Fracture Risk In Patients Research Articles

CORR Insights®: Can a Novel Scoring System Improve on the Mirels Score in Predicting the Fracture Risk in Patients with Multiple Myeloma?

CORR Insights®: Can a Novel Scoring System Improve on the Mirels Score in Predicting the Fracture Risk in Patients with Multiple Myeloma?

Association of Bariatric Surgery With Risk of Fracture in Patients With Severe Obesity

Given the complex relationship between body mass index, body composition, and bone density and the correlative nature of the studies that have established the prevailing notion that higher body mass indices may be protective against osteopenia and osteoporosis and, therefore, fracture, the absolute risk of fracture in patients with severe obesity who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) compared with those who do not undergo bariatric surgery is unknown. To assess the rates of fractures associated with obesity and compare rates between those who do not undergo bariatric surgery, those who undergo RYGB, and those who undergo SG. In this retrospective multicenter cohort study of Medicare Standard Analytic Files derived from Medicare parts A and B records from January 2004 to December 2014, patients classified as eligible for bariatric surgery using the US Centers of Medicare & Medicaid criteria who either did not undergo bariatric surgery or underwent RYGB or SG were exactly matched in a 1:1 fashion based on their age, sex, Elixhauser Comorbidity Index, hypertension, smoking status, nonalcoholic fatty liver disease, hyperlipidemia, type 2 diabetes, osteoporosis, osteoarthritis, and obstructive sleep apnea status. Data were analyzed from November to December 2019. RYGB or SG. The primary outcome measured in this study was the odds of fracture overall based on exposure to bariatric surgery. Secondary outcomes included the odds of type of fracture (humerus, radius or ulna, pelvis, hip, vertebrae, and total fractures) based on exposure to bariatric surgery. A total of 49 113 patients were included and were equally made up of 16 371 bariatric surgery-eligible patients who did not undergo weight loss surgery, 16 371 patients who had undergone RYGB, and 16 371 patients who had undergone SG. Each group consisted of an equal number of 4109 men (25.1%) and 12 262 women (74.9%) and had an equal distribution of ages, with 11 780 patients (72.0%) 64 years or younger, 4230 (25.8%) aged 65 to 69 years, 346 (2.1%) aged 70 to 74 years, and 15 (0.1%) aged 75 to 79 years. Patients undergoing RYGB were found to have no significant difference in odds of fractures compared with bariatric surgery-eligible patients who did not undergo surgery. Patients undergoing undergone SG were found to have decreased odds of fractures of the humerus (odds ratio [OR], 0.57; 95% CI, 0.45-0.73), radius or ulna (OR, 0.38; 95% CI, 0.25-0.58), hip (OR, 0.49; 95% CI, 0.33-0.74), pelvis (OR, 0.34; 95% CI, 0.18-0.64), vertebrae (OR, 0.60; 95% CI, 0.48-0.74), or fractures in general (OR, 0.53; 95% CI, 0.46-0.62). Compared with patients undergoing SG, patients undergoing RYGB had a significantly greater risk of total fractures (OR, 1.79; 95% CI, 1.55-2.06) and humeral fractures (OR, 1.60; 95% CI, 1.24-2.07). In this cohort study, bariatric surgery was associated with a reduced risk of fracture in bariatric surgery-eligible patients. Sleeve gastrectomy might be the best option for weight loss in patients in which fractures could be a concern, as RYGB may be associated with an increased fracture risk compared with SG.

Management of Fracture Risk in Patients with Chronic Obstructive Pulmonary Disease (COPD): Building a UK Consensus Through Healthcare Professional and Patient Engagement.

IntroductionOsteoporosis and bone fractures are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to morbidity and mortality. Current national guidance on COPD management recommends addressing bone health in patients, however, does not detail how. This consensus outlines key elements of a structured approach to managing bone health and fracture risk in patients with COPD.MethodsA systematic approach incorporating multifaceted methodologies included detailed patient and healthcare professional (HCP) surveys followed by a roundtable meeting to reach a consensus on what a pathway would look like.ResultsThe surveys revealed that fracture risk was not always assessed despite being recognised as an important aspect of COPD management by HCPs. The majority of the patients also stated they would be receptive to discussing treatment options if found to be at risk of osteoporotic fractures. Limited time and resource allocation were identified as barriers to addressing bone health during consultations. The consensus from the roundtable meeting was that a proactive systematic approach to assessing bone health should be adopted. This should involve using fracture risk assessment tools to identify individuals at risk, investigating secondary causes of osteoporosis if a diagnosis is made and reinforcing non-pharmacological and preventative measures such as smoking cessation, keeping active and pharmacological management of osteoporosis and medicines management of corticosteroid use. Practically, prioritising patients with important additional risk factors, such as previous fragility fractures, older age and long-term oral corticosteroid use for an assessment, was felt required.ConclusionThere is a need for integrating fracture risk assessment into the COPD pathway. Developing a systematic and holistic approach to addressing bone health is key to achieving this. In tandem, opportunities to disseminate the information and educational resources are also required.

Vertebral bone quality score predicts fragility fractures independently of bone mineral density

BackgroundCurrent evidence suggests that dual-energy x-ray absorptiometry (DXA) scans, the conventional method defining osteoporosis, is underutilized and, when used, may underestimate patient risk for skeletal fragility. It has recently been suggested that other imaging modalities may better estimate bone quality, such as the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score which also may assess vertebral compression fracture risk in patients with spine metastases. PurposeTo evaluate whether VBQ score is predictive of fragility fractures in a population with pre-existing low bone density and at high-risk for fracture. Study Design/SettingRetrospective single-center cohort. Patient SamplePatients followed at a metabolic bone clinic for osteopenia and/or osteoporosis. Outcome MeasuresRadiographically-documented new-onset fragility fracture. MethodsPatients with a DXA and MRI scans at the time of consultation and ≥2-year follow-up were included. Details were gathered about patient demographics, health history, current medication use, and serological studies of kidney function and bone turnover. For each patient, VBQ score was calculated using T1-weighted lumbar MRI images. Univariable and multivariable analyses were used to identify the independent predictors of a new fragility fracture. To support the construct validity of VBQ, patient VBQ scores were compared to those in a cohort of 45 healthy adults. ResultsSeventy-two (39.1%) study participants suffered fragility fractures, the occurrence of which was associated with higher VBQ score (3.50 vs. 3.01; p<.001), chronic glucocorticoid use (30.6% vs. 15.2%; p=.014), and a history of prior fragility fracture (36.1% vs. 21.4%; p=.030). Mean VBQ score across all patients in the study cohort was significantly higher than the mean VBQ score in the healthy controls (p<.001). In multivariable analysis, new-onset fracture was independently associated with history of prior fracture (OR=6.94; 95% confidence interval [2.48–19.40]; p<.001), higher VBQ score (OR=2.40 per point; [1.30–4.44]; p=.003), higher body mass index (OR=1.09 per kg/m²; [1.01–1.17]; p=.03), and chronic glucocorticoid use (OR=2.89; [1.03–8.17]; p=0.043). Notably, DXA bone mineral density (BMD) was not found to be significantly predictive of new-onset fractures in the multivariable analysis (p=.081). ConclusionsHere we demonstrate the novel, MRI-derived VBQ score is both an independent predictor of fragility fracture in at-risk patients and a superior predictor of fracture risk than DXA-measured BMD. Given the frequency with which MRIs are obtained by patients undergoing spine surgery consultation, we believe the VBQ score could be a valuable tool for estimating bone quality in order to optimize the management of these patients.

The impact of metformin in chronic kidney disease-mineral and bone disorder

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a disorder of mineral and bone metabolism due to chronic kidney disease (CKD). Bone disease and mortality are more common in patients with CKD. In addition of antidiabetic properties of metformin (MET), it possesses anti-inflammatory, anti-fibrotic properties and increases the markers of osteogenic effects. Therefore, it improves bone quality and decreases the risk of fractures in patients with type 2 diabetes. Metformin can also inhibit arterial calcification, maintain calcium-phosphorus balance, decrease cellular infiltration, fibrosis, and inflammation in kidney. Based on evidence, the prevalence of lactic acidosis due to metformin in patients with type 2 diabetes (T2D) and renal dysfunction is lower compared to other oral antidiabetic agents. Metformin decreases all-cause mortality in patients with diabetic nephropathy. The administration of metformin showed no difference in the prevalence of lactic acidosis in patients with T2D who had normal, mild, moderate, or severe renal dysfunction. Therefore, metformin can be used in patients with significant CKD to inhibit CKD-MBD due to its osteogenic effects.

