Monthly Ibandronate Research Articles

Abstract P4-16-04: Oral ibandronate for osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: secondary 5-year survival outcomes analysis of the single-center phase 2 BONADIUV trial

Abstract Background. Several randomized trials demonstrated aromatase inhibitors (AI) superiority in terms of disease-free survival (DFS) compared to tamoxifen treatment for postmenopausal hormone receptor-positive breast cancer (BC) patients. Anyway, AI toxicity profile is a concern due to estrogen suppression. Pivotal trials demonstrated a significant bone mineral density (BMD) loss due to AI, with a consistent 5-year risk of bone fractures, thus impacting on patients' quality of life. Bisphosphonates represent an effective treatment in postmenopausal osteoporosis fractures prevention. However, an adequate patient's selection for adjuvant bisphosphonates treatment during AI endocrine therapy is still a challenge. Final results of BONADIUV trial presented at San Antonio Breast cancer Symposium in 2016 showed that treatment with ibandronate, as compared to placebo, significantly improved BMD change in osteopenic women treated with adjuvant AI, and consistently protected patients' bone loss. We present the secondary 5-year analysis on survival outcomes of the trial. Patients and methods. The BONADIUV trial is a single-blind, randomized, placebo-controlled phase 2 study designed to evaluate the impact of ibandronate treatment on BMD in osteopenic women taking AI. Between January 2011 and May 2014, 171 osteopenic patients (lumbar spine [LS] and/or trochanter -1< T-score <-2.5), were randomized in a 1:1 ratio to receive either placebo or oral monthly ibandronate (150 mg). Treatment duration was 2 years, with 6-months evaluation. Primary endpoint was the mean BMD difference between the two arms at a 2-year follow up. Secondary analysis on survival outcomes (overall survival [OS] and invasive DFS [iDFS]) have been performed at 5-year median follow-up time. ClinicalTrials.gov identifier: NCT02616744. Results. At the database cutoff time for the present analysis on May 4, 2018, median follow up was 63.3 months (mean 61.2; range 2.7-87.3) for whole series, 64.9 months (range 33.8-84.0) for the placebo arm, and 62.2 months (range 24.2-87.3) for the ibandronate arm. Ten patients in the placebo group and 17 patients in the ibandronate group withdrew the allocated arm before any follow up data collection, and so were excluded from the analysis, performed on 144 patients (72 patients per arm). At the database cutoff time, the OS rate was 97.2% in the placebo group and 100% in the ibandronate arm. We observed four loco-regional relapse (three in the placebo arm, one in the ibandronate arm; p=0.33), three distant metastases (none in the placebo arm, three in the ibandronate arm; p=0.075), and three contralateral BC (one in the placebo arm, two in the ibandronate arm; p=0.65). The number of iDFS events did not differ between groups: four in the placebo group and six in the ibandronate group (p=0.56). Up to data cutoff, two deaths have occurred; none in the placebo arm and two in the ibandronate arm (p=0.15). The OS rate did not differ between arms. Conclusions. The secondary analysis of survival outcomes showed no difference between arms in terms of OS and iDFS rates. Further large investigations and mature follow-up from the published ones are awaited. Citation Format: Meattini I, Scotti V, Desideri I, Saieva C, Visani L, Salvestrini V, Cecchini S, De Feo ML, Mariotti M, Olmetto E, Delli Paoli C, Francolini G, Bernini M, Orzalesi L, Sanchez L, Nori J, Bianchi S, Livi L. Oral ibandronate for osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: secondary 5-year survival outcomes analysis of the single-center phase 2 BONADIUV trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-04.

Phase 2 placebo-controlled, single-blind trial to evaluate the impact of oral ibandronate on bone mineral density in osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: 5-year results of the single-centre BONADIUV trial

AimWe present the final results of the BONADIUV trial, a single-blind, randomised, placebo-controlled phase 2 study to evaluate the impact of ibandronate treatment on bone mineral density (BMD) in osteopenic women taking aromatase inhibitors (AI). Patients and methodsBetween 2011 and 2014, 171 osteopenic patients were randomised in a 1:1 ratio to receive either placebo or oral monthly ibandronate (150 mg). Treatment duration was 2 years, with 6-month evaluation. Primary end-point was the 2-year lumbar spine (LS) and total hip (TH) T-score mean differences as measure of BMD variation. Secondary analyses of survival outcomes have been performed at a 5-year median follow-up. ClinicalTrials.gov identifierNCT02616744. ResultsMedian age of study population was 60.2 years (range 44–75). At the database cut-off time, the median follow-up was 63.3 months (range 2.7–87.3). No difference in terms of T-score was shown at baseline between arms both for TH (P = 0.61) and LS (P = 0.96). At 2-year follow up, the mean change was statistically significant in favour of ibandronate arm both at TH (P = 0.0002) and LS (P < 0.0001). No significant difference in terms of adverse events was observed between arms. At a median follow-up of 63.3 months (range 2.7–87.3), the overall survival (OS) rate was 97.5% in the placebo group and 93.0% in the ibandronate arm (P = 0.19). The invasive disease-free survival (iDFS) rates did not differ between groups (P = 0.42). ConclusionsIbandronate compared to placebo improved BMD change in osteopenic women treated with adjuvant AI. Five-year survival analyses showed no difference between arms in terms of OS and iDFS rates.

Abstract P2-09-12: A single-blind, randomized, placebo-controlled phase II study to evaluate the impact of oral ibandronate on bone mineral density in osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: Final results of the single-center BONADIUV trial

Abstract Background. Several randomized trials demonstrated aromatase inhibitors (AI) superiority in terms of disease-free survival compared to tamoxifen treatment for postmenopausal hormone receptor-positive breast cancer (BC) patients. Anyway AI toxicity profile due to estrogen suppression is a concern. Pivotal trials demonstrated a significant bone mineral density (BMD) loss due to AI, with a consistent risk of fractures, thus impacting on patients' quality of life. Bisphosphonates represent an effective treatment in postmenopausal osteoporosis fractures prevention. Several studies demonstrated that upfront bisphosphonates therapy prevents bone loss in postmenopausal women receiving adjuvant AI for early-stage BC. However an adequate patients selection for adjuvant bisphosphonates treatment during AI endocrine therapy is still a challenge. We present the final results of the BONADIUV trial, a single-blind, randomized, placebo-controlled phase 2 study designed to evaluate the impact of ibandronate treatment on BMD in osteopenic women taking AI. Methods. Between January 2011 and May 2014, 561 patients underwent a baseline BMD assessment before starting AI as planned adjuvant treatment. Overall 171 osteopenic patients (lumbar spine [LS] and/or trochanter -1&amp;lt; T-score &amp;lt;-2.5), were randomized in a 1:1 ratio to receive either placebo or oral monthly ibandronate (150 mg). All patients receive oral supplementation of calcium and vitamin D3. Study duration was 2 years. Exclusion criteria were: premenopausal status at time of randomization; comorbidities with increased risk of osteoporosis; body mass index &amp;lt;18; chronic use of steroids; previous use of bisphosphonates; psychiatric disorders. Primary endpoint was the mean BMD difference between the two arms at a 2-year follow up. ClinicalTrials.gov identifier: NCT02616744. A total of 72 patients per arm of treatment were needed to obtain an 85% statistical power in order to detect a 2% BMD mean difference between the two arms. Considering a 10% dropout, at least 158 patients were required. Results. A total of 171 patients were randomized in the study. Overall 27 patients (15.8%) withdrew the protocol (17 ibandronate vs 10 placebo arm): the final analysis was performed on 144 patients (72 patients per arm). P-value from Wilcoxon test showed no significant difference between arms at baseline both for LS (p=0.94) and trochanter (p=0.83). At 2-year, osteopenic patients treated with ibandronate gained +18.7% and +15.5% at the LS and trochanter BMD, respectively. Patients treated with placebo lost -13.3% at the LS, and gained +2.9% at the trochanter. Trochanter p-value from covariance analysis showed a mean BMD change significantly in favor of ibandronate arm at 1-year (p=0.012), and borderline at 2-year (p=0.087). Concerning LS, the mean BMD change was significantly in favor of ibandronate arm both at 1-year (p=0.002) and 2-year (p&amp;lt;0.0001). Conclusions. Final results of our study showed that treatment with ibandronate, as compared to placebo, improved BMD change in osteopenic women treated with adjuvant AI, and consistently protected patients' bone loss. Citation Format: Livi L, Saieva C, Desideri I, Scotti V, De Luca Cardillo C, Carta G, Cecchini S, Orzalesi L, Sanchez LJ, Casella D, Bernini M, Nori J, Bianchi S, De Feo ML, Meattini I. A single-blind, randomized, placebo-controlled phase II study to evaluate the impact of oral ibandronate on bone mineral density in osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: Final results of the single-center BONADIUV trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-09-12.

