Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update.

BACKGROUND: In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older. METHODS: This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework. RECOMMENDATIONS: The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized. INTERPRETATION: The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.

Co-administration of viscous fiber, Salba-chia and ginseng on glycemic management in type 2 diabetes: a double-blind randomized controlled trial.

PURPOSE: Viscous dietary fiber, functional seeds and ginseng roots have individually been proposed for the management of diabetes. We explored whether their co-administration would improve glycemic control in type 2 diabetes beyond conventional therapy. METHODS: In a randomized, double-blind, controlled trial conducted at two academic centers (Toronto, Canada and Zagreb, Croatia), individuals with type 2 diabetes were assigned to either an active intervention (10 g viscous fiber, 60 g white chia seeds, 1.5 g American and 0.75 g Korean red ginseng extracts), or energy and fiber-matched control (53 g oat bran, 25 g inulin, 25 g maltodextrose and 2.25 g wheat bran) intervention for 24 weeks, while on conventional standard of care. The prespecified primary endpoint was end difference at week 24 in HbA1c, following an intent-to-treat analysis adjusted for center and baseline. RESULTS: Between January 2016 and April 2018, 104 participants (60M:44F; mean ± SEM age 59 ± 0.8 years; BMI 29.0 ± 0.4 kg/m2; HbA1c 7.0 ± 0.6%) managed with antihyperglycemic agent(s) (n = 98) or lifestyle (n = 6), were randomized (n = 52 test; n = 52 control). At week 24, HbA1c levels were 0.27 ± 0.1% lower on test compared to control (p = 0.03). There was a tendency towards an interaction by baseline HbA1c (p = 0.07), in which a greater reduction was seen in participants with baseline HbA1c > 7% vs ≤ 7% (- 0.56 ± 0.2% vs 0.03 ± 0.2%). Diet and body weight remained unchanged. The interventions were well tolerated with no related adverse events and with high retention rate of 84%. CONCLUSIONS: Co-administration of selected dietary and herbal therapies was well-tolerated and may provide greater glycemic control as add-on therapy in type 2 diabetes. Registration: Clinicaltrials.gov NCT02553382 (registered on September 17, 2015).

Vertebral Fractures: Which Radiological Criteria Are Better Associated With the Clinical Course of Osteoporosis?

STUDY PURPOSE: Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. MATERIALS AND METHODS: We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. RESULTS: At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. CONCLUSIONS: This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.

Correction to: Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

In contrast to statements made in the above paper, measurements of waist and hip circumference were in fact available.

Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

AIMS/HYPOTHESIS: In line with current advice, we assessed the effect of replacing carbohydrate consumption with mixed nut consumption, as a source of unsaturated fat, on cardiovascular risk factors and HbA1c in type 2 diabetes. The data presented here are from a paper that was retracted at the authors' request ( https://doi.org/10.2337/dc16-rt02 ) owing to lack of adjustment for repeated measures in the same individual. Our aim, therefore, was to fix the error and add new complementary data of interest, including information on clotting factors and LDL particle size. METHODS: A total of 117 men and postmenopausal women with type 2 diabetes who were taking oral glucose-lowering agents and with HbA1c between 47.5 and 63.9 mmol/mol (6.5-8.0%) were randomised after stratification by sex and baseline HbA1c in a parallel design to one of three diets for 3 months: (1) 'full-dose nut diet' (n = 40): a diet with 2.0 MJ (477 kcal) per 8.4 MJ (2000 kcal) energy provided as mixed nuts (75 g/day); (2) 'full-dose muffin diet' (n = 39): a diet with 1.97 MJ (471 kcal) per 8.4 MJ (2000 kcal) energy provided as three whole-wheat muffins (188 g/day), with a similar protein content to the nuts, and the same carbohydrate-derived energy content as the monounsaturated fatty acid-derived energy content in the nuts; or (3) 'half-dose nut diet' (n = 38): a diet with 1.98 MJ (474 kcal) per 8.4 MJ (2000 kcal) energy provided as half portions of both the nuts and muffins. The primary outcome was change in HbA1c. The study was carried out in a hospital clinical research centre and concluded in 2008. Only the statistician, study physicians and analytical technicians could be blinded to the group assessment. RESULTS: A total of 108 participants had post-intervention data available for analysis (full-dose nut group, n = 40; full-dose muffin group, n = 35; half-dose nut group, n = 33). Compared with the full-dose muffin diet, the full-dose nut diet provided 9.2% (95% CI 7.1, 11.3) greater total energy intake from monounsaturated fat. The full-dose nut diet (median intake, 75 g/day) also reduced HbA1c compared with the full-dose muffin diet by -2.0 mmol/mol (95% CI -3.8, -0.3 mmol/mol) (-0.19% [95% CI -0.35%, -0.02%]), (p = 0.026). Estimated cholesterol levels in LDL particles with a diameter <255 ångström [LDL-c<255Å]) and apolipoprotein B were also significantly decreased after the full-dose nut diet compared with the full-dose muffin diet. According to the dose response, the full-dose nut diet is predicted to reduce HbA1c (-2.0 mmol/mol [-0.18%]; p = 0.044), cholesterol (-0.25 mmol/l; p = 0.022), LDL-cholesterol (-0.23 mmol/l; p = 0.019), non-HDL-cholesterol (-0.26 mmol/l; p = 0.020), apolipoprotein B (-0.06 g/l, p = 0.013) and LDL-c<255Å (-0.42 mmol/l; p < 0.001). No serious study-related adverse events occurred, but one participant on the half-dose nut diet was hospitalised for atrial fibrillation after shovelling snow. CONCLUSIONS/INTERPRETATION: Nut intake as a replacement for carbohydrate consumption improves glycaemic control and lipid risk factors in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00410722 FUNDING: The study was funded by the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Loblaw Companies and the Canada Research Chairs Program of the Government of Canada.

Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus: International Insights From the TECOS Trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin).

BACKGROUND: Intensive risk factor modification significantly improves outcomes for patients with diabetes mellitus and cardiovascular disease. However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown. METHODS: Attainment of 5 secondary prevention parameters-aspirin use, lipid control (low-density lipoprotein cholesterol <70 mg/dL or statin therapy), blood pressure control (<140 mm Hg systolic, <90 mm Hg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and nonsmoking status-was evaluated among 13 616 patients from 38 countries with diabetes mellitus and known cardiovascular disease at entry into TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Logistic regression was used to evaluate the association between individual and regional factors and secondary prevention achievement at baseline. Cox proportional hazards regression analysis was used to determine the association between baseline secondary prevention achievement and cardiovascular death, myocardial infarction, or stroke. RESULTS: Overall, 29.9% of patients with diabetes mellitus and cardiovascular disease achieved all 5 secondary prevention parameters at baseline, although 71.8% achieved at least 4 parameters. North America had the highest proportion (41.2%), whereas Western Europe, Eastern Europe, and Latin America had proportions of ≈25%. Individually, blood pressure control (57.9%) had the lowest overall attainment, whereas nonsmoking status had the highest (89%). Over a median 3.0 years of follow-up, a higher baseline secondary prevention score was associated with improved outcomes in a step-wise graded relationship (adjusted hazard ratio, 0.60; 95% confidence interval, 0.47-0.77 for those patients achieving all 5 measures versus those achieving ≤2). CONCLUSIONS: In an international trial population, significant opportunities exist to improve the quality of cardiovascular secondary prevention care among patients with diabetes mellitus and cardiovascular disease, which in turn could lead to reduced risk of downstream cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205.

Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes.

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). There were no significant between-group differences in rates of acute pancreatitis (P=0.07) or pancreatic cancer (P=0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events. (Funded by Merck Sharp & Dohme; TECOS ClinicalTrials.gov number, NCT00790205.).

Actualisation 2023 des lignes directrices de pratique clinique pour la prise en charge de l'ostéoporose et la prévention des fractures au Canada.

CONTEXTE: Au Canada, plus de 2 millions de personnes vivent avec l'ostéoporose, une maladie qui accroît le risque de fracture, ce qui fait augmenter la morbidité et la mortalité, et entraîne une perte de qualité de vie et d'autonomie. La présente actualisation des lignes directrices vise à accompagner les professionnelles et professionnels de la santé au Canada dans la prestation de soins visant à optimiser la santé osseuse et à prévenir les fractures chez les femmes ménopausées et les hommes de 50 ans et plus. MÉTHODES: Le présent document fournit une actualisation des lignes directrices de pratique clinique de 2010 d'Ostéoporose Canada sur le diagnostic et la prise en charge de l'ostéoporose au pays. Nous avons utilisé l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) et effectué l'assurance de la qualité conformément aux normes de qualité et de présentation des rapports de la grille AGREE II (Appraisal of Guidelines for Research & Evaluation). Les médecins de premier recours et les patientes et patients partenaires ont été représentés à tous les niveaux des comités et des groupes ayant participé à l'élaboration des lignes directrices, et ont participé à toutes les étapes du processus pour garantir la pertinence des informations pour les futurs utilisateurs et utilisatrices. Le processus de gestion des intérêts concurrents a été entamé avant l'élaboration des lignes directrices et s'est poursuivi sur toute sa durée, selon les principes du Réseau international en matière de lignes directrices. Dans la formulation des recommandations, nous avons tenu compte des avantages et des risques, des valeurs et préférences de la patientèle, des ressources, de l'équité, de l'acceptabilité et de la faisabilité; la force de chacune des recommandations a été déterminée en fonction du cadre GRADE. RECOMMANDATIONS: Les 25 recommandations et les 10 énoncés de bonne pratique sont répartis en sections : activité physique, alimentation, évaluation du risque de fracture, instauration du traitement, interventions pharmacologiques, durée et séquence du traitement, et monitorage. La prise en charge de l'ostéoporose devrait se fonder sur le risque de fracture, établi au moyen d'une évaluation clinique réalisée avec un outil d'évaluation du risque de fracture validé. L'activité physique, l'alimentation et la pharmacothérapie sont des éléments essentiels à la stratégie de prévention des fractures, qui devraient être personnalisés. INTERPRÉTATION: Les présentes lignes directrices ont pour but d'outiller les professionnelles et professionnels de la santé et la patientèle afin qu'ensemble ils puissent parler de l'importance de la santé osseuse et du risque de fracture tout au long de la vie adulte avancée. La détection et la prise en charge efficace de la fragilité osseuse peuvent contribuer à réduire les fractures et à préserver la mobilité, l'autonomie et la qualité de vie.

Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: outcomes from TECOS.

AIMS: To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). MATERIALS AND METHODS: For participants with baseline eGFR measurements (n = 14 528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR < 60 mL/min per 1.73 m2 ) vs those without CKD. Within the CKD cohort, the same analyses were performed, comparing sitagliptin- and placebo-assigned participants. Baseline characteristics were summarized for all participants, and serious adverse events were analysed in those who received at least 1 dose of study medication. Adverse events of interest and diabetes complications were summarized for the intention-to-treat population. RESULTS: CKD was present in 3324 (23%) participants at entry into TECOS. The mean (SD) age for this CKD cohort was 68.8 (7.9) years, mean diabetes duration was 13.7 (9.0) years, and 62% were men. Incidences of serious adverse events, malignancy, bone fracture, severe hypoglycaemia and most categories of diabetes complications were higher in the CKD cohort compared with those without CKD. Over ~2.8 median years of follow-up, CKD participants assigned to sitagliptin had rates of diabetic eye disease, diabetic neuropathy, renal failure, malignancy, bone fracture, pancreatitis and severe hypoglycaemia similar to those of placebo-assigned participants. CONCLUSIONS: Participants in TECOS with CKD had higher incidences of serious adverse events and diabetes complications than those without CKD. Treatment with sitagliptin was generally well tolerated, with no meaningful differences in safety outcomes observed between those with CKD assigned to sitagliptin or placebo.

Sitagliptin and risk of fractures in type 2 diabetes: Results from the TECOS trial.

AIM: To examine fracture incidence among participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). RESEARCH DESIGN AND METHODS: We used data from 14 671 participants in the TECOS study who were randomized double-blind to sitagliptin (n = 7332) or placebo (n = 7339). Cumulative fracture incidence rates were calculated and their association with study treatment assignment was examined using multivariable Cox proportional hazards regression. RESULTS: The baseline mean (standard deviation) participant age was 65.5 (8.0) years, diabetes duration was 11.6 (8.1) years and glycated haemoglobin level was 7.2 (0.5)% [55.2 (5.5) mmol/mol], and 29.3% of participants were women and 32.1% were non-white. During 43 222 person-years' follow-up, 375 (2.6%; 8.7 per 1000 person-years) had a fracture; 146 were major osteoporotic fractures (hip, n = 34; upper extremity, n = 81; and clinical spine, n = 31). Adjusted analyses showed fracture risk increased independently with older age (P < .001), female sex (P < .001), white race (P < .001), lower diastolic blood pressure (P < .001) and diabetic neuropathy (P = .003). Sitagliptin, compared with placebo, was not associated with a higher fracture risk [189 vs 186 incident fractures: unadjusted hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.82 to 1.23, P = .944; adjusted HR 1.03, P = .745], major osteoporotic fractures (P = .673) or hip fractures (P = .761). Insulin therapy was associated with a higher fracture risk (HR 1.40, 95% CI 1.02-1.91; P = .035), and metformin with a lower risk (HR 0.76, 95% CI 0.59-0.98; P = .035). CONCLUSION: Fractures were common among people with diabetes in the TECOS study, but were not related to sitagliptin therapy. Insulin and metformin treatment were associated with higher and lower fracture risks, respectively.

Latent variable mixture models to test for differential item functioning: a population-based analysis.

BACKGROUND: Comparisons of population health status using self-report measures such as the SF-36 rest on the assumption that the measured items have a common interpretation across sub-groups. However, self-report measures may be sensitive to differential item functioning (DIF), which occurs when sub-groups with the same underlying health status have a different probability of item response. This study tested for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scales in population-based data using latent variable mixture models (LVMMs). METHODS: Data were from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective national cohort study. LVMMs were applied to the ten PF and five MH SF-36 items. A standard two-parameter graded response model with one latent class was compared to multi-class LVMMs. Multivariable logistic regression models with pseudo-class random draws characterized the latent classes on demographic and health variables. RESULTS: The CaMos cohort consisted of 9423 respondents. A three-class LVMM fit the PF sub-scale, with class proportions of 0.59, 0.24, and 0.17. For the MH sub-scale, a two-class model fit the data, with class proportions of 0.69 and 0.31. For PF items, the probabilities of reporting greater limitations were consistently higher in classes 2 and 3 than class 1. For MH items, respondents in class 2 reported more health problems than in class 1. Differences in item thresholds and factor loadings between one-class and multi-class models were observed for both sub-scales. Demographic and health variables were associated with class membership. CONCLUSIONS: This study revealed DIF in population-based SF-36 data; the results suggest that PF and MH sub-scale scores may not be comparable across sub-groups defined by demographic and health status variables, although effects were frequently small to moderate in size. Evaluation of DIF should be a routine step when analysing population-based self-report data to ensure valid comparisons amongst sub-groups.

Densitometer-Specific Differences in the Correlation Between Body Mass Index and Lumbar Spine Trabecular Bone Score.

Trabecular bone score (TBS) is a gray-level texture measure derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images that predicts fractures independent of bone mineral density (BMD). Increased abdominal soft tissue in individuals with elevated body mass index (BMI) absorbs more X-rays during image acquisition for BMD measurement and must be accommodated by the TBS algorithm. We aimed to determine if the relationship between BMI and TBS varied between 2 major manufacturers' densitometers, because different densitometers accommodate soft tissues differently. We identified 1919 women and 811 men, participants of the Canadian Multicentre Osteoporosis Study, aged ≥40 yr with lumbar spine DXA scans acquired on GE Lunar (4 centers) or Hologic (3 centers) densitometers at year 10 of follow-up. TBS was calculated for L1-L4 (TBS iNsight® software, version 2.1). A significant negative correlation between TBS and BMI was observed when TBS measurements were performed on Hologic densitometers in men (Pearson r = -0.36, p <0.0001) and in women (Pearson r = -0.33, p <0.0001); significant correlations were not seen when TBS was measured on GE Lunar densitometers (Pearson r = 0.00 in men, Pearson r = -0.02 in women). Age-adjusted linear regression models confirmed significant interactions between BMI and densitometer manufacturer for both men and women (p < 0.0001). In contrast, comparable positive correlations were observed between BMD and BMI on both Hologic and GE Lunar densitometers in men and women. In conclusion, BMI significantly affects TBS values in men and women when measured on Hologic but not GE Lunar densitometers. This finding has implications for clinical and research applications of TBS, especially when TBS is measured sequentially on DXA densitometers from different manufacturers or when results from different machines are pooled for analysis.

Case-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management From the International Task Force on ONJ.

Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence.

Bilateral atypical femoral fractures: how much symmetry is there on imaging?

OBJECTIVE: To evaluate bilateral atypical femoral fractures (AFFs) and to compare imaging features of paired fractures. MATERIALS AND METHODS: Bilateral femoral imaging studies of 124 patients on bisphosphonate therapy with at least one AFF were retrospectively reviewed. Time between AFF diagnoses was determined. The following imaging features were evaluated for each AFF: fracture location, femoral angle, length of cortical thickening, medial spike location, fracture orientation, and comminution. Associations between imaging findings on pairs of bilateral AFFs were assessed with Spearman's correlation (rs) and the Kappa statistic (κ). RESULTS: Bilateral AFFs were present in 78/124 (62.9%) cases (3 men, 75 women; mean age 67.3 years). Average time between contralateral AFF diagnoses was 10.3 months. Contralateral AFFs were diagnosed within 12 months of the index fracture in 60/78 (76.9%) cases and within 3 years in 69/78 (88.5%) cases. There was a strong correlation between bilateral AFF locations (rs = 0.65), with 58/76 (76.3%) occurring within a distance of <5 cm and 41/76 (53.9%) within a distance of ≤2.5 cm. Bilateral AFF pairs had moderately correlated femoral angles (rs = 0.42), and weakly correlated lengths of cortical thickening (rs = 0.28). There was substantial agreement for medial spike location (κ = 0.68) and fracture orientation (κ = 0.64), and moderate agreement for lack of comminution (κ = 0.42). All findings were independent of time between AFF diagnoses. CONCLUSIONS: Patients with unilateral atypical femoral fractures are likely to be diagnosed with a contralateral AFF within the first year of presentation. Bilateral AFFs commonly have similar imaging features, including location along the femur.

Intensive blood pressure control, falls, and fractures in patients with type 2 diabetes: the ACCORD trial.

BACKGROUND: There are few rigorous studies to confirm or refute the commonly cited concern that control of blood pressure to lower thresholds may result in an increased risk of falls and fractures. OBJECTIVE: To compare falls and fractures in participants with type 2 diabetes in the intensive (targeting a systolic blood pressure of < 120 mmHg) and standard (targeting a systolic blood pressure of < 140 mmHg) blood pressure control arms of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial (N = 4,733). PARTICIPANTS: A subset of 3,099 participants self-reported annually on the occurrence of falls and non-spine fractures. Fractures were centrally adjudicated. MAIN MEASURES: The incidence of falls in the two treatment groups was compared using a random-effects negative binomial model, and fracture risk was compared using Cox proportional hazards models. KEY RESULTS: At enrollment in both groups, the mean age was 62 years, 44% were women, 25% were Black, and mean blood pressure was 138/75 mmHg. During follow-up, all classes of medications, particularly thiazide diuretics, were more commonly prescribed in the intensive group. After 1 year of follow-up, the mean systolic blood pressure was 133 ± 15 mmHg in the standard group and 119 ± 14 mmHg in the intensive group. The adjusted rate of falls did not differ in the intensive and standard groups (62.2/100 person-years vs. 74.1/100 person-years, RR = 0.84, 95% CI 0.54-1.29, p = 0.43). The risk of non-spine fractures was nonsignificantly lower in the intensive than in the standard blood pressure group (HR 0.79, 95% CI 0.62-1.01, p = 0.06). CONCLUSIONS: We conclude that intensive antihypertensive treatment that lowered mean systolic blood pressure to below 120 mmHg was not associated with an increased risk of falls or non-spine fractures in patients age 40 to 79 years with type 2 diabetes.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. METHODS: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks' duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non-high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. RESULTS: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference -0.17 mmol/L, 95% confidence interval -0.25 to -0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. INTERPRETATION: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01594567.

Effect of Anticholinergic Medications on Falls, Fracture Risk, and Bone Mineral Density Over a 10-Year Period.

BACKGROUND: Many medications used in older adults have strong anticholinergic (ACH) properties, which may increase the risk of falls and fractures. Use of these medications was identified in a population-based Canadian cohort. OBJECTIVE: To identify the fall and fracture risk associated with ACH medication use. METHODS: Data collection and analysis were conducted at baseline, year 5, and year 10. Cross-sectional analyses were performed to examine associations between ACH medication use and falls. Time-dependent Cox regression was used to examine time to first nontraumatic fracture. Finally, change in bone mineral density (BMD) over 10 years was compared in ACH medication users versus nonusers. RESULTS: Strongly ACH medications were used by 618 of 7753 participants (8.0%) at study baseline, 592 (9.5%) at year 5, and 334 (7.7%) at year 10. Unadjusted ACH medication use was associated with falls at baseline (odds ratio = 1.50; 95% CI = 1.14-1.98; P = 0.004), but the association was no longer significant after covariate adjustment. Similar results occurred at years 5 and 10. ACH medication use was associated with increased incident fracture risk before (hazard ratio = 1.22; CI = 1.13-1.32; P < 0.001) but not after covariate adjustment. Mean (SD) change in femoral neck BMD T-score over 10 years, in those using ACH medications at both years 0 and 5, was -0.60 (0.63) in ACH users versus -0.49 (0.45) in nonusers (P = 0.041), but this was not significant after covariate adjustment. CONCLUSIONS: ACH medications were not found to be independently associated with an increased risk of falling, fractures, or BMD loss. Rather, factors associated with ACH medication use explained the apparent associations.

Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men.

PURPOSE: To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data. METHODS: Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences. RESULTS: Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high. CONCLUSIONS: Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.

Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.

BACKGROUND: Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. OBJECTIVE: The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. METHODS: Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. RESULTS: No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased ß-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted ß-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; ß-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; ß-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and ß-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels. CONCLUSION: Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.