Adherence to osteoporosis therapy after an upper extremity fracture: a pre-specified substudy of the C-STOP randomized controlled trial.

Despite their proven efficacy for secondary fracture prevention, long-term adherence with oral bisphosphonates is poor. INTRODUCTION: To compare the effectiveness of two interventions on long-term oral bisphosphonate adherence after an upper extremity fragility fracture. METHODS: Community-dwelling participants 50 years or older with upper extremity fragility fractures not previously treated with bisphosphonates were randomized to either a multi-faceted patient and physician educational intervention (the active control arm) vs. a nurse-led case manager (the study arm). Primary outcome was adherence (taking > 80% of prescribed doses) with prescribed oral bisphosphonates at 12 months postfracture between groups; secondary outcomes included rates of primary non-adherence and 24-month adherence. We also compared quality of life between adherent and non-adherent patients. RESULTS: By 12 months, adherence with the initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48 (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case manager arm. By 24 months, adherence rates were 67% (32/48) in the educational intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary non-adherence was 6% (11 patients) in the educational intervention group and 12% (21 patients) in the case managed group (p = 0.07). Prior family history of osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income < $30,000 per annum) was associated with poorer rates of adherence. There were no differences in health-related quality of life scores at baseline or during follow-up between patients who were adherent and those who were not. CONCLUSION: While both interventions achieved higher oral bisphosphonate adherence compared to previously reported adherence rates in the general population, primary non-adherence and long-term adherence to bisphosphonates were similar in both arms. Adherence was influenced by family history of osteoporosis, satisfaction with current medical care, and income. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01401556.

Effects of obesity and diabetes on rate of bone density loss.

In this large registry-based study, women with diabetes had marginally greater bone mineral density (BMD) loss at the femoral neck but not at other measurement sites, whereas obesity was not associated with greater BMD loss. Our data do not support the hypothesis that rapid BMD loss explains the increased fracture risk associated with type 2 diabetes and obesity observed in prior studies. INTRODUCTION: Type 2 diabetes and obesity are associated with higher bone mineral density (BMD) which may be less protective against fracture than previously assumed. Inconsistent data suggest that rapid BMD loss may be a contributing factor. METHODS: We examined the rate of BMD loss in women with diabetes and/or obesity in a population-based BMD registry for Manitoba, Canada. We identified 4960 women aged ≥ 40 years undergoing baseline and follow-up BMD assessments (mean interval 4.3 years) without confounding medication use or large weight fluctuation. We calculated annualized rate of BMD change for the lumbar spine, total hip, and femoral neck in relation to diagnosed diabetes and body mass index (BMI) category. RESULTS: Baseline age-adjusted BMD was greater in women with diabetes and for increasing BMI category (all P < 0.001). In women with diabetes, unadjusted BMD loss was less at the lumbar spine (P = 0.017), non-significantly greater at the femoral neck (P = 0.085), and similar at the total hip (P = 0.488). When adjusted for age and BMI, diabetes was associated with slightly greater femoral neck BMD loss (- 0.0018 g/cm2/year, P = 0.012) but not at the lumbar spine or total hip. There was a strong linear effect of increasing BMI on attenuated BMI loss at the lumbar spine with negligible effects on hip BMD. CONCLUSIONS: Diabetes was associated with slightly greater BMD loss at the femoral neck but not at other measurement sites. BMD loss at the lumbar spine was reduced in overweight and obese women but BMI did not significantly affect hip BMD loss.

Performance of FRAX in clinical practice according to sex and osteoporosis definitions: the Manitoba BMD registry.

Among 62,275 women and 6455 men, FRAX stratified risk for incident major osteoporotic fracture (MOF) and incident hip fracture (HF) without sex interaction. Performance was good in those with osteoporosis regardless of how this was defined. INTRODUCTION: Some studies have reported that FRAX performance differs according to sex and/or osteoporosis definitions. We evaluated whether the performance of FRAX to predict incident MOF and HF in women and men was affected by the presence or absence of osteoporosis defined by World Health Organization (WHO) or National Osteoporosis Foundation (NOF) criteria. METHODS: We studied women and men age ≥ 40 years with baseline hip and spine DXA scans (1996-2013). Individuals were classified into four non-overlapping subgroups: osteoporosis by WHO criteria, osteoporosis exclusively by NOF criteria, high fracture risk by FRAX (MOF ≥ 20% or HF ≥ 3%, without osteoporosis), and low fracture risk (MOF < 20% and HF < 3% without osteoporosis). In each subgroup, we evaluated stratification (hazard ratios [HR]) and calibration (observed vs predicted 10-year fracture probability) for incident fracture. RESULTS: The population included 62,275 women (5345 MOF and 1471 HF) and 6455 men (405 MOF and 108 HF). FRAX scores were strongly predictive of MOF (HR per SD: women 2.12, 95% CI 2.06-2.18; men 1.89, 95% CI 1.73-2.08; sex interaction p value = 0.97) and HF (women 4.78, 95% CI 4.44-5.14; men 4.20, 95% CI 3.22-5.49; sex interaction p value = 0.71). FRAX scores gave similar HRs for MOF among the four subgroups (subgroup interaction p value 0.34 for women, 0.22 for men). Observed versus predicted 10-year MOF and HF probability for the defined subgroups demonstrated a high level of concordance for women and men (all r2 ≥ 0.9). CONCLUSIONS: FRAX was a strong and consistent predictor of MOF and HF in both women and men and performed well in those with osteoporosis whether defined by WHO or NOF criteria.

