Factors associated with the contemplative stage of readiness to initiate osteoporosis treatment.

We investigated the factors associated with readiness for initiating osteoporosis treatment in women at high risk of fracture. We found that women in the contemplative stage were more likely to report previously being told having osteoporosis or osteopenia, acknowledge concern about osteoporosis, and disclose prior osteoporosis treatment. INTRODUCTION: Understanding factors associated with reaching the contemplative stage of readiness to initiate osteoporosis treatment may inform the design of behavioral interventions to improve osteoporosis treatment uptake in women at high risk for fracture. METHODS: We measured readiness to initiate osteoporosis treatment using a modified form of the Weinstein Precaution Adoption Process Model (PAPM) among 2684 women at high risk of fracture from the Activating Patients at Risk for OsteoPOroSis (APROPOS) clinical trial. Pre-contemplative participants were those who self-classified in the unaware and unengaged stages of PAPM (stages 1 and 2). Contemplative participants were those in the undecided, decided not to act, or decided to act stages of PAPM (stages 3, 4, and 5). Using multivariable logistic regression, we evaluated participant characteristics associated with levels of readiness to initiate osteoporosis treatment. RESULTS: Overall, 24% (N = 412) self-classified in the contemplative stage of readiness to initiate osteoporosis treatment. After adjusting for age, race, education, health literacy, and major osteoporotic fracture in the past 12 months, contemplative women were more likely to report previously being told they had osteoporosis or osteopenia (adjusted odds ratio [aOR] (95% CI) 11.8 (7.8-17.9) and 3.8 (2.5-5.6), respectively), acknowledge concern about osteoporosis (aOR 3.5 (2.5-4.9)), and disclose prior osteoporosis treatment (aOR 4.5 (3.3-6.3)) than women who self-classified as pre-contemplative. CONCLUSIONS: For women at high risk for future fractures, ensuring women's recognition of their diagnosis of osteoporosis/osteopenia and addressing their concerns about osteoporosis are critical components to consider when attempting to influence stage of behavior transitions in osteoporosis treatment.

Fracture healing: a consensus report from the International Osteoporosis Foundation Fracture Working Group.

UNLABELLED: We used the RAND UCLA appropriateness method to decide appropriateness of use of osteoporosis medication after incident fracture and potential for fracture healing and make suggestions for trial design for clinical and preclinical research. PURPOSE: To develop appropriateness criteria to assist in the use and study of osteoporosis medications in patients with recent fracture and in the potential use of osteoporosis medications to enhance delayed fracture healing. To promote further research by suggesting preclinical and clinical trial design for studies where fracture healing is the endpoint. DESIGN: RAND/UCLA appropriateness method (RUAM). PARTICIPANTS: A panel of experts, both members and non-members of the International Osteoporosis Foundation Fracture Working Group, were identified consisting of geriatricians, rheumatologists, orthopedists, endocrinologists, and internists. This resulted in a round 1 panel of 15 panelists, round 2 panel of 15 members, and a round 3 panel of 14 members. MAIN OUTCOME MEASURE: Agreement on statements and scenarios using RUAM. Three rounds of voting by panelists took place. Agreement in a third round was reached for 111 statements and scenarios, measured by median panel ratings and the amount of dispersion of panel ratings, based on the interpercentile range. RESULTS: An expert panel validated a set of statements and scenarios about the use of osteoporosis medications after incident fracture and use of these medications to enhance delayed fracture healing and made recommendations for study designs to investigate the effect of osteoporosis medications on fracture healing. CONCLUSIONS: The result of this exercise is intended to assist in improving patient care by identifying the appropriateness of use of osteoporosis medications after fracture and in fracture healing and to make suggestions for further preclinical and clinical research.

Comorbidity indices for clinical trials: adaptation of two existing indices for use with the FREEDOM trial in women with postmenopausal osteoporosis.

