E S Siris

New York Presbyterian Hospital, New York City, New York, United States

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Publications (153)947.68 Total impact

  • Salila Kurra, Dorothy A Fink, Ethel S Siris
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    ABSTRACT: Osteoporosis and diabetes mellitus are chronic diseases with significant associated morbidity and mortality. Recent evidence suggests that both type 1 and type 2 diabetes are associated with an increased fracture risk. Fracture as a complication of diabetes must be considered when evaluating and treating patients with diabetes.
    Endocrinology and metabolism clinics of North America 03/2014; 43(1):233-243. · 3.56 Impact Factor
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    ABSTRACT: Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3 % (hip) or 20 % (major) 10-year fracture risk also confer an osteoporosis diagnosis. Osteoporosis is a common disorder of reduced bone strength that predisposes to an increased risk for fractures in older individuals. In the USA, the standard criterion for the diagnosis of osteoporosis in postmenopausal women and older men is a T-score of ≤ -2.5 at the lumbar spine, femur neck, or total hip by bone mineral density testing. Under the direction of the National Bone Health Alliance, 17 clinicians and clinical scientists were appointed to a working group charged to determine the appropriate expansion of the criteria by which osteoporosis can be diagnosed. The group recommends that postmenopausal women and men aged 50 years should be diagnosed with osteoporosis if they have a demonstrable elevated risk for future fractures. This includes having a T-score of less than or equal to -2.5 at the spine or hip as one method for diagnosis but also permits a diagnosis for individuals in this population who have experienced a hip fracture with or without bone mineral density (BMD) testing and for those who have osteopenia by BMD who sustain a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture. Finally, the term osteoporosis should be used to diagnose individuals with an elevated fracture risk based on the World Health Organization Fracture Risk Algorithm, FRAX. As new ICD-10 codes become available, it is our hope that this new understanding of what osteoporosis represents will allow for an appropriate diagnosis when older individuals are recognized as being at an elevated risk for fracture.
    Osteoporosis International 02/2014; · 4.04 Impact Factor
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    ABSTRACT: Context. Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired. Objective. To improve model discrimination by developing a 5-yr composite fracture prediction model for fracture sites that display similar risk profiles. Design. Prospective, observational cohort study. Setting. Primary care practices in 10 countries. Patients. Women aged ≥55 years. Intervention. Self-administered questionnaires collected data on patient characteristics, fracture risk factors and previous fractures. Main Outcome Measure. Main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age. Results. Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index 0.75, 47,066 women), and lowest for FRAX major fracture and a 10-site model (c indices 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 yr of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 yr of age from a 10% decrease to a 60% increase. Conclusions. After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.
    The Journal of clinical endocrinology and metabolism 01/2014; · 6.50 Impact Factor
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    ABSTRACT: Abstract Background: Multiple therapies are approved for the treatment of osteoporosis (OP), but many patients with osteoporosis may not initiate treatment upon osteoporosis diagnosis. Objective: To characterize initiation of pharmacologic OP treatment among women within 1 year of OP diagnosis in a US managed care population. Research design and methods: The retrospective cohort study included women aged ≥ 55 years with a claims-documented diagnosis of OP who were naïve to OP medications prior to OP diagnosis (index date) during 2001-2010. Continuous enrollment for 12 months before (baseline) and after (follow-up) the index date was required. Patients who received OP medications but did not have an OP diagnosis were excluded. Differences in baseline characteristics between the treated and untreated cohorts were compared using Wilcoxon rank-sum (continuous variables) and chi-square tests (categorical variables). Main outcomes measures: During the follow-up period, the percentages of patients treated with bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid) and non-bisphosphonates (calcitonin, raloxifene, teriparatide) were determined. Results: A total of 65,344 patients, mean age 65.7 years, met study inclusion exclusion criteria. During the follow-up period, 42,033 patients (64.3%) received no OP medication and 23,311 patients (35.7%) received OP treatment. A total of 20,200 patients (30.9% of total study population) received bisphosphonates and 3,111 (4.8% of total) patients received non-bisphosphonates as their index medication. At baseline, untreated patients were slightly older and had higher rates of hypertension, chronic inflammatory joint disease, diabetes mellitus, and gastrointestinal events (P≤0.01) compared with treated patients. Conclusions: Among women aged ≥55 years in a US managed care population, 64.3% received no pharmacologic treatment within 1 year after being diagnosed with OP. We were not able to determine if untreated patients did not receive or did not fill a prescription. Further research is needed to understand the barriers to OP treatment and reasons for non-treatment.
    Current Medical Research and Opinion 10/2013; · 2.37 Impact Factor
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    ABSTRACT: Fractures may be associated with higher morbidity in obese postmenopausal women than in nonobese women. We compared health-care utilization, functional status, and health-related quality of life (HRQL) in obese, nonobese, and underweight women with fractures. Information from the GLOW study, started in 2006, was collected at baseline and at 1, 2, and 3 years. In this subanalysis, self-reported incident clinical fractures, health-care utilization, HRQL, and functional status were recorded and examined. Women in GLOW (n = 60,393) were aged ≥55 years, from 723 physician practices at 17 sites in 10 countries. Complete data for fracture and body mass index were available for 90 underweight, 3,270 nonobese, and 941 obese women with one or more incident clinical fractures during the 3-year follow-up. The median hospital length of stay, adjusted for age, comorbidities, and fracture type, was significantly greater in obese than nonobese women (6 vs. 5 days, p = 0.017). Physical function and vitality score were significantly worse in obese than in nonobese women, both before and after fracture; but changes after fracture were similar across groups. Use of antiosteoporosis medication was significantly lower in obese than in nonobese or underweight women. In conclusion, obese women with fracture undergo a longer period of hospitalization for treatment and have poorer functional status and HRQL than nonobese women. Whether these differences translate into higher economic costs and adverse effects on longer-term outcomes remains to be established.
    Calcified Tissue International 09/2013; · 2.50 Impact Factor
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    ABSTRACT: Accurate patient risk perception of adverse health events promotes greater autonomy over, and motivation towards, health-related lifestyles. Introduction We 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). Methods GLOW 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. Results In 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. Conclusions Postmenopausal 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.
    Osteoporosis International 07/2013; · 4.04 Impact Factor
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    ABSTRACT: Increased expression of DKK1 gene was reported in pagetic osteoblasts and stromal cells, and increased serum levels of DKK1 and SOST proteins were reported in patients with Paget disease of bone (PDB). This study aimed at identifying rare genetic variants of the DKK1 and SOST genes and at testing for genetic association with PDB in the French-Canadian population. Exons, promoters, and exon-intron junctions of these genes were sequenced in patients with PDB and healthy controls. An association study of Tag SNPs of both genes was also performed in 239 pagetic patients and 297 healthy individuals. Three rare variants were identified in this study, all located in the DKK1 gene: one variant in the second exon leading to alteration in a highly conserved amino acid (p.R120L), one in the 5'-untranslated region (-50 C/A), and one in a splice site of intron 1 (IVS1 184 T/C), although none of these rare variants were associated with PDB. A genetic association of a Tag SNP of the DKK1 gene was found: the G allele of rs1569198 was significantly decreased in patients in comparison to controls (42 vs. 49 %, uncorrected P = 0.03, OR = 0.77, 95 % CI 0.61-0.98). In conclusion, this study identified three rare genetic variants in DKK1 in the French-Canadian population. In addition, a weak genetic association of a common variant of DKK1, rs1569198, which is located on a predicted new acceptor site for splicing of this gene, was observed in PDB, whereas no rare variant or genetic association was found in the SOST gene.
    Calcified Tissue International 07/2013; · 2.50 Impact Factor
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    ABSTRACT: Anti-osteoporosis medication (AOM) does not abolish fracture risk, and some individuals experience multiple fractures while on treatment. Therefore, criteria for treatment failure have recently been defined. Using data from the Global Longitudinal study of Osteoporosis in Women (GLOW), we analyzed risk factors for treatment failure, defined as sustaining ≥2 fractures while on AOM. GLOW is a prospective, observational cohort study of women aged ≥55 years sampled from primary care practices in 10 countries. Self-administered questionnaires collected data on patient characteristics, fracture risk factors, previous fractures, AOM use, and health status. Data were analyzed from women who used the same class of AOM continuously over 3 survey-years and had data available on fracture occurrence. Multivariable logistic regression was used to identify independent predictors of treatment failure. Data from 26,918 women were available, of whom 5550 were on AOM. During follow-up, 73/5550 women in the AOM group (1.3%) and 123/21,368 in the non-AOM group (0.6%) reported occurrence of ≥2 fractures. The following variables were associated with treatment failure: lower SF-36 score (physical function and vitality) at baseline, higher FRAX score, falls in the past 12 months, selected comorbid conditions, prior fracture, current use of glucocorticoids, need of arms to assist to standing, and unexplained weight loss ≥10 lb (≥4.5 kg). Three variables remained predictive of treatment failure after multivariable analysis: worse SF-36 vitality score (odds ratio [OR] per 10-point increase 0.85; 95% confidence interval [CI] 0.76-0.95; p = 0.004), ≥2 falls in the past year (OR 2.40; 95% CI 1.34-4.29; p = 0.011), and prior fracture (OR 2.93; 95% CI 1.81-4.75; p < 0.0001). The C statistic for the model was 0.712. Specific strategies for fracture prevention should therefore be developed for this subgroup of patients.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2013; · 6.04 Impact Factor
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    ABSTRACT: To examine when, where and how fractures occur in postmenopausal women. 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. 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. 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.
    PLoS ONE 01/2013; 8(12):e83306. · 3.73 Impact Factor
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    ABSTRACT: Fragility fractures are common, affecting almost one in two older women and one in three older men. Every fragility fracture signals increased risk of future fractures as well as risk of premature mortality. Despite the major health care impact worldwide, currently there are few systems in place to identify and ''capture'' individuals after a fragility fracture to ensure appropriate assessment and treatment (according to national guidelines) to reduce future fracture risk and adverse health outcomes. The Task Force reviewed the current evidence about different systematic interventional approaches, their logical background, as well as the medical and ethical rationale. This included reviewing the evidence supporting cost-effective interventions and developing a toolkit for reducing secondary fracture incidence. This report presents this evidence for cost-effective interventions versus the human and health care costs associated with the failure to address further fractures. In particular, it summarizes the evidence for various forms of Fracture Liaison Service as the most effective intervention for secondary fracture prevention. It also summarizes the evidence that certain interventions, particularly those based on patient and/or community-focused educational approaches, are consistently, if unexpectedly, ineffective. As an international group, representing 36 countries throughout Asia-Pacific, South America, Europe, and North America, the Task Force reviewed and summarized the international data on barriers encountered in implementing risk-reduction strategies. It presents the ethical imperatives for providing quality of care in osteoporosis management. As part of an implementation strategy, it describes both the quality improvement methods best suited to transforming care and the research questions that remain outstanding. The overarching outcome of the Task Force's work has been the provision of a rational background and the scientific evidence underpinning secondary fracture prevention and stresses the utility of one form or another of a Fracture Liaison Service in achieving those quality outcomes worldwide. ß 2012 American Society for Bone and Mineral Research.
    Journal of Bone and Mineral Research 10/2012; J Bone Miner Res. 2012 Oct;27(10):2039-46. · 6.13 Impact Factor
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    ABSTRACT: BACKGROUND: Fracture is the major complication of osteoporosis, and it allows the identification of individuals needing medical intervention for osteoporosis. After nonvertebral fracture, patients often do not receive osteoporosis medical treatment despite evidence that this treatment reduces the risk of subsequent fracture. In this preplanned analysis of the results of the three-year, placebo-controlled FREEDOM trial, we evaluated the effect of denosumab administration on fracture-healing to address theoretical concerns related to initiating or continuing denosumab therapy in patients presenting with a nonvertebral fracture. METHODS: Postmenopausal women aged sixty to ninety years with osteoporosis were randomized to receive 60 mg of denosumab (n = 3902) or a placebo (n = 3906) subcutaneously every six months for three years. Investigators reported complications associated with a fracture or its management and with fracture-healing for all nonvertebral fractures that occurred during the study. Delayed healing was defined as incomplete fracture-healing six months after the fracture. RESULTS: Six hundred and sixty-seven subjects (303 treated with denosumab and 364 who received a placebo) had a total of 851 nonvertebral fractures (386 in the denosumab group and 465 in the placebo group), including 199 fractures (seventy-nine in the denosumab group and 120 in the placebo group) that were treated surgically. Delayed healing was reported in seven subjects (two in the denosumab group and five in the placebo group), including one with subsequent nonunion (in the placebo group). Neither delayed healing nor nonunion was observed in any subject who had received denosumab within six weeks preceding or following the fracture. A complication associated with the fracture or intervention occurred in five subjects (2%) and twenty subjects (5%) in the denosumab and placebo groups, respectively (p = 0.009). CONCLUSIONS: Denosumab in a dose of 60 mg every six months does not seem to delay fracture-healing or contribute to other complications, even when it is administered at or near the time of the fracture. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
    The Journal of Bone and Joint Surgery 10/2012; · 3.23 Impact Factor
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    ABSTRACT: INTRODUCTION: Many women at risk of fracture do not receive anti-osteoporosis medication (AOM), while others may be receiving unnecessary treatment. PURPOSE: To examine the characteristics associated with AOM use among women at low and high risks of fracture. METHODS: The Global Longitudinal Study of Osteoporosis in Women (GLOW) is a prospective cohort study in which data were collected, via self-administered questionnaires, from 60,393 non-institutionalized women aged ≥55years in 10 countries between October 1, 2006 and April 30, 2008. This is a cross-sectional analysis of baseline USA data, in which women were classified as having low fracture risk (<65years; no FRAX risk factors) or high fracture risk (≥65years; prior fracture or ≥2 other FRAX risk factors). RESULTS: Of 27,957 women, 3013 were at low risk of fracture and 3699 were at high risk. Only 35.7% of high-risk women reported AOM treatment, rising to 39.5% for those with self-reported osteopenia and 65.4% for those with self-reported osteoporosis. Conversely, 13.4% of low-risk women reported AOM, rising to 28.7% for osteopenia and 62.4% for osteoporosis. Characteristics associated with significantly higher AOM treatment rates among low- and high-risk women were: osteoporosis (odds ratios 75.3 and 18.1, respectively), osteopenia (17.9 and 6.3), concern about osteoporosis (2.0 and 1.8), higher perceived risk of fracture (2.3 and 1.6), and higher vitality score (1.7 and 1.6). CONCLUSION: Use of AOM is frequently inconsistent with published guidelines in both high- and low-risk women. Characteristics other than FRAX fracture risk appear to influence this use, particularly the presence of self-reported osteoporosis.
    Bone 09/2012; 51(6):975-980. · 3.82 Impact Factor
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    ABSTRACT: We performed a genetic association study of rare variants and single nucleotide polymorphisms (SNPs) of UCMA/GRP and OPTN genes, in French-Canadian patients with Paget's disease of bone (PDB) and in healthy controls from the same population. We reproduced the variant found in the UCMA/GRP basal promoter and tested its functionality using in vitro transient transfection assays. Interestingly, this SNP rs17152980 appears to affect the transcription level of UCMA/GRP. In addition, we have identified five rare genetic variants in UCMA/GRP gene, four of them being population-specific, although none were found to be associated with PDB. Six Tag SNPs of UCMA/GRP gene were associated with PDB, particularly the SNP rs17152980 (uncorrected P=3.8 × 10(-3)), although not significant after Bonferroni's correction. More importantly, we replicated the strong and statistically significant genetic association of two SNPs of the OPTN gene, the rs1561570 (uncorrected P=5.7 × 10(-7)) and the rs2095388 (uncorrected P=4.9 × 10(-3)), with PDB. In addition, we identified a very rare variant found to be located close to the basal promoter of the OPTN gene, at -232bp from its distal transcription start site. Furthermore, depending on the type of allele present (G or A), the binding of several important nuclear factors such as the vitamin D or the retinoic acid receptors is predicted to be altered at this position, suggesting a significant effect in the regulation of transcription of the OPTN gene. In conclusion, we identified a functional SNP located in the basal promoter of the UCMA/GRP gene which provided a weak genetic association with PDB. In addition, we replicated the strong genetic association of two already known SNPs of the OPTN gene, with PDB in a founder effect population. We also identified a very rare variant in the promoter of OPTN, and through bioinformatic analysis, identified putative transcription factor binding sites likely to affect OPTN gene transcription.
    Bone 07/2012; 51(4):720-8. · 3.82 Impact Factor
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    ABSTRACT: OBJECTIVES: Patients with osteoarthritis have increased bone mass but no decrease in fractures. The association between self-reported osteoarthritis and incident falls and fractures was studied in postmenopausal women. METHODS: The Global Longitudinal Study of Osteoporosis in Women is a prospective multinational cohort of 60 393 non-institutionalised women aged ≥55 years who had visited primary care practices within the previous 2 years. Questionnaires were mailed at yearly intervals. Patients were classified as having osteoarthritis if they answered yes to the question, 'Has a doctor or other health provider ever said that you had osteoarthritis or degenerative joint disease?', and this was validated against primary care records in a subsample. Information on incident falls, fractures and covariates was self-reported. Cox and Poisson models were used for incident fractures and number of falls, respectively, to compute hazard ratios (HRs) and rate ratios (RRs) for baseline osteoarthritis status. RESULTS: Of 51 386 women followed for a median of 2.9 years (interquartile range 2.1-3.0), 20 409 (40%) reported osteoarthritis. The adjusted HR for osteoarthritis predicting fracture was 1.21 (95% CI 1.13 to 1.30; p<0.0001) and the adjusted RR for falls was 1.24 (95% CI 1.22 to 1.26; p<0.0001). However, the association between osteoarthritis and fracture was not significant after adjustment for incident falls (HR 1.06 (95% CI 0.98 to 1.15; p=0.13)). CONCLUSIONS: Postmenopausal women with self-reported osteoarthritis have a 20% increased risk of fracture and experience 25% more falls than those without osteoarthritis. These data suggest that increased falls are the causal pathway of the association between osteoarthritis and fractures.
    Annals of the rheumatic diseases 06/2012; · 8.11 Impact Factor
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    ABSTRACT: Osteoporosis is a skeletal disorder in which reductions in bone strength predispose to an increased risk for fractures. Currently, the diagnosis is officially made based exclusively on bone mineral density T-scores that are ≤-2.5 at the spine or hip. Limiting the clinical diagnosis of osteoporosis solely to a T-score-based criterion, which is the official convention in the USA, creates uncertainty about the use of the term osteoporosis to diagnose older women and men who have T-scores >-2.5, but either have already sustained low-trauma fractures or are recognized as having high fracture risk based on absolute fracture risk calculations from FRAX or other algorithms. A failure to diagnose such patients as having osteoporosis may be one component of the well-documented underdiagnosis and undertreatment of this disease which limits our ability to reduce the burden of fractures worldwide. There is a need to expand the criteria for making a clinical diagnosis and to codify these changes in order to help patients, physicians, policy makers, and payers better understand who has this disease and the elevated risk for fracture that it represents.
    Osteoporosis International 04/2012; 23(8):2093-7. · 4.04 Impact Factor
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    ABSTRACT: We 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. INTRODUCTION: The 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. METHODS: Information 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. RESULTS: During 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. CONCLUSIONS: While 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.
    Osteoporosis International 04/2012; · 4.04 Impact Factor
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    ABSTRACT: Denosumab has been shown to reduce the incidence of vertebral, nonvertebral, and hip fractures. The aim of the current study was to determine whether the antifracture efficacy of denosumab was dependent on baseline fracture probability assessed by FRAX. The primary data of the phase 3 FREEDOM study of the effects of denosumab in women with postmenopausal osteoporosis were used to compute country-specific probabilities using the FRAX tool (version 3.2). The outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. At baseline, the median 10-year probability of a major osteoporotic fracture (with bone mineral density) was approximately 15% and for hip fracture was approximately 5% in both groups. In the simplest model adjusted for age and fracture probability, treatment with denosumab over 3 years was associated with a 32% (95% confidence interval [CI] 20% to 42%) decrease in clinical osteoporotic fractures. Denosumab reduced fracture risk to a greater extent in those at moderate to high risk. For example, at 10% probability, denosumab decreased fracture risk by 11% (p = 0.629), whereas at 30% probability (90th percentile of study population) the reduction was 50% (p = 0.001). The reduction in fracture was independent of prior fracture, parental history of hip fracture, or secondary causes of osteoporosis. A low body mass index (BMI) was associated with greater efficacy. Denosumab significantly decreased the risk of clinical osteoporotic fractures in postmenopausal women. Overall, the efficacy of denosumab was greater in those at moderate to high risk of fracture as assessed by FRAX.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2012; 27(7):1480-6. · 6.04 Impact Factor
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    ABSTRACT: Greater awareness of the relationship between co-morbidities and fracture risk may improve fracture-prediction algorithms such as FRAX. We used a large, multinational cohort study (GLOW) to investigate the effect of co-morbidities on fracture risk. Women completed a baseline questionnaire detailing past medical history, including co-morbidity history and fracture. They were re-contacted annually to determine incident clinical fractures. A co-morbidity index, defined as number of baseline co-morbidities, was derived. The effect of adding the co-morbidity index to FRAX risk factors on fracture prevention was examined using chi-squared tests, the May-Hosmer test, c index and comparison of predicted versus observed fracture rates. Of 52,960 women with follow-up data, enrolled between October 2006 and February 2008, 3224 (6.1%) sustained an incident fracture over 2 years. All recorded co-morbidities were significantly associated with fracture, except for high cholesterol, hypertension, celiac disease, and cancer. The strongest association was seen with Parkinson's disease (age-adjusted hazard ratio [HR]: 2.2; 95% CI: 1.6-3.1; P<0.001). Co-morbidities that contributed most to fracture prediction in a Cox regression model with FRAX risk factors as additional predictors were: Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, osteoarthritis, and heart disease. Co-morbidities, as captured in a co-morbidity index, contributed significantly to fracture risk in this study population. Parkinson's disease carried a particularly high risk of fracture; and increasing co-morbidity index was associated with increasing fracture risk. Addition of co-morbidity index to FRAX risk factors improved fracture prediction.
    Bone 03/2012; 50(6):1288-93. · 3.82 Impact Factor
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    ABSTRACT: To determine the proportion of untreated women who reported receiving treatment after incident fracture and to identify factors that predict treatment across an international spectrum of individuals. Prospective observational study. Self-administered questionnaires were mailed at baseline and 1 year. Multinational cohort of noninstitutionalized women recruited from 723 primary physician practices in 10 countries. Sixty thousand three hundred ninety-three postmenopausal women aged 55 and older were recruited with a 2:1 oversampling of women aged 65 and older. Data collected included participant demographics, medical history, fracture occurrence, medications, and risk factors for fracture. Anti-osteoporosis medications (AOMs) included estrogen, selective estrogen receptor modulators, bisphosphonates, calcitonin, parathyroid hormone, and strontium. After the first year of follow-up, 1,075 women reported an incident fracture. Of these, 17% had started AOM, including 15% of those with a single fracture and 35% with multiple fractures. Predictors of treatment included baseline calcium use (P = .01), baseline diagnosis of osteoporosis (P < .001), and fracture type (P < .001). In multivariable analysis, women taking calcium supplements at baseline (odds ratio (OR) = 1.67) and with a baseline diagnosis of osteoporosis (OR = 2.55) were more likely to be taking AOM. Hip fracture (OR = 2.61), spine fracture (OR = 6.61), and multiple fractures (OR = 3.79) were associated with AOM treatment. Age, global region, and use of high-risk medications were not associated with treatment. More than 80% of older women with new fractures were not treated, despite the availability of AOM. Important factors associated with treatment in this international cohort included diagnosis of osteoporosis before the incident fracture, spine fracture, and to a lesser degree, hip fracture.
    Journal of the American Geriatrics Society 02/2012; 60(3):455-61. · 3.98 Impact Factor
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    ABSTRACT: Previous fractures of the hip, spine, or wrist are well-recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women aged ≥55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow-up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures, respectively, since age 45 years. During the first 2 years of follow-up, 3149 women suffered 3683 incident fractures. Compared with women with no previous fractures, women with 1, 2, or ≥3 prior fractures were 1.8-, 3.0-, and 4.8-fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1-fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio [HR] = 7.3) and hip (HR = 3.5). Prior rib fractures were associated with a 2.3-fold risk of subsequent vertebral fracture, and previous upper leg fracture predicted a 2.2-fold increased risk of hip fracture. Women with a history of ankle fracture were at 1.8-fold risk of future fracture of a weight-bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 11/2011; 27(3):645-53. · 6.04 Impact Factor

Publication Stats

7k Citations
947.68 Total Impact Points

Institutions

  • 1998–2014
    • New York Presbyterian Hospital
      • Department of Pain Medicine
      New York City, New York, United States
  • 2011–2013
    • Cambridge University Hospitals NHS Foundation Trust
      Cambridge, England, United Kingdom
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
    • Alfried Krupp Krankenhaus
      Essen, Lower Saxony, Germany
    • Merck
      Whitehouse Station, New Jersey, United States
  • 1981–2013
    • Columbia University
      • • Division of Endocrinology
      • • Department of Medicine
      • • College of Physicians and Surgeons
      New York City, New York, United States
  • 2012
    • University of Pittsburgh
      • School of Medicine
      Pittsburgh, PA, United States
  • 2010–2012
    • McMaster University
      • Division of Geriatric Medicine
      Hamilton, Ontario, Canada
    • Laval University
      • Département de Médecine
      Québec, Quebec, Canada
  • 1997–2012
    • CUNY Graduate Center
      New York City, New York, United States
  • 1991–2011
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States
  • 1996–2009
    • New York University
      • Department of Medicine
      New York City, NY, United States
  • 1984–2009
    • New York Medical College
      • Department of Medicine
      New York City, New York, United States
  • 2008
    • New Mexico Clinical Research and Osteoporosis Center
      Albuquerque, New Mexico, United States
    • Ottawa Hospital Research Institute
      • Clinical Epidemiology Program
      Ottawa, Ontario, Canada
  • 2003–2005
    • University of California, San Diego
      • Department of Family and Preventive Medicine
      San Diego, CA, United States
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
  • 2004
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2001
    • Texas Woman's University
      Denton, Texas, United States