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Cognitive decline and osteoporosis often coexist and some evidence suggests a causal link. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging. This study aimed to determine the association between: (i) cognitive decline and bone loss; and (ii) clinically significant cognitive decline (≥3 points) on Mini Mental State Examination (MMSE) over the first 5 years and subsequent fracture risk over the following 10 years. A total of 1741 women and 620 men aged ≥65 years from the population-based Canadian Multicentre Osteoporosis Study were followed from 1997 to 2013. Association between cognitive decline and (i) bone loss was estimated using mixed-effects models; and (ii) fracture risk was estimated using adjusted Cox models. Over 95% of participants had normal cognition at baseline (MMSE ≥ 24). The annual % change in MMSE was similar for both genders (women -0.33, interquartile range [IQR] -0.70 to +0.00; and men -0.34, IQR: -0.99 to 0.01). After multivariable adjustment, cognitive decline was associated with bone loss in women (6.5%; 95% confidence interval [CI], 3.2% to 9.9% for each percent decline in MMSE from baseline) but not men. Approximately 13% of participants experienced significant cognitive decline by year 5. In women, fracture risk was increased significantly (multivariable hazard ratio [HR], 1.61; 95% CI, 1.11 to 2.34). There were too few men to analyze. There was a significant association between cognitive decline and both bone loss and fracture risk, independent of aging, in women. Further studies are needed to determine mechanisms that link these common conditions. © 2021 American Society for Bone and Mineral Research (ASBMR).

Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current under-management of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and consequences. The study involved 8965 people aged ≥60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death ascertained though contact with a family member or obituary review. We used multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture, and mortality, accounting for their complex inter-relationships, confounding effects and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow up of 13 years (IQR: 7, 15). The prediction model included gender, age, BMD, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension and cancer. The model accurately predicted fragility fractures up to 11 years of follow up, and post-fracture mortality up to 9 years, ranging from 7 years following hip fractures to 15 years following non-hip fractures. For example, a 70-year old woman with a T-score of -1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% following a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualisation of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different ri

Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into

© 2019, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. Introduction: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. Methods: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. Results: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48–0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66–1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031–0.70)] for n-BP vs. etidronate]. Conclusion: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to

In this study, we report that self-perception of fracture risk captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is associated with improved medication uptake. It suggests that adequate appreciation of fracture risk may be beneficial and lead to greater healthcare engagement and treatment.IntroductionThis study aimed to assess how well self-perception of fracture risk, and fracture risk as estimated by the fracture prediction tool FRAX, related to fracture incidence and uptake and persistence of anti-osteoporosis medication among women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW).MethodsGLOW is an international cohort study involving 723 physician practices across 10 countries in Europe, North America and Australia. Aged ≥ 55 years, 60,393 women completed baseline questionnaires detailing medical history, including co-morbidities, fractures and self-perceived fracture risk (SPR). Annual follow-up included self-reported incident fractures and anti-osteoporosis medication (AOM) use. We calculated FRAX risk without bone mineral density measurement.ResultsOf the 39,241 women with at least 1 year of follow-up data, 2132 (5.4%) sustained an incident major osteoporotic fracture over 5 years of follow-up. Within each SPR category, risk of fracture increased as the FRAX categorisation of risk increased. In GLOW, only 11% of women with a lower baseline SPR were taking AOM at baseline, compared with 46% of women with a higher SPR. AOM use tended to increase in the years after a reported fracture. However, women with a lower SPR who were fractured still reported lower AOM rates than women with or without a fracture but had a higher SPR.ConclusionsThese results suggest that SPR captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is also associated with improved medication uptake.

IntroductionRheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures.MethodsUsing the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibl

© 2017 American Society for Bone and Mineral Research Data on long-term consequences of non-hip non-vertebral (NHNV) fractures, accounting for approximately two-thirds of all fragility fractures, are scanty. Our study aimed to quantify the population-wide impact of NHNV fractures on mortality. The national population-based prospective cohort study (Canadian Multicentre Osteoporosis Study) included 5526 community dwelling women and 2163 men aged 50 years or older followed from July 1995 to September 2013. Population impact number was used to quantify the average number of people for whom one death would be attributable to fracture and case impact number to quantify the number of deaths out of which one would be attributable to a fracture. There were 1370 fragility fractures followed by 296 deaths in women (mortality rate: 3.49; 95% CI, 3.11 to 3.91), and 302 fractures with 92 deaths in men (5.05; 95% CI, 4.12 to 6.20). NHNV fractures accounted for three-quarters of fractures. In women, the population-wide impact of NHNV fractures on mortality was greater than that of hip and vertebral fractures because of the greater number of NHNV fractures. Out of 800 women, one death was estimated to be attributable to a NHNV fracture, compared with one death in 2000 women attributable to hip or vertebral fracture. Similarly, out of 15 deaths in women, one was estimated to be attributable to a NHNV fracture, compared with one in over 40 deaths for hip or vertebral fracture. The impact of forearm fractures (ie, one death in 2400 women and one out of 42 deaths in women attributable to forearm fracture) was similar to that of hip, vertebral, or rib fractures. Similar, albeit not significant, results were noted for men. The study highlights the important contribution of NHNV fractures on mortality because many NHNV fracture types, except for the most distal fractures, have serious adverse consequences that affect a significant proportion of the population. © 2017 American Society for

IntroductionRheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures.MethodsUsing the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibl

In this study, we report that self-perception of fracture risk captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is associated with improved medication uptake. It suggests that adequate appreciation of fracture risk may be beneficial and lead to greater healthcare engagement and treatment.IntroductionThis study aimed to assess how well self-perception of fracture risk, and fracture risk as estimated by the fracture prediction tool FRAX, related to fracture incidence and uptake and persistence of anti-osteoporosis medication among women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW).MethodsGLOW is an international cohort study involving 723 physician practices across 10 countries in Europe, North America and Australia. Aged ≥ 55 years, 60,393 women completed baseline questionnaires detailing medical history, including co-morbidities, fractures and self-perceived fracture risk (SPR). Annual follow-up included self-reported incident fractures and anti-osteoporosis medication (AOM) use. We calculated FRAX risk without bone mineral density measurement.ResultsOf the 39,241 women with at least 1 year of follow-up data, 2132 (5.4%) sustained an incident major osteoporotic fracture over 5 years of follow-up. Within each SPR category, risk of fracture increased as the FRAX categorisation of risk increased. In GLOW, only 11% of women with a lower baseline SPR were taking AOM at baseline, compared with 46% of women with a higher SPR. AOM use tended to increase in the years after a reported fracture. However, women with a lower SPR who were fractured still reported lower AOM rates than women with or without a fracture but had a higher SPR.ConclusionsThese results suggest that SPR captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is also associated with improved medication uptake.

UnlabelledAccurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles.IntroductionWe compared self-perceived fracture risk and 3-year incident fracture rates in postmenopausal women with a range of morbidities in the Global Longitudinal study of Osteoporosis in Women (GLOW).MethodsGLOW is an international cohort study involving 723 physician practices across ten countries (Europe, North America, Australasia); 60,393 women aged ≥55 years completed baseline questionnaires detailing medical history and self-perceived fracture risk. Annual follow-up determined self-reported incident fractures.ResultsIn total 2,945/43,832 (6.8%) sustained an incident fracture over 3 years. All morbidities were associated with increased fracture rates, particularly Parkinson's disease (hazard ratio [HR]; 95% confidence interval [CI], 3.89; 2.78-5.44), multiple sclerosis (2.70; 1.90-3.83), cerebrovascular events (2.02; 1.67-2.46), and rheumatoid arthritis (2.15; 1.53-3.04) (all p < 0.001). Most individuals perceived their fracture risk as similar to (46%) or lower than (36%) women of the same age. While increased self-perceived fracture risk was strongly associated with incident fracture rates, only 29% experiencing a fracture perceived their risk as increased. Under-appreciation of fracture risk occurred for all morbidities, including neurological disease, where women with low self-perceived fracture risk had a fracture HR 2.39 (CI 1.74-3.29) compared with women without morbidities.ConclusionsPostmenopausal women with morbidities tend to under-appreciate their risk, including in the context of neurological diseases, where fracture rates were highest in this cohort. This has important implications for health education, particularly among women with Parkinson's disease, multiple sclerosis, or cerebrovascular disease.

UnlabelledAccurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles.IntroductionWe compared self-perceived fracture risk and 3-year incident fracture rates in postmenopausal women with a range of morbidities in the Global Longitudinal study of Osteoporosis in Women (GLOW).MethodsGLOW is an international cohort study involving 723 physician practices across ten countries (Europe, North America, Australasia); 60,393 women aged ≥55 years completed baseline questionnaires detailing medical history and self-perceived fracture risk. Annual follow-up determined self-reported incident fractures.ResultsIn total 2,945/43,832 (6.8%) sustained an incident fracture over 3 years. All morbidities were associated with increased fracture rates, particularly Parkinson's disease (hazard ratio [HR]; 95% confidence interval [CI], 3.89; 2.78-5.44), multiple sclerosis (2.70; 1.90-3.83), cerebrovascular events (2.02; 1.67-2.46), and rheumatoid arthritis (2.15; 1.53-3.04) (all p < 0.001). Most individuals perceived their fracture risk as similar to (46%) or lower than (36%) women of the same age. While increased self-perceived fracture risk was strongly associated with incident fracture rates, only 29% experiencing a fracture perceived their risk as increased. Under-appreciation of fracture risk occurred for all morbidities, including neurological disease, where women with low self-perceived fracture risk had a fracture HR 2.39 (CI 1.74-3.29) compared with women without morbidities.ConclusionsPostmenopausal women with morbidities tend to under-appreciate their risk, including in the context of neurological diseases, where fracture rates were highest in this cohort. This has important implications for health education, particularly among women with Parkinson's disease, multiple sclerosis, or cerebrovascular disease.

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

UnlabelledThe Committee of Scientific Advisors of International Osteoporosis Foundation (IOF) recommends that papers describing the descriptive epidemiology of osteoporosis using bone mineral density (BMD) at the femoral neck include T-scores derived from an international reference standard.IntroductionThe prevalence of osteoporosis as defined by the T-score is inconsistently reported in the literature which makes comparisons between studies problematic.MethodsThe Epidemiology and Quality of Life Working Group of IOF convened to make its recommendations and endorsement sought thereafter from the Committee of Scientific Advisors of IOF.ResultsThe Committee of Scientific Advisors of IOF recommends that papers describing the descriptive epidemiology of osteoporosis using BMD at the femoral neck include T-scores derived from the National Health and Nutrition Examination Survey III reference database for femoral neck measurements in Caucasian women aged 20-29 years.ConclusionsIt is expected that the use of the reference standard will help resolve difficulties in the comparison of results between studies and the comparative assessment of new technologies.

Objective: To examine when, where and how fractures occur in postmenopausal women. Methods: We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3. Results: Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling. Conclusion: In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year. © 2013 Costa et al.

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

Objective: To examine when, where and how fractures occur in postmenopausal women. Methods: We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3. Results: Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling. Conclusion: In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year. © 2013 Costa et al.

UnlabelledAmong 50,461 postmenopausal women, 1,822 fractures occurred (57% minor non-hip, non-vertebral [NHNV], 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D, followed by major NHNV and hip fractures. Decreases in physical function and health status were greatest for spine or hip fractures.IntroductionThere is growing evidence that NHNV fractures result in substantial morbidity and healthcare costs. The aim of this prospective study was to assess the effect of these NHNV fractures on quality of life.MethodsWe analyzed the 1-year incidences of hip, spine, major NHNV (pelvis/leg, shoulder/arm) and minor NHNV (wrist/hand, ankle/foot, rib/clavicle) fractures among women from the Global Longitudinal study of Osteoporosis in Women (GLOW). Health-related quality of life (HRQL) was analyzed using the EuroQol EQ-5D tool and the SF-36 health survey.ResultsAmong 50,461 women analyzed, there were 1,822 fractures (57% minor NHNV, 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D summary scores, followed by major NHNV and hip fractures. The number of women with mobility problems increased most for those with major NHNV and spine fractures (both +8%); spine fractures were associated with the largest increases in problems with self care (+11%), activities (+14%), and pain/discomfort (+12%). Decreases in physical function and health status were greatest for those with spine or hip fractures. Multivariable modeling found that EQ-5D reduction was greatest for spine fractures, followed by hip and major/minor NHNV. Statistically significant reductions in SF-36 physical function were found for spine fractures, and were borderline significant for major NHNV fractures.ConclusionThis prospective study shows that NHNV fractures have a detrimental effect on HRQL. Efforts to optimize the care of osteoporosis patients should include the prevention of NHNV fractures.

UnlabelledWe examined variations in proportions of hip fractures and major fractures among postmenopausal women using the Global Longitudinal Study of Osteoporosis in Women (GLOW). The proportion of major fractures that were hip fractures varied with age and region, whereas variations in the proportion of fractures that were major fractures appeared modest.IntroductionIn many countries, the World Health Organization fracture risk assessment tool calculates the probability of major fractures by assuming a uniform age-associated proportion of major fractures that are hip fractures in different countries. We further explored this assumption, using data from the GLOW.MethodsGLOW is an observational population-based study of 60,393 non-institutionalized women aged ≥55 years who had visited practices within the previous 2 years. Main outcome measures were self-reported prevalent fractures after the age of 45 years and incident fractures during the 2 years of follow-up.ResultsThe adjusted proportion of prevalent and incident major fractures after the age of 45 years that were hip fractures was higher in North America (16%, 17%) than in northern (13%, 12%) and southern Europe (10%, 10%), respectively. The proportion of incident major fractures that were hip fractures increased more than five-fold with age, from 6.6% among 55-59-year-olds to 34% among those aged ≥85 years. Regional and age-associated variations in the proportion of all incident fractures that were major fractures were less marked, not exceeding 16% and 28%, respectively.ConclusionsThe data suggest that there may be regional differences in the proportion of major fractures that are hip fractures in postmenopausal women. In contrast, the regional and age-related variations in the proportion of fractures that are major fractures appear to be modest. However, because of the limited number of fractures in our sample, further studies are necessary to confirm these findings.

UNLABELLED: Guidelines concerning the definition of failure of therapies used to reduce the risk of fracture are provided. INTRODUCTION: This study aims to provide guidelines concerning the definition of failure of therapies used to reduce the risk of fracture. METHODS: A working group of the Committee of Scientific Advisors of the International Osteoporosis Foundation was convened to define outcome variables that may assist clinicians in decision making. RESULTS: In the face of limited evidence, failure of treatment may be inferred when two or more incident fractures have occurred during treatment, when serial measurements of bone remodelling markers are not suppressed by anti-resorptive therapy and where bone mineral density continues to decrease. CONCLUSION: The provision of pragmatic criteria to define failure to respond to treatment provides an unmet clinical need and may stimulate research into an important issue.

UnlabelledAmong 50,461 postmenopausal women, 1,822 fractures occurred (57% minor non-hip, non-vertebral [NHNV], 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D, followed by major NHNV and hip fractures. Decreases in physical function and health status were greatest for spine or hip fractures.IntroductionThere is growing evidence that NHNV fractures result in substantial morbidity and healthcare costs. The aim of this prospective study was to assess the effect of these NHNV fractures on quality of life.MethodsWe analyzed the 1-year incidences of hip, spine, major NHNV (pelvis/leg, shoulder/arm) and minor NHNV (wrist/hand, ankle/foot, rib/clavicle) fractures among women from the Global Longitudinal study of Osteoporosis in Women (GLOW). Health-related quality of life (HRQL) was analyzed using the EuroQol EQ-5D tool and the SF-36 health survey.ResultsAmong 50,461 women analyzed, there were 1,822 fractures (57% minor NHNV, 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D summary scores, followed by major NHNV and hip fractures. The number of women with mobility problems increased most for those with major NHNV and spine fractures (both +8%); spine fractures were associated with the largest increases in problems with self care (+11%), activities (+14%), and pain/discomfort (+12%). Decreases in physical function and health status were greatest for those with spine or hip fractures. Multivariable modeling found that EQ-5D reduction was greatest for spine fractures, followed by hip and major/minor NHNV. Statistically significant reductions in SF-36 physical function were found for spine fractures, and were borderline significant for major NHNV fractures.ConclusionThis prospective study shows that NHNV fractures have a detrimental effect on HRQL. Efforts to optimize the care of osteoporosis patients should include the prevention of NHNV fractures.

UnlabelledWe examined variations in proportions of hip fractures and major fractures among postmenopausal women using the Global Longitudinal Study of Osteoporosis in Women (GLOW). The proportion of major fractures that were hip fractures varied with age and region, whereas variations in the proportion of fractures that were major fractures appeared modest.IntroductionIn many countries, the World Health Organization fracture risk assessment tool calculates the probability of major fractures by assuming a uniform age-associated proportion of major fractures that are hip fractures in different countries. We further explored this assumption, using data from the GLOW.MethodsGLOW is an observational population-based study of 60,393 non-institutionalized women aged ≥55 years who had visited practices within the previous 2 years. Main outcome measures were self-reported prevalent fractures after the age of 45 years and incident fractures during the 2 years of follow-up.ResultsThe adjusted proportion of prevalent and incident major fractures after the age of 45 years that were hip fractures was higher in North America (16%, 17%) than in northern (13%, 12%) and southern Europe (10%, 10%), respectively. The proportion of incident major fractures that were hip fractures increased more than five-fold with age, from 6.6% among 55-59-year-olds to 34% among those aged ≥85 years. Regional and age-associated variations in the proportion of all incident fractures that were major fractures were less marked, not exceeding 16% and 28%, respectively.ConclusionsThe data suggest that there may be regional differences in the proportion of major fractures that are hip fractures in postmenopausal women. In contrast, the regional and age-related variations in the proportion of fractures that are major fractures appear to be modest. However, because of the limited number of fractures in our sample, further studies are necessary to confirm these findings.

UnlabelledWe compared self-perception of fracture risk with actual risk among 60,393 postmenopausal women aged ≥55 years, using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Most postmenopausal women with risk factors failed to appreciate their actual risk for fracture. Improved education about osteoporosis risk factors is needed.IntroductionThis study seeks to compare self-perception of fracture risk with actual risk among postmenopausal women using data from GLOW.MethodsGLOW is an international, observational, cohort study involving 723 physician practices in 17 sites in ten countries in Europe, North America, and Australia. Participants included 60,393 women ≥55 years attended by their physician during the previous 24 months. The sample was enriched so that two thirds were ≥65 years. Baseline surveys were mailed October 2006 to February 2008. Main outcome measures were self-perception of fracture risk in women with elevated risk vs women of the same age and frequency of risk factors for fragility fracture.ResultsIn the overall study population, 19% (10,951/58,434) of women rated their risk of fracture as a little/much higher than that of women of the same age; 46% (27,138/58,434) said it was similar; 35% (20,345/58,434) believed it to be a little/much lower. Among women whose actual risk was increased based on the presence of any one of seven risk factors for fracture, the proportion who recognized their increased risk ranged from 19% for smokers to 39% for current users of glucocorticoid medication. Only 33% (4,185/12,612) of those with ≥2 risk factors perceived themselves as being at higher risk. Among women reporting a diagnosis of osteopenia or osteoporosis, only 25% and 43%, respectively, thought their risk was increased.ConclusionIn this international, observational study, most postmenopausal women with risk factors failed to appreciate their actual risk for fracture.

UnlabelledWe compared self-perception of fracture risk with actual risk among 60,393 postmenopausal women aged ≥55 years, using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Most postmenopausal women with risk factors failed to appreciate their actual risk for fracture. Improved education about osteoporosis risk factors is needed.IntroductionThis study seeks to compare self-perception of fracture risk with actual risk among postmenopausal women using data from GLOW.MethodsGLOW is an international, observational, cohort study involving 723 physician practices in 17 sites in ten countries in Europe, North America, and Australia. Participants included 60,393 women ≥55 years attended by their physician during the previous 24 months. The sample was enriched so that two thirds were ≥65 years. Baseline surveys were mailed October 2006 to February 2008. Main outcome measures were self-perception of fracture risk in women with elevated risk vs women of the same age and frequency of risk factors for fragility fracture.ResultsIn the overall study population, 19% (10,951/58,434) of women rated their risk of fracture as a little/much higher than that of women of the same age; 46% (27,138/58,434) said it was similar; 35% (20,345/58,434) believed it to be a little/much lower. Among women whose actual risk was increased based on the presence of any one of seven risk factors for fracture, the proportion who recognized their increased risk ranged from 19% for smokers to 39% for current users of glucocorticoid medication. Only 33% (4,185/12,612) of those with ≥2 risk factors perceived themselves as being at higher risk. Among women reporting a diagnosis of osteopenia or osteoporosis, only 25% and 43%, respectively, thought their risk was increased.ConclusionIn this international, observational study, most postmenopausal women with risk factors failed to appreciate their actual risk for fracture.

Background: A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study predicts the five- and ten-year absolute risk of fracture using age, bone mineral density and history of falls and low-trauma fracture. We assessed the discrimination and calibration of these nomograms among participants in the Canadian Multicentre Osteoporosis Study. Methods: We included participants aged 55-95 years for whom bone mineral density measurement data and at least one year of follow-up data were available. Self-reported incident fractures were identified by yearly postal questionnaire or interview (years 3, 5 and 10). We included low-trauma fractures before year 10, except those of the skull, face, hands, ankles and feet. We used a Cox proportional hazards model. Results: Among 4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years. Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3 years. Increasing age, lower bone mineral density, prior fracture and prior falls were associated with increased risk of fracture. For low-trauma fractures, the concordance between predicted risk and fracture events (Harrell C) was 0.69 among women and 0.70 among men. For hip fractures, the concordance was 0.80 among women and 0.85 among men. The observed fracture risk was similar to the predicted risk in all quintiles of risk except the highest quintile of women, where it was lower. The net reclassification index (19.2%, 95% confidence interval [CI] 6.3% to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for men. Interpretation: The published nomograms provide good fracture-risk discrimination in a representative sample of the Canadian population. © 2011 Canadian Medical Association or its licensors.

Background: A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study predicts the five- and ten-year absolute risk of fracture using age, bone mineral density and history of falls and low-trauma fracture. We assessed the discrimination and calibration of these nomograms among participants in the Canadian Multicentre Osteoporosis Study. Methods: We included participants aged 55-95 years for whom bone mineral density measurement data and at least one year of follow-up data were available. Self-reported incident fractures were identified by yearly postal questionnaire or interview (years 3, 5 and 10). We included low-trauma fractures before year 10, except those of the skull, face, hands, ankles and feet. We used a Cox proportional hazards model. Results: Among 4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years. Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3 years. Increasing age, lower bone mineral density, prior fracture and prior falls were associated with increased risk of fracture. For low-trauma fractures, the concordance between predicted risk and fracture events (Harrell C) was 0.69 among women and 0.70 among men. For hip fractures, the concordance was 0.80 among women and 0.85 among men. The observed fracture risk was similar to the predicted risk in all quintiles of risk except the highest quintile of women, where it was lower. The net reclassification index (19.2%, 95% confidence interval [CI] 6.3% to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for men. Interpretation: The published nomograms provide good fracture-risk discrimination in a representative sample of the Canadian population. © 2011 Canadian Medical Association or its licensors.

Clinical risk factors are associated with increased probability of fracture in postmenopausal women. We sought to compare prediction models using self-reported clinical risk factors, excluding BMD, to predict incident fracture among postmenopausal women. The GLOW study enrolled women aged 55 years or older from 723 primary-care practices in 10 countries. The population comprised 19,586 women aged 60 years or older who were not receiving antiosteoporosis medication and were followed annually for 2 years. Self-administered questionnaires were used to collect data on characteristics, fracture risk factors, previous fractures, and health status. The main outcome measure compares the C index for models using the WHO Fracture Risk (FRAX), the Garvan Fracture Risk Calculator (FRC), and a simple model using age and prior fracture. Over 2 years, 880 women reported incident fractures including 69 hip fractures, 468 "major fractures" (as defined by FRAX), and 583 "osteoporotic fractures" (as defined by FRC). Using baseline clinical risk factors, both FRAX and FRC showed a moderate ability to correctly order hip fracture times (C index for hip fracture 0.78 and 0.76, respectively). C indices for "major" and "osteoporotic" fractures showed lower values, at 0.61 and 0.64. Neither algorithm was better than the model based on age + fracture history alone (C index for hip fracture 0.78). In conclusion, estimation of fracture risk in an international primary-care population of postmenopausal women can be made using clinical risk factors alone without BMD. However, more sophisticated models incorporating multiple clinical risk factors including falls were not superior to more parsimonious models in predicting future fracture in this population. © 2011 American Society for Bone and Mineral Research.

Clinical risk factors are associated with increased probability of fracture in postmenopausal women. We sought to compare prediction models using self-reported clinical risk factors, excluding BMD, to predict incident fracture among postmenopausal women. The GLOW study enrolled women aged 55 years or older from 723 primary-care practices in 10 countries. The population comprised 19,586 women aged 60 years or older who were not receiving antiosteoporosis medication and were followed annually for 2 years. Self-administered questionnaires were used to collect data on characteristics, fracture risk factors, previous fractures, and health status. The main outcome measure compares the C index for models using the WHO Fracture Risk (FRAX), the Garvan Fracture Risk Calculator (FRC), and a simple model using age and prior fracture. Over 2 years, 880 women reported incident fractures including 69 hip fractures, 468 "major fractures" (as defined by FRAX), and 583 "osteoporotic fractures" (as defined by FRC). Using baseline clinical risk factors, both FRAX and FRC showed a moderate ability to correctly order hip fracture times (C index for hip fracture 0.78 and 0.76, respectively). C indices for "major" and "osteoporotic" fractures showed lower values, at 0.61 and 0.64. Neither algorithm was better than the model based on age + fracture history alone (C index for hip fracture 0.78). In conclusion, estimation of fracture risk in an international primary-care population of postmenopausal women can be made using clinical risk factors alone without BMD. However, more sophisticated models incorporating multiple clinical risk factors including falls were not superior to more parsimonious models in predicting future fracture in this population. © 2011 American Society for Bone and Mineral Research.

SummaryThe Global Longitudinal study of Osteoporosis in Women (GLOW) is a prospective cohort study involving 723 physicians and 60,393 women subjects >or=55 years. The data will provide insights into the management of fracture risk in older women over 5 years, patient experience with prevention and treatment, and distribution of risk among older women on an international basis.IntroductionData from cohort studies describing the distribution of osteoporosis-related fractures and risk factors are not directly comparable and do not compare regional differences in patterns of patient management and fracture outcomes.MethodsThe GLOW is a prospective, multinational, observational cohort study. Practices typical of each region were identified through primary care networks organized for administrative, research, or educational purposes. Noninstitutionalized patients visiting each practice within the previous 2 years were eligible. Self-administered questionnaires were mailed, with 2:1 oversampling of women >or=65 years. Follow-up questionnaires will be sent at 12-month intervals for 5 years.ResultsA total of 723 physicians at 17 sites in ten countries agreed to participate. Baseline surveys were mailed (October 2006 to February 2008) to 140,416 subjects. After the exclusion of 3,265 women who were ineligible or had died, 60,393 agreed to participate.ConclusionsGLOW will provide contemporary information on patterns of management of fracture risk in older women over a 5-year period. The collection of data in a similar manner in ten countries will permit comparisons of patient experience with prevention and treatment and provide insights into the distribution of risk among older women on an international basis.

SummaryThe Global Longitudinal study of Osteoporosis in Women (GLOW) is a prospective cohort study involving 723 physicians and 60,393 women subjects >or=55 years. The data will provide insights into the management of fracture risk in older women over 5 years, patient experience with prevention and treatment, and distribution of risk among older women on an international basis.IntroductionData from cohort studies describing the distribution of osteoporosis-related fractures and risk factors are not directly comparable and do not compare regional differences in patterns of patient management and fracture outcomes.MethodsThe GLOW is a prospective, multinational, observational cohort study. Practices typical of each region were identified through primary care networks organized for administrative, research, or educational purposes. Noninstitutionalized patients visiting each practice within the previous 2 years were eligible. Self-administered questionnaires were mailed, with 2:1 oversampling of women >or=65 years. Follow-up questionnaires will be sent at 12-month intervals for 5 years.ResultsA total of 723 physicians at 17 sites in ten countries agreed to participate. Baseline surveys were mailed (October 2006 to February 2008) to 140,416 subjects. After the exclusion of 3,265 women who were ineligible or had died, 60,393 agreed to participate.ConclusionsGLOW will provide contemporary information on patterns of management of fracture risk in older women over a 5-year period. The collection of data in a similar manner in ten countries will permit comparisons of patient experience with prevention and treatment and provide insights into the distribution of risk among older women on an international basis.