[Show abstract][Hide abstract] ABSTRACT: In a 3-year randomized, double-blind, osteoporosis treatment study (N = 7,492), bazedoxifene 20 mg and bazedoxifene 40 mg significantly (P < 0.05) reduced the risk of new vertebral fractures by 42% and 37%, respectively, compared with placebo in postmenopausal women with osteoporosis. This study evaluated the long-term (7-y) efficacy and safety of bazedoxifene in generally healthy postmenopausal women with osteoporosis.
This was a second 2-year extension of the 3-year multicenter outpatient core study. During extension I (years 4-5), women receiving bazedoxifene 40 mg transitioned to bazedoxifene 20 mg. In extension II (years 6-7; N = 1,530), all bazedoxifene-treated women continued bazedoxifene 20 mg. Main outcome measures included year 7 endpoints: incidences of new vertebral and nonvertebral fractures, bone mineral density changes, and safety assessments.
At 7 years, the cumulative incidences of new vertebral fractures were significantly lower in the bazedoxifene (6.4%) and bazedoxifene 20 mg (7.6%) groups than in the placebo group (9.9%); the relative risk reductions were 36.5% and 30.4%, respectively (both P < 0.001). Bazedoxifene had no effect on the overall incidence of nonvertebral fractures (bazedoxifene, 11.2%; bazedoxifene 20 mg, 12.0%; placebo, 10.8%). The mean changes from baseline in lumbar spine bone mineral density were 2.95%, 2.73%, and 2.19%, respectively. Seven-year decreases in total hip bone mineral density were significantly smaller in the bazedoxifene (-1.15%) and bazedoxifene 20 mg (-1.19%) groups than in the placebo group (-2.53%; P ≤ 0.002). Bazedoxifene showed a favorable safety/tolerability profile across 7 years, with similar adverse events, serious adverse events, and study discontinuations in all groups.
Efficacy and safety of bazedoxifene are sustained across 7 years in postmenopausal women with osteoporosis.
Full-text · Article · Feb 2015 · Menopause (New York, N.Y.)
[Show abstract][Hide abstract] ABSTRACT: Objective
To compare the efficacy, discontinuation rates, and safety of once nightly versus twice daily dosing of pregabalin in a community-based trial. Methods
This multicenter, double-blind, 8-week randomized clinical trial compared the effects of 300-mg daily doses of pregabalin given either twice daily or once nightly for the treatment of fibromyalgia in 177 patients. The primary outcome was the comparison of end point mean pain scores derived from a daily diary. ResultsBoth twice daily (88 patients randomized) and once nightly (89 patients) pregabalin significantly reduced the average severity of pain experienced by patients (P < 0.001 for both). Treatment-emergent adverse events were reported by significantly more patients in the twice daily group than those in the once nightly group (P = 0.023). There were no significant differences between the groups for the frequencies of individual adverse events (P > 0.05 for all). There was no significant difference in adverse events or efficacy in patients taking both pregabalin and a selective serotonin and norepinephrine reuptake inhibitor or selective serotonin uptake inhibitor. Conclusion
While a nightly dosing schedule of pregabalin has been used by clinicians hoping to improve treatment, this study showed no significant difference (either beneficial or detrimental) between either treatment option. While there was a decrease in total patient-reported adverse events in the once nightly arm, the lack of specificity in relation to a particular adverse event suggested no real difference in adverse events.
[Show abstract][Hide abstract] ABSTRACT: To quantify the prevalence of potential drug-drug/drug-condition interactions (DDI/DCI) among fibromyalgia patients initiating pregabalin or duloxetine, and to determine the impact of potential DDI/DCI on health care expenditures.
Retrospective cohort study.
U.S. clinical practice, as reflected within a large administrative claims database.
Fibromyalgia patients newly initiating pregabalin or duloxetine between July 1, 2008 and October 1, 2010 (initiation date = index).
Potential DDI measured using clinical software that identifies co-prescription of medications that potentially interact with pregabalin or duloxetine. Potential DCI, drawn from the contraindications and warnings and precautions sections of pregabalin and duloxetine prescribing information, measured using administrative claims-based algorithms. All-cause health care expenditures measured throughout a 6-month postindex period. Analyses included univariate, bivariate, and multivariable statistical approaches.
Seven thousand seven hundred fifty-one pregabalin and 7,785 duloxetine initiators were selected for study: mean age 49 years, 88% female. Only 1.4% of pregabalin initiators had ≥1 potential pregabalin DCI; none had potential pregabalin DDI. In contrast, 67% of duloxetine initiators had potential duloxetine DDI/DCI, driven mostly by potential duloxetine DDI (62% of duloxetine initiators). Compared between pregabalin and duloxetine initiators, differences in the prevalence of potential DDI/DCI were statistically significant (P < 0.001). Multivariable analyses indicated that, among duloxetine initiators, those with potential duloxetine DDI/DCI had postinitiation health care expenditures that were $670 higher (P < 0.001) than those without potential duloxetine DDI/DCI. Among pregabalin initiators, potential pregabalin DDI/DCI were not associated with health care expenditures.
Among fibromyalgia patients initiating pregabalin or duloxetine, potential duloxetine DDI could be highly prevalent. Among duloxetine initiators, potential duloxetine DDI/DCI were significantly associated with increased health care expenditures.
[Show abstract][Hide abstract] ABSTRACT: The frequency and financial impact of potential drug-drug interactions (DDIs) and drug-condition interactions (DCIs) in patients with painful diabetic peripheral neuropathy (DPN) treated with either pregabalin or duloxetine were compared.
This retrospective cohort study was conducted using a large U.S. administrative claims database. Patients selected for study inclusion had a diagnosis of DPN and were newly initiated on either pregabalin or duloxetine between July 1, 2008, and October 1, 2010. Data on potential DDIs and DCIs were collected. Health care costs were measured as the sum of gross covered payments for all medical and prescription claims incurred during the six months after the index date.
The study sample comprised 2499 pregabalin users and 1354 duloxetine users. Among pregabalin users, 48 (1.8%) had at least one potential pregabalin DCI; none had potential pregabalin DDIs. Among duloxetine users, 966 (71%) had at least one potential duloxetine DDI or DCI. The frequencies of potential DDIs and DCIs differed significantly between pregabalin and duloxetine users (p < 0.001). Potential duloxetine DDIs and DCIs were associated with a significant increase in mean health care costs in duloxetine users (p = 0.002). Potential pregabalin DDIs and DCIs were not associated with additional health care costs in pregabalin users.
Among patients with painful DPN treated with either pregabalin or duloxetine, the frequency of potential duloxetine DDIs and DCIs was substantially higher than that of pregabalin. Potential DDIs and DCIs were associated with significantly increased health care costs in duloxetine users.
No preview · Article · Dec 2013 · American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists
[Show abstract][Hide abstract] ABSTRACT: Ibandronate reduces the risk of vertebral and non-vertebral fractures versus placebo in postmenopausal women with osteoporosis. This analysis, in which fractures were reported as safety events, showed that long-term use of ibandronate was associated with low fracture rates over 5 years of treatment.
A previous post-hoc meta-analysis of 2-3 year studies found that ibandronate regimens with annual cumulative exposure (ACE) of ≥10.8 mg reduced the risk of vertebral and nonvertebral fractures (NVFs) versus placebo in postmenopausal women. This post-hoc analysis used individual patient data from the 2-year monthly oral ibandronate in ladies (MOBILE) and dosing intravenous administration (DIVA) studies, including the 3-year long-term extensions (LTEs), to assess fracture risk in patients treated with ibandronate for 5 years.
Patients treated for 2 years in MOBILE with monthly oral ibandronate 150 mg (n = 176) and in DIVA with IV ibandronate every 2 months 2 mg (n = 253) or quarterly 3 mg (n = 263) who continued on the same regimens for 3 additional years in the LTEs were included. Three-year placebo data (n = 1,924) were obtained from the ibandronate osteoporosis vertebral fracture trial in North America and Europe (BONE) and IV Fracture Prevention trials. The primary endpoint was clinical fracture rate; clinical fracture data were collected as adverse events. Time to fracture was analyzed using Kaplan-Meier and statistical analysis was conducted using the log-rank test. All clinical fractures included all NVFs and symptomatic vertebral fractures.
For ibandronate regimens with ACE ≥10.8 mg, time to fracture was significantly longer for all clinical fractures, NVFs, and clinical vertebral fractures versus placebo (P = 0.005). For all fracture types, the rate of fracture appeared stable during the 5-year treatment period.
In women with postmenopausal osteoporosis, continuous treatment with ibandronate over 5 years results in low sustained clinical fracture rate.
No preview · Article · Oct 2013 · Osteoporosis International
[Show abstract][Hide abstract] ABSTRACT: Establishing a Fracture Liaison Service (FLS) to identify and treat patients with a recent fragility fracture has been shown to be effective, save money, useful to document high quality of care, and makes good clinical sense. A FLS starts with an osteoporosis champion and encompasses identification of patients with a recent fracture, diagnostic workup, treatment, and follow-up. A FLS is most effective when it is able to function in multiple settings: the hospital, emergency department, and outpatient clinic. Implementation may be somewhat easier in a closed healthcare system but can be feasible even in an open system. There are many barriers to implementation which can be addressed. The future of FLS care lies in a collaborative systems-based approach with appropriate stakeholder engagement, leading to seamless integration of osteoporosis care.
No preview · Article · Oct 2013 · Current Osteoporosis Reports
[Show abstract][Hide abstract] ABSTRACT: We know improving the quality of care in osteoporosis is an important goal. We have made some strides toward measuring quality of osteoporosis care, focusing on process measures regarding care that is provided. Unfortunately, improving care as measured by these process measures does not always yield improved outcomes. We need to hold health care providers and health care systems responsible not only for health care production but for production of health and well-being. However, there is a multiplicity of factors that will need to be considered to make this next step.
No preview · Article · Oct 2013 · Current Osteoporosis Reports
[Show abstract][Hide abstract] ABSTRACT: Recognizing the significant impact of osteoporosis, The Joint Commission has worked since 2005 to develop performance measures in osteoporosis across the care continuum. This work has led to the development of 3 measures, which may be used at any time to meet hospital quality improvement goals. Plans are in place to submit to the National Quality Forum for endorsement as national consensus standards. The measures were developed under the guidance of a 12 member Technical Advisory Panel.
No preview · Article · Sep 2013 · Current Osteoporosis Reports
[Show abstract][Hide abstract] ABSTRACT: The Committee of Scientific Advisors of International Osteoporosis Foundation (IOF) recommends that papers describing the descriptive epidemiology of osteoporosis using bone mineral density (BMD) at the femoral neck include T-scores derived from an international reference standard.
The prevalence of osteoporosis as defined by the T-score is inconsistently reported in the literature which makes comparisons between studies problematic.
The Epidemiology and Quality of Life Working Group of IOF convened to make its recommendations and endorsement sought thereafter from the Committee of Scientific Advisors of IOF.
The Committee of Scientific Advisors of IOF recommends that papers describing the descriptive epidemiology of osteoporosis using BMD at the femoral neck include T-scores derived from the National Health and Nutrition Examination Survey III reference database for femoral neck measurements in Caucasian women aged 20–29 years.
It is expected that the use of the reference standard will help resolve difficulties in the comparison of results between studies and the comparative assessment of new technologies.
No preview · Article · Jul 2013 · Osteoporosis International
[Show abstract][Hide abstract] ABSTRACT: This observational study showed that after 2 years, both risedronate and alendronate lowered the risk of hip and nonvertebral fractures compared with patients filling in a single bisphosphonate prescription.
Post hoc analyses of the placebo-controlled trials suggested earlier effects for risedronate (6–12 months) than for alendronate (18–24 months). The present study extends our 1-year observational data that confirmed an earlier fracture reduction with risedronate and evaluated the absolute and relative effectiveness of alendronate and risedronate in clinical practice over 2 years.
We observed three cohorts of women aged 65 years and older who initiated once-a-week dosing of bisphosphonate therapy; (1) patients adherent to alendronate (n = 21,615), (2) patients adherent to risedronate (n = 12,215), or (3) patients filling only a single bisphosphonate prescription (n = 5,390) as a referent population. Proportional hazard modeling compared the incidence of hip and nonvertebral fractures among the cohorts over 2 years after the initial prescription.
In this cohort, we previously showed at 12 months a significant reduction of hip and nonvertebral fractures with risedronate but not with alendronate. At the end of 2 years, the cumulative incidence of hip fractures in the referent cohort was 1.9 %, and incidence of nonvertebral fractures was 6.3 %. Relative to the referent, 6 months after initiating therapy and continuing through 2 years, both risedronate and alendronate cohorts had approximately a 45 % lower incidence of hip fractures and a 30 % lower incidence of nonvertebral fractures.
These observations suggest that both risedronate and alendronate are effective at reducing the risk of hip and nonvertebral fracture after 2 years of treatment and support the post hoc analyses of placebo-controlled trials indicating an earlier effect of risedronate.
Full-text · Article · Apr 2013 · Osteoporosis International
[Show abstract][Hide abstract] ABSTRACT: The quality of life during the first 4 months after fracture was estimated in 2,808 fractured patients from 11 countries. Analysis showed that there were significant differences in the quality of life (QoL) loss between countries. Other factors such as QoL prior fracture and hospitalisation also had a significant impact on the QoL loss. INTRODUCTION: The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) was initiated in 2007 with the objective of estimating costs and quality of life related to fractures in several countries worldwide. The ICUROS is ongoing and enrols patients in 11 countries (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, UK and the USA). The objective of this paper is to outline the study design of ICUROS and present results regarding the QoL (measured using the EQ-5D) during the first 4 months after fracture based on the patients that have been thus far enrolled ICUROS. METHODS: ICUROS uses a prospective study design where data (costs and quality of life) are collected in four phases over 18 months after fracture. All countries use the same core case report forms. Quality of life was collected using the EQ-5D instrument and a time trade-off questionnaire. RESULTS: The total sample for the analysis was 2,808 patients (1,273 hip, 987 distal forearm and 548 vertebral fracture). For all fracture types and countries, the QoL was reduced significantly after fracture compared to pre-fracture QoL. A regression analysis showed that there were significant differences in the QoL loss between countries. Also, a higher level of QoL prior to the fracture significantly increased the QoL loss and patients who were hospitalised for their fracture also had a significantly higher loss compared to those who were not. CONCLUSIONS: The findings in this study indicate that there appear to be important variations in the QoL decrements related to fracture between countries.
No preview · Article · Jan 2013 · Osteoporosis International
[Show abstract][Hide abstract] 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.
Full-text · Article · Oct 2012 · Journal of Bone and Mineral Research
[Show abstract][Hide abstract] ABSTRACT: This position paper reviews how the National Bone Health Alliance (NBHA) will execute a project to help assure health professionals of the clinical utility of bone turnover markers; the current clinical approaches concerning osteoporosis and the status and use of bone turnover markers in the USA; the rationale for focusing this effort around two specific bone turnover markers; the need to standardize bone marker sample collection procedures, reference ranges, and bone turnover marker assays in clinical laboratories; and the importance of harmonization for future research of bone turnover markers.
Osteoporosis is a major global health problem, with the prevalence and incidence of osteoporosis for at-risk populations estimated to be 44 million Americans. The potential of bone markers as an additional tool for health care professionals to improve patient outcomes and impact morbidity and mortality is crucial in providing better health care and addressing rising health care costs. This need to advance the field of bone turnover markers has been recognized by a number of organizations, including the International Osteoporosis Foundation (IOF), National Osteoporosis Foundation, International Federation of Clinical Chemistry, and Laboratory Medicine (IFCC), and the NBHA.
This position paper elucidates how this project will standardize bone turnover marker sample collection procedures in the USA, establish a USA reference range for one bone formation (serum procollagen type I N propeptide, s-PINP) and one bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) marker, and standardize bone turnover marker assays used in clinical laboratories. This effort will allow clinicians from the USA to have confidence in their use of bone turnover markers to help monitor osteoporosis treatment and assess future fracture risk. This project builds on the recommendations of the IOF/IFCC Bone Marker Standards Working Group by developing USA reference standards for s-PINP and s-CTX, the markers identified as most promising for use as reference markers.
The goals of this project will be realized through the NBHA and will include its governmental, academic, for-profit, and non-profit sector stakeholders as well as major academic and commercial laboratories. Upon completion, a parallel effort will be pursued to make bone turnover marker measurements reliable and accepted by all health care professionals for facilitating treatment decisions and ultimately be reimbursed by all health insurance payers.
Successful completion of this project will help assure health professionals from the USA of the clinical utility of bone turnover markers and ties in with the parallel effort of the IOF/IFCC to develop worldwide bone turnover reference ranges.
No preview · Article · Jul 2012 · Osteoporosis International
[Show abstract][Hide abstract] ABSTRACT: Guidelines for osteoporosis treatment are available; however, these guidelines suggest when to treat patients, without specific recommendations on what drugs to prescribe in various situations. Choice of osteoporosis therapy should be individualized based on consideration of the efficacy, safety, cost, convenience (i.e., dosing regimen and delivery), and other non-osteoporosis-related benefits associated with each agent. Bisphosphonates, administered orally or intravenously, should be considered first-line therapy, particularly in older patients, owing to their efficacy across multiple skeletal sites; however, there are potential short- and long-term safety concerns. Selective estrogen receptor modulators should be considered for younger postmenopausal women at greater risk for vertebral than hip fractures or as second-line therapy in women who cannot tolerate first-line therapies. Low-dose hormone therapy may be appropriate as prevention in women with menopausal symptoms at lower fracture risk. Calcitonin, with its relatively benign safety profile, may be appropriate for elderly women who may have difficulty following the complex dosing schedules of oral bisphosphonates. Anabolic therapies such as teriparatide should be considered for high-risk patients. Strontium ranelate (approved outside of North America), with both anabolic and antiresorptive properties, may be appropriate for women who cannot tolerate or are unable to take bisphosphonates. Denosumab is a monoclonal antibody appropriate for women at high fracture risk or who have failed other osteoporosis therapies, and may be considered in patients with renal insufficiency. It will be important to incorporate newer agents (e.g., bazedoxifene, tissue selective estrogen complex) into this individualized treatment paradigm to optimize clinical outcomes in patients with osteoporosis.
No preview · Article · Jan 2012 · Osteoporosis International
[Show abstract][Hide abstract] ABSTRACT: The FRAX calculator combines a set of clinical risk factors with country-specific incidence rates to determine the ten-year absolute risk of major osteoporotic fracture. However, regional or country-specific databases from Central American countries are not available. We compared the use of various FRAX databases and the Pluijm algorithm in determining risk of fracture.
We collected clinical risk factor data needed for the FRAX calculator and Pluijm algorithm of Hispanic women in Guatemala and calculated the FRAX absolute risk measures of major osteoporotic fracture and hip fracture. Subjects were postmenopausal women greater than age 40 with no history of using medication that affect bone. A random sample of 204 women in 34 different regions women in Guatemala City was visited in their homes to complete the surveys. The Pluijm risk score and FRAX risk score using the US Hispanic, Spain, and Mexican databases were calculated.
We used the US NOF guidelines for treatment which suggest a treatment threshold for patients with a 10-year hip fracture probability ≥ 3% or a 10-year major osteoporotic fracture risk ≥ 20%. The number of patients meeting the suggested threshold limits for treatment using the Spain and Mexico calculators were identical. There was 100% conformity in threshold limits for both hip and major osteoporotic fracture risk. The mean conformity for any fracture risk between US Hispanic and the other two databases was 97.5%. Conformity was 99.0% based on major osteoporotic fracture and 97.5% based on risk of hip fracture. The Pluijm evaluation shows conformity of 87.2% and 83.3%, respectively, when compared to the US Hispanic and Spain/Mexico FRAX thresholds for risk of fracture.
Although the different FRAX databases provide variations in the absolute risk of fracture, the overall conformity to treatment thresholds amongst the US Hispanic, Spain, and Mexico databases show the database used would have little effect as to the decision to treat. The Pluijm tool conforms to the FRAX thresholds and can be used as well. It does not matter which country-specific calculator or assessment tool is used, as there are a similar number of patients that would meet the intervention threshold.
[Show abstract][Hide abstract] ABSTRACT: Summary In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated. Introduction This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years. Methods A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year, randomized, double-blind, placebo-controlled, phase 3 trial. In the core study (N = 7,492), subjects received bazedoxifene 20 or 40 mg/day, raloxifene 60 mg/day, or placebo. The raloxifene arm was discontinued after 3 years; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years. Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo. Endpoints included incidence of new vertebral fractures (primary) and non-vertebral fractures, and changes in bone mineral density (BMD) and bone turnover markers. Results At 5 years, the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg (4.5%) and 40/20 mg (3.9%) versus placebo (6.8%; P n = 1,324; femoral neck T-score ≤−3.0 and/or ≥1 moderate or severe or ≥2 mild vertebral fracture[s]), bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo (37%; P = 0.06); combined data for bazedoxifene 20 and 40/20 mg reached statistical significance (34% reduction; P P Conclusions The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women.
No preview · Article · Jul 2011 · Osteoporosis International