Probability Of Major Osteoporotic Fracture Research Articles

Efficacy of zoledronic acid in older prostate cancer patients undergoing androgen deprivation therapy

ObjectivesThe purpose of this study is to evaluate the efficacy of annual zoledronic acid treatment in Japanese patients with nonmetastatic prostate cancer during androgen deprivation therapy (ADT). MethodsThis is a single institution 12-month study. Between 2016 and 2019, patients aged 70 years or older on ADT for nonmetastatic prostate cancer had bone mineral density (BMD) measured and 10-year probability of fracture calculated using fracture risk assessment tool (FRAX). Patients who showed osteopenia or had a 10-year hip fracture risk ≥ 3% or a 10-year probability of major osteoporotic fracture ≥ 20% were offered treatment with zoledronic acid 5 mg intravenously (ZA group). The patients who did not receive treatment were set as the control group. Lumbar and hip BMD were measured 6 and 12 months after treatment in the ZA group and 12 months after baseline in the control group. The yearly BMD change of both groups was compared. ResultsThe mean ages of the ZA group (n = 26) and control group (n = 12) were 80.5 ± 9.1 and 76.1 ± 6.7 years, respectively. In the ZA group, lumbar and hip BMD changes at 12 months were +2.1% and +0.8%, respectively. In the control group, lumbar and hip BMD changes were −0.9% and −4.9%, respectively. There were statistically significant differences between the 2 groups in BMD percent changes (P < 0.05). ConclusionsWithout intervention, BMD tends to continue to decrease during ADT. Our findings suggest that administration of zoledronic acid enables maintenance of BMD in the older adults.

Predicting the intervention threshold for initiating osteoporosis treatment among postmenopausal women in China: a cost-effectiveness analysis based on real-world data

SummaryThis study built a micro-simulation Markov model to determine the treatment threshold of osteoporosis in postmenopausal women in Mainland China. Treatment with zoledronate is cost-effective when FRAX-based (Fracture risk assessment tool) fracture probability is over 7%.IntroductionThe purpose of this study is to estimate FRAX-based fracture probabilities in Mainland China using real-world data, at which intervention could be cost-effective.MethodsWe developed a micro-simulation Markov model to capture osteoporosis states and relevant morbidities including hip fracture, vertebral fracture, and wrist fracture. Baseline characteristics including incidences of osteoporosis and distribution of risk factors were derived from the Peking Vertebral Fracture study, the largest prospective cohort study of postmenopausal women in Mainland China. We projected incidences of fractures and deaths by age groups under two treatment scenarios: 1) no treatment, and 2) zoledronate. We also projected total quality-adjusted life-years (QALY) and total costs including fracture management and osteoporosis drugs for cost-effectiveness analysis. Cost-effective intervention thresholds were calculated based on the Chinese FRAX model.ResultsTreatment with zoledronate was cost-effective when the 10-year probability of major osteoporotic fracture based on FRAX was above 7%. The FRAX threshold increased by age from 51 to 65 years old, and decreased in elder age groups, ranging from 4% to 9%.ConclusionsUsing real-world data, our model indicated that widespread use of zoledronate was of both clinical and economic benefit among Chinese postmenopausal women. Using a FRAX-based intervention threshold of 7% with zoledronate should permit cost-effective access to therapy to patients and contribute to reducing the disease burden of osteoporosis in Mainland China.

Clinical analysis of FRAX in the assessment of fracture risk in patients with rheumatic disease in three medical center

Objective: The aim is to analyze the fracture risk in rheumatic patients by fracture risk assessment tool (FRAX), which is recommended by World Health Organization (WHO), so that we can prevent the occurrence of osteoporotic fracture earlier. Methods: Totally 617 participants, 204 out-patients with rheumatism, 204 in-patients with rheumatism and 209 healthy controls, from March to October in 2018 of Fourth Medical Center of PLA General Hospital, Jishuitan Hospital and China-Japan Friendship Hospital, were enrolled in this study. The probability of hip fracture (PHF) and major osteoporotic fracture (PMOF) in 10 years with FRAX were compared, and the differences between taking sleroids or not and with or without bone mass density (BMD) of femoral neck were evaluated. Correlation analysis was conducted between PHF, PMOF and clinical information, including age, disease duration, gender, steroid usage, osteocalcin, P1NP and β-crosslaps. Results: There was no significant difference in PMOF within 10 years (3.455±2.690 vs 2.973±2.149 vs 3.323±1.828) among the three groups (P>0.05), but the PHF (0.986±1.619 vs 0.515±0.873 vs 0.149±0.311) was different (P<0.05). PHF and PMOF increased gradually with age. PMOF of patients without glucocorticoid therapy in 10 years was lower than that of patients with glucocorticoid (3.554±2.584 vs 2.857±2.238, P<0.05). There is no difference between the results of FRAX calculated with BMD or not (3.012±2.231 vs 3.207±2.601, P>0.05). PHF and PMOF were positively correlated with age, course of disease, glucocorticoid use and osteocalcin level, while PHF was negatively correlated with TP1NP among in-patients. Conclusion: The prevalence of 10-year hip fracture calculated by FRAX in rheumatism patients is higher than that of healthy group. FRAX can be used to calculate fracture risk without BMD. Combination of FRAX and bone turnover markers may be more effective in prediction of osteoporotic fracture in rheumatic patients.

Novel algorithm generating strategy to identify high fracture risk population using a hybrid intervention threshold.

The aim of this study was to develop an algorithm to identify high-risk populations of fragility fractures in Taiwan. A total of 16,539 postmenopausal women and men (age ≥ 50years) were identified from the Taiwan Osteoporosis Survey database. Using the Taiwan FRAX® tool, the 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) and the individual intervention threshold (IIT) of each participant were calculated. Subjects with either a probability above the IIT or those with MOF ≥ 20% or HF ≥ 9% were included as group A. Subjects with a bone mineral density (BMD) T-score at femoral neck based on healthy subjects of ≤ -2.5 were included in group B. We tested several cutoff points for MOF and HF so that the number of patients in group A and group B were similar. A novel country-specific hybrid intervention threshold along with an algorithm was generated to identify high fracture risk individuals. 3173 (19.2%) and 3129 (18.9%) participants were categorized to groups A and B, respectively. Participants in group B had a significantly lower BMD (p < 0.001), but clinical characteristics, especially the 10-year probability of MOF (p < 0.001) or HF (p < 0.001), were significantly worse in group A. We found the algorithm generated from the hybrid intervention threshold is practical. The strategy of generating an algorithm for fracture prevention by novel hybrid intervention threshold is more efficient as it identifies patients with a higher risk of fragility fracture and could be a template for other country-specific policies.

857P - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial

BackgroundAndrogen deprivation therapy (ADT) for prostate cancer (PC) increases fracture risk. In non-cancer populations, FRAX, a fracture risk assessment tool, is used routinely to calculate 10-year probability of major osteoporotic fracture (MOF; spine/hip/forearm/humeral fractures) and hip fracture alone to determine the need for bone density (BMD) assessment and/or treatment. We calculated FRAX using risk factors at entry to the large STAMPEDE PC study. MethodsSTAMPEDE includes men with newly diagnosed metastatic/high risk non-metastatic PC about to commence ADT, randomised to add or substitute other therapies. Our pre-planned analysis included 6379 men, 86% of enrolment at the time of analysis (2018) for whom FRAX clinical risk factors (excluding femoral neck BMD) were collected prospectively. Secondary osteoporosis in FRAX was set to ‘yes’ for all, as they were about to receive ADT. Glucocorticoid use was set to ‘yes’ for men allocated to abiraterone due to potentially long concomitant use, but not for those allocated shorter treatment with docetaxel. ResultsBaseline characteristics for this largest dataset of its kind, are shown below. The mean (SD) baseline FRAX 10-year probability was 3.06(2.96)% for hip fracture and 8.70(4.02)% for MOF. Risk increased with increased age at entry, eg MOF probability at age 50-54 years was 4.9% rising to 11.3% in those aged 75 years or older. Using UK National Osteoporosis Guideline Thresholds, 2221 (34.8%) men were classified as high/intermediate risk (meriting BMD scan).The need for BMD assessment varied across planned treatment arms (18.4% in men receiving ADT only to 80.0% in men also planned to receive abiraterone).Table857PTableCharacteristicRandomisation years2006- 2018Age (y)67.4±7.2Height (cm)174.7±6.9Weight (kg)85.6±14.8BMI (kg/m2)28.0±4.5Prevalence of FRAX risk factors (%) Previous fracture after age 50yr6.1Glucocorticoid use (≥4mo)27.4Parental hip fracture7.7Rheumatoid arthritis2.4Alcohol (≥3 units daily)15.5Current smoking11.5 ConclusionsFRAX fracture risk assessment in men starting ADT suggests 1 in 3 require BMD assessment to decide on the need for bone protection. Planned treatment in addition to ADT, rather than age, was the main determinant for consideration of bone health. Clinical trial identification2004-000193-31. Legal entity responsible for the studyUniversity of Sheffield. FundingUniversity of Sheffield. DisclosureJ.E. Brown: Honoraria (self), Research grant / Funding (institution): Amgen; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): BMS; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Ipsen; Honoraria (self): Sandoz; Honoraria (self): Merck Sharpe Dome. All other authors have declared no conflicts of interest.

Clinical Impact of the Fracture Risk Assessment Tool on the Treatment Decision for Osteoporosis in Patients with Knee Osteoarthritis: A Multicenter Comparative Study of the Fracture Risk Assessment Tool and World Health Organization Criteria

Background: To compare the frequency of high-risk osteoporotic fracture in patients with knee OA (OA) using the fracture risk assessment tool (FRAX) and the bone mineral density (BMD). Methods: We retrospectively assessed 282 Korean patients with knee OA who visited five medical centers and 1165 healthy controls (HCs) aged ≥50 years without knee OA. After matching for age, sex, and body mass index, 478 subjects (239 patients with knee OA and 239 HCs) were included. Results: Based on the BMD, the frequency of osteoporosis was 40.2% in patients with knee OA and 36.4% in HCs. The predicted mean FRAX major osteoporotic fracture probabilities calculated with or without femur neck BMD differed significantly between the knee OA and HCs (6.9 ± 3.8% versus 6.1 ± 2.8%, p = 0.000 and 8 ± 3.6% versus 6.8 ± 2.3%, p < 0.001, respectively). The mean FRAX hip fracture probabilities calculated with or without femur neck BMD differed significantly in the knee OA and HCs (2.1 ± 2.4% versus 1.7 ± 1.8%, p = 0.006 and 3 ± 2.3% versus 2.4 ± 1.6%, p < 0.001, respectively). Conclusion: Our study suggests that FRAX may have a clinical impact on treatment decisions to reduce osteoporotic facture in patients with knee OA.

Correlations between periodontal disease, mandibular inferior cortex index and the osteoporotic fracture probability assessed by means of the fracture risk assessment body mass index tool

BackgroundThe aim was to examine correlations between radiological signs of chronic periodontitis, Mandibular Inferior Cortex (MIC) index and osteoporotic fracture probability based on the FRAX BMI tool.MethodsThe material comprised 422 panoramic radiographs taken in patients aged 40–89, 270 females and 152 males. The severity of chronic periodontitis and resorption of mandibular inferior cortex based on MIC index were assessed. A diagnostic survey was conducted to estimate 10-year major and hip osteoporotic fracture probability (MOFP, HOFP) by means of the FRAX BMI tool - an algorithm that allows to calculate osteoporotic fracture probability based on assessing bone fracture risk factors knowing only BMI value.ResultsThe conducted analysis based on U Mann-Whitney test revealed that mean 10-year MOFP was significantly higher (p = 0.00) in women than in men. Mean 10-year MOFP in females was 4.8% (SD = 3.95%) and in males 3.21% (SD = 2.35%). Mean 10-year HOFP in women was 1.35% (SD = 2.07%) and was significantly higher (p = 0.03) than in men – 0.79% (SD = 1.18%).MOFP is significantly higher in patients with moderate and severe periodontitis than in those with mild periodontitis. Significant difference between MIC values and MOFP (p = 0.00) and HOFP (p = 0.00) was found. Osteoporotic fracture probability was significantly higher in patients with MIC stages C2 and C3 than C1.ConclusionsThe FRAX BMI tool with radiological evaluation of periodontal disease severity and MIC index may be used in dental practice in determining individual risk of osteoporotic fracture in females and provide new opportunities of selecting those potentially more prone to such fractures.Trial registrationThe approval of the local bioethics committee was obtained (KE-0254/107/2017).

