In vivo precision of three HR-pQCT-derived finite element models of the distal radius and tibia in postmenopausal women.

BACKGROUND: The distal radius is the most common osteoporotic fracture site occurring in postmenopausal women. Finite element (FE) modeling is a non-invasive mathematical technique that can estimate bone strength using inputted geometry/micro-architecture and tissue material properties from computed tomographic images. Our first objective was to define and compare in vivo precision errors for three high-resolution peripheral quantitative computed tomography (HR-pQCT, XtremeCT; Scanco) based FE models of the distal radius and tibia in postmenopausal women. Our second objective was to assess the role of scan interval, scan quality, and common region on precision errors of outcomes for each FE model. METHODS: Models included: single-tissue model (STM), cortical-trabecular dual-tissue model (DTM), and one scaled model using imaged bone mineral density (E-BMD). Using HR-pQCT, we scanned the distal radius and tibia of 34 postmenopausal women (74 ± 7 years), at two time points. Primary outcomes included: tissue stiffness, apparent modulus, average von Mises stress, and failure load. Precision errors (root-mean-squared coefficient of variation, CV%RMS) were calculated. Multivariate ANOVA was used to compare the mean of individual CV% among the 3 HR-pQCT-based FE models. Spearman correlations were used to characterize the associations between precision errors of all FE model outcomes and scan/time interval, scan quality, and common region. Significance was accepted at P < 0.05. RESULTS: At the distal radius, CV%RMS precision errors were <9 % (Range STM: 2.8-5.3 %; DTM: 2.9-5.4 %; E-BMD: 4.4-8.7 %). At the distal tibia, CV%RMS precision errors were <6 % (Range STM: 2.7-4.8 %; DTM: 2.9-3.8 %; E-BMD: 1.8-2.5 %). At the radius, Spearman correlations indicated associations between the common region and associated precision errors of the E-BMD-derived apparent modulus (ρ = -0.392; P < 0.001) and von Mises stress (ρ = -0.297; P = 0.007). CONCLUSION: Results suggest that the STM and DTM are more precise for modeling apparent modulus, average von Mises stress, and failure load at the distal radius. Precision errors were comparable for all three models at the distal tibia. Results indicate that the noted differences in precision error at the distal radius were associated with the common scan region, illustrating the importance of participant repositioning within the cast and reference line placement in the scout view during the scanning process.

Lower leg muscle density is independently associated with fall status in community-dwelling older adults.

UNLABELLED: Muscle density is a risk factor for fractures in older adults; however, its association with falls is not well described. After adjusting for biologically relevant confounding factors, a unit decrease in muscle density was associated with a 17 % increase in odds of reporting a fall, independent of functional mobility. INTRODUCTION: Falls are the leading cause of injury, disability, and fractures in older adults. Low muscle density (i.e., caused by muscle adiposity) and functional mobility have been identified as risk factors for incident disability and fractures in older adults; however, it is not known if these are also independently associated with falls. The purpose of this study was to explore the associations of muscle density and functional mobility with fall status. METHODS: Cross-sectional observational study of 183 men and women aged 60-98 years. Descriptive data, including a 12-month fall recall, Timed Up and Go (TUG) test performance, lower leg muscle area, and density. Odds ratio (OR) of being a faller were calculated, adjusted for age, sex, body mass index, general health status, diabetes, and comorbidities. RESULTS: Every mg/cm(3) increase in muscle density (mean 70.2, SD 2.6 mg/cm(3)) independently reduced the odds of being a faller by 19 % (OR 0.81 [95 % CI 0.67 to 0.97]), and every 1 s longer TUG test time (mean 9.8, SD 2.6 s) independently increased the odds by 17 % (OR 1.17 [95 % CI 1.01 to 1.37]). When both muscle density and TUG test time were included in the same model, only age (OR 0.93 [95 % CI 0.87 to 0.99]) and muscle density (OR 0.83 [95 % CI 0.69 to 0.99]) were independently associated with fall status. CONCLUSIONS: Muscle density was associated with fall status, independent of functional mobility. Muscle density may compliment functional mobility tests as a biometric outcome for assessing fall risk in well-functioning older adults.

Role of endocortical contouring methods on precision of HR-pQCT-derived cortical micro-architecture in postmenopausal women and young adults.

UNLABELLED: Precision errors of cortical bone micro-architecture from high-resolution peripheral quantitative computed tomography (pQCT) ranged from 1 to 16 % and did not differ between automatic or manually modified endocortical contour methods in postmenopausal women or young adults. In postmenopausal women, manually modified contours led to generally higher cortical bone properties when compared to the automated method. INTRODUCTION: First, the objective of the study was to define in vivo precision errors (coefficient of variation root mean square (CV%RMS)) and least significant change (LSC) for cortical bone micro-architecture using two endocortical contouring methods: automatic (AUTO) and manually modified (MOD) in two groups (postmenopausal women and young adults) from high-resolution pQCT (HR-pQCT) scans. Second, it was to compare precision errors and bone outcomes obtained with both methods within and between groups. METHODS: Using HR-pQCT, we scanned twice the distal radius and tibia of 34 postmenopausal women (mean age ± SD 74 ± 7 years) and 30 young adults (27 ± 9 years). Cortical micro-architecture was determined using AUTO and MOD contour methods. CV%RMS and LSC were calculated. Repeated measures and multivariate ANOVA were used to compare mean CV% and bone outcomes between the methods within and between the groups. Significance was accepted at P < 0.05. RESULTS: CV%RMS ranged from 0.9 to 16.3 %. Within-group precision did not differ between evaluation methods. Compared to young adults, postmenopausal women had better precision for radial cortical porosity (precision difference 9.3 %) and pore volume (7.5 %) with MOD. Young adults had better precision for cortical thickness (0.8 %, MOD) and tibial cortical density (0.2 %, AUTO). In postmenopausal women, MOD resulted in 0.2-54 % higher values for most cortical outcomes, as well as 6-8 % lower radial and tibial cortical BMD and 2 % lower tibial cortical thickness. CONCLUSIONS: Results suggest that AUTO and MOD endocortical contour methods provide comparable repeatability. In postmenopausal women, manual modification of endocortical contours led to generally higher cortical bone properties when compared to the automated method, while no between-method differences were observed in young adults.

Least significant changes and monitoring time intervals for high-resolution pQCT-derived bone outcomes in postmenopausal women.

BACKGROUND: Least Significant Change (LSC) assists in determining whether observed bone change is beyond measurement precision. Monitoring Time Interval (MTI) estimates time required to reliably detect skeletal changes. MTIs have not been defined for bone outcomes provided by high resolution peripheral quantitative computed tomography (HR-pQCT). The purpose of this study was to determine the LSCs and MTIs for HR-pQCT derived bone area, density and micro-architecture with postmenopausal women. METHODS: Distal radius and tibia of 33 postmenopausal women (mean age: 77, SD: ±7 years), from the Saskatoon cohort of the Canadian Multicentre Osteoporosis Study (CaMos), were measured using HR-pQCT at baseline and 1-year later. We determined LSC from precision errors and divided them by the median annual percent changes to define MTIs for bone area, density, and micro-architecture. RESULTS: Distal radius: HR-pQCT LSCs indicated a 1-8% observed change was needed for reliable monitoring of bone area and density while a 3-18% change was needed for micro-architectural measures. The longest MTIs (>3 years) pertained to cortical and trabecular area and density measures, cortical thickness and bone volume fraction; the shortest MTIs (~2 years) pertained to bone micro-architectural measures (trabecular number, thickness, separation and heterogeneity). Distal tibia: LSCs indicated a <1-5% observed change was needed for reliable monitoring of bone area and density, while a 3-19% change was needed for micro-architectural measures. The longest MTIs (>3 years) pertained to trabecular density, bone volume fraction, number, separation and heterogeneity; the shortest MTIs (~1 year) pertained to cortical and trabecular area, cortical density and thickness. CONCLUSION: MTIs suggest that performing HR-pQCT follow-up measures in postmenopausal women every 2 years at the distal radius and every 1 year at the distal tibia to monitor true skeletal changes as indicated by the LSCs.

Community-dwelling female fallers have lower muscle density in their lower legs than non-fallers: evidence from the Saskatoon Canadian Multicentre Osteoporosis Study (CaMos) cohort.

