Family History Of Hip Fracture Research Articles

The outcome of an automated assessment of trabecular pattern in intraoral radiographs as a fracture risk predictor.

This study aims to investigate if automated analyses of the trabecular pattern in intraoral radiographs independently contribute to fracture risk assessment when other risk factors incorporated in the Fracture Risk Assessment Tool (FRAX) are taken into account. A secondary aim is to explore the correlation between the automated trabecular pattern assessment in intraoral radiographs and Trabecular Bone Score (TBS). A total of 567 intraoral radiographs from older females participating in a large population-based study (SUPERB) based in Gothenburg, Sweden, were selected to analyse trabecular pattern using semi-automated and fully automated software. Associations between trabecular pattern analysis and incident fractures were studied using Cox proportional hazard model, unadjusted and adjusted for FRAX risk factors (previous fracture, family history of hip fracture, smoking, corticosteroids, rheumatoid arthritis, without and with bone mineral density (BMD) of the femoral neck). In addition, the correlation between trabecular pattern analysis and TBS of the lumbar spine was investigated using Pearson correlation analysis. Neither the unadjusted nor the adjusted trabecular pattern analysis in intraoral radiographs was significantly associated with any fracture or major osteoporotic fracture (MOF). A weak correlation was found between semi-automated trabecular pattern analysis and TBS. No correlation was found between the fully automated trabecular pattern analysis and TBS. The present study shows that semi-automated and fully automated digital analyses of the trabecular pattern in intraoral radiographs do not contribute to fracture risk prediction. Furthermore, the study shows a weak correlation between semi-automated trabecular pattern analysis and TBS.

Фактори ризику переломів проксимального відділу стегнової кістки у хворих старших вікових груп

Актуальність. На сьогодні переломи проксимального відділу стегнової кістки (ПВСК) залишаються важливою медико-соціальною проблемою. Продовжується вивчення факторів ризику, оскільки доведено, що їх вплив істотно відрізняється в різних популяціях. Метою даного дослідження була оцінка факторів ризику в осіб старших вікових груп з переломами ПВСК. Матеріали і методи. Обстежено 122 особи віком 50 років і старше (88 жінок та 34 чоловіки з внутрішньо- та позасуглобовими переломами ПВСК). Оцінку факторів ризику остеопорозу та переломів проводили за допомогою анкетування (українська версія опитувальника FRAX®, доповнена авторами). Результати. У 79,4 % чоловіків і 73,9 % обстежених жінок встановлено клінічно діагностовані переломи в минулому. Найбільш часто у жінок були зареєстровані переломи кісток передпліччя (39,4 %), тіл хребців (25,8 %) і плечової кістки (12,1 %), у чоловіків — переломи плечової кістки та кісток гомілки (25 %), кісток передпліччя та переломи тіл хребців (17,9 %). Термін від попереднього перелому у 80,3 % обстежених жінок і 78,6 % чоловіків становив більше 5 років. У 52,3 % жінок і 50 % у чоловіків з переломами ПВСК підтверджено сімейний анамнез перелому стегнової кістки в близьких родичів (матері або батька). У 79,4 % чоловіків і 71,6 % обстежених жінок встановлено наявність переломів іншої локалізації у близьких родичів. До перелому ПВСК 85,3 % чоловіків і 52,1 % жінок мали показники 10-річної ймовірності перелому стегнової кістки (FRAX®) 3 і більше, що свідчить про необхідність їх оцінки для своєчасного лікування остеопорозу. Висновки. Вищезазначене слід враховувати для планування профілактичних заходів щодо остеопорозу та його ускладнень в осіб старших вікових груп.

Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin.

Direct-acting oral anticoagulants (DOACs) are therapeutic alternatives to warfarin that act independently of vitamin K, thus not affecting bone matrix formation. The aim of this study was to compare bone mineral density (BMD) and microarchitecture in patients treated with DOACs versus warfarin. Cross-sectional, observational study in patients using oral anticoagulants for >1year and a paired control group (CG). Based on the type of anticoagulant used, the patients were grouped into a DOAC (DOACG) or warfarin (WG) group. All patients filled out a questionnaire and underwent BMD evaluation and trabecular bone score (TBS) measurement. In all, 150 patients were included (50 patients in each group). The mean age was 60.49±7.48years, and most participants were men (64%). The most frequent comorbidities were hypertension, dyslipidemia, and hyperglycemia (comparison between groups p>0.05). Low bone mass was diagnosed in 42%, 50%, and 66% of the patients in the CG, DOACG, and WG, respectively (p=0.012). On logistic regression analysis, BMD was associated with body mass index (BMI; odds ratio [OR] 0.846, 95% confidence interval [CI] 0.763-0.926, p=0.001), creatinine level (OR 0.024, 95%CI 0.001-0.434, p=0.017), and TBS value (OR 17.777, 95%CI 4.526-96.903, p=0.000). The mean TBS decreased progressively from the CG to the DOACG and WG (1.328±0.112, 1.264±0.138, and 1.203±0.112, respectively, p<0.001). On multivariate linear regression, negative predictors of TBS included warfarin use (-0.06, 95%CI -0.11 to -0.02, p=0.006), BMI (-0.01, 95%CI -0.01 to -0.00, p<0.001), and hyperglycemia (-0.07, 95%CI -0.11 to -0.03, p=0.003), while positive predictors were an active IPAQ classification (0.06, 95%CI 0.01-0.11, p=0.029) and family history of hip fracture (0.07, 95%CI 0.01-0.14, p=0.029). Patients using anticoagulants have lower BMD and TBS values compared with controls. This negative effect on bone was more pronounced with warfarin, but was also seen with DOACs.

Premenopausal Osteoporosis &amp; Perfluoroalkyl Substance Exposure; Is There a Link?

Introduction: Perfluoroalkyl substances (PFAS) like Perflouroctanoate (PFOA) and Perflurooctane sulfonate (PFOS) are ubiquitous environmental contaminants that have been in industrial use for many years. Many known adverse effects include malignancies, reproductive and thyroid dysfunction. However, there is limited literature regarding PFAS causing low bone density. We report a case of a premenopausal woman with a history of exposure to PFAS who was recently diagnosed with osteoporosis.Clinical Case: A 36-year-old lady with a history of hypothyroidism, on levothyroxine, presented to the orthopedics clinic with complaints of sudden onset right foot pain with no trauma. She was found to have a fracture of her right second metatarsal bone. Notably, over a period of five years she had suffered multiple fractures including metatarsal, elbow and a wrist fracture, all with minimal or no trauma. She denied smoking, alcohol, chronic steroid or PPI use, history of malabsorption, celiac disease, kidney stones, malignancy or liver problems. Her menstrual cycles were regular; she was on oral contraceptives in the past for dysmenorrhea. She is on Vitamin D supplementation and consumes adequate dairy products daily. There is no family history of hip fracture or osteoporosis. Labs showed: Calcium 8.9mg/dl, Phosphorus 2.4mg/dl (2.5–4.5mg/dl), intact PTH was 92.7pg/ml (8-97pg/ml), 24-hour urine calcium was undetectable. Vitamin D was 56.6ng/ml (30-100ng/ml). CBC, TSH, FSH, liver & kidney functions were all normal. Anti-endomysial, anti-gliadin and anti-tissue trans glutaminase antibodies were all unremarkable. IgA level was 362mg/dl (8–352 mg/dl). DXA scan revealed the lowest Z-score (-3.1) in the lumbar spine. She reported a history of exposure to PFAS with a blood level of 22.3ng/ml for PFOA and 48.4ng/ml for PFOS in the year 2005. Plan is to initiate bisphosphonate therapy for the treatment of osteoporosis.Discussion: PFAS are known endocrine disruptive agents that have been used widely in making a wide range of consumer products including nonstick and stain-resistant coatings of cookware, food containers. Recent studies suggest that serum PFAS concentrations were associated with lower bone density. There was a higher incidence of lower lumbar spine bone density in patients exposed to PFOS. PFOA is believed to compete with calcitriol at the same binding site on Vitamin D receptor resulting in changes in the osteoblasts thereby decreasing bone mineralization.Conclusion: There needs to be increased awareness about the association of low bone density in patients exposed to PFAS. This is especially important in the evaluation of premenopausal osteoporosis.

Self-perceived Fracture Risk in the Global Longitudinal Study of Osteoporosis in Women: Its Correlates and Relationship with Bone Microarchitecture

The purpose of this study is to examine correlates of self-perceived fracture risk (SPR) and relationships between SPR and subsequent bone density and microarchitecture in the UK arm of the Global Longitudinal Study of Osteoporosis in Women. 3912 women completed baseline questionnaires detailing medical history and SPR; 492 underwent HRpQCT scans of the radius and tibia and DXA scans of total body, hip, femoral neck and lumbar spine a median of 7.5 years later. Correlates of SPR were examined and a cluster analysis of potential predictors of SPR performed. SPR in relation to HRpQCT and aBMD parameters was examined using linear regression with and without adjustment for anthropometric, demographic and lifestyle covariates. Mean (SD) baseline age was 69.0 (9.0) years; 56.6% reported a similar SPR; 28.6% lower SPR; 14.9% higher SPR compared to women of similar age. In mutually-adjusted analysis, higher SPR was associated (p < 0.05) with: lower physical activity and educational attainment; use of anti–osteoporosis medications (AOM) and calcium supplements; greater number of falls in the previous year; history of fracture since aged 45; family history of hip fracture; and increased comorbidity. Higher SPR, history of fracture, and use of AOM, calcium and vitamin D clustered together. Even after adjustments that included AOM use, higher SPR was associated with: lower radial trabecular volumetric density and number, and higher trabecular separation; lower tibial cortical area and trabecular volumetric density; and lower aBMD at the femoral neck. Despite greater AOM use, women with higher baseline SPR had poorer subsequent bone health.

Management manual for cancer treatment-induced bone loss (CTIBL): position statement of the JSBMR.

Androgen deprivation therapy and aromatase inhibitors are known to cause a decrease in bone mineral density and an increase in fractures. Patients receiving these treatments have been shown to have a fracture risk equal to or greater than that of patients with osteoporosis with prevalent fractures. This manual was created to prevent fractures in patients with cancer treatment-induced bone loss with high fracture risks who cannot be treated under the current Japanese guideline for the prevention and treatment of osteoporosis. This manual recommends drug treatment for patients with BMD -2.0≤T score<-1.5 with the family history of hip fracture or 15% or more 10-year probability of major osteoporotic fractures by FRAX®; or in patients with BMD T score<-2.0. It is important to verify whether the use of this manual can reduce fractures and improve the quality of life of patients with cancer treatment-induced bone loss by prospective studies.

Knowledge and perception of women at risk for osteoporosis: Educational intervention

Background Women’s awareness and perceptions about risk for osteoporosis must increase and should be the priority in the future through educational programs. Aim The aim of this study was to evaluate the effect of educational intervention on the knowledge and perception of women at risk for osteoporosis. Patients and methods The study was conducted in the outpatient clinics (Antenatal Outpatient Clinic and Orthopedic Clinic) affiliated to Ain Shams University Hospitals. The purposive sample included 60 women above 35 years of age. Three tools were used before educational intervention, after educational intervention, and after 8 weeks of educational intervention. First, an interviewing questionnaire sheet was used, which included three parts: part I, sociodemographic data and obstetric history; part II, predisposing factors of osteoporosis; and part III, women’s knowledge about osteoporosis. Second, a perception questionnaire sheet was used to measure the level of women’s health beliefs as regards osteoporosis. Third, women’s complaint tool was used to measure the studied women’s complaints of preclimacteric symptoms. Results In total, 83.3% of the studied women had dental problems and women with galactorrhea represented 15%; 10% of the studied women had a family history of hip fracture in the elderly. In total, 8.3% of the studied women had been using cortisone for more than 6 months and 3.3% were smokers and suffered from weight loss. There were statistically significant differences as regards their knowledge after application of program. Significant differences were detected as regards benefits of exercise and susceptibility to disease occurrence from 0% and 30% before intervention to 90% after intervention. However, there were percentage changes from 10 to 95% as regards seriousness of disease development and benefits of Ca+ intake. Moreover, there were changes in health motivation from 20 to 100%. There was improvement as regards psychological symptoms and miscellaneous complaints. There were correlations among total knowledge, perception, and their complaints. Conclusion The current study supports the first hypothesis by significantly improving the level of the studied women’s knowledge and perception, and the second hypothesis. As regards women’s complaints of preclimacteric symptoms, the results revealed significantly decreasing psychological problems and miscellaneous complaints. Moreover, there was a positive correlation among knowledge, perception, and their complaints as regards osteoporosis. Recommendations Illustrated booklet about osteoporosis must be available in outpatient clinics and brochures on phytoestrogen-rich diet should be available for each woman.

Relationships Between Inflammation, Immune Activation, and Bone Health Among HIV-Infected Adults on Stable Antiretroviral Therapy

The aim was to determine the association between bone health and inflammation, T-cell activation, and monocyte activation among HIV-infected persons on stable antiretroviral therapy. We performed a cross-sectional analysis of all the subjects enrolling in the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV trial with available skeletal assessments by dual-energy x-ray absorptiometry, inflammation, and immune activation markers. Analyses used were Wilcoxon rank-sum tests, Spearman correlation coefficients, and linear regression. One hundred forty-two subjects were included: 78% men, 69% African American, median age 46.3 years, CD4 count 604 cells per microliter, and 77% with undetectable HIV-1 RNA. Twenty-three percent had osteopenia/osteoporosis at the hip, and 21% had this at the lumbar spine. Soluble vascular cell adhesion molecule-1 was correlated with hip (r = -0.22) and spine (r = -0.23) bone mineral density (BMD), and bone turnover markers (r = 0.20-0.33; all P < 0.05). No significant correlations were observed between the BMD and T-cell activation (%CD38HLA-DR on CD4 or CD8 T cells), monocyte activation (CD14CD16, sCD14, and sCD163), or inflammatory markers [interleukin (IL)-6, tumor necrosis factor-α, highly sensitive C-reactive protein, D-dimer, receptor activator of NF-kB ligand, osteoprotegerin, soluble tumor necrosis factor-RI and II]. In regression models including traditional bone risk factors, hip BMD was associated with age, race, and body mass index; spine BMD was associated with race, family history of hip fracture, trunk fat, tenofovir, and HIV RNA; bone resorption (c-terminal collagen crosslinks) was associated with intracellular adhesion molecule-1 and trunk fat; bone formation (P1NP) was associated with soluble vascular cell adhesion molecule-1, trunk and limb fat (P ≤ 0.05). Future studies should evaluate the longitudinal association of the adhesion molecules to further elucidate potential contributory mechanisms of bone loss among HIV-infected persons on stable antiretroviral therapy.

Use of the FRAX Screening Tool to Assess Fracture Risk in a Long-Term Care Facility

The primary objective of this study was to determine the percentage of nursing residents at high risk of fracture as determined by FRAX score, calculated without bone mineral density (BMD) data. The secondary objective was to quantify FRAX components able to be ascertained through pharmacist chart review. Retrospective chart review. 130-bed long-term care facility in Arizona. Inclusion criteria comprised designation as a skilled nursing facility, residents older than 50 years of age, and postmenopausal, if female. Exclusion criteria comprised current osteoporosis diagnosis/treatment, and hospice. Eighty-eight residents were screened, and 52 completed the study. The FRAX clinical risk assessment tool was used without incorporation of BMD data to determine 10-year risk of major osteoporotic and hip fracture. FRAX components unable to be determined by chart review were recorded. The primary outcome measure was calculated FRAX score for each participant. The secondary outcome measure was component(s) of FRAX unable to be ascertained via chart review. 90.3% of participants had high (≥ 3%) 10-year risk of hip fracture and 55.8% had high (≥ 20%) 10-year risk of major osteoporotic fracture. FRAX components unable to be ascertained through chart review included family history of hip fracture (absent from 51.9% of charts) and/or ethanol use (absent from 3.8% of charts). Nursing facility residents are at high risk for fracture as determined by FRAX, without BMD data. The ability to determine FRAX scores via pharmacist chart review demonstrates an opportunity for pharmacist involvement in long-term care fracture risk screening.

THU0064 Comparison of estimated fracture risk using the FRAX index calculated with and without bone densitometry in patients with early arthritis

BackgroundThe FRAX index is a tool developed by the WHO that estimates the 10-year probability of hip fracture and a major osteoporotic fracture. It is calculated using an algorithm that...

Cost-effectiveness of alendronate for the treatment of osteopenic postmenopausal women in Japan

Many postmenopausal women have osteopenia, a condition characterized by loss of bone mineral density (BMD) that is not as severe as in osteoporosis. The objective of this study was to estimate the cost-effectiveness of alendronate to prevent fractures in osteopenic postmenopausal women without a history of fracture in Japan. An individual simulation model was developed to predict lifetime costs and quality-adjusted life years (QALYs) of 5 years of preventive alendronate therapy versus no preventive therapy. The risk of hip and vertebral fracture associated with age and BMD was derived from epidemiologic studies in Japan. We ran the model with different combinations of age (65, 70, and 75 years), BMD (70%, 75%, and 80% of young adult mean [YAM]), and additional clinical risk factors. For 70-year-old women with a BMD of 70% of the YAM having one of the following risk factors: a family history of hip fracture, high alcohol intake, or current smoking, the incremental cost-effectiveness ratio (ICER) of alendronate was $92,937, $126,251, and $129,067 per QALY, respectively. These results were sensitive to age, BMD, and number of clinical risk factors. Probabilistic sensitivity analysis for the base case showed that in the presence of one, two, and three risk factors, alendronate was cost-effective in 0.2% to 2.6%, 13.1% to 56.1%, and 99.1% of the simulations, respectively, if society is willing to pay $50,000 per QALY. Additional analysis indicated that alendronate can be a good value in osteopenic women if the 10-year probability for a osteoporotic hip or vertebral fracture is more than 26.2%. Our results indicate that whether to treat osteopenia with alendronate should be determined on the basis of age, BMD, and number of clinical risk factors in terms of cost-effectiveness.

Assessment of the 10-year risk of fracture in Italian postmenopausal women using FRAX®: a north Italian multicenter study.

The aim of the study was to estimate the absolute risk of fracture in a sample of postmenopausal women with the Italian version of FRAX®, using femoral neck bone mineral density (BMD) and 3 internationally validated clinical risk factors (CRFs) (history of fragility fracture, family history of hip fracture, current smoking). We retrospectively studied 9586 women (mean age 64.1 yr) examined in three osteoporosis centers from Northern Italy over two years (2001-2002). The risk of major osteoporotic (clinical spine, hip, forearm and humerus) and hip fractures was estimated using the online version of the FRAX algorithm adapted for Italy. The median 10-year risk was 7.5% for osteoporotic fracture and 1.7% for hip fracture. 25% of subjects had a 10-year risk ≥ 12.1% for osteoporotic fracture and ≥ 4.1% for hip fracture. The median 10-year risk of fracture increased with the number of prevalent CRFs. For major osteoporotic fractures risk rose from 6.3% to 10.9%, 21.4% and 40.9% with 1, 2 and 3 prevalent CRFs, respectively. For hip fractures the corresponding figures were: 1.3%, 2.7%, 7.0% and 21.9%, respectively. However, it must be emphasized that in 2 out of 3 women, none of the CRFs examined was present and the assessment of risk was limited to age and BMD. Our data provide the first description of the effect of the combination of BMD, age and CRFs on fracture risk stratification in a large sample of Italian postmenopausal women using FRAX®. The results are a useful starting point to define criteria for the application of FRAX® in clinical practice in Italy.

Risk factors for fracture in elderly men: a population-based prospective study

Risk factors for fractures were assessed in a random sample of 4,696 elderly men followed for 5.4 years. Results highlighted the importance of assessment of falls and dizziness as well as novel risk factors including frequent urination and erectile dysfunction. Knowledge about risk factors for fracture in men is limited. The aim of this study was to evaluate factors potentially associated with fracture risk in men. A questionnaire enquiring about potential risk factors for fractures in men was posted to a random sample of 9,314 men aged 60-74 years. A completed questionnaire was returned by 4,696 (50.4%). Follow-up on incident fractures over 5.4 years was performed using public registries. During the study, 203 individuals experienced a first clinical fracture, of which 85 patients were considered osteoporotic (9 in humerus, 10 vertebral, 32 in the hip and 34 in the forearm). Cox proportional hazard regression models were used to evaluate risk factors for any and osteoporotic fractures. The following variables were found to be associated with increased risk of any fracture in adjusted models family history of a hip fracture (HR; 95%CI: 1.56; 1.05-2.33), falls (2-4/year: 2.10; 1.35-3.27, >4/year: 2.46; 1.12-5.41, both compared to no falls), dizziness (2.36; 1.51-3.71), erectile dysfunction (1.41; 1.06-1.87) and frequent urination (2.06; 1.26-3.39). Similarly, falls (2.36; 1.45-3.86), dizziness (2.83; 1.52-5.25), erectile dysfunction (2.01; 1.30-3.09) and pulmonary illness (1.90; 1.03-3.53) were associated with increased risk of osteoporotic fractures in adjusted models. These results underline the importance of assessment of dizziness, falls and those with a family history of hip fracture. Frequent urination and erectile dysfunction were independently associated with increased fracture risk. Although the mechanism of association is unknown, these variables are likely to be indicators of frailty or hypogonadism.

Mikkeli Osteoporosis Index Identifies Fracture Risk Factors and Osteoporosis and Intervention Thresholds Parallel with FRAX

Osteoporosis Index (MOI) was developed from Fracture Index (FI), a validated fracture risk score, to identify also osteoporosis. MOI risk factors are age, weight, previous fracture, family history of hip fracture or spinal osteoporosis, smoking, shortening of the stature, and use of arms to rise from a chair. The association of these risk factors with BMD was examined in development cohorts of 300 Finnish postmenopausal women with a fracture and in a population control of 434 women aged 65–72. Validation cohorts included 200 fracture patients and a population control of 943 women aged 58–69. MOI identified femoral neck osteoporosis in these cohorts as well as the Osteoporosis Self-Assessment Tool (OST). In the pooled fracture cohort, the association of BMI-based FRAX fracture risk with MOI was good. After BMD measurement, MOI identified well FRAX hip fracture risk-based Intervention Thresholds (ITs) (AUC 0.74–0.90).

Assessment of fracture risk

Fractures are a common complication of osteoporosis. Although osteoporosis is defined by bone mineral density at the femoral neck, other sites and validated techniques can be used for fracture prediction. Several clinical risk factors contribute to fracture risk independently of BMD. These include age, prior fragility fracture, smoking, excess alcohol, family history of hip fracture, rheumatoid arthritis and the use of oral glucocorticoids. These risk factors in conjunction with BMD can be integrated to provide estimates of fracture probability using the FRAX ® tool. Fracture probability rather than BMD alone can be used to fashion strategies for the assessment and treatment of osteoporosis.

Human genetics of osteoporosis

A family history of hip fracture carries a twofold increased risk of fracture among descendants. Genetic factors indeed play a major role in the determination of bone mineral density (BMD) and osteoporosis risk. Multiple chromosomal loci have been mapped by linkage approaches which potentially carry hundreds of genes involved in the determination of bone mass and quality. Association studies based on candidate gene polymorphisms and subsequent meta-analyses, and the more recent genome-wide association studies (GWAS), have clearly identified a handful of genes associated with BMD and/or fragility fractures. Among them are genes coding for the LDL-receptor related protein 5 (LRP5), estrogen receptor alpha (ESR1) and osteoprotegerin, OPG (TNFRSf11b). However, the percentage of osteoporosis risk explained by any of these polymorphisms is small, indicating that most genetic risk factors remain to be discovered and/or that interaction with environmental factors needs further consideration.

Practical guidance for the management of aromatase inhibitor-associated bone loss

BackgroundRecent studies indicate that women with breast cancer are at increased risk of fracture compared with their age-matched peers. Current treatment guidelines are inadequate for averting fractures in osteopenic women, especially those receiving aromatase inhibitor (AI) therapy. Therefore, we sought to identify clinically relevant risk factors for fracture that can be used to assess overall fracture risk and to provide practical guidance for preventing and treating bone loss in women with breast cancer receiving AI therapy. MethodsSystematic review of pertinent information from published literature and meeting abstracts through December 2007 was carried out to identify factors contributing to fracture risk in women with breast cancer. An evidence-based medicine approach was used to select risk factors that can be used to determine when to initiate bisphosphonate treatment of aromatase inhibitor-associated bone loss (AIBL). ResultsFracture risk factors were chosen from large, well-designed, controlled, population-based trials in postmenopausal women. Evidence from multiple prospective clinical trials in women with breast cancer was used to validate AI therapy as a fracture risk factor. Overall, eight fracture risk factors were validated in women with breast cancer: AI therapy, T-score <-1.5, age >65 years, low body mass index (BMI <20 kg/m2), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking. Treatment recommendations were derived from randomized clinical trials. ConclusionsThe authors recommend the following for preventing and treating AIBL in women with breast cancer. All patients initiating AI therapy should receive calcium and vitamin D supplements. Any patient initiating or receiving AI therapy with a T-score ≥-2.0 and no additional risk factors should be monitored every 1–2 years for change in risk status and bone mineral density (BMD). Any patient initiating or receiving AI therapy with a T-score <-2.0 should receive bisphosphonate therapy. Any patient initiating or receiving AI therapy with any two of the following risk factors—T-score <-1.5, age >65 years, low BMI (<20 kg/m2), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking—should receive bisphosphonate therapy. BMD should be monitored every 2 years, and treatment should continue for at least 2 years and possibly for as long as AI therapy is continued. To date, the overwhelming majority of clinical evidence supports zoledronic acid 4 mg every 6 months to prevent bone loss in women at high risk. Although there is a trend towards fewer fractures with zoledronic acid, studies completed to date have not been designed to capture significant differences in fracture rate, and longer follow-up is needed.

Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS)

The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older. The prevalence of fragility fractures is about 15.1% in the women and 12.8% in the men. Moreover, advanced age, sedentarism, family history of hip fracture, current smoking, recurrent falls, diabetes mellitus and poor quality of life are the main clinical risk factors associated with fragility fractures. The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older with the purpose of identifying the prevalence and the main clinical risk factors (CRF) associated with osteoporotic fracture in our population. A total of 2,420 individuals (women, 70%) from 150 different cities in the five geographic regions in Brazil, and all different socio-economical classes were selected to participate in the present survey. Anthropometrical data as well as life habits, fracture history, food intake, physical activity, falls and quality of life were determined by individual quantitative interviews. The representative sampling was based on Brazilian National data provided by the 2000 and 2003 census. Low trauma fracture was defined as that resulting of a fall from standing height or less in individuals 50 years or older at specific skeletal sites: forearm, femur, ribs, vertebra and humerus. Sampling error was 2.2% with 95% confidence intervals. Logistic regression analysis models were designed having the fragility fracture as the dependent variable and all other parameters as the independent variable. Significance level was set as p < 0.05. The average of age, height and weight for men and women were 58.4 +/- 12.8 and 60.1 +/- 13.7 years, 1.67 +/- 0.08 and 1.56 +/- 0.07 m and 73.3 +/- 14.7 and 64.7 +/- 13.7 kg, respectively. About 15.1% of the women and 12.8% of the men reported fragility fractures. In the women, the main CRF associated with fractures were advanced age (OR = 1.6; 95% CI 1.06-2.4), family history of hip fracture (OR = 1.7; 95% CI 1.1-2.8), early menopause (OR = 1.7; 95% CI 1.02-2.9), sedentary lifestyle (OR = 1.6; 95% CI 1.02-2.7), poor quality of life (OR = 1.9; 95% CI 1.2-2.9), higher intake of phosphorus (OR = 1.9; 95% CI 1.2-2.9), diabetes mellitus (OR = 2.8; 95% CI 1.01-8.2), use of benzodiazepine drugs (OR = 2.0; 95% CI 1.1-3.6) and recurrent falls (OR = 2.4; 95% CI 1.2-5.0). In the men, the main CRF were poor quality of life (OR = 3.2; 95% CI 1.7-6.1), current smoking (OR = 3.5; 95% CI 1.28-9.77), diabetes mellitus (OR = 4.2; 95% CI 1.27-13.7) and sedentary lifestyle (OR = 6.3; 95% CI 1.1-36.1). Our findings suggest that CRF may contribute as an important tool to identify men and women with higher risk of osteoporotic fractures and that interventions aiming at specific risk factors (quit smoking, regular physical activity, prevention of falls) may help to manage patients to reduce their risk of fracture.

Bone health in postmenopausal women (PMW) with hormone-sensitive breast cancer (HSBC) receiving adjuvant aromatase inhibitor (AI) therapy

11556 Background: AIs are approved for PMW with HSBC. The near complete reduction in estrogen synthesis with AIs exacerbates the risk for bone loss, osteoporosis, and bone fractures. Methods: Incidence of fracture and osteoporosis, bone mineral density (BMD), and bone turnover markers were evaluated in adjuvant AI trials (ATAC, BIG 1–98, ALIQUOT, IES, LEAP, MA.17). Results: In healthy PMW, all AIs (steroidal or nonsteroidal) are associated with increased bone turnover markers. In PMW with HSBC, any AI (anastrozole [ANA], exemestane [EXE], or letrozole [LET]) decreases BMD and increases fracture and osteoporosis rate vs either placebo (PLA) or tamoxifen (TAM) regardless of treatment setting (Table). After 5 years of ANA, PMW shifted from normal to osteopenic BMD and lost about 8% BMD at the spine and hip. In IES, increased bone turnover was seen in PMW who switched to EXE following prior TAM. Similar findings were seen in PMW who had prior TAM in ALIQUOT. AI-associated bone loss stabilizes with completion of therapy and is attenuated when zoledronic acid (ZOL) is added to the treatment regimen in either pre- or PMW. Conclusions: Irrespective of setting and class, all AIs decrease BMD and increase bone turnover markers, resulting in increased risk for osteoporosis and bone fractures. Concomitant use of ZOL can attenuate these risks. Current guidelines rely solely on the presence of osteoporosis (BMD < -2.5) to guide bisphosphonate intervention. As 80% of fractures occur in osteopenic women, this threshold appears inadequate for averting fractures in PMW with HSBC. It would be prudent to give ZOL 4 mg twice yearly to PMW who are taking AIs and have a T-score < -2.0, and those with any 2 following risk factors: T-score < - 1.5, age >65 years, family history of hip fracture, personal history of fragility fracture after age 50, smoking, or oral corticosteroid use >6 months. Setting Trial N FU (mo) Lumbar BMD (%) Fracture rate (%) Ref Upfront ATAC bone substudy 167 60 − 6.1 ANA +2.8 TAM Coleman 2006 ASCO abs 511 ATAC 6241 68 11.0 ANA* 7.7 TAM Howell 2005 Lancet BIG 1–98 8010 25.6 NR NR 5.7 LET* 4.0 TAM Thürlimann 2005 NEJM Switch IES bone substudy 206 24 −4.0* EXE −0.6 TAM Coleman 2007 Lancet Oncol IES 4724 58 7.0 EXE* 5.0 TAM Coleman 2007 Lancet Oncol Extended MA.17B 226 24 −5.4 LET* −0.7 PLA Perez 2006 JCO MA.17 5187 30 5.3 LET 4.6 PLA Goss 2005 JNCI *P<0.01; NR=not reported. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, Elly Lilly, GlaxoSmithKline, Novartis, Novo Nordisk, Pfizer, Roche, Schering, Solvay, Wyeth

Effects of Raloxifene on Fracture Risk in Postmenopausal Women: The Raloxifene Use for The Heart Trial

Using data from a randomized placebo-controlled trial of 10,101 postmenopausal women not selected on the basis of osteoporosis, we examined whether the effect of raloxifene treatment on fractures was consistent across categories of fracture risk. Treatment with raloxifene for 5 yr reduced the risk of clinical vertebral fractures, but not nonvertebral fractures, irrespective of the presence or absence of risk factors for fracture. In The Raloxifene Use for The Heart (RUTH) trial, women assigned to raloxifene had a lower risk of clinical vertebral fractures but not nonvertebral fractures. However, it is uncertain whether the effect of raloxifene on fractures in this population not selected for low BMD differs according to risk factors for fractures. We randomly assigned 10,101 postmenopausal women >or=55 yr of age with documented coronary heart disease or at high risk for coronary events to 60 mg raloxifene daily or placebo and followed them for a median of 5.6 yr. Fractures (nonvertebral and clinical vertebral) were prespecified secondary endpoints that were reported at semiannual visits. Fractures were adjudicated and confirmed using X-ray reports or medical records. There was no difference between raloxifene and placebo groups in risk of nonvertebral fractures (428 versus 438 events; hazard ratio [HR], 0.96; 95% CI, 0.84-1.10), including hip/femur (89 versus 103 events; HR, 0.85; 95% CI, 0.64-1.13) and wrist (107 versus 111 events; HR, 0.95; 95% CI, 0.73-1.24) fractures. Women treated with raloxifene had a lower risk of clinical vertebral fractures (64 versus 97 events; HR, 0.65; 95% CI, 0.47-0.89). The effect of treatment with raloxifene on risk of nonvertebral and clinical vertebral fractures was consistent across fracture risk categories defined at baseline by age, smoking status, physical activity level, prior history of fracture, family history of hip fracture, diabetes mellitus, previous use of hormone therapy, thyroid hormone use, statin use, weight loss, body mass index, or fracture specific summary risk score. In older women with or at high risk of coronary heart disease not selected on the basis of osteoporosis or increased fracture risk, treatment with raloxifene for 5 yr reduced the risk of clinical vertebral fractures, but not nonvertebral fractures, irrespective of presence or absence of risk factors for fracture.