UNLABELLED: Two comorbidity indices were adapted for use in the FREEDOM trial and significantly correlated with the number of medications and impaired health status at baseline. The indices have applications for the analysis of clinical trial data and would allow for the appropriate adjustment of comorbidities when evaluating clinical trial outcomes. INTRODUCTION: The purpose of this study is to adapt two published comorbidity indices for use with the FREEDOM clinical trial evaluating postmenopausal women with osteoporosis. METHODS: FREEDOM enrolled women aged 60-90 years with a bone mineral density T-score <-2.5 at the lumbar spine or total hip and ≥-4.0 at both sites. Comorbidity indices were calculated using methods described by Sangha (Arthritis Rheum 49:156-163, 2003) and Wolfe (J Rheumatol 37:305-315, 2010) following modification. The adapted Sangha index included 12 conditions with a summary score of 0-12; the adapted Wolfe index included 7 conditions with a weighted summary score of 0-8. Higher scores indicated greater comorbidity. A panel of clinicians independently reviewed subjects' medical histories using a systematic process based on Medical Dictionary for Regulatory Activities (MedDRA) preferred terms to map specified comorbid conditions. Spearman correlations between the adapted indices and baseline subject characteristics expected to be associated with comorbidities were examined. RESULTS: Of the 7808 subjects in this study, 74 % had ≥1 comorbidities based on the adapted Sangha or Wolfe comorbidity indices. The mean (SD) adapted Sangha and Wolfe comorbidity indices were 1.4 (1.2) and 1.4 (1.3), respectively. Both indices correlated positively with age, body mass index, and the number of medications (r = 0.54 to 0.55) at baseline and inversely correlated with health-related quality of life (r = -0.22 to -0.30) (all P < 0.0001). Further, when either the adapted Sangha or Wolfe index was included as a covariate for assessing mortality over 36 months in the FREEDOM population, the hazard ratio of the comorbidity index indicated that the mortality risk increased by 27 or 28 %, respectively, for each unit increase in the adapted index (both P < 0.0001). CONCLUSIONS: Our work suggests these comorbidity indices may be adapted for use with clinical trial data, thereby allowing for the appropriate adjustment and reporting of covariates in the evaluation of clinical trial outcomes in an osteoporotic population.

Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study.

UNLABELLED: To determine persistence with subcutaneous denosumab every 6 months in women being treated for osteoporosis, we conducted a single-arm prospective, observational study in the United States and Canada. Among 935 patients enrolled, 12-month persistence was 82%, with 66 patients (7%) reporting serious adverse events and 19 patients (2%) reporting fractures. INTRODUCTION: Increased persistence with osteoporosis therapy is associated with reduced fracture risk. Denosumab reduced fracture risk in clinical trials; persistence in community settings is undetermined. This study evaluates persistence with denosumab in community practice in the United States (US) and Canada. METHODS: In a 24-month multicenter, prospective, single-arm, observational study, women being treated for osteoporosis were enrolled ≤4 weeks after the first subcutaneous injection of denosumab. For this 12-month prespecified interim analysis, endpoints include persistence (one injection at study entry and another within 6 months + 8 weeks), attributes associated with persistence (univariate analysis), and serious adverse events (SAEs). RESULTS: Among 935 patients (mean age 71 years), mean baseline T-scores were -2.18 (femoral neck) and -2.00 (lumbar spine); 50% of patients had experienced osteoporotic fracture(s). At 12 months, 82 % of patients were persistent with denosumab. Baseline factors significantly (p < 0.05) associated with higher persistence included use of osteoporosis medications >5 years previously, lumbar spine T-score > -2.5, and treatment by female physicians (US). Lower persistence was associated (p < 0.05) with psychiatric diagnoses including depression, southern US residence, being divorced, separated, or widowed (US), and prior hip fracture (Canada). SAEs were reported in 66 patients (7%); no SAEs of osteonecrosis of the jaw, atypical femoral fracture, fracture healing complications, hypocalcemia, eczema, or hypersensitivity were reported. Nineteen patients (2%) reported osteoporotic fractures. CONCLUSIONS: The 12-month persistence observed in this single-arm open-label study of US and Canadian community practice extends the evidence regarding denosumab's potential role in reducing fracture risk in postmenopausal women with osteoporosis.

Standardising the descriptive epidemiology of osteoporosis: recommendations from the Epidemiology and Quality of Life Working Group of IOF.

