Probability Of Major Osteoporotic Fracture Research Articles

Associations of accelerometer-estimated free-living daily activity impact intensities with 10-year probability of osteoporotic fractures in adults

PurposeAccelerometers are used to objectively measure physical activity; however, the relationship between accelerometer-based activity parameters and bone health is not well understood. This study examines the association between accelerometer-estimated daily activity impact intensities and future risk estimates of major osteoporotic fractures in a large population-based cohort. MethodsParticipants were 3165 adults 46 years of age from the Northern Finland Birth Cohort 1966 who agreed to wear a hip-worn accelerometer during all waking hours for 14 consecutive days. Raw accelerometer data were converted to resultant acceleration. Impact magnitude peaks were extracted and divided into 32 intensity bands, and the osteogenic index (OI) was calculated to assess the osteogenic effectiveness of various activities. Additionally, the impact peaks were categorized into three separate impact intensity categories (low, medium, and high). The 10-year probabilities of hip and all major osteoporotic fractures were estimated with FRAX-tool using clinical and questionnaire data in combination with body mass index collected at the age of 46 years. The associations of daily activity impact intensities with 10-year fracture probabilities were examined using three statistical approaches: multiple linear regression, partial correlation, and partial least squares (PLS) regression. ResultsOn average, participants’ various levels of impact were 8331 (SD = 3478) low; 2032 (1248) medium; and 1295 (1468) high impacts per day. All three statistical approaches found a significant positive association between the daily number of low-intensity impacts and 10-year probability of hip and all major osteoporotic fractures. In contrast, increased number of moderate to very high daily activity impacts was associated with a lower probability of future osteoporotic fractures. A higher OI was also associated with a lower probability of future major osteoporotic fractures. ConclusionLow-intensity impacts might not be sufficient for reducing fracture risk in middle-aged adults, while high-intensity impacts could be beneficial for preventing major osteoporotic fractures.

Geriatric nutritional risk index as a predictor for fragility fracture risk in elderly with type 2 diabetes mellitus: A 9-year ambispective longitudinal cohort study

The elderly are prone to fragility fractures, especially those suffering from type 2 diabetes mellitus (T2DM) combined with osteoporosis. Although studies have confirmed the association between GNRI and the prevalence of osteoporosis, the relationship between GNRI and fragility fracture risk and the individualized 10-year probability of osteoporotic fragility fractures estimated by FRAX remains unclear. This study aims to delve into the association between the GNRI and a fragility fracture and the 10-year probability of hip fracture (HF) and major osteoporotic fracture (MOF) evaluated by FRAX in elderly with T2DM. A total of 580 patients with T2DM aged ≥60 were recruited in the study from 2014 to 2023. This research is an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 3.8 years through outpatient services, medical records, and home fixed-line telephone interviews. According to the tertiles of GNRI, all subjects were divided into three groups: low-level (59.72-94.56, n=194), moderate-level (94.56-100.22, n=193), and high-level (100.22-116.45, n=193). The relationship between GNRI and a fragility fracture and the 10-year probability of HF and MOF calculated by FRAX was assessed by receiver operating characteristic (ROC) analysis, Spearman correlation analyses, restricted cubic spline (RCS) analyses, multivariable Cox regression analyses, stratified analyses, and Kaplan-Meier survival analysis. Of 580 participants, 102 experienced fragile fracture events (17.59%). ROC analysis demonstrated that the optimal GNRI cut-off value was 98.58 with a sensitivity of 75.49% and a specificity of 47.49%, respectively. Spearman partial correlation analyses revealed that GNRI was positively related to 25-hydroxy vitamin D [25-(OH) D] (r=0.165, P<0.001) and bone mineral density (BMD) [lumbar spine (LS), r=0.088, P=0.034; femoral neck (FN), r=0.167, P<0.001; total hip (TH), r=0.171, P<0.001]; negatively correlated with MOF (r=-0.105, P=0.012) and HF (r=-0.154, P<0.001). RCS analyses showed that GNRI was inversely S-shaped dose-dependent with a fragility fracture event (P<0.001) and was Z-shaped with the 10-year MOF (P=0.03) and HF (P=0.01) risk assessed by FRAX, respectively. Multivariate Cox regression analysis demonstrated that compared with high-level GNRI, moderate-level [hazard ratio (HR)=1.950; 95% confidence interval (CI)=1.076-3.535; P=0.028] and low-level (HR=2.538; 95% CI=1.378-4.672; P=0.003) had an increased risk of fragility fracture. Stratified analysis exhibited that GNRI was negatively correlated with the risk of fragility fracture, which the stratification factors presented in the forest plot were not confounding factors and did not affect the prediction effect of GNRI on the fragility fracture events in this overall cohort population (P for interaction>0.05), despite elderly females aged ≥70, with body mass index (BMI) ≥24, hypertension, and with or without anemia (all P<0.05). Kaplan-Meier survival analysis identified that the lower-level GNRI group had a higher cumulative incidence of fragility fractures (log-rank, all P<0.001). This study confirms for the first time that GNRI is negatively related to a fragility fracture and the 10-year probability of osteoporotic fragility fractures assessed by FRAX in an inverse S-shaped and Z-shaped dose-dependent pattern in elderly with T2DM, respectively. GNRI may serve as a valuable predictor for fragility fracture risk in elderly with T2DM. Therefore, in routine clinical practice, paying attention to the nutritional status of the elderly with T2DM and giving appropriate dietary guidance may help prevent a fragility fracture event.

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

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

Assessment of the bone biological age using multiple regression and neural network analysis

Background. Nowadays, many studies confirm the increased risk of osteoporosis in the elderly. Strategies for optimizing diagnosis include a combined use of various methods, so calculating bone biological age (BA) can also be important for disease prediction. Recently, some new methodological approaches to BA calculation with the mathematical methods implementation were proposed. However, studies utilizing advanced approaches, particularly neural network (NN) in Ukraine, are limited. The purpose of this study was to develop a bone BA model and compare its accuracy using stepwise multiple regression (MLR) and NN analysis methods. Materials and methods. In a single-center cohort study, we retrospectively analyzed the data of 3,071 healthy women aged 40–90 years. The analysis of the study indices included the anthropometric parameters, dual-energy X-ray absorptiometry indices (DXA), and the parameters of the 10-year probability of major osteoporotic fractures (FRAX). For the development of bone BA models, MLR methods were used and the construction of the NN model was performed using a multilayer perceptron model. Results. As a result of the calculation, we received the MLR formula for bone BA determining bone mineral density (BMD) of lumbar spine and radius, minimal femoral and hip BMD as well as Trabecular Bone Score, and FRAX. The MLR equation allowed to calculation of the bone BA with an error of less than 4.9 years for study and control groups and demonstrated the high connection between calculated and chronological (ChrA) ages (R = 0.77; p &lt; 0.00001). The use of NN analysis showed the best results using 6 input variables and 1 internal layer of 7 neurons. The assessment of the connection between BA and ChrA demonstrated a high coefficient of correlation (R = 0.88; p &lt; 0.000001) with an average error of age calculation of less than 3.7 years for the study and control groups. Conclusions. A comparison of the accuracy of both models in bone BA estimation revealed a significant advantage of the deep learning NN, however, the use trained NN model requires specialized software, whereas the MLR formula can be used without additional costs.

Probability of the 10-year Risk of Hip and Major Osteoporotic Fracture in Non-radiographic Axial Spondyloarthritis.

Fracture risk in non-radiographic spondyloarthritis is underestimated. A reliable tool such as the Fracture Risk Assessment tool (FRAX) may assess this risk probability. This study aimed to assess the fracture risk by the FRAX score in patients with nr-axSpA and to determine factors associated with high fracture risk. We conducted a retrospective study of nr-axSpA patients meeting the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for spondyloarthritis. All patients had Bone Mineral Density (BMD) by dual-energy X-ray absorptiometry (DEXA). The 10- year probability of major osteoporotic fracture (MOF) and hip fracture (HF) was calculated using the Fracture Risk Assessment Tool (FRAX). Among 40 patients with nr-axSpA, 27 were women (67.5%). Their mean age was 43.7 ± 12.1 years. The mean disease duration was 3.15 ± 2.7 years. Eighteen patients (45%) had osteopenia, and 12 patients (30%) had osteoporosis. The median HF FRAX was 0% [0-1.2]. The median MOF FRAX was 0.5% [0.3-1.8]. MOF FRAX was positively correlated with age (p = 0.002), disease onset age (p = 0.006), disease duration (p = 0.024), and the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) (p < 0.0001), and negatively correlated with daily calcium intake (p < 0.0001). HF FRAX was positively correlated with mSASSS (p < 0.0001) and negatively correlated with daily calcium intake (p = 0.005). Our study confirmed the frequency of bone loss during nr-axSpA and showed that osteoporotic risk fracture was related not only to traditional risk factors for osteoporosis but also to disease-related factors.

Association of secondhand smoke with fracture risk in community-dwelling nonsmoking adults in Korea.

Although the detrimental effects of active smoking on bone health have been widely recognized, the impact of secondhand smoke exposure on fracture risk in non-smokers remains less understood. A total of 4843 nonsmokers aged 40-69yr, who participated in the Korean Genome and Epidemiology Study from 2001 to 2018, were analyzed. The participants were categorized into two groups based on their exposure status to secondhand smoke: currently exposed and unexposed. The exposure group was subsequently divided into two subgroups based on the median weekly exposure time (high vs low). The incidence of new fractures was determined using self-reported questionnaires. The identified fractures were categorized according to the fracture site: overall, vertebral, hip, non-vertebral, and non-vertebral non-hip fractures. The mean age of the participants was 52.4yr (84.1% women). Exposure to secondhand smoke was associated with an increased risk of fracture (adjusted hazard ratio [aHR]: 1.27, P =0.028) after adjusting for multiple covariates including age, sex, BMI, household income, bone density of mid-shaft tibia, C-reactive protein, alcohol consumption, and fracture history. Secondhand smoke remained as a significant risk factor for fracture, independent of the major osteoporotic fracture probabilities estimated using a fracture risk assessment tool (aHR: 1.24, P =0.038). The high exposure group had higher risk of fracture than that of the unexposed group (aHR: 1.33, P =0.025), whereas the fracture risk did not differ significantly between low exposure and unexposed groups (aHR: 1.18, P =0.253), suggesting a potential dose-response relationship. Secondhand smoke showed robust association with increased risk of non-vertebral (aHR: 1.37, P =0.008) or non-vertebral non-hip fractures (aHR: 1.36, P =0.013), while its association with vertebral fracture was attenuated (aHR: 1.03, P =0.908). Secondhand smoke was associated with an elevated risk of fracture in nonsmokers, independent of clinical risk factors.

Fracture prediction in rheumatoid arthritis: validation of FRAX with bone mineral density for incident major osteoporotic fractures

Abstract Objectives FRAX uses clinical risk factors, with or without BMD, to calculate 10-year fracture risk. RA is a risk factor for osteoporotic fracture and a FRAX input variable. FRAX predates the current era of RA treatment. We examined how well FRAX predicts fracture in contemporary RA patients. Methods Administrative data from patients receiving BMD testing were linked to the Manitoba Population Health Research Data Repository. Observed cumulative 10-year major osteoporotic fracture (MOF) probability was compared with FRAX-predicted 10-year MOF probability with BMD for assessing calibration. MOF risk stratification was assessed using Cox regression. Results RA patients (n = 2099, 208 with incident MOF) and non-RA patients (n = 2099, with 165 incident MOF) were identified. For RA patients, FRAX-predicted 10-year risk was 13.2% and observed 10-year MOF risk was 13.2% (95% CI 11.6, 15.1). The slope of the calibration plot was 0.67 (95% CI 0.53, 0.81) in those with RA vs 0.98 (95% CI 0.61, 1.34) in non-RA patients. Risk was overestimated in RA patients with high FRAX scores (&amp;gt;20%), but FRAX was well calibrated in other groups. FRAX stratified risk in those with and without RA [hazard ratio (HR) 1.52 (95% CI 1.25, 1.72) vs 2.00 (95% CI 1.73, 2.31)], with slightly better performance in the latter (P for interaction = 0.004). Conclusions FRAX predicts fracture risk in contemporary RA patients but may slightly overestimate risk in those already at high predicted risk. Thus the current FRAX tool continues to be appropriate for fracture risk assessment in RA patients.

Effect of BMI-Discordant Abdominal Tissue Thickness on Fracture Probability: A Registry-Based Study.

FRAX, which is used to assess fracture probability, considers body mass index (BMI), but BMI may not reflect individual variation in body composition and distribution. We examined the effect of BMI-discordant abdominal thickness on FRAX-derived fracture probability for major osteoporotic fracture (MOF) and hip fracture. We studied 73,105 individuals, mean age 64.2 years. During mean 8.7 years, 7048 (9.6%) individuals sustained incident MOF, including 2155 (3.0%) hip fractures. We defined abdominal thickness index (ATI) as the difference between abdominal thickness measured by dual-energy X-ray absorptiometry (DXA) and thickness predicted by BMI using sex-stratified regression. ATI was categorized from lower (<-2 cm, -2 to -1 cm) to higher (1-2 cm, >+2 cm) with referent around zero (-1 to +1 cm). Adjusted for FRAX probability, increasing ATI was associated with incident MOF and hip fracture (p < 0.001). For the highest ATI category, MOF risk was increased (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.12-1.35) independent of FRAX probability. Similar findings were noted for hip fracture probability (HR = 1.28, 95% CI 1.09-1.51). There was significant age-interaction with much larger effects before age 65 years (HR = 1.44, 95% CI 1.23-1.69 for MOF; 2.29, 95% CI 1.65-3.18 for hip fracture). In contrast, for the subset of individuals with diabetes, there was also increased risk for those in the lowest ATI category (HR = 1.73, 95% CI 1.12-2.65 for MOF; 2.81, 95% CI 1.59-4.97 for hip fracture). Calibration plots across ATI categories demonstrated deviation from the line of identity in women (calibration slope 2.26 for MOF, 2.83 for hip fracture). An effect of ATI was not found in men, but this was inconclusive as the sex-interaction terms did not show significant effect modification. In conclusion, these data support the need to investigate increased abdominal thickness beyond that predicted by BMI and sex as a FRAX-independent risk factor for fracture. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

SAT339 Osteopenia In The Setting of Mild Autonomous Cortisol Secretion

Abstract Disclosure: J.J. Mao: None. K.C. McCowen: None. C. Choe: None. Jimmy J. Mao, MD (1); Karen C. McCowen (1); Charles H. Choe (1)(1) Division of Endocrinology, Diabetes, and Metabolism, University of California San Diego, La Jolla, CA. Background: Over 80% of adrenal incidentalomas are benign adrenal cortical adenomas, of which 30-50% are found to have mild autonomous cortisol secretion (MACS). Bone fragility is a known complication of MACS. Clinical Case: A 57-year-old postmenopausal female with no prior history of fracture, venous thromboembolism, and atherosclerotic cardiovascular disease, was referred for incidental bilateral adrenal nodules. Body mass index was normal at 21 kg/m2, and no clinical stigmata of Cushing syndrome were noted on physical exam. Unenhanced computed tomography scan revealed a 4.6 cm right adrenal nodule and a 3.3 cm left adrenal nodule; both nodules measured less than -18 Hounsfield Units. Biochemical work-up for pheochromocytoma, primary aldosteronism, and non-classical congenital adrenal hyperplasia was negative. Evaluation for hypercortisolism revealed a morning cortisol of 20.3 mcg/dL (ref. 4-22 mcg/dL) with concurrent adrenocorticotropic hormone of &amp;lt;5 pg/mL (ref. 6-50 pg/mL), 24-hour urine free cortisol of 16.9 mcg (ref. 4-50 mcg), and midnight salivary cortisol of 0.07 mcg/dL (ref. &amp;lt;0.09 mcg/dL). A 1 mg dexamethasone suppression test measured on two separate occasions was elevated at 6.3 mcg/dL and 7.9 mcg/dL (ref. &amp;lt;1.8 mcg/dL). A subsequent 8 mg dexamethasone suppression test was also elevated at 6.1 mcg/dL (ref. &amp;lt;1.8 mcg/dL). The diagnosis of MACS was made. A bone mineral density (BMD) scan revealed T-scores at the right femoral neck, left femoral neck, and lumbar spine at -1.6, -1.3, and -0.8, respectively. Ten-year probability of major osteoporotic fracture and hip fracture were 8.3% and 1.0%, respectively. To reduce the risk for future fractures, the decision was made to proceed with adrenal vein sampling (AVS) in preparation for potential adrenalectomy. Conclusion: MACS is the most frequent hormonal abnormality in adrenal incidentalomas, with an estimated prevalence of 0.8-2 cases per 1000 persons. A previous prospective study found that surgical cure of unilateral MACS may lead to a substantial risk reduction (up to 15-fold) of future incident asymptomatic vertebral fractures. Additionally, the highest risk for clinical fracture in those with adrenal adenomas (either nonfunctional or with cortisol hypersecretion) appears to occur at 7-10 years after initial diagnosis. BMD does not perfectly correlate with fracture risk, so unilateral adrenalectomy (if lateralization is observed on AVS) and/or pharmacotherapy should be strongly considered in patients with an expected longevity of &amp;gt;10 years even with mild osteopenia and low fracture risk assessment tool scores. Presentation: Saturday, June 17, 2023

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.

Romosozumab Efficacy in Postmenopausal Women With No Prior Fracture Who Fulfill Criteria for Very High Fracture Risk

ObjectiveWe evaluated the efficacy of romosozumab in women from FRAME who had no prior fracture but met other criteria for very high fracture risk (VHFR). MethodsIn FRAME, postmenopausal women received romosozumab or placebo for 12 months (year 1) followed by denosumab for 12 months (year 2). In this post hoc analysis, we applied the following criteria from the American Association of Clinical Endocrinology to define VHFR: lumbar spine or total hip T-score <−3.0 and/or Fracture Risk Assessment Tool probability of major osteoporotic fracture >30% or hip fracture >4.5% to women with no fracture history at baseline (no fracture-VHFR [NF-VHFR]). Incidence of new vertebral, clinical, and nonvertebral fractures and mean bone mineral density (BMD) percentage change from baseline were assessed at years 1 and 2. ResultsOf the 7180 women in FRAME, 2825 were included in the NF-VHFR subgroup analysis. At year 1, romosozumab versus placebo reduced the incidence of new vertebral fracture (relative risk reduction [RRR]: 76%), clinical fracture (RRR: 60%), and nonvertebral fracture (RRR: 54%) (all P <.05). This fracture reduction was maintained through year 2 in women receiving the romosozumab-to-denosumab sequence versus the placebo-to-denosumab sequence for new vertebral, clinical, and nonvertebral fractures (RRR: 77%, 54%, and 46%, respectively; all P <.05). The mean BMD changes in both treatment groups were similar to those in the overall FRAME population at years 1 and 2. ConclusionRomosozumab significantly reduced vertebral, clinical, and nonvertebral fracture risk and increased the BMD more than placebo in women at VHFR.

FRAX-based intervention thresholds for men in the Russian Federation: Expert consensus of the Russian association on osteoporosis

According to the European guidelines for osteoporosis, the same FRAX intervention threshold is suggested for men as for women. At the same time, in the Russian Federation, according to research data, an extremely low proportion of identified men who are subject to the initiation of osteoporosis therapy. The female intervention threshold identifies only 1.1 to 4% of men for treatment. Aim – to develop and evaluate various options for the intervention threshold using the FRAX calculator for men in the Russian Federation and adopt the most acceptable intervention threshold by consensus. Material and methods. Delphi voting was conducted among 18 Russian experts who have publications and personal reports about their experience with the FRAX calculator. For discussion, 5 intervention threshold options with the corresponding rationale based on the literature reference were presented, as well as the proportion of men of different ages to be initiated in each of the options (based on several Russian population-based studies). Anonymous voting was carried out using the Delphi method with questionnaire placed in the Google form. It was proposed to evaluate all options for intervention thresholds on a 9-point Likert scale. Consensus was considered reached if the intervention threshold reached a Likert score of 7 or more points in 80% or more of the experts. The rating of each intervention threshold option was expressed as mean and standard deviations. Results. In the first round of voting, the maximum rating and percentage of agreement is reached for the 9% fixed interference threshold option based on the FRAX calculation. The rating was 7.72±1.6 points, the percentage of experts’ agreement was 88.9%. A fixed threshold of 9% determined 13–19.5% of men aged 50 years and older to be treated for osteoporosis, while their proportion increased to 26–38% at the age of 85 years and older. Conclusion. The consensus of experts of the Russian association on osteoporosis suggests initiating treatment of osteoporosis in Russian men with a 10-year probability of major osteoporotic fractures according to FRAX of 9% or higher.

Optimized calculator for a qualitative risk assessment of osteoporotic fractures for the population of Moscow

BACKGROUND: The FRAX tool (a 10-year fracture risk assessment) is recommended to diagnose osteoporosis and optimize the number of patients who need to undergo X-ray densitometry. Due to various circumstances, the integration of a full-fledged FRAX tool into the digital circuits of the Moscow City Health Department is problematic.&#x0D; AIM: The study aimed to develop a calculator of the 10-year probability of osteoporotic fractures to optimize the routing of patients for examination.&#x0D; METHODS: An optimized Half-FRAX calculator was created based on the FRAX tool from the University of Sheffield, which was developed using the results of population studies of the Russian Federation. All data used in the original FRAX algorithm, i.e. sex, age, height, weight, and T-criterion (if available) and other important parameters such as a history of fractures, parental hip fractures, smoking, rheumatoid arthritis, secondary osteoporosis, and glucocorticoid and alcohol intake were included in the risk assessment calculator. An algorithm for interaction with the FRAX website was developed and implemented to verify critical levels of patient stratification by multiple consecutive enumerations of different combinations of body mass index (BMI) measurements (0.1 discretization) and age (1-year discretization). Data from clinical guidelines were taken as thresholds.&#x0D; RESULTS: When implementing the developed algorithm by modeling various combinations of BMI, T-criterion, and risk factors (RF), the absence of RFs and BMI 25 (upper limit of normal) in women was shown to guarantee the exclusion from the orange zone where densitometry should be performed. In men, BMI was not a RF. If a RF was present, a patient was recommended to consult a doctor. If no T-criterion was present, but a RF was detected, the patient was indicated for densitometry. Similar results were reported for women with the same indices. In the absence of the RF and with a T-criterion 2.5, low fracture risk factor was indicated for both men and women.&#x0D; CONCLUSIONS: An optimized Half-FRAX calculator for the 10-year probability of major osteoporotic fractures was developed, which may optimize the routing of patients for densitometry and reduce the burden on radiology departments in Moscow. This will allow patients to be timely referred to the clinical specialists for consultations. Half-FRAX is integrated into the Osteoporosis Digital Platform (https://telemedai.ru/cifrovaya-platforma-osteoporoz/half-frax).

Jump Power Predicts Fracture Risk in Older Adults Independent of Sarcopenia and FRAX.

Low countermovement jump power is associated with prevalent fracture, osteoporosis, and sarcopenia in older adults. However, whether jump power predicts incident fracture risk remains uninvestigated. Data of 1366 older adults in a prospective community cohort were analyzed. Jump power was measured using a computerized ground force plate system. Fracture events were ascertained by follow-up interview and linkage to the national claim database (median follow-up 6.4 years). Participants were divided into normal and low jump power groups using a predetermined threshold (women <19.0 W/kg; men <23.8 W/kg; or unable to jump). Among the study participants (mean age 71.6 years, women 66.3%), low jump power was associated with a higher risk of fracture (hazard ratio [HR] = 2.16 versus normal jump power, p < 0.001), which remained robust (adjusted HR = 1.45, p = 0.035) after adjustment for fracture risk assessment tool (FRAX) major osteoporotic fracture (MOF) probability with bone mineral density (BMD) and Asian Working Group for Sarcopenia (AWGS) 2019 sarcopenia definition. In the AWGS no sarcopenia group, participants with low jump power had a significantly higher risk of fracture than those with normal jump power (12.5% versus 6.7%; HR = 1.93, p = 0.013), comparable to that of possible sarcopenia without low jump power (12.0%). Possible sarcopenia group with low jump power had a similar risk of fracture (19.3%) to sarcopenia group (20.8%). When the definition of sarcopenia was modified with jump power measurement (step-up approach: no sarcopenia to possible sarcopenia; possible sarcopenia to sarcopenia when low jump power present), jump power-modified sarcopenia improved sensitivity (18%-39.3%) to classify individuals who sustained MOF during follow-up to high risk compared with AWGS 2019 sarcopenia, while maintaining positive predictive value (22.3%-20.6%). In summary, jump power predicted fracture risk in community-dwelling older adults independently of sarcopenia and FRAX MOF probabilities, suggesting potential contribution of complex motor function measurement in fracture risk assessment. © 2023 American Society for Bone and Mineral Research (ASBMR).

