Correction to: Comparison of the clinical effectiveness and safety between the use of denosumab vs bisphosphonates in renal transplant patients.

The original version of this article, published on 03 January 2020 contained a mistake. An author's name was misspelled.

Comparison of the clinical effectiveness and safety between the use of denosumab vs bisphosphonates in renal transplant patients.

A retrospective chart review was conducted on 85 renal transplant patients aged 19-88 years, treated with denosumab or bisphosphonate therapy. Bone densitometry measures were compared between treatment groups at baseline; at years 1, 2, and 3; and at final follow-up (average of 3.4 years). Both bisphosphonate and denosumab treatments increased lumbar spine bone density; however, the effect of denosumab was greater compared with that of bisphosphonate treatment. Denosumab treatment increased femoral neck BMD, whereas bisphosphonate treatment had a mean decrease in femoral neck BMD at final follow-up. Thus, our study provides evidence for the efficacy of denosumab treatment in renal transplant patients. Caution around hypocalcemia is warranted. We recommend more prospective studies to analyze the effects of long-term antiresorptive therapy in patients with a renal transplant. INTRODUCTION: To compare the clinical effectiveness and safety between the use of denosumab and bisphosphonates on bone density and incidence of adverse events in renal transplant patients. METHODS: A retrospective chart review was conducted on 85 renal transplant patients aged 19-88 years, treated with denosumab or bisphosphonate therapy. Bone densitometry measures were compared between treatment groups at baseline; years 1, 2, and 3; and at final follow-up (average of 3.4 years). RESULTS: Absolute change in lumbar spine and femoral neck BMD over the treatment period was 0.029 ± 0.075 g/cm2 and - 0.003 ± 0.064 g/cm2, respectively, in the bisphosphonate group. Absolute change in lumbar spine and femoral neck BMD at final follow-up was 0.072 ± 0.094 g/cm2 and 0.025 ± 0.063 g/cm2, respectively, in the denosumab group. Denosumab resulted in significantly greater increases in lumbar spine BMD (0.045 g/cm2 greater in the denosumab group). Similarly, the absolute change in BMD at the femoral neck was 0.022 g/cm2 greater in the denosumab group as compared with the bisphosphonate group. The denosumab group had one event of severe hypocalcemia following first injection and one report of hospitalized pneumonia. No serious adverse events were reported in the bisphosphonate group. CONCLUSIONS: Both treatments increased lumbar spine BMD; however, the effect of denosumab was greater compared with that of bisphosphonate treatment. Our study provides evidence for the efficacy of denosumab treatment in renal transplant patients. Caution around hypocalcemia is warranted. We recommend more prospective studies to analyze the effects of long-term antiresorptive therapy in patients with a renal transplant.

Testing a theoretical model of imminent fracture risk in elderly women: an observational cohort analysis of the Canadian Multicentre Osteoporosis Study.

We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health. INTRODUCTION: This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk. METHODS: Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI). RESULTS: The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ2(172) = 1122.10 < .001, RMSEA = .03, TLI = .99, CFI = .99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p < .001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p < .001). CONCLUSIONS: We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds.

An international study to revise the EORTC questionnaire for assessing quality of life in lung cancer patients.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 was the first module to be used in conjunction with the core questionnaire, the QLQ-C30. Since the publication of the LC13 in 1994, major advances have occurred in the treatment of lung cancer. Given this, an update of the EORTC QLQ-LC13 was undertaken. METHODS: The study followed phases I to III of the EORTC Module Development Guidelines. Phase I generated relevant quality-of-life issues using a mix of sources including the involvement of 108 lung cancer patients. Phase II transformed issues into questionnaire items. In an international multicenter study (phase III), patients completed both the EORTC QLQ-C30 and the 48-item provisional lung cancer module generated in phases I and II. Patients rated each of the items regarding relevance, comprehensibility, and acceptance. Patient ratings were assessed against a set of prespecified statistical criteria. Descriptive statistics and basic psychometric analyses were carried out. RESULTS: The phase III study enrolled 200 patients with histologically confirmed lung cancer from 12 centers in nine countries (Cyprus, Germany, Italy, Israel, Spain, Norway, Poland, Taiwan, and the UK). Mean age was 64 years (39 - 91), 59% of the patients were male, 82% had non-small-cell lung cancer, and 56% were treated with palliative intent. Twenty-nine of the 48 questions met the criteria for inclusion. CONCLUSIONS: The resulting module with 29 questions, thus currently named EORTC QLQ-LC29, retained 12 of the 13 original items, supplemented with 17 items that primarily assess treatment side-effects of traditional and newer therapies.