Trabecular bone score in patients with chronic kidney disease.

We sought to determine whether trabecular bone score (TBS) either independently or adjusted for The Fracture Risk Assessment Tool (FRAX) could predict risk of major osteoporotic fractures (MOFs) in a large population-based sample of patients with all stages of chronic kidney disease (CKD). We used population-based administrative databases to identify patients above age 20 years who had dual-energy X-ray absorptiometry (DXA) scan and serum creatinine measured within 1 year, during the years 2005 to 2010. Patients were excluded if they were on dialysis or had a functioning renal transplant. We stratified patients by estimated glomerular filtration rate (eGFR). We collected femoral neck bone mineral density (BMD), lumbar spine TBS, incident major osteoporotic fractures (MOF) and hip fractures, and other clinical characteristics. Among 8289 patients, there were 6224 (75.1%) with eGFR ≥ 60 mL/min/1.73 m2, 1624 (19.6%) with eGFR 30-60 mL/min/1.73 m2, and 441 (5.3%) with eGFR < 30 mL/min/1.73 m2. There were 593 patients (7.2%) with MOFs and 163 (2.0%) with hip fractures. Lower TBS score was associated with increased risk of MOF and hip fractures across all eGFR strata in unadjusted Cox proportional hazards models but after adjusting for FRAX with BMD, lower TBS was only statistically significant for MOF prediction for eGFR ≥ 60 mL/min/1.73 m2. Lower TBS scores were associated with lower eGFR and increased fracture risk in patients with eGFR ≥ 60 mL/min/1.73 m2. However, the addition of TBS to the FRAX score with BMD did not significantly improve fracture risk prediction in patients with CKD.

Post-yield mechanical properties of bovine trabecular bone – Relationships with bone volume fraction and strain rate

Bone finite element models, which are increasingly used to assess fracture risk in patients with degenerative bone diseases, require extensive experimental data to adequately model the material properties being assigned. Previous studies have demonstrated that bone elastic mechanical properties are dependent on density as well as strain rate, however, the effect these same variables on the post-yield behaviour of trabecular bone has not been thoroughly studied. For this study, bovine femoral samples were tested at several strain rates using three different tests devices: a conventional constant strain rate apparatus for low strain rates, a Drop Weight Impact Test device for the intermediate regime and a Split Hopkinson Pressure Bar System with magnesium bar and a PVCA pulse shaper for high strain rates. Ultimate and plateau stress, as well as absorbed energy were recorded. The results of this experimentation show that post-yield mechanical properties of trabecular bone are strain rate and volume fraction dependant. Two constitutive material models describing the Ultimate strength, Plateau stress and absorbed energy are proposed based on published models valid for elastic properties of trabecular bone.

Hip fracture risk in patients with atrial fibrillation receiving oral anticoagulants: a meta-analysis based on current observational studies.

Hip fracture risk in patients with atrial fibrillation receiving oral anticoagulants: a meta-analysis based on current observational studies.

Hip fracture risk in patients with atrial fibrillation receiving oral anticoagulants.

Hip fracture risk in patients with atrial fibrillation receiving oral anticoagulants.

Hip Fracture Risk among Hemodialysis-Dependent Patients Prescribed Opioids and Gabapentinoids.

