Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Comparison of the cost-effectiveness of sequential treatment with abaloparatide in US men and women at very high risk of fractures.

BACKGROUND: Osteoporotic-related fractures represent an increasing burden to patients, health care systems and society. AIMS: This study estimated cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) compared to relevant alternative strategies in US men and women aged 50 to 80 years at very high fracture risk (bone mineral density T-score ≤ - 2.5 and a recent fracture). METHODS: A lifetime Markov-based microsimulation model was used to estimate healthcare costs and quality-adjusted life years (QALYs). Comparators were sequential treatment with unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Analyses were conducted based on initial fracture site (hip, vertebral, or any fracture) and treatment efficacy data (derived from clinical trials or a recent network meta-analysis). RESULTS: From all analyses completed, sequential ABL/ALN demonstrated more QALYs for lower healthcare costs versus unbranded TPTD/ALN. No treatment was dominated (higher costs for less QALYs) versus ALN monotherapy. Sequential ABL/ALN resulted in favorable cost-effectiveness (at US threshold of $150,000/QALY) versus generic ALN monotherapy in men aged ≥ 50 years with any fracture type, women aged ≥ 65 years with any fracture type, and women aged ≥ 55 years having a hip or vertebral fracture. DISCUSSION: Similar cost-effectiveness of sequential ABL/ALN versus unbranded TPTD/ALN, ALN monotherapy, and no treatment was observed in both US men and women at very high fracture risk, with a moderate improvement in cost-effectiveness in men versus women and in patients with a hip or vertebral fracture. CONCLUSIONS: Sequential therapy with ABL/ALN was cost-effective in US men and women at very high risk of fractures.

Economic and Humanistic Burden Among Medicare-Aged Women With Fragility Fracture in the United States.

OBJECTIVE: Describe patient characteristics, health care resource utilization, costs, and humanistic burden of women with Medicare insurance with incident fragility fracture who were admitted to post-acute-care (PAC). DESIGN: Retrospective cohort study using 100% Medicare Fee-for-Service (FFS) data. SETTING AND PARTICIPANTS: Community-dwelling female Medicare beneficiaries with incident fragility fracture January 1, 2017, to October 17, 2019, resulting in PAC admission to a skilled nursing facility (SNF), home-health care, inpatient-rehabilitation facility, or long-term acute-care hospital. METHODS: Patient demographic/clinical characteristics were measured during 1-year baseline. Resource utilization and costs were measured during baseline, PAC event, and PAC follow-up. Humanistic burden was measured among SNF patients with linked Minimum Data Set assessments. Multivariable regression examined predictors of PAC costs after discharge and changes in functional status during SNF stay. RESULTS: A total of 388,732 patients were included. Compared with baseline, hospitalization rates were 3.5, 2.4, 2.6, and 3.1 times higher and total costs 2.7, 2.0, 2.5, and 3.6 times higher for SNF, home-health, inpatient-rehabilitation, and long-term acute-care, respectively, following PAC discharge. Utilization of dual-energy X-ray absorptiometry (DXA) and osteoporosis medications remained low: 8.5% to 13.7% received DXA during baseline vs 5.2% to 15.6% following PAC; 10.2% to 12.0% received osteoporosis medication during baseline vs 11.4% to 22.3% following PAC. Dual eligibility for Medicaid (ie, low income) was associated with 12% higher costs; Black patients had 14% higher costs. Activities of daily living scores improved 3.5 points during SNF stay, but Black patients had 1.22-point lower improvement than White patients. Pain intensity scores showed small improvement (-0.8 points). CONCLUSIONS AND IMPLICATIONS: Women admitted to PAC with incident fracture had high humanistic burden with little improvement in pain and functional status and significantly higher economic burden after discharge compared with baseline. Disparities in outcomes related to social risk factors were observed, with consistently low utilization of DXA and osteoporosis medications even after fracture. Results indicate a need for improved early diagnosis and aggressive disease management to prevent and treat fragility fractures.

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research. PURPOSE: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated. METHODS: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice. RESULTS: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research. CONCLUSIONS: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings.

Understanding Physicians' Perceptions of Patient-Identified Barriers to Osteoporosis Medication Initiation: A Cognitive Mapping Approach.

Objective: Interventions to initiate medication and increase adherence for postmenopausal women who have had a fragility fracture were not always successful. The purpose of this study was to derive an empirical framework for patient-identified barriers to osteoporosis medication initiation and adherence from physician experts. Methods: A cognitive mapping approach involving nominal group technique (NGT) meetings and a card sorting and rating task were used to obtain formative data. We first conducted four NGT meetings with 18 women patients who were not on osteoporosis treatment to identify barriers to osteoporosis medication, then invited 27 osteoporosis physicians to sort and rate 25 patients identified barriers. Descriptive analysis, multidimensional scaling analysis, and hierarchical cluster analysis were applied for data analysis. Results: A two-dimensional five-cluster cognitive map was derived to provide an organizational framework for understanding patients perceived barriers to medication initiation and adherence. The five clusters were concerns about side effects, experience of side effects, lifestyle changes, medication access and complexity, and patient uncertainty about treatment and trust in the provider. The two dimensions were interpreted as internal to patients (X-axis) and external to patients (Y-axis). Conclusions/Implications: Views of patients solicited in a structured format provided directions to help in designing interventions to improve osteoporosis medication initiation and adherence.

Analytical considerations and plans to standardize or harmonize assays for the reference bone turnover markers PINP and ß-CTX in blood.

Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (ß-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and ß-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of ß-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and ß-CTX.

Persistence at 24 months with denosumab among postmenopausal women with osteoporosis: results of a prospective cohort study.

Persistence with prescribed medications for chronic diseases is important; however, persistence with osteoporosis treatments is historically poor. In this prospective cohort study of postmenopausal women treated for osteoporosis in real-world clinical practice settings in the USA and Canada, 24-month persistence with denosumab was 58%. PURPOSE: Patients who persist with their prescribed osteoporosis treatment have increased bone mineral density (BMD) and reduced risk of fracture. Twelve-month persistence with denosumab in routine clinical practice is as high as 95%, but there are limited data on longer-term persistence with denosumab in this setting. METHODS: This single-arm, prospective, cohort study evaluated 24-month persistence with denosumab administered every 6 months in postmenopausal women receiving treatment for osteoporosis in real-world clinical practice in the USA and Canada. Endpoints and analyses included the percentage of patients who persist with denosumab at 24 months (greater than or equal to four injections with a gap between injections of no more than 6 months plus 8 weeks), the total number of injections received by each patient, changes in BMD in persistent patients, and the incidence of serious adverse events (SAEs) and fractures. RESULTS: Among 935 enrolled patients, 24-month persistence was 58% (50% in US patients and 75% in Canadian patients). A majority of patients received at least four injections over the observation period (62% of US patients and 81% of Canadian patients). Among patients who were persistent at 24 months and who had a baseline, 12-month, and 24-month DXA scan, mean BMD increased from baseline to 24 months by 7.8% at the lumbar spine and 2.1% at the femoral neck. SAEs and fractures were reported for 122 (13.0%) patients and 54 (5.8%) patients, respectively. CONCLUSIONS: Persistence with denosumab for 24 months yields improvement in BMD among postmenopausal women with osteoporosis treated in routine clinical practice in the USA and Canada.

Evaluation of a Multimodal, Direct-to-Patient Educational Intervention Targeting Barriers to Osteoporosis Care: A Randomized Clinical Trial.

Osteoporosis treatment rates are declining, even among those with past fractures. Novel, low-cost approaches are needed to improve osteoporosis care. We conducted a parallel group, controlled, randomized clinical trial evaluating a behavioral intervention for improving osteoporosis medication use. A total of 2684 women with self-reported fracture history after age 45 years not using osteoporosis therapy from US Global Longitudinal Study of Osteoporosis in Women (GLOW) sites were randomized 1:1 to receive a multimodal, tailored, direct-to-patient, video intervention versus usual care. The primary study outcome was self-report of osteoporosis medication use at 6 months. Other outcomes included calcium and vitamin D supplementation, bone mineral density (BMD) testing, readiness for behavioral change, and barriers to treatment. In intent-to-treat analyses, there were no significant differences between groups (intervention versus control) in osteoporosis medication use (11.7% versus 11.4%, p = 0.8), calcium supplementation (31.8% versus 32.6%, p = 0.7), vitamin D intake (41.3% versus 41.9%, p = 0.8), or BMD testing (61.8% versus 57.1%, p = 0.2). In the intervention group, fewer women were in the precontemplative stage of behavior change, more women reported seeing their primary care provider, had concerns regarding osteonecrosis of the jaw, and difficulty in taking/remembering to take osteoporosis medications. We found differences in BMD testing among the subgroup of women with no prior osteoporosis treatment, those who provided contact information, and those with no past BMD testing. In per protocol analyses, women with appreciable exposure to the online intervention (n = 257) were more likely to start nonbisphosphonates (odds ratio [OR] = 2.70; 95% confidence interval [CI] 1.26-5.79) compared with the usual care group. Although our intervention did not increase the use of osteoporosis therapy at 6 months, it increased nonbisphosphonate medication use and BMD testing in select subgroups, shifted participants' readiness for behavior change, and altered perceptions of barriers to osteoporosis treatment. Achieving changes in osteoporosis care using patient activation approaches alone is challenging. © 2018 American Society for Bone and Mineral Research.

Effect of Baseline Characteristics on the Pain Response to Pregabalin in Fibromyalgia Patients with Comorbid Depression.

Objective: To evaluate the effect of baseline characteristics on the treatment response to pregabalin in fibromyalgia (FM) patients with depression. Design: Post hoc analysis from a randomized, double-blind, placebo-controlled, two-way crossover study of pregabalin (300 or 450 mg/day, twice daily). Subjects: A total of 193 FM patients taking an antidepressant for comorbid depression. Methods: The effect of patient baseline characteristics on the treatment response to pregabalin vs placebo was assessed for the primary efficacy end point (mean pain score on an 11-point numeric rating scale). Variables were analyzed using a linear mixed effects model with sequence, period, and treatment as fixed factors, and subject within sequence and within subject error as random factors. Results: Pregabalin significantly improved mean pain scores vs placebo irrespective of age, duration of FM, number of prior FM medications, depression diagnosis, shorter-term depression (<10 years), prior or no prior opioid use, pain severity, anxiety severity, and sleep disruption severity (all P < 0.05). Compared with placebo, pregabalin did not significantly affect mean pain scores in patients with comorbid insomnia, irritable bowel syndrome, or gastroesophageal reflux disease; severe FM; a diagnosis of depression before FM, longer-term depression (≥ 10 years), more severe depression, or who were taking a high dose of antidepressant. Conclusions: Pregabalin significantly improved mean pain scores when compared with placebo for the majority of baseline characteristics assessed in FM patients taking an antidepressant for comorbid depression.

A multi-modal intervention for Activating Patients at Risk for Osteoporosis (APROPOS): Rationale, design, and uptake of online study intervention material.

OBJECTIVE: To develop an innovative and effective educational intervention to inform patients about the need for osteoporosis treatment and to determine factors associated with its online uptake. METHODS: Postmenopausal women with a prior fracture and not currently using osteoporosis therapy were eligible to be included in the Activating Patients at Risk for OsteoPOroSis (APROPOS). Four nominal groups with a total of 18 racially/ethnically diverse women identified osteoporosis treatment barriers. We used the Information, Motivation, Behavior Skills conceptual model to develop a direct-to-patient intervention to mitigate potentially modifiable barriers to osteoporosis therapy. The intervention included videos tailored by participants' race/ethnicity and their survey responses: ranked barriers to osteoporosis treatment, deduced barriers to treatment, readiness to behavior change, and osteoporosis treatment history. Videos consisted of "storytelling" narratives, based on osteoporosis patient experiences and portrayed by actresses of patient-identified race/ethnicity. We also delivered personalized brief phone calls followed by an interactive voice-response phone messages aimed to promote uptake of the videos. RESULTS: To address the factors associated with online intervention uptake, we focused on participants assigned to the intervention arm (n = 1342). These participants were 92.9% Caucasian, with a mean (SD) age 74.9 (8.0) years and the majority (77.7%) had some college education. Preference for natural treatments was the barrier ranked #1 by most (n = 130; 27%), while concern about osteonecrosis of the jaw was the most frequently reported barrier (at any level; n = 322; 67%). Overall, 28.1% (n = 377) of participants in the intervention group accessed the videos online. After adjusting for relevant covariates, the participants who provided an email address had 6.07 (95% CI 4.53-8.14) higher adjusted odds of accessing their online videos compared to those who did not. CONCLUSION: We developed and implemented a novel tailored multi-modal intervention to improve initiation of osteoporosis therapy. An email address provided on the survey was the most important factor independently associated with accessing the intervention online. The design and uptake of this intervention may have implications for future studies in osteoporosis or other chronic diseases.

Progression of fibromyalgia: results from a 2-year observational fibromyalgia and chronic pain study in the US.

BACKGROUND: A previous fibromyalgia (FM) research reports that 20%-47% of diagnosed patients may not meet the study definition of FM 1-2 years after diagnosis. The aim of this study was to gain a better understanding of the progression of FM in a geographically diverse cohort over a 2-year time period. METHODS: This cohort study followed 226 subjects recruited online to assess FM and chronic widespread pain (CWP) diagnosis stability over time. At enrollment (baseline), subjects provided informed consent, completed an online questionnaire consisting of the London Fibromyalgia Epidemiology Study Screening Questionnaire to screen for CWP (bilateral pain above/below waist lasting ≥1 week in the past 3 months), visited a site for physician evaluation for FM, and completed a questionnaire with validated patient-reported outcome instruments. Subjects were classified into mutually exclusive groups: FM+CWP+ (screened positive for CWP and received physician diagnosis of FM), FM-CWP+ (screened positive for CWP but did not receive physician diagnosis of FM), and FM-CWP- (screened negative for CWP). Approximately 2 years later (follow-up), subjects were reassessed at the same study site and completed a questionnaire with the same patient-reported outcomes. RESULTS: Seventy-six FM+CWP+ subjects completed assessments at both time points; 56 (73.7%) met the FM study definition at follow-up. Twenty subjects no longer met the FM study definition (eleven became FM-CWP- and nine became FM-CWP+). Ten subjects (two from FM-CWP- and eight from FM-CWP+) transitioned into the FM+CWP+ group at follow-up; they reported more tender points and pain interference with sleep and worse physical function at baseline compared with subjects who did not transition to FM+CWP+. Most (76.7%) of the subjects who transitioned into/out of FM+CWP+ experienced changes in CWP, number of positive tender points, or both. CONCLUSION: The results suggest that some FM+CWP+ patients experience fluctuation in symptoms over time, which may reflect the waxing and waning nature of FM and affect diagnosis and treatment.

Fibromyalgia and Chronic Pain Syndromes: A White Paper Detailing Current Challenges in the Field.

This manuscript, developed by a group of chronic pain researchers and clinicians from around the world, aims to address the state of knowledge about fibromyalgia (FM) and identify ongoing challenges in the field of FM and other chronic pain syndromes that may be characterized by pain centralization/amplification/hypersensitivity. There have been many exciting developments in research studies of the pathophysiology and treatment of FM and related syndromes that have the potential to improve the recognition and management of patients with FM and other conditions with FM-like pain. However, much of the new information has not reached all clinicians, especially primary care clinicians, who have the greatest potential to use this new knowledge to positively impact their patients' lives. Furthermore, there are persistent misconceptions about FM and a lack of consensus regarding the diagnosis and treatment of FM. This paper presents a framework for future global efforts to improve the understanding and treatment of FM and other associated chronic pain syndromes, disseminate research findings, identify ways to enhance advocacy for these patients, and improve global efforts to collaborate and reach consensus about key issues related to FM and chronic pain in general.

Systemic lupus erythematosus and primary fibromyalgia can be distinguished by testing for cell-bound complement activation products.

OBJECTIVE: We sought to establish the performance of cell-bound complement activation products (CB-CAPs) as a diagnostic tool to distinguish primary fibromyalgia (FM) from systemic lupus erythematosus (SLE). METHODS: A total of 75 SLE and 75 primary FM adult subjects who fulfilled appropriate classification criteria were enrolled prospectively. CB-CAPs (erythrocyte-C4d (EC4d) and B-lymphocyte-C4d (BC4d)) were determined by flow cytometry. Antinuclear antibodies (ANAs) were determined using indirect immunofluorescence while other autoantibodies were determined by solid-phase assays. The CB-CAPs in a multi-analyte assay with algorithm (MAAA) relied on two consecutive tiers of analysis that was reported as an overall positive or negative assessment. Test performance was assessed using sensitivity, specificity, positive and negative likelihood ratio (LR). RESULTS: ANAs yielded 80% positives for SLE and 33% positives for FM. High CB-CAP expression (EC4d >14 units or BC4d >60 units) was 43% sensitive and 96% specific for SLE. The CB-CAPs in MAAA assessment was evaluable in 138 of the 150 subjects enrolled (92%) and yielded 60% sensitivity (CI 95% 48% to 72%) for SLE with no FM patient testing positive (100% specificity). A positive test result was associated with a strong positive LR for SLE (>24, CI 95%; 6 to 102), while a negative test result was associated with a moderate negative LR (0.40; CI 95% 0.30 to 0.54). CONCLUSION: Our data indicate that CB-CAPs in MAAA can distinguish FM from SLE.

Fibromyalgia Outcomes Over Time: Results from a Prospective Observational Study in the United States.

BACKGROUND: Longitudinal research on outcomes of patients with fibromyalgia is limited. OBJECTIVE: To assess clinician and patient-reported outcomes over time among fibromyalgia patients. METHODS: At enrollment (Baseline) and follow-up (approximately 2 years later), consented patients were screened for chronic widespread pain (CWP), attended a physician site visit to determine fibromyalgia status, and completed an online questionnaire assessing pain, sleep, function, health status, productivity, medications, and healthcare resource use. RESULTS: Seventy-six fibromyalgia patients participated at both time points (at Baseline: 86.8% white, 89.5% female, mean age 50.9 years, and mean duration of fibromyalgia 4.1 years). Mean number of tender points at each physician visit was 14.1 and 13.5, respectively; 11 patients no longer screened positive for CWP at follow-up. A majority reported medication use for pain (59.2% at Baseline, 62.0% at Follow-up). The most common medication classes were opioids (32.4%), SSRIs (16.9%), and tramadol (14.1%) at Follow-up. Significant mean changes over time were observed for fibromyalgia symptoms (modified American College of Rheumatology 2010 criteria: 18.4 to 16.9; P=0.004), pain interference with function (Brief Pain Inventory-Short Form: 5.9 to 5.3; P=0.013), and sleep (Medical Outcomes Study-Sleep Scale: 58.3 to 52.7; P=0.004). Patients achieving ≥2 point improvement in pain (14.5%) experienced greater changes in pain interference with function (6.8 to 3.4; P=0.001) and sleep (62.4 to 51.0; P=0.061). CONCLUSION: Fibromyalgia patients reported high levels of burden at both time points, with few significant changes observed over time. Outcomes were variable among patients over time and were better among those with greater pain improvement.

Identification of a potential fibromyalgia diagnosis using random forest modeling applied to electronic medical records.

BACKGROUND: Diagnosis of fibromyalgia (FM), a chronic musculoskeletal condition characterized by widespread pain and a constellation of symptoms, remains challenging and is often delayed. METHODS: Random forest modeling of electronic medical records was used to identify variables that may facilitate earlier FM identification and diagnosis. Subjects aged ≥18 years with two or more listings of the International Classification of Diseases, Ninth Revision, (ICD-9) code for FM (ICD-9 729.1) ≥30 days apart during the 2012 calendar year were defined as cases among subjects associated with an integrated delivery network and who had one or more health care provider encounter in the Humedica database in calendar years 2011 and 2012. Controls were without the FM ICD-9 codes. Seventy-two demographic, clinical, and health care resource utilization variables were entered into a random forest model with downsampling to account for cohort imbalances (<1% subjects had FM). Importance of the top ten variables was ranked based on normalization to 100% for the variable with the largest loss in predicting performance by its omission from the model. Since random forest is a complex prediction method, a set of simple rules was derived to help understand what factors drive individual predictions. RESULTS: The ten variables identified by the model were: number of visits where laboratory/non-imaging diagnostic tests were ordered; number of outpatient visits excluding office visits; age; number of office visits; number of opioid prescriptions; number of medications prescribed; number of pain medications excluding opioids; number of medications administered/ordered; number of emergency room visits; and number of musculoskeletal conditions. A receiver operating characteristic curve confirmed the model's predictive accuracy using an independent test set (area under the curve, 0.810). To enhance interpretability, nine rules were developed that could be used with good predictive probability of an FM diagnosis and to identify no-FM subjects. CONCLUSION: Random forest modeling may help to quantify the predictive probability of an FM diagnosis. Rules can be developed to simplify interpretability. Further validation of these models may facilitate earlier diagnosis and enhance management.

Electronic medical record data to identify variables associated with a fibromyalgia diagnosis: importance of health care resource utilization.

BACKGROUND: Diagnosis of fibromyalgia (FM) is often challenging. Identifying factors associated with an FM diagnosis may guide health care providers in implementing appropriate diagnostic and management strategies. METHODS: This retrospective study used the de-identified Humedica electronic medical record (EMR) database to identify variables associated with an FM diagnosis. Cases (n=4,296) were subjects ≥18 years old with ≥2 International Classification of Diseases, Ninth Revision (ICD-9) codes for FM (729.1) ≥30 days apart during 2012, associated with an integrated delivery network, with ≥1 encounter with a health care provider in 2011 and 2012. Controls without FM (no-FM; n=583,665) did not have the ICD-9 codes for FM. Demographic, clinical, and health care resource utilization variables were extracted from structured EMR data. Univariate analysis identified variables showing significant differences between the cohorts based on odds ratios (ORs). RESULTS: Consistent with FM epidemiology, FM subjects were predominantly female (78.7% vs 64.5%; P<0.0001) and slightly older (mean age 53.3 vs 52.7 years; P=0.0318). Relative to the no-FM cohort, the FM cohort was characterized by a higher prevalence of nearly all evaluated comorbidities; the ORs suggested a higher likelihood of an FM diagnosis (P<0.0001), especially for musculoskeletal and neuropathic pain conditions (OR 3.1 for each condition). Variables potentially associated with an FM diagnosis included higher levels of use of specific health care resources including emergency-room visits, outpatient visits, hospitalizations, and medications. Units used per subject for emergency-room visits, outpatient visits, hospitalizations, and medications were also significantly higher in the FM cohort (P<0.0001), confirming resource utilization as an important variable associated with an FM diagnosis. CONCLUSION: Significant differences between the FM and no-FM cohorts were observed for nearly all the demographic, clinical, and health care resource variables, suggesting an association with FM diagnosis. These results also support use of EMR data for identifying variables associated with FM, which may help in the diagnosis and management of this condition.

A 7-year randomized, placebo-controlled trial assessing the long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: effects on bone density and fracture.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Efficacy and safety of bazedoxifene are sustained across 7 years in postmenopausal women with osteoporosis.

Use of FRAX®-based fracture risk assessments to identify patients who will benefit from osteoporosis therapy.

Several pharmacological interventions, including selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab, and strontium ranelate have demonstrated efficacy in reducing the incidence of osteoporotic fractures, the most severe consequence of postmenopausal osteoporosis. Until recently, bone mineral density (BMD) was the primary factor used to determine which postmenopausal women may require osteoporosis treatment. However, clinical guidelines now recommend the use of the Fracture Risk Assessment Tool (FRAX(®)), a computer-based algorithm introduced by the World Health Organization, to help primary care physicians identify postmenopausal women who may be candidates for pharmacological osteoporosis therapy based on the level of fracture risk. Beyond its utility as a resource for determining whether or not to initiate osteoporosis treatment, clinical studies have begun to evaluate the correlation between FRAX(®)-based 10-year fracture probability and efficacy of different osteoporosis treatments. Bazedoxifene, clodronate, and denosumab have shown greater fracture risk reduction at higher FRAX(®)-based 10-year fracture probabilities, but the efficacy of raloxifene, alendronate, and strontium ranelate were relatively stable regardless of fracture probability. In summary, these data suggest that the relationship between FRAX(®)-based fracture probability and efficacy of different osteoporosis treatments varies depending upon the agent in question.

Potential drug-drug and drug-condition interactions among fibromyalgia patients initiating pregabalin or duloxetine: prevalence and health care expenditure impact.

OBJECTIVE: 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. DESIGN: Retrospective cohort study. SETTING: U.S. clinical practice, as reflected within a large administrative claims database. SUBJECTS: Fibromyalgia patients newly initiating pregabalin or duloxetine between July 1, 2008 and October 1, 2010 (initiation date = index). OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Twice daily versus once nightly dosing of pregabalin for fibromyalgia: a double-blind randomized clinical trial of efficacy and safety.

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. RESULTS: Both 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.