BRCA1 and BRCA2 mutation testing in Cyprus; a population based study.

This paper presents the largest study in Cyprus evaluating the frequency and distribution of BRCA1/2 mutations in a high risk patient cohort. Deleterious mutations in the BRCA1/2 genes were identified in 68 of the 527 patients tested (13%). It is of interest that a quarter of those tested positive, did not have an extensive family history of breast/ovarian cancer but were diagnosed with early onset breast cancer, ovarian cancer under the age of 60 or triple negative breast cancer. The spectrum of mutations identified in our patient cohort is different compared to other Mediterranean countries. Furthermore, several of the mutations detected are novel and have not been identified in other ethnic populations. This highlights the importance of operating a national reference center for cancer genetic diagnosis which offers services tailored to the needs of the Cypriot population.

Measuring frailty in clinical practice: a comparison of physical frailty assessment methods in a geriatric out-patient clinic.

BACKGROUND: The objectives of this study were to determine: 1) the prevalence of frailty using Fried's phenotype method and the Short Performance Physical Battery (SPPB), 2) agreement between frailty assessment methods, 3) the feasibility of assessing frailty using Fried's phenotype method and the SPPB. METHODS: This cross-sectional study was conducted at a geriatric out-patient clinic in Hamilton, Canada. A research assistant conducted all frailty assessments. Patients were classified as non-frail, pre-frail or frail according to Fried's phenotype method and the SPPB. Agreement among methods is reported using the Cohen kappa statistic (standard error). Feasibility data included the percent of eligible participants agreeing to attempt the frailty assessments (criterion for feasibility: ≥90% of patients agreeing to the frailty assessment), equipment required, and safety considerations. A p-value of <0.05 is considered significant. RESULTS: A total of 110 participants (92%) and 109 participants (91%) agreed to attempt Fried's phenotype method and SPPB, respectively. No adverse events occurred during any assessments. According to Fried's phenotype method, the prevalence of frailty and pre-frailty was 35% and 56%, respectively, and according to the SPPB, the prevalence of frailty and pre-frailty was 50% and 35%, respectively. There was fair to moderate agreement between methods for determining which participants were frail (0.488 [0.082], p < 0.001) and pre-frail (0.272 [0.084], p = 0.002). CONCLUSIONS: Frailty and pre-frailty are common in this geriatric outpatient population, and there is fair to moderate agreement between Fried's phenotype method and the SPPB. Over 90% of the patients who were eligible for the study agreed to attempt the frailty assessments, demonstrating that according to our feasibility criteria, frailty can be assessed in this patient population. Assessing frailty may help clinicians identify high-risk patients and tailor interventions based on baseline frailty characteristics.

Comparative trends in incident fracture rates for all long-term care and community-dwelling seniors in Ontario, Canada, 2002-2012.

SUMMARY: In this population-based study, we compared incident fracture rates in long-term care (LTC) versus community seniors between 2002 and 2012. Hip fracture rates declined more rapidly in LTC than in the community. An excess burden of fractures occurred in LTC for hip, pelvis, and humerus fractures in men and hip fractures only in women. INTRODUCTION: This study compares trends in incident fracture rates between long-term care (LTC) and community-dwelling seniors ≥65 years, 2002-2012. METHODS: This is a population-based cohort study using administrative data. Measurements were age/sex-adjusted incident fracture rates and rate ratios (RR) and annual percent change (APC). RESULTS: Over 11 years, hip fracture rates had a marked decline occurring more rapidly in LTC (APC, -3.49 (95% confidence interval (CI), -3.97, -3.01)) compared with the community (APC, -2.93 (95% CI, -3.28, -2.57); p < 0.05 for difference in slopes). Humerus and wrist fracture rates decreased; however, an opposite trend occurred for pelvis and spine fractures with rates increasing over time in both cohorts (all APCs, p < 0.05). In 2012, incident hip fracture rates were higher in LTC than the community (RRs: women, 1.55 (95% CI, 1.45, 1.67); men, 2.18 (95% CI, 1.93, 2.47)). Higher rates of pelvis (RR, 1.48 (95% CI, 1.22, 1.80)) and humerus (RR, 1.40 (95% CI, 1.07, 1.84)) fractures were observed in LTC men, not women. In women, wrist (RR, 0.76 (95% CI, 0.71, 0.81)) and spine (RR, 0.52 (95% CI, 0.45, 0.61)) fracture rates were lower in LTC than the community; in men, spine (RR, 0.75 (95% CI, 0.57, 0.98) but not wrist fracture (RR, 0.91 (95% CI, 0.67, 1.23)) rates were significantly lower in LTC than the community. CONCLUSION: Previous studies in the community have shown declining hip fracture rates over time, also demonstrated in our study but at a more rapid rate in LTC. Rates of humerus and wrist fractures also declined. An excess burden of fractures in LTC occurred for hip fractures in women and for hip, pelvis, and humerus fractures in men.

PKM2 as a biomarker for chemosensitivity to front-line platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer.

BACKGROUND: Tumour cells exclusively express the embryonic M2 isoform of pyruvate kinase (PKM2). PKM2 expression levels have been correlated with the effect of platinum compounds in cancer cell lines and xenograft models. The potential predictive role of PKM2 in patients with metastatic/advanced non-small-cell lung cancer (NSCLC) receiving platinum-based chemotherapy as first-line was investigated. METHODS: Quantitative real-time PCR was used to assess the expression of PKM2 in tumour samples from 148 and 157 NSCLC patients in the training and the validation set, respectively. All patients received front-line platinum-based chemotherapy. PKM2 mRNA expression was also analysed in a control group of 85 NSCLC patients treated with non-platinum containing regimens. RESULTS: In the training set, high PKM2 mRNA levels were associated with decreased progression-free survival (PFS; 4.9 months vs 6.4, P=0.006), overall survival (OS; 10.1 vs 17.0 months, P=0.01) and disease control rate (DCR; 57.7% vs 74.3%; P=0.021) compared to patients with low PKM2 levels. In the validation set, high PKM2 mRNA levels were also associated with deceased PFS (3.7 vs 5.9 months, P=0.006), OS (8.3 vs 16.8 months, P=0.003) and DCR (57.7% vs 70.9%; P=0.049) compared to those with low PKM2 mRNA levels. There was no correlation between the PKM2 mRNA levels and the PFS (5.6 vs 5.9, P=0.43) or the OS (9.8 vs 10.1, P=0.51) in the control group. Multivariate analysis revealed high PKM2 mRNA expression as an independent predictive factor for the poor patients' outcome. CONCLUSIONS: PKM2 expression may be a predictive biomarker of platinum sensitivity in advanced NSCLC patients treated with platinum-based chemotherapy.

A Frailty Index predicts 10-year fracture risk in adults age 25 years and older: results from the Canadian Multicentre Osteoporosis Study (CaMos).