Despite opioids' known association with hip fracture risk in the general population, they are commonly prescribed to patients with ESKD. Whether use of opioids or gabapentinoids (also used to treat pain in patients with ESKD) contributes to hip fracture risk in patients with ESKD on hemodialysis remains unknown. In a case-control study nested within the US Renal Data System, we identified all hip fracture events recorded among patients dependent on hemodialysis from January 2009 through September 2015. Eligible cases were risk-set matched on index date with ten eligible controls. We required >1 year of Medicare Parts A and B coverage and >3 years of part D coverage to study cumulative longer-term exposure. To examine new, short-term exposure, we selected individuals with >18 months of Part D coverage and no prior opioid or gabapentinoid use between 18 and 7 months before index. We used conditional logistic regression to estimate unadjusted and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI). For the longer-term analyses, we identified 4912 first-time hip fracture cases and 49,120 controls. Opioid use was associated with increased hip fracture risk (adjusted OR, 1.39; 95% CI, 1.26 to 1.53). Subgroups of low, moderate, and high use yielded adjusted ORs of 1.33 (95% CI, 1.20 to 1.47), 1.53 (95% CI, 1.36 to 1.72), and 1.66 (95% CI, 1.45 to 1.90), respectively. The association with hip fractures was also elevated with new, short-term use (adjusted OR, 1.38; 95% CI, 1.25 to 1.52). There were no associations between gabapentinoid use and hip fracture. Among patients dependent on hemodialysis in the United States, both short-term and longer-term use of opioid analgesics were associated with hip fracture events.

Metacarpal bone mineral density by radiographic absorptiometry predicts fracture risk in patients undergoing maintenance hemodialysis

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guideline update suggests bone mineral density testing to assess fracture risk in patients with chronic kidney disease, but dual-energy X-ray absorptiometry is not available in most dialysis facilities. Radiographic absorptiometry is an inexpensive and quick method for evaluating bone mineral density. Therefore, we analyzed a historical cohort of 456 maintenance hemodialysis patients to determine whether metacarpal bone mineral density measured by digital image processing, a computer-assisted radiographic absorptiometry technique, predicts fracture risk. At baseline, the median metacarpal bone mineral density T-score was -2.05 (interquartile range, -3.35 to -0.99). During a mean follow-up of 5.3 years, there were 16 clinical fractures and 11 asymptomatic vertebral fractures as estimated by height loss. Metacarpal bone mineral density T-score was significantly lower in patients who sustained a clinical fracture than in those remaining event-free. Decreasing metacarpal bone mineral density T-score was significantly associated with increased risk of clinical fracture (hazard ratio, 1.41 per 1 standard deviation decrease in bone mineral density T-score [95% confidence interval, 1.09 to 1.83]; the hazard ratio for lowest versus highest tertile was 4.86 [1.03 to 22.92]. Similar associations were observed between metacarpal bone mineral density T-score and vertebral fracture or any fracture. The results were robust to different analysis strategies and were consistent across different subgroups. Thus, radiographic absorptiometry could be a useful tool for primary screening of hemodialysis patients at high risk for fracture. Additional studies are required to determine the predictive ability of radiographic absorptiometry techniques compared to dual-energy X-ray absorptiometry or other established methods.

Autonomous FEs (AFE) - A stride toward personalized medicine

Finite element analysis (FEA), introduced more than half a century ago, requires a (qualified) analyst to generate the necessary input data, verify the output and post process the analysis results for a meaningful conclusion. The required expertise and labor efforts have precluded the use of FEA in daily medical practice by orthopedic surgeons for example.Patient-specific analyses of the mechanical response of human bones may have a tremendous impact in clinical practice should they be easily accessible by orthopedic surgeons. Recent scientific advancements such as low dose CT scans, machine learning, and high order FEA which facilitates an inherent methodology for assessing numerical accuracy allow a fully autonomous process for assessing bone strength and fracture risk. This autonomous process, that we shall refer to here as “Autonomous Finite Element” (AFE) analysis, introduces a paradigm shift in the use of FEA.We shall describe herein a novel process that utilizes AFE to produce a patient-specific assessment of bone strength. The process consists of an automatic segmentation of femurs from CT-scans by convolution neural networks, an automatic mesh generation and application of boundary conditions based on anatomical points, a high-order FE analysis with numerical error control, and finally an automatic report with a clear assessment of bone fracture risk. One specific application of AFE is the determination of the risk of fracture for patients with tumors of the femur and whether a prophylactic surgery is needed. To the best of our knowledge this is the first CE accredited AFE application being used by orthopedic surgeons in clinical practice.

Effect of subclinical hyperthyroidism on osteoporosis: A meta-analysis of cohort studies.

The effect of subclinical hyperthyroidism (SH) on bone mineral density (BMD) remains unclear, as do the linking mechanisms. This review aims to investigate the relationship between SH and bone loss in terms of the gender-dependent effects of SH on BMD. The PUBMED, EMBASE, OVID, MEDLINE, SINOMED and COCHRANE LIBRARY databases (inception to August 12, 2019) were searched for cohort studies investigating the effects of SH on BMD. Eligible studies were subjected to qualitative and quantitative analysis using a random-effects model meta-analysis with the Cochrane systematic evaluation method. Twelve cohort studies involving 275,086 participants who were followed for 3 months to 13 years were included based on predefined inclusion and exclusion criteria. The results indicated that SH did not affect lumbar spine BMD in females or males. However, a significant reduction in femoral neck BMD was observed in females, but not in males. Further, there was a significant increase in hip fractures events in both females and males with SH. The present findings indicate that SH is significantly associated with hip fracture risk, and therefore, it is important to assess the risk of fractures in patients with SH. Future studies should focus on methods for accurately determining this risk in patients with SH and providing them with timely and efficient diagnosis and treatment.

Effects of carbamazepine, eslicarbazepine, valproic acid and levetiracetam on bone microarchitecture in rats.

Metabolic bone disease and fractures are a great problem for patients with epilepsy. The use of antiepileptic drugs (AEDs) is known to play an essential role in the progression of bone loss by various pathophysiological mechanisms. The aim of this study was to evaluate the effects of AEDs on bone microstructure as an additional cause of an increased fracture risk in patients with epilepsy. Five groups of each of 12 female rats were orally dosed daily for 8weeks with either carbamazepine (CBZ) (60mg/kg), eslicarbazepine (ESL) (80mg/kg), valproic acid (VPA) (300mg/kg), levetiracetam (LEV) (50mg/kg) or saline (control (CTL)). Following killing, dissected femurs were analyzed using X-ray micro-computed tomography (µCT), dual-energy X-ray absorptiometry (DXA) and biomechanical testing. In addition, serum bone turnover markers (BTM) were monitored throughout the experiment. Compared to CTL treatment, VPA decreased bone volume fraction by 19%, decreased apparent density by 14% and increased structural model index by 41%. No changes were observed in bone biomechanics nor mineral density evaluated by DXA or in levels of BTM. Our findings suggest that VPA affects the microarchitectural properties of the bone. The AEDs CBZ, ESL and LEV appear to have less adverse effects on bone biology and may be a better choice when treating patients with respect to bone health.

Effect of size and location of simulated lytic lesions on the structural properties of human vertebral bodies, a micro-finite element study

Currently, the Spinal Instability Neoplastic Score system is used in clinics to evaluate the risk of fracture in patients with spinal metastases. This method, however, does not always provide a clear guideline due to the complexity in accounting for the effect of metastatic lesions on vertebral stability. The aim of this study was to use a validated micro Finite Element (microFE) modelling approach to analyse the effect of the size and location of lytic metastases on the mechanical properties of human vertebral bodies. Micro Computed Tomography based microFE models were generated with and without lytic lesions simulated as holes within a human vertebral body. Single and multiple lytic lesions were simulated with four different sizes and in five different locations. Bone was assumed homogenous, isotropic and linear elastic, and each vertebra was loaded in axial compression. It was observed that the size of lytic lesions was linearly related with the reduction in structural properties of the vertebral body (reduction of stiffness between 3% and 30% for lesion volume between 4% and 35%). The location of lytic lesions did not show a clear effect on predicted structural properties. Single or multiple lesions with the same volume provided similar results. Locally, there was a homogeneous distribution of axial principal strains among the models with and without lytic lesions. This study highlights the potential of microFE models to study the effect of lesions on the mechanical properties of the human vertebral body.

Skeletal and mineral metabolic effects of risedronate in a rat model of high-turnover renal osteodystrophy.

High-turnover bone disease is a major consequence of SHPT and may explain the high risk for fracture in patients with advanced chronic kidney disease (CKD). Bisphosphonates suppress bone turnover and improve bone strength, but their effects have not been fully characterized in advanced CKD with severe SHPT. Bisphosphonates also increase 1,25-dihydroxyvitamin D levels in normal and uremic rats, but the underlying mechanism remains to be determined. We investigated the skeletal and mineral metabolic effects of RIS, a pyridinyl bisphosphonate, in rats with severe SHPT induced by 5/6 nephrectomy plus a high phosphate diet. Nephrectomized rats developed severe SHPT, along with hyperphosphatemia, low 1,25-dihydroxyvitamin D, and markedly increased FGF23. Moreover, these rats exhibited characteristic features of high-turnover renal osteodystrophy, including increased indices of trabecular bone turnover, decreased cortical bone thickness, inferior cortical biomechanical properties, and a prominent increase in peritrabecular fibrosis. RIS treatment increased bone volume and partially attenuated trabecular bone remodeling, cortical bone loss, and mechanical properties, whereas it produced a marked improvement in peritrabecular fibrosis along with a corresponding decrease in osteogenic gene markers. RIS treatment also suppressed the elevation of FGF23, which was associated with increased 1,25-dihydroxyvitamin D. In a rat model of severe SHPT, treatment with RIS partially attenuated histological manifestations of high-turnover bone disease. RIS treatment also suppressed the elevation of FGF23, which may explain the increased 1,25-dihydroxyvitamin D production during the treatment.

Abaloparatide in Postmenopausal Women With Osteoporosis and Type 2 Diabetes: A Post Hoc Analysis of the ACTIVE Study.

ABSTRACTType 2 diabetes mellitus (T2DM) increases fracture risk despite normal or increased BMD. Abaloparatide reduces fracture risk in patients with postmenopausal osteoporosis (PMO); however, its efficacy in women with T2DM is unknown. This post hoc analysis evaluated the efficacy and safety of abaloparatide in patients with T2DM. The analysis included patients with T2DM from the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), a phase 3, double‐blind, randomized, placebo‐ and active‐controlled trial. In ACTIVE, participants were randomized 1:1:1 to daily s.c. injections of placebo, abaloparatide (80 μg), or open‐label teriparatide (20 μg) for 18 months. A total of 198 women with PMO and T2DM from 21 centers in 10 countries were identified from ACTIVE through review of their medical records. The main outcomes measured included effect of abaloparatide versus placebo on BMD and trabecular bone score (TBS), with secondary outcomes of fracture risk and safety, in patients from ACTIVE with T2DM. Significant (p < 0.001) improvements in BMD at total hip (mean change 3.0% versus −0.4%), femoral neck (2.6% versus −0.2%), and lumbar spine (8.9% versus 1.3%) and TBS at lumbar spine (3.72% versus −0.56%) were observed with abaloparatide versus placebo at 18 months. Fracture events were fewer with abaloparatide treatment in patients with T2DM, and differences were not significant between groups except nonvertebral fractures in the abaloparatide versus placebo groups (p = 0.04). Safety was consistent with the ACTIVE population. In conclusion, in women with PMO and T2DM, abaloparatide treatment resulted in significant improvements in BMD and TBS versus placebo, consistent with the overall ACTIVE population © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

No decrease in fracture risk despite 15 years of treatment evolution for multiple myeloma patients: A Danish nationwide case-control study.

While treatment strategies for multiple myeloma have evolved radically over the last decades, little is known about the risk of fractures for symptomatic multiple myeloma patients over time. To determine the effect of different treatment periods (1996-2000, 2001-2006 and 2007-2011) on the risk of fractures in patients with multiple myeloma. This retrospective case-control study included patients with multiple myeloma in Denmark, using the Danish National Health Service. Cases were defined as patients who had sustained a fracture between 1996 and 2011, and controls were those without a fracture. Exposure was defined as an ICD code for multiple myeloma. Vertebral fractures, gender, and age were considered in secondary analyses. Conditional logistic regression was used to estimate odd ratios (ORs) of fracture risk, and the analyses were adjusted for comorbidities and recent drug use. The study population consisted of 925,341 cases, and the same number of matched controls, of whom 1334 patients with multiple myeloma. Among cases, the risk of any fracture was higher in multiple myeloma patients compared to patients without multiple myeloma (any fracture: ORadj[95% CI] 1996-2000: 1.7[1.3-2.3]; 2001-2006: 1.3[1.1-1.6]; 2007-2011: 1.7[1.4-2.2]). Although fractures were mainly non-vertebral, the risk of vertebral fractures in particular was higher in multiple myeloma patients (vertebral fracture: ORadj[95% CI] 1996-2000: 3.5[1.4-8.6]; 2001-2006: 4.0[1.9-8.2]; 2007-2011: 3.0[1.6-5.7]). Despite new treatment strategies and improved supportive care, this study showed no decreased fracture risk for multiple myeloma patients over time. New treatment strategies, even if they have a positive impact on overall survival, offer no guarantee for a corresponding reduction in bone lesions.