OBJECTIVES: Our objectives were to determine whether peripheral quantitative computed tomography (pQCT)-derived lower leg muscle density and area, and basic functional mobility differ between community-dwelling older women who do and do not report recent falls. DESIGN: Matched case-control comparison. SETTING: Academic biomedical imaging laboratory. PARTICIPANTS: 147 Women, 60 years or older (mean age 74.3 y, SD 7.7) recruited from a longitudinal, population-based cohort representing community-dwelling residents in the area of Saskatoon, Canada. MEASUREMENTS: A cross-sectional pQCT scan of the non-dominant lower leg was acquired to determine muscle density and area. Basic functional mobility (Timed Up and Go Test [TUG]) and SF36 health status were also measured. Fallers (one or more falls) and non-fallers (no falls) were grouped according to a 12-month retrospective survey and matched on measured covariates. RESULTS: The muscle density of fallers (n = 35) was a median of 2.1 mg/cm3 lower (P = 0.019, 95% C.I. -3.9 to -0.1) than non-fallers (n = 78) after matching and adjusting for age, body mass index, and SF36 general health scores. Muscle area and TUG did not differ between fallers and non-fallers. CONCLUSIONS: Muscle density may serve as a physiological marker in the assessment of lower leg muscular health and fall risk in community-dwelling elderly women. These results are limited to our study population who were mostly Caucasian. Prospective studies are required for verification.

Characterizing microarchitectural changes at the distal radius and tibia in postmenopausal women using HR-pQCT.

UNLABELLED: Limited prospective evidence exists regarding bone microarchitectural deterioration. We report annual changes in trabecular and cortical bone microarchitecture at the distal radius and tibia in postmenopausal women. Lost trabeculae with corresponding increase in trabecular thickness at the radius and thinning tibial cortex indicated trabecularization of the cortex at both sites. INTRODUCTION: Osteoporosis is characterized by low bone mass and the deterioration of bone microarchitecture. However, limited prospective evidence exists regarding bone microarchitectural changes in postmenopausal women: a population prone to sustaining osteoporotic fractures. Our primary objective was to characterize the annual change in bone area, density, and microarchitecture at the distal radius and distal tibia in postmenopausal women. METHODS: Distal radius and tibia were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 1 year later in 51 women (mean age ± SD, 77 ± 7 years) randomly sampled from the Saskatoon cohort of the Canadian Multicentre Osteoporosis Study (CaMos). We used repeated measures analysis of variance (ANOVA) with Bonferroni adjustment for multiple comparisons to characterize the mean annual change in total density, cortical perimeter, trabecular and cortical bone area, density, content, and microarchitecture. Significant changes were accepted at P < 0.05. RESULTS: At the distal radius in women without bone-altering drugs, total density (-1.7%) and trabecular number (-6.4%) decreased, while trabecular thickness (+6.0%), separation (+8.6%), and heterogeneity (+12.1%) increased. At their distal tibia, cortical area (-4.5%), density (-1.9%), content (-6.3%), and thickness (-4.4%) decreased, while trabecular area (+0.4%) increased. CONCLUSIONS: The observed loss of trabeculae with concomitant increase in trabecular size at the distal radius and the declined cortical thickness, density, and content at the distal tibia indicated a site-specific trabecularization of the cortical bone in postmenopausal women.

Monitoring time interval for pQCT-derived bone outcomes in postmenopausal women.

UNLABELLED: Evidence of measurement precision, annual changes and monitoring time interval is essential when designing and interpreting longitudinal studies. Despite the precise measures, small annual changes in bone properties led to monitoring time intervals (MTIs) of 2-6 years in peripheral quantitative computed tomography (pQCT)-derived radial and tibial bone area, density, and estimated strength in postmenopausal women. INTRODUCTION: The purpose of the study was to determine the precision error, annual change, and MTI in bone density, area, and strength parameters in postmenopausal women. METHODS: Postmenopausal women (n = 114) from the Saskatoon cohort of the Canadian Multicentre Osteoporosis Study had annual pQCT scans of the distal and shaft sites of the radius and tibia for 2 years. Median annualized rates of percent change and the MTI were calculated for bone density, area, and strength parameters. Root mean squared coefficients of variation (CV%) were calculated from duplicate scans in a random subgroup of 35 postmenopausal women. RESULTS: CV% ranged from 1.4 to 6.1 % at the radius and 0.7 to 2.1 % at the tibia. MTIs for the distal radius were 3 years for total bone density (ToD) and 4 years for total bone cross sectional area (ToA), trabecular area, and bone strength index. At the diaphyseal radius, MTI was 3 years for ToA, 5 years for cortical density, and 6 years for polar stress strain index (SSIp). Similarly, MTI for total and trabecular density was 3 years at the distal tibia. At the diaphyseal tibia, MTI for ToA was 3 years and SSIp 4 years. CONCLUSION: MTI for longitudinal studies in older postmenopausal women should be at least 2-6 years at the radius and tibia, with specific monitoring of the total and trabecular area, total density, and bone strength at the radius and total and trabecular density, total area, and bone strength at the tibia.

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.

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.

Effectiveness of antiresorptives for the prevention of nonvertebral low-trauma fractures in a population-based cohort of women.

UNLABELLED: Observational studies are needed to quantify real-life effectiveness of antiresorptive therapy in the prevention of clinical fractures. Antiresorptive therapies were associated with an overall 32% reduction in low-trauma nonvertebral fracture risk among women 50 and older. Effectiveness may be lower among older women and those without risk factors. INTRODUCTION: Randomized controlled trials have shown that antiresorptive therapies reduce the risk of fracture in selected populations, but further study is needed to quantify their real-life effectiveness. The study objective was to determine the association between antiresorptive use and low-trauma nonvertebral fracture in women 50 and older. METHODS: The design was a retrospective nested case-control study (density-based sampling) within the Canadian Multicentre Osteoporosis Study. There were 5,979 eligible women with 453 cases and 1,304 matched controls. RESULTS: The current use of antiresorptives was associated with a decreased risk of fracture with OR = 0.68, 95% CI: 0.52-0.91; where OR is the adjusted odds ratio and CI is the confidence interval. Subgroup analysis yielded OR = 0.61, 95% CI: 0.42-0.89 for ages 50-74; OR = 0.76, 95% CI: 0.50-1.17 for ages 75+; OR = 0.58, 95% CI: 0.40-0.83 for those with a major risk factor; and OR = 0.92; 95% CI: 0.59-1.42 for those without a major risk factor. Major risk factors were prevalent low-trauma fracture, vertebral deformity (grade 2+), and BMD T-score < or = -2.5. CONCLUSIONS: Antiresorptive therapy is associated with a clinically important reduction in low-trauma nonvertebral fracture risk among community-dwelling women aged 50 and older. Antiresorptive therapy may be less effective for women 75 and older and women without major risk factors.

Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index.

BACKGROUND: Enthesitis is a recommended core domain for assessment of ankylosing spondylitis (AS), but no measurement has yet been validated according to Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) criteria. OBJECTIVE: The purpose of this study was to seek to validate an enthesitis index for patients with AS according to OMERACT criteria. METHODS: An enthesitis index was validated in two AS patient cohorts: (1) a longitudinal cohort (n = 223) and (2) 22 patients from three Canadian sites participating in a 24-week randomised placebo-controlled trial of adalimumab in AS. Construct validity was evaluated by correlation analysis with the Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI) and quality of life instruments. Reproducibility was assessed by intraclass correlation coefficient (ICC), and responsiveness was assessed by Guyatt's effect size and standardised response mean. RESULTS: The most frequently affected sites were the greater trochanter and supraspinatus insertion ( approximately 20%). Patients with enthesitis had significantly greater scores for the BASDAI, BASFI, patient global, AS-specific quality of life index (ASQOL) and the Short Form 36 (SF-36) General Health Survey (p<0.001). The enthesitis score contributed significantly to variance in the BASDAI and BASFI. Interobserver ICCs were 0.96 in the longitudinal cohort and 0.89 and 0.77 in the adalimumab clinical trial cohort (for status and change score, respectively). Significant differences in change scores were evident for all patients after 24 weeks of adalimumab treatment, (p = 0.04), this being more significant when a subset of the most commonly affected entheses were analysed (p = 0.01). CONCLUSION: AS patients with enthesitis constitute a more severe subset of disease, and the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index is feasible and reliable for measurement of this condition. Discrimination requires further study in larger trials.

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.

Alendronate for the treatment of osteoporosis in men.