Trabecular Bone Score Vertebral Exclusions Affect Risk Classification and Treatment Recommendations: The Manitoba Bmd Registry

Lumbar spine trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. Lumbar vertebral levels that show structural artifact are excluded from BMD measurement. TBS is relatively unaffected by degenerative artifact, and it is uncertain whether the same exclusions should be applied to TBS reporting. To gain insight into the clinical impact of vertebral exclusion on TBS, we examined the effect of lumbar vertebral exclusions in routine clinical practice on tertile-based TBS categorization and TBS adjusted FRAX-based treatment recommendations. The study population consisted of 71,209 individuals aged 40 years and older with narrow fan-beam spine DXA examinations and retrospectively-derived TBS. During BMD reporting, 34.3% of the scans had one or more vertebral exclusions for structural artifact. When TBS was derived from the same vertebral levels used for BMD reporting, using fixed L1-L4 tertile cutoffs (1.23 and 1.31 from the McCloskey meta-analysis) reclassified 17.9% to a lower and 6.5% to a higher TBS category, with 75.6% unchanged. Reclassification was reduced from 24.4% overall to 17.2% when level-specific tertile cutoffs from the software manufacturer were used. Treatment reclassification based upon FRAX major osteoporotic fracture probability occurred in 2.9% overall, but in 9.6% of those with baseline risk ≥15%. For treatment based upon FRAX hip fracture probability, reclassification occurred in 3.4% overall, but in 10.4% in those with baseline risk ≥2%. In summary, lumbar spine TBS measurements based upon vertebral levels other than L1-L4 can alter the tertile category and treatment recommendations based upon TBS-adjusted FRAX calculation, especially for those close to or exceeding the treatment cut-off. Manufacturer level-specific tertile cut-offs should be used if vertebral exclusions are applied.

Association of C-peptide level with bone mineral density in type 2 diabetes mellitus.

To explore the relationship between C-peptide and BMD and fracture risk in T2DM patients. 530 T2DM patients were enrolled and divided into three groups by FCP tertiles, and the clinical data were collected. BMD was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fractures (MOFs) and hip fractures (HFs) was evaluated by adjusted fracture risk assessment tool (FRAX). In the FCP ≤ 1.14ng/ml group, FCP level was positively correlated with WB, LS, and FN BMD, while FCP was negatively correlated with fracture risk and osteoporotic fracture history. However, FCP was not correlated with BMD and fracture risk and osteoporotic fracture history in the 1.14 < FCP ≤ 1.73ng/ml and FCP > 1.73ng/ml groups. The study has shown that FCP was an independent factor influencing BMD and fracture risk in the FCP ≤ 1.14ng/ml group. There is no significant linear relationship between FCP level and BMD or fracture risk in T2DM patients. In the FCP ≤ 1.14ng/ml group, FCP is positively correlated with WB, LS, and FN BMD and negatively correlated with fracture risk, and FCP is an independent influencing factor of BMD and fracture risk. The findings suggest that FCP may predict the risk of osteoporosis or fracture in some T2DM patients, which has a certain clinical value.

Osteoporosis: Spotlight on current approaches to pharmacological treatment.

Despite the availability of safe and effective anti-osteoporosis treatments, osteoporosis continues to be undertreated. The increase in fragility fractures, which is the main clinical consequence of osteoporosis, is a major problem for healthcare systems of countries. A broad range of drugs including antiresorptive and anabolic agents are used in the pharmacological treatment of osteoporosis. Fracture risk assessment in drug selection is of utmost importance in terms of guiding treatment. The recommended thresholds for osteoporosis treatment decision making are based on major osteoporotic and hip fracture probabilities from the Fracture Risk Assessment Tool (FRAX®). Currently, antiresorptive agents are usually the first choice to increase bone mineral density (BMD) and reduce the fracture risk. Bisphosphonates and antiresorptive drugs such as denosumab, a nuclear factor kappa-B ligand (RANKL) inhibitor, are the most widely used drugs in the treatment of osteoporosis. Bisphosphonates alone are unlikely to provide long-term protection against fracture and restore BMD in patients with severe osteoporosis and high fracture risk. In such patients, treatment with an anabolic agent such as teriparatide, abaloparatide, or romosozumab should be ideally initiated to achieve maximal gain in bone mass and preserve the microarchitecture. Ideally, an antiresorptive drug should be continued to maintain gain in bone mass.

FRAX calculation with and without bone mineral density for assessment of osteoporotic fracture risk in patients of rheumatic disease: a cross-sectional study.

A cross-sectional was conducted at outpatient Department of Rheumatology. Eighty-one Patients of more than 40 years of age having either sex. Diagnosed case of Rheumatic diseases were according to American College of Rheumatology (ACR) /European Alliance of Associations for Rheumatology (EULAR) criteria were included in our study. FRAX score without BMD was calculated and information was recorded in proforma. These patients were advised dual energy X-ray absorptiometry Scan and after that FRAX with BMD was calculated, after which comparison between result of two scores was made. The data were analyzed by SPSS software version 24. Effect modifiers were controlled by stratification. Post-stratification χ2 test were applied. P value less than 0.05 was considered as significant. This study consisted of 63 participants, who were assessed for osteoporotic risk fracture, with and without BMD. Data analysis revealed a significant association between the type of fracture and age (p value=0.009), previous fracture (p value=0.25), parent fractured hip (p values) and treatment with bone mineral dismissal. There was no statistically significant association seen of fractures with bone deterioration with sex, weight, height, or current smoking. FRAX may be crucial in rural areas where dual energy X-ray absorptiometry scanning is not available since it is a readily available instrument. FRAX is a useful substitute for estimating osteoporosis risk when funds are scarce. Given the possible effect it will have on healthcare costs, this is extremely pertinent.

Association of Plasma Sex-Related Hormones Levels with Bone Mineral Densities and Risk of Osteoporosis and Osteopenia in Men and Menopausal Women with Type 2 Diabetes Mellitus.

This study aimed to examine associations between plasma sex-related hormones with bone mineral density (BMD) and risks of osteoporosis or osteopenia in men and postmenopausal women patients with type 2 diabetes mellitus (T2DM). Baseline information on an ongoing cohort of 149 men and 102 postmenopausal women with T2DM in Xiamen, China were analyzed. Plasma estradiol (E2), total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) were measured. BMD of lumbar spine (L2-4), femoral neck (FN) and total hip (TH) were determined by dual-energy X-ray absorptiometry (DXA). Osteoporosis or osteopenia was defined as the minimum T-scores of BMD of these three different sites of -1.0 or below. T2DM patients with osteoporosis/osteopenia (66.4% in men and 79.4% in postmenopausal women), compared to those without, showed significantly decreased level of E2 (75.3±28.9 vs. 107.8±25.9pmol/L and 18.4 (18.4-29.5) vs. 22.8 (18.4-40.5) pmol/L for men and postmenopausal women, respectively, both p-values <0.05), but not other sex-related hormones (including T, FSH, LH, or PRL). For all T2DM patients together and men separately, multivariable linear regression and logistic regression analyses showed that higher E2 levels were significantly associated with higher BMD T-scores in L2-4, FN, TH and minimum of these three different sites, lower 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HFs) estimated by Fracture Risk Assessment Tool score, as well as decreased risk of osteoporosis/osteopenia. As for postmenopausal women T2DM patients, E2 level was positively associated with BMD T-scores in L2-4 and minimum of three different sites but was not independently associated with risk of osteoporosis/osteopenia. Higher plasma E2 was significantly associated with increased BMD and lower risk of osteoporosis or osteopenia in T2DM patients, especially for men. Screening of BMD and estradiol levels as well as evaluating risks of osteoporosis/osteopenia are important for T2DM patients.

Routine Use of Lateral Vertebral Assessment With DXA Scan for Detection of Silent But Debilitating Vertebral Fractures

Reduced bone mineral density is a major public health dilemma with high prevalence. Vertebral fracture (VF) is an independent risk factor for fragility fracture. Lateral vertebral assessment (LVA) in dual-energy x-ray absorptiometry is a reliable, low-radiation, accurate, and cost-effective method for VF assessment. Five hundred seventy-five scans of oncologic and nononcologic patients were retrospectively reviewed irrespective of age or sex. Patients' symptoms, bone mineral density, and risk factors were also evaluated. Scans in which LVA was not acquired or had previously known VFs were excluded. The mean age of patients was 66 ± 11.5 years. Eleven percent of patients had VFs on LVA, of which 7 were excluded due to known VFs. Ten percent had new VFs, most of whom were women (n = 42). The most common risk factor was secondary osteoporosis in women and rheumatoid arthritis in men. Sixty-eight percent of the patients had solitary fractures, whereas 32% had multiple fractures. Most of these patients had underlying osteopenia (n = 19). FRAX was calculated twice: once with the history of personal fracture marked and the other time unmarked as these would not have been discovered if LVA was not acquired. Statistically significant mean percent difference of 5.4% was found in probability of major osteoporotic fracture and 2.1% in the mean risk of hip fracture. In our population, 10% patients had unsuspected VFs on LVA in dual-energy x-ray absorptiometry scan. Most of these were nononcologic patients with associated risk factors. Based on the FRAX tool, there is a significant difference in the 10-year risk of fracture when unsuspected fractures discovered on LVA are marked.