Adherence to oral bisphosphonates: 30 more minutes in dosing instructions matter

Objectives Low adherence to treatment with bisphosphonates significantly impedes its effectiveness. The objectives were: (1) to compare adherence to oral weekly and monthly bisphosphonates with emphasis on dosing instructions; and (2) to study associations between adherence and beliefs about the bisphosphonate treatment among women ≥ 55 years.Methods A multicenter survey was performed in secondary-care patients with osteoporosis. Osteoporosis Specific Morisky Medication Adherence Scale (OS-MMAS), questions on compliance with five dosing instructions and Beliefs about Medicines Questionnaire (BMQ) Specific were used.Results As many as 363 questionnaires (response rate 95%) were analyzed. Respondents (mean age 69 years) were treated with weekly bisphosphonates (37%) or monthly ibandronate (63%). Based on OS-MMAS, 67% of respondents showed high adherence with no differences between the subgroups. Only 44% of respondents were compliant with all dosing instructions. Compliance with dosing instructions concerning time interval (fasting and staying upright) was 71% in weekly and 52% in monthly subgroups, respectively (p < 0.001). Compliance with dosing instructions correlated positively with education (p = 0.009). The mean BMQ necessity score of 18.4 was greater than the mean BMQ concerns score of 13.3. OS-MMAS score correlated with necessity (p = 0.010). Persistence derived from OS-MMAS correlated with both necessity (p = 0.014) and concerns (p = 0.041).Conclusion Despite relatively high adherence to the treatment, most patients do not follow dosing instructions. Reduced bioavailability, particularly of monthly ibandronate, can be expected in clinical practice. Adherence-related outcomes are associated with beliefs about the oral treatment with bisphosphonates.

Randomized trial comparing monthly ibandronate and weekly alendronate for osteoporosis in patients with primary biliary cirrhosis

Osteoporosis resulting in bone fractures is a complication in patients with primary biliary cirrhosis (PBC). Once-weekly alendronate improves bone mass and is well tolerated in these patients, but there is a concern because of poor compliance. Therefore, the efficacy, adherence, and safety of monthly ibandronate (150 mg) with weekly alendronate (70 mg) were compared in a randomized, 2-year study in 42 postmenopausal women with PBC and osteoporosis. Bone mineral density (BMD) of the lumbar spine and proximal femur (by DXA), liver function, and bone markers were measured at entry and every 6 months over 2 years. Adherence to therapy was assessed by the Morisky-Green score. At enrollment, the two groups were similar with respect to age, BMD, severity of cholestasis, previous fractures, and bone markers. Thirty-three patients, 14 in the ibandronate group and 19 in the alendronate group, completed the trial. At 2 years both treatments resulted in a significant increase in BMD at the lumbar spine (from 0.875 ± 0.025 to 0.913 ± 0.026 g/cm(2), P < 0.001 with alendronate, and from 0.898 ± 0.024 to 0.949 ± 0.027 g/cm(2), P < 0.001 with ibandronate). The mean percentage change was 4.5% and 5.7%, respectively (P = not significant). BMD increased at the total hip by 2.0% and 1.2%, respectively. Changes in bone markers were similar in both groups and one patient with alendronate developed a new vertebral fracture. Adherence to therapy was higher with ibandronate (P = 0.009). Neither treatment impaired liver function or cholestasis. Both regimens, weekly alendronate and monthly ibandronate, improve bone mass and are comparable in safety for osteoporosis therapy in patients with PBC, although adherence is higher with the monthly regimen. Further larger studies are needed to assess fracture prevention.

AB1012 The efficacy and safety of ibandronate in patients with osteoporosis – importance of risk factors and fractures

BackgroundTreatment of osteoporosis may be expected to affect the remodelling phase of bone repair and therefore promote fracture healing. Ibandronat significantly increase bone mineral density (BMD) and reduce the risk...

THU0403 Switching to IV Zoledronate for Osteoporosis Results in Recurrent Annual Drug Cost-Savings – Results of a Quality Improvement Project

BackgroundAnnual IV zoledronate has been shown to be the most effective bisphosphonate in fracture prevention. It is therefore first-choice now when starting new IV therapy in our department when osteoporosis...

The effect of monthly Ibandronate on bone mineral density and bone turnover markers in patients with hemophilia A or B and increased risk for fracture

The effect of monthly Ibandronate on bone mineral density and bone turnover markers in patients with hemophilia A or B and increased risk for fracture

A candidate identification questionnaire for postmenopausal osteoporosis patients switched from daily or weekly bisphosphonate to once-monthly ibandronate: An open, prospective, multicenter study—BONCURE study

A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once-monthly dosing. This was a prospective, open-label, multicenter international study in patients with postmenopausal osteoporosis who had been receiving once-daily or once-weekly alendronate or risendronate for at least 3 months. Patients completed a CIQ, then commenced 150 mg monthly ibandronate for 6 months. Patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-QTM) at baseline for 6 months. Scores were converted to composite satisfaction scores (CSS, scale 0-100). Totally 677 patients completed a CIQ, 645 were enrolled in the treatment phase and comprised the intent-to-treat (ITT) population, and 630 completed the study. In the ITT population, 68.1% patients answered “yes” to one or more CIQ questions. OPSAT-Q scores increased for the convenience, quality of life and overall satisfaction domains (p scores for the side effects domains were significant (p preferred the once-monthly dosing schedule and 563 patients (90.7%) found it more convenient. The most common adverse events were dyspepsia (1.9%), nausea (1.1%), and upper abdominal pain (0.9%). Patients are likely to prefer treatment with monthly ibandronate to a weekly or monthly bisphosphonate irrespective of their stated preference before switching treatment.

The effect of monthly ibandronate on bone mineral density and bone turnover markers in patients with haemophilia A and B and increased risk for fracture

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, no study has so far evaluated the effects of anti-osteoporotic therapy on BMD in haemophilia.The primary endpoint of this prospective study was to estimate the effect of 12-month therapy of oral ibandronate 150 mg/month on BMD in patients with haemophilia A and B. Secondary endpoint was its effect on turnover markers (BTM) of bone resorption [serum C-terminal telopeptide of type 1 collagen (sCTX), tartrate-resistant acid phosphatase band 5b] and bone formation (osteocalcin and bone-specific alkaline phosphatase. Ten adult patients with T-score < -2.5 SD or Z-score < -2 and/or increased risk of fracture according to FRAX model were included. All received 1,000 mg/day calcium carbonate with 800 IU/d cholecalciferol. Males with haemophilia A (n=7) or B (n=3) (mean age 43.5 ± 13.5 years) were studied. Ibandronate resulted in an increase in lumbar BMD (from 0.886 ± 0.169 to 0.927 ± 0.176 g/cm2, 4.7%, p=0.004). No change in BMD of total hip (from 0.717 ± 0.128 to 0.729 ± 0.153 g/cm2, p=0.963) or femoral neck (0.741 ± 0.135 to 0.761 ± 0.146 g/cm2, p=0.952) was noticed. Ibandronate led to a decrease in sCTX (from 0.520 ± 0.243 to 0.347 ± 0.230 ng/ml, -29.9%, p=0.042). No change was observed in other BTM. Ibandronate was generally well-tolerated. In conclusion, ibandronate significantly improved BMD in lumbar spine and reduced bone resorption in adults with haemophilia at increased risk of fracture. Its effect on hip BMD and bone formation markers was not significant.

Six Months of Parathyroid Hormone (1–84) Administered ConcurrentlyVersusSequentially with Monthly Ibandronate Over Two Years: The PTH and Ibandronate Combination Study (PICS) Randomized Trial

PTH therapy improves bone mineral density (BMD) and decreases fractures in postmenopausal osteoporosis, but cost and the burden of daily injections limit its use. We evaluated two novel approaches to the use of 6 months of PTH therapy over 2 yr. We conducted a randomized, double-blinded trial of two combinations of daily PTH(1-84) and monthly ibandronate in 44 postmenopausal women with low bone mass. Participants received either 6 months of concurrent PTH and ibandronate, followed by 18 months of ibandronate (concurrent) or two sequential courses of 3 months of PTH followed by 9 months of ibandronate (sequential) over 2 yr. Bone turnover markers were measured. Areal and volumetric BMD were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography, respectively. Over 2 yr, areal BMD at the spine and hip increased similarly in both groups, with 7.5 and 8.2% increases in spine BMD in the concurrent and sequential arms, respectively (difference -0.6%, 95% confidence interval=-3.4-2.1%). Volumetric BMD also increased similarly between groups. With concurrent therapy, mean N-propeptide of type I collagen increased 75% between baseline and month 1 and then declined. With sequential therapy, the second 3-month PTH course increased N-propeptide of type I collagen markedly (209%), although to a lesser absolute degree than the first. Six months of PTH(1-84), used over 2 yr with a bisphosphonate in either of our dosing regimens increased BMD substantially. Short PTH courses may provide the benefits of anabolic osteoporosis therapy with reduced burden for patients.

Treatment of bone loss in patients with chronic liver disease awaiting liver transplantation

BackgroundMost of the patients awaiting liver transplantation already have osteopenia or even osteoporosis by end-stage liver disease.In a retrospective study, we investigated the effect of pre-treatment with oral monthly ibandronate (150 mg), vitamin D3 (800 IU/day) and calcium (1 g/day) for osteopenia and osteoporosis caused by end-stage liver disease in patients before and after liver transplantation (LT).MethodsThe bone mineral density (BMD) of the lumbar spine (LS) and the femoral neck was measured prospectively pre- and post-LT in 31 patients with existing pre-transplant osteopenia. Patients had osteopenia of the LS prior to LT (T-score −1.8 ± 1.5) so that the treatment medication was initiated immediately after the diagnosis.ResultsThe study group showed a permanently increased BMD with significant differences (g/cm²) from baseline up to 12 months post LT at the lumbar spine (LS: pre-LT 0.80 ± 0.11 g/cm², three months: 0.90 ± 0.08 (P <0.005); six months: 0.95 ± 0.11 (P < 0.008); 12 months: 1.00 ± 0.09 -0.85 (P <0.012).ConclusionThe combined pre- and post-operative treatment with oral ibandronate had significantly improved bone mineral density of the lumbar spine at 3, 6 and 12 months post LT. The immediate post-operative bone loss after LT can be significantly avoided by pre-treatment of liver transplant candidates affected by osteopenia.

Effect of oral monthly ibandronate on bone microarchitecture in women with osteopenia—a randomized placebo-controlled trial

We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia. We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150mg monthly ibandronate or placebo over 24months. Bone microarchitecture was assessed at baseline, 6, 12, and 24months, using HR-pQCT at the distal radius and tibia; areal bone mineral density (aBMD) was measured with DXA at the spine, hip, and radius. At 12months, there was no significant difference in trabecular bone volume at the radius (the primary end point) between women on ibandronate (10.8 ± 2.5%) and placebo (10.5 ± 2.9%), p = 0.25. There was no significant difference in other radius trabecular and cortical microarchitecture parameters at 12 and 24months. In contrast, at the tibia, cortical vBMD in the ibandronate group was significantly greater than in the placebo group at 6, 12, and 24months, with better cortical thickness at 6, 12, and 24months. With ibandronate, aBMD was significantly increased at the hip and spine at 12 and 24months but at the radius was significantly superior to placebo only at 24months. Most of the adverse events related to ibandronate were expected with bisphosphonate use, and none of them were serious. We conclude that 12months of treatment with ibandronate in women with osteopenia did not affect trabecular bone microarchitecture, but improved cortical vBMD at the tibia at 12 and 24months, and preserved cortical thickness at the tibia.

Monthly or weekly bisphosphonate? Evaluation of satisfaction in patients with postmenopausal osteoporosis using OPSAT-Q questionnaire during the BOOSTER study in Croatia

A prospective, open-labelled, multicentre 6-month study was designed to assess three categories that have high impact on Health-Related Quality of Life (HR-QoL). These categories were: satisfaction, preference and drug tolerability in postmenopausal patients with osteoporosis in Croatia, at first treated with weekly oral bisphosphonates, followed by monthly oral ibandronate. Three hundred eighty-five postmenopausal women who were treated with one of the weekly bisphosphonates for at least 6months were included into the study and after they had signed written informed consent, the therapy was changed to monthly ibandronate. Satisfaction with the treatment was assessed with the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q). Patients completed OPSAT-Q at the baseline visit before the change of therapy (visit 1) and 6months after the change of therapy (visit 2). Following 6months ibandronate therapy, the values in all four domains of the OPSAT-Q (convenience, confidence with daily activities, overall satisfaction, side effects) as well as in the Composite Satisfaction Score were higher in visit 2 (p < 0.001). Values in subjects enrolled into the patient assistance programme did not differ significantly from the values in subjects that were not (p = 0.399) except for the domain convenience (p = 0.026). This study demonstrates significantly higher satisfaction in patients who switched from the weekly bisphosphonate therapy regimen to monthly ibandronate in all observed aspects of treatment. Patients expressed preference for monthly bisphosphonate (ibandronate) in comparison with weekly bisphosphonates and found it to be a more convenient method of treatment. At the time of study, however, it was not known that the anti-fracture effect of ibandronate was smaller for hip fractures than with other bisphosphonates.

Efficacy of monthly oral ibandronate is sustained over 5 years: the MOBILE long-term extension study

The long-term efficacy and safety of once-monthly ibandronate were studied in this extension to the 2-year Monthly Oral Ibandronate in Ladies (MOBILE) trial. Over 5 years, lumbar spine bone mineral density (BMD) increased from baseline with monthly ibandronate 150 mg (8.4%). Long-term monthly ibandronate is effective and well tolerated for up to 5 years in women with postmenopausal osteoporosis. Once-monthly therapy with ibandronate has been studied for up to 5 years in a long-term extension (LTE) to the 2 year MOBILE trial. This multicenter, double-blind extension study of monthly ibandronate involved postmenopausal women who had completed 2 years of the MOBILE core study, with ≥75% adherence. Patients were reallocated, or were randomized from daily therapy, to ibandronate 100 mg monthly or 150 mg monthly for a further 3 years. A pooled intent-to-treat (ITT) analysis of 344 patients receiving monthly ibandronate from the core MOBILE baseline showed increases over 5 years in lumbar spine BMD (8.2% with 100 mg and 8.4% with 150 mg). Three-year data relative to MOBILE LTE baseline in the full ITT population of all 698 patients randomized or reallocated from MOBILE (including those previously on daily treatment) showed, on average, maintenance of proximal femur BMD gains achieved in the core 2-year study, with further small gains in lumbar spine BMD. In general, maintenance of efficacy was also indicated by markers of bone metabolism. There were no tolerability concerns or new safety signals. Monthly treatment with ibandronate 100 and 150 mg is effective and well tolerated for up to 5 years in women with postmenopausal osteoporosis.

Effect of monthly ibandronate on hip structural geometry in men with low bone density

Hip structural analysis (HSA) performed in a subset of participants from the STudy Researching Osteoporosis iN Guys (STRONG) demonstrated that 1 year of ibandronate treatment was associated with a significant improvement in some but not all parameters of hip geometry relative to placebo in men with low bone density. HSA was performed on dual-energy X-ray absorptiometry (DXA) images in a subset of participants from the STRONG to examine the impact of monthly ibandronate on geometric properties of the hip in men with low bone density. This prespecified subgroup analysis evaluated men in the intent-to-treat population of STRONG with baseline and 12-month DXA data. Cross-sectional geometric parameters of the femoral shaft (FS), intertrochanter region (IT), and narrow neck (NN) were calculated from femoral DXA scans. All analyses were exploratory. Treatment differences were evaluated using analysis of covariance, which adjusted for baseline parameter value, testosterone level, and treatment. HSA was performed on DXA scans from 89 men (34 placebo; 55 monthly ibandronate). Significant increases in average cortical thickness and cross-sectional area and decreases (i.e., improvements) in the buckling ratio were observed at the FS and IT at 12 months for ibandronate-treated men compared with placebo-treated men. No significant differences were observed between ibandronate and placebo for any NN HSA parameters. One year of ibandronate treatment was associated with a significant improvement in some but not all parameters of hip geometry relative to placebo in men with low bone density, suggesting that ibandronate may improve resistance to axial compressive forces and bending forces at the hip.

Adverse cutaneous drug reactions to ibandronate

Bisphosphonates are frequently used to treat bone diseases characterized by increased osteoclastic bone resorption. Adverse skin reactions to bisphosphonates are rare and range from benign to severe. Different cutaneous skin reactions have been reported with ibandronate in clinical and pharmacovigilance studies, from macula-papular rashes to toxic epidermal necrolysis. We report two new cases of erythematous and oedematous skin lesions to oral monthly ibandronate, appearing after multiple intakes of the drug. Prick tests were positive in both cases at 48 or 96 hours, and one could be confirmed histologically. Lesions did not relapse after substituting the culprit bisphosphonate with another one. A wide range of rare-to-very-rare adverse skin reactions exist with bisphosphonates, and especially ibandronate. We review the reported cases of adverse cutaneous drug reactions to bisphosphonates and illustrate the polymorphism and variety of the skin lesions. These reactions are not well known and may be misdiagnosed as they do not always suggest drug-induced eruptions. Furthermore, delays between drug intake and the first lesions can be misleading. The absence of cross-reactions among bisphosphonates allows substitution.

Efficacy and Safety of Monthly 150 mg Oral Ibandronate in Women with Postmenopausal Osteoporosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background/AimsThe aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO).MethodsA systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo.ResultsEight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < 1 × 10-8) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < 1 × 10-8). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups.ConclusionsOnce monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.

Health-Related Quality of Life Among Patients with Postmenopausal Osteoporosis Treated with Weekly and Monthly Bisphosphonates

Objective. The present study was designed to assess the effect of monthly ibandronate on health-related quality of life (HR-QoL) in patients with postmenopausal osteoporosis previously treated with weekly bisphosphonates. Methods. HR-QoL was assessed by Euroqol (EQ-5D) and Osteoporosis Targeted Quality of Life (OPTQoL) questionnaires. Results. The EQ-5D questionnaire showed significant improvement associated with ibandronate treatment, occurring in mobility (p < 0.01), usual activity (p < 0.01), pain/discomfort (p < 0.05), and anxiety/depression (p < 0.05). In addition, ibandronate treatment considerably improved patients' perceived health on a visual analog scale (p < 0.001). For the OPTQoL questionnaire, patients reported less physical difficulty (p < 0.001), fewer adaptations in their lives (p < 0.001), and less fear (p < 0.001) with ibandronate than with weekly bisphosphonates. Conclusion. The study demonstrated that patients who were transferred from weekly bisphosphonates to a monthly ibandronate experienced improved HR-QoL.

The Utility of Changes in Serum Levels of C-Terminal Telopeptide of Type I Collagen in Predicting Patient Response to Oral Monthly Ibandronate Therapy

Bone turnover markers may provide a more rapid indication of patient response to osteoporosis treatment than bone mineral density (BMD) measurements. This post hoc analysis of data from the MOBILE (Monthly Oral iBandronate In LadiEs) study assessed the relationship between increases in BMD at 12 mo from baseline after starting ibandronate treatment and changes in bone resorption marker serum C-terminal telopeptide of type I collagen (sCTX) from baseline at 3 and 6 mo. MOBILE enrolled postmenopausal women aged 55–80 yr with mean lumbar spine (LS) BMD T-score of −2.5 to −5.0. This analysis included women who received 150-mg monthly oral ibandronate (n = 323). A high proportion of women were classified as BMD responders after 1 yr (BMD increase was ≥0%, i.e., 74–91% depending on skeletal site; BMD increase was ≥3%, i.e., 34–67%). Women with larger decreases in sCTX were more likely to be BMD responders. The percent increase in LS BMD at 12 mo was significantly associated with the percent decrease in sCTX at 3 mo from baseline (Pearson correlation coefficient: −0.19, p = 0.0016). In linear regression models, percent decrease in sCTX at 3 mo from baseline was a significant predictor of 1-yr LS BMD response ( R 2 = 0.61, p = 0.0007). These data suggest that 3-mo changes in sCTX levels are associated with 1-yr LS BMD increases in postmenopausal women treated with once-monthly oral ibandronate.