BACKGROUND: Men have higher rates of osteoporosis and suffer fragility fractures more often than previously believed. Fracture-related morbidity and mortality in men is substantially higher than in women. OBJECTIVE: To investigate alendronate for treating osteoporosis in men. METHODS: Search limited to 'men' and 'English'; keywords were 'osteoporosis' or 'bone density' or 'fracture' and 'alendronate'. RESULTS/CONCLUSIONS: Alendronate is an amino-bisphosphonate with proved efficacy for increasing bone mineral density in men with idiopathic or secondary osteoporosis and has demonstrated an ability to prevent vertebral fractures in men with low bone mass. There are trends for alendronate to decrease the risk of non-vertebral fracture, but larger trials are needed to conclusively establish this benefit. Alendronate is a well-tolerated and comparatively safe drug with an attractive once-a-week dosing regimen.

Monthly dosing of 75 mg risedronate on 2 consecutive days a month: efficacy and safety results.

UNLABELLED: Postmenopausal women with osteoporosis received 75 mg risedronate on two consecutive days each month or 5 mg daily for 12 months. Changes in bone mineral density and bone turnover markers were similar between treatments. Risedronate 75 mg twice monthly was effective and safe suggesting a new, convenient dosing schedule. INTRODUCTION: Patients perceive less frequent dosing as being more convenient. This 2-year trial evaluates the efficacy and safety of a new monthly oral regimen of risedronate; 1 year results are presented here. METHODS: Postmenopausal women with osteoporosis (n = 1229) were randomly assigned to double-blind treatment with 75 mg risedronate on two consecutive days each month (2CDM), or 5 mg daily. The primary endpoint was the percent change from baseline in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary efficacy was evaluated by mean percent changes from baseline in BMD in LS, total hip, trochanter, and femoral neck, and bone turnover markers (BTMs). RESULTS: Risedronate 75 mg 2CDM was non-inferior to 5 mg daily (treatment difference 0.21; 95% CI -0.19 to 0.62). Mean percent change in LS-BMD was 3.4% +/- 0.16 and 3.6% +/- 0.15 respectively. Mean percent changes in BMD and BTMs were significant and similar for both treatment groups. New vertebral fractures occurred in 1% of subjects with either treatment. Both treatments were generally well tolerated and safe. CONCLUSIONS: Risedronate 75 mg 2CDM was non-inferior in efficacy and did not show a difference in safety vs. 5 mg daily after 12 months, leading to a similar benefit.

A Randomized Clinical Trial of Aquatic versus Land Exercise to Improve Balance, Function, and Quality of Life in Older Women with Osteoporosis.

PURPOSE: Despite the decreased gravitational loading that is experienced in an aquatic environment, little research has been conducted on this exercise medium for women with osteoporosis (OP). Aquatic exercise (AE) may improve function and balance, thus ultimately decreasing fall risk and the potential for hip fractures in this high-risk population. METHOD: A total of 68 women with OP, aged 60 years or older, were recruited into a randomized clinical trial evaluating the impact of AE, land exercise (LE), and no exercise (NE) on balance, functional mobility, and quality of life (QOL). RESULTS: Only one balance measure (backward tandem walk) significantly improved with AE compared to LE, but this did not translate into a greater improvement in self-report function. There were no significant differences between the exercise interventions and NE, except for in ratings of global change, where participants in the AE group were three times more likely to report improvement than those in the NE group. CONCLUSION: There were no differences in balance, function, or QOL in women with OP who followed an AE or LE programme compared to those in an NE control group. However, the significant differences in backward tandem walk between the AE and LE groups and self-reported global change between the AE and NE groups warrant further investigation. Significant improvements in balance and global change suggest that AE is a viable alternative for older women with OP who have difficulty exercising on land.

Fracture risk remains reduced one year after discontinuation of risedronate.

UNLABELLED: One year after discontinuation of three year's treatment with risedronate, BMD decreased at the lumbar spine and femoral neck and bone turnover markers returned to control group levels. Despite these changes, the risk of new morphometric vertebral fractures remained lower in previous risedronate patients compared with previous control patients. INTRODUCTION: Differences in bisphosphonate pharmacology and pharmacokinetics could influence persistence or resolution of the effects once treatment is stopped. We investigated changes in intermediate markers--bone mineral density (BMD) and bone turnover markers (BTM)--and fracture risk after discontinuation of treatment with risedronate. METHODS: Patients who received risedronate 5 mg daily (N = 398) or placebo (N = 361) during the VERT-NA study stopped therapy per protocol after 3 years but continued taking vitamin D (if levels at study entry were low) and calcium and were reassessed one year later. RESULTS: In the year off treatment, spine BMD decreased significantly, but remained higher than baseline (p < or = 0.001) and placebo (p < 0.001), with similar findings at the femoral neck and trochanter. Urinary NTX and bone-specific alkaline phosphatase, which decreased significantly with treatment, were not significantly different from placebo after 1 year off treatment. Despite the changes in intermediate markers, the incidence of new morphometric vertebral fractures was 46% lower in the former risedronate group compared with the former placebo group (RR 0.54 [95% CI, 0.34, 0.86, p = 0.009]). CONCLUSIONS: Despite the apparent resolution of effect on BMD and BTM, the risk reduction of new vertebral fractures remained in the year after treatment with risedronate was stopped.

The osteoporosis care gap in men with fragility fractures: the Canadian Multicentre Osteoporosis Study.

UNLABELLED: We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap. INTRODUCTION: Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five. RESULTS: Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five). CONCLUSIONS: In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.

Effectiveness of alendronate and etidronate in the treatment of osteoporosis in men: a prospective observational study.

The prevalence of osteoporosis in men is higher than previously assumed; consequently, numerous therapies are being investigated to treat these patients. The Canadian Database of Osteoporosis and Osteopenia patients (CANDOO) was analyzed to examine changes in bone mineral density (BMD) in consecutively seen osteoporotic men administered alendronate, etidronate or no bone-active drugs (control) over 1 year. A total of 244 men attending six Canadian osteoporosis clinics were included in the study (42 alendronate, 102 etidronate and 100 control). Multiple imputation was used to model missing data to provide a more robust statistical model. The imputed datasets (five) were analyzed using multivariable linear regression to determine differences between groups in the percent change of lumbar spine (LS) and femoral neck (FN) BMD from baseline to 1 year. Differences in the percent change in BMD from baseline were most notable at the LS in favor of alendronate (4.3%; 95% CI: 2.1, 6.6 ) and etidronate (2.1%; 95% CI: 0.3, 4.0) therapy when compared with controls. At the LS, alendronate therapy led to significantly greater (2.2%; 95% CI: 0.2, 4.2) gains in BMD as compared to etidronate therapy. Compared to controls, there were no significant differences in FN BMD with alendronate (2.1%; 95% CI: -0.4, 4.7) or etidronate therapy (0.9%; 95% CI: -1.1, 2.8), nor were there significant differences between bisphosphonate groups (1.3%; 95% CI: -1.1, 3.6, in favor of alendronate). While both alendronate and etidronate significantly increased LS BMD in osteoporotic men after 1 year in real-world settings, alendronate therapy resulted in significantly superior gains in LS BMD. The effect of these two bisphosphonates on fractures and FN BMD in osteoporotic men is likely positive, but requires further study.

The influence of motor vehicle legislation on injury claim incidence.

BACKGROUND: Although there have been numerous strategies to prevent motor vehicle collisions and their subsequent injuries, few have been effective in preventing motor vehicle injury claims. In this paper, we examine the role of legislation and compensation system in altering injury claim incidence. METHODS: The population base for our natural experiment was all Saskatchewan, Manitoba, British Columbia and Quebec residents who submitted personal injury claims to their respective motor vehicle insurance provider from 1990 to 1999. The provinces of Saskatchewan and Manitoba switched from Tort to pure No-Fault insurance on January 1, 1995 and on March 1, 1994 respectively. British Columbia maintained tort insurance and Quebec maintained pure no-fault insurance throughout the entire 10-year period. RESULTS: The conversion from tort insurance to pure no-fault motor vehicle insurance resulted in a five-year 31% (RR = 0.69; 95% CI 0.68-0.70) reduction in total injury claims per 100,000 residents in Saskatchewan and a five-year 43% (RR = 0.57; 95% CI 0.56-0.58) reduction in Manitoba. At the same time, the province of British Columbia retained tort insurance and had a five-year 5% reduction (RR = 0.95; 95% CI 0.94-0.99). Quebec, which retained pure no-fault throughout the entire 10-year period, had less than one third of the injury claims per 100,000 residents than the tort province of British Columbia. INTERPRETATION: The conversion from tort to pure no-fault legislation has a large influence in reducing motor vehicle injury claim incidence in Canada. Legislative system and injury compensation scheme have an observable impact on injury claim incidence and can therefore have significant impact on the health care system.