UNLABELLED: 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. INTRODUCTION: The prevalence of osteoporosis as defined by the T-score is inconsistently reported in the literature which makes comparisons between studies problematic. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effectiveness of risedronate and alendronate on nonvertebral fractures: an observational study through 2 years of therapy.

UNLABELLED: 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. INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The effect of teriparatide compared with risedronate on reduction of back pain in postmenopausal women with osteoporotic vertebral fractures.

UNLABELLED: The effect of teriparatide and risedronate on back pain was tested, and there was no difference in the proportion of patients experiencing a reduction in back pain between groups after 6 or 18 months. Patients receiving teriparatide had greater increases in bone mineral density and had fewer vertebral fractures. INTRODUCTION: This study aimed to understand the effect of teriparatide in reducing back pain in patients with prevalent back pain and vertebral fracture compared to risedronate. METHODS: In an 18-month randomized, double-blind, double-dummy trial, we investigated the effects of teriparatide (20 µg/day) vs. risedronate (35 mg/week) in postmenopausal women with back pain likely due to vertebral fracture. The primary objective was to compare the proportion of subjects reporting ≥30% reduction in worst back pain severity from baseline to 6 months as assessed by a numeric rating scale in each treatment group. Pre-specified secondary and exploratory outcomes included assessments of average and worst back pain at additional time points, disability and quality of life, bone mineral density, incidence of fractures, and safety. RESULTS: At 6 months, 59% of teriparatide and 57% of risedronate patients reported ≥30% reduction in worst back pain and there were no differences between groups in the proportion of patients experiencing reduction in worst or average back pain at any time point, disability, or quality of life. There was a greater increase from baseline in bone mineral density at the lumbar spine (p = 0.001) and femoral neck (p = 0.02) with teriparatide compared to risedronate and a lower incidence of vertebral fractures at 18 months (4% teriparatide and 9% risedronate; p = 0.01). Vertebral fractures were less severe (p = 0.04) in the teriparatide group. There was no difference in the overall incidence of adverse events. CONCLUSIONS: Although there were no differences in back pain-related endpoints, patients receiving teriparatide had greater skeletal benefit than those receiving risedronate.

Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study.

UNLABELLED: 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 < 0.05), with relative risk reductions of 35% and 40%, respectively. Non-vertebral fracture incidence was similar among groups. In a subgroup of higher-risk women (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 < 0.05). Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo (P < 0.05) and was generally safe and well tolerated. 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.

Impact of bone turnover markers and/or educational information on persistence to oral bisphosphonate therapy: a community setting-based trial.

UNLABELLED: We examined how the use of bone turnover markers and educational information affects persistence of bisphosphonate use in osteoporotic patients. We found that reporting bone turnover results and/or educational information did not affect persistence. INTRODUCTION: Long-term adherence and persistence to osteoporosis medication are poor. We examined whether reporting of bone turnover marker results, education about osteoporosis, or a combination of both would increase persistence to oral bisphosphonates. METHODS: Two hundred and forty women who were 5 years postmenopausal with BMD at least 2.0 standard deviations below normal were recruited for the study. All women were given a new prescription for alendronate and randomly assigned to one of four groups: (1) bone marker results at baseline, 3 and 12 months; (2) educational materials every month and a membership in the National Osteoporosis Foundation; (3) bone marker and educational information; and (4) control, no information other than usual care. Persistence among randomization groups was tested using survival analysis adjusting for the delay between intervention methods. RESULTS: Of those filling their initial prescription, 95.5% refilled their prescription at the end of the first month, 87% at 3 months, 82% at 6 months, and 78% at 10 months. Overall persistence through 12 months was 54%. There was no difference found among the four groups for persistence time using (p > 0.58). CONCLUSION: Providing bone turnover marker results is not an effective way to enhance early compliance and persistence with drug therapy. While the women in our study felt that bone marker results and educational information were helpful to them, there was no difference in persistence between those who received either bone marker information and/or educational information and those who did not. Because of the unexpected rate of primary nonadherence, this study may be underpowered.

Measuring health-related quality of life (HRQOL) in osteoporotic males using the Male OPAQ.

UNLABELLED: The Male Osteoporosis Assessment Questionnaire (OPAQ™) is a health-related quality of life (HRQOL) instrument that can differentiate between men with and without fracture. The Male OPAQ™ is a reliable and validated instrument that may be utilized in clinical trials seeking to include male populations. INTRODUCTION: Men with osteoporosis (OP) experience poorer clinical outcomes than do women with the disorder, but little is known about the impact of OP on men's HRQOL. This study aimed to test the validity, reliability, and ability to differentiate between men with and without fracture of an HRQOL for men with osteoporosis, the Male OPAQ™. METHODS: The OPAQ and OPAQ-SV were tested for face validity in interviews with male OP patients, and a revised, male-specific instrument was developed. Thirty-seven men ages 50+ completed the Male OPAQ™ and SF-12 at baseline and a two-week retest of the Male OPAQ™. To analyze both the domain and dimension scores, a normalization procedure was performed on the data to determine health status scores from 0 to 100. Descriptive statistics were calculated for each item and site. Reliability and validity of the Male OPAQ™ were assessed using Pearson's r. RESULTS: The Male OPAQ™ can discriminate between men with and without fracture, and men who have more fractures have poorer scores. Instrument domains correspond to those of the SF-12. CONCLUSIONS: The Male OPAQ(TM) is a brief and sensitive tool for measuring HRQOL in men with OP. Further testing in a more diverse and large sample is warranted.

Effect of acetaminophen and fluvastatin on post-dose symptoms following infusion of zoledronic acid.

UNLABELLED: A randomized, double-blind, placebo-controlled study assessed the efficacy of acetaminophen or fluvastatin in preventing post-dose symptoms (increases in body temperature or use of rescue medication) following a single infusion of the intravenous (IV) bisphosphonate zoledronic acid (ZOL). Acetaminophen, but not fluvastatin, significantly reduced the incidence and severity of post-dose symptoms. INTRODUCTION: Transient symptoms including myalgia and pyrexia have been reported post-infusion of IV bisphosphonates, typically starting the day after infusion and resolving within several days. The cause is unknown but may be related to transient cytokine elevations. Statins' potential to block release of these cytokines has been hypothesized. This study was aimed to evaluate efficacy of acetaminophen and fluvastatin in preventing/reducing post-dose symptoms following ZOL 5 mg infusion. METHODS: Randomized, double-blind, placebo-controlled study of efficacy of acetaminophen or fluvastatin in preventing increases in body temperature or use of rescue medication (ibuprofen) following a single ZOL infusion. Bisphosphonate-naive postmenopausal women with low bone mass (N = 793) were randomized into three treatment groups and given 650 mg acetaminophen or 80 mg fluvastatin or placebo 45 min before ZOL infusion. The acetaminophen group continued taking 650 mg acetaminophen every 6 h over the next 3 days, and the other two groups took matching placebo according to the same schedule. Subjects recorded body temperature, symptoms in a diary. Inflammatory cytokines and C-reactive protein (CRP) were measured at baseline, 24, and 72 h in a study subset. RESULTS: Acetaminophen four times/day significantly reduced the incidence and severity of post-dose symptoms following ZOL infusion. Single-dose fluvastatin 80 mg prior to ZOL infusion did not prevent/reduce post-dose symptoms. Cytokine levels increased by 24 h and returned towards baseline by 72 h, similar to the pattern for post-infusion symptoms. CRP levels increased from baseline to 72 h. CONCLUSIONS: Acetaminophen four times/day for 3 days significantly reduced the incidence and severity of post-dose symptoms following ZOL infusion.

Oral bisphosphonate compliance and persistence: a matter of choice?

Compliance to oral bisphosphonates is suboptimal, with negative consequences of increased healthcare utilization and less effective fracture risk reduction. Extending dose interval increased adherence only moderately. We used literature derived from multiple chronic conditions to examine the problem of noncompliance with osteoporosis medication. We reviewed the literature on adherence to osteoporosis medication as well as that across multiple chronic conditions to understand what is known about the cause of the poor adherence. Poor compliance to oral medications is due mostly, not to forgetfulness, but to deliberate choice. Gender differences and style of healthcare management also play a role. Preliminary data suggest psychobehavioral interventions may help to improve motivation. We need to understand better reasons for poor compliance before effective interventions can be developed. Forgetfulness is only a small part of poor compliance. Patient preferences must be considered in medication decision making.

Monthly ibandronate suppresses serum CTX-I within 3 days and maintains a monthly fluctuating pattern of suppression.

UNLABELLED: Bone turnover markers such as serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) can be used to assess drug efficacy in osteoporosis. This study evaluated the pattern of CTX-I suppression in postmenopausal osteoporotic women receiving ibandronate. Ibandronate decreased serum CTX-I levels within 3 days of therapy initiation. Over 6 months, the levels remained suppressed below baseline. INTRODUCTION: This randomized, double-blind, placebo-controlled study evaluated the rapidity of onset and pattern of suppression of the bone resorption marker serum CTX-I in women with postmenopausal osteoporosis (PMO) who received once-monthly oral ibandronate. METHODS: Women diagnosed with PMO received once-monthly oral ibandronate (150 mg) or placebo for 6 months. Serum CTX-I was measured at baseline and after study dose administration on day 3 (month 1 only) and days 7, 14, 21, and 28 (months 1-6). Bone-specific alkaline phosphatase was measured on days 7 and 28 (months 1-6). RESULTS: This study enrolled 67 women: 49 received ibandronate, 17 received placebo, and one took no study drug. At day 3, median reduction in serum CTX-I from baseline was 70.2% with ibandronate and 6.0% with placebo (difference, -64.2%; 95% confidence interval, -80.3% to -46.2%; p < 0.0001). In women receiving ibandronate, serum CTX-I levels remained consistently below baseline, exhibiting a regular monthly fluctuating pattern of suppression over 6 months. Ibandronate was well-tolerated. CONCLUSIONS: Monthly ibandronate decreased serum CTX-I within 3 days. Over 6 months, in women receiving once-monthly ibandronate, serum CTX-I remained suppressed below baseline. A monthly fluctuation, related to time from last dose, was observed.

Risk of fracture in women treated with monthly oral ibandronate or weekly bisphosphonates: the eValuation of IBandronate Efficacy (VIBE) database fracture study.

The eValuation of IBandronate Efficacy (VIBE) head-to-head database fracture study compared fracture rates between patients treated with monthly ibandronate and weekly oral bisphosphonates (BPs). This large study included women >/=45 years old, newly prescribed monthly oral ibandronate or weekly oral alendronate or risedronate, and without malignancy or Paget's disease of bone. The primary analysis included patients who were adherent to treatment during the first 90 days after the index date. The risks of hip, nonvertebral, vertebral and any clinical fracture were compared using Cox proportional hazards models and adjusted for potential confounding factors. A secondary, "intent-to-treat" analysis included all patients who received at least one BP prescription. Sensitivity analyses based on the primary analysis compared patients receiving ibandronate with patients receiving weekly alendronate or risedronate separately, and explored the effect of excluding patients with potential confounding factors from the analysis. Further sensitivity analyses varied the requirement for adherence during the first 90 days after the index date. The primary analysis population included 7345 monthly ibandronate and 56,837 weekly BP patients. Fracture rates after the 12-month observational period were <2% and fracture risk was not significantly different between patients receiving monthly ibandronate or weekly BPs for hip, nonvertebral or any clinical fracture (adjusted relative risk: hip=1.06, p=0.84; nonvertebral=0.88, p=0.255; any clinical fracture=0.82, p=0.052). Ibandronate patients had a significantly lower risk of vertebral fracture than weekly BP patients (adjusted relative risk 0.36, 95% confidence interval 0.18-0.75, p=0.006). In the secondary, "intent-to-treat" analysis, relative risks of fracture were not significantly different between treatment groups for any fracture type. The results of the sensitivity analyses were generally consistent with the primary analysis. This retrospective cohort study found that patients treated with oral monthly ibandronate or weekly BPs (alendronate and risedronate) had similar, low risks of hip fracture, nonvertebral fracture and any clinical fracture. Ibandronate patients had a significantly lower relative risk of vertebral fracture than weekly BP patients; the clinical implications of these findings require further exploration and validation.

A systematic review of persistence and compliance with bisphosphonates for osteoporosis.

UNLABELLED: Fourteen reports utilizing data from de-identified administrative databases were reviewed. Studies contained at least one measure of patient persistence or compliance with bisphosphonates or bisphosphonates and other anti-osteoporosis medications. These studies confirm that women with osteoporosis have suboptimal persistence and compliance rates with bisphosphonate therapy. INTRODUCTION: This review summarizes patient persistence and compliance with bisphosphonates for the treatment of osteoporosis. METHODS: We conducted a MEDLINE search for the period from January 1998 to May 2006, using a detailed list of terms related to persistence and compliance with anti-osteoporosis medications. Studies were included if they contained at least one measure of persistence or compliance derived from de-identified administrative databases containing patient demographics and prescription information. RESULTS: We reviewed 14 reports, which described 14 databases. The percentage of patients persisting with therapy for 1 year ranged from 17.9% to 78.0%. Compliance, assessed as mean medication possession ratio (MPR), ranged from 0.59 to 0.81. When comparing compliance with weekly and daily bisphosphonates, the mean MPR was consistently higher for weekly versus daily therapy (0.58 to 0.76 versus 0.46 to 0.64 for patients receiving weekly and daily bisphosphonate therapy respectively). Persistence was also improved in patients receiving weekly bisphosphonates, assessed by both length of persistence (194 to 269 days [weekly] and 134 to 208 days [daily]) and percentage of persistent patients at the end of the follow-up period (35.7% to 69.7% [weekly] and 26.1% to 55.7% [daily]). CONCLUSION: Although patients using weekly bisphosphonate medication follow their prescribed dosing regimens better than those using daily therapy, overall compliance and persistence rates were suboptimal.

Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study.

INTRODUCTION: Randomized clinical trials have shown that risedronate and alendronate reduce fractures among women with osteoporosis. The aim of this observational study was to observe, in clinical practice, the incidence of hip and nonvertebral fractures among women in the year following initiation of once-a-week dosing of either risedronate or alendronate. METHODS: Using records of health service utilization from July 2002 through September 2004, we created two cohorts: women (ages 65 and over) receiving risedronate (n = 12,215) or alendronate (n = 21,615). Cox proportional hazard modeling was used to compare the annual incidence of nonvertebral fractures and of hip fractures between cohorts, adjusting for potential differences in risk factors for fractures. RESULTS: There were 507 nonvertebral fractures and 109 hip fractures. Through one year of therapy, the incidence of nonvertebral fractures in the risedronate cohort (2.0%) was 18% lower (95% CI 2% - 32%) than in the alendronate cohort (2.3%). The incidence of hip fractures in the risedronate cohort (0.4%) was 43% lower (95% CI 13% - 63%) than in the alendronate cohort (0.6%). These results were consistent across a number of sensitivity analyses. CONCLUSION: Patients receiving risedronate have lower rates of hip and nonvertebral fractures during their first year of therapy than patients receiving alendronate.

The role of socioeconomic status on hip fracture.

INTRODUCTION: The impact of socioeconomic status-income and acculturation-on hip fracture is not well understood. We studied 116,919 fractures among 8,144,469 people in California. Greater income and English fluency predict lower fracture incidence. Lower income and immigrant populations are at increased risk for hip fracture and require intervention. Race/ethnicity is a major determinant of hip fracture risk. Although socioeconomic status (e.g., income and acculturation) is often associated with race/ethnicity, its impact on hip fracture incidence is less well understood. METHODS: We carried out a retrospective, population-based, study of persons with hip fractures in California, 1996 to 2000, compared to census estimates by zip code. We performed Poisson regression analyses to calculate hip fracture incident rate ratios for gender, age, race/ethnicity, income, language (percent non-English speakers)-a proxy for acculturation-and living in rural areas. RESULTS: During the 5-year period, 116,919 fractures occurred among 8,144,469 persons (2.87 fractures/1,000 persons per year). Higher income predicted lower hip fracture incidence. Persons in the highest decile of estimated income had an incident rate ratio (IRR) of 0.79 (95% confidence interval (CI) 0.77 to 0.82) compared with those in the lowest decile. Greater IRR of hip fracture was predicted for persons living in areas with a greater percent of non-English speakers (IRR 1.004, 95% CI 1.003 to 1.005). CONCLUSIONS: Low income and language fluency are predictors of greater hip fracture incidence. Although much attention is given to the aging of the "baby boomers", low income and immigrant populations are at increased risk for hip fracture and require intervention.

Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study.

BACKGROUND: Reducing bisphosphonate dosing frequency may improve suboptimal adherence to treatment and therefore therapeutic outcomes in postmenopausal osteoporosis. Once-monthly oral ibandronate has been developed to overcome this problem. OBJECTIVE: To confirm the 1 year results and provide more extensive safety and tolerability information for once-monthly dosing by a 2 year analysis. METHODS: MOBILE, a randomised, phase III, non-inferiority study, compared the efficacy and safety of once-monthly ibandronate with daily ibandronate, which has previously been shown to reduce vertebral fracture risk in comparison with placebo. RESULTS: 1609 postmenopausal women were randomised. Substantial increases in lumbar spine bone mineral density (BMD) were seen in all treatment arms: 5.0%, 5.3%, 5.6%, and 6.6% in the daily and once-monthly groups (50 + 50 mg, 100 mg, and 150 mg), respectively. It was confirmed that all once-monthly regimens were at least as effective as daily treatment, and in addition, 150 mg was found to be better (p<0.001). Substantial increases in proximal femur (total hip, femoral neck, trochanter) BMD were seen; 150 mg produced the most pronounced effect (p<0.05 versus daily treatment). Independent of the regimen, most participants (70.5-93.5%) achieved increases above baseline in lumbar spine or total hip BMD, or both. Pronounced decreases in the biochemical marker of bone resorption, sCTX, observed in all arms after 3 months, were maintained throughout. The 150 mg regimen consistently produced greater increases in BMD and sCTX suppression than the 100 mg and daily regimens. Ibandronate was well tolerated, with a similar incidence of adverse events across groups. CONCLUSIONS: Once-monthly oral ibandronate is at least as effective and well tolerated as daily treatment. Once-monthly administration may be more convenient for patients and improve therapeutic adherence, thereby optimising outcomes.

Association of severe vertebral fractures with reduced quality of life: reduction in the incidence of severe vertebral fractures by teriparatide.

OBJECTIVE: The association between vertebral fracture severity and health-related quality of life (HRQOL) was investigated in a subset of patients in the Fracture Prevention Trial. We sought to determine whether vertebral fracture severity was associated with HRQOL scores, and if so, to determine the effects of teriparatide (recombinant human parathyroid hormone 1-34) on vertebral fracture grades that most strongly impact HRQOL in postmenopausal women with osteoporosis. METHODS: Vertebral fracture severity was assessed by the visual semiquantitative (SQ) method. A subset of 444 patients with a baseline radiograph completed the Osteoporosis Assessment Questionnaire. Baseline HRQOL scores were modeled as a function of maximum baseline vertebral fracture grade, while controlling for age, bone mineral density, body mass index, and back pain. RESULTS: The effect of baseline vertebral fracture grade on baseline HRQOL was statistically significant, while interactions between vertebral fracture grade and the other variables were not statistically significant. SQ grade 3 (SQ3) vertebral fractures were associated with a significantly lower overall HRQOL score and with significantly lower physical function, symptoms, and emotional status dimension scores. After a median of 19 months of therapy, new or worsening SQ3 vertebral fractures occurred in 21 of 448 patients (4.7%) in the placebo group compared with 3 of 444 patients (0.7%) in the 20 mug/day teriparatide group. The risk of developing a new or worsened SQ3 vertebral fracture was reduced by 86% (P < 0.001) in patients treated with 20 mug/day teriparatide. CONCLUSION: Compared with prevalent fractures of lesser severity, SQ3 vertebral fractures were associated with reduced HRQOL. Teriparatide treatment significantly reduced the risk of new or worsening SQ3 vertebral fractures. These findings suggest, but do not directly demonstrate, a benefit of teriparatide on HRQOL.