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Summary: Awareness of the prevalence of osteoporosis and fractures across jurisdictions can guide the development of local preventive programs and healthcare policies. We observed geographical variations in total hip bone mineral density and in the prevalence of major osteoporotic fractures across Canadian provinces, which persisted after adjusting for important covariates. Purpose: We aimed to describe sex-specific total hip bone mineral density (aBMD) and prevalent major osteoporotic fractures (MOF) variation between Canadian provinces. Methods: We used baseline data from 21,227 Canadians (10,716 women, 10,511 men) aged 50–85 years in the Canadian Longitudinal Study on Aging (CLSA; baseline: 2012–2015). Linear and logistic regression models were used to examine associations between province of residence and total hip aBMD and self-reported MOF, stratified by sex. CLSA sampling weights were used to generate the prevalence and regression estimates. Results: The mean (SD) age of participants was 63.9 (9.1) years. The mean body mass index (kg/m2) was lowest in British Columbia (27.4 [5.0]) and highest in Newfoundland and Labrador (28.8 [5.3]). Women and men from British Columbia had the lowest mean total hip aBMD and the lowest prevalence of MOF. Alberta had the highest proportion of participants reporting recent falls (12.0%), and Manitoba (8.4%) the fewest (p-value=0.002). Linear regression analyses demonstrated significant differences in total hip aBMD: women and men from British Columbia and Alberta, and women from Manitoba and Nova Scotia had lower adjusted total hip aBMD than Ontario (p-values<0.02). Adjusted odds ratios (95% confidence intervals, CI) for prevalent MOF were significantly lower in women from British Columbia (0.47 [95% CI: 0.32; 0.69]) and Quebec (0.68 [95% CI: 0.48; 0.97]) and in men from British Columbia (0.40 [95% CI:0.22; 0.71]) compared to Ontario (p-values<0.03). Results were similar when adjusting for physical performance measures and when restricting the analyses to participants who reported White race/ethnicity. Conclusion: Geographical variations in total hip aBMD and in the prevalence of MOF between provinces persisted after adjusting for important covariates which suggests an association with unmeasured individual and environmental factors. [ABSTRACT FROM AUTHOR]

Summary: Prior non-vertebral fractures, except of the ankle, are associated with increased likelihood of vertebral fracture. As knowledge of vertebral fracture presence may alter care, vertebral fracture assessment (VFA) is indicated in patients with prior fracture. Introduction: Vertebral fractures are often unappreciated. It was recently advocated that all Fracture Liaison Service (FLS) patients have densitometric VFA performed. We evaluated the likelihood of vertebral fracture identification with VFA in patients with prior fracture using the Manitoba Bone Density database. Methods : VFA was performed in patients with T-scores below − 1.5 and age 70 + (or younger with height loss or glucocorticoid use) obtaining bone densitometry in Manitoba from 2010 to 2018. Those with prior clinical vertebral fracture, pathologic fracture, or uninterpretable VFA were excluded. Vertebral fractures were identified using the modified ABQ method. Health records were assessed for non-vertebral fracture (excluding head, neck, hand, foot) diagnosis codes unassociated with trauma prior to DXA. Multivariable odds ratios (ORs) for vertebral fracture were estimated without and with adjustment for age, sex, body mass index, ethnicity, area of residence, income level, comorbidity score, diabetes mellitus, falls in the last year, glucocorticoid use, and lowest BMD T-score. Results: The study cohort consisted of 12,756 patients (94.4% women) with mean (SD) age 75.9 (6.8) years. Vertebral fractures were identified in 1925 (15.1%) overall. Vertebral fractures were significantly more likely (descending order) in those with prior pelvis, hip, humerus, other sites, and forearm, but not ankle fracture. There was modest attenuation with covariate adjustment but statistical significance was maintained. Conclusions: Prior hip, humerus, pelvis, forearm, and other fractures are associated with an increased likelihood of previously undiagnosed vertebral fracture, information useful for risk stratification and monitoring. These data support recommending VFA in FLS patients who are age 70 + with low BMD. [ABSTRACT FROM AUTHOR]

Summary : Fractures are associated with increased long-term mortality in patients surviving to undergo baseline DXA. Notably, excess mortality risk does not decline with increasing time since prior hip or humerus fractures, even after accounting for comorbid medical conditions and other risk factors. Introduction: Mortality risk increases following most types of fracture. In routine clinical practice, patients with prior fractures seen for dual-energy X-ray absorptiometry scan (DXA) are "survivors;" whether they remain at increased mortality risk is unknown. We tested the association between prior fracture and all-cause mortality, stratified by time since fracture, in patients undergoing baseline DXA. Methods: We conducted a DXA registry-based cohort study and linked to population-based health services data for the Province of Manitoba, Canada. We identified women and men ≥ 40 years with minimum 10 years of prior healthcare coverage undergoing baseline DXA and ascertained prior fracture codes since 1984 and mortality to 2017. Time since prior fracture was calculated between the clinical encounter for the fracture and baseline DXA (index date). Cox proportional hazards models estimated hazard ratios for all-cause mortality in those with compared to those without prior fracture adjusted for (1) age and sex, and (2) age, sex, comorbidities, and other covariates. Results: The study cohort consisted of 74,474 individuals (mean age 64.6 years, 89.7% female). During mean follow-up 9.2 years, we ascertained 14,923 (20.0%) deaths. Except for forearm fractures, all fracture sites were associated with increased mortality risk compared to those without prior fracture, even after multivariable adjustment. Excess mortality risk tended to decline slightly with time since fracture and was no longer significant > 10 years after vertebral fracture. However, excess mortality persisted > 10 years following hip or humerus fracture. Conclusions: Prior fractures are associated with increased long-term mortality in patients surviving to undergo baseline DXA. Excess mortality risk does not decline with time since prior hip or humerus fractures, after accounting for potential confounders. Fracture prevention may have important long-term benefits preserving life expectancy. [ABSTRACT FROM AUTHOR]

Summary: The G arvan Fracture Risk Calculator predicts risk of osteoporotic fractures. We evaluated its predictive performance in 16,682 women and 2839 men from Manitoba, Canada, and found significant risk stratification, with a strong gradient across scores. The tool outperformed clinical risk factors and bone mineral density for fracture risk stratification. Introduction: The optimal model for fracture risk estimation to guide treatment decision-making remains controversial. Our objective was to evaluate the predictive performance of the Garvan Fracture Risk Calculator (FRC) in a large clinical registry from Manitoba, Canada. Methods: Using the population-based Manitoba Bone Mineral Density (BMD) registry, we identified women and men aged 50–95 years undergoing baseline BMD assessment from September 1, 2012, onwards. Five-year Garvan FRC predictions were generated from clinical risk factors (CRFs) with and without femoral neck BMD. We identified incident non-traumatic osteoporotic fractures (OFs) and hip fractures (HFs) from population-based healthcare data sources to March 31, 2018. Fracture risk was assessed from area under the receiver operating characteristic curve (AUROC). Cox regression analysis and calibration ratios (5-year observed/predicted) were assessed for risk quintiles. All analyses were sex stratified. Results: We included 16,682 women (mean age 66.6 + / − SD 8.7 years) and 2839 men (mean age 68.7 + / − SD 10.2 years). During a mean observation time of 2.6 years, incident OFs were identified in 681 women and 140 men and HFs in 199 women and 22 men. AUROC showed significant fracture risk stratification with the Garvan FRC. Tool predictions without BMD were better than from age or decreasing weight, and the tool with BMD performed better than BMD alone. Garvan FRC with BMD performed better than without BMD, especially for HF prediction (AUROC 0.86 in women, 0.82 in men). There was a strong gradient of increasing risk across Garvan FRC quintiles (highest versus lowest, hazard ratios women 5.75 and men 3.43 for any OF; women 101.6 for HF). Calibration differences were noted, with both over- and underestimation in risk. Conclusions: Garvan FRC outperformed CRFs and BMD alone for fracture risk stratification, particularly for HF, but may require recalibration for accurate predictions in this population. [ABSTRACT FROM AUTHOR]

Summary: We analyzed patterns in recurrent major osteoporotic fracture (MOF) following a first major osteoporotic fracture in a large population-based cohort. Re-fracture risk remained elevated over 10 years, with only modest and inconsistent attenuation in risk over time. Introduction: Recurrent fracture risk remains elevated for up to 25 years, and is reportedly highest in the initial 2 years (imminent risk). Our aim was to characterize early time dependency in re-fracture rates up to 10 years after a first fracture in a population-based cohort. Methods: Using Province of Manitoba (Canada) healthcare databases, we performed a matched cohort study in 22,105 women (mean age 74.1 ± 10.6 years) and 7589 men (mean age 71.8 ± 11.2 years) after a first MOF (age ≥ 50 years) during 1989–2006 and matched fracture-free controls (3 for each case). Incident fractures were ascertained over the next 10 years. Fracture rate ratios (RRs, cases versus controls) stratified by sex and age were computed, and tested for linear trend using linear regression. Joinpoint regression was performed to determine non-linear change in fracture rates over time, with particular attention to the first 2-year post-fracture. Results: RRs for incident MOF and hip fracture exceeded unity for the primary analyses in all subgroups and follow-up intervals. There was a tendency of RRs to decline over time, but this was inconsistent. Absolute rates per 100,000 person-years for fracture cases were consistently greater than for controls in all subgroups and observation times. Among fracture cases, there was a tendency for rates to decline gradually in all subgroups except younger women, but these temporal trends appeared monotonic without an inflection at 2 years. Joinpoint regression analyses did not detect an inflection in risk between the first 2 years and subsequent years. No significant time dependency was seen for incident hip fracture. Conclusions: MOF and hip re-fracture risk was elevated in all age and sex subgroups over 10 years. There was inconsistent and only modest time dependency in early MOF risk, most evident in women after age 65 years. No strong transition in risk was seen between the first 2-year post-fracture and subsequent years. [ABSTRACT FROM AUTHOR]

Summary: The risk of subsequent major osteoporotic and hip fracture following an initial fracture was increased in both sexes over 25 years, with modest time-dependent attenuation. This risk was highest in men, underscoring the importance of targeted treatment strategies particularly in this under-treated population. Introduction: The risk of subsequent fractures is increased following an index fracture, and declines over time. We aimed to determine whether this risk was sustained over 25 years and evolved similarly in men and women. Methods: Using population-based databases, we performed a matched cohort study in 16,876 men and 39,230 women ≥ 50 years who sustained an index fracture during 1989–2006. Rates of subsequent major osteoporotic fractures (MOF) and hip fractures until 2016 were compared to rates for matched controls (n = 160,983). Age- and sex-stratified cumulative incidences to 25 years were estimated in the presence of competing mortality. Hazard ratios (HRs) with 95% confidence intervals (CI) for subsequent fractures were estimated for each on the first 15 years of follow-up with a final category ≥ 15 years, adjusted for comorbidities. Results: Risk for MOF and hip fractures remained elevated up to 25 years in both sexes. The cumulative incidence of fractures was higher in cases vs controls in both sexes and across all age categories except in those > 90 years. Crude rate ratios for subsequent MOF were 2.5 (95% CI 2.3–2.7) in men and 1.6 (95% CI 1.6–1.7) in women and were higher in the younger age groups. Adjusted HRs (aHRs) for subsequent MOF were higher in men than in women in the first year (men aHR 2.6, 95% CI 2.1–3.3; women aHR 1.6, 95% CI 1.4–1.7). Conclusions: The risk of subsequent fractures following an initial fracture was increased over 25 years and the magnitude of risk was initially greater in men than in women. [ABSTRACT FROM AUTHOR]

Summary: This registry-based cohort study assessed the percentage of women with prior or incident fracture who had normal bone defined as a normal bone mineral density T-score and normal trabecular bone score (TBS). Inclusion of TBS reduced the percentage with normal bone. Normal bone measurement is rare in women with fracture. Introduction: Some fractures occur in women with normal BMD. We hypothesized that adding trabecular bone score (TBS) to DXA would (1) demonstrate that few women with fracture have normal bone, i.e., normal BMD T-score and TBS and (2) increase the percentage of women with fracture that have abnormal bone defined as a BMD T-score ≤ − 2.5 or low TBS. Methods: The public healthcare system in Manitoba, Canada, makes it possible to link clinical DXA data to population databases. This study included all women age 50+ with a first DXA from February 1999 to March 2018 with valid BMD, TBS, and fracture data. Bone status was defined as Normal = BMD T-score of the spine, femoral neck, and total femur ≥ − 1.0 AND TBS > 1.31; Abnormal = BMD T-score ≤ − 2.5 OR TBS < 1.23; and borderline = all others. Analyses were stratified by age decade. Results: Among women with prior (n = 4649) or incident (n = 2547) fracture, bone status assessed by both BMD and TBS was normal in only 6% and 4%, respectively. In women with prior or incident hip fracture, normal bone was present in < 1%. The prevalence of normal bone declined (p trend < 0.001) with age as expected. BMD T-score osteoporosis was present in 40% with any prior and 46% with any incident fracture. BMD T-score osteoporosis was present in 65% and 60% with prior and incident hip fracture, respectively. Including TBS with BMD increased the percentage of women with abnormal bone to 61% and 68% for any prior or incident fracture and to 80% and 81% for prior or incident hip fracture, respectively (all p < 0.001). Conclusion: Including TBS with BMD increases identification of abnormal bone in women with fracture compared with BMD alone. Normal bone is present in < 6% of women with any fracture and < 1% of those with hip fracture. What is thought to be normal bone in women with fracture is rarely normal. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were (1) to assess the prevalence of ultrasound (US) features of adenomyosis in an infertile population undergoing in-vitro fertilization (IVF), (2) to define the inter- and intrarater agreement of three-dimensional (3D) US assessment of adenomyosis, and (3) to evaluate sonographic features of adenomyosis with respect to pregnancy outcome following transfer of a single thawed euploid blastocyst.Methods: This was a prospective cohort study. Subjects scheduled to undergo a single thawed euploid blastocyst transfer between April and December 2017 at a large IVF center were eligible for inclusion. Enrolled subjects underwent endometrial preparation for frozen embryo transfer. 3D-US was performed on the day prior to embryo transfer, with images stored for subsequent evaluation. Subjects then underwent transfer of a single thawed euploid blastocyst, and pregnancy outcomes were collected. All 3D-US volumes were de-identified and reviewed independently by five reproductive endocrinologists/infertility specialists with expertise in gynecological US for the presence of seven sonographic features of adenomyosis: global uterine enlargement, myometrial wall asymmetry, heterogeneous echogenicity, irregular junctional zone, myometrial cysts, fan-shaped shadowing and ill-defined myometrial lesions. Adenomyosis was considered to be present if the majority of the reviewers noted at least one of the seven sonographic features. Inter- and intrarater agreement was evaluated using Fleiss's kappa. Clinical and cycle characteristics of subjects with and those without adenomyosis were compared. The primary outcome of interest was live birth rate. Secondary outcomes included clinical pregnancy rate and miscarriage rate. Logistic regression analysis was performed to account for potential confounders.Results: A total of 648 subjects were included. The prevalence of adenomyosis on US was 15.3% (99/648). On retrospective chart review, very few patients with adenomyosis had symptoms. The inter- and intrarater agreement amongst five independent specialists conducting the 3D-US assessments of adenomyosis were poor (κ = 0.23) and moderate (κ = 0.58), respectively. Subjects with adenomyosis were older (37.1 vs 35.9 years, P = 0.02) and more likely to undergo a gonadotropin-releasing hormone agonist downregulation protocol when compared with those without adenomyosis (12.1% vs 5.1%, P = 0.02). Clinical pregnancy (80.0% vs 75.0%) and live birth (69.5% vs 66.5%) rates were similar between the groups. When adjusting for potential confounders, there was no difference in the rate of clinical pregnancy (adjusted odds ratio (aOR), 1.47 (95% CI, 0.85-2.56)), miscarriage (aOR, 1.3 (95% CI, 0.62-2.72)) or live birth (aOR, 1.28 (95% CI, 0.78-2.08)) between subjects with and those without adenomyosis. No individual sonographic marker of adenomyosis was predictive of pregnancy outcome.Conclusions: The inter-rater agreement of 3D-US assessment of adenomyosis is poor. Furthermore, sonographic markers of adenomyosis in asymptomatic patients may not be associated with altered pregnancy outcome following transfer of a single thawed euploid blastocyst. These findings suggest that routine screening for asymptomatic adenomyosis in an unselected infertile patient population undergoing frozen embryo transfer may not be warranted. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Study Question: Do supraphysiologic estradiol (E2) levels in the ranges attained during normal and high response superovulation cycles modify the onset of endometrial secretory transformation?Summary Answer: Highly supraphysiologic levels of E2 do not alter the ability of physiologic levels of progesterone (P4) to induce secretory transformation.What Is Known Already: Previous studies have demonstrated that premature P4 elevations during IVF cycles are associated with a decrement in clinical pregnancy rates after fresh embryo transfer due to shifts in the window of implantation (WOI). However, alterations in the onset of secretory transformation may not apply uniformly to all patients. High responders with supraphysiologic E2 levels accompanied by similar subtle increases in P4 have not been shown to have decreased sustained implantation rates. This prospective investigation in which whole-genome transcriptomic and methylomic analysis of the endometrium is performed for individual patients under a range of E2 concentrations brings clarity to a long-debated issue.Study Design, Size, Duration: A randomized, prospective and paired trial was conducted in which 10 participants were enrolled and randomized to the order in which they completed three distinct uterine stimulation cycles, each at a specific E2 concentration: physiologic (∼180 pg/ml), moderately supraphysiologic (600-800 pg/ml) or supraphysiologic (2000 pg/ml). Target E2 ranges were selected to mimic those seen in natural, controlled ovarian stimulation and IVF cycles. E2 valerate was administered in order to maintain stable E2 levels for 12 days followed by intramuscular P4 in oil 10 mg/day for two doses, after which an endometrial biopsy was performed. A total of 30 endometrial biopsies were included in a whole-genome transcriptomic and methylomic analysis.Participants/materials, Setting, Methods: Healthy volunteers without a history of infertility were included in this study at a single large infertility center. DNA was isolated from the endometrial biopsy specimens and bisulfite sequencing was performed to construct a methylation array. Differential methylation analysis was conducted based on differences in M-values of individuals across treatment groups for each probe as well as carrying out t-tests. RNA was isolated for RNA-Seq analysis and gene expression values were compared using DESeq2. All analyses were performed in a pairwise fashion to compare among the three stimulation cycles within individuals and secondarily to compare all participants in each of the cycles.Main Results and the Role Of Chance: The mean peak E2 and P4 levels were 275 pg/ml and 4.17 ng/ml in the physiologic group, 910 pg/ml and 2.69 ng/ml in the moderate group was, and 2043 pg/ml and 2.64 ng/ml in the supraphysiologic group, respectively. Principal component analysis of 834 913 CpG sites was performed on M-values of individuals within the low, moderate and supraphysiologic conditions in a paired approach. There were no differences in genome-wide methylation within participants across E2 groups. A paired analysis revealed that gene expression profiles did not differ within the same individual at each of the three E2 levels. No significant alterations in gene expression as related to endometrial physiology were identified between the low, moderate and supraphysiologic groups in an inter-participant analysis.Limitations, Reasons For Caution: Although each participant completed a physiologic cycle in which E2 levels were maintained in a range that would simulate a natural cycle, our findings are limited by lack of an unmedicated control to assess if there was a potential effect from E2V. Additionally, our results were obtained in fertile individuals, who may have a different endometrial response compared to an infertile population. Despite the whole genomic endometrial assessment and rigorous, paired study design, the sample size was limited.Wider Implications Of the Findings: Given that the endometrial response to P4 is unaffected by E2 levels in the supraphysiologic range, diminutions in implantation seen in stimulated cycles may result from embryonic-endometrial dyssynchrony following early P4 elevations or slowly blastulating embryos, which occur independently of the magnitude of the E2 rise.Study Funding/competing Interest(s): This study was funded by the Foundation for Embryonic Competence, Basking Ridge, NJ, USA. Dr E.S. reports consultancy work for The Foundation for Embryonic Competence, Basking Ridge, NJ, USA. The other authors declare no conflict of interests related to this topic.Trial Registration Number: NCT02458404. [ABSTRACT FROM AUTHOR]

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

Summary: Prior high-trauma fractures identified through health services data are associated with low bone mineral density (BMD) and future fracture risk to the same extent as fractures without high-trauma. Introduction: Some have questioned the usefulness of distinguishing high-trauma fractures from low-trauma fractures. The aim of this study is to compare BMD measurements and risk of subsequent low-trauma fracture in patients with prior high- or low-trauma fractures. Methods: Using a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40 years or older with fracture records from linked population-based healthcare data. Age- and sex-adjusted BMD Z-scores and covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CI) for incident fracture were studied in relation to prior fracture status, categorized as high-trauma if associated with external injury codes and low-trauma otherwise. Results: The study population consisted of 64,428 women and men with no prior fracture (mean age 63.7 years), 858 with prior high-trauma fractures (mean age 65.1 years), and 14,758 with prior low-trauma fractures (mean age 67.2 years). Mean Z-scores for those with any prior high-trauma fracture were significantly lower than in those without prior fracture (P < 0.001) and similar to those with prior low-trauma fracture. Median observation time for incident fractures was 8.8 years (total 729,069 person-years). Any prior high-trauma fracture was significantly associated with increased risk for incident major osteoporotic fracture (MOF) (adjusted HR 1.31, 95% CI 1.08–1.59) as was prior low-trauma fracture (adjusted HR 1.55, 95% CI 1.47–1.63), and there was no significant difference between the two groups (prior trauma versus low-trauma fracture P = 0.093). A similar pattern was seen when incident MOF was studied in relation to prior hip fracture or prior MOF, or when the outcome was incident hip fracture or any incident fracture. Conclusions: High-trauma and low-trauma fractures showed similar relationships with low BMD and future fracture risk. This supports the inclusion of high-trauma fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk. [ABSTRACT FROM AUTHOR]

Summary: We previously found that population-based postfracture notification, which informed primary care physicians of their patient's recent fracture and suggested assessment for osteoporosis, led to an improvement in postfracture care in the context of a randomized controlled trial (ClinicalTrials.gov identifier NCT00594789, fractures from late 2007 to mid-2010). Since June 2010, a province-wide postfracture notification program was implemented. This study was to (1) determine whether this program has resulted in sustained improvement in postfracture care and (2) test factors associated with receiving osteoporosis care. Methods: A retrospective matched cohort study was performed using population-based health administrative data in Manitoba, Canada. We selected individuals aged 50+ years with an incident major osteoporosis fracture (MOF; N = 18,541) in fiscal years 2000/2001 to 2013/2014 and controls without a MOF (N = 92,705) matched (5:1) on age, sex, and residential area. The Cochran-Armitage test tested for a linear trend in osteoporosis care outcomes for cases and controls. Logistic regressions were used to test characteristics associated with the likelihood of receiving osteoporosis care. Results: The percentage of individuals receiving DXA testing and/or osteoporosis medication increased in fracture cases (p < 0.001), but decreased in controls (p < 0.001). Odds ratios for osteoporosis care in years following the postfracture notification program were approximately double of those prior to the clinical trial. In addition to prior MOF (OR 9.03, 95% CI 8.60–9.48), factors associated with osteoporosis care included lower income (OR 0.72, 95% CI 0.67–0.78), glucocorticoid use (OR 4.37, 95% CI 3.72–5.14), diabetes diagnosis (OR = 0.74, 95% CI 0.68–0.80), and Charlson Comorbidity Index (indexes 1–2: OR 1.27, 95% CI 1.20–1.34; indexes 3–5: OR 1.26, 95% CI 1.13–1.40). Conclusions: Adopting a population-based postfracture notification program led to sustained improvements in postfracture care. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]