic fractures (MOFs). A cohort study using the Clinical Practice Research Datalink (CPRD) Aurum database was conducted. All patients aged 18 years and older with a first-ever prescription for a DPP-4 inhibitor or an SGLT2 inhibitor as add-on to metformin between January 1, 2013 and June 30, 2020 were selected. Patients starting with SGLT2 inhibitors were matched (up to 1:3) on propensity scores to patients starting with DPP-4 inhibitors. Propensity scores were calculated based on sex, age, body mass index, comorbidities, comedication and lifestyle factors. Cox proportional hazard models were used to estimate the risk of fracture with SGLT2 inhibitor use as compared to DPP-4 inhibitor use. A total of 13 807 SGLT2 inhibitor users (age 55.4 ± 10.6 years, 36.7% female) were included in this study, matched with 28 524 DPP-4 inhibitor users (age 55.4 ± 8.0 years, 36.4% female). The risk of any fracture with current SGLT2 inhibitor use was similar compared with current DPP-4 inhibitor use (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 0.91-1.31), as was the risk of MOFs (aHR 0.89, 95% CI 0.64-1.22) and the risk of fractures at any of the individual MOF sites. Additionally, no association was found with duration of SGLT2 inhibitor use (longest duration >811 days) for any of the individual SGLT2 inhibitor agents, or after stratification by sex and age. Use of SGLT2 inhibitors was not associated with the risk of any fracture, MOFs or fracture at the individual MOF sites when compared to DPP-4 inhibitor use.

Orcinol glucoside targeted p38 as an agonist to promote osteogenesis and protect glucocorticoid-induced osteoporosis

BackgroundGlucocorticoids (GC)-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis, which leads to an increased risk of fracture in patients. The inhibition of the osteoblast effect is one of the main pathological characteristics of GIOP, but without effective drugs on treatment. PurposeThe aim of this study was to investigate the potential effects of orcinol glucoside (OG) on osteoblast cells and GIOP mice, as well as the mechanism of the underlying molecular target protein of OG both in vitro osteoblast cell and in vivo GIOP mice model. MethodsGIOP mice were used to determine the effect of OG on bone density and bone formation. Then, a cellular thermal shift assay coupled with mass spectrometry (CETSA-MS) method was used to identify the target of OG. Surface plasmon resonance (SPR), enzyme activity assay, molecular docking, and molecular dynamics were used to detect the affinity, activity, and binding site between OG and its target, respectively. Finally, the anti-osteoporosis effect of OG through the target signal pathway was investigated in vitro osteoblast cell and in vivo GIOP mice model. ResultsOG treatment increased bone mineral density (BMD) in GIOP mice and effectively promoted osteoblast proliferation, osteogenic differentiation, and mineralization in vitro. The CETSA-MS result showed that the target of OG acting on the osteoblast is the p38 protein. SPR, molecular docking assay and enzyme activity assay showed that OG could direct bind to the p38 protein and is a p38 agonist. The cellular study found that OG could promote p38 phosphorylation and upregulate the proteins expression of its downstream osteogenic (Runx2, Osx, Collagen Ⅰ, Dlx5). Meanwhile, it could also inhibit the nuclear transport of GR by increasing the phosphorylation site at GR226 in osteoblast cell. In vivo GIOP mice experiment further confirmed that OG could prevent bone loss in the GIOP mice model through promoting p38 activity as well as its downstream proteins expression and activity. ConclusionsThis study has established that OG could promote osteoblast activity and revise the bone loss in GIOP mice by direct binding to the p38 protein and is a p38 agonist to improve its downstream signaling, which has great potential in GIOP treatment for targeting p38. This is the first report to identify OG anti-osteoporosis targets using a label-free strategy (CETSA-MS).

Impact of Medication Adherence on Bone Mineral Density and Fracture Risk in Patients With Osteoporosis: A Systematic Review.

Osteoporosis is a chronic, prevalent disease marked by decreased bone mass and changes in bone anatomy associated with significant morbidity. The management of osteoporosis necessitates long-term therapy for which patient adherence is of vital importance. In the present review, we aim to collect all potential evidence from relevant studies that reported the impact of medication adherence on bone mineral density and fracture risk in patients with osteoporosis. We have conducted both electronic and manual search strategies within the potential databases and included articles and reviews to find relevant studies. We have assessed the effects of osteoporotic medication adherence on fracture rates and bone mineral density. The study participants were divided into two groups, adherent and non-adherent. Studies from the year 2010-2023 were included. Final inclusion consisted of 14 studies that showed variation in adherence rates with only three studies reporting optimal adherence followed by two studies with nearly half adherent population while the rest of the studies reported low medication adherence. The highest adherence rate reported was 82% while the lowest was 8%. Among the included studies the fracture rates varied significantly. Decreased rates of fracture were observedin the adherent population however two of the included studies were contrary to these findings. Additionally, only three studies discussed the effect of adherence on bone mineral density. Lack of medication adherence is linked to an increased risk of fracture, and low bone mineral density, further associated with more severe complications as per the evidence from the literature. However, variation in the fracture rates as observed in our findings advocates the need for further research for the generalizability of results.

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

Spinal osteoporosis is a prevalent health condition characterized by the thinning of bone tissues in the spine, increasing the risk of fractures. Given its high incidence, especially among older populations, it is critical to have accurate and effective predictive models for fracture risk. Traditionally, clinicians have relied on a combination of factors such as demographics, clinical attributes, and radiological characteristics to predict fracture risk in these patients. However, these models often lack precision and fail to include all potential risk factors. There is a need for a more comprehensive, statistically robust prediction model that can better identify high-risk individuals for early intervention. To construct and validate a model for forecasting fracture risk in patients with spinal osteoporosis. The medical records of 80 patients with spinal osteoporosis who were diagnosed and treated between 2019 and 2022 were retrospectively examined. The patients were selected according to strict criteria and categorized into two groups: Those with fractures (n = 40) and those without fractures (n = 40). Demographics, clinical attributes, biochemical indicators, bone mineral density (BMD), and radiological characteristics were collected and compared. A logistic regression analysis was employed to create an osteoporotic fracture risk-prediction model. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the model's performance. Factors significantly associated with fracture risk included age, sex, body mass index (BMI), smoking history, BMD, vertebral trabecular alterations, and prior vertebral fractures. The final risk-prediction model was developed using the formula: (logit [P] = -3.75 + 0.04 × age - 1.15 × sex + 0.02 × BMI + 0.83 × smoking history + 2.25 × BMD - 1.12 × vertebral trabecular alterations + 1.83 × previous vertebral fractures). The AUROC of the model was 0.93 (95%CI: 0.88-0.96, P < 0.001), indicating strong discriminatory capabilities. The fracture risk-prediction model, utilizing accessible clinical, biochemical, and radiological information, offered a precise tool for the evaluation of fracture risk in patients with spinal osteoporosis. The model has potential in the identification of high-risk individuals for early intervention and the guidance of appropriate preventive actions to reduce the impact of osteoporosis-related fractures.

Machine learning algorithms for predicting the risk of fracture in patients with diabetes in China

BackgroundPatients with diabetes are more likely to be predisposed to fractures compared to those without diabetes. In clinical practice, predicting fracture risk in diabetics is still difficult because of the limited availability and accessibility of existing fracture prediction tools in the diabetic population. The purpose of this study was to develop and validate models using machine learning (ML) algorithms to achieve high predictive power for fracture in patients with diabetes in China. MethodsIn this study, the clinical data of 775 hospitalized patients with diabetes was analyzed by using Decision Tree (DT), Gradient Boosting Decision Tree (GBDT), Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), eXtreme Gradient Boosting (XGBoost) and Probabilistic Classification Vector Machines (PCVM) algorithms to construct risk prediction models for fractures. Moreover, the risk factors for diabetes-related fracture were identified by the feature selection algorithms. ResultsThe ML algorithms extracted 17 most relevant factors from raw clinical data to maximize the accuracy of the prediction results, including bone mineral density, age, sex, weight, high-density lipoprotein cholesterol, height, duration of diabetes, total cholesterol, osteocalcin, N-terminal propeptide of type I, diastolic blood pressure, and body mass index. The 7 ML models including LR, SVM, RF, DT, GBDT, XGBoost, and PCVM had f1 scores of 0.75, 0.83, 0.84, 0.85, 0.87, 0.88, and 0.97, respectively. ConclusionsThis study identified 17 most relevant risk factors for diabetes-related fracture using ML algorithms. And the PCVM model proved to perform best in predicting the fracture risk in the diabetic population. This work proposes a cheap, safe, and extensible ML algorithm for the precise assessment of risk factors for diabetes-related fracture.

Validating the Fracture Risk Assessment Tool Score in a US Population-Based Study of Patients With Rheumatoid Arthritis.

The World Health Organization fracture risk assessment tool (FRAX) algorithm for risk prediction of major osteoporotic and hip fractures accounts for several risk factors, including rheumatoid arthritis (RA), since individuals with RA have an excess burden of fractures. FRAX has not been validated in population-based RA cohorts in the US. We aimed to determine the accuracy of FRAX predictions for individuals with RA in the US. This retrospective population-based cohort study included residents of Olmsted County, Minnesota, who were followed until death, migration, or last medical record review. Each patient with RA (1987 American College of Rheumatology criteria met in 1980-2007, age 40-89 years) was matched 1:1 on age and sex to an individual without RA from the same underlying population. Ten-year predictions for major osteoporotic and hip fractures were estimated using the FRAX tool. Fractures were ascertained through follow-up, truncated at 10 years. Standardized incidence ratios (SIRs) and 95% CI were calculated to compare observed and predicted fractures. The study included 662 patients with RA and 658 non-RA comparators (66.8% vs 66.9% female and a mean age of 60.6 vs 60.5 years, respectively). Among patients with RA, 76 major osteoporotic fractures and 21 hip fractures were observed during follow-up (median follow-up: 9.0 years) compared to 67.0 predicted major osteoporotic fractures (SIR 1.13, 95% CI 0.91-1.42) and 23.3 predicted hip fractures (SIR 0.90, 95% CI 0.59-1.38). The observed and predicted major osteoporotic and hip fracture risks were similar for patients with RA and non-RA comparators. The FRAX tool is an accurate method for estimating major osteoporotic and hip fracture risk in patients with RA.

Bones of contention: Predicting and preventing fractures in patients receiving peritoneal dialysis.

Low bone density is common among those individuals receiving peritoneal dialysis. While cross-sectional studies support an association between low bone mineral density (BMD) and prevalent fracture, relying on bone density alone, particularly at the lumbar spine and in those with high degrees of hyperparathyroidism may underestimate fracture risk. Commonly used risk calculators in the general population have been shown to perform reasonably well in those receiving dialysis although they do not include any risk factors for high turnover bone disease that may play a role in increased fracture risk. The best options for decreasing fracture risk in patients receiving peritoneal dialysis are unclear. The evidence for bisphosphonates is limited to small studies of BMD, and concerns about drug accumulation have limited their use. Denosumab is more commonly used and has some evidence for improvement in BMD but carries with it a high risk of hypocalcaemia requiring rigorous prophylaxis. More research is needed to explore practical methods to identify those at risk of fracture and determine the efficacy of antiresorptive and anabolic therapies to decrease this risk.

#5342 ASSOCIATION BETWEEN LONGITUDINAL GFR TRAJECTORIES AND BMD DECLINE RATE IN PATIENTS WITH CKD STAGE 2­–4

Abstract Background and Aims Bone mineral density (BMD) predicts fracture risk in patients with chronic kidney disease (CKD). However, there are few studies regarding BMD decline rates in CKD population. In this study, we investigated whether BMD decline rate is associated with baseline estimated glomerular filtration rate (eGFR) and further evaluated with longitudinal eGFR trajectories. Method A prospective cohort study of 1,006 patients with CKD stages 2 through 4 who enrolled in the KoreaN Cohort Study for Outcome in Patients With CKD between 2011 and 2016. BMD was measured using dual-energy X-ray absorptiometry at baseline and year 4. Estimated GFR was measured 2–5 times during 4 years of follow-up. Mixed linear regression model was used for the longitudinal analysis and trajectory analysis was performed using semiparametric group-based modeling using maximum likelihood. Results Declined renal function was associated with increased rate of decline in total hip BMD (Stage 2: −0.23, Stage 3A: −0.39, Stage 3B: −0.80, Stage 4: −1.20 in men; −0.86, −1.19, −1.20, −1.58% change/year respectively in women). Trajectory analysis revealed two distinct trajectories of eGFR for each CKD Stages 2 through 4: Class 1, stable group; Class 2, rapid decline group. Trajectory group that represented rapid eGFR decline showed consistent trends of increased rate of decline in total hip BMD. There was significant difference between stable and rapid decline group in Stage 3A, 3B (Stage 3A: −0.18 vs. −0.67 [p = 0.009], Stage 3B: −0.36 vs. −1.10 [p = 0.031] in men; Stage 3A: −0.79 vs. −1.67 [p = 0.006], Stage 3B: −0.60 vs. −1.52% change/year [p = 0.001] in women; p for interaction). Conclusion Declined renal function and faster GFR decline is associated with rapid BMD decline in CKD stage 2–4.

The impact of CHOP versus bendamustine on bone mineral density in patients with follicular lymphoma enrolled in the GALLIUM study

Introduction: A standard treatment with CHOP or CVP includes a cumulative dose of 3,000–4,000 mg prednisone. Observational studies have shown increased risk of fractures in patients treated with R-CHOP/R-CVP. However, it is not clear whether reductions in bone mineral density (BMD) are mainly caused by glucocorticoids or the combined impact of chemotherapy and glucocorticoids. The objective of this study was to investigate the impact of G/R-bendamustine versus G/R-CHOP on BMD in patients with follicular lymphoma (FL) enrolled in the GALLIUM study. Methods: Patients enrolled in the GALLIUM study, an international randomized phase 3 trial of first-line treatment for FL, were included if they were ≥60 years at inclusion and in complete remission following treatment with G/R-bendamustine or G/R-CHOP. Exclusion criteria were treatment with anabolic or antiresorptive therapies prior to baseline, co-existing medical conditions associated with low BMD, and new anti-lymphoma treatment during the initial 5 years of follow-up. CT scans were performed at baseline, induction treatment completion (ITC), and annually in five years after inclusion. Hounsfield units (HU) measured in an ovoid region in the anterior of L1 were used as surrogate for BMD, which has been shown to correlate with BMD measurements from conventional dual-energy X-ray absorptiometry (DXA). Low HU values represent lower bone density while high values represent more dense bone. Vertebral compression fractures were defined as vertebral height loss of ≥20%. Results: At ITC, 244 patients ≥60 years old were in CR. Of those, 155 fulfilled the inclusion criteria, 55 (35%) received G/R-CHOP and 100 (65%) received G/R-bendamustine. CT scans with contrast were performed at baseline and ITC in 143 patients. Baseline characteristics, including age and gender, were balanced between groups. The mean baseline HU was 143.8 in the CHOP group and 141.5 in the bendamustine group (P = 0.74). The mean HU decrease from baseline to ITC was 27.8 after CHOP versus 17.1 after bendamustine, corresponding to a difference of 12.5 (95% CI: 5.5–19.5) after adjusting for age, sex, B-symptoms, and baseline HU. BMD remained at the ITC level, and thus below baseline, during the first 3 years of follow-up. During treatment and 5 years follow up, a total of nine new compression fractures were recorded in five patients. One patient in the bendamustine group and four patients in the CHOP group developed new vertebral fractures. Keywords: Indolent non-Hodgkin lymphoma, Late Effects in Lymphoma Survivors No conflicts of interests pertinent to the abstract.

The role of bone metastases on the mechanical competence of human vertebrae

Spine is the most common site for bone metastases. The evaluation of the mechanical competence and failure location in metastatic vertebrae is a biomechanical and clinical challenge. Little is known about the failure behaviour of vertebrae with metastatic lesions. The aim of this study was to use combined micro-Computed Tomography (microCT) and time-lapsed mechanical testing to reveal the failure location in metastatic vertebrae.Fifteen spine segments, each including a metastatic and a radiologically healthy vertebra, were tested in compression up to failure within a microCT. Volumetric strains were measured using Digital Volume Correlation. The images of undeformed and deformed specimens were overlapped to identify the failure location.Vertebrae with lytic metastases experienced the largest average compressive strains (median ± standard deviation: −8506 ± 4748microstrain), followed by the vertebrae with mixed metastases (−7035 ± 15605microstrain), the radiologically healthy vertebrae (−5743 ± 5697microstrain), and the vertebrae with blastic metastases (−3150 ± 4641microstrain). Strain peaks were localised within and nearby the lytic lesions or around the blastic tissue. Failure between the endplate and the metastasis was identified in vertebrae with lytic metastases, whereas failure localised around the metastasis in vertebrae with blastic lesions.This study showed for the first time the role of metastases on the vertebral internal deformations. While lytic lesions lead to failure of the metastatic vertebra, vertebrae with blastic metastases are more likely to induce failure in the adjacent vertebrae. Nevertheless, every metastatic lesion affects the vertebral deformation differently, making it essential to assess how the lesion affects the bone microstructure. These results suggest that the properties of the lesion (type, size, location within the vertebral body) should be considered when developing clinical tools to predict the risk of fracture in patients with metastatic lesions.

Osteoporosis in patients with chronic liver disease: pathogenesis, diagnosis and treatment

Osteoporosis (OP) is a common complication in patients with chronic liver disease (CLD), which remains under the radar of clinicians. About 30% of patients with CLD suffer from OP. The increased risk of fractures in patients with CLD poses a serious socio-economic burden on the healthcare system and requires more effective measures of prevention, diagnosis, and treatment. The purpose of this review is to describe the pathophysiological mechanisms of OP development in CLD and existing diagnostic and therapeutic approaches in the management of such patients. The search in the PubMed database using the keywords "osteoporosis, bone disease, chronic liver diseases, liver cirrhosis" allowed us to select 42 sources published in 2001 – 2023. This review summarises potential mechanisms that underlie and may contribute to the development of OP in CLD. These include changes in vitamin D and calcium metabolism, vitamin K deficiency, hormonal dysregulation, the release of cytokines, sclerostin, changes in gut microbiota, deficiency of insulin-like growth factor-1 (IGF-1), and effects caused by drug intake. The prevalence, risk factors, diagnosis, screening strategies, and treatment of OP in patients with CLD are discussed.