Performance of FRAX and FRAX-Based Treatment Thresholds in Women Aged 40 Years and Older: The Manitoba BMD Registry

We examined among women aged ≥40 years the performance of the Fracture Risk Assessment Tool (FRAX) and FRAX-based osteoporosis treatment thresholds under the US National Osteoporosis Foundation (NOF) and UK National Osteoporosis Guideline Group (NOGG) guidelines. We used registry data for all women aged ≥40 years in Manitoba, Canada, with baseline bone mineral density (BMD) testing (n = 54,459). Incident major osteoporotic fracture (MOF), hip fracture, and clinical fracture were assessed from population-based health services data (mean follow-up 10.5 years). Age-stratified hazard ratios (HR) were estimated from Cox regression models. We assessed the sensitivity, specificity, positive predictive value (PPV), number needed to screen (NNS), and number needed to treat (NNT) to prevent a fracture (assuming 20% relative risk reduction on treatment) for osteoporosis treatment thresholds under the NOF and NOGG guidelines. Femoral neck T-score and FRAX (with and without BMD) predicted all fracture outcomes at all ages. There was good calibration in FRAX-predicted versus observed 10-year MOF and hip fracture probability. Overall sensitivity (PPV) for incident MOF was 25.7% (24.0%) for femoral neck T-score ≤ -2.5; 20.3% (26.3%) for FRAX (with BMD)-predicted 10-year MOF risk ≥20% (NOF threshold); 27.3% (22.0%) for FRAX-predicted 10-year MOF risk ≥ age-dependent cut-off (NOGG threshold), 59.4% (19.0%) for the NOF treatment algorithm; and 28.5% (18.4%) for the NOGG treatment algorithm. Sensitivity for identifying incident MOF varied by age, ranging from 0.0% to 26.3% in women 40 to 49 years old and from 49.0% to 93.3% in women aged 80+ years. The gradient of risk for fracture prediction from femoral neck T-score and FRAX (with and without BMD) as continuous measures was strong across the age spectrum. The sensitivity and PPV of the strategies based on dichotomous cut-offs are low, especially among women aged 40 to 49 years (who have lowest incidence rates). Threshold-based approaches should be reassessed, particularly in younger women. © 2019 American Society for Bone and Mineral Research.

Accuracy of FRAX® in People With Multiple Sclerosis.

People with multiple sclerosis (MS) have a higher risk of low bone mineral density (BMD), osteoporosis, and osteoporotic fractures than healthy adults. The Fracture Risk Assessment tool (FRAX® ) has been reported to underestimate fracture risk in people with MS when BMD is unknown. We tested FRAX performance for people with MS when BMD is known, and determined if MS is a risk factor for fracture independent of FRAX score. Using population-based databases in Manitoba, Canada, we identified people with MS who underwent BMD screening after MS diagnosis (n = 744) and controls matched on age, sex, and first BMD screening date (n = 3721). We calculated FRAX 10-year probabilities at the BMD screening date, and ascertained incident major osteoporotic fractures (MOF). Using Cox proportional hazards modeling we assessed the effect of MS on the hazard of MOF, adjusting for FRAX 10-year probabilities. MS cases had a higher mean FRAX 10-year probability of MOF calculated with BMD (8.32 ± 7.53) than controls (6.98 ± 5.18; p < 0.01). MS increased the risk for MOF after controlling for FRAX 10-year probability without BMD (HR 1.67; 95% confidence interval [CI], 1.29 to 2.16), and after controlling for FRAX individual risk factors (HR 1.45; 95% CI, 1.12 to 1.89). MS remained a risk factor for MOF even when controlling for FRAX 10-year probability of MOF with BMD (HR 1.48; 95% CI, 1.14 to 1.92). The FRAX 10-year probability with and without BMD underestimated the observed 10-year MOF risk in MS cases by 3% to 5%. Calibration improved when secondary osteoporosis was used to calculate FRAX without BMD. Calibration was best when the rheumatoid arthritis input was used to calculate FRAX probability along with BMD. Using secondary osteoporosis or rheumatoid arthritis as proxies for MS improves performance of FRAX and accurately predicts MOF outcomes in those with MS. This provides clinicians with a readily available approach to improve the accuracy of fracture prediction in MS. © 2019 American Society for Bone and Mineral Research.

FRAX® based intervention thresholds for management of osteoporosis in Singaporean women.

We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation. One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity + specificity - 1) used to identify the optimal MOF and HF ITs. The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis. The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.

Feasibility of Serum Pentosidine Level as a Potential Risk Factor for Osteoporotic Vertebral Compression Fracture.

Study DesignFeasibility study.PurposeTo evaluate the feasibility of using serum pentosidine level as a potential marker for osteoporotic vertebral compression fracture (OVCF).Overview of LiteratureA review of previous studies suggests a negative correlation between serum pentosidine concentration and bone strength. However, it is unclear whether serum pentosidine level might be a potential marker of OVCF in Koreans.MethodsForty patients who underwent bone mineral density examination were included in this study, and their serum pentosidine levels were prospectively analyzed. Serum pentosidine level was evaluated using enzyme-linked immunosorbent assay. Among all the patients, 11 with OVCF were assigned to the vertebral fracture group and 29 who did not have vertebral fracture were included in the non-fracture group. In addition, we used the Fracture Risk Assessment (FRAX) tool Korean version for assessing the 10-year probability of fracture.ResultsThere was a statistically significant difference in the mean serum pentosidine level (p=0.04) of the vertebral fracture group (110.8 ng/mL) and the non-fracture group (64.3 ng/mL). Logistic regression analyses showed that serum pentosidine was significantly associated with OVCF. The vertebral fracture group had significantly higher 10-year probability of major osteoporotic fracture as per FRAX than the non-fracture group. There was a positive correlation between pentosidine level and FRAX results (r=0.35, p=0.02).ConclusionsThese results suggest that increased serum pentosidine level could be a potential marker for OVCF.

FRAX Calculated without BMD Resulting in a Higher Fracture Risk Than That Calculated with BMD in Women with Early Breast Cancer.

Background (and Purpose) The aim of this study was to investigate the importance of including the measurement of bone mineral density (BMD) in reliable fracture risk assessment for women diagnosed with early nonmetastatic breast cancer (EBC) before AI treatment if zoledronic acid is not an option. Material and Methods One hundred and sixteen women with EBC were included in the study before initiating AI treatment. Most participants were osteopenic. The 10-year probability of hip fracture and major osteoporotic fracture was calculated with and without BMD based on clinical information collected at baseline using the fracture risk assessment (FRAX) tool. To compare data, the nonparametric tests were used. Results There was a significant difference (p<0.001) in the number of high-risk and low-risk FRAX score of hip fracture between before and after including BMD values. The high-risk category decreased by 50.9%, while the low-risk category increased by 42.9%. In FRAX score of major osteoporotic the findings were similar (p<0.001): The high-risk and moderate-risk category decreased by 70.4% and 4.9%, respectively, while the low-risk category increased by 43.8% when including BMD value. When stratified by age, patients aged 65 years or older were at a significantly (p<0.001) higher risk of suffering a hip or major osteoporotic fracture, highlighting the importance of including BMD measurements in this age group. Conclusions Our data support that DXA scanning of women with EBC should be performed to avoid overestimation of osteoporosis before AI treatment. It is particularly important in patients older than 65 years of age and when zoledronic acid is not an option.

The association between 10-year fracture risk by FRAX and osteoporotic fractures with disease activity in patients with rheumatoid arthritis.

As rheumatoid arthritis (RA) is an independent risk factor for osteoporotic fractures, the severity of disease activity may correlate with fracture risk. Our objectives were to determine the prevalence of major osteoporotic and hip fractures in patients with RA and to identify the factors related to their 10-year probabilities. This study enrolled 232 patients with RA, aged 40-90years, who participated in the Siriraj RA Cohort in 2016 and 2017. Demographic data, disease activity scores 28 (DAS28), and health assessment questionnaires (HAQ) were collected. All participants were evaluated for asymptomatic vertebral fractures by thoracolumbar spine radiography. The osteoporotic fracture risks were determined using the fracture risk assessment tool (FRAX). Most subjects were postmenopausal women in their sixth decade; the median disease duration was 12.95years. Forty-six percent of patients had osteoporotic fractures, and most (87%) were vertebral fractures. Eighty-one patients had asymptomatic vertebral compression fractures. Of those, 57%, 25%, and 18% had low, moderate, and high 10-year probabilities of major osteoporotic fractures, respectively, while 51%, 34%, and 15% had low, moderate, and high 10-year probabilities of hip fractures, respectively. Factors significantly associated with the 10-year probabilities of major osteoporotic and hip fractures were disease duration (p 0.017, 0.009), menopause duration (p < 0.001 both), cumulative disease activity (DAS28; p 0.004, 0.029), and cumulative functional disability (HAQ; p < 0.001 both). Moderate to high 10-year probabilities of major osteoporotic and hip fractures are common in RA. Cumulative disease severity is a high risk for osteoporotic fractures.

Cost-effective but clinically inappropriate: new NICE intervention thresholds in osteoporosis (Technology Appraisal 464).

To comment on the latest technology appraisal of the National Institute for Clinical Excellence (NICE) in osteoporosis. Review of NICE Technology Appraisal (TA464) on bisphosphonate use in osteoporosis. The NICE appraisal on bisphosphonate use in osteoporosis indicates that treatment with oral bisphosphonates may be instituted at a FRAX 10-year probability of major osteoporotic fracture above 1%. Implementation would mean that all women aged 50years or older are deemed eligible for treatment, a position that would increase the burden of rare long-term side effects across the population. Cost-effectiveness thresholds for low-cost interventions should not be used to set intervention thresholds but rather to validate the implementation of clinically driven intervention thresholds.

Progress of osteoporosis: stratification of fracture risk

Background: There are two approaches to identify candidates for the prescription of osteoporosis treatment: identification of patients with low bone mineral density using DEXA of the axial skeleton and calculation of the 10-year probability of major osteoporotic fractures using FRAX®.&#x0D; Aims: to assess the diagnostic accuracy of different FRAX® thresholds in the Russian population.&#x0D; Materials and methods: the value of individual 10-year probability of osteoporotic fracture by FRAX® at the time of inclusion in the study was retrospectively estimated in 224 postmenopausal women, whom the major osteoporotic fractures were recorded over 10 years of prospective observation. The diagnostic accuracy of different thresholds were compared: "European" and Russian age-dependent thresholds, fixed 20% threshold, the average FRAX® of patients who had a major osteoporotic fracture during follow-up (16%), FRAX® value corresponding to the "cut-off point" (12,5%).&#x0D; Results: The Russian FRAX model showed the acceptable diagnostic accuracy of the method (AUC=0.665±0.036; 95% CI 0.595; 0.736). The "European" threshold of therapeutic intervention demonstrated 72% sensitivity and 38% specificity, 20% threshold – 27% and 87%, the Russian threshold – 41% and 77%, 12.5% threshold – 68% and 58%, 16% threshold – 57% and 73%, respectively. The diagnostic precision of the specified thresholds was 54%, 58%, 60%, 63% and 65%, respectively.&#x0D; Conclusions: the Russian age-dependent threshold remains the optimal way to decide whether to initiate anti-osteoporotic therapy based on an assessment of the 10-year probability of fracture by the Russian model for FRAX®.

Prospective risk of osteoporotic fractures in patients with advanced chronic obstructive pulmonary disease.

Despite the high prevalence of osteoporosis in chronic obstructive pulmonary disease (COPD) patients, the fracture risk prediction tools are not routinely undertaken in the management of COPD. We quantified fracture risk using a validated risk prediction tool (Fracture Risk Assessment (FRAX®)) and determined potential bone-protection treatment needs in patients with advanced COPD. The 10-year probability of major osteoporotic or hip fracture was calculated using the FRAX tool in a cohort of patients attending a hospital complex COPD service. Patients were identified to be at low, intermediate and high risk based on their FRAX scores, in accordance with the National Osteoporosis Guideline Group recommendations, to assess the number of patients requiring bone mineral density (BMD) testing or bone protection therapy. Two hundred forty-seven patients [mean (standard deviation (SD)) age 66 (9.1) years, 26% current smokers, 40% women and median (interquartile range (IQR)) Medical Research Council (MRC) breathlessness scale 4 (0)] had a 10-year probability of 9.5% (6.1) and 3.8% (4.6) for major osteoporotic and hip fractures, respectively. Thirty-six percentage of patients were identified to be at intermediate risk of developing fragility fracture, requiring BMD assessment, while 9% were at high risk, requiring treatment. Thirty-two percentage of high-risk patients were on bisphosphonates. The FRAX score can be used to assess the fracture risk within the COPD cohort and assist with decision-making about BMD measurement and provision of bone protection therapy.

Prevention of Glucocorticoid-Induced Osteoporosis: Clinical audit to evaluate the implementation of National Osteoporosis Guideline Group 2017 guidelines in a primary care setting

Treatment with glucocorticoids is the leading cause of drug-induced osteoporosis. National Osteoporosis Guideline Group (NOGG) 2017 guidelines advise a case-finding strategy for patients at risk. The aims of the audit were to evaluate the implementation of the NOGG 2017 guidelines for patients receiving long-term glucocorticoid therapy in a suburban general practice, to instigate changes to ensure 90% of patients are investigated and treated appropriately, and to evaluate impact at a 6-mo re-audit. Reporting Analysis and Intelligence Delivering Results (RAIDR) is a health-care intelligence tool accessing primary care clinical data. Using RAIDR, data on relevant osteoporotic risk factors were combined to produce FRAX scores for patients who had been prescribed glucocorticoids 3 or more times in the past 12 months. FRAX data were displayed in a NOGG guidance graph for major osteoporotic fracture probability. Patients were assessed as high, intermediate, or low risk. High- and intermediate-risk patients above the NOGG threshold were recommended to start bisphosphonates; these patients were sent a prescription for alendronate and a letter of explanation. There were no intermediate patients below the NOGG threshold. Low-risk patients were recommended to have lifestyle advice; a leaflet was produced and sent to these patients. Initial results showed that only 25% of patients recommended to be on bisphosphonates were taking them. Steps were taken to educate the general practitioners in the FRAX tool and NOGG guidelines; the chronic obstructive pulmonary disease annual template was amended to aid adherence by alerting the nurse to the number of glucocorticoid courses prescribed, with additional boxes for prescribing alendronate and printing the lifestyle leaflet; and 2-monthly RAIDR searches by the practice pharmacist were started. A re-audit 6 mo later showed improvement to 92%. This audit showed that education, reminders, and simple computer prompts can greatly improve the implementation of NOGG guidelines for glucocorticoid-induced osteoporosis.

Volumetric Bone Mineral Density and Failure Load of Distal Limbs Predict Incident Clinical Fracture Independent HR-pQCT BMD and Failure Load Predicts Incident Clinical Fracture of FRAX and Clinical Risk Factors Among Older Men.

Our objective was to determine the associations of peripheral bone strength and microarchitecture with incident clinical and major osteoporotic fracture among older men after adjusting for major clinical risk factors. We used a prospective cohort study design with data from 1794 men (mean age 84.4 years) in the Osteoporotic Fractures in Men (MrOS) study. Eligible men attended the year 14 visit, had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia, DXA measured BMD, and were followed for mean 1.7 years for incident fracture. Failure load was estimated using finite element analysis. We used Cox proportional hazards models with standardized HR-pQCT parameters as exposure variables. Primary outcome was clinical fracture (n = 108). Covariates included either Fracture Risk Assessment Tool (FRAX) major osteoporotic fracture probability calculated with BMD (FRAX-BMD), or individual clinical risk factors (CRF) including age, total hip BMD, race, falls, and prevalent fracture after age 50 years. Lower failure load was associated with higher risk of incident clinical fracture and incident major osteoporotic fracture. For clinical fracture with FRAX-BMD adjustment, the associations ranged from hazard ratio (HR) 1.58 (95% CI, 1.25 to 2.01) to 2.06 (95% CI, 1.60 to 2.66) per SD lower failure load at the diaphyseal tibia and distal radius. These associations were attenuated after adjustment for individual CRFs, but remained significant at the distal sites. Associations of volumetric BMD with these outcomes were similar to those for failure load. At the distal radius, lower trabecular BMD, number, and thickness, and lower cortical BMD, thickness, and area were all associated with higher risk of clinical fracture, but cortical porosity was not. Among community-dwelling older men, HR-pQCT measures including failure load, volumetric BMD, and microstructure parameters at peripheral sites (particularly distal radius) are robust independent predictors of clinical and major osteoporotic fracture. © 2018 American Society for Bone and Mineral Research.

OSTEOPOROTIC FRACTURE RISK IN RHEUMATOID ARTHRITIS

Objective: Osteoporosis is an extra-articular complication of rheumatoid arthritis (RA) with increased risk of fractures. FRAX is an online tool for assessing risk of osteoporotic fracture. However, the relationship between the FRAX score and disease specific risk factors has not yet been investigated in RA. Hence, we assessed 10-year fracture risk using FRAX and its relationship with disease activity score, inflammation and disease duration in RA.Methods: 50 RA patients enrolled and recruited consecutively in a special camp organized for RA patients on the occasion of World Osteoporosis Day, 2016to estimate the osteoporotic fracture risk from Rheumatology clinic. Predicted 10-year risk of hip fracture and major osteoporotic fracture (MOF) by FRAX score without information on bone mineral density (BMD). Inflammatory disease activity measures included disease activity score of 28 joints (DAS28), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured. FRAX score also estimated in 40 age and sex matched healthy controls.Results: FRAX estimated significantly enhanced fracture risk in active RA, both for MOF (13.34±1.26%) and hip fracture (6.84±1.03%) as compared to controls for MOF (5.46±0.95%) and hip fracture (1.97±0.49%). In RA patients, MOF and hip fracture risk correlated with DAS28 and disease duration and MOF risk correlated with ESR and CRP.Conclusion: Active RA patients, even in the absence of BMD have an increased FRAX score indicating an enhanced 10-year probability of MOF and hip fracture. Long disease duration, high disease activity and an elevated ESR and CRP are potential disease specific risk factors for osteoporotic fractures in RA.

Russian federal clinical guidelines on the diagnostics, treatment, and prevention of osteoporosis

Screening using the Fracture Risk Assessment Tool (FRAX) is recommended in all postmenopausal woman and mеn over 50 (A1) in order to identify individuals with high probability of fractures. It is recommended to diagnose osteoporosis and start treatment in patients with fragility fracture of large bones of the skeleton and/or high individual probability of major fragility fractures (FRAX) and/or detected decrease in bone mineral density (BMD) up to –2.5 T-score as assessed by DXA in the femoral neck and/or lumbar vertebrae (A1). Patients with back pain, lifetime height loss of 4 cm or height loss of 2 cm since a previous medical examination, those who receive glucocorticoids, patients with long lasting decompensated type 2 diabetes mellitus, or those receiving insulin therapy, as well as patients who were previously diagnosed with fragility fractures at the other sites are advised to underwent standard lateral X-ray imaging of the spine (Th4—L5) in order to verify the presence of compression vertebral fractures (B1).&#x0D; Dual-energy X-ray absorptiometry (DXA) is recommended for individuals whose 10-year probability of major osteoporotic fracture (FRAX) falls within the medium risk group (B1). It is recommended to include the trabecular bone score (TBS) the FRAX algorithm in order to improve the sensitivity of this method (B1).&#x0D; Laboratory testing is recommended for the differential diagnosis with other causes of increased skeletal fragility in all patients with newly diagnosed osteoporosis and when previously prescribed antiosteoporostic treatment was ineffective (B1).&#x0D; Bisphosphonates (BPs), antibodies to receptor activator of nuclear factor kappa-beta ligand (RANKL) (denosumab), or parathyroid hormone analogue (teriparatide) are equally recommended to prevent fragility fractures and increase BMD in patients with osteoporosis (A1). Denosumab is also recommended to prevent BMD loss and fractures in females receiving aromatase inhibitors therapy for breast cancer and males with prostate cancer receiving hormone-deprivation therapy and having no bone metastases (A1). Since teriparatide has the anabolic effect, it is recommended as the first line treatment in patients with severe osteoporosis having history of vertebral fractures, in the individuals with very high risk of fragility fractures, or in the cases when antiresorptive treatment was ineffective (B1). All medications for treatment of osteoporosis are recommended in combination with calcium and vitamin D supplements (A1).