Ibandronate Group Research Articles

Rationale, baseline characteristics and methodology of the non-interventional VIVA study in postmenopausal osteoporosis

SummaryIt is important to understand compliance and persistence with medication use in the clinical practice of osteoporosis treatment. The purpose of this work is to describe the “intravenous ibandronate versus oral alendronate” (VIVA) study, a non-interventional trial to assess the compliance and persistence of osteopenic postmenopausal women with treatment via weekly oral alendronate or intravenous ibandronate (Bonviva®) every three months.4477 patients receiving ibandronate 3 mg i. v. quarterly and 1491 patients receiving alendronate 70 mg orally weekly were included in the study. Matched pairs of 901 subjects in each group were also generated. Matching was performed on the basis of age, body mass index, fracture history at study inclusion, prior treatment with bisphosphonates and the number of concomitant disorders. Secondary outcome measures of osteoporosis related fractures, mobility restriction and pain, analgesia, quality of life questionnaires as well as attitudes to medications were assessed. The primary outcome parameters of compliance and persistence will be tracked in these subjects.At baseline, the entire collectives differed significantly on body weight (less in ibandronate group), duration since osteo - porosis diagnosis (longer in ibandronate), and incidence of prior osteoporotic fracture (higher in ibandronate group). The matched-pairs differed only on mobility restriction and quality of life (both worse in ibandronate group).The results from the VIVA study trial will provide scientific rationale for clinical recommendations in the pharmacological treatment of postmenopausal osteoporosis.

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.

Do bisphosphonates inhibit direct fracture healing?

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague-Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm(-2) (sd 7.63) vs 24.65 Nmm(-2) (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

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...

AB1015 Vitamin D level pre-intravenous bisphosphonate therapy

BackgroundIntravenous-bisphosphonates (IVB) are effective and very widely used in treatment of osteoporosis. Prior inadequate serum 25 hydroxyvitamin-D (25OHD), before administering IVB could lead to rapid life-threatening hypocalcaemia1,2. Also, it is...

Administration of PTH and ibandronate increases ovariectomized rat compact bone viscoelasticity

In this study, the bone mineral density (BMD), geometry, macroscopic viscoelastic properties and mechanical strength in five different groups of Sprague-Dawley rats (sham operated, ovariectomized with vehicle, parathyroid hormone and/or ibandronate administration) were examined by peripheral quantitative computed tomography (pQCT), dynamic mechanical analysis (DMA) and three-point bending test. At the end of the study, storage modulus (E′), loss tangent (tanδ), ultimate force (Fu) and stiffness (S) had greatly decreased in vehicle-treated ovariectomized group as compared to sham group (p<0.05). The concurrent administration of parathyroid hormone and ibandronate group exhibited the largest cortical area (Ct.Ar) and thickness (Ct.Th), E′, tanδ (0.3Hz) and subsequently highest Fu as compared to the mono-therapy groups (p<0.05). However, significant changes were not observed in the BMD values of different groups (p>0.05). The relationships between these potential predictors of bone strength (E′, tanδ, BMD and Ct.Ar) and bone mechanical strength parameters (Fu, S and ultimate stress σu) were also examined. Interestingly, during normal daily activity frequency range (0.9–6Hz), tanδ and Fu were positively correlated. Taken together, these data suggest that DMA can serve as an effective tool to assess bone strength which would be ignored under the normal clinical screenings due to an unchanged BMD. DMA can therefore be used as a better tool to assess the osteoporotic drug efficacy.

Treatment of bone marrow edema syndrome with intravenous Ibandronate

In this pilot study, we investigated the therapeutic efficacy of intravenous Ibandronate compared to pain medication on the outcome of bone marrow edemas (BME) of the knee and talus. Fifteen patients with a painful BME of the knee and 15 patients with a BME of the ankle, confirmed on MRI, were enrolled and treated with three ambulatory infusions of each 6mg Ibandronate (group 1). A control group (group 2) of 10 patients with a BME of the knee and 10 patients with a BME of the talus was treated with pain medication and partial weight bearing. Patients were evaluated clinically at baseline and at 1, 3, 6 and 12months after therapy start with a visual analog pain-scale (VAS) and specific joint scores (Larson knee- and Mazur ankle-score). BMEs were assessed with MRI at baseline and after 6months in both groups. In the knee group, the mean VAS pain score decreased from 8.5 at baseline to 1.2 at 12months (p<0.0001) in patients treated with Ibandronate and, respectively, from 8.1 to 4.0 in the control group (p<0.001). In the ankle group, the mean VAS pain score decreased from 8.2 at baseline to 0.9 at 12months (p<0.0001) in patients treated with Ibandronate and, respectively, from 7.9 to 3.9 in the control group (p<0.001). The mean Mazur ankle score increased from 51 to 91points (p<0.001) in group 1, and from 52 to 72points in group 2 (p<0.01). The mean Larson knee score increased from 54 to 89points (p<0.001) at 12months in group 1, and from 51 to 70points in group 2 (p<0.01). For both joints, we observed a significant clinical improvement in the Ibandronate treatment group and in the control group, but functional results were significantly more improved in the Ibandronate treatment group. Only the Ibandronate treatment group showed a significant BME regression at the 6months MRI follow-up. Intravenous Ibandronate therapy showed significantly better clinical results and BME regression rates on MR-imaging compared to analgesic medication in combination with partial weight bearing in the treatment of BME of the knee and talus and shortens the natural course of the disease.

Once-monthly oral ibandronate provides significant improvement in bone mineral density in postmenopausal women treated with glucocorticoids for inflammatory rheumatic diseases: a 12-month, randomized, double-blind, placebo-controlled trial

Objectives: To study the efficacy and safety of once-monthly oral ibandronate in the prevention of glucocorticoid (GC)-induced osteoporosis (GIOP) in postmenopausal women with inflammatory rheumatic diseases.Method: A randomized, double-blind, placebo-controlled, parallel-group study of 140 postmenopausal women was conducted. At baseline, the mean lumbar spine (LS) (L1–L4) bone mineral density (BMD) was normal or osteopaenic (T-score ≥ –2.0) and the patients were receiving treatment with 5–15 mg/day of prednisone equivalent. Patients were randomized 1:1 to receive either monthly oral ibandronate 150 mg or placebo for 12 months. All patients received vitamin D and calcium supplements. The primary endpoint was the relative change in mean LS BMD from baseline to 12 months.Results: Mean LS BMD increased significantly by 2.6% and 3.2% from baseline to 6 and 12 months with ibandronate compared to 0.3% and –0.1% with placebo, respectively (p < 0.001). Comparable significant mean increases were also found in trochanter, femoral neck and total hip BMDs at 12 months. Reductions in the serum levels of bone turnover markers C-terminal telopeptide of type I collagen (sCTX), N-terminal propeptide of type I procollagen (P1NP), and tartrate-resistant acid phosphatase (TRACP) were significantly more marked in the ibandronate group than in the placebo group at 1, 6, and 12 months. Adverse events (AEs) were reported at a similar frequency in both groups. A higher proportion of serious AEs (SAEs) were reported in the ibandronate group without emergence of any single SAE.Conclusions: Once-monthly oral ibandronate provides a significant increase in LS and total hip BMD with an acceptable safety profile in postmenopausal women treated with low-dose GCs for inflammatory rheumatic diseases.

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.

Local Administration of Ibandronate and Bone Morphogenetic Protein-2 After Ischemic Osteonecrosis of the Immature Femoral Head

Bisphosphonate therapy has been shown to preserve the osteonecrotic femoral head in experimental and short-term clinical studies. However, a lack of new bone formation within the preserved femoral head due to the inhibition of bone remodeling is a concern. The purpose of this investigation was to determine if combined therapy consisting of ibandronate and bone morphogenetic protein-2 (BMP-2) can preserve the shape of the femoral head and stimulate new bone formation in an immature animal model of ischemic osteonecrosis. Ischemic osteonecrosis was surgically induced in immature pigs. Four groups were studied: normal, treated with saline solution, treated with ibandronate, and treated with both ibandronate and BMP-2 (the ibandronate + BMP-2 group). The animals were killed eight weeks after surgery. Radiographic, histological, and histomorphometric assessments were performed. Radiographic assessment showed better preservation of the femoral head shape-i.e., a 54% (CI [95% confidence interval]: 22%, 86%) higher mean epiphyseal quotient-in the ibandronate + BMP-2 group than in the saline group. Histological assessment showed increased trabecular bone in the ibandronate + BMP-2 group as compared with that in the saline group. The mean values for trabecular bone volume, thickness, and number and for osteoblast surface were an average of 400% (CI: 242%, 558%), 212% (CI: 166%, 259%), 71% (CI: 6%, 137%), and 2402% (CI: 2113%, 2693%) higher, respectively, in the ibandronate + BMP-2 group than in the saline group. The osteoclast number was significantly reduced in the ibandronate + BMP-2 group compared with that in the saline group (-59% [CI: -75%, -42%]). The mean osteoblast surface value in the ibandronate + BMP-2 group was significantly higher (2567% [CI: 2258%, 2877%]) than that in the ibandronate group. Heterotopic ossifications were present in the capsule of the hip joint in the ibandronate + BMP-2 group. A combination of ibandronate and BMP-2 decreased femoral head deformity while stimulating bone formation in an immature animal model of ischemic osteonecrosis.

Four-year Results of a Phase 2 Study of the Cathepsin K Inhibitor Odanacatib in Postmenopausal Women with Low Bone Mineral Density: Effects on Bone Mineral Density and Bone Turnover Markers

Monthly oral ibandronate is indicated for the prevention and treatment of osteoporosis in postmenopausal women. The STudy Researching Osteoporosis iN Guys (STRONG) investigated the efficacy and safety of 150-mg monthly oral ibandronate in men with primary, idiopathic, or hypogonadism-related low bone density.STRONG was a 1-year, placebo-controlled, randomized (2 ibandronate: 1 placebo), double-blind study that enrolled ambulatory men aged ≥ 30 years with baseline femoral neck (FN) bone mineral density (BMD) T-scores ≤ − 2.0 and lumbar spine (LS) BMD T-scores ≤ − 1.0 or LS BMD T-scores ≤ − 2.0, FN BMD T-scores ≤ − 1.0, and BMD T-scores ≥ − 4.0 at any site assessed by dual-energy X-ray absorptiometry. The primary endpoint was mean percent change from baseline in LS BMD at 1 year (intent-to-treat [ITT] population). Secondary endpoints included mean BMD changes from baseline at the FN, total hip (TH), and trochanter (TR) and changes in bone turnover markers (BTMs), as measured by the bone resorption marker serum C-terminal telopeptide of type 1 collagen (sCTX) and the bone formation marker bone-specific alkaline phosphatase (BSAP). All men received twice daily calcium carbonate (1000 mg/day) and vitamin D (400 IU/day). Changes in BMD for treatment groups were compared using analysis of covariance with treatment, investigative site, and baseline testosterone as factors and baseline BMD as a covariate.The ITT population consisted of 132 men; 47 received placebo and 85 received monthly ibandronate. Men who received ibandronate achieved greater increases in LS BMD at 12 months than those who received placebo (3.5% vs. 0.9%, respectively; difference, 2.6; p < 0.001). The ibandronate group also achieved greater 12-month BMD increases than the placebo group, respectively, at the TH (1.8% vs. − 0.3%; difference, 2.1; p < 0.001), FN (1.2% vs. − 0.2%; difference, 1.4; p = 0.012), and TR (2.2% vs. 0.4%; difference, 1.7; p < 0.005). In men who completed the study and adhered to the protocol (per-protocol (PP) population), percent decreases in median sCTX and BSAP levels from baseline were also greater with ibandronate versus placebo (p ≤ 0.001 for both comparisons). Overall, monthly ibandronate was well tolerated.In men with low BMD, 1 year of treatment with oral once-monthly 150-mg ibandronate significantly increased BMD at the LS and hip (TH, TR, and FN), significantly reduced BTM levels in the PP population, and was generally well tolerated.

Intravenous Ibandronate Acutely Reduces Bone Hyperresorption in Chronic Critical Illness

Patients who remain critically ill for prolonged periods and require tracheotomy, defined as chronic critical illness (CCI), display elevated levels of bone resorption. The measurement of bone turnover markers reveals that osteoclastic bone resorption is not only enhanced but also uncoupled from osteoblastic bone formation. We examine the effect of ibandronate on bone turnover in patients with CCI. This study is a prospective, double-blind, placebo-controlled trial, in which 20 postmenopausal female participants with CCI were followed for an 11-day period after the administration of a single intravenous dose of ibandronate (3 mg). All participants were treated with ergocalciferol (2000 IU daily), calcium carbonate (1250 mg daily), and calcitriol (0.25 μg daily). The ibandronate group showed a 34% decrease in serum C-telopeptide (CTX) levels (a marker of osteoclastic activity) on day 6, while the placebo group showed a 13% increase (P = .01). By day 11, CTX levels in ibandronate group were not significantly different than baseline or from the placebo group. Osteocalcin (OCN) levels (a marker of osteoblast activity) increased by 78% compared to baseline in the ibandronate group (P = .01) and by 42% in the placebo group (P = .05). There were no significant differences in OCN between the 2 groups throughout the study. Parathyroid hormone levels remained constant throughout the study. No adverse events were observed. A single dose of intravenous ibandronate causes a significant but transient reduction in osteoclast activity in patients with CCI, which persists over a 6-day period.

Effects of intravenous zoledronic acid and oral ibandronate on early changes in markers of bone turnover in patients with bone metastases from non-small cell lung cancer

The aim of this study was to assess the early effects of zoledronic acid (ZOL) and oral ibandronate (IBA) on the bone resorption marker s-CTX (serum C-telopeptide of collagen type I) and the bone formation marker B-ALP (bone-alkaline phosphatase) in patients with bone metastases from non-small cell lung cancer (NSCLC). Fifty-five patients with at least one site of bone metastasis secondary to NSCLC were randomly assigned to receive intravenous ZOL 4 mg every 4 weeks, or oral IBA 50 mg/day. At 1 month of treatment, s-CTX was reduced by 54.8% (95% CI 40.4-59.8%) in the ZOL group (26 evaluable patients) compared with 38.2% (95% CI 29.8-48.7%) in the oral IBA group (27 evaluable patients) (p = 0.03). At 3 months, s-CTX was reduced by 72.6% (95% CI 58.6-71.3%) in the ZOL group, compared with 66.4% (95% CI 54.3-79.5%) in the oral IBA group (p = 0.22). Both bisphosphonates similarly decreased the bone marker B-ALP at 1 month (ZOL 24.7%, 95% CI 3.6-39.5%, and IBA 24.2%, 95% CI 2.8-43.4%) and 3 months (ZOL 28.6%, 95% CI +2.8-43.3%, and IBA 24.2%, 95% CI 3.2-47.4%). Both bisphosphonates were well tolerated. Considering the changes in bone markers, ZOL and oral IBA show comparable efficacy in patients with NSCLC and bone metastases.

Bones and Crohn's: no benefit of adding sodium fluoride or ibandronate to calcium and vitamin D.

To compare the effect of calcium and cholecalciferol alone and along with additional sodium fluoride or ibandronate on bone mineral density (BMD) and fractures in patients with Crohn's disease (CD). Patients (n =148) with reduced BMD (T-score < -1) were randomized to receive cholecalciferol (1000 IU) and calcium citrate (800 mg) daily alone(group A, n = 32) or along with additional sodium fluoride (25 mg bid) (group B, n = 62) or additional ibandronate (1 mg iv/3-monthly) (group C, n = 54). Dual energy X-ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur and X-rays of the spine were performed at baseline and after 1.0, 2.25 and 3.5 years. Fracture-assessment included visual reading of X-rays and quantitative morphometry of vertebral bodies (T4-L4). One hundred and twenty three (83.1%) patients completed the first year for intention-to-treat (ITT) analysis. Ninety two (62.2%) patients completed the second year and 71 (47.8%) the third year available for per-protocol (PP) analysis. With a significant increase in T-score of the lumbar spine by +0.28 ± 0.35 [95% confidence interval (CI): 0.162-0.460, P < 0.01], +0.33 ± 0.49 (95% CI: 0.109-0.558, P < 0.01), +0.43 ± 0.47 (95% CI: 0.147-0.708, P < 0.01) in group A, +0.22 ± 0.33 (95% CI: 0.125-0.321, P < 0.01); +0.47 ± 0.60 (95% CI: 0.262-0.676, P < 0.01), +0.51 ± 0.44 (95% CI: 0.338-0.682, P < 0.01) in group B and +0.22 ± 0.38 (95% CI: 0.111-0.329, P < 0.01), +0.36 ± 0.53 (95% CI: 0.147-0.578, P < 0.01), +0.41 ± 0.48 (95% CI: 0.238-0.576, P < 0.01) in group C, respectively, during the 1.0, 2.25 and 3.5 year periods (PP analysis), no treatment regimen was superior in any in- or between-group analyses. In the ITT analysis, similar results in all in- and between-group analyses with a significant in-group but non-significant between-group increase in T-score of the lumbar spine by 0.38 ± 0.46 (group A, P < 0.01), 0.37 ± 0.50 (group B, P < 0.01) and 0.35 ± 0.49 (group C, P < 0.01) was observed. Follow-up in ITT analysis was still 2.65 years. One vertebral fracture in the sodium fluoride group was detected. Study medication was safe and well tolerated. Additional sodium fluoride or ibandronate had no benefit over calcium and cholecalciferol alone in managing reduced BMD in CD.

Ibandronate does not increase risk of atrial fibrillation in analysis of pivotal clinical trials

To determine the incidence of adverse events or serious adverse events of atrial fibrillation in the pivotal trials of ibandronate and to assess whether increasing dose or duration of exposure had any effect on the incidence of atrial fibrillation. Pooled data from all four pivotal ibandronate clinical trials were analysed to assess the incidence of atrial fibrillation as an adverse event and serious adverse event with ibandronate vs. placebo. The incidence of atrial fibrillation with ibandronate was also assessed by dose, by annual cumulative exposure (ACE) and by patient age. This analysis included 6830 patients treated with ibandronate and 1924 treated with placebo. The incidence of atrial fibrillation as an adverse event (ibandronate, 0.8% and placebo, 0.9%) and serious adverse event (0.4% for both ibandronate and placebo) was comparable between the ibandronate and placebo groups. There was no increase in the incidence of atrial fibrillation as an adverse event or serious adverse event with increasing oral or intravenous (i.v.) ibandronate dose. No correlation between the incidence of atrial fibrillation as a serious adverse event and ibandronate duration of exposure was observed. Based on various ACE categories, none of the ibandronate regimens evaluated in these trials was associated with an increased incidence of atrial fibrillation. In this pooled analysis of all four ibandronate pivotal trials, including analysis by ACE, all studied ibandronate regimens, including the licensed doses of 150 mg monthly oral and 3 mg quarterly i.v., were not associated with an increased incidence of atrial fibrillation.

Efficacy and safety of monthly ibandronate in men with low bone density

Introduction Monthly oral ibandronate is indicated for the prevention and treatment of osteoporosis in postmenopausal women. The STudy Researching Osteoporosis iN Guys (STRONG) investigated the efficacy and safety of 150-mg monthly oral ibandronate in men with primary, idiopathic, or hypogonadism-related low bone density. Methods STRONG was a 1-year, placebo-controlled, randomized (2 ibandronate: 1 placebo), double-blind study that enrolled ambulatory men aged ≥ 30 years with baseline femoral neck (FN) bone mineral density (BMD) T-scores ≤ − 2.0 and lumbar spine (LS) BMD T-scores ≤ − 1.0 or LS BMD T-scores ≤ − 2.0, FN BMD T-scores ≤ − 1.0, and BMD T-scores ≥ − 4.0 at any site assessed by dual-energy X-ray absorptiometry. The primary endpoint was mean percent change from baseline in LS BMD at 1 year (intent-to-treat [ITT] population). Secondary endpoints included mean BMD changes from baseline at the FN, total hip (TH), and trochanter (TR) and changes in bone turnover markers (BTMs), as measured by the bone resorption marker serum C-terminal telopeptide of type 1 collagen (sCTX) and the bone formation marker bone-specific alkaline phosphatase (BSAP). All men received twice daily calcium carbonate (1000 mg/day) and vitamin D (400 IU/day). Changes in BMD for treatment groups were compared using analysis of covariance with treatment, investigative site, and baseline testosterone as factors and baseline BMD as a covariate. Results The ITT population consisted of 132 men; 47 received placebo and 85 received monthly ibandronate. Men who received ibandronate achieved greater increases in LS BMD at 12 months than those who received placebo (3.5% vs. 0.9%, respectively; difference, 2.6; p < 0.001). The ibandronate group also achieved greater 12-month BMD increases than the placebo group, respectively, at the TH (1.8% vs. − 0.3%; difference, 2.1; p < 0.001), FN (1.2% vs. − 0.2%; difference, 1.4; p = 0.012), and TR (2.2% vs. 0.4%; difference, 1.7; p < 0.005). In men who completed the study and adhered to the protocol (per-protocol (PP) population), percent decreases in median sCTX and BSAP levels from baseline were also greater with ibandronate versus placebo ( p ≤ 0.001 for both comparisons). Overall, monthly ibandronate was well tolerated. Conclusions In men with low BMD, 1 year of treatment with oral once-monthly 150-mg ibandronate significantly increased BMD at the LS and hip (TH, TR, and FN), significantly reduced BTM levels in the PP population, and was generally well tolerated.

Comparison of Monthly Ibandronate Versus Weekly Risedronate in Preference, Convenience, and Bone Turnover Markers in Korean Postmenopausal Osteoporotic Women

Patient preferences, convenience, and bone turnover markers were evaluated for the monthly ibandronate over the weekly risedronate regimen in Korean postmenopausal osteoporotic women. This was a 6-month, prospective, randomized, open-label, multicenter study with a two-period and two-sequence crossover treatment design. After a 30-day screening period, eligible participants with postmenopausal osteoporosis were randomized to receive either monthly oral ibandronate 150 mg for 3 months followed by weekly oral risedronate 35 mg for 12 weeks (sequence A) or the same regimen in reverse order (sequence B). Patient preference and convenience were evaluated by questionnaire. The changes in serum C-telopeptide after 3 months of treatment were analyzed. A total of 365 patients were enrolled in this study (sequence A 182, sequence B 183). Of patients expressing a preference (83.4%), 74.8% preferred the monthly ibandronate regimen over the weekly regimen (25.2%). More women stated that the monthly ibandronate regimen was more convenient (84.2%) than the weekly regimen (15.8%). There was no significant difference in the change in bone turnover marker between the two treatments. The two regimens were similarly tolerable. There were fewer adverse events in the monthly ibandronate group compared to the weekly risedronate group in terms of gastrointestinal side effects (nausea and abdominal distension). This study revealed a strong preference and convenience for monthly ibandronate over weekly risedronate in Korean postmenopausal osteoporotic women. There was no significant difference in change of bone turnover marker and safety profile between the two regimens.

Ibandronate Prevents Bone Loss and Reduces Vertebral Fracture Risk in Male Cardiac Transplant Patients: A Randomized Double-Blind, Placebo-Controlled Trial

Bone loss and fractures are common complications after cardiac transplantation (CTP). The aim of this study was to investigate whether intravenous ibandronate is an effective preventive option. Thirty-five male cardiac transplant recipients received either ibandronate (IBN) 2 mg intravenously every 3 mo or matching placebo (CTR) in addition to 500 mg calcium carbonate and 400 IE vitamin D(3). Sera were collected at CTP and every 3 mo thereafter. At baseline and 6 and 12 mo, standardized spinal X-rays and BMD measurements were taken. Bone biopsies were taken at CTP and after 6 mo from six patients. In the IBN group, 13% of the patients sustained a new morphometric vertebral fracture compared with 53% in the CTR group (absolute risk reduction [ARR], 40%; relative risk reduction [RRR], 75%; p = 0.04). BMD remained unchanged with IBN treatment but in the CTR group decreased at the lumbar spine by 25% and at the femoral neck by 23% (both p < 0.0001) over the 1-yr period. Serum bone resorption markers carboxy-terminal telopeptide region of type I collagen (sCTX) and TRACP 5b were significantly increased in the CTR group and decreased in the IBN group at all time points compared with baseline. In contrast, both osteocalcin and bone-specific alkaline phosphatase levels showed, after a similar decrease over the first 3 mo in both groups, a marked rise in the CTR subjects and steadily declining levels in the IBN patients throughout the remainder of the study period. Three paired biopsies were available from each group. Despite the small sample size, a difference in the relative change of eroded surface (68% in the CTR versus -23% in the IBN group, p < 0.05) could be shown. Intravenous IBN reduced fractures, preserved bone mass, and prevented uncoupling of bone formation and resorption after CTP. The favorable effects on bone turnover were also supported by histomorphometric findings.

The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats

Immobilized bisphosphonates (BPs) have been introduced to improve implant fixation, however, no information could be found about the efficiency of this approach in osteoporotic bone. This study was designed to evaluate the bone response to surface immobilized BPs on implants inserted in tibiae of ovariectomized (OVX) rats. Three months after bilateral ovariectomy, 40 rats were randomly assigned into four groups for implantation of hydroxyapatite-coated titanium implants with or without immobilized BPs: (1) control group (without BP treatments); (2) pamidronate (PAM) group (1 mg/ml of PAM immersing); (3) ibandronate group (1 mg/ml of ibandronate immersing); and (4) zoledronic acid (ZOL) group (1 mg/ml of ZOL immersing). After implantation periods of 3 months, the peri-implant–bone density, trabecular microstructure, bone–implant interface and mechanical fixation of implants were evaluated by dual energy X-ray absorptiometry, micro-computed tomography, histology and push-out test. We found that three BPs triggered pronounced bone–implant integration and early bone formation around implants in OVX rats, with a rank order of ZOL > ibandronate > PAM. These results provide new evidence that immobilized BPs have positive effects on implant fixation in osteoporotic bone, in addition to their well-documented potency to inhibit implant loosening in normal bone.

Efficacy and safety of monthly oral ibandronate in the prevention of postmenopausal bone loss

Introduction Monthly oral ibandronate has been shown to increase bone mineral density (BMD) and reduce bone turnover in postmenopausal women with osteoporosis, but its efficacy has not been investigated in women with low bone mass. The objective of this study was to examine the efficacy and safety of monthly oral ibandronate (150 mg) treatment in postmenopausal women with low bone mass. Methods This 1-year, double-blind, placebo-controlled, randomized study enrolled ambulatory postmenopausal women aged 45–60 years with baseline lumbar spine (LS) BMD T-score < − 1.0 and > − 2.5 and baseline T-score > − 2.5 at the total hip, trochanter, and femoral neck (collectively defined as the proximal femur) and no prior vertebral or low-trauma osteoporotic fractures at baseline. Subjects received either 150 mg monthly oral ibandronate or placebo. All subjects received calcium and vitamin D supplements. The primary endpoint was the relative change from baseline (%) in mean LS BMD at 1 year (intent-to-treat population). Treatment groups were compared by means of a two-way ANOVA model which adjusted for independent factors including treatment group, baseline LS BMD T-score, and time since menopause. Responder analyses examined the percentage of participants with changes from baseline in LS BMD and proximal femur BMD ≥ 0%. Adverse events and safety laboratory parameters were monitored continuously. Results A total of 77 women received monthly ibandronate and 83 women received placebo. Subjects treated with ibandronate achieved larger increases in LS BMD after 1 year compared with subjects receiving placebo (3.7% vs − 0.4% [difference of 4.1%, p < 0.0001]). After 3 months, median serum C-terminal telopeptide of type I collagen levels were reduced by > 55% in the ibandronate group compared with ∼ 4% in the placebo group. At 1 year, 88.2% of the participants treated with ibandronate achieved increases in LS BMD ≥ 0% compared with 38.6% of subjects receiving placebo. Treatment regimens were well tolerated in both the ibandronate-treated and placebo groups. Conclusion Monthly ibandronate therapy prevents bone loss in postmenopausal women with low bone mass.