Risk of prostate cancer across different racial/ethnic groups in men with diabetes: a retrospective cohort study.

AIM: To examine the associations between prostate cancer, diabetes and race/ethnicity. METHODS: Using administrative data from British Columbia, Canada for the period 1994 to 2012, we identified men aged ≥50 years with and without diabetes. Validated surname algorithms identified men as Chinese, Indian or of other race/ethnicity. Multivariable Cox regression was used to estimate adjusted risks of prostate cancer according to diabetes status and race/ethnicity. RESULTS: Our cohort of 160 566 men had a mean (sd) age of 64.7 (9.4) years and a median of 9 years' follow-up. The incidence rates of prostate cancer among those with and without diabetes were 177.4 (171.7-183.4) and 216.0 (209.7-222.5) per 1000 person-years, respectively. The incidence among Chinese men was 120.9 (109.2-133.1), among Indian men it was 144.1 (122.8-169.0) and in men of other ethnicity it was 204.8 (200.2-209.5). Diabetes was independently associated with a lower risk of prostate cancer (adjusted hazard ratio 0.82, 95% CI 0.78-0.86), as was Chinese (adjusted hazard ratio 0.54, 95% CI 0.46,0.63) and Indian (adjusted hazard ratio 0.66, 95% CI 0.49,0.89) race/ethnicity; however, there was no statistically significant interaction between diabetes status and race/ethnicity (all P>0.1). CONCLUSION: Diabetes and Chinese and Indian race/ethnicity were each independently associated with a lower risk of prostate cancer.

Risk factors for pneumococcal endocarditis.

Bacteremia is one of the most common manifestations of invasive pneumococcal disease (IPD). One complication of bacteremia is endocarditis; yet, few studies have evaluated the overall incidence and risk factors for IPD-associated endocarditis. Thus, we evaluated the overall incidence and risk factors of endocarditis compared to those without endocarditis in a large population of IPD patients. We prospectively collected all IPD cases from 2000 to 2014 in Northern Alberta, Canada. Descriptive statistics were used to compare sociodemographic variables, clinical characteristics, and IPD-related outcomes between patients with and without endocarditis. Endocarditis complicated the course of only 28 (0.3%) of 3251 adult patients with IPD. Endocarditis patients were more likely to use illicit drugs and have a higher severity of illness at presentation (i.e., higher rate of altered mental status and rate of intensive care unit [ICU] utilization, p < 0.05); however, no other major risk factors were identified. New murmur development among endocarditis patients was common: 39.3% compared to 2.2% of non-endocarditis patients (p < 0.001). The mortality rate of 39.3% was more than twice that of the rate of 14.7% for the patients with IPD but without endocarditis. There was no pneumococcal serotype predilection for endocarditis. Endocarditis is an uncommon complication of IPD, but, when present, is associated with a significantly increased risk of mortality. Overall, few specific risk factors were identified for IPD-related endocarditis, with the exception of illicit drug use.

Clinical performance of an updated trabecular bone score (TBS) algorithm in men and women: the Manitoba BMD cohort.

This is the first study to directly compare the original and recently updated versions of the trabecular bone score (TBS) algorithm. We confirmed improved performance of the new algorithm, especially among men. INTRODUCTION: Lumbar spine trabecular bone score (TBS) predicts major osteoporotic fractures (MOFs) and hip fractures (HFs) independent of bone density. The original TBS algorithm (version 1; [TBS-v1]) was optimized for women of average body size. Limitations were identified when used in men or extremes of body mass index (BMI). The current study evaluates an updated TBS algorithm (version 2; [TBS-v2]) modified to address these issues. METHODS: From a registry with all DXA results for Manitoba, Canada, we identified 47,736 women and 4348 men age ≥ 40 with baseline spine DXA (GE Prodigy, 1999-2011). Spine TBS was measured using both TBS-v1 and TBS-v2 algorithms. Risk stratification for incident fractures identified from population-based data was assessed from area under the receiver operating characteristic curve (AUROC). RESULTS: With the TBS-v1 algorithm, average TBS for men was significantly lower than for women (p < 0.001) and showed significant inverse correlations with BMI (Pearson r-0.40 in men, -0.18 in women [both p < 0.001]). With the TBS-v2 algorithm, average values for men were slightly greater than for women (p < 0.001) and there were no significant correlations with BMI (Pearson r 0.01 in men, -0.01 in women [both p > 0.1]). During mean follow-up of 5 years in men, there were 214 incident MOFs and 47 HFs; during 6 years mean follow-up in women, there were 2895 incident MOFs and 694 HFs. Improvements in fracture prediction were seen with TBS-v2 in both men (change in AUROC for MOFs +0.021 [p = 0.17], HFs +0.046 [p = 0.04]) and women (change in AUROC for MOFs +0.012 [p < 0.001], HFs +0.020 [p < 0.001]). CONCLUSION: The updated TBS algorithm is less affected by BMI, gives higher mean results for men than women consistent with their lower fracture risk, and improves fracture prediction in both men and women.

Economic evaluation of a population-based osteoporosis intervention for outpatients with non-traumatic non-hip fractures: the "Catch a Break" 1i [type C] FLS.

Fracture liaison services (FLS) are advocated to improve osteoporosis treatment after fragility fracture, but there are few economic analyses of different models. A population-based 1i [=type C] FLS for non-hip fractures was implemented and it costs $44 per patient and it was very cost-effective ($9200 per QALY gained). Small operational changes would convert it from cost-effective to cost-saving. INTRODUCTION: After fragility fracture, <20% of patients receive osteoporosis treatment. FLS are recommended to address this deficit but there are very few economic analyses of different FLS models. Therefore, we conducted an economic analysis of a 1i (=type C) FLS called "Catch a Break (CaB)." METHODS: CaB is a population-based FLS in Alberta, Canada, that case-finds older outpatients with non-traumatic upper extremity, spine, pelvis, or "other" non-hip fractures and provides telephonic outreach and printed educational materials to patients and their physicians. Cost-effectiveness was assessed using Markov decision-analytic models. Costs were expressed in 2014 Canadian dollars and effectiveness based on model simulations of recurrent fractures and quality-adjusted life years (QALYs). Perspective was healthcare payer; horizon was lifetime; and costs and benefits were discounted 3%. RESULTS: Over 1 year, CaB enrolled 7323 outpatients (mean age 67 years, 75% female, 69% upper extremity) at average cost of $44 per patient. Compared with usual care, CaB increased rates of bisphosphonate treatment by 4.3 to 17.5% (p < 0.001). Over their lifetime, for every 10,000 patients enrolled in CaB, 4 hip fractures (14 fractures total) would be avoided and 12 QALYs gained. Compared with usual care, incremental cost-effectiveness of CaB was estimated at $9200 per QALY. CaB was cost-effective in 85% of 10,000 probabilistic simulations. Sensitivity analyses showed if "other" fractures were excluded and intervention costs reduced 25% that CaB would become cost-saving. CONCLUSIONS: A relatively inexpensive population-based 1i (=type C) FLS was implemented in Alberta and it was very cost-effective. If CaB excluded "other" fractures and decreased intervention costs by 25%, it would be cost-saving, as would any FLS that was more effective and less expensive.

FRAX for fracture prediction shorter and longer than 10 years: the Manitoba BMD registry.

In a large clinical registry for the province of Manitoba, Canada, FRAX predicted incident MOF and hip fracture from 1 to 15 years following baseline assessment. A simple linear rescaling of FRAX outputs seems useful for predicting both short- and long-term fracture risk in this population. INTRODUCTION: FRAX® estimates 10-year probability of major osteoporotic fracture (MOF) and hip fracture. We examined FRAX predictions over intervals shorter and longer than 10 years. METHODS: Using a population-based clinical registry for Manitoba, Canada, we identified 62,275 women and 6455 men 40 years and older with baseline dual-energy X-ray absorptiometry scans and FRAX scores. Incident MOF and hip fracture were assessed up to 15 years from population-based data. We assessed agreement between estimated fracture probability from 1 to 15 years using linearly rescaled FRAX scores and observed cumulative fracture probability. The gradient of risk for FRAX probability and incident fracture was examined overall and for 5-year intervals. RESULTS: FRAX predicted incident MOF and hip fracture for all time intervals. There was no attenuation in the gradient of risk for MOF even for years >10. Gradient of risk was slightly lower for hip fracture prediction in years >10 vs years <5, though HRs remained high. Linear agreement was seen in the relationships between observed vs predicted (rescaled) FRAX probabilities (R 2 0.95-1.00). Among women, there was near-perfect linearity in MOF predictions. Deviations from linearity, with a slightly higher observed than predicted MOF probability, were most evident in the first years following a fracture event and after 10 years for hip fracture prediction in women using FRAX with BMD. Simulations showed that results were robust to large differences in fracture rates and moderate differences in mortality rates. CONCLUSIONS: FRAX predicts incident MOF and hip fracture up to 15 years and could be adapted to predict fracture over time periods shorter and longer term than 10 years in populations with fracture and mortality epidemiology similar to Canada.

Understanding fragility fracture patients' decision-making process regarding bisphosphonate treatment.

We aimed to understand how patients 50 years and older decided to persist with or stop osteoporosis (OP) treatment. Processes related to persisting with or stopping OP treatments are complex and dynamic. The severity and risks and harms related to untreated clinical OP and the favorable benefit-to-risk profile for OP treatments should be reinforced. INTRODUCTION: Older adults with fragility fracture and clinical OP are at high risk of recurrent fracture, and treatment reduces this risk by 50 %. However, only 20 % of fracture patients are treated for OP and half stop treatment within 1 year. We aimed to understand how older patients with new fractures decided to persist with or stop OP treatment over 1 year. METHODS: We conducted a grounded theory study of patients 50 years and older with upper extremity fracture who started bisphosphonates and then reported persisting with or stopping treatment at 1 year. We used theoretical sampling to identify patients who could inform emerging concepts until data saturation was achieved and analyzed these data using constant comparison. RESULTS: We conducted 21 interviews with 12 patients. Three major themes emerged. First, patients perceived OP was not a serious health condition and considered its impact negligible. Second, persisters and stoppers differed in weighting the risks vs benefits of treatments, where persisters perceived less risk and more benefit. Persisters considered treatment "required" while stoppers often deemed treatment "optional." Third, patients could change treatment status even 1-year post-fracture because they re-evaluated severity and impact of OP vs risks and benefits of treatments over time. CONCLUSIONS: The processes and reasoning related to persisting with or stopping OP treatments post-fracture are complex and dynamic. Our findings suggest two areas of leverage for healthcare providers to reinforce to improve persistence: (1) the severity and risks and harms related to untreated clinical OP and (2) the favorable benefit-to-risk profile for OP treatments.

Direct comparison of FRAX(R) and a simplified fracture risk assessment tool in routine clinical practice: a registry-based cohort study.

UNLABELLED: FRAX(R) incrementally improved prediction of incident major osteoporotic fractures compared with the simplified Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tool. INTRODUCTION: There is debate over the value of seemingly more complex fracture prediction tools over simpler fracture prediction tools. FRAX(R) and the simplified CAROC tool are both widely used in Canada for estimating 10-year probability of major osteoporotic fractures. We compared the performance of these tools for predicting fracture outcomes. METHODS: Using a bone densitometry registry for Manitoba, Canada, we identified 34,060 individuals age ≥50 years not receiving anti-osteoporosis therapy. Fracture Risk Assessment (FRAX) and CAROC were used to classify 10-year fracture risk as low (<10 %), moderate (10-20 %) and high (>20 %). Net reclassification improvement (NRI) was used to quantify the performance of FRAX versus CAROC. RESULTS: During mean 9.8 years of follow-up, 3905 individuals sustained fractures. There were 10 (of 35 total) situations where observed fracture risk fell outside of the predicted range, and all 10 discordances favoured FRAX. NRI among incident fracture cases was not significantly changed, but there was a significant improvement in risk categorization for those who remained fracture-free (+1.7 %, P < 0.001) resulting in overall improvement (NRI overall +0.028, P < 0.001). Within nine pre-specified subgroups, there was no case of significant worsening in NRI when using FRAX instead of CAROC. In absolute terms, only 36 individuals would need to be assessed using FRAX instead of CAROC to yield an improvement in prediction (8 among individuals with prior fracture and 4 among those with prolonged glucocorticoid use). CONCLUSIONS: FRAX provides improvement in fracture risk prediction compared with the simplified CAROC tool in individuals referred for osteoporosis screening, supporting the use of FRAX as the international reference tool for fracture risk assessment.

Antiresorptive therapy and newly diagnosed diabetes in women: a historical cohort study.

AIMS: Undercarboxylated osteocalcin (ucOC) promotes increased insulin sensitivity and increased secretion. Since antiresorptive therapy (AT) decreases ucOC levels, AT could increase the risk of diabetes and this would have serious clinical ramifications. We sought to test this hypothesis by examining the association between new use of AT and newly-diagnosed diabetes. METHODS: Using a bone mineral density (BMD) registry for Manitoba, Canada, we identified 33 640 women aged ≥50 years without diabetes at their first BMD test for 1998-2013. We linked these women to a province-wide retail pharmacy database to identify new AT exposure each year for up to 5 years after a BMD test. Time-dependent analysis was used to test the independent association between new use of AT and newly diagnosed diabetes. RESULTS: This cohort had a mean age of 65 years, a mean body mass index of 26.8 kg/m(2) , and 12% were receiving glucocorticoid and 13% hormone replacement therapy at BMD test. In the first year after BMD test, 29% of women started AT (bisphosphonates, 92%). Over a mean 4.2 years of follow-up, 3.7% new AT users and 4.2% non-users had diabetes (adjusted hazard ratio 1.01, 95% confidence interval 0.87-1.16). Sensitivity analyses using AT dose-response gradients also found no significant associations with diabetes. CONCLUSIONS: Despite the plausible biological mechanisms related to ucOC, new use of AT was not a risk factor for diabetes in this cohort. The clinical implications of these findings are reassuring, as AT is widely prescribed for treating osteoporosis in older women who are also at high risk of developing diabetes.

Sex- and age-specific associations between income and incident major osteoporotic fractures in Canadian men and women: a population-based analysis.

UNLABELLED: We investigated sex- and age-specific associations between income and fractures at the hip, humerus, spine, and forearm in adults aged ≥50 years. Compared to men with the highest income, men with the lowest income had an increased fracture risk at all skeletal sites. These associations were attenuated in women. INTRODUCTION: Associations between income and hip fractures are contested, even less is known about other fracture sites. We investigated sex- and age-specific associations between income and major osteoporotic fractures (MOF) at the hip, humerus, spine, and forearm. METHODS: Incident fractures were identified from administrative health data for adults aged ≥50 years in Manitoba, Canada, 2000-2007. Mean neighborhood (postal code area) annual household incomes were extracted from 2006 census files and categorized into quintiles. We calculated age-adjusted and age-specific sex-stratified fracture incidence across income quintiles. We estimated relative risks (RR) and 95% CI for income quintile 1 (Q1, lowest income) vs. income quintile 5 (Q5) and tested the linear trend across quintiles. RESULTS: We identified 15,094 incident fractures (4736 hip, 3012 humerus, 1979 spine, and 5367 forearm) in 2718 men and 6786 women. For males, the RR of fracture for the lowest vs. highest income quintile was 1.63 (95% CI 1.42-1.87) and the negative trend was statistically significant (p < 0.0001); individual skeletal sites showed similar associations. For females, the RR of fracture for the lowest vs. highest income quintile was 1.14 (95% CI 1.01-1.28), with a statistically significant negative trend (p = 0.0291); however, the only skeletal site associated with income in women was the forearm (Q1 vs. Q5 RR 1.09, 95% CI 1.01-1.28). CONCLUSIONS: Compared to men with the highest income, men with the lowest income had an increased fracture risk at all skeletal sites. These associations were attenuated in women. For men, these effect sizes seem large enough to warrant public health concern.

Cost-effectiveness analysis of adding pharmacists to primary care teams to reduce cardiovascular risk in patients with Type 2 diabetes: results from a randomized controlled trial.

BACKGROUND: Adding pharmacists to primary care teams significantly improved blood pressure control and reduced predicted 10-year cardiovascular risk in patients with Type 2 diabetes. This pre-specified sub-study evaluated the economic implications of this cardiovascular risk reduction strategy. METHODS: One-year outcomes and healthcare utilization data from the trial were used to determine cost-effectiveness from the public payer perspective. Costs were expressed in 2014 Canadian dollars and effectiveness was based on annualized risk of cardiovascular events derived from the UKPDS Risk Engine. RESULTS: The 123 evaluable trial patients included in this analysis had a mean age of 62 ( ± 11) years, 38% were men, and mean diabetes duration was 6 ( ± 7) years. Pharmacists provided 3.0 ( ± 1.9) hours of additional service to each intervention patient, which cost $226 ( ± $1143) per patient. The overall one-year per-patient costs for healthcare utilization were $190 lower in the intervention group compared with usual care [95% confidence interval (CI): -$1040, $668). Intervention patients had a significant 0.3% greater reduction in the annualized risk of a cardiovascular event (95% CI: 0.08%, 0.6%) compared with usual care. In the cost-effectiveness analysis, the intervention dominated usual care in 66% of 10,000 bootstrap replications. At a societal willingness-to-pay of $4000 per 1% reduction in annual cardiovascular risk, the probability that the intervention was cost-effective compared with usual care reached 95%. A sensitivity analysis using multiple imputation to replace missing data produced similar results. CONCLUSIONS: Within a randomized trial, adding pharmacists to primary care teams was a cost-effective strategy for reducing cardiovascular risk in patients with Type 2 diabetes. In most circumstances, this intervention may also be cost saving.

Rates and risk factors for recurrent pneumonia in patients hospitalized with community-acquired pneumonia: population-based prospective cohort study with 5 years of follow-up.

BACKGROUND: The rates and risk factors for developing recurrent pneumonia following hospitalization with community-acquired pneumonia (CAP) are poorly understood. METHODS: We examined a population-based cohort of patients with CAP who survived hospital admission and who were free of pneumonia for at least 3 months. We collected clinical, functional, and medication-related information and pneumonia severity index (PSI). Using linked databases we followed patients for 5 years and captured any clinical episode of pneumonia 90 days or more post-discharge. We used Cox proportional hazards models (adjusted for age, sex, PSI, functional status, medications) to determine rates and independent correlates of recurrent pneumonia. RESULTS: The final cohort included 2709 inpatients; 43% were 75 years or older, 34% were not fully independent, and 56% had severe pneumonia. Over 5 years of follow-up, 245 (9%; 95% confidence interval [CI], 8%-10%) patients developed recurrent pneumonia, and 156 (64%) of these episodes required hospitalization. Rate of recurrence was 3.0/100 person-years and median time to recurrence was 317 days (interquartile range, 177-569); 32 (13%) patients had 2 or more recurrences. In multivariable analyses only age >75 years (adjusted P = .047) and less than fully independent functional status (12% recurrence rate with impaired functional status vs 7% for fully independent; adjusted hazard ratio, 1.7; 95% CI, 1.3-2.2; P < .001) were significantly associated with recurrent pneumonia. CONCLUSIONS: One of 11 patients who survived CAP hospitalization had recurrent pneumonia over 5 years and those with impaired functional status were at particularly high risk. Recurrent pneumonia is common and more attention to preventive strategies at discharge and closer follow-up over the long-term seem warranted.

Vigorous physical activity and longitudinal associations with cardiometabolic risk factors in youth.

OBJECTIVE: To examine the longitudinal associations between different physical activity (PA) intensities and cardiometabolic risk factors among a sample of Canadian youth. METHODS: The findings are based on a 2-year prospective cohort study in a convenience sample of 315 youth aged 9-15 years at baseline from rural and urban schools in Alberta, Canada. Different intensities (light, moderate and vigorous) of PA were objectively assessed with Actical accelerometers. The main outcome measures were body mass index (BMI) z-score, waist circumference, cardiorespiratory fitness and systolic blood pressure at 2-year-follow-up and conditional BMI z-score velocity. A series of linear regression models were conducted to investigate the associations after adjusting for potential confounders. RESULTS: At follow-up, cardiorespiratory fitness increased (quartile 1 vs quartile 4=43.3 vs 50.2; P(trend)<0.01) and waist circumference decreased (quartile 1 vs quartile 4=79.0 vs 72.6; P(trend)=0.04; boys only) in a dose-response manner across quartiles of baseline vigorous-intensity PA. A similar trend was observed for systolic blood pressure (quartile 1 vs quartile 4=121.8 vs 115.3; P(trend)=0.07; boys only). Compared with quartile 1 of vigorous-intensity PA, BMI z-score at follow-up and conditional BMI z-score velocity were significantly lower in the quartile 2 and 3 (P<0.05). Waist circumference at follow-up also decreased (quartile 1 vs quartile 4=75.3 vs 73.8; P(trend)=0.04) across quartiles of baseline moderate-intensity PA. CONCLUSIONS: Time spent in vigorous-intensity PA was associated with several positive health outcomes 2 years later. These findings suggest that high-intensity activities in youth help to reduce the risk for several chronic diseases.

Does diabetes modify the effect of FRAX risk factors for predicting major osteoporotic and hip fracture?

UNLABELLED: In an observational study population of 62,413 individuals (6,455 [10 %] with diabetes), diabetes was independently associated with major osteoporotic fractures (MOFs) but did not significantly modify the effect of FRAX(TM) risk factors or prior fracture site. However, the presence of diabetes exerted a much stronger effect on hip fracture risk in younger versus older individuals. INTRODUCTION: Diabetes mellitus increases fracture risk independent of risk factors that comprise the WHO FRAX(TM) tool. We explored whether diabetes modifies the effect of FRAX clinical risk factors on MOF and hip fracture risk. METHODS: Using a registry of clinical dual-energy X-ray absorptiometry (DXA) results for Manitoba, Canada, we identified women and men aged 40 years and older undergoing baseline DXA in 1996-2011. Health services data were used to identify diabetes diagnosis, FRAX risk factors and incident fractures using previously validated algorithms. Prior fracture was stratified as clinical vertebral, hip, humerus, forearm, pelvis and 'other'. Cox proportional hazards models were used to test for statistical interactions of diabetes with FRAX clinical risk factors and prior fracture site. RESULTS: During a mean follow-up of 6 years, there were 4,218 MOF and 1,108 hip fractures. Diabetes was a significant independent risk factor for MOF adjusted for FRAX risk factors including bone mineral density (BMD) (adjusted hazard ratio [aHR] 1.32 [95 % confidence interval (CI) 1.20-1.46]). No significant interactions of FRAX risk factors or prior fracture site with diabetes were identified in analyses of MOF. For predicting hip fractures, age significantly modified the effect of diabetes (aHR age <60, 4.67 [95 % CI 2.76-7.89], age 60-69, 2.68 [1.77-4.04], age 70-79, 1.57 [1.20-2.04], age >80, 1.42 [1. 10-1.99]; pinteraction <0.001). CONCLUSIONS: Diabetes is an independent risk factor for MOFs and does not significantly modify the effect of FRAX risk factors or prior fracture site. However, diabetes exerts a much stronger effect on hip fracture risk in younger than older individuals which needs to be considered in hip fracture prediction.

Critical impact of patient knowledge and bone density testing on starting osteoporosis treatment after fragility fracture: secondary analyses from two controlled trials.

UNLABELLED: Most patients are not treated for osteoporosis after their fragility fracture "teachable moment." Among almost 400 consecutive wrist fracture patients, we determined that better-than-average osteoporosis knowledge (adjusted odds = 2.6) and BMD testing (adjusted odds = 6.5) were significant modifiable facilitators of bisphosphonate treatment while male sex, working outside the home, and depression were major barriers. INTRODUCTION: In the year following fragility fracture, fewer than one quarter of patients are treated for osteoporosis. Although much is known regarding health system and provider barriers and facilitators to osteoporosis treatment, much less is understood about modifiable patient-related factors. METHODS: Older patients with wrist fracture not treated for osteoporosis were enrolled in trials that compared a multifaceted intervention with usual care controls. Baseline data included a test of patient osteoporosis knowledge. We then determined baseline factors that independently predicted starting bisphosphonate treatment within 1 year. RESULTS: Three hundred seventy-four patients were enrolled; mean age 64 years, 78 % women, 90 % white, and 54 % with prior fracture. Within 1 year, 86 of 374 (23 %) patients were treated with bisphosphonates. Patients who were treated had better osteoporosis knowledge at baseline (70 % correct vs 57 % for untreated, p < 0.001) than patients who remained untreated; conversely, untreated patients were more likely to be male, still working, and report depression. In fully adjusted models, osteoporosis knowledge was independently associated with starting bisphosphonates (adjusted OR 2.6, 95 %CI 1.3-5.3). Obtaining a BMD test (aOR 6.5, 95 %CI 3.4-12.2) and abnormal BMD results (aOR 34.5, 95 %CI 16.8-70.9) were strongly associated with starting treatment. CONCLUSIONS: The most important modifiable facilitators of osteoporosis treatment in patients with fracture were knowledge and BMD testing. Specifically targeting these two patient-level factors should improve post-fracture treatment rates.

Influence of recency and duration of glucocorticoid use on bone mineral density and risk of fractures: population-based cohort study.

UNLABELLED: Although systemic glucocorticoids are commonly used, it is difficult to obtain accurate exposure history. In 50,000 patients, we confirmed that glucocorticoids were associated with reductions in bone mineral density (BMD) and increases in fracture and documented that recent and prolonged durations of exposure were particularly associated with adverse events-dose information did not improve risk prediction. INTRODUCTION: Systemic glucocorticoid use, defined as ever having taken supra-physiologic doses for 90-days or more, is a risk factor for low BMD and fractures. This definition does not distinguish recent (vs remote) exposure. METHODS: Within a population-based clinical BMD registry in Manitoba, Canada, we identified all adults over age 40 years tested between 1998 and 2007 and then undertook a cohort study. We identified all oral glucocorticoid dispensations from 1995 to 2009 and stratified exposure by timing ("recent" if within 12 months vs "remote") and duration (short [<90 days] vs prolonged [≥90 days]). Osteoporosis-related risk factors and treatments and major fractures were obtained using administrative health data. RESULTS: A total of 12,818 of 52,070 (25%) subjects had used glucocorticoids prior to BMD testing; the most common exposure was remote short (n = 6453) vs recent prolonged (n = 2896) vs recent short (n = 2644) vs remote prolonged (n = 825). Compared to 39,252 never-users, only recent prolonged glucocorticoid use was significantly associated with femoral neck T-score (ANCOVA-adjusted difference -0.13, 95% CI -0.16 to -0.10, p < 0.001). There were 2,842 major (566 hip) fractures over median 5-year follow-up. Compared with never-users, only recent prolonged glucocorticoid use was significantly associated with BMD-independent increases in risk of incident major fracture (5.4 vs 7.7%, adjusted HR 1.25, 95% CI 1.07-1.45, p = 0.004) and hip fracture (1.1 vs 1.8%, adjusted HR 1.61, 95% CI 1.18-2.20, p = 0.003). CONCLUSIONS: Recent and prolonged glucocorticoid use (but neither remote nor recent short courses) was independently associated with reduced BMD and increased risk of fractures. These findings should permit clinicians to identify a high-risk group of patients that might benefit from osteoporosis prevention.

Direct healthcare costs for 5 years post-fracture in Canada: a long-term population-based assessment.

UNLABELLED: High direct incremental healthcare costs post-fracture are seen in the first year, but total costs from a third-party healthcare payer perspective eventually fall below pre-fracture levels. We attribute this to higher mortality among fracture cases who are already the heaviest users of healthcare ("healthy survivor bias"). Economic analyses that do not account for the possibility of a long-term reduction in direct healthcare costs in the post-fracture population may systematically overestimate the total economic burden of fracture. INTRODUCTION: High healthcare costs in the first 1-2 years after an osteoporotic fracture are well recognized, but long-term costs are uncertain. We evaluated incremental costs of non-traumatic fractures up to 5 years from a third-party healthcare payer perspective. METHODS: A total of 16,198 incident fracture cases and 48,594 matched non-fracture controls were identified in the province of Manitoba, Canada (1997-2002). We calculated the difference in median direct healthcare costs for the year pre-fracture and 5 years post-fracture expressed in 2009 Canadian dollars with adjustment for expected age-related healthcare cost increases. RESULTS: Incremental median costs for a hip fracture were highest in the first year ($25,306 in women, $21,396 in men), remaining above pre-fracture baseline to 5 years in women but falling below pre-fracture costs by 5 years in men. In those who survived 5 years following a hip fracture, incremental costs remained above pre-fracture costs at 5 years ($12,670 in women, $7,933 in men). Incremental costs were consistently increased for 5 years after spine fracture in women. Total incremental healthcare costs for all incident fractures combined showed a large increase over pre-fracture costs in the first year ($137 million in women, $57 million in men), but fell below pre-fracture costs within 3-4 years. Elevated total healthcare costs were seen at year 5 in women after wrist, humerus and spine fractures, but these were somewhat offset by decreases in total healthcare costs for other fractures. CONCLUSIONS: High direct healthcare costs post-fracture are seen in the first year, but total costs eventually fall below pre-fracture levels. Among those who survive 5 years following a fracture, healthcare costs remain above pre-fracture levels.

Temporal trends in the incidence of osteoporotic fractures.

Osteoporotic fractures are associated with excess mortality and decreased functional capacity and quality of life. Age-standardized incidence rates of fragility fractures, particularly of the hip and forearm, have been noted to be decreasing in the last decade across many countries with the notable exception of Asia. The causes for the observed changes in fracture risk have not been fully identified but are likely the result of multiple factors, including birth cohort and period effects, increasing obesity, and greater use of anti-osteoporosis medications. Changing rates of fragility fractures would be expected to have an important impact on the burden of osteoporosis.