Bone material strength index is associated with prior fracture in men with and without moderate chronic kidney disease.

Patients with chronic kidney disease (CKD) are at high risk for fracture. The ability of bone mineral density (BMD) to predict fractures in CKD patients has been inconsistent. Other measures such as trabecular bone score (TBS) and impact microindentation (IMI) may be more useful in this group. This study aimed to determine if TBS or IMI values differed between men with and without CKD and examine associations between prior fracture, TBS and IMI values. Men (n=343, age 33-96yr) from the Geelong Osteoporosis Study were included. Femoral neck (FNBMD) and lumbar spine BMD (LSBMD) were measured using DXA (Lunar ProdigyPro). TBS was determined from lumbar spine scans (TBS iNsight software Version 2.2). IMI values (bone material strength index; BMSi) were measured using an OsteoProbe. CKD was defined as an eGFR<60mL/min/1.73m2 (n=53). Prior low trauma fractures (n=37) were ascertained from radiological reports. Associations were examined using binary logistic regression, adjusting for potential confounders. Interaction terms were tested in all models. Men with CKD tended to have a higher likelihood of prior fracture (adjusted OR 2.27, 95%CI 1.02-5.01). Higher BMSi was associated with a lower likelihood of prior fracture (adjusted OR for 1SD increase: 0.70; 95%CI 0.51-0.97). This association was sustained after adjustment for FNBMD (OR 0.68; 95%CI 0.49-0.96) or LSBMD (OR 0.69; 95%CI 0.49-0.95). No interaction was detected between BMSi and CKD (p=0.898). No associations were detected between FNBMD, LSBMD or TBS and prior fracture in either population and there were no interactions with CKD for FNBMD, LSBMD or TBS. BMSi was associated with prior fracture in men with and without CKD, however, FNBMD, LSBMD and TBS were not. Lack of an interaction term suggests that BMSi performed similarly in identifying the likelihood of prior fracture, regardless of CKD status. IMI may have clinical utility for assessing fracture risk in patients with CKD.

Sodium-glucose cotransporter 2 inhibitors and fracture risk in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.

Background:Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fracture compared with those without T2DM. Some oral glucose-lowering agents may increase the incidence of fracture. Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) are associated with increased risk of fracture remains unclear.Methods:We retrieved articles from PubMed, Embase, Cochrane Library database, and other sources up to 24 October 2019. We included randomized controlled trials (RCTs) that reported fractures and analyzed the fracture incidence of SGLT2i, canagliflozin, dapagliflozin, and empagliflozin. Subgroup analysis was also performed based on baseline characteristics.Results:A total of 78 RCTs with 85,122 patients were included in our analysis. The overall SGLT2i fracture incidence was 2.56% versus 2.77% in the control group [odds ratio (OR), 1.03; 95% confidence interval (CI) (0.95, 1.12); p = 0.49]. Compared with the control treatment, treatment with canagliflozin led to a higher rate of fractures [OR, 1.17; 95% CI (1.00, 1.37); p = 0.05], but no significant difference was observed when compared with dapagliflozin [OR, 1.02; 95% CI (0.90, 1.15); p = 0.79] or empagliflozin [OR, 0.89; 95% CI (0.73, 1.10); p = 0.30]. Subgroup analysis showed that, in a follow-up of less than 52 weeks, SGLT2i decreased the incidence of fracture by 29% [OR, 0.71; 95% CI (0.55, 0.93); p = 0.01], but this benefit was lost when the follow-up extended to more than 52 weeks [OR, 1.08; 95% CI (0.98, 1.18); p = 0.12].Conclusion:Canagliflozin seems to increase the risk of fracture, while other SGLT2is do not result in a higher incidence of fracture.