Effects of Oral Ibandronate Administered Daily or Intermittently on Fracture Risk in Postmenopausal Osteoporosis (original) (raw)
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Annals of the Rheumatic Diseases, 2006
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 oncemonthly 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.
Monthly Oral Ibandronate Therapy in Postmenopausal Osteoporosis: 1Year Results From the MOBILE Study
2005
Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year. Introduction: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of >2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens. Materials and Methods: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly. Results: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated. Conclusions: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis.
Efficacy and Safety of Oral Weekly Ibandronate in the Treatment of Postmenopausal Osteoporosis
Adherence to oral daily bisphosphonate regimens in postmenopausal osteoporosis is currently suboptimal. Less frequent dosing regimens are likely to improve patient adherence and thus, potentially, patient outcomes. A multicenter, randomized, double-blind, noninferiority study was conducted in 235 women (53-80 yr old; time since menopause > 3 yr) with postmenopausal osteoporosis [lumbar spine (L1-L4) bone mineral density (BMD) T-score < ؊2] to demonstrate the noninferiority of an oral weekly (20 mg) ibandronate regimen compared with an oral daily (2.5 mg) ibandronate regimen. All patients received daily calcium (500 mg) and vitamin D (400 IU). The primary analysis was the relative change in lumbar spine (L1-L4) BMD from baseline after 48 wk in the per-protocol population. Daily and weekly ibandronate significantly increased spinal BMD by 3.47 and 3.53%, respectively, and provided substantial and similar decreases in biochemical markers of bone turnover. In the primary analysis, noninferiority of the weekly regimen to the daily regimen was demonstrated, with the boundary of the one-sided confidence interval, ؊0.96%, within both the ؊1.65% prespecified margin and a more stringent margin of ؊1.10%. These results demonstrate that oral weekly ibandronate provides the same efficacy and safety as oral daily ibandronate in women with postmenopausal osteoporosis. (J Clin Endocrinol Metab 88:
Ibandronate: The Evolution of a Once-a-Month Oral Therapy for Postmenopausal Osteoporosis
Journal of Clinical Densitometry, 2006
Bisphosphonates have been shown to be highly effective in preventing and treating postmenopausal osteoporosis (PMO) and the associated risk of fracture. However, poor adherence with bisphosphonate therapies for PMO results in a high incidence of otherwise preventable fractures. The chronicity of this condition requires long-term treatment, but fewer than one in two women remains on daily bisphosphonate therapy for 1 yr. A good way to reduce the risk of osteoporotic fractures is through development of equally efficacious formulations with more convenient dosing regimens. Weekly formulations of bisphosphonates have been introduced that demonstrate comparable efficacy to daily formulations with slightly improved adherence. Recently, a new formulation utilizing a third-generation nitrogencontaining bisphosphonatedibandronatedhas been approved with a monthly dosing regimen. The pharmacokinetics and high potency of ibandronate, similar with other bisphosphonates, facilitate lower mg doses and longer-interval dosing frequencies with similar efficacy and enhanced tolerability. Preclinical studies and clinical trials have consistently demonstrated that it is the total cumulative dose of ibandronate that determines efficacy. The convenience of once-monthly dosing may ultimately improve adherence and clinical outcomes among the growing population of postmenopausal women at risk of osteoporosis.
International Journal of Women's Health, 2014
Several second-generation bisphosphonates (BPs) are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration. A literature search using "ibandronate", "postmenopausal osteoporosis", "fracture", and "bone mineral density" (BMD) revealed 168 publications. The Phase III BONE study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative risk reduction (RRR) in clinical vertebral fracture after 3 years. Non-vertebral fracture (NVF) reduction was demonstrated in a subgroup (pretreatment T-score −3.0; RRR 69%) and a metaanalysis of high annual doses (150 mg oral monthly or intravenous equivalent of ibandronate; RRR 38%). Hip fracture reduction was not demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long term safety is comparable to placebo over 3 years apart from flu-like symptoms which are more common with oral monthly and intravenous treatments. No cases of atypical femoral fracture or osteonecrosis of the jaw have been reported in randomized controlled trial studies. Ibandronate inhibits FPPS more than alendronate but less than other BPs which could explain rate of action onset. Ibandronate has a higher affinity for hydroxyapatite compared with risedronate but less than other BPs which could affect skeletal distribution and rate of action offset. High doses (150 mg oral monthly or intravenous equivalent) were superior to low doses (oral 2.5 mg daily) according to 1 year BMD change. Data are limited by patient selection, statistical power, under-dosing, and absence of placebo groups in high dose studies. Ibandronate treatment offers different doses and modalities of administration which could translate into higher adherence rates, an important factor when the two main limitations of BP treatment are initiation and adherence rates. However, lack of consistency in NVF reduction and absence of hip fracture data limits more generalized use of this agent.
Srpski arhiv za celokupno lekarstvo, 2011
Introduction. Osteoporosis is a serious problem, since about 50% of women over the age of 50 suffer at least one osteoporotic fracture. Objective. The aim of this study was to evaluate compliance as well as the efficiency and safety of ibandronate treatment over a 6-month period in reducing the risk of subsequent fracture in women with postmenopausal osteoporosis. Methods. A multicenter, prospective, observational study was conducted during one year in thirteen medical centres in Serbia. In the first part of the study the participants received ibandronate tablets (150 mg) once a month for six months. In the second part, the patients were under clinical follow-up. Results. The mean age of the 184 menopausal women included in the study was 66.2?9.4 years. In 40.2% of the subjects the disease had been clinically manifest during the five preceding years. The mean T-score value at the onset of our investigation was -3.1?0.84 in 160 (87%) patients who were diagnosed osteoporosis. Compress...
The Journal of rheumatology, 2008
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...
Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis
The American journal of medicine, 1997
Oral treatment of osteoporosis with bisphosphonates relies on compliance, the absorption being low and suppressed by simultaneous food intake. Intravenous (IV) treatment with an aminobisphosphonate, pamidronate (once every 3 months) was effective, but required infusions. Ibandronate, a new very potent aminobisphosphonate, can be administered safely as an IV bolus injection, and therefore offers an interesting alternative suitable for outpatient treatment. To test the efficacy of this bolus IV treatment in postmenopausal osteoporosis in randomized partly double-blind, placebo controlled study, 125 postmenopausal women (mean age, 64 years) with osteoporosis (bone mineral density [BMD] < -2.5 SD T score) received a placebo or ibandronate (0.25, 0.5, 1, or 2 mg) every 3 months. All patients received 1 g calcium/day. BMD, in g/cm2, was measured by dual-energy x-ray absorptiometry at all standard sites. Lumbar spine BMD (L2 to L4) did not change (0.85%) in the placebo group, but increa...
Arthritis & Rheumatism, 2006
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 inter-vals, 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.
Osteoporosis International, 2011
Long-term bone mineral density (BMD) gains, bone marker levels, and safety of 3 mg quarterly intravenous (IV) ibandronate were studied in this 3-year extension to the Dosing IntraVenous Administration (DIVA) trial. Quarterly IV ibandronate consistently increased lumbar spine bone mineral density measured with dual-energy X-ray absorptiometry (DXA-BMD) over 5 years (8.1%) and was well tolerated in women with postmenopausal osteoporosis. Introduction Treatment with IV ibandronate regimens, 2 mg bimonthly and 3 mg quarterly, has been studied for up to 5 years in a long-term extension (LTE) to the 2-year DIVA trial. Methods DIVA LTE is an open-label extension to a 2-year randomized, double-blind, double-dummy, noninferiority, Funding sources The DIVA study LTE was funded by F. Hoffmann-La Roche and GlaxoSmithKline.