Efficacy and safety of sodium RISedronate for glucocorticoid-induced OsTeoporosis with rheumaTOid arthritis (RISOTTO study): A multicentre, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA. METHODS: This was a six-month randomized, double-blind, placebo-controlled trial of 95 patients with GIO complicated with RA from 19 centers. The primary endpoint was the change from baseline in lumbar spine bone mineral density (L-BMD). Secondary endpoints included changes in femoral neck and total hip BMD and bone turnover markers, as well as rheumatoid arthritis Disease Activity Score with 28-joint counts. Incident of non-traumatic spine fractures and adverse events were tracked as safety endpoints. RESULTS: Increase in L-BMD was significantly greater in the Risedronate group compared to the Placebo group (Risedronate: 3.49% [95% CI: 1.92-5.05] vs Placebo: 0.12% [95% CI: -2.07 to 2.30], p < .0001). No significant difference was found in the femoral neck and total hip BMD. Although adverse events were observed in 28 patients, none were considered serious. Non-traumatic vertebral fractures were identified in 10 patients. CONCLUSION: Risedronate was effective in increasing L-BMD and was well tolerated in patients with GIO complicated with RA.

Efficacy of combined medication of risedronate sodium and selective estrogen receptor modulator on the postmenopausal osteoporosis.

To evaluate the efficacy of combined medication of risedronate sodium and raloxifene, a selective estrogen receptor modulator (SERM) on the postmenopausal osteoporosis (PMOP). PMOP patients underwent the combined medication of risedronate sodium and raloxifene (SERM, Treatment group), or only medication of risedronate sodium (Control group). After medication, more significant increases were observed in the bone densities of the lumber vertebra (L1-4) and the neck of left femur of patients in the treatment group. Simultaneously, the levels of estrogen and progesterone in serum decreased sharply in the treatment group. After treatment, P1NP and ß-CTX levels in serum decreased significantly in two groups in comparison with the levels prior to treatment, with evident elevations in the levels of BAP and BGP; similarly, ameliorations in the treatment group were much more evident than those in the control group. In addition, significant declines were identified in the VAS scores of two groups after treatment when comparing to the scores prior to the treatment, and the decline in the treatment group was more evident than that in the control group. Combined medication of risedronate sodium and SERM (raloxifene) performs better in treatment of osteoporosis than the single use of risedronate sodium, without the deterioration of adverse effect of medication.

Comparison of the efficacy between once-monthly oral ibandronate and risedronate among Korean women with osteoporosis: a nationwide population-based study.

Using a nationwide database from the Korean National Health Insurance Service, this study showed that once-monthly oral ibandronate (150 mg) had better anti-fracture efficacy than once-monthly oral risedronate (150 mg), as seen on assessing overall and non-vertebral fractures among Korean elderly women with osteoporosis. INTRODUCTION: Once-monthly oral bisphosphonates have been used widely without appropriate comparison. Therefore, we aimed to compare the anti-fracture efficacy of once-monthly ibandronate (150 mg) and once-monthly risedronate (150 mg). METHODS: We conducted a retrospective cohort study among Korean women aged ≥ 60 years from 2006 to 2015 using a nationwide database from the National Health Insurance Service Senior Cohort. The primary outcome was the first occurrence of fracture related to osteoporosis after the initial prescription of bisphosphonates. A Cox proportional model was used to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for overall and site-specific fractures between the two treatments, after adjusting for possible confounding factors. RESULTS: After propensity score matching, the ibandronate and risedronate groups, with 3454 patients each, were assembled from 36,701 new once-monthly ibandronate or risedronate users. After 4 years of follow-up, the ibandronate group had significantly lower incidence rates of overall and non-vertebral fractures than the risedronate group (IRR 0.822, 95% CI 0.698-0.968, P = 0.919 and IRR 0.798, 95% CI 0.647-0.985, P = 0.036, respectively). CONCLUSIONS: Once-monthly ibandronate (150 mg) shows better anti-fracture efficacy than once-monthly risedronate (150 mg). However, further large-scale studies are required to confirm our findings and to determine site-specific differences, especially regarding the vertebral and hip areas.

Cost-effectiveness of gastro-resistant risedronate tablets for the treatment of postmenopausal women with osteoporosis in France.

The use of gastro-resistant risedronate, a convenient dosing regimen for oral bisphosphonate therapy, seems a cost-effective strategy compared with weekly alendronate, generic risedronate, and no treatment for the treatment of postmenopausal women with osteoporosis in France. INTRODUCTION: Gastro-resistant (GR) risedronate tablets are associated with improved persistence compared to common oral bisphosphonates but are slightly more expensive. This study assessed its cost-effectiveness compared to weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France. METHODS: A previously validated Markov microsimulation model was used to estimate the lifetime costs (expressed in €2017) per quality-adjusted life-years (QALY) of GR risedronate compared with weekly alendronate, generic risedronate, and no treatment. Pooled efficacy data for bisphosphonates derived from a previous meta-analysis were used for all treatment options, and persistence data (up to 3 years) were obtained from a large Australian longitudinal study. Evaluation was done for high-risk women 60-80 years of age, with a bone mineral density (BMD) T-score ≤ - 2.5 and/or prevalent vertebral fractures. RESULTS: In all of the simulated populations, GR risedronate was cost-effective compared to alendronate, generic risedronate, and no treatment at a threshold of €60,000 per QALY gained. In women with a BMD T-score ≤ - 2.5 and prevalent vertebral fractures, the cost per QALY gained of GR risedronate compared to alendronate, generic risedronate, and no treatment falls below €20,000 per QALY gained. In women aged 75 years and older, GR risedronate was even shown to be dominant (more QALYs, less costs) compared to alendronate, generic risedronate, and no treatment. CONCLUSION: This study provides the first economic results about GR risedronate, suggesting that it represents a cost-effective strategy compared with weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France.

Efficacy and safety of once-monthly risedronate in osteoporosis subjects with mild-to-moderate chronic kidney disease: a post hoc subgroup analysis of a phase III trial in Japan.

Limited data are available on the safety and efficacy of anti-resorptive agents, particularly once-monthly bisphosphonates, for use in osteoporotic patients with chronic kidney disease (CKD). We conducted a post hoc analysis of data from a 12-month, randomized, double-blind, phase III study to evaluate the safety and efficacy of once-monthly risedronate (RIS-OM) 75 mg tablets in Japanese osteoporosis patients with mild-to-moderate CKD. Patients who received RIS-OM 75 mg were stratified by baseline estimated glomerular filtration rate (eGFR; ≥ 90, ≥ 60 to < 90, or ≥ 30 to < 60 mL/min/1.73 m2). Safety endpoints were incidence of adverse events (AEs) and percent change from baseline in eGFR, serum creatinine, calcium, and phosphorus. Efficacy endpoints were percent change from baseline in lumbar spine bone mineral density (BMD) and bone turnover markers (BTMs). In 420 patients included (age 67.7 ± 6.7 years, women 98.8%), the incidence of all AEs, gastrointestinal disorders, acute phase reaction, non-vertebral fractures, and renal and urinary disorders was not significantly different among subgroups. Interaction between subgroups and time was significant for eGFR (p = 0.010) and serum creatinine (p = 0.001) but considered to be regression to the mean and clinically insignificant. BMD significantly increased while BTMs significantly decreased from baseline with a similar degree of change among the subgroups. In conclusion, RIS-OM 75 mg showed consistent safety and efficacy in suppressing bone turnover and increasing BMD in Japanese primary osteoporosis patients with mild-to-moderate CKD. These results should, however, be interpreted with caution because the number of patients with moderate CKD was limited.

Bioactive injectable triple acting thermosensitive hydrogel enriched with nano-hydroxyapatite for bone regeneration: in-vitro characterization, Saos-2 cell line cell viability and osteogenic markers evaluation.

Hydrogels forming in-situ have gained great attention in the area of bone tissue engineering recently, they were also showed to be a good and less invasive alternative to surgically applied ones. The primal focus of this study was to prepare chitosan-glycerol phosphate thermosensitive hydrogel formed in-situ and loaded with risedronate (bone resorption inhibitor) in an easy way with no requirement of complicated processes or large number of equipment. Then we investigated its effectiveness for bone regeneration. In-situ forming hydrogels were prepared using chitosan cross-linked with glycerol phosphate and loaded with risedronate and nano-hydroxyapatite as bone cement. The prepared hydrogels were characterized by analyzing their gelation time at 37 °C, % porosity, swelling index, in-vitro degradation, rheological properties, and in-vitro drug release. Results showed that the in-situ hydrogels prepared using 2.5% (w/v) chitosan cross-linked with 50% (w/v) glycerol phosphate in the ratio (9:1, v/v) reinforced with 20 mg/mL and nano-hydroxyapatite possessed the most sustained drug release profile. This optimized formulation was further evaluated using DSC and FTIR studies, in addition to their morphological properties using scanning electron microscopy. The effect on Saos-2 cell line viability was evaluated also using MTT assay on the optimized hydrogel formulation in addition to their action on cell proliferation using fluorescence microscope. Moreover, calcium deposition on the hydrogel and alkaline phosphatase activity were evaluated. Risedronate-nano-hydroxyapatite loaded hydrogels significantly enhanced the Saos-2 cell proliferation in addition to enhanced alkaline phosphatase activity and calcium deposition. Such results suggest that risedronate-nano-hydroxyapatite loaded hydrogels present great biocompatibility for bone regeneration. Proliferation of cells, as well as deposition of mineral on the hydrogel, was an evidence of the biocompatible nature of the hydrogel. This hydrogel formed in-situ present a good less invasive alternative for bone tissue engineering.

Improved treatment efficacy of risedronate functionalized chitosan nanoparticles in osteoporosis: formulation development, in vivo, and molecular modelling studies.

Delivery of bisphosphonates-like risedronate has been a major challenge till date due to its poor bioavailability and gastrointestinal tract adverse effects. In this study, we explored the prospective use of risedronate functionalised chitosan nanoparticle (RISCN) for management and treatment of osteoporosis. The prepared nanoparticle was characterised by using scanning electron microscopy, atomic force microscopy, and dynamic light scattering technique. Osteoporosis was induced on quarantined female Wistar rats and treated with RISCN. Docking studies were performed to establish the molecular mechanism of RISCN in improving the bone microarchitecture. Results indicated that there was a significant improvement in bone mineral density and healing of trabecular microarchitecture with less cortical porosity on the bone surfaces of the treatment groups. Docking studies indicated a high affinity and binding of chitosan and RISCN towards the human farnesyl diphosphate synthase (FDPS). Thus, a novel risedronate-loaded chitosan nanoparticle revealed promising results in an effective bone bridging process and osteoporosis treatment.

QbD Approach for Novel Crosslinker-Free Ionotropic Gelation of Risedronate Sodium-Chitosan Nebulizable Microspheres: Optimization and Characterization.

Risedronate sodium (RS) is a potent inhibitor of bone resorption, having an extreme poor permeability and limited oral bioavailability (0.62%). RS should be orally administered under fasting conditions while keeping in an upright posture for at least 30 min to diminish common gastroesophageal injuries. To surmount such limitations, novel risedronate-chitosan (RS-CS) crosslinker-free nebulizable microspheres were developed adopting the quality by design (QbD) approach and risk assessment (RA) thinking. RS:CS ratio, surfactant (Pluronic® F127) concentration, homogenization duration, speed, and temperature were identified using Ishikawa diagrams as the highest formulation and process risk factors affecting the critical quality attributes (CQAs), average particle size (PS), and entrapment efficiency (EE%). The risk factors were screened using the Plackett-Burman design, and the levels of the most significant factors were optimized using a multilevel factorial design to explore the optimized system with the least PS, maximum EE%, and a prolonged drug release profile. The optimized system (B6) was developed at a RS:CS ratio of 1:7, a surfactant concentration of 2% (w/v), and a homogenization speed of 14,000 rpm. It revealed good correlation with QbD theoretical prediction, where positively charged (47.9 ± 3.39 mV) discrete, spherical microspheres (3.47 ± 0.16 µm) having a high EE% (94.58 ± 0.19%) and prolonged RS release over 12 h (Q12 h, 89.70 ± 0.64%) were achieved. In vivo lung deposition after intratracheal instillation of B6 confirmed the delivery of high RS percentage to rat lung tissues (87 ± 3.54%) and its persistence for 24 h. This investigation demonstrated the effectiveness of QbD philosophy in developing RS-CS crosslinker-free nebulizable microspheres.

Risedronate-Loaded Macroporous Gel Foam Enriched with Nanohydroxyapatite: Preparation, Characterization, and Osteogenic Activity Evaluation Using Saos-2 Cells.

The application of minimally invasive surgical techniques in the field of orthopedic surgery has created a growing need for new injectable synthetic materials that can be used for bone grafting. In this work, novel injectable thermosensitive foam was developed by mixing nHAP powder with a thermosensitive polymer with foaming power (Pluronic F-127) and loaded with a water-soluble bisphosphonate drug (risedronate) to promote osteogenesis. The foam was able to retain the porous structure after injection and set through temperature change of PF-127 solution to form gel inside the body. The effect of different formulation parameters on the gelation time, porosity, foamability, injectability, and in vitro degradation in addition to drug release from the prepared foams were analyzed using a full factorial design. The addition of a co-polymer like methylcellulose or sodium alginate into the foam was also studied. Results showed that the prepared optimized thermosensitive foam was able to gel within 1 min at 37°C, and sustain the release of drug for 72 h. The optimized formulation was further tested for any interactions using DSC and IR, and revealed no interactions between the drug and the used excipients in the prepared foam. Furthermore, the ability of the pre-set foam to support osteoblastic-like Saos-2-cell proliferation and differentiation was assessed, and revealed superior function on promoting cellular proliferation as confirmed by fluorescence microscope compared to the plain drug solution. The activity of the foam treated cells was also assessed by measuring the alkaline phosphatase activity and calcium deposition, and confirmed that the cellular activity was greatly enhanced in foam treated cells compared to those treated with the plain drug solution only. The obtained results show that the prepared risedronate-loaded thermosensitive foam would represent a step forward in the design of new materials for minimally invasive bone regeneration.

Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density.

The antiresorptive potency varies between different bisphosphonates. We investigated the effect of stopping oral bisphosphonate treatment for postmenopausal osteoporosis (ibandronate, alendronate, risedronate) on BTMs and BMD. After stopping treatment, all three groups showed an increase in BTMs and a decrease in hip BMD; however, none returned to pre-treatment baseline values. INTRODUCTION: Bisphosphonates (BPs) continue to suppress bone turnover markers (BTMs) after treatment has stopped, leading to the suggestion that a pause in treatment could be considered for low-risk patients. Indirect comparisons suggest that after cessation of treatment, the effects on bone may differ between drugs. We investigated the effects of stopping oral BP treatments for postmenopausal osteoporosis on BTMs and bone mineral density (BMD). METHODS: We studied postmenopausal osteoporotic women who had previously taken part in a 2-year randomised study of three oral BPs (ibandronate, alendronate, or risedronate). At the end of the study, women with hip BMD T-score > - 2.5 and considered clinically appropriate to discontinue treatment were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs, and BMD was measured by dual-energy X-ray absorptiometry. RESULTS: All BTMs increased after treatment withdrawal but remained below the pre-treatment baseline with less suppression of BTMs for the risedronate group compared to alendronate and ibandronate up to 48 weeks. There was no difference between the BP groups 96 weeks after stopping treatment. The change in BMD during the 96 weeks after stopping treatment was - 1.6% (95% CI - 1.9 to - 1.2, P < 0.001) for the total hip and - 0.6% (95% CI - 1.1 to - 0.2, P = 0.17) at the lumbar spine with no difference between the three BP groups (P = 0.85 and P = 0.48, respectively). CONCLUSION: For all treatment groups, there was an increase in BTMs and a decrease in hip BMD after stopping BPs for 2 years; however, none returned to pre-treatment baseline values.

Effects of once-monthly minodronate versus risedronate in osteoporosis patients with rheumatoid arthritis: a 12-month randomized head-to-head comparison.

A head-to-head comparison of once-monthly oral bisphosphonates minodronate (MIN) and risedronate (RIS) in patients with rheumatoid arthritis (RA) demonstrated that MIN has the same effect as RIS on increase in bone mineral density (BMD) and a stronger effect on inhibition of bone resorption than RIS, suggesting that MIN is a promising treatment option for osteoporosis patients with RA. INTRODUCTION: To evaluate the effect of once-monthly oral MIN in patients with RA, a prospective, randomized, open-label, head-to-head comparison with once-monthly oral RIS was conducted. METHODS: A total of 83 patients with RA were randomly assigned to either once-monthly oral MIN 50 mg (n = 42) or once-monthly oral RIS 75 mg (n = 41). Serial BMD and bone turnover markers were measured and compared between the treatment groups. RESULTS: BMD (lumbar spine, total hip, femoral neck) increased significantly after 12 months of treatment with MIN (3.8, 2.0, and 2.2%, respectively, P < 0.05) and RIS (3.6, 1.9, and 1.9%, respectively, P < 0.05). There were no significant differences between the treatment groups. Percent changes of bone turnover markers from baseline to 12 months in the MIN group were significantly greater than those in the RIS group (TRACP-5b: - 36.3 vs - 19.3%, P < 0.05; NTX: - 27.1 vs - 17.3%, P < 0.05; BAP: -30.2 vs -19.4%, P < 0.05). CONCLUSIONS: The present study of RA patients demonstrated that MIN has the same effect as RIS on increase in BMD and a stronger effect on inhibition of bone resorption than RIS. The results suggest that MIN is a promising treatment option for osteoporosis patients with RA.

Bone Loss After Romosozumab/Denosumab: Effects of Bisphosphonates.

Romosozumab and denosumab are monoclonal antibodies for the treatment of osteoporosis. Both have a rapid offset of effect resulting in loss of bone density (BMD) gained on-treatment and, in some cases, multiple vertebral fractures following treatment cessation. We recently reported disappointing results from transitioning patients from denosumab to intravenous zoledronate at the time the next denosumab injection is due. The present report re-assesses the role of bisphosphonates following the use of denosumab. In the FRAME trial, osteoporotic women were randomized to romosozumab or placebo for 1 year, then both groups were provided with open-label denosumab for the subsequent 2 years. In women completing this study at our center, we offered treatment with either oral or intravenous bisphosphonates. In the eleven women opting for intravenous treatment, zoledronate was given after a median delay of 65 days from trial-end, in the hope that this might increase skeletal uptake of the drug and, thereby, its efficacy to maintain bone density. In these women, spine BMD was 17.3% above baseline at trial-end, and still 12.3% above baseline a year later, a 73% (CI: 61%, 85%) retention of the treatment benefit. The comparable BMD figures for the total hip were 10.7 and 9.2% above baseline, a 87% (CI: 77%, 98%) retention of treatment effect. In contrast, those not receiving treatment after the conclusion of the FRAME trial lost 80-90% of the BMD gained on-trial in the following 12 months. Women treated with risedronate showed an intermediate response. In the zoledronate group, mean PINP 6 months post-FRAME was 23 ± 4 µg/L and at 12 months it was 47 ± 8 µg/L, suggesting that repeat zoledronate dosing is needed at 1 year to maintain the BMD gains. In conclusion, delaying administration of intravenous bisphosphonate when transitioning from short-term denosumab appears to increase the extent to which the gains in BMD are maintained.

Efficacy of discontinuing risedronate for patients with systemic lupus erythematosus: a prospective study.

Objective The objective of this study is to investigate the effectiveness of discontinuation of risedronate for patients with systemic lupus erythematosus (SLE) treated with glucocorticoid (GC). Methods The participants were patients with SLE treated with prednisolone (PSL) ≥ 2 mg/day and risedronate for at least three years. Lumbar spine and total hip bone mineral density (BMD) measurements were taken at baseline and 24 and 48 weeks after discontinuation of risedronate, and bone turnover markers were evaluated at baseline, 12, 24, 36, and 48 weeks. Results A total of 36 patients were enrolled, 25 of whom discontinued risedronate. The mean age was 46.8 ± 11.2 years, and 23 were female. The mean duration of GC treatment was 14.8 ± 11.4 years, the mean dose of PSL was 7.8 ± 3.9 mg/day, and the mean duration of risedronate was 5.8 ± 2.4 years. Seventeen patients showed decreased lumbar spine BMD at 48 weeks after discontinuation of risedronate, with a mean lumbar spine lumbar decrease of 1.42% ± 3.20% ( p = 0.034); 17 patients (71%) showed a decreased total hip BMD at 48 weeks after discontinuation of risedronate, with a mean total hip BMD decrease of 0.99% ± 2.10% ( p = 0.021). Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) ≥ 309 mU/dl at baseline was a risk factor for decreased total hip BMD at 48 weeks compared with serum TRACP-5b < 309 mU/dl (56% vs 0%, p = 0.0098). One patient developed a clinical fracture of the lumbar spine at 20 weeks. Conclusions Discontinuation of risedronate treatment in patients with SLE who had received GC therapy led to decreases in lumbar spine and total hip BMD, particularly in patients with high baseline serum TRACP-5b levels.

Effect of monthly intravenous ibandronate injections on vertebral or non-vertebral fracture risk in Japanese patients with high-risk osteoporosis in the MOVER study.

We examined the efficacy of intravenous (IV) ibandronate 1 mg/month in patient subgroups in the phase III MOVER study. Here we present results of analyses on the incidence of fractures in patients with prevalent vertebral fractures (1 or ≥2, and ≥3) at screening and femoral neck (FN) bone mineral density (BMD) T scores ≥-2.5 or <-2.5, and <-3.0 at baseline. The per-protocol set comprised 1134 patients (ibandronate 0.5 mg/month n = 376; ibandronate 1 mg/month n = 382; risedronate oral 2.5 mg/day n = 376). The incidence of vertebral fractures in patients with 1 or ≥2 prevalent vertebral fractures was 11.2 and 20.4 %, respectively, with ibandronate 1 mg/month, and 12.6 and 22.1 %, respectively, with risedronate. In patients with FN BMD T scores ≥-2.5 or <-2.5, the vertebral fracture incidence was 13.7 and 16.4 %, respectively, with ibandronate 1 mg/month, and 17.3 and 19.1 %, respectively, with risedronate. The incidence of non-vertebral fractures in patients with ≥2 prevalent vertebral fractures or FN BMD T score <-2.5 was 7.6 and 7.6 %, respectively, with ibandronate 1 mg/month, and 9.5 and 9.4 %, respectively, with risedronate. Fracture incidence was consistently lower, but not significant, with ibandronate 1 mg/month than with risedronate in patients with ≥2 prevalent vertebral fractures and FN BMD T score <-2.5. The efficacy of the fracture reduction of monthly IV ibandronate appears consistent and seemingly independent of the number of prevalent vertebral fractures or baseline BMD values.

Efficacy on the risk of vertebral fracture with administration of once-weekly 17.5 mg risedronate in Japanese patients of established osteoporosis with prevalent vertebral fractures: a 156-week longitudinal observational study in daily practice.

Currently, the only available evidence for the efficacy of once-weekly 17.5 mg risedronate in preventing vertebral fractures was obtained in a 48-week study in Japan. We performed a 156-week prospective, longitudinal, observational study to determine the efficacy of the 17.5 mg risedronate in preventing vertebral fractures. We included Japanese patients with established osteoporosis who were older than 50 years and had radiographically confirmed vertebral fractures. The primary endpoint was the incidence of vertebral fractures every 24 weeks, with the final interval spanning 36 weeks. We also calculated the change in bone mineral density of the lumbar spine (L2-4 BMD) and urinary N-telopeptide of type I collagen (u-NTX), and assessed the incidence of adverse drug reactions and the drug adherence rate. Data from 241 patients were available for analysis of vertebral fracture prevention. The incidence rate of vertebral fractures decreased in a time-dependent manner (P = 0.0006; Poisson regression analysis). The risk ratio (fracture incidence per 100 person-years in the final 36 weeks versus that in the first 24 weeks) was 0.21 (95 % confidence interval 0.08-0.55). Compared to baseline values, L2-4 BMD increased by 6.41 % at 156 weeks, while u-NTX decreased by 36 % at 24 weeks and was maintained thereafter (P < 0.0001). The incidence rate of adverse drug reactions was 9.18 %. Drug adherence rates assessed every 4 weeks were over 90 %. Our results indicate that 156 weeks of treatment with once-weekly 17.5 mg risedronate effectively reduced the risk of vertebral fracture in Japanese patients with established osteoporosis older than 50 years.

Effects of switching weekly alendronate or risedronate to monthly minodronate in patients with rheumatoid arthritis: a 12-month prospective study.

UNLABELLED: Switching weekly ALN or RIS to monthly MIN in patients with RA, of whom two-thirds were treated with low-dose PSL, significantly decreased bone turnover markers and increased BMD at 12 months, suggesting that monthly MIN may be an effective alternative treatment option of oral bisphosphonate treatment. INTRODUCTION: The aim of this prospective, observational study was to evaluate the effects of switching weekly alendronate (ALN 35 mg) or risedronate (RIS 17.5 mg) to monthly minodronate (MIN 50 mg) in patients with rheumatoid arthritis (RA). METHODS: Patient characteristics were as follows: n = 172; 155 postmenopausal women, age 65.5 (44­87) years; T-score of lumbar spine (LS), −1.4; total hip (TH), −1.8; femoral neck (FN), −2.1; dose and rate of oral prednisolone (2.3 mg/day), 69.1 %; prior duration of ALN or RIS, 46.6 months; were allocated, based on their preference, to either the (1) continue group (n = 88), (2) switch-from-ALN group (n = 44), or (3) switch-from-RIS group (n = 40). RESULTS: After 12 months, increase in BMD was significantly greater in group 3 compared to group 1: LS (4.1 vs 1.2 %; P < 0.001), TH (1.9 vs −0.7 %; P < 0.01), and FN (2.7 vs −0.5 %; P < 0.05); and in group 2 compared to group 1: LS (3.2 vs 1.2 %; P < 0.05) and TH (1.5 vs −0.7 %; P < 0.01). The decrease in bone turnover markers was significantly greater in group 3 compared to group 1: TRACP-5b (−37.3 vs 2.5 %; P < 0.001), PINP (−24.7 vs −6.2 %; P < 0.05), and ucOC (−39.2 vs 13.0 %; P < 0.05); and in group 2 compared to group 1: TRACP-5b (−12.5 vs 2.5 %; P < 0.05) at 12 months. CONCLUSIONS: Switching weekly ALN or RIS to monthly MIN in patients with RA may be an effective alternative treatment option of oral bisphosphonate treatment.

Determinants of change in bone mineral density and fracture risk during bisphosphonate holiday.

UNLABELLED: In a retrospective analysis of 208 osteoporotic patients followed during a bisphosphonate holiday, lower body weight and risedronate use were associated with a more rapid decline in bone mineral density during the bisphosphonate holiday, while bone mineral density (BMD) trends were similar in patients who sustained vs. did not sustain a fracture. INTRODUCTION: A drug holiday has been suggested for some bisphosphonate-treated patients with osteoporosis to minimize potential side effects from prolonged use. However, there is limited information on the evolution of BMD during a bisphosphonate holiday. Our study analyzed the longitudinal course of BMD following bisphosphonate discontinuation and assessed its determinants. METHODS: Retrospective single-center cohort study of osteoporosis patients treated with alendronate or risedronate for at least 2 years and then discontinued their bisphosphonate for a drug holiday. Patients were stratified by bisphosphonate type and by fracture occurrence during drug holiday. RESULTS: A total of 208 patients were included in this analysis (87.5 % female). At the time of bisphosphonate cessation, mean ± SD age was 66.9 ± 8.9 years and BMI 24.5 ± 4.4 kg/m(2). Duration of bisphosphonate treatment was 5.2 ± 2.3 years, and follow-up during holiday was 3.3 ± 1.7 years. During the first 2 years of the holiday, BMD remained stable at the lumbar spine and femoral neck, but declined significantly at the total hip. BMD declined significantly at all sites thereafter. Significant predictors of BMD decline during bisphosphonate holiday included lower BMI at the start of the holiday and change in body weight during the holiday. BMD decline was more pronounced in former risedronate compared to former alendronate users. BMD trends were similar in patients who sustained vs. did not sustain a fracture during the holiday. CONCLUSIONS: BMD at the total hip declines significantly within 1 year of bisphosphonate discontinuation, particularly in lean patients. Additional studies are needed to identify predictors of fracture incidence during a bisphosphonate holiday.

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study.

UNLABELLED: We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80 % of her medication. INTRODUCTION: Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers. METHODS: Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomised to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for 2 years. The LSC for each marker was derived within the study population, