Incidence Of Fragility Fractures Research Articles

Early Denosumab for the prevention of osteoporotic fractures in breast cancer women undergoing aromatase inhibitors: A case-control retrospective study.

Aromatase inhibitors (AIs) might have a detrimental impact on bone health in breast cancer (BC) women. Denosumab has been shown to reduce the risk of fractures, but the appropriate time for starting is yet to be clearly defined. To evaluate the effects of early treatment with Denosumab (⩽ 12 months after starting AIs) compared to a delayed treatment in BC women. In this retrospective case-control study, we included medical records of BC post-menopausal women, treated with AIs therapy; they were divided as: study group (starting Denosumab ⩽ 12 months after AIs) and control group (> 12 months). At the baseline (T0) and at 18 months (T1), we evaluated the lumbar spine (LS) Tscore and femoral neck (FN) Tscore. Furthermore, at T1 we assessed the incident fragility fractures. Fifty-nine BC survivors (mean age: 61.5 ± 11.5 years) were included: 28 with Early Denosumab and 31 with Late Denosumab. At T1, the study group did not show any incident hip or vertebral fragility fracture, whereas the Late Denosumab group showed 2 incident hip fractures (6.5%) and 4 (12.9%) vertebral fragility fractures. Early Denosumab showed a significant positive effect on both LS (p= 0.044) and FN (p= 0.024) Tscore variations. Taken together, our findings suggest that an early start of Denosumab might be considered for the osteoporosis management in BC women undergoing AIs.

Real-life short-term effectiveness of anti-osteoporotic treatments: a longitudinal cohort study

Introduction:Randomized clinical trials have shown that anti-osteoporotic treatments can increase bone mineral density (BMD) and reduce the incidence of fragility fractures. However, data on the real-life effectiveness of anti-osteoporotic medications are still scarce.Methods:We conducted a cohort study on women at high risk of fracture. We retrieved clinical and densitometric data from the DeFRA database, which derives from the DeFRA tool, a web-based fracture risk assessment tool. Multivariable Cox regression survival models were employed to analyze the effectiveness of different anti-osteoporotic drugs on fracture. In sensitivity analyses, we conducted 1:1 propensity score matching analyses.Results:Data on 50,862 women were available. Among these, 3574 individuals had at least two consecutive visits. The crude fracture rate was 91.9/1000 person-year for non-treated patients. The crude fracture rate in bisphosphonate users was 72.1/1000 person-year, in denosumab users was 58.2/1000 person-year, and in teriparatide users was 19.3/1000 person-year. Overall, we found that bisphosphonate use was associated with a 30% lower risk of fracture compared to no treatment [adjusted hazard ratio (aHR): 0.70, 95% confidence interval (CI): 0.50–0.98]. Treatment with denosumab and teriparatide were associated with 60% and 90% lower risk of fracture, respectively (aHR: 0.43, 95% CI: 0.24–0.75 and aHR: 0.09, 95% CI: 0.01–0.70). Bisphosphonate use was associated with a lower risk of fracture only after 1 year of treatment.Conclusion:In conclusion, we found that all anti-osteoporotic medications considered in the study effectively reduced the risk of fracture in the real-life. The effect of bisphosphonate on fracture risk was apparent only after the first year of treatment. Our findings do not support the use of bisphosphonates in patients at imminent risk of fracture.

10-Year Fracture Risk in Postmenopausal Women with Osteopenia and Osteoporosis in South Korea.

BackgroundIn South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015.MethodsBMD was classified as normal (T-score ≥−1.0 standard deviation [SD]), osteopenia (T-score <−1.0 SD and >−2.5 SD), and osteoporosis (T score ≤−2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD.ResultsAmong the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD.ConclusionWomen with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.

Polypharmacy, chronic kidney disease, and incident fragility fracture: a prospective cohort study.

Polypharmacy is associated with an increased risk of fracture in aging populations, but no study has accounted for the impact of kidney function on this association. This study aimed to examine the association between polypharmacy and incident fragility fracture based on chronic kidney disease (CKD) status. Participants were 2023 patients (55% men; mean age, 69years) of Sado General Hospital enrolled in the Project in Sado for Total Health (PROST) between June 2008 and December 2016. Among these, 65%, 28%, and 7% had non-CKD, non-dialysis-dependent CKD, and dialysis-dependent CKD, respectively. Multivariable Cox proportional hazards analysis was conducted with adjustments for potential confounders. Prevalences of polypharmacy (≥ 5 medications) and hyperpolypharmacy (≥ 10 medications) among participants were 43% and 9% for non-CKD, 62% and 23% for non-dialysis-dependent CKD, and 85% and 34% for dialysis-dependent CKD, respectively. During a median follow-up of 5.6years, 256 fractures occurred. More medications were associated with a higher risk of fractures. Specifically, compared to participants without polypharmacy, adjusted hazard ratios were 1.32 (95% CI 0.96-1.79) and 1.99 (1.35-2.92) for those with polypharmacy and hyperpolypharmacy, respectively, after adjusting for osteoporosis risk factors, CKD status, and comorbidities. No effect modification by CKD status was observed (interaction P = 0.51). Population-attributable fractions of hyperpolypharmacy for fracture were 9.9% in the total cohort and 42.1% in dialysis-dependent CKD patients. Hyperpolypharmacy is associated with an increased risk of fragility fracture regardless of CKD status, and has a strong impact on incident fragility fractures in dialysis-dependent CKD patients.

Predicting Imminent Fractures in Patients With a Recent Fracture or Starting Oral Bisphosphonate Therapy: Development and International Validation of Prognostic Models.

The availability of anti-osteoporosis medications with rapid onset and high potency requires tools to identify patients at high imminent fracture risk (IFR). There are few tools that predict a patient's IFR. We aimed to develop and validate tools for patients with a recent fracture and for patients initiating oral bisphosphonate therapy. Models for two separate cohorts, those with incident fragility fracture (IFx) and with incident oral bisphosphonate prescription (OBP), were developed in primary care records from Spain (SIDIAP database), UK (Clinical Practice Research Datalink GOLD), and Denmark (Danish Health Registries). Separate models were developed for hip, major, and any fracture outcomes. Only variables present in all databases were included in Lasso regression models for the development and logistic regression models for external validation. Discrimination was tested using area under curve (AUC) and calibration was assessed using observed versus predicted risk plots stratified by age, sex, and previous fracture history. The development analyses included 35,526 individuals in the IFx and 41,401 in the OBP cohorts, with 671,094 in IFx and 330,256 in OBP for the validation analyses. Both the IFx and OBP models demonstrated similarly good performance for hip fracture at 1 year (with AUCs of 0.79 [95% CI 0.75 to 0.82] and 0.87 [0.83 to 0.91] in Spain, 0.71 [0.71 to 0.72] and 0.73 [0.72 to 0.74] in the UK, and 0.70 [0.70 to 0.70] and 0.69 [0.68 to 0.70] in Denmark), and lower discrimination for major osteoporotic and any fracture sites. Calibration was good across all three countries. Discrimination and calibration for the 2-year models was similar. The proposed IFR prediction models could be used to identify more precisely patients at high imminent risk of fracture and inform anti-osteoporosis treatment selection. The freely available model parameters permit local validation and implementation. © 2021 American Society for Bone and Mineral Research (ASBMR).

Demographic changes in pelvic fracture patterns at a Swiss academic trauma center from 2007 to 2017.

BACKGROUNDIncreasing life expectancy has led to higher incidence of fragility fractures of the pelvis. These demographic changes may have a direct impact on fracture patterns. The goal of this study was (1) to evaluate demographical trends in patients with pelvic ring injuries at a tertiary Swiss trauma center and (2) to analyze the influence on fracture patterns.METHODSWe performed a retrospective cross-sectional study including 958 patients (mean ± SD age, 57 ± 21 years; 48% women) with a pelvic ring injury between 2007 and 2017. Fractures were classified according to Tile, Young and Burgess or Rommens and Hofmann (fragility fractures) using conventional and computer tomography imaging. Low-energy fractures were defined as fractures resulting from fall from standing height or less. Fracture classifications, age, sex, Injury Severity Score, and trauma mechanism were compared using analysis of variance or χ2 test. Cluster analysis was performed to identify groups with similarities in fracture patterns and demographic parameters.RESULTSFrom 2007 to 2017, the frequency of pelvic ring injuries increased by 115% (increase per decade), and mean age increased by 15% (p = 0.031). A trimodal age distribution was found; highest increase for fractures occurred in the older (265%) patient group. Low-energy fracture was the most common trauma mechanism (43% of all fractures, an increase of 249%). Changes in fracture pattern showed a disproportioned increase of lateral compression (LC) fractures (LC type 1 in 64%) or partially stable fracture (B2, with 39%). In patient older than 65 years, the strongest increase was found for nondisplaced posterior fractures with an overall prevalence of 62%. Five clusters were found with the most frequent cluster representing older female patients with low-energy fracture (LC, Tile type B) in 30%.CONCLUSIONThe current results corroborate the trend of increasing frequency of fragility fractures in an aging society. The demographic shift has a direct impact on fracture pattern with a disproportionate increase in partially stable compression fracture of the pelvis.LEVEL OF EVIDENCEPrognostic/Epidemiologic, Level III.

Bone Health Outcomes at 1 Year after Hematopoietic Stem Cell Transplantation in a Heterogeneous Pediatric Population

Impaired bone mineral density (BMD) is a known complication of hematopoietic stem cell transplantation (HSCT) in adults and may lead to increased fracture risk. Less is known in children about the risks for impaired BMD and fragility (low trauma) fractures after HSCT. In this study, we evaluated the incidence of fragility fractures in a large diverse pediatric HSCT recipient population and identified risk factors for both fracture and impaired BMD. We reviewed the records of 237 patients age ≤21 years at the time of transplantation who underwent HSCT at our institution between January 2015 and March 2018. The primary endpoint was the incidence of fragility fractures, and the secondary endpoint was assessment of BMD on dual-energy X-ray absorptiometry (DXA). DXA studies were available for analysis in 79 of 206 patients who were alive at 1 year after HSCT, and the median height-for-age adjusted z-score for spine BMD was 0.15. Among the 237 patients in this study, 25 (10.5%) had evidence of at least 1 fragility fracture on imaging. In the patients with at least 1 fragility fracture, 18 (72%) sustained spine fractures. The median time to fracture was 5.9 months after HSCT. Mortality at 1 year was proportionally higher, although not statistically significantly so (P=.11) in patients who had at least 1 fragility fracture (24%; 6 of 25) compared with patients without a fragility fracture (12%; 25 of 212). Vitamin D status at 1 year post-HSCT was sufficient (>20 ng/mL) in 94% of the patients assessed (160 of 171). There was no difference in the incidence of fracture between vitamin D-sufficient patients and vitamin D-insufficient patients (P=1.0). The incidence of fracture was significantly higher in patients with graft-versus-host disease (GVHD) compared with those without GVHD (15% vs 6%; P=.02). There was no significant difference in fracture occurrence between patients who received reduced-intensity conditioning and those who received myeloablative conditioning. The cumulative glucocorticoid dose was significantly associated with fracture in patients exposed to glucocorticoids for >3 months (P=.03). The incidence of fragility fractures, especially vertebral compression fractures, after pediatric HSCT is striking. Furthermore, there may have been additional, asymptomatic patients in our cohort with undetected, occult fractures. The high incidence of fragility fractures seen in this study advocates for establishing bone health screening protocols with attention to spinal imaging in pediatric patients undergoing HSCT.

Socio-economic inequalities in fragility fracture incidence: a systematic review and meta-analysis of 61 observational studies.

This systematic review and meta-analysis aimed to evaluate the impact of socio-economic status (SES) on fragility fracture risk. Medline, Embase, and CINAHL databases were searched from inception to 28 April 2021 for studies reporting an association between SES and fragility fracture risk among individuals aged ≥50 years. Risk ratios (RR) were combined in meta-analyses using random restricted maximum likelihood models, for individual-based (education, income, occupation, cohabitation) and area-based (Index of Multiple Deprivation, area income) SES measures. A total of 61 studies from 26 different countries including more than 19 million individuals were included. Individual-based low SES was associated with an increased risk of fragility fracture (RR 1.27 [95%CI 1.12, 1.44]), whilst no clear association was seen when area-based measures were used (RR 1.08 [0.91, 1.30]). The strength of associations was influenced by the type and number of covariates included in statistical models: RR 2.69 [1.60, 4.53] for individual-based studies adjusting for age, sex and BMI, compared with RR 1.06 [0.92, 1.22] when also adjusted for health behaviours (smoking, alcohol, and physical activity). Overall, the quality of the evidence was moderate. Our results show that low SES, measured at the individual level, is a risk factor for fragility fracture. Low BMI and unhealthy behaviours are important mediators of the effect of SES on fracture risk. Strategies to prevent fractures and reduce unhealthy behaviours should aim to tackle structural inequalities in society thereby reducing health inequalities in fragility fracture incidence.

Association of incident fragility fractures in patients hospitalised due to unexplained syncope and orthostatic hypotension

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The study was funded by The Swedish Heart-Lung Foundation, The Greta and Johan Kock Foundation, and an Agreement for Medical Education and Research (ALF) grant by Swedish Research Council funding for clinical research in medicine. Background Fragility fractures are caused by low-energy insults such as falls from standing height or less and pose a growing health challenge as their incidence rises with increasing age. Impaired orthostatic blood pressure response and a number of cardiovascular biomarkers have been previously identified as risk factors for fractures. It is likely that severe episodes of syncope and orthostatic hypotension increase the risk of subsequent fragility fractures, however this relationship has not been thoroughly examined. Purpose To investigate the relationship of hospital admissions due to unexplained syncope and OH with incident fragility fractures in a middle-aged population. Methods We analysed a large population-based prospective cohort of 30,446 middle-aged individuals (age, 57.5 ± 7.6; men, 39.8%). We included patients hospitalised due to unexplained syncope and OH. Cox regression analysis adjusted for age, sex, prevalent fractures, body mass index (BMI) were applied to assess the impact of unexplained syncope/OH hospitalisations on subsequent incident fragility fractures. Prevalent fractures occurring before syncope/OH hospitalisation were excluded (n = 39) as well as cases with no follow-up time after the event of syncope/OH (n= 8). Results The mean follow-up from baseline to first incident fracture or end of follow-up was 17.8 + 6.5 years, and 8201 (27%) suffered incident fracture. The mean age of patients with unexplained syncope (n = 493) and OH patients (n = 406) at baseline was 61.5 ± 7.1 years (50.1%, male) and 62.6 ± 6.6 years (49.8% male), respectively. The mean time between baseline and first admission for syncope and OH was 12.3 ± 4.5 years, and the mean age at first hospitalisation was 74.4 ± 7.6 years. In the multivariable-adjusted Cox regression, the risk of subsequent incident fractures was increased among patients hospitalised due to unexplained syncope (HR: 1.20; 95% CI 1.03–1.40; p &amp;lt; 0.02) and OH (HR: 1.40; 95% CI 1.20–1.64; p &amp;lt; 0.001), respectively (Kaplan-Meier curves; Figure 1). Conclusions Patients hospitalised due to unexplained syncope and OH demonstrate increased risk of subsequent fragility fractures. We suggest that patients who are hospitalised for unexplained syncope and OH should be clinically assessed for true syncope aetiology, systematically treated against fall risk, and evaluated for additional risk factors for fragility fractures. Abstract Figure 1. Kaplan-Meier curves

POS0163 INCIDENT FRACTURE RISK PREDICTION USING THE FRAGILITY SCORE CALCULATED BY LUMBAR SPINE RADIOFREQUENCY ECHOGRAPHIC MULTI SPECTROMETRY (REMS) SCANS

Background:The main consequence of osteoporosis is the occurrence of fractures due to bone fragility, with important sequelae in terms of disability and mortality. It has been already demonstrated that the information about bone mass density (BMD) alone is not sufficient to predict the risk of fragility fractures, since several fractures occur in patients with normal BMD [1].The Fragility Score is a parameter that allows to estimate skeletal fragility thanks to a trans-abdominal ultrasound scan performed with Radiofrequency Echographic Multi Spectrometry (REMS) technology. It is calculated by comparing the results of the spectral analysis of the patient’s raw ultrasound signals with reference models representative of fragile and non-fragile bones [2]. It is a dimensionless parameter, which can vary from 0 to 100, in proportion to the degree of fragility, independently from BMD.Objectives:This study aims to evaluate the effectiveness of Fragility Score, measured during a bone densitometry exam performed with REMS technology at lumbar spine, in identifying patients at risk of incident osteoporotic fractures at a follow-up period of 5 years.Methods:Caucasian women with age between 30 and 90 were scanned with spinal REMS and DXA. The incidence of osteoporotic fractures was assessed during a follow-up period of 5 years. The ability of the Fragility Score to discriminate between patients with and without incident fragility fractures was subsequently evaluated and compared with the discriminatory ability of the T-score calculated with DXA and with REMS.Results:Overall, 533 women (median age: 60 years; interquartile range [IQR]: 54-66 years) completed the follow-up (median 42 months; IQR: 35-56 months), during which 73 patients had sustained an incident fracture.Both median REMS and DXA measured T-score values were significantly lower in fractured patients than for non-fractured ones, conversely, REMS Fragility Score was significantly higher (Table 1).Table 1.Analysis of T-score values calculated with REMS and DXA and Fragility Score calculated with REMS. Median values and interquartile ranges (IQR) are reported. The p-value is derived from the Mann-Whitney test.Patients without incident fragility fracturePatients with incident fragility fracturep-valueT-score DXA[median (IQR)]-1.9 (-2.7 to -1.0)-2.6 (-3.3 to -1.7)0.0001T-score REMS[median (IQR)]-2.0 (-2.8 to -1.1)-2.7 (-3.5 to -1.9)&lt;0.0001Fragility Score[median (IQR)]29.9 (25.7 to 36.2)53.0 (34.2 to 62.5)&lt;0.0001By evaluating the capability to discriminate patients with/without fragility fractures, the Fragility Score obtained a value of the ROC area under the curve (AUC) of 0.80, higher than the AUC of the REMS T-score (0.66) and of the T-score DXA (0.64), and the difference was statistically significant (Figure 1).Figure 1.ROC curve comparison of Fragility Score, REMS and DXA T-score values in the classification of patients with incident fragility fractures.Furthermore, the correlation between the Fragility Score and the T-score values was low, with Pearson correlation coefficient r=-0.19 between Fragility Score and DXA T-score and -0.18 between the Fragility Score and the REMS T-score.Conclusion:The Fragility Score was found to be an effective tool for the prediction of fracture risk in a population of Caucasian women, with performances superior to those of the T-score values. Therefore, this tool presents a high potential as an effective diagnostic tool for the early identification and subsequent early treatment of bone fragility.

Risk Factors for Incident Fracture in Older Adults With Type 2 Diabetes: The Framingham Heart Study.

OBJECTIVETo identify risk factors for fracture in type 2 diabetes.RESEARCH DESIGN AND METHODSThis prospective study included members of the Framingham Original and Offspring Cohorts. Type 2 diabetes was defined as fasting plasma glucose >125 mg/dL or use of type 2 diabetes therapy. We used repeated-measures Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% CIs for associations between potential predictors and incidence of fragility fracture.RESULTSParticipants included 793 individuals with type 2 diabetes. Mean ± SD age was 70 ± 10 years; 45% were women. A total of 106 incident fractures occurred over 1,437 observation follow-up intervals. Fracture incidence increased with age (adjusted HRs 1.00, 1.44 [95% CI 0.65, 3.16], and 2.40 [1.14, 5.04] for <60, 60–70, and >70 years, respectively; Ptrend = 0.02), female sex (2.23 [1.26, 3.95]), HbA1c (1.00, 2.10 [1.17, 3.75], and 1.29 [0.69, 2.41] for 4.45–6.46% [25–47 mmol/mol], 6.50–7.49% [48–58 mmol/mol], and 7.50–13.86% [58–128 mmol/mol]; Ptrend =0.03), falls in past year (1.00, 1.87 [0.82, 4.28], and 3.29 [1.34, 8.09] for no falls, one fall, and two or more falls; Ptrend =0.03), fracture history (2.05 [1.34, 3.12]), and lower grip strength (0.82 [0.69, 0.99] per 5-kg increase). Femoral neck bone mineral density, BMI, smoking, physical function, chronic diseases, medications, and physical function were not associated with fracture incidence.CONCLUSIONSPrior falls, fractures, low grip strength, and elevated HbA1c are risk factors for fractures in older adults with type 2 diabetes. Evaluation of these factors may improve opportunities for early intervention and reduce fractures in this high-risk group.

O03 Prevalence of fragility fractures and medication prescription for osteoporosis in patients with polymyalgia rheumatica: results from the PMR Cohort Study

Abstract Background/Aims Polymyalgia rheumatica (PMR) is one of the commonest indications for long term glucocorticoid (GC) use, leading to an increased risk of osteoporosis and fragility fractures. Clinical guidelines recommend prescribing medication including vitamin D, calcium and anti-resorptives, such as bisphosphonates. The aim of this study was to examine the association of reported falls and prescriptions of medications for osteoporosis with future fragility fractures in a cohort of people with PMR. Methods 652 people with an incident diagnosis of PMR responded to a baseline survey between June 2012 and June 2014. This included data on general health, sociodemographics, history of falls and medication. Data on fractures and prescriptions were collected at 12 and 24 months. Fragility fractures were defined as fractures of the hip, wrist or spine. Logistic regression models were used to assess the association between baseline characteristics and fractures at 12 and 24 months. Analysis was conducted unadjusted and adjusted for age, gender, reported medication use and falls history. Results 112 (17.2%) baseline respondents reported a previous fragility fracture. 60 (83.3%) of the 72 respondents who reported a fragility fracture between baseline and month 12 also reported a fragility fracture at baseline. 49 (79.1%) of the 60 respondents who reported a fragility fracture at between the month 12 and 24 also reported a fragility fracture at baseline. Falls before baseline was the most significant predictor of fragility fracture at 12 (OR 2.35 95% CI 1.35-4.12) and 24 (OR 1.91 95% CI 1.05-3.49) months. Fewer than 50% of respondents were ever prescribed treatment for osteoporosis. Being prescribed treatment for osteoporosis was associated with a reduced incidence of fragility fractures at 24 months (adjusted OR 0.28 95% CI 0.10-0.80), but an increased incidence at 12 months (adjusted OR 2.10 95% CI (1.3-3.48). Calcium and vitamin D prescription, gender and age were not significantly associated with fracture outcome. Conclusion Despite guidelines, fewer than 50% of patients were prescribed medications for osteoporosis. This data highlights the risks of fractures in PMR patients who have experienced previous falls. Over a period of two years, medication for osteoporosis was significantly protective, hence more needs to be done to encourage adherence to guidelines. Further studies need to address reasons for non-adherence to guidelines and the effects of long-term treatment. Disclosure B. Sokhal: None. S.L. Hider: None. Z. Paskins: None. C.D. Mallen: None. S. Muller: None.

Efficacy and safety of calcium and vitamin D supplementation to prevent osteoporotic fracture

Dietary supplementation of calcium and vitamin D has been deemed one of the most important tools to fight against osteoporotic fractures increasing with aging of the population globally. Reports from early clinical trials demonstrated that supplementation of calcium and vitamin D for patients with osteoporosis can reduce the incidence of fragility fractures by decreasing bone loss and falls. However, following trials failed to demonstrate the efficacy of calcium and vitamin D for the prevention of osteoporotic fractures, questioning the need of calcium and vitamin D supplementation. Even metanalyses and system reviews presented opposite conclusions , depending on clinical trials included. Recent studies reported that excessive calcium supplement can increase cardiovascular risk such as non-fatal myocardial infarction and that excessive vitamin D supplement can produce more frequent falls than it is supposed to be. However, in spite of some arguments regarding the efficacy and safety of calcium and vitamin D supplementation, it seems to be essential to provide 800 to 1,000 mg elementary calcium and 800 to 1,000 IU vitamin D for the elderly whose intake of calcium and vitamin D is insufficient to prevent osteoporotic fracture.

The yawning gap between osteoporosis diagnosis and treatment after a fragility fracture in Mexico

Osteoporosis is a highly prevalent and disabling disease. While there is typically a gap between osteoporosis diagnosis and treatment after a fragility fracture, this gap has not been measured in Mexico. The study aimed to describe and quantify the gap between osteoporosis diagnosis and treatment after an incident fragility fracture. A descriptive and 3-year retrospective chart review study was conducted on patients over the age of 50 with a diagnosis of an incident acute low-energy fracture of either the hip, distal radius, or vertebrae. We included 838 patients with a mean age of 76.3 ± 12.2 years. The sample was mostly women (665 participants, 79.4%); 589 (70.3%) had a hip fracture, 173 (20.6%) had a distal radius fracture, and 76 (9.1%) had a vertebral fracture. Only 28 (3.3%) had a previous diagnosis and were taking a pharmacological treatment for osteoporosis; 11 (1.3%) received their diagnosis while hospitalized. Immediately after the fracture, and 1 and 3 years later, 144 (17.1%), 71 (8.4%), and 96 (11.4%) respectively received a pharmacological treatment, 195 (23.2%), 65 (7.7%), and 45 (5.3%) supplementation, and 16 (1.9%), 16 (1.9%), and 21 (2.5%) a non-pharmacologic treatment. No significant differences in treatment prescriptions were found after a second or third fracture. The study quantifies the too high frequency of failure to diagnose and treat osteoporosis in patients with fragility fractures. Measures should be established to reduce the yawning gap between osteoporosis diagnosis and treatment after a fragility fracture.

Risk factors for imminent fractures: A substudy of the Frisbee cohort

Multiple factors increase the risk of an imminent fracture, including a recent fracture, older age, osteoporosis, comorbidities, and the fracture site. These findings could be a first step in the development of a model to predict an imminent fracture and select patients most at need of immediate treatment. The risk of a recurrent fragility fracture is maximal during the first 2 years following an incident fracture. In this prospective cohort study, we looked at the incidence of recurrent fractures within 2 years after a first incident fracture and we assessed independent clinical risk factors (CRFs) increasing this imminent fracture risk. A total of 3560 postmenopausal women recruited from 2007 to 2013 were surveyed yearly for the occurrence of fragility fractures. We identified patients who sustained a fracture during the first 2 years following a first incident fragility fracture. We quantified the risk of a new fracture and assessed independent CRFs, associated with an imminent fracture at various sites. A recent fracture was a significant CRF for an imminent fracture (OR (95% CI): 3.7 (2.4–5.7) [p < 0.0001]). The incidence of an imminent fracture was higher in subjects above 80 years (p < 0.001). Other CRFs highly predictive in a multivariate analysis were osteoporosis diagnosis (p < 0.01), a central fracture as the index fracture (p < 0.01), and the presence of comorbidities (p < 0.05), with likelihood ratios of 1.9, 1.9, and 2.2, respectively. An imminent fracture was better predicted by a central fracture (p < 0.01) than by a major osteoporotic fracture. The hazard ratio was the highest for a central fracture. In patients with a recent fracture, older age, osteoporosis, comorbidities, and fracture site were associated with an imminent fracture risk. These findings could be a first step in the development of a model to predict an imminent fracture and select patients most at need of immediate and most appropriate treatment.

Longitudinal Bone Loss Occurs at the Radius in CKD

IntroductionChronic kidney disease (CKD) exposes to an increased incidence of fragility fractures. International guidelines recommend performing bone mineral density (BMD) if the results will impact treatment decisions. It remains unknown where bone loss occurs and what would preclude the longitudinal loss in patients with CKD. Here, we aimed to investigate factors influencing BMD and to analyze the longitudinal BMD changes.MethodsIn the NephroTest cohort, we measured BMD at the femoral neck, total hip, lumbar spine, and proximal radius, together with circulating biomarkers and standardized measured glomerular filtration rate (mGFR) by 51Cr-EDTA in a subset of patients with CKD stage 1 to 5 followed during 4.3 ± 2.0 years. A linear mixed model explored the longitudinal bone loss and the relationship of associated factors with BMD changes. A total of 858 patients (mean age 58.9 ± 15.2 years) had at least 1 and 477 had at least 2 BMD measures.ResultsAt baseline, cross-sectional analysis showed a significantly lower BMD at femoral neck and total hip and a significant higher serum parathyroid hormone (PTH) along with CKD stages. Baseline age, gender, tobacco, low body mass index (BMI), and high PTH levels were significantly associated with low BMD. Longitudinal analysis during the mean 4.3 years revealed a significant bone loss at the radius only. BMD changes at the femoral neck were associated with BMI, but not CKD stages or basal PTH levels.ConclusionsCKD is associated with low BMD and high PTH in the cross-sectional analysis. Longitudinal bone loss occurred at the proximal radius after 4.3 years.

Boron Nano-hydroxyapatite Composite Increases the Bone Regeneration of Ovariectomized Rabbit Femurs.

Osteoporosis is a systemic metabolic disease defined by a decreased bone mineral density, microarchitectural deterioration, and an increased incidence of fragility fractures that may lead to morbidity and mortality. Boron may stimulate new bone formation and regeneration, when combined with nano-hydroxyapatite. We questioned whether injecting boron-containing nano-hydroxyapatite composites with hyaluronan increased the bone mineral density and new bone formation in osteoporotic rabbit femurs. The regenerative effects of injectable boron-containing nano-hydroxyapatite composites from 6 to 12 weeks, which may prevent osteoporotic femoral fractures, were assessed. Boron-containing (10 μg/ml) nano-hydroxyapatite composites were injected into the intramedullary femoral cavity with hyaluronan. These significantly increased the histomorphometric new bone surface to the total bone surface ratio at 6 and 9 weeks. The micro-tomographic bone volume to the total volume ratio and bone mineral density in osteoporotic rabbit femurs increased when compared to the hyaluronan (p = 0.004, p = 0.004, p = 0.004, p = 0.01, respectively) and the sham-control (p = 0.01, p = 0.004, p = 0.01, p = 0.037, respectively) groups. The boron-containing group had a higher bone mineralization and new bone formation compared to the nano-hydroxyapatite group, although the difference was not statistically significant. These findings reveal that intramedullary injection of boron-containing nano-hydroxyapatite with hyaluronan increases new bone formation and mineralization in ovariectomized rabbit femurs. Boron-containing nano-hydroxyapatite composites are promising tissue engineering biomaterials that may have regenerative potential in preventing primary and/or secondary femoral fractures in osteoporosis patients.

Fragility fracture identifies patients at imminent risk for subsequent fracture: real-world retrospective database study in Ontario, Canada

BackgroundThe secondary fracture prevention gap in the osteoporosis field has been previously described as a ‘crisis’. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1–2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures.MethodsThis retrospective observational study used de-identified health services data from the publicly funded healthcare system in Ontario, the largest province of Canada. Patients aged > 65 with an index fragility fracture occurring between 2011 and 2015 were identified from the ICES Data Repository using International Classification of Diseases (ICD)-10 codes. We examined median time to subsequent fragility fractures for osteoporotic fracture sites until the end of follow-up (2017). BMD assessment and use of osteoporosis therapies following index fracture were also characterized.ResultsAmong 115,776 patients with an index fragility fracture, 17.8% incurred a second fragility fracture. Median time between index and second fracture occurring at any site was 555 days (interquartile range: 236–955). For each index fracture site examined, median time from index to second fracture was < 2 years. The proportion of patients with BMD assessment was 10.3% ≤1 year prior to and 16.4% ≤1 year post index fracture. The proportion of patients receiving osteoporosis therapy was 29.8% ≤1 year prior, 34.6% ≤1 year post, and 25.9% > 3 years post index fracture.ConclusionsThis cohort of Canadian patients aged > 65 years who experienced a fragility fracture at any site are at imminent risk of experiencing subsequent fracture within the next 2 years and should be proactively assessed and treated.

Incremental costs of fragility fractures: a population-based matched -cohort study from Ontario, Canada

SummaryUsing a matched cohort design, the 1-year excess cost of incident fragility fractures at any site was $26,341 per patient, with 43% of total excess costs attributed to hospitalization. The high economic burden of fractures in Ontario underscores the urgency of closing the secondary fracture prevention gap.IntroductionThis retrospective real-world observational study was conducted to document the incremental costs associated with fragility fractures in Ontario, Canada.MethodsPatients aged >65 years with an index fragility fracture occurring between January 2011 and March 2015 were identified from administrative databases and matched 1:1 to a cohort of similar patients without a fracture. Healthcare resource utilization data were extracted from healthcare records and associated costs were calculated on a per-patient level and for the province of Ontario. Costs were presented as 2017 Canadian dollars.ResultsThe eligible cohort included 115,776 patients with a fragility fracture. Of these, 101,773 patients were successfully matched 1:1 to a non-fracture cohort. Overall, hip fractures (n = 31,613) were the most common, whereas femur fractures (n = 3002) were the least common type. Hospitalization and continuing care/home care/long-term care accounted for more than 60% of 1-year direct costs, whereas 5% was attributed to medication costs. First-year costs per patient in the fracture cohort were approximately threefold higher versus the non-fracture cohort (mean $37,362 versus $11,020, respectively). The incremental first-year direct healthcare costs of fragility fractures for the province of Ontario were calculated at $724 million per year.ConclusionsFragility fractures were associated with a threefold increase in overall mean healthcare costs per patient compared to patients without fractures. With an aging population, there is an urgent need for improved prevention strategies for patients at high-risk of fracture to decrease the economic burden of fragility fractures on the Canadian healthcare system.

Analysis of Risk Factors Affecting Incidence of Osteoporosis and Fragility Fractures in Liver Transplant Recipients

BackgroundFragility fractures caused by osteoporosis are common complications seen in recipients of organ transplantation who survive long term. Although many risk factors have been identified for osteoporosis after organ transplantation, none of them have been recognized as the main cause of development of the condition. Several studies have examined vitamin D receptor (VDR) gene single-nucleotide polymorphisms (SNPs) for their influence on bone mineral density (BMD) and fracture risk, but with variable results. We aimed to elucidate the risk factors that affect incidence of osteoporosis and fragility fractures in liver transplant recipients.Material/MethodsIn this study, we monitored incidence of fragility fracture and osteoporosis in 45 patients who had been evaluated with dual-energy X-ray absorptiometry (DXA) after liver transplantation. We also analyzed the association between VDR SNPs such as BsmI, ApaI, FokI, and TaqI with osteoporosis and fracture incidence in 27 patients in our cohort in whom SNPs were evaluated and DXA performed after liver transplantation.ResultsOsteoporosis was diagnosed in 17 of 45 patients in whom BMD was measured after liver transplantation. Of the patients with osteoporosis, 15 (88.2%) subsequently had fragility fractures. The incidence of postoperative osteoporosis was significantly higher in the recipients who had alcoholic liver cirrhosis as their primary disease. Interestingly, there were significantly more patients with a homozygous BsmI GG genotype in the group diagnosed with osteoporosis.ConclusionsOur study suggests that patients who undergo liver transplantation and have alcoholic liver cirrhosis or the BsmI GG genotype may be at increased risk for osteoporosis. Further research is necessary to confirm these findings.