Oral ibandronate preserves trabecular microarchitecture: micro-computed tomography findings from the oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe study.

Micro-computed tomography (micro-CT) is a quantitative 3-dimensional (3D) scanning procedure used to assess trabecular architecture. In the 3-yr oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe (BONE) study, it was found that oral ibandronate administered daily (2.5 mg) or intermittently (20 mg) significantly reduced vertebral fracture risk by 62% (p=0.0001) and 50% (p=0.0006), respectively, vs placebo. Two-dimensional histomorphometric analysis of BONE study biopsies indicated that newly formed bone was of normal quality. In the current analysis, micro-CT was used to assess 3D trabecular microarchitecture. Rod and plate distribution was quantified by differential analysis of the triangulated bone surface. Biopsies were obtained from 110 patients, with 84 evaluable by micro-CT. Median structural model index (SMI; a lower SMI indicates an increased ratio of plates to rods and thus, improved trabecular microarchitecture) was 1.001 with ibandronate vs 1.365 with placebo (90% confidence interval [CI] for difference in medians: -0.626, -0.033), and connectivity density was higher in ibandronate-treated patients (median: 3.904 vs 3.112/mm3, 90% CI for difference in medians: 0.159, 1.517). This indicates that trabecular microarchitecture was better preserved in patients receiving ibandronate than placebo. Taken together with previous results from BONE, these findings indicate that ibandronate treatment preserves bone strength by maintaining good quality trabecular microarchitecture in women with postmenopausal osteoporosis.

Patient preference for once-monthly ibandronate versus once-weekly alendronate in a randomized, open-label, cross-over trial: the Boniva Alendronate Trial in Osteoporosis (BALTO).

OBJECTIVE: Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered with extended interval dosing. Patient preferences were assessed for once-monthly versus once-weekly bisphosphonate treatment using a previously developed, open-label, cross-over trial design. RESEARCH DESIGN AND METHODS: This was a 6-month, prospective, randomized, open-label, multi-center study with a two-period and two-sequence cross-over treatment design. After screening, eligible patients (postmenopausal women with osteoporosis) were randomized to once-monthly ibandronate 150 mg followed by once-weekly alendronate 70 mg for a total of 6 months (Sequence A) or once-weekly alendronate followed by once-monthly ibandronate for a total of 6 months (Sequence B). The primary objective was to evaluate patient-reported preference for either the once-monthly ibandronate regimen or the once-weekly alendronate regimen based on responses to a preference questionnaire. RESULTS: A total of 342 patients were enrolled into this study (Sequence A, 170; Sequence B, 172). In the primary analysis of patient preference, 71.4% of women selected once-monthly ibandronate and 28.6% of women selected once-weekly alendronate. Overall, 66.1% preferred the once-monthly ibandronate regimen to the once-weekly alendronate regimen (26.5%) and 7.4% of participants stated no preference for either regimen. The preference rate for once-monthly ibandronate was statistically significant (p < 0.0001). 'Ease of following a treatment regimen for a long time' was the most common reason given for patient preference for both the once-monthly ibandronate (61%, 169/276) and once-weekly alendronate (25%, 70/276) regimens. Additionally, 17% (47/276) of patients who preferred once-monthly ibandronate chose 'it is easier to tolerate side effects' as did 4.3% (12/276) of patients who preferred alendronate. Significantly more women found once-monthly ibandronate to be more convenient (p < 0.0001). CONCLUSIONS: Significantly more women with postmenopausal osteoporosis preferred once-monthly ibandronate therapy to once-weekly alendronate therapy, and found the once-monthly regimen to be more convenient. Ease of following a treatment regimen for a long time was the most common reason given for the patients' preferences.

Mood effect of raloxifene in postmenopausal women.

OBJECTIVE: Some experimental and observational data suggest a role of estrogen in depression. Raloxifene is a selective estrogen receptor modulator (SERM) approved for the prevention and treatment of postmenopausal osteoporosis. Its influence on mood in postmenopausal women has not been fully established. Thus, we investigated the effect of raloxifene on mood. METHODS: In a randomized double-blind osteoporosis prevention study, the action of raloxifene on mood was assessed in a subgroup of non-depressed postmenopausal women (mean age: 58.9 years) receiving raloxifene 60 mg/day (n=18) or placebo (n=18). The Hamilton Depression Rating Scale (HDRS) was applied to evaluate mood 3 and 12 months following treatment. RESULTS: Baseline HDRS scores were not different among treatment groups. Overall scores decreased from baseline at 3 and 12 months in the raloxifene group (P

Effects of intermittent intravenous ibandronate injections on bone quality and micro-architecture in women with postmenopausal osteoporosis: the DIVA study.

In the Dosing IntraVenous Administration (DIVA) study, IV ibandronate injections (15-30 s duration) provided significantly greater gains in bone mineral density than daily oral ibandronate (P<0.001). Single transiliac bone biopsy was performed in a subgroup of women (n=109/1395) from DIVA to assess the impact of ibandronate on newly formed bone and bone remodeling. Patients received ibandronate IV injections 2 mg every 2 months, 3 mg every 3 months or oral ibandronate 2.5 mg daily, plus oral or IV placebo, as appropriate to maintain blinding. Of the 1395 participants from the DIVA study, 122 were enrolled in the substudy. Qualitative histological analysis was performed on all biopsy cores and 89 cores were considered to be evaluable for quantitative histomorphometry. Following 2 years of ibandronate treatment, trabecular bone maintained its normal lamellar structure with no evidence of woven bone, marrow fibrosis, cellular toxicity, or other qualitative abnormalities. Primary mineralization of new bone remained normal, as indicated by the slightly lower osteoid thickness and osteoid volume, with normal mineral apposition rate compared to healthy, postmenopausal women. Mineralizing surface, osteoid surface, activation frequency and bone formation rate were decreased in all ibandronate-treated groups compared with values from healthy, postmenopausal women. Specifically, the bone formation rate (BFR/BV and BFR/BS) was approximately 5 times lower in the ibandronate-treated (3 mg) group than in healthy, postmenopausal women. Histomorphometric analysis of transiliac bone biopsies demonstrated normal micro-structure of newly formed bone with normal mineralization and reduced remodeling after oral or IV ibandronate.

Treatment preference for monthly oral ibandronate and weekly oral alendronate in women with postmenopausal osteoporosis: A randomized, crossover study (BALTO II).

OBJECTIVES: Patient preference strongly influences long-term medication use in chronic diseases such as postmenopausal osteoporosis. METHODS: This 6-month, open-label, crossover, international study randomized 350 women with postmenopausal osteoporosis to monthly oral ibandronate 150mg for 3months followed by weekly alendronate 70mg for 12weeks, or vice versa. RESULTS: Of patients expressing a preference (93.1%), more preferred the monthly ibandronate regimen (70.6%) than the weekly alendronate regimen (29.4%). The monthly ibandronate preference rate was statistically significant (P<0.0001). The most common reasons for ibandronate preference were ease of staying on treatment long-term (81.5%) and better lifestyle fit (75.4%). More women found the monthly ibandronate regimen more convenient (76.6%) than the weekly alendronate regimen (23.4%). The monthly ibandronate convenience rate was statistically significant (P<0.0001). The safety profiles of the two regimens were similar. CONCLUSION: The strong patient preference for monthly ibandronate over weekly alendronate replicates previous study findings and may lead to improved treatment adherence in women with postmenopausal osteoporosis.

Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study.

OBJECTIVE: An effective and well tolerated intravenous (IV) bisphosphonate could provide a new treatment method for patients with osteoporosis. The Dosing IntraVenous Administration (DIVA) study was designed to identify the optimal ibandronate IV injection schedule for the treatment of postmenopausal osteoporosis by comparing the efficacy and tolerability of 2- and 3-monthly injections with the previously evaluated daily oral ibandronate regimen. We report the effects on lumbar spine and proximal femur bone mineral density (BMD) and bone resorption markers over 2 years. METHODS: This randomized, double-blind, double-dummy, noninferiority study recruited 1395 women (aged 55-80 yrs; > or = 5 yrs since menopause) with osteoporosis [mean lumbar spine (L2-L4) BMD T-score < -2.5 and > or = -5.0]. Patients received IV ibandronate (2 mg every 2 mo or 3 mg every 3 mo) plus daily oral placebo, or 2.5 mg daily oral ibandronate plus 2- or 3-monthly IV placebo. Supplemental vitamin D (400 IU) and calcium (500 mg) were provided throughout the 2-year study. RESULTS: At 2 years, the 2- and 3-monthly IV regimens achieved statistically noninferior and also superior increases in lumbar spine BMD compared with the daily regimen (6.4% and 6.3% vs 4.8%, respectively; p < 0.001). Greater increases were also obtained with IV ibandronate versus daily in proximal femur BMD. Serum concentrations of the biochemical marker of bone resorption C-telopeptide of the alpha-chain of type I collagen were reduced to a similar extent in all treatment arms (53.4%-59.9%). The tolerability profile of the IV regimens was similar to that observed with daily oral therapy. CONCLUSION: Ibandronate IV injections are an effective and well tolerated treatment for postmenopausal osteoporosis and provide a useful alternative to oral dosing.

Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study.

OBJECTIVE: Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis, oral dosing may be unsuitable for some patients. An efficacious intravenously administered bisphosphonate could be beneficial for such patients. Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered using extended dosing intervals, either orally or by rapid intravenous injection. The aim of this study was to identify the optimal intravenous dosing regimen for ibandronate in postmenopausal women with osteoporosis. METHODS: In a randomized, double-blind, double-dummy, phase III, noninferiority study, we compared 2 regimens of intermittent intravenous injections of ibandronate (2 mg every 2 months and 3 mg every 3 months) with a regimen of 2.5 mg of oral ibandronate daily, the latter of which has proven antifracture efficacy. The study group comprised 1,395 women (ages 55-80 years) who were at least 5 years postmenopausal. All patients had osteoporosis (lumbar spine [L2-L4] bone mineral density [BMD] T score less than -2.5). Participants also received daily calcium (500 mg) and vitamin D (400 IU). The primary end point was change from baseline in lumbar spine BMD at 1 year. Changes in hip BMD and in the level of serum C-telopeptide of type I collagen (CTX) were also measured, as were safety and tolerability. RESULTS: At 1 year, mean lumbar spine BMD increases were as follows: 5.1% among 353 patients receiving 2 mg of ibandronate every 2 months, 4.8% among 365 patients receiving 3 mg of ibandronate every 3 months, and 3.8% among 377 patients receiving 2.5 mg of oral ibandronate daily. Both of the intravenous regimens not only were noninferior, but also were superior (P < 0.001) to the oral regimen. Hip BMD increases (at all sites) were also greater in the groups receiving medication intravenously than in the group receiving ibandronate orally. Robust decreases in the serum CTX level were observed in all arms of the study. Both of the intravenous regimens were well tolerated and did not compromise renal function. CONCLUSION: As assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated.