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Biomedical subjects

Jean-Yves Reginster

Publications and source records attributed to Jean-Yves Reginster.

At least 19 recordsLinked to original sources
PubMed2026

GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. OBJECTIVE: This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid&#xae; platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). RESULTS: From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I2 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. CONCLUSIONS: This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings.

Journal Article↗
PubMed2006

Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors.

UNLABELLED: Strontium ranelate (2 g/day) was studied in 5082 postmenopausal women. A reduction in incident vertebral fracture risk by 40% was shown after 3 years. This effect was independent of age, initial BMD, and prevalent vertebral fractures. INTRODUCTION: Strontium ranelate is an orally active treatment able to decrease the risk of vertebral and hip fractures in osteoporotic postmenopausal women. The aim of this study was to assess the efficacy of strontium ranelate according to the main determinants of vertebral fracture risk: age, baseline BMD, prevalent fractures, family history of osteoporosis, baseline BMI, and addiction to smoking. MATERIALS AND METHODS: We pooled data of two large multinational randomized double-blind studies with a population of 5082 (2536 receiving strontium ranelate 2 g/day and 2546 receiving a placebo), 74 years of age on average, and a 3-year follow-up. An intention-to-treat principle was used, as well as a Cox model for comparison and relative risks. RESULTS: The treatment decreased the risk of both vertebral (relative risk [RR] = 0.60 [0.53-0.69] p < 0.001) and nonvertebral (RR = 0.85 [0.74-0.99] p = 0.03) fractures. The decrease in risk of vertebral fractures was 37% (p = 0.003) in women <70 years, 42% (p < 0.001) for those 70-80 years of age, and 32% (p = 0.013) for those > or = 80 years. The RR of vertebral fracture was 0.28 (0.07-0.99) in osteopenic and 0.61 (0.53-0.70) in osteoporotic women, and baseline BMD was not a determinant of efficacy. The incidence of vertebral fractures in the placebo group increased with the number of prevalent vertebral fractures, but this was not a determinant of the effect of strontium ranelate. In 2605 patients, the risk of experiencing a first vertebral fracture was reduced by 48% (p < 0.001). The risk of experiencing a second vertebral fracture was reduced by 45% (p < 0.001; 1100 patients). Moreover, the risk of experiencing more than two vertebral fractures was reduced by 33% (p < 0.001; 1365 patients). Family history of osteoporosis, baseline BMI, and addiction to smoking were not determinants of efficacy. CONCLUSIONS: This study shows that a 3-year treatment with strontium ranelate leads to antivertebral fracture efficacy in postmenopausal women independently of baseline osteoporotic risk factors.

Bone Density↗
PubMed2006

Adherence and persistence: impact on outcomes and health care resources.

Non-adherence to and poor persistence with antiresorptive medication are significant problems in preventing adverse consequences of osteoporosis. Adherence rates for oral bisphosphonate therapy drop off dramatically during the first year of treatment and continue to decline thereafter. Inadequate adherence is associated with smaller decreases in rate of bone turnover, smaller bone mineral density (BMD) gains, and greater risk of fracture. Measures to improve patient adherence include improved physician/patient communication, close monitoring, and early intervention in declining adherence. Another approach is strengthening of patient commitment through reinforcement of the connection between treatment response and quality of life benefits. Use of biochemical markers of response or BMD measurements to illustrate response to patients may be useful in this regard. Simplification of treatment regimens would also be of considerable value in improving adherence and persistence.

Biomarkers↗
PubMed2006

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.

Administration, Oral↗
PubMed2006

Osteoporosis: a still increasing prevalence.

It is estimated that over 200 million people worldwide have osteoporosis. The prevalence of osteoporosis is continuing to escalate with the increasingly elderly population. The major complication of osteoporosis is an increase in fragility fractures leading to morbidity, mortality, and decreased quality of life. In the European Union, in 2000, the number of osteoporotic fractures was estimated at 3.79 million. A baseline fracture is a very strong predictor of further fractures with 20% of patients experiencing a second fracture within the first year. The costs to health care services are already considerable and, on current trends, are predicted to double by 2050. The direct costs of osteoporotic fractures to the health services in the European Union in the year 2000 were estimated at 32 billion Euros. Guidelines for the diagnosis and treatment of osteoporosis are available in many countries; however, implementation is generally poor despite the availability of treatments with proven efficacy. Programs to increase awareness of osteoporosis and its outcomes are necessary for healthcare specialists and the general public. Earlier diagnosis and intervention prior to the first fracture are highly desirable.

Bone Density↗
PubMed2006

Raloxifene reduces fractures in postmenopausal women with osteoporosis.

UNLABELLED: Recently, selective estrogen receptor modulators have been developed for the management of osteoporosis based on antiosteoclastic properties similar to that of estrogens but with a safety profile including potential benefits on the breast, heart, and cognitive function. Raloxifene, the first selective estrogen receptor modulator to be marketed for the treatment of osteoporosis has shown reduction in spinal fracture risk in patients with low bone mineral density with (48%) or without (35%) prevalent vertebral fracture. Raloxifene also reduces nonvertebral fractures in high risk patients (47%). The decrease in Type I procollagen N-terminal propeptide at 1 year accounts for 28% of the total reduction in vertebral fracture risk. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84%. Among subjects with increased cardiovascular risk at baseline, those assigned to raloxifene had a 40% decrease in the risk of cardiovascular events compared with placebo. The definite anti-fracture efficacy of raloxifene at the spine, its plausible effect on non-spine fracture in high-risk patients and its beneficial effect on breast and heart make this compound an interesting approach for women presenting with osteoporosis. LEVEL OF EVIDENCE: Therapeutic study, level II (lesser quality randomized controlled trial [eg, < 80% followup, no blinding, or improper randomization]). See the Guidelines for Authors for a complete description of the levels of evidence.

Animals↗
PubMed2006

Strontium ranelate: the first dual acting treatment for postmenopausal osteoporosis.

UNLABELLED: Currently available medications, such as bisphosphonates, selective estrogen receptor modulators, and teriparatides, have shown their ability to reduce vertebral and/or nonvertebral fractures. Questions remain regarding their long-term innocuousness and several studies showed that adhering to currently marketed anti-osteoporotic medications remain sub-optimal. There is, therefore, an urgent need for the development of new effective, safe, and user-friendly medications to optimize the treatment of postmenopausal osteoporosis. The current review was designed to assess, through an extensive literature search, the antifracture efficacy of strontium ranelate on the axial and appendicular skeleton. Two multinational Phase 3 clinical trials have shown its efficacy and safety in the treatment of postmenopausal osteoporosis. In the Spinal Osteoporosis Therapeutic Intervention trial, strontium ranelate (2 g/day) treatment reduced the relative risk of a new vertebral fracture by 41% after 3 years compared with placebo. Data from the Treatment of Peripheral Osteoporosis study showed a 16% reduction in the relative risk of nonvertebral fracture in all patients and a 36% reduction in hip fracture in high-risk patients. Strontium rane-late reduces the risk of all fragility fractures and is well tolerated, which makes it a new first-line alternative in the treatment of postmenopausal osteoporosis. LEVEL OF EVIDENCE: Therapeutic study, Level II (lesser quality randomized controlled trial [eg, < 80% followup, no blinding, or improper randomization]). See the Guidelines for Authors for a complete description of the levels of evidence.

Animals↗
PubMed2006

Development of an algorithm for using PINP to monitor treatment of patients with teriparatide.

INTRODUCTION: Teriparatide effects are mediated via the preferential stimulation of osteoblastic activity over osteoclastic activity. Amino-terminal propeptide of type I procollagen (PINP) is an indicator of osteoblastic activity. OBJECTIVE: Develop an algorithm using PINP as an aid in the management of patients with postmenopausal osteoporosis treated with teriparatide. RESEARCH DESIGN AND METHODS: For inclusion in this post-hoc analysis, trials had to be investigations of teriparatide 20 microg/day in postmenopausal women with osteoporosis having measurements of PINP at 3 months and bone mineral density (BMD) at 12 months. Signal-to-noise ratio was calculated for a series of markers of bone turnover in the Fracture Prevention Trial. An algorithm was developed to monitor patients treated with teriparatide using PINP. RESULTS: Three trials met inclusion criteria and included the Fracture Prevention, Forteo-Alendronate Comparator and Anabolic After Antiresorptive trials. PINP had the highest signal-to-noise ratio of all bone-turnover markers. Positive PINP responses defined as increases > 10 microg/L were observed in 77-79% of teriparatide- and in 6% of placebo-treated patients after 3 months of study drug. Mean lumbar spine BMD increases after 12 months of teriparatide in patients having PINP changes > 10 microg/L ranged from 8.3% to 9.5% and in patients with PINP changes < or = 10 microg/L ranged from 5.9% to 7.6%. In the algorithm, PINP is measured at baseline and after 1-3 months of therapy. Patients with PINP increases > 10 microg/L are given a positive message. Patients with PINP increases < or = 10 microg/L are assessed for adherence, teriparatide administration and storage techniques, and for the presence of medical conditions that might limit their therapeutic response, and these issues are addressed as appropriate. Patients without these issues and with PINP increases < or = 10 microg/L should be given a neutral message because BMD may significantly increase with continued therapy. CONCLUSIONS: The PINP algorithm provides information regarding the anabolic response to teriparatide therapy and has the potential to identify patients requiring help with issues of adherence, injection technique, teriparatide storage, and medical problems limiting therapeutic responsiveness to teriparatide treatment. Data assessing the relationship of changes in PINP to fracture risk reduction are not available. We recommend physicians audit the use of the algorithm in practice so that improvements can be made.

Adult↗
PubMed2006

Developments in the pharmacotherapeutic management of osteoporosis.

During the last two decades, several medications have been granted a marketing authorisation for the management of osteoporosis. Bisphosphonates are the most widely prescribed drugs in this area, worldwide. Alendronate and risedronate are given daily or weekly and have demonstrated their ability to reduce fracture rates at the spine and hip. Ibandronate has demonstrated spine antifracture efficacy with intervals between dosings greater than weekly. New developments in this class include intravenous administration of ibandronate or zoledronate, once every three months or once yearly. Raloxifene, a selective estrogen-receptor modulator, reduces spine fractures and, in post-hoc analyses, non-spine fractures in high-risk subjects. New selective estrogen-receptor modulators, including lasofoxifene, bazedoxifene and arzoxifene, are expected to demonstrate antifracture efficacy at the hip level, whilst retaining the extra-skeletal benefits (such as in the breast) that are obtained with raloxifene. The peptides from the parathyroid hormone family are potent stimulators of bone formation. Teriparatide (1 - 34 amino acid fragment of the parathyroid hormone) reduces spine and non-spine fractures, an effect that is sustained for up to 30 months after the withdrawal of treatment. The intact hormone (1 - 84 amino acids) showed similar results on spine fractures, and more data are requested to evaluate its effect on non-spine or hip fractures. Strontium ranelate is suggested to be the first medication to uncouple bone formation from bone resorption. It has shown antifracture efficacy at all sites in a large number of postmenopausal women. New developments include: denosumab, an antibody against receptor activator of NF-kappaB ligand (RANKL); a cytokine that is responsible for osteoclastogenesis; and inhibitors of cathepsin K, a cysteine protease that is involved in the cleavage of collagen.

Antibodies, Monoclonal↗
PubMed2006

The treatment of severe postmenopausal osteoporosis : a review of current and emerging therapeutic options.

Several chemical entities have shown their ability to reduce axial and/or appendicular fractures in patients with osteoporosis. Since patients who have experienced a previous fracture are at high risk for subsequent vertebral or hip fracture, it is of prime importance to treat such patients with medications that have unequivocally demonstrated their ability to reduce fracture rates in patients with prevalent fractures. Results obtained with calcium and vitamin D, in this particular population, are not fully satisfactory and these medications are probably better used in conjunction with other therapeutic regimens. Bisphosphonates have shown their ability to reduce vertebral (alendronate, risedronate, ibandronate) and non-vertebral (alendronate, risedronate) fractures in patients with established osteoporosis. Raloxifene has also shown similar properties, notwithstanding its effect on non-vertebral fractures, which has only been derived from a post hoc analysis limited to patients with prevalent severe vertebral fractures at baseline. This compound also has interesting non-skeletal benefits, including effects on the breast and heart. Teriparatide, a bone-forming agent, promptly reduces the rate of vertebral and all non-vertebral fractures, without significant adverse effects. Strontium ranelate, the first agent shown to concomitantly decrease bone resorption and stimulate bone formation, has also shown its ability to reduce rates of vertebral and non-vertebral fractures in patients with established osteoporosis. It significantly reduces hip fractures in elderly individuals at high risk for such events. Its safety profile is also excellent.

Alendronate↗
PubMed2006

Direct and indirect costs attributable to osteoarthritis in active subjects.

OBJECTIVE: To estimate the direct and indirect costs of osteoarthritis (OA) in an active population, and to identify factors significantly influencing these expenditures. METHODS: A cohort of 3,440 subjects employed by the Liège City Council was followed prospectively for 6 months. Subjects were asked to report monthly OA related health resource utilization (contacts with health professionals, medical examinations, drug consumption, etc.) and absence from work. Health related quality of life (HRQOL) was evaluated at baseline using the Medical Outcomes Study Short-form 36 (SF-36). Logistic regression analysis identified factors associated with the probability that the individual incurred costs, and multiple regression identified factors influencing the magnitude of these costs. RESULTS: A total of 1,811 subjects filled in at least one questionnaire (response rate 52%). The mean duration of followup was 3.46 months. Self-reported prevalence of OA was 34.1%. The mean total direct costs were 44.5 euros per OA patient-month. Contacts with health professionals, medical examinations, drugs, and hospital stays accounted for 23.7 euros, 8.7 euros, 6.7 euros, and 4.9 euros, respectively, per OA patient-month. The average number of sick-leave days was 0.8 per OA patient-month. From a payer's perspective, this loss of productivity represented a mean cost of 64.5 euros per OA patient-month. We also recorded 0.02 mean days off work per active subject-month due to informal care by relatives, yielding a mean cost of 1.8 euro per active subject-month for the employer. Poorer scores for most of the dimensions of the SF-36 at baseline were significantly associated with greater likelihood of incurring direct and indirect costs and with higher costs among subjects who reported costs. If we consider the overall cohort of active subjects, the burden of OA related to the direct and indirect costs was 15.2 euros and 23.8 euros, respectively, per active subject-month. CONCLUSION: Direct and indirect costs attributable to OA are substantial, with productivity related costs being predominant. Poorer HRQOL was a major determinant of these expenditures.

Adult↗
PubMed2005

Evidence-based guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis: a consensus document of the Belgian Bone Club.

Glucocorticoids (GCs) are frequently prescribed for various inflammatory and/or life-threatening conditions concerning many systems in the body. However, they can provoke many aftereffects, of which osteoporosis (OP) is one of the most crippling complications, with its host of fractures. The dramatic increase in bone fragility is mainly attributable to the GC-induced rapid bone loss in all skeletal compartments. We have reviewed the meta-analyses and randomized controlled studies reporting medical therapeutic interventions currently registered in Belgium for the management of GC-OP comparatively with a placebo. Based on this research, an expert meeting developed a consensus on the prevention and therapy of GC-OP. The pathophysiology of GC-OP is complex. Several factors, acting separately or synergistically, have been described. Their great number could help to understand the rapidity of bone loss and of bone fragility occurrence, indicating that a rapid therapeutic intervention should be implemented to avoid complications. All patients on GCs are threatened with OP, so the prevention and/or therapy of GC-OP should be considered not only for postmenopausal females, but also for osteopenic premenopausal females and for males put on a daily dose of at least 7.5 mg equivalent prednisolone that is expected to last at least 3 months. Non-pharmacological interventions, such as exercise and avoidance of tobacco and alcohol, should be recommended, even if their role is not definitely settled in GC-OP prevention. Supplemental calcium and vitamin D should be considered as the first-line therapy because of the decrease in intestinal calcium absorption provoked by GCs. They also could be considered either as isolated therapy in patients taking less than 7.5 mg prednisolone daily and/or for a predicted period shorter than 3 months or as adjuvant therapy to other more potent drugs. Hormone replacement therapy could be considered in young postmenopausal females on GC, such as in postmenopausal OP, or in men with low androgen levels. Calcitonin appears to have a protective effect on trabecular bone in GC-OP, just as in postmenopausal OP. There is an increasing body of evidence supporting the antifracture efficacy of bisphosphonates, notably alendronate and risedronate. Preventative and curative therapy of GC-OP should be maintained as long as the patient is on GC treatment and could be stopped after weaning from GC, because there is more than circumstantial evidence of some recovery of BMD when GCs are stopped. There is no indication in GC-OP for any combination of two antiresorptive agents (except for calcium and vitamin D) or for an antiresorptive and an anabolic agent. There is indeed no proof that the increased costs of combined treatments will translate into increased therapeutic efficacy.

Bone Density↗
PubMed2005

Reduced risk of back pain following teriparatide treatment: a meta-analysis.

Vertebral fractures are the most common osteoporotic fracture and may result in back pain with functional limitations and diminished quality of life. Teriparatide [rhPTH (1-34)] has been shown to increase bone mass and reduce the risk of vertebral and other osteoporotic fractures. The aim of this study was to evaluate the effects of teriparatide on the risk of back pain in patients with osteoporosis. A systematic review of the literature was performed, and five trials were identified and included in our analyses. All trials were randomized, double-blinded, and parallel with either new vertebral fracture (n=1) or bone mineral density as the primary endpoint (n=4). Four studies were in postmenopausal women with osteoporosis, and one was in men with idiopathic or hypogonadal osteoporosis. Two trials were placebo controlled, two trials were alendronate controlled, and one trial involved teriparatide plus hormone replacement therapy versus hormone replacement therapy alone. Reports of back pain, defined as new or worsened back pain after initiating the study drug, were obtained from adverse event databases, and the risk of back pain was analyzed using a multivariate Cox proportional hazards model. Results were not statistically heterogeneous (P=0.60) across trials, and there were no differences between groups administered teriparatide 20 or 40 mcg/day doses (P=0.64). The rates of back pain, moderate or severe back pain, and severe back pain per 100 patient-years were numerically lower in the teriparatide versus comparator groups in each study. Compared with the pooled comparator, patients in the pooled teriparatide group had reduced risk for any back pain [relative risk, 0.66 (95% CI, 0.55-0.80)], moderate or severe back pain [relative risk, 0.60 (95% CI, 0.48-0.75)] and severe back pain [relative risk, 0.44 (95% CI, 0.28-0.68)]. Separate meta-analyses comparing teriparatide versus placebo or antiresorptive drugs gave similar results. In conclusion, patients randomized to teriparatide had a reduced risk of new or worsening back pain compared to patients randomized to placebo, hormone replacement therapy or alendronate.

Adult↗
PubMed2005

Recommendations for an update of the current (2001) regulatory requirements for registration of drugs to be used in the treatment of osteoporosis in postmenopausal women and in men.

Recent advances in the understanding of the epidemiology of osteoporosis suggest that certain parts of the current European guidelines for the registration of drugs in osteoporosis might be no longer substantiated. The object of this review is to provide the European regulatory authorities with an evidence-based working document providing suggestions for the revision of the "Note for guidance for the approval of drugs to be used in postmenopausal osteoporosis" (CPMP/EWP/552/95). Following an extensive review of the literature (1990-2004), the Group for the Respect of Ethics and Excellence in Science (GREES) organized a workshop including European regulators, academic scientists and representatives of the pharmaceutical industry. The outcomes of this meeting reflect the personal views of those who attended and should not, in any case, be seen as an official position paper of any regulatory agency. The group identified a certain number of points that deserve discussion. They mainly relate to the nature of the indication being granted to new chemical entities (treatment of osteoporosis in women at high risk of fracture instead of prevention and treatment of osteoporosis), the requirements of showing an anti-fracture efficacy on all or on major nonvertebral fractures (instead of the hip), the duration of pivotal trials (2 years instead of 3) and the possibility of considering bridging studies for new routes of administration, new doses or new regimens of previously approved drugs. The group also recommends that an indication could be granted for the treatment of osteoporosis in males on the basis of a placebo-controlled study, with bone mineral density changes after 1 year as the primary endpoint, for medications approved in the treatment of osteoporosis in women at high risk of fractures.

Female↗
PubMed2005

Monthly oral ibandronate is well tolerated and efficacious in postmenopausal women: results from the monthly oral pilot study.

CONTEXT: Ibandronate, a potent, nitrogen-containing bisphosphonate developed for intermittent administration in postmenopausal osteoporosis, aims to overcome current adherence issues with daily and weekly oral bisphosphonates through once-monthly oral dosing. OBJECTIVE: The purpose of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of once-monthly oral ibandronate. DESIGN: A randomized, 3-month, double-blind, placebo-controlled, phase I study (Monthly Oral Pilot Study) was conducted. SETTING: The study was conducted at five clinical trial centers in the United Kingdom and Belgium. PATIENTS OR OTHER PARTICIPANTS: Subjects were postmenopausal women (age, 55-80 yr; > or =3 yr post menopause; n = 144). INTERVENTION(S): Once-monthly oral ibandronate 50, 100, or 150 mg or placebo was used. After the first cycle, the 50-mg arm was split, with participants continuing on either 50 or 100 mg. MAIN OUTCOME MEASURE(S): Primary outcome measures were safety, serum and urinary C-telopeptide (CTX), and serum ibandronate AUC0-infinity. RESULTS: Once-monthly oral ibandronate was well tolerated, with a similar overall and upper gastrointestinal safety profile to placebo. Once-monthly ibandronate was also highly effective in decreasing bone turnover; substantial reductions from baseline in serum CTX (-56.7% and -40.7% in the 150- and 100-mg arms, respectively; P < 0.001 vs. placebo) and urinary CTX (-54.1% and -34.6%, respectively; P < 0.001 vs. placebo) were observed at d 91 (30 d after the final dose). Analysis of the area under the effect curve (d 1-91) for change from baseline (percent x days) in serum CTX and urinary CTX indicated a dose-response relationship. The AUC0-infinity for ibandronate increased with dose but not in a dose-proportional manner. CONCLUSIONS: These findings indicate a potential role for once-monthly oral ibandronate in the treatment of postmenopausal osteoporosis.

Administration, Oral↗
PubMed2005

A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate.

Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval>2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that can result from frequent, repeated exposure). Greater convenience and tolerability may enhance the therapy adherence and, hence, improve long-term therapeutic outcomes in PMO.

Administration, Oral↗