Low-trauma Fractures Research Articles

Assesment of osteoporotic fractures risk and osteoporosis prevalence among patients over 50 years old undergoing medical rehabilitation

Background. Back pain, limitation of mobility, spinal deformity, decreased ability to self-care due to osteoporotic fractures (vertebrae, femoral neck, humerus, etc.) are one of the reasons for referring patients to rehabilitation and rehabilitation treatment, which involves the use of physical therapy methods, physiotherapy exercises and mechanotherapy.
 Objective: to assess the prevalence of osteoporosis (OP), individual risk factors for OP, as well as the proportion of people with high risk of osteoporotic low-energy fractures among patients over 50 years old undergoing treatment according to the medical rehabilitation profile.
 Methods. The study group comprised of 600 patients (426 women and 174 men) aged 50 to 84 years, average age 64.2510.17 years, undergoing treatment in a rehabilitation department. This was a cross-sectional study in the form of unified questionnaire, including data conserning age, weight, height, BMI, clinical and rehabilitation diagnosis, anamnesis of the main disease, anamnesis vitae, presence of OP diagnosis in the anamnesis, its treatment, OP risk factors estimation. An assessment of 10-year probability of osteoporotic fractures was carried out using Russian model of online FRAX calculator.
 Results. 41.8% patients in the study sample had OP risk factors, including 31.2% ― 3 risk factors or more. 38% patients over 50 years old undergoing medical rehabilitation showed a high fracture risk according to the FRAX calculator. 34.1% had a diagnosis of OP stated, and 45.8% already had osteoporotic fractures. Among those who did not undergo densitometry examination, 69.9% had a history of low-traumatic fractures, and only 58.5% of patients with an established diagnosis of OP and 26.8% of those at high risk of fractures received effective therapy for OP.
 Conclusion. Among patients over 50 years old undergoing medical rehabilitation a high frequency of OP and high fracture risk were stated. At the same time, insufficient quality of OP diagnostics and anti-osteoporotic therapy administaration were revealed.

Differences in fracture prevalence and in bone mineral density between Chinese and White Canadians: the Canadian Multicentre Osteoporosis Study (CaMos).

We aimed to compare clinical risk factors, bone mineral density, prevalence of osteoporosis, and fractures between Chinese and White Canadians to identify ethnicity-specific risks. We studied 236 Chinese and 8945 White Canadians aged 25+ years from the Canadian Multicentre Osteoporosis Study (CaMos). The prevalence of osteoporosis using ethnicity-specific peak bone mass (PBM), and of prior and incident low trauma fractures were assessed and compared between groups. Linear regressions, adjusting for age and anthropometric measures, were used to examine the association between baseline and 5-year changes in BMD and ethnicity. Chinese participants had shorter stature, lower BMI, and lower rate of falls than White participants. Adjusted models showed no significant differences in baseline BMD between ethnic groups except in younger men where total hip BMD was 0.059 g/cm2 (0.009; 0.108) lower in Chinese. Adjusted 5-year BMD change at lumbar spine was higher in older Chinese women and men compared with Whites. When using Chinese-specific PBM, the prevalence of osteoporosis in Chinese women was 2-fold lower than when using that of White women The prevalence of fractures was higher in White women compared with Chinese with differences up to 14.5% (95% CI 9.2; 19.7) and 10.5% (95% CI 4.5-16.4) in older White men. Incident fractures were rare in young Chinese compared with White participants and not different in the older groups. Our results support the importance of characterizing bone strength predictors in Chinese Canadians and the development of ethnicity-specific fracture prediction and prevention strategies.

Circulating MicroRNAs as Novel Biomarkers for Osteoporosis and Fragility Fracture Risk: Is There a Use in Assessment Risk?

Osteoporosis is a multifactorial skeletal disease that is associated with both bone mass decline and microstructure damage. The fragility fractures—especially those affecting the femur—that embody the clinical manifestation of this pathology continue to be a great medical and socioeconomic challenge worldwide. The currently available diagnostic tools, such as dual energy X-ray absorptiometry, Fracture Risk Assessment Tool (FRAX) score, and bone turnover markers, show limited specificity and sensitivity; therefore, the identification of alternative approaches is necessary. As a result of their advantageous features, such as non-invasiveness, biofluid stability, and easy detection, circulating cell-free miRs are promising new potential biomarkers for the diagnosis of osteoporosis and low-traumatic fracture risk assessment. However, due to the absence of both standardized pre-analytical, analytical, and post-analytical protocols for their measurement and universally accepted guidelines for diagnostic use, their clinical utility is limited. The aim of this review was to record all the data currently available in the literature concerning the use of circulating microRNAs as both potential biomarkers for osteoporosis diagnosis and fragility fracture risk evaluation, and group them according to the experimental designs, in order to support a more conscious choice of miRs for future research in this field.

Bone health in young adult survivors born extremely preterm or extremely low birthweight in the post surfactant era.

Most infants born extremely preterm (EP; <28weeks' gestation) or extremely low birthweight (ELBW; <1000g birthweight) in the post surfactant era (early 1990s) are now surviving into adulthood. Preterm birth/low birthweight are risk factors for reduced bone growth and mineralisation in infants and children. However, little is known about their bone health around peak bone mass and through adult life. To compare bone health (bone mineral measures, bone structure and strength) in young adults born EP/ELBW with controls (>2499g birthweight), and within the EP/ELBW group examine perinatal and later variables associated with long term bone health. A geographic cohort comprising all 297 survivors born EP/ELBW in 1991-92 in the state of Victoria, Australia, and 260 contemporaneous controls (>2499g birthweight) were recruited into a longitudinal study from birth. At age 25years, investigations included dual energy X ray absorptiometry and peripheral quantitative computed tomography to measure bone, muscle and soft tissue variables, and fasting blood samples to measure serum 25 hydroxyvitamin D (25(OH)D) and bone turnover markers (BTM). Linear regression analysis, with models fitted using generalised estimating equations, was used to compare outcomes between groups, adjusting for height and weight. Compared with controls (n=129), young adults born EP/ELBW (n=162) had lower areal bone mineral density (g/cm2) (mean difference [MD] -0.044; 95% confidence interval [CI] -0.076,-0.013) and Z-scores (MD -0.53; 95% CI -0.75, -0.30) in the femoral neck, and lower total hip Z-score (MD -0.35; 95% CI -0.54, -0.15) after adjusting for height and weight. EP/ELBW males generally displayed more bone and soft tissue deficits than females, compared with their respective controls. Within the EP/ELBW group, early growth, male sex, height and lean mass, muscle measures, 25(OH)D levels, and BTM were independently associated with bone mineral measures, structure or strength. Young adults born EP/ELBW had evidence of impaired bone health around the age of peak bone mass compared with controls. Further follow-up of the EP/ELBW groups will determine if they have a heightened low-trauma fracture risk in later life.

FRAX without BMD can be used to risk-stratify Veterans who recently sustained a low trauma non-vertebral/non-hip fracture.

The objective of this study was to evaluate the performance of the fracture risk assessment tool (FRAX) without bone mineral density (BMD) in predicting treatment recommendations for patients who recently sustained a low trauma fracture other than hip or vertebral. We utilized a clinical database established by the Fracture Liaison Service at the Durham Veterans Affairs Medical Center to identify male and female Veterans age ≥ 50years who sustained a low trauma non-hip/non-vertebral fracture and underwent dual-energy x-ray absorptiometry (DXA) between October 2013 and April 2018. FRAX without BMD (FRAX-BMI) and FRAX with BMD (FRAX-BMD) were calculated for the 229 patients identified, and whether or not they met the National Osteoporosis Foundation (NOF) guideline treatment thresholds was compared. There were 55 (24.0%) patients that met criteria for treatment based on NOF guideline established FRAX-BMD thresholds including 27 (11.8%) patients with osteoporosis by DXA. The concordance of FRAX-BMI in predicting treatment recommendations was 75.6% with a sensitivity of 67.3% and a specificity of 78.2%. The area under the curve (AUC) of FRAX-BMI hip fracture risk was 0.79. Assessment/treatment thresholds for hip fracture risk of 1%<FRAX-BMI < 4% were proposed to maximize sensitivity and specificity. Among patients who sustained a low trauma non-hip/non-vertebral fracture, FRAX-BMI can be used to stratify risk and identify high-risk patients who could be treated without DXA, low-risk patients who may not need treatment, and intermediate-risk patients to undergo DXA testing.

Osteosarcopenia: pathogenesis, diagnosis and therapeutic approaches

Osteosarcopenia was identified as a separate syndrome in 2009, and is defined as a combination of sarcopenia and osteopenia/osteoporosis. Osteosarcopenia develops mainly in old age, leads to a decrease in quality of life, an increased risk of falls and low-traumatic fractures. Patients with osteosarcopenia have worse indicators of physical functions, compared with people suffering from only one of the components of the syndrome. An important role in the osteosarcopenia prevention is played by the lifestyle of patients, Adherence to diet with the consumption of adequate amount of protein, physical activity and preventive prescription of calcium and vitamin D are important for osteosarcopenia prevention. The article summarizes data on the prevalence, pathogenesis and risk factors of osteosarcopenia, provides diagnostic criteria for the disease and discusses therapeutic approaches.

The assessment of trabecular bone score to improve the sensitivity of FRAX in patients with type 2 diabetes mellitus

Aim. To estimate the trabecular bone score (TBS) for evaluation of fracture probability in order to make decisions about starting osteoporosis treatment in patients with type 2 diabetes mellitus (T2DM).&#x0D; Materials and methods. We obtained the bone mineral density (BMD) and trabecular bone score (TBS) using dual energy X-ray absorptiometry (iDXA) in patients with T2DM (with and without a history of osteoporotic fractures) versus the control group. Before and after TBS measurements we assessed the ten-year probability of fracture using the Fracture Risk Assessment Tool (FRAX).&#x0D; Results. We enrolled 48 patients with T2DM, including 17 with a history of low-traumatic fracture, 31 patients without fractures and 29 subjects of a control group. BMD was higher in patients with T2DM compared to the control group at L1L4 (mean T-score 0.44, 95% CI -3.2 4.9 vs mean T-score 0.33, 95% CI -2.9 3.0 in a control group p=0.052) and Total Hip (mean T-score 0.51, 95% CI -2.1 3.0 vs mean T-score -0.03, 95% CI -1.4 1.2 in a control group p=0,025). The TBS and 10-year probability of fracture (FRAX) was not different in patients with T2DM versus the control group. However, when the TBS was entered as an additional risk factor, the 10-year probability of fracture became higher in patients with T2DM (10-year probability of fracture in T2DM- 8.68, 95% CI 0.3-25.0 versus 6.68, 95% CI 0.415.0 in control group, p=0.04). Among patients with diabetes with and without fractures the FRAX score was higher in subjects with fractures, but no difference was found in regards to BMD or TBS. Entering BMD and TBS values into the FRAX tool in subjects with diabetes and fractures decreased the FRAX score. However, patients with low-traumatic fractures should be treated for osteoporosis without a BMD, TBS or FRAX assessment.&#x0D; Conclusion. TBS improves the results of FRAX assessment in patients with T2DM and should be entered while evaluating FRAX in patients with T2DM. However, additional research is needed to develop a more sensitive tool to evaluate fracture risk in patients with T2DM.

Low-trauma ankle fractures in Brazil: secular trends in patients over 50years old from 2004 to 2013.

The most common sites of low-energy trauma fractures are the femur, vertebra, humerus, and forearm. Ankle fractures have significant morbidity and high costs for surgical procedure. Forearm fractures are common nonvertebral fractures. Forearm fractures are classified as fragility fractures and predictive for fractures at other sites, although do not allow osteoporosis diagnosis. It is controversial whether ankle fractures are osteoporosis fractures. Retrospective observational study, with secular trend analysis, in patients over 50years old admitted in the Brazilian Public Health System, from 2004 to 2013. We collected hospitalization data according to the ICD-10 for low-trauma ankle and forearm fractures. Fracture rate was calculated according to gender, age, and geographic region, performed linear regression analysis, and estimated fracture rates for 2030. Comparison of ankle and forearm rates was also performed, grouping them in 3-year block. ANOVA test was used to compare each block. Ankle fracture rate was 21.39 fractures per 100,000 inhabitants, 23.98 in females and 18.49 in males. Fracture rates were higher in the South and Southeast regions. In absolute numbers, although ankle fracture rate increased with age, there was a significant decrease in the population over 80years old. Data showed stabilization in ankle fractures from 2004 to 2013, in women and men. In 3-year block analysis, men had higher ankle fracture rates than forearm. However, in women, forearm rates were higher than ankle. Our data suggest that ankle fractures in men would be considered as a sentinel fracture with a similar clinical impact of forearm fracture.

Down-regulation of FTX promotes the differentiation of osteoclasts in osteoporosis through the Notch1 signaling pathway by targeting miR-137

BackgroundOsteoporosis (OP) is one of the commonly seen bone diseases with low bone mineral densities and trauma fractures. Accumulative studies have demonstrated that the occurrence of OP is closely related to osteoclasts differentiation. LncRNA FTX has been demonstrated to inhibit the development of some human cancers. However, its potential functions in human OP remains to be elusive.MethodsThe expressions of FTX and miR-137 in bone and serum samples of patients with or without OP were measured. Bioinformatics analysis, RIP assays and luciferase reporter assays were performed to examine the upstream and downstream transactional factors of miR-137. Functional assays were conducted to check the roles of the Notching1 signaling pathway OP.ResultsFTX was suppressed in OP samples and serums, however, miR-137 was greatly elevated. FTX reduced osteoclast-genesis and inhibited osteogenic differentiation by targeting miR-137. This also inhibited the Notch1 signaling pathway.ConclusionOur experiments and results pointed out that lncRNA FTX up-regulated miR-137 in OP through the Notch1 signaling pathway.

Decline in Muscle Strength and Performance Predicts Fracture Risk in Elderly Women and Men.

Muscle strength and performance are associated with fractures. However, the contribution of their rate of decline is unclear. To assess the independent contribution of the rate of decline in muscle strength and performance to fracture risk. Community-dwelling women (n = 811) and men (n = 440) aged 60 years or older from the prospective Dubbo Osteoporosis Epidemiology Study followed from 2000 to 2018 for incident fracture. Clinical data, appendicular lean mass/height2 (ht)2, bone mineral density, quadricep strength/ht (QS), timed get-up-and-go (TGUG), 5 times repeated sit-to-stand (5xSTS), and gait speed (GS) measured biennially. Rates of decline in muscle parameters were calculated using ordinary least squares regression and fracture risk was assessed using Cox's models. Incident low-trauma fracture ascertained by x-ray report. Apart from lean mass in women, all muscle parameters declined over time. Greater rates of decline in physical performance were associated with increased fracture risk in women (Hazard ratios [HRs] ranging from 2.1 (95% CI: 1.5-2.9) for GS to 2.7 (95% CI: 1.9-3.6) for 5xSTS, while in men only the decline in GS was associated with fracture risk (HR: 3.4 [95% CI: 1.8-6.3]). Baseline performance and strength were also associated with increased fracture risk in men (HRs ranging from 1.8 (95% CI: 1.1-3.0) for QS to 2.5 (95% CI: 1.5-4.1) for TGUG, but not in women. Rate of decline in physical performance in both genders, and baseline strength and performance in men, contributed independently to fracture risk. Sit-to-stand and GS were the tests most consistently associated with fractures. Further studies are required to determine whether muscle strength and/or performance improve the predictive accuracy of fracture prediction models.

BONE REMODELING MARKERS AS PREDICTORS OF BONE METABOLIC CHANGES IN MALES WITH DIABETIC OSTEOPATHY

Diabetic osteopathy is one of the little studied complications of diabetes mellitus (DM), which leads to common lowtrauma fractures and, as a consequence, disability and death. The level of insulin is connected with bone functional and morphological changes followed by decreased bone mineral density (BMD) in the early stages of diabetic osteopathy. Objective: to study bone morphofunctional properties in males with type 1 and 2 DM (T1DM and T2DM). Subjects and methods. Examinations were made in 41 male patients with T1DM and 52 male patients with T2DM without a history of fractures. Their age varied from 40 to 70 years (mean age, 55.8±0.7 years and 58.4±0.9 years, respectively). A control group consisted of 34 patients (mean age, 55.9±0.9 years) without a history of DM. Patients with other endocrine disorders, end-stage complications, or chronic liver and kidney diseases were excluded from the investigation. BMD was determined by dual-energy X-ray absorptiometry (DXA). Serum bone remodeling markers (procollagen type 1 amino-terminal propeptide and C-terminal telopeptide), as well as 25(OH)D, parathyrin, insulin, glycated hemoglobin (HbA1c), and electrolytes (Ca2+, P+) were evaluated. Results and discussion. An association of BMD with renal function, HbA1c, and body mass index was observed in patients with T2DM. In the T1MD group, BMD was closely related to insulin deficiency and was significantly lower than that in the control group. In patients with vitamin D deficiency, BMD was significantly lower than in those with normal vitamin D levels (p&lt;0.05). The patients with T1DM displayed both a decrease in BMD (p&lt;0.05) and a pronounced change in the levels of bone markers (p&lt;0.05). Those with T2DM had impaired bone remodeling processes, which was determined by the level of these markers (p&lt;0.05) and observed in the presence of normal BMD due to the complex pathophysiology of the underlying disease. Conclusion. Vitamin D deficiency, insufficient and decreased insulin sensitivity, hyperglycemia, and overweight are important causes of osteopathy in patients with DM. The markers of bone remodeling may become promising indicators for diagnosing osteopathy, but additional studies are needed to elaborate recommendations for their use in routine practice in order to predict and prevent this complication of DM.

Absence of association between inflammatory dietary pattern and low trauma fractures: Results of the French cohort NutriNet-Santé.

The aim of our study was to assess the association between the Alternate Dietary Inflammatory Index (ADII) and the risk of fracture in a French cohort of women and men older than 50 years. A total of 15,096 participants were included from the French NutriNet-Santé cohort. The ADII score was calculated at inclusion. Incident low trauma fractures were retrospectively self-reported by participants on a specific additional questionnaire. Multivariate hazard ratio obtained from Cox proportional hazard regression models were used to characterize an association between ADII (in quartiles) and incident low trauma fractures. In all, 12,046 participants (7607 (63.2%) women and 4439 (36.8%) men) were included in our study. For fractures, 806 (10.6%) and 191 (4.3%) low trauma fractures were recorded respectively in women and in men. Mean ADII was -1.23 (±3.13) for women and -0.87 (±3.64) for men. No association was detected between the ADII score and the risk of vertebral fracture (P=0.21), major osteoporotic fracture (P=0.93) and any low trauma fracture (P=0.72) in women nor in men (P=0.06 for major fracture and P=0.10 for low trauma fracture) after adjustment for sociodemographic, lifestyle variables and for bone treatments. This study in postmenopausal women and men older than 50 years from the general population did not show any association between inflammatory dietary pattern measured using the ADII and the risk of incident low trauma fracture.

SUN-065 Bone Health Outcomes in a Large, Diverse Pediatric Cohort Undergoing Hematopoietic Stem Cell Transplant

Background:Impaired bone mineral density (BMD) is a known complication of hematopoietic stem cell transplantation (HSCT) in adults and may lead to increased fracture risk. Little is known in pediatrics about the risks for impaired BMD and fragility (low trauma) fractures after HSCT. Factors that may influence the risk of bone disease include underlying diagnosis, glucocorticoid exposure, and HSCT complications (e.g. graft versus host disease (GVHD)). Our study aims to describe the incidence of fragility fractures in a large diverse pediatric HSCT population and to identify risk factors of both fracture and impaired BMD.Methods:We reviewed the records of 237 patients (age ≤ 21 years at time of transplant) who underwent HSCT at our institution between January 2015 and March 2018. The primary endpoint was incidence of fragility fractures and the secondary endpoint was assessment of BMD on dual-energy X-ray absorptiometry (DXA). We analyzed DXA results at one-year post-HSCT in 72 out of 206 patients alive at 1 year.Results:There were 25/237 (10.5%) patients with evidence of fragility fracture on x-ray. Of those, 18/25 (72%) were spine fractures. For patients who had fractures, median time to fracture was 5.9 months after BMT. Mortality at one-year was proportionally higher, though not significant (p=0.11) in patients who had at least one fragility fracture (24%; 6/25) compared to patients without fragility fracture (12%; 25/212). Vitamin D status at one-year post transplant was sufficient (>20ng/mL) in 94% (160/171) of patients measured. There was no difference in incidence of fracture between vitamin D sufficient and insufficient patients. The median height-for-age adjusted Z-score (HAZ) for spine BMD at one-year post transplant was 0.13 in all patients. The median HAZ spine BMD Z-score in patients with fragility fracture was -1.64, though data was available for only 5 patients.Conclusions:The incidence of fragility fractures, especially vertebral compression fractures, after pediatric HSCT is striking and is higher than in adult populations. Furthermore, there are likely additional asymptomatic patients with occult fractures not detected in out cohort. Additional analysis will assess the associations between underlying medical diagnosis, GVHD, and chronic glucocorticoid exposure on fragility fracture risk. The high incidence of fragility fractures seen in this study advocates for establishing bone health screening protocols with attention toward spinal imaging in pediatric patients undergoing HSCT.

OR13-03 Understanding Why Older People with Low Trauma Fractures Die Prematurely

There is increasing evidence that all proximal and not just hip fractures are associated with increased mortality risk. However, the cause of this increased mortality is unknown. We sought to determine the post-fracture trajectories of subsequent hospital admissions and mortality to develop an understanding of why patients with non-hip fractures die prematurely.This nationwide Danish population-based study included all individuals aged 50+ years who sustained an incident fragility fracture between 2001 and 2014. High-trauma fractures or individuals with fracture prior to 2001 were excluded. Fracture patients were matched 1:4 by sex, age and comorbidity status with non-fracture subjects alive at the time of fracture. Comorbidities included 33 unique medical conditions of the Charlson or Elixhauser comorbidity index. We modelled the contribution of specific fractures on the risk of subsequent admissions or death within the following 2 years.There were 212,498 women and 95,372 men with fracture followed by 30,677 and 19,519 deaths, respectively over 163,482 and 384,995 person-years of follow up. Mean age at fracture was 72± 11 for women and 75± 11 for men. Proximal fractures including hip, femur, pelvis, rib, clavicle and humerus had increased mortality compared with their matched non-fracture counterparts with HRs ranging from 1.5-4.0, while distal fractures such as ankle, forearm, hand or foot fractures had similar or lower mortality risk.Almost 75% of men and 60% of women had ≥1 comorbidity. For every additional comorbidity, risk of mortality increased for all fracture types. However, only for proximal fractures did the fracture itself independently increase mortality risk over and above co-morbidity status.The 2-yr post fracture admission and mortality patterns differed between proximal and distal fractures. Proximal, but not distal fracture subjects had greater risk of any major hospital admission (including cardiovascular disease, cancer, stroke, diabetes, pneumonia and pulmonary disease) within 2 years compared with their non-fracture counterparts. Distal fractures in general had similar admission patterns as their non-fractured matched counterparts.Furthermore, 2 year mortality risk was increased for proximal fractures whether or not they were admitted to hospital post fracture. By contrast, mortality risk was similar or reduced for distal fractures compared with non-fracture controls.This study has not only confirmed the increased mortality following proximal fractures but has demonstrated differing clinical trajectories between proximal and distal fractures that contribute to this increased mortality. These findings provide important insights as to why proximal fracture subjects die prematurely that may lead to specific avenues for intervention.

MON-392 Bone Health in Diabetes - Are We Addressing It?

Osteoporosis is a silent disease with decreased bone strength and increased risk of low-trauma fractures. These fractures lead to significant morbidity and mortality and are a major source of medical costs as well as indirect costs from reduced quality of life, disability and death. Calcium and vitamin D (vit D) are important interventions in preventing and treating osteoporosis along with anti-osteoporotic agents. Patients with diabetes mellitus (DM) are at an increased risk of fractures, particularly hip fractures (1). Additionally, bone healing after a fracture is compromised in patients with DM (2). Therefore, addressing bone health can have a significant impact on the well-being of a patient with DM. Optimal management of DM requires a multidisciplinary approach with care that is typically focused on glucose, lipid, and blood pressure management. We hypothesized that bone health may not be addressed consistently in patients with DM due to the need to address these other aspects of their care. We, therefore, conducted a retrospective chart review of patients with DM over the age of 50 with the aim to determine if bone health is being identified and if treatment is being initiated.A total of 100 patients (67 female, 33 male) were studied at the University of New Mexico Diabetes Comprehensive Care Center. Information regarding age, sex, DM type, vit D status and therapy, BMD, and FRAX score were collected. Vit D levels were checked in 68% female and 76% male patients. Mean vit D level was 31.8 ng/ml (reference range 30–100 ng/ml). Low vit D was identified in 33 patients of which only 18% were started on treatment. None of the 10 men identified received treatment for low vit D. BMD was obtained in only 21% of patients even though more than half met criteria for BMD screening based on age alone. Younger women (age < 65y) had more DXA scans performed than older women. Osteoporosis was diagnosed in one female and one male patient. Two female patients over age 65 met criteria for treatment based on FRAX. None of these 4 patients received osteoporosis therapy other than vit D replacement.In conclusion, vit D levels were checked in the majority of our patients indicating that bone health is being considered to some extent. However, low vit D levels were treated in only a minority of women, and in none of the men. Also, none of the patients who met criteria for osteoporosis treatment were started on therapy suggesting a lack of appropriate interventions. Using the results from this study, we plan to improve our clinical practice by incorporating bone health more into the care of our patients with DM, identify those at risk for osteoporosis-related fractures, and institute appropriate interventions.

Vertebral fracture assessment (VFA) in patients over 50years of age with a non-severe peripheral fracture.

The aim of this study was to evaluate the utility of VFA in detecting vertebral fractures (VFs) in patients over 50years of age, who suffered from a recent low-trauma non-severe peripheral fracture. This was an observational, single-center, cross-sectional study conducted in patients over 50years of age, who presented a recent low-trauma non-severe peripheral fracture and were identified by the Fracture Liaison Service (FLS) of Amiens University Hospital between December 2017 and March 2019. VFA was interpreted by two trained rheumatologists providing a consensual reading using Genant semi-quantitative assessment. Of the 359 eligible patients, 114 patients (31.8%) were included (mean age 65.6 ± 8.4years; 89.5% female). Twenty-four patients (21%) had one or more VF diagnosed by VFA. The total number of VF diagnosed by VFA was 30: 20 VF (66.7%) grade 1, 7 VF (23.3%) grade 2, and 3 VF (10%) grade 3. Among the 24 patients with at least one prevalent VF diagnosed by VFA, 18 patients had an osteoporosis medication adaptation after the VFA results (16 osteoporosis medication initiation and 2 treatment intensification), and 6 patients would have had an osteoporosis medication even without the VFA results (66.7% versus 33.3% respectively, p < 0.001). Of the 51 patients receiving an osteoporosis medication after DXA and VFA, 18 patients (35.3%) had a change in the management of osteoporosis after knowing the outcome of VFA. All the VFs diagnosed by VFA were unknown before. We did not evidence any threshold (age, T-score, height loss) below which no VF was detected. Our study demonstrates the usefulness of systematic VFA to detect prevalent VF in patients over 50years of age who suffer from a recent non-severe peripheral fracture.

O01 Hypophosphatasia in adults at a specialist centre in the UK: the spectrum of musculoskeletal disease

Abstract Background Hypophosphatasia (HPP) is a condition arising due to mutations in the gene encoding the tissue-non-specific alkaline phosphatase (TNSALP) isoenzyme (ALPL), leading to deficient activity of TNSALP. It can be inherited as an autosomal dominant or recessive disorder. There are over 300 known mutations in the ALPL gene associated with HPP, leading to varying degrees of deficiency in the activity of TNSALP. There are six clinical forms of HPP, with a great degree of heterogeneity in clinical presentation. The adult form is generally milder than perinatal and infantile forms, which may be fatal. Estimates of the prevalence of HPP range from 0.3/100,000 (more severe forms), to 1/6370 (less severe forms). Diagnosis is based on clinical features, biochemical abnormalities (low serum alkaline phosphatase (ALP), raised serum pyridoxal-5’-phosphate and raised urinary phosphoethanolamine), and genetic testing. The dentition and musculoskeletal system are often affected. Low trauma, metatarsal and atypical subtrochanteric femoral fractures may be seen, often with poor healing. However in some cases, individuals may present with calcium pyrophosphate deposition disease (CPPD) or non-specific musculoskeletal features. Under-recognition of HPP and diagnostic delay are therefore common. This retrospective observational study, performed at a specialist centre, aimed to characterise the spectrum of musculoskeletal manifestations in adults with HPP. Methods Patient records of adults with a confirmed diagnosis of HPP seen in the Rheumatology department at St George’s Hospital, London, were consulted. Clinical features at presentation and those developed subsequently were recorded, with a focus on musculoskeletal manifestations. Biochemical, genetic and radiographic data were also obtained. Results Fifteen individuals (two male, thirteen female) with a confirmed diagnosis of HPP were identified. Average delay to diagnosis was 21 years. The commonest presenting feature for the whole cohort was joint pain or swelling, followed by dental caries. The commonest presenting musculoskeletal feature in childhood was fracture (often low trauma and recurrent); in adults it was joint pain followed by poor mobility. There were eight diagnoses of osteoarthritis, five cases of tendinopathy and three of bursitis. Four patients had previously been diagnosed with psoriatic arthritis and three with pseudogout. Other musculoskeletal diagnoses included patellofemoral dysfunction, hypermobility and musculoskeletal tumours (two individuals). The upper limb joints were most commonly affected; some individuals reported back and knee pain. Musculoskeletal morbidity was high: eight individuals had poor mobility or abnormal gait, and three were unable to work through ill health. Conclusion There is a long delay to diagnosis of HPP. The condition may present in adults with non-specific musculoskeletal or dental features. It is therefore important to consider the diagnosis in individuals with a low ALP and musculoskeletal features which may suggest HPP, such as fractures or CPPD. Earlier recognition may avoid potential harm through inappropriate bisphosphonate or high-dose vitamin D therapy. Disclosures J. Kotecha None. S. Mansour None. C. Hall None. K.E. Moss None.

Increased prevalence of self-reported fractures in Asian Indians with diabetes: Results from the ICMR-INDIAB population based cross-sectional study.

Diabetes mellitus (DM), has been associated with increased fracture risk. However, there are no data pertaining to the prevalence of fractures for patients with DM in India. The aim of this study was to determine the prevalence of fractures in Asian Indians with and without diabetes. The study used the data of Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a community- based cross sectional survey conceived with the aim of obtaining the prevalence rates of diabetes in India as a whole. A community-based sample of 57,117 individuals aged ≥20 years was obtained. Diabetes was diagnosed by oral glucose tolerance test using capillary blood (except in self-reported diabetes). Fractures were self-reported. Fracture data were available in 54,093 subjects. Out of these, 1416 (2.6%) had fractures. Overall prevalence of diabetes and prediabetes was 7.1% and 10.5% respectively. Prevalence of fractures was significantly higher in diabetes group (4%) compared with non-diabetes group (2.5%). In multivariate logistic regression analysis, diabetes was associated with an increased risk (1) of any fracture (OR=1.28, 95% CI: 1.07-1.5) and (2) of low trauma fracture (hip and spine combined) (OR = 1.8, 95% CI:1.1-2.8). After gender stratification, diabetes was a risk factor for fracture only in women. Age (>40 years) in women, high waist circumference (>90 cm) in men, alcohol consumption and urban residence in both men and women were other significant contributors to fracture risk. Increased prevalence of self-reported fractures was seen in individuals with diabetes in this population-based study from India.

Fracture risk following high-trauma versus low-trauma fracture: a registry-based cohort study.

Some have questioned the usefulness of distinguishing high-trauma fractures from low-trauma fractures. The aim of this study is to compare BMD measurements and risk of subsequent low-trauma fracture in patients with prior high- or low-trauma fractures. Using a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40years or older with fracture records from linked population-based healthcare data. Age- and sex-adjusted BMD Z-scores and covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CI) for incident fracture were studied in relation to prior fracture status, categorized as high-trauma if associated with external injury codes and low-trauma otherwise. The study population consisted of 64,428 women and men with no prior fracture (mean age 63.7years), 858 with prior high-trauma fractures (mean age 65.1years), and 14,758 with prior low-trauma fractures (mean age 67.2years). Mean Z-scores for those with any prior high-trauma fracture were significantly lower than in those without prior fracture (P < 0.001) and similar to those with prior low-trauma fracture. Median observation time for incident fractures was 8.8years (total 729,069 person-years). Any prior high-trauma fracture was significantly associated with increased risk for incident major osteoporotic fracture (MOF) (adjusted HR 1.31, 95% CI 1.08-1.59) as was prior low-trauma fracture (adjusted HR 1.55, 95% CI 1.47-1.63), and there was no significant difference between the two groups (prior trauma versus low-trauma fracture P = 0.093). A similar pattern was seen when incident MOF was studied in relation to prior hip fracture or prior MOF, or when the outcome was incident hip fracture or any incident fracture. High-trauma and low-trauma fractures showed similar relationships with low BMD and future fracture risk. This supports the inclusion of high-trauma fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk.

Verifying participant-reported clinical outcomes: challenges and implications

BackgroundResearchers often rely on trial participants to self-report clinical outcomes (for example, fractures, re-operations). Little information exists as to the ‘accuracy’ of participant-reported clinical outcomes, particularly in randomised controlled trials (RCTs). To help address this evidence gap, we report four case studies, nested within different RCTs where participant-reported clinical outcome data were compared with those reported by clinicians or extracted from medical notes.MethodsFour publicly-funded RCTs with different methods of verifying participant-reported outcomes were identified. In KAT, the participants were asked about hospital admissions for any reason. Where it was thought to be relevant to the trial knee, further information was sought from the lead surgeon at the admitting site to confirm whether or not the admission was relevant to the trial knee. In REFLUX, participants were asked about hospital admissions for any reason. For participants who reported a re-operation, further information was sought from the lead surgeon at the admitting site to confirm this. In RECORD, participants were asked three questions regarding broken bones. Where low-trauma fractures were reported, clinical verification was sought, initially from the research nurse at the site.In CATHETER, participants were asked about urinary tract infections (UTIs), and a prescription of antibiotics was provided for the treatment of UTIs following urethral catheterisation. The GPs of those who reported a UTI were contacted to confirm that an antibiotic prescription had been issued for the suspected UTI.ResultsIn KAT, 397 of 6882 (6%) participant-reported hospital admissions were confirmed as relevant to the trial knee. In REFLUX, 16 of 19 participants (84%) who appeared to have had a re-operation were confirmed as having had one. In RECORD, 473 of 781 (61%) fractures reported by participants were confirmed as being low-trauma fractures. In CATHETER, 429 of 830 participant-reported UTIs (52%) were confirmed as such by the GPs.ConclusionsWe used different approaches in our verification of participant-reported outcomes in clinical trials, and we believe there is no one optimal solution. Consideration of issues such as what information is sought from participants, the phrasing of questions, whether the medical records are a true ‘gold standard’ and costs and benefits to the RCT may help determine the appropriate approach.