UNLABELLED: We created a 30-item Frailty Index in the Canadian Multicentre Osteoporosis Study. A Frailty Index is a sensitive measure that can quantify fracture risk according to degree of frailty. Our results indicated that at any age, frailty was an important independent risk factor for fracture over 10 years. INTRODUCTION: In later life, frailty has been linked to fractures. It is likely that the antecedents of fracture are seen across the life course, in ways not entirely captured by traditional osteoporosis risk factors. Using data collected from the prospective, population-based Canadian Multicentre Osteoporosis Study (CaMos), we created the 30-item CaMos Frailty Index and examined whether it was associated with incident fractures over 10 years. METHODS: All CaMos participants aged 25 years and older (n = 9,423) were included in the analysis. To examine the relationship between baseline Frailty Index scores and incident fractures, a competing risk proportional sub-distribution hazards model was used with death considered a competing risk. Analyses were adjusted for age, sex, body mass index, education level, femoral neck T-score, and antiresorptive therapy. RESULTS: At baseline, the mean age was 62.1 years [standard deviation (SD) 13.4], and 69.4 % were women. The mean Frailty Index score was 0.13 (SD 0.11), ranging from 0 to 0.66. For every 0.10 increase in Frailty Index scores (approximately one SD), the hazard ratio was 1.25 (p < 0.001) for all fractures, 1.18 (p = 0.043) for hip fractures, and 1.30 (p ≤ 0.001) for clinical vertebral fractures. CONCLUSION: The CaMos Frailty Index quantified fracture risk according to degree of frailty. Irrespective of age and bone mineral density, the Frailty Index was associated with hip, vertebral, and all-type clinical fractures. Predicting late onset illnesses may have to consider overall health status and not just traditional risk factors.

Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS).

UNLABELLED: We used data from a large, prospective Canadian cohort to assess the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased risk of fractures in individuals who used SSRI or SNRI, even after controlling for multiple risk factors. INTRODUCTION: Previous studies have suggested an association between SSRIs and increasing risk of fragility fractures. However, the majority of these studies were not long-term analyses or were performed using administrative data and, thus, could not fully control for potential confounders. We sought to determine whether the use of SSRIs and SNRIs is associated with increased risk of fragility fracture, in adults aged 50 + . METHODS: We used data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly selected population-based community cohort; our analyses focused on subjects aged 50+. Time to event methodology was used to assess the association between SSRI/SNRI use, modeled time-dependently, and fragility fracture. RESULTS: Among 6,645 subjects, 192 (2.9%) were using SSRIs or/and SNRIs at baseline. During the 10-year study period, 978 (14.7%) participants experienced at least one fragility fracture. In our main analysis, SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95% confidence intervals (CI), 1.48-2.39). After controlling for multiple risk factors, including Charlson score, previous falls, and bone mineral density hip and lumbar bone density, the adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95% CI, 1.32-2.14). CONCLUSIONS: Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.

Anti-cyclic citrullinated peptide antibody as a marker of erosive arthritis in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVE: Anti-cyclic citrullinated peptide (CCP) antibody is an established marker in the diagnosis and prognostication of rheumatoid arthritis (RA). Infrequently, systemic lupus erythematosus (SLE) patients also develop a deforming erosive arthritis, similar to that of RA. Our objective was to determine whether anti-CCP antibody is a useful marker of erosive disease in SLE patients presenting with arthritis. METHODS: Electronic databases EMBASE, MEDLINE and non-indexed MEDLINE citations were searched through April 11, 2014, using the outlined key terms. Studies meeting predefined inclusion and exclusion criteria were reviewed. Two reviewers independently assessed the quality of included articles using previously described criteria. The DerSimonian-Laird random effects model was used to calculate pooled sensitivity and specificity of anti-CCP antibody for erosive arthritis in SLE. RESULTS: Seven articles met inclusion and exclusion criteria. A total of 609 SLE patients with arthritis were identified, 70 of whom had erosive disease. Pooled sensitivity and specificity of anti-CCP antibody for erosive arthritis was 47.8% (95% CI, 26.2%-70.2%) and 91.8% (95% CI, 78.4%-97.2%), respectively. CONCLUSION: Our findings suggest that anti-CCP antibody is a highly specific marker for erosive arthritis in SLE. Longitudinal prospective studies are needed to determine if anti-CCP antibody can be used as a predictor of erosive disease.

Non-hip, non-spine fractures drive healthcare utilization following a fracture: the Global Longitudinal Study of Osteoporosis in Women (GLOW).

UNLABELLED: We evaluated healthcare utilization associated with treating fracture types in >51,000 women aged ≥55 years. Over the course of 1 year, there were five times more non-hip, non-spine fractures than hip or spine fractures, resulting in twice as many days of hospitalization and rehabilitation/nursing home care for non-hip, non-spine fractures. INTRODUCTION: The purpose of this study is to evaluate medical healthcare utilization associated with treating several types of fractures in women ≥55 years from various geographic regions. METHODS: Information from the Global Longitudinal Study of Osteoporosis in Women (GLOW) was collected via self-administered patient questionnaires at baseline and year 1 (n = 51,491). Self-reported clinically recognized low-trauma fractures at year 1 were classified as incident spine, hip, wrist/hand, arm/shoulder, pelvis, rib, leg, and other fractures. Healthcare utilization data were self-reported and included whether the fracture was treated at a doctor's office/clinic or at a hospital. Patients were asked if they had undergone surgery or been treated at a rehabilitation center or nursing home. RESULTS: During 1-year follow-up, there were 195 spine, 134 hip, and 1,654 non-hip, non-spine fractures. Clinical vertebral fractures resulted in 617 days of hospitalization and 512 days of rehabilitation/nursing home care; hip fractures accounted for 1,306 days of hospitalization and 1,650 days of rehabilitation/nursing home care. Non-hip, non-spine fractures resulted in 3,805 days in hospital and 5,186 days of rehabilitation/nursing home care. CONCLUSIONS: While hip and vertebral fractures are well recognized for their associated increase in health resource utilization, non-hip, non-spine fractures, by virtue of their 5-fold greater number, require significantly more healthcare resources.

Ankle fractures do not predict osteoporotic fractures in women with or without diabetes.

UNLABELLED: It is not clear whether ankle fractures predict future osteoporotic fractures in women, and whether diabetes influences this relationship. We found that a prior ankle fracture does not predict subsequent osteoporotic fractures in women with or without diabetes. INTRODUCTION: We aimed to determine: (1) whether a prior ankle fracture was a risk factor for a subsequent major osteoporotic fracture in older women; (2) whether this risk was modified by the presence of diabetes; (3) the risk factors for ankle fracture in older women. METHODS: We identified 3,054 women age 50 years and older with diabetes and 9,151 matched controls using the Manitoba Bone Density Program database. Multivariable regression models were used to examine factors associated with prior ankle fracture, and the importance of prior ankle fracture as a predictor of subsequent major osteoporotic fracture during a mean 4.8 years of observation. RESULTS: A prior ankle fracture was not a significant predictor of subsequent major osteoporotic fracture for women with diabetes (hazard ratio [HR] 1.13; 95% confidence interval [CI], 0.68-1.83; p = 0.623) or women without diabetes (HR 1.16; 95% CI, 0.79-1.71; p = 0.460), and there was no interaction between diabetes and ankle fracture after pooling all women in the cohort (p = 0.971). The presence of diabetes was not independently associated with prior ankle fracture (adjusted odds ratio [OR] 1.14 [95% CI, 0.93-1.38], p = 0.200), whereas higher body mass index (adjusted OR 1.04 per standard deviation increase [95% CI, 1.03-1.06], p < 0.001), previous major osteoporotic fracture (adjusted OR 1.40 [95% CI, 1.13-1.75], p = 0.002), and multiple comorbidities (>6 ambulatory diagnostic groups) (adjusted OR 1.81 [95% CI, 1.40-2.36], p < 0.001) were related to prior ankle fracture. CONCLUSIONS: Ankle fracture was not a significant predictor of major osteoporotic fracture in women, and a diagnosis of diabetes did not influence the relationship.

Fragility fractures and the osteoporosis care gap in women: the Canadian Multicentre Osteoporosis Study.

UNLABELLED: Canadian women over 50 years old were studied over a 10-year period to see if those who sustained a fracture (caused by minimal trauma) were receiving the recommended osteoporosis therapy. We found that approximately half of these women were not being treated, indicating a significant care gap in osteoporosis treatment. INTRODUCTION: Prevalent fragility fracture strongly predicts future fracture. Previous studies have indicated that women with fragility fractures are not receiving the indicated treatment. We aimed to describe post fracture care in Canadian women using a large, population-based prospective cohort that began in 1995-1997. METHODS: We followed 5,566 women over 50 years of age from across Canada over a period of 10 years in the Canadian Multicentre Osteoporosis Study. Information on medication use and incident clinical fragility fractures was obtained during a yearly questionnaire or interview and fractures were confirmed by radiographic/medical reports. RESULTS: Over the 10-year study period, 42-56% of women with yearly incident clinical fragility fractures were not treated with an osteoporosis medication. During year 1 of the study, 22% of the women who had experienced a fragility fracture were on treatment with a bisphosphonate and 26% were on hormone therapy (HT). We were not able to differentiate HT use for menopause symptoms vs osteoporosis. Use of bisphosphonate therapy increased over time; odds ratio (OR) for use at year 10 compared to use at year 1 was 3.65 (95% confidence interval (CI) 1.83-7.26). In contrast, HT use declined, with an OR of 0.07 (95%CI 0.02-0.24) at year 10 compared to year 1 of the study. CONCLUSION: In a large population-based cohort study, we found a therapeutic care gap in women with osteoporosis and fragility fractures. Although bisphosphonate therapy usage improved over time, a substantial gap remains.

Construction and validation of a simplified fracture risk assessment tool for Canadian women and men: results from the CaMos and Manitoba cohorts.

UNLABELLED: A procedure for creating a simplified version of fracture risk assessment tool (FRAX®) is described. Calibration, fracture prediction, and concordance were compared with the full FRAX tool using two large, complementary Canadian datasets. INTRODUCTION: The Canadian Association of Radiologists and Osteoporosis Canada (CAROC) system for fracture risk assessment is based upon sex, age, bone mineral density (BMD), prior fragility fracture, and glucocorticoid use. CAROC does not require computer or web access, and categorizes 10-year major osteoporotic fracture risk as low (<10%), moderate (10-20%), or high (>20%). METHODS: Basal CAROC fracture risk tables (by age, sex, and femoral neck BMD) were constructed from Canadian FRAX probabilities for major osteoporotic fractures (adjusted for prevalent clinical risk factors). We assessed categorization and fracture prediction with the updated CAROC system in the CaMos and Manitoba BMD cohorts. RESULTS: The new CAROC system demonstrated high concordance with the Canadian FRAX tool for risk category in both the CaMos and Manitoba cohorts (89% and 88%). Ten-year fracture outcomes in CaMos and Manitoba BMD cohorts showed good discrimination and calibration for both CAROC (6.1-6.5% in low-risk, 13.5-14.6% in moderate-risk, and 22.3-29.1% in high-risk individuals) and FRAX (6.1-6.6% in low-risk, 14.4-16.1% in moderate-risk, and 23.4-31.0% in high-risk individuals). Reclassification from the CAROC risk category to a different risk category under FRAX occurred in <5% for low-risk, 20-24% for moderate-risk, and 27-30% for high-risk individuals. Reclassified individuals had 10-year fracture outcomes that were still within or close to the original nominal-risk range.. CONCLUSION: The new CAROC system is well calibrated to the Canadian population and shows a high degree of concordance with the Canadian FRAX tool. The CAROC system provides s a simple alternative when it is not feasible to use the full Canadian FRAX tool.

Fracture prediction and calibration of a Canadian FRAX® tool: a population-based report from CaMos.

UNLABELLED: A new Canadian WHO fracture risk assessment (FRAX®) tool to predict 10-year fracture probability was compared with observed 10-year fracture outcomes in a large Canadian population-based study (CaMos). The Canadian FRAX tool showed good calibration and discrimination for both hip and major osteoporotic fractures. INTRODUCTION: The purpose of this study was to validate a new Canadian WHO fracture risk assessment (FRAX®) tool in a prospective, population-based cohort, the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: A FRAX tool calibrated to the Canadian population was developed by the WHO Collaborating Centre for Metabolic Bone Diseases using national hip fracture and mortality data. Ten-year FRAX probabilities with and without bone mineral density (BMD) were derived for CaMos women (N = 4,778) and men (N = 1,919) and compared with observed fracture outcomes to 10 years (Kaplan-Meier method). Cox proportional hazard models were used to investigate the contribution of individual FRAX variables. RESULTS: Mean overall 10-year FRAX probability with BMD for major osteoporotic fractures was not significantly different from the observed value in men [predicted 5.4% vs. observed 6.4% (95%CI 5.2-7.5%)] and only slightly lower in women [predicted 10.8% vs. observed 12.0% (95%CI 11.0-12.9%)]. FRAX was well calibrated for hip fracture assessment in women [predicted 2.7% vs. observed 2.7% (95%CI 2.2-3.2%)] but underestimated risk in men [predicted 1.3% vs. observed 2.4% (95%CI 1.7-3.1%)]. FRAX with BMD showed better fracture discrimination than FRAX without BMD or BMD alone. Age, body mass index, prior fragility fracture and femoral neck BMD were significant independent predictors of major osteoporotic fractures; sex, age, prior fragility fracture and femoral neck BMD were significant independent predictors of hip fractures. CONCLUSION: The Canadian FRAX tool provides predictions consistent with observed fracture rates in Canadian women and men, thereby providing a valuable tool for Canadian clinicians assessing patients at risk of fracture.

Reproducibility of computer-assisted joint alignment measurement in OA knee radiographs.

OBJECTIVES: (1) To investigate the reproducibility of computer-assisted measurements of knee alignment angle (KA) from digitized radiographs of osteoarthritis (OA) participants requiring total knee arthroplasty (TKA) and (2) to determine whether landmark choice affects the precision of KA measurements on radiographs. METHODS: Using a custom algorithm, femoral, central, and tibial measurement-guiding rules were interactively placed on digitized posteroanterior fixed-flexion knee radiographs by mouse control and positioned according to different anatomic landmarks. The angle subtended by lines connecting these guiding rules was measured by three readers to assess interobserver, intraobserver and experience-inexperience reproducibility. Test-retest reproducibility was evaluated with duplicate radiographs from a healthy cohort. Reproducibility was assessed using root-mean square coefficients of variation (RMSCV%). The Bland-Altman method was performed on data obtained from varying anatomic landmarks (confidence interval, CI= 95%). RESULTS: From 16 healthy and 30 TKA participants, reproducibility analyses revealed a high degree of intraobserver (n=38, RMSCV=0.56%), interobserver (n=38, RMSCV=0.72%), test-retest (n=16, RMSCV=0.87%) and experience-inexperience (n=38, RMSCV=0.73%) reproducibility with variances below 1%. Varying the orientation of tibial and femoral rules according to anatomic landmarks produced a difference that exceeded an a priori limit of agreement of -1.11 degrees to +1.67 degrees. CONCLUSION: Our custom-designed software provides a robust method for measuring KAs within digitized knee radiographs. Although test-retest analyses were only performed in a healthy cohort, we anticipate a similar degree of reproducibility in an OA sample. A standardized set of anatomic landmarks employed for KA measurement is recommended since arbitrary selection of landmarks resulted in imprecise KA measurement even with a computer-assisted technique.

Quantitative analysis of subchondral sclerosis of the tibia by bone texture parameters in knee radiographs: site-specific relationships with joint space width.

OBJECTIVES: To determine the ability of radiographic bone texture (BTX) parameters to quantify subchondral tibia sclerosis and to examine clinical relevance for assessing osteoarthritis (OA) progression. We examined the relationship between BTX parameters and each of (1) location-specific joint space width (JSW) [JSW(x)] and minimum JSW (mJSW) of the affected compartment, and (2) knee alignment (KA) angle in knee radiographs of participants undergoing total knee arthroplasty (TKA). DESIGN: Digitized fixed-flexion knee radiographs were analyzed for run-length and topological BTX parameters in a subchondral region using an algorithm. Medial JSW(x) was computed at x=0.200, 0.225, 0.250 and 0.275 according to a coordinate system defined by anatomic landmarks. mJSW was determined for medial and lateral compartment lesions. KA angles were determined from radiographs using an anatomic landmark-guided algorithm. JSW measures and the magnitude of knee malalignment were each correlated with BTX parameters. Reproducibility of BTX parameters was measured by root-mean square coefficients of variation (RMSCV%). RESULTS: Run-length BTX parameters were highly reproducible (RMSCV%<1%) while topological parameters showed poorer reproducibility (>5%). In TKA participants (17 women, 13 men; age: 66+/-9 years; body mass index (BMI): 31+/-6 kg m(-2); WOMAC: 41.5+/-16.1; Kellgren-Lawrence score mode: 4), reduced trabecular spacing (Tb.Sp) and increased free ends (FE) were correlated with decreased JSW after accounting for BMI, gender and knee malalignment. These relationships were dependent on site of JSW measurement. CONCLUSION: High reproducibility in quantifying bone sclerosis using Tb.Sp and its significant relationship with JSW demonstrated potential for assessing OA progression. Increased trabecular FE and reduced porosity observed with smaller JSW suggest collapsing subchondral bone or trabecular plate perforation in advanced knee OA.

Treating osteoporosis in Canada: what clinical efficacy data should be considered by policy decision makers?

UNLABELLED: SAUMMARY: Using a Markov state-transition model, we estimated fractures averted with risedronate using two different types of clinical efficacy data. Summary data, as opposed to individual patient data (IPD), underestimated the number of fractures averted when applied in a specified high risk population. The choice of clinical efficacy data is an important consideration in health economic models evaluating osteoporosis therapies. INTRODUCTION: This paper contrasts fracture reduction estimates for risedronate utilizing efficacy data from two approaches to meta-analysis: summary data versus individual patient data. We also examined differences in fracture reduction explained by varied cohort selection, especially the inclusion of low- versus high-risk populations. METHODS: Using a Markov state-transition model, we compared fractures averted over 3 years in a hypothetical cohort by inputting fracture risk reduction estimates (risedronate versus placebo) from two data sources (summary data versus IPD). The cohort consisted of 100,000 Canadian women, age > or =65 years with osteoporosis (WHO criteria T-score < or = -2.5) and prevalent morphometric vertebral fracture. RESULTS: Non-vertebral fractures averted with risedronate were: 3,571 and 6,584 per 100,000 women for summary data and IPD, respectively. For vertebral fractures, the numbers were 8,552 and 10,127. When IPD versus summary data was used, an additional 3,013 more non-vertebral fractures and 1,575 vertebral fractures were averted. DISCUSSION: Relative risk estimates from IPD analyses were the best choice for modelling fracture outcomes when applied in a specified high-risk population. In addition to superior statistical methodology, they utilized RCT cohorts that are more representative of higher risk patients requiring treatment (osteoporotic women > or =65 years with a prevalent vertebral fracture).

The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study.

UNLABELLED: Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time. INTRODUCTION: This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI. METHODS: The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses. RESULTS: Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores. CONCLUSION: The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies.