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

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

Calcium and vitamin D intake influence bone mass,but not short-term fracture risk,in Caucasian postmenopausal women from the National Osteoporosis Risk Assessment (NORA) study

Summary The impact of calcium and vitamin D intake on bone density and one-year fracture risk was assessed in 76,507 postmenopausal Caucasian women. Adequate calcium with or without vitamin D significantly reduced the odds of osteoporosis but not the risk of fracture in these Caucasian women. Introduction Calcium and vitamin D intake may be important for bone health; however, studies have produced mixed results. Methods The impact of calcium and vitamin D intake on bone mineral density (BMD) and one-year fracture incidence was assessed in 76,507 postmenopausal Caucasian women who completed a dietary questionnaire that included childhood, adult, and current consumption of dairy products. Current vitamin D intake was calculated from milk, fish, supplements and sunlight exposure. BMD was measured at the forearm, finger or heel. Approximately 3 years later, 36,209 participants returned a questionnaire about new fractures. The impact of calcium and vitamin D on risk of osteoporosis and fracture was evaluated by logistic regression adjusted for multiple covariates. Results Higher lifetime calcium intake was associated with reduced odds of osteoporosis (peripheral BMD T-score ≤−2.5; OR = 0.80; 95% CI 0.72, 0.88), as was a higher current calcium (OR = 0.75; (0.68, 0.82)) or vitamin D intake (OR = 0.73; 95% CI 0.0.66, 0.81). Women reported 2,205 new osteoporosis-related fractures. The 3-year risk of any fracture combined or separately was not associated with intake of calcium or vitamin D. Conclusions Thus, higher calcium and vitamin D intakes significantly reduced the odds of osteoporosis but not the 3-year risk of fracture in these Caucasian women. Sources of support: This work was supported by grant AG1406701 from the National Institute on Aging. The National Osteoporosis Risk Assessment (NORA) was funded and managed by Merck & Co Inc.     

Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday

Summary  Based upon interest in a bisphosphonate drug holiday, we evaluate the risk for hip fracture after bisphosphonate discontinuation. Among women compliant with bisphosphonates for ≥2 years, the risk of hip fracture was increased after discontinuation, although with higher compliance and a longer duration of preceding bisphosphonate therapy, this risk was attenuated. Introduction  Recent data suggest that hip fracture risk was not significantly increased among women receiving 5 years of bisphosphonate therapy who were subsequently randomized to placebo. We studied older women compliant with bisphosphonates ≥2 years to evaluate the risk of hip fracture after bisphosphonate discontinuation. Methods  Using administrative databases from a large U.S. healthcare organization, we identified women initiating bisphosphonate therapy compliant (Medication Possession Ratio, MPR ≥66%) for 2 years. We examined the rate of hip fracture among women who discontinued bisphosphonates versus those who remained on therapy. Results  At 2 years, 9,063 women were eligible for analysis. Hip fracture incidence among women who discontinued bisphosphonates versus those who did not was 8.43 versus 4.67 per 1000 person years (p = 0.016). The adjusted hazard ratio of hip fracture per 90 days following discontinuation was 1.2 (1.1–1.3). For women with higher compliance at 2 years (MPR ≥80%) or compliant for 3 years, there were no significant differences in risk associated with discontinuation. Conclusions  The rate of hip fracture was increased among women compliant with bisphosphonate therapy for 2 years who subsequently discontinued, suggesting that discontinuation is not advisable under these conditions. This association was attenuated with higher compliance and a longer duration of previous bisphosphonate therapy. Funding This project was funded by Novartis Pharmaceuticals and the Arthritis Foundation. The investigators also receive support from the National Institutes of Health (AR053351, AR052361). The authors independently developed the analysis plan, extracted the data, conducted the analysis, and interpreted the results.     

Genetic Variation in Candidate Osteoporosis Genes, Bone Mineral Density, and Fracture Risk: The Study of Osteoporotic Fractures

Candidate osteoporosis gene variants were examined for associations with fracture risk and bone mineral density (BMD). A total of 9704 white women were recruited at four U.S. clinical centers and enrolled into the Study of Osteoporotic Fractures, a longitudinal cohort study. Genotyping of 31 polymorphisms from 18 candidate osteoporosis genes was performed in 6752 women. Incident radiographic fractures were identified at the third and eighth examinations compared with the baseline examination. BMD was measured at the total hip by dual-energy X-ray absorptiometry. Analyses were adjusted for age, clinic site, and self-reported ethnicity. During a mean follow-up of 14.5 years, a total of 849 hip, 658 vertebral, and 2496 nonhip/nonvertebral fractures occurred in 6752 women. Women carrying the ALOX15_G48924T T/T genotype had a higher rate of hip fracture (hazard ratio [HR] = 1.33;95% confidence interval [95% CI] = 1.00–1.77) compared with the G/G genotype. Compared with those carrying the PRL_T228C T/T genotype, women with either the C/C (HR = 0.80; 95% CI = 0.67–0.95) or C/T (HR = 0.81; 95% CI = 0.68–0.97) genotype had a lower rate of nonvertebral/nonhip fractures. Women carrying the BMP2_A125611G G/G genotype had a higher rate of vertebral fracture (odds ratio [OR] = 1.51; 95% CI = 1.03–2.23) compared with the A/A genotype. Women with the ESR1_C1335G G/G genotype had a higher rate of vertebral fracture (OR = 1.64; 95% CI = 1.07–2.50) compared with the C/C genotype. Compared with those with the MMP2_C595T C/C genotype, women with the C/T (OR = 0.79; 95% CI = 0.65–0.96) or T/T (OR = 0.44; 95% CI = 0.27–0.72) genotype had a lower rate of vertebral fracture. In conclusion, polymorphisms in several candidate genes were associated with hip, vertebral, and nonhip/nonvertebral fractures but not with total hip BMD in this large population based cohort study.     

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

Summary  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. Introduction  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. Methods  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. Results  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). Conclusion  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.     

Effects of treatment with fluoride on bone mineral density and fracture risk - a meta-analysis

Summary Fluoride has fallen into discredit due to the absence of an anti-fracture effect. However, in this meta-analysis, a fracture reducing potential was seen at low fluoride doses [≤20 mg fluoride equivalents (152 mg monofluorophosphate/44 mg sodium fluoride)]: OR = 0.3, 95% CI: 0.1–0.9 for vertebral and OR = 0.5, 95% CI: 0.3–0.8 for non-vertebral fractures. Introduction Fluoride is incorporated into bone mineral and has an anabolic effect. However, the biomechanical competence of the newly formed bone may be reduced. Methods A systematic search of PubMed, Embase, and ISI web of science yielded 2,028 references. Results Twenty-five eligible studies were identified. Spine BMD increased 7.9%, 95% CI: 5.4–10.5%, and hip BMD 2.1%, 95% CI: 0.9–3.4%. A meta-regression showed increasing spine BMD with increasing treatment duration (5.04 ± 2.16%/year of treatment). Overall there was no significant effect on the risk of vertebral (OR = 0.8, 95% CI: 0.5–1.5) or non-vertebral fracture (OR = 0.8, 95% CI: 0.5–1.4). With a daily dose of ≤20 mg fluoride equivalents (152 mg monofluorophosphate/44 mg sodium fluoride), there was a statistically significant reduction in vertebral (OR = 0.3, 95% CI: 0.1–0.9) and non-vertebral (OR = 0.5, 95% CI: 0.3–0.8) fracture risk. With a daily dose >20 mg fluoride equivalents, there was no significant reduction in vertebral (OR = 1.3, 95% CI: 0.8–2.0) and non-vertebral (OR = 1.5, 95% CI: 0.8–2.8) fracture risk. Conclusions Fluoride treatment increases spine and hip BMD, depending on treatment duration. Overall there was no effect on hip or spine fracture risk. However, in subgroup analyses a low fluoride dose (≤20 mg/day of fluoride equivalents) was associated with a significant reduction in fracture risk.     

Fracture incidence and changes in quality of life in women with an inadequate clinical outcome from osteoporosis therapy: the Observational Study of Severe Osteoporosis (OSSO)

Summary In this observational study of women with an inadequate clinical outcome to osteoporosis therapy, those with a fracture at baseline were more likely to sustain an incident fracture and have a worse health-related quality of life than those without prior fracture. Introduction The Observational Study of Severe Osteoporosis (OSSO) was designed to assess the fracture incidence and health-related quality of life (HRQoL) in women with an inadequate clinical outcome to osteoporosis therapy. Methods Post-menopausal women (N = 1,885) with established osteoporosis and an inadequate clinical response to osteoporosis drug therapy defined as: a) a fragility fracture despite therapy for one year (index fracture, N = 988), or b) discontinued drug therapy due to adverse effects and/or non-compliance (N = 897), were assessed during one year for HRQoL using the EQ-5D and the QUALEFFO questionnaires. Results One hundred and sixty-six (8.8%) women had a total of 209 incident fractures (1,139 fractures/10,000 women-years). Women with an index fracture were more likely to sustain an incident fracture than those without prior fractures (hazard ratio 1.91; 95% CI: 1.37–2.66; p < 0.001). Co-morbidities or antidepressant use at baseline also increased the risk of incident fracture. Median total EQ-5D Health State Values and QUALEFFO scores were worse in women with an incident fracture regardless of index fracture status. The worst scores were reported in the EQ-5D sub-domains of self-care, usual activities and pain/discomfort. Conclusions Women with an inadequate response to osteoporosis therapy had a high rate of incident fracture which had an adverse impact on HRQoL.     

Stress urinary incontinence and counseling and practice of pelvic floor exercises postpartum in low-income Hispanic women

The purpose of the study was to provide estimates of stress urinary incontinence (SUI) and practice of pelvic floor muscle training (PFMT) postpartum as well as counseling during and after pregnancy among Hispanic women. Two hundred Hispanic women were surveyed 6 months postpartum. Twenty-three percent had SUI with onset primarily during pregnancy (70%). Only 20% had received information regarding SUI and PFMT during pregnancy or postpartum. Most women not counseled wished they were (81%). Less counseling occurred among Hispanic women with lower levels of education (odds ratio [OR] = .39; 95% confidence interval [CI] = 0.19–0.82; p = 0.02) and those whose primary language was Spanish (OR = .36; 95% CI = 0.15–0.87; p = 0.02), while higher rates occurred among women with a forceps delivery (OR = 2.94; 95% CI = 1.06–7.78; p = 0.03). Fifty-seven percent of women counseled practiced the exercises. Primary reasons for noncompliance were belief that PFMT would not help (47%), and not understanding the instructions (39%). SUI and PFMT counseling is low among Hispanic women. Most women desire such information, and improvement in performance of PFMT among this group is possible. An erratum to this article can be found at     

Loss of treatment benefit due to low compliance with bisphosphonate therapy

Summary Among 8,822 new female bisphosphonate users, non-compliant bisphosphonate use was associated with a 45% increased risk of osteoporotic fracture compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance. These results emphasize the importance of treatment compliance in obtaining maximal treatment benefit. Introduction Bisphosphonates are widely used to treat osteoporosis and reduce fracture risk. Low compliance is frequent and will limit treatment benefit. Methods New female users of alendronate or risedronate between 1999–2004, aged ≥45 years were identified from PHARMO-RLS, including drug-dispensing and hospitalization data of ≥2 million residents of the Netherlands. Patients were followed until first hospitalisation for an osteoporotic fracture, death, or end of study period. Compliance with bisphosphonates during follow-up was measured over 90-day intervals using Medication Possession Ratio (MPR). The association between compliance and fracture risk was analyzed using time-dependent Cox-regression. Results The study cohort included 8,822 new female bisphosphonate users, contributing in total 22,484 person-years of follow-up. During follow-up, 176 osteoporotic fractures occurred (excluding the first six months). Non-compliant bisphosphonate use was associated with a 45% increased fracture risk compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance (p-value <0.05 for trend). A MPR <20% was associated with an 80% increased fracture risk compared to a MPR ≥90%. Conclusions These results show a statistically significant association between level of compliance with bisphosphonates and level of fracture risk, emphasizing the importance of treatment compliance in obtaining maximal treatment benefit. The study was financially supported by an unrestricted grant from Novartis Pharma AG, Basel, Switzerland.     

A Retrospective Case–Control Study Assessing the Role of Trabecular Bone Score in Postmenopausal Caucasian Women with Osteopenia: Analyzing the Odds of Vertebral Fracture

This case–control study assessed whether the trabecular bone score (TBS), determined from gray-level analysis of DXA images, might be of any diagnostic value, either alone or combined with bone mineral density (BMD), in the assessment of vertebral fracture risk among postmenopausal women with osteopenia. Of 243 postmenopausal Caucasian women, 50–80 years old, with BMD T-scores between –1.0 and –2.5, we identified 81 with osteoporosis-related vertebral fractures and compared them with 162 age-matched controls without fractures. Primary outcomes were BMD and TBS. For BMD, each incremental decrease in BMD was associated with an OR = 1.54 (95% CI = 1.17–2.03), and the AUC was 0.614 (0.550–0.676). For TBS, corresponding values were 2.53 (1.82–3.53) and 0.721 (0.660–0.777). The difference in the AUC for TBS vs. BMD was statistically significant (p = 0.020). The OR for (TBS + BMD) was 2.54 (1.86–3.47) and the AUC 0.732 (0.672–0.787). In conclusion, the TBS warrants a closer look to see whether it may be of clinical usefulness in the determination of fracture risk in postmenopausal osteopenic women.     

Effectiveness of interventions to improve the detection and treatment of osteoporosis in primary care settings: a systematic review and meta-analysis

This study aims to evaluate the effectiveness of primary care interventions to improve the detection and treatment of osteoporosis. Eight electronic databases and six gray literature sources were searched. Randomized controlled trials, controlled clinical trials, quasi-randomized trials, controlled before–after studies, and interrupted time series written in English or French from 1985 to 2009 were considered. Eligible studies had to include patients at risk (women ≥ 65 years, men ≥ 70 years, and men/women ≥ 50 years with at least one major risk factor for osteoporosis) or at high risk (men/women using oral glucocorticoids or with previous fragility fractures) for osteoporosis and fractures. Outcomes included bone mineral density (BMD) testing, osteoporosis treatment initiation, and fractures. Data were pooled using a random effects model when applicable. Thirteen studies were included. The majority were multifaceted and involved patient educational material, physician notification, and/or physician education. Absolute differences in the incidence of BMD testing ranged from 22% to 51% for high-risk patients only and from 4% to 18% for both at-risk and high-risk patients. Absolute differences in the incidence of osteoporosis treatment initiation ranged from 18% to 29% for high-risk patients only and from 2% to 4% for at-risk and high-risk patients. Pooling the results of six trials showed an increased incidence of osteoporosis treatment initiation (risk difference (RD) = 20%; 95% CI: 7–33%) and of BMD testing and/or osteoporosis treatment initiation (RD = 40%; 95% CI: 32–48%) for high-risk patients following intervention. Multifaceted interventions targeting high-risk patients and their primary care providers may improve the management of osteoporosis, but improvements are often clinically modest.     

Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: results from the Women’s Health Initiative

Summary  Risk for falls and fractures increases after breast cancer or other cancer diagnosis in postmenopausal women. Factors other than falls may be the major causes for the increased fracture risk. Introduction  Cancer treatment and prognosis may have detrimental effects on bone health. However, there is a lack of prospective investigations on fracture risk among incident cancer cases. Methods  In this study, postmenopausal women (N = 146,959) from the Women’s Health Initiative prospective cohort, who had no cancer history at baseline, were followed for up to 9 years and classified into no cancer, incident breast cancer (BC) and incident other cancer (OC) groups. The main outcomes measured were incident fractures and falls before and after cancer diagnosis. Hazards ratios (HR) and 95% confidence intervals (CI) were computed from Cox proportional hazards model. Results  While hip fracture risk before a cancer diagnosis was similar between the no cancer and cancer groups, hip fracture risk was significantly higher after BC diagnosis (HR = 1.55, CI = 1.13–2.11) and the elevated risk was even more notable after OC diagnosis (HR = 2.09, CI = 1.65–2.65). Risk of falls also increased after BC (HR = 1.15, CI = 1.06–1.25) or OC diagnosis (HR = 1.27, CI = 1.18–1.36), but could not fully explain the elevated hip fracture risk. Incident clinical vertebral and total fractures were also significantly increased after OC diagnosis (p < 0.05). Conclusions  Postmenopausal women have significantly elevated risks for falls and fractures after a cancer diagnosis. The causes for this increased risk remained to be investigated.     

Comparison of direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate: a population-based study

Summary  This population-based study aimed to compare direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. During a 2-year follow-up period, compared to those with medication possession ratio (MPR) ≥ 80%, women with MPR < 80% incurred significantly higher physician care costs and hospital care costs. Introduction  This study aimed to compare direct health care costs related to the treatment of osteoporosis and osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. Methods  A cohort of 15,027 women having initiated alendronate or risedronate was identified. MPR and direct health care costs (physician care, hospital care, drugs) were assessed during a 2-year period. Regression models were used to estimate mean predicted cost for compliant (MPR ≥ 80%) and noncompliant (MPR < 80%) women. Results  Mean predicted physician care cost (in Canadian dollars) was $51 among women with MPR < 80% and $34 among those with MPR ≥ 80%: mean difference $17, 95% confidence interval (CI) $2–22. Mean predicted hospital care cost was $568 among women with MPR < 80% and $379 among those with MPR ≥ 80%: mean difference $189, 95% CI $56–320. Mean predicted drug cost was $439 among women with MPR < 80% and $1,068 among those with MPR ≥ 80%: mean difference $−639, 95% CI $−649 to −629. Conclusion  Compared to compliant women, noncompliant women incurred significantly higher physician care and hospital care costs. Due to lower drug costs, total direct health care costs were lower among noncompliant women.    This study was funded by a grant from the Canadian Institutes of Health Research (Ottawa, Canada)     

The prevalence of radiographic vertebral fractures in Latin American countries: the Latin American Vertebral Osteoporosis Study (LAVOS)

Summary  In the first population-based study of vertebral fractures in Latin America, we found a 11.18 (95% CI 9.23–13.4) prevalence of radiographically ascertained vertebral fractures in a random sample of 1,922 women from cities within five different countries. These figures are similar to findings from studies in Beijing, China, some regions of Europe, and slightly lower than those found in the USA using the same standardized methodology. Introduction  We report the first study of radiographic vertebral fractures in Latin America. Methods  An age-stratified random sample of 1,922 women aged 50 years and older from Argentina, Brazil, Colombia, Mexico, and Puerto Rico were included. In all cases a standardized questionnaire and lateral X-rays of the lumbar and thoracic spine were obtained after informed consent. Results  A standardized prevalence of 11.18 (95% CI 9.23–13.4) was found. The prevalence was similar in all five countries, increasing from 6.9% (95% CI 4.6–9.1) in women aged 50–59 years to 27.8% (95% CI 23.1–32.4) in those 80 years and older (p for trend < 0.001). Among different risk factors, self-reported height loss OR = 1.63 (95% CI: 1.18–2.25), and previous history of fracture OR = 1.52 (95% CI: 1.14–2.03) were significantly (p < 0.003 and p < 0.04 respectably) associated with the presence of radiographic vertebral fractures in the multivariate analysis. In the bivariate analyses HRT was associated with a 35% lower risk OR = 0.65 (95% CI: 0.46–0.93) and physical activity with a 27% lower risk of having a vertebral fracture OR = 0.73 (95% CI: 0.55–0.98), but were not statistically significant in multivariate analyses Conclusion  We conclude that radiographically ascertained vertebral fractures are common in Latin America. Health authorities in the region should be aware and consider implementing measures to prevent vertebral fractures.     

Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women

Summary The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk. Introduction Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5’-splicing site of exon 5 of ESR1. Methods The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models. Results Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (β = 0.008; p = 0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score<−2.5 at the spine: OR 2.46, 95% CI 1.30–4.65; at the hip: OR 3.79(1.64–8.74)) and low trauma fractures (OR 2.31(1.29–4.14)) than those with ≥18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with ≥18 repeats (−1.96% vs. −1.61%, p = 0.029). Conclusions ESR1 CA repeat polymorphism is associated with BMD variation, rate of bone loss and fracture risk, and this may be a useful genetic marker for fracture risk assessment. Funding Source: This project is supported by CRCG Grant, Bone Health Fund, Matching Grant and Osteoporosis and Endocrine Research Fund of the University of Hong Kong.     

Use of Bisphosphonates and Risk of Breast Cancer

A decreased risk of breast cancer has been reported among patients given bisphosphonates. The present aims were to study potential associations between different antiosteoporosis drugs, including bisphosphonates, and the risk of breast cancer before and after start of treatment and to appraise possible dose–effect relationships. From national Danish registers, all female users of bisphosphonates aged ≥40 years and other drugs against osteoporosis between 1996 and 2006 were identified (n = 87,104). This cohort was compared with a control group, where each patient was matched on age with three nonexposed women from the general population (n = 261,322). Before start of most drugs against osteoporosis an increased risk of breast cancer was seen compared to controls (e.g., adjusted OR = 1.09, 95% CI 1.04–1.16 for alendronate). This excess risk was higher in younger women (e.g., OR = 4.48, 95% CI 2.98–6.75 for alendronate in women ≤50 years) and disappeared in women older than 70 years (e.g., OR = 0.95, 95% CI 0.88–1.01 for alendronate). In contrast, a decreased risk of breast cancer was seen after start of alendronate (HR = 0.53, 95% CI 0.38–0.73), etidronate (HR = 0.80, 95% CI 0.73–0.89), and raloxifene (HR = 0.53, 95% CI 0.38–0.73). No dose–response relationship was present for alendronate and etidronate, whereas a decreasing risk was seen with increasing daily dose of raloxifene. Bisphosphonate treatment in women was associated with a reduced risk of breast cancer. However, no causal relationship seemed to be present.     

Ventriculostomy-related hemorrhage in patients on antiplatelet therapy for endovascular treatment of acutely ruptured intracranial aneurysms. A meta-analysis

The risk of ventriculostomy-related hemorrhage among patients requiring antiplatelet therapy (AT) for the endovascular treatment of acutely ruptured intracranial aneurysms needed further investigation. The authors performed a systematic review and meta-analysis of the literature examining the EVD-related hemorrhage rate among patients with and without AT (controls). According to PRISMA guidelines, a comprehensive review of studies published between January 1990 and April 2018 was carried out. The authors identified series with > 5 patients reporting the EVD-associated hemorrhage rate among the AT group and the control group. Variables influencing outcomes were analyzed using a random-effects meta-analysis model. We included 13 studies evaluating 516 (with AT) and 647 (without AT) patients requiring ventriculostomy. EVD-related hemorrhage rates were higher among the AT group (125/516 = 20.9%, 95% CI = 11.9–30%, I2 = 90% vs 57/647 = 9%, 95% CI = 5.5–12.5%, I2 = 45.8%) (p < 0.0001). Major EVD-associated hemorrhage rates were low in both the AT and control group (25/480 = 4.4%, 95% CI = 1.7–7.7%, I2 = 53.9% vs 6/647 = 0.7%, 95% CI = 0.03–1.7%, I2 = 0%) (p < 0.0001). Ventriculostomy before embolization and intraprocedural AT were associated with lower rates of EVD-related bleeding (32/230 = 9.6%, 95% CI = 2.1–17.1%, I2 = 75.4% vs 6/24 = 25.1%, 95% CI = 8.8–41%, I2 = 0%) (p < 0.02). The rate of major hemorrhage was higher after dual AT (CP + ASA) compared to single AT (ASA or CP) used as an intraprocedural loading dose (13/173 = 7%, 95% CI = 3.3–10.7%, I2 = 0% vs 6/210 = 1.7%, 95% CI = 0.1–3.4%, I2 = 0%) (p < 0.009). AT during endovascular treatment of acutely ruptured intracranial aneurysms increases the risk of EVD-related hemorrhages, although most of them are small and asymptomatic. When ventriculostomy is performed before endovascular procedures requiring antiplatelet administration, the hemorrhagic risk is minimized. A single antiplatelet therapy is associated with a lower rate of major bleeding than a dual therapy.     

Strap stabilization for proximal junctional kyphosis prevention in instrumented posterior spinal fusion

This is a retrospective, single-institution, cohort study. To evaluate the association of Mersilene tape use and risk of proximal junctional kyphosis (PJK), after surgical correction of adult spinal deformity (ASD) by posterior instrumented fusion (PIF). PJK, following long spinal PIF, is a complication which often requires reoperation. Mersilene tape, strap stabilization of the supra-adjacent level to upper instrumented vertebra (UIV) seems a preventive measure. Patients who underwent PIF for ASD with Mersilene tape stabilization (case group) or without (control group) between 2006 and 2016 were analyzed preoperatively to 2-year follow-up. Matching of potential controls to each case was performed. Radiographic sagittal Cobb angle (SCA), lumbar lordosis, pelvic tilt, sacral slope, and pelvic incidence were measured pre- and postoperatively, using a deformity measuring software program. PJK was defined as progression of postoperative junctional SCA at UIV ≥ 10°. Eighty patients were included: 20 cases and 60 controls. The cumulative rate of PJK ≥ 10° at 2-year follow-up was 15% in cases versus 38% of controls (OR = 0.28; P = 0.04) with higher latent period in cases, (20 vs. 7.5 months), P = 0.018. Mersilene tape decreased risk of PJK linked with the impact of the following confounders: age, ≥ 55 years old (OR = 0.19; 0.02 ≥ P ≤ 0.03); number of spinal levels fused 7–15 (OR = 0.13; 0.02 ≥ P ≤ 0.06); thoracic UIV (T12–T1) (OR = 0.13; 0.02 ≥ P ≤ 0.06); BMI ≥ 27 kg/m2 (OR = 0.22; 0.03 ≥ P ≤ 0.08); and osteoporosis (OR = 0.13; 0.02 ≥ P ≤ 0.08). Mersilene tape at UIV + 1 level decreases the risk of PJK following PIF for ASD. These slides can be retrieved under Electronic Supplementary Material.     

Combined trans- and periurethral injections of bulking agents for the treatment of intrinsic sphincter deficiency

The purpose of this study was to compare Contigen combined with Durasphere to Contigen injections alone for the treatment of stress urinary incontinence (SUI) with intrinsic sphincter deficiency (ISD). Subjective and objective incontinence outcomes were compared at 2 weeks and 6 months. We compared rates of urinary retention and future incontinence surgery between groups. Thirty-three women underwent combined injections, and 51 underwent Contigen injections. Two weeks postoperatively, more women in the combined group were cured (72.7 vs. 39.2%, P = 0.003), but this difference diminished at 6 months (33.3 vs. 29.4%, P = 0.70). Retention was more common in the combined group (P = 0.002, odds ratio [OR] = 0.062 [95% confidence interval {CI} = 0.007, 0.52]). Twenty-three women in the Contigen and ten in the combined group underwent subsequent incontinence surgery (P = 0.17, OR = 2.03 [95% CI = 0.80, 5.1]). Combining Contigen and Durasphere injections to treat SUI with ISD does not improve outcomes compared to Contigen injections alone. This paper was presented at the 32nd Annual Meeting of the American Association of Gynecologic Laparoscopists, Las Vegas, Nevada, November 19–22, 2003.     

Mild prevalent and incident vertebral fractures are risk factors for new fractures

Summary This prospective four-year study indicates that post-menopausal osteoporotic women with mild prevalent and incident vertebral fractures have an increased risk of incident fractures. Introduction Mild vertebral fractures are under diagnosed as there is disagreement about their clinical significance. Our aim was to assess the risk of subsequent fractures induced by both prevalent and incident mild vertebral fractures in osteoporotic post-menopausal women. Patients and methods Three thousand three hundred and fifty-eight patients, aged 74 ± 6 years, with post-menopausal osteoporosis included in the placebo groups of two clinical trials of strontium ranelate were followed for 4 years. A Cox regression model adjusted on age, body mass index and bone mineral density was used to calculate the relative risk (RR) of fracture in subjects with only mild fractures as compared to patients without fracture, and to patients with at least one grade ≥ 2 fracture. These calculations were made for prevalent and then incident fractures. Results The RR of vertebral fracture in 4 years was 1.8 (1.3–2.4) p < 0.001, and 2.7 (2.3–3.3) p < 0.001 for patients having only mild vertebral fractures and at least one grade ≥ 2 fracture at baseline respectively. The RR of vertebral fracture in the 3rd and 4th years of follow-up was 1.7 (1.1–2.6) p = 0.01, and 1.9 (1.3–2.6) p < 0.001 for patients having during the first 2 years incident mild fractures only, and for patients having at least one grade ≥ 2 incident fracture respectively. The RR of non-vertebral fracture in 4 years was 1.3 (0.9–1.9) p = 0.15 and 1.7 (1.4–2.1) p < 0.001 for patients having only mild or at least one grade ≥ 2 vertebral fracture at baseline respectively. For patients aged more than 70 years, these RR were 1.45 (0.99–2.11) (p = 0.06), and 1.72 (1.36–2.18) p < 0.001 respectively. The RR of non-vertebral fracture in the 3rd and 4th years was 1.68 (1.36–2.09) p < 0.001 for patients having at least one grade ≥ 2 incident fracture during the 2 first years of follow-up. Conclusion Mild vertebral fractures are a risk factor for subsequent vertebral and non-vertebral fracture in postmenopausal women with osteoporosis; 1 out of 4 patients with an incident mild vertebral fracture in 2 years will fracture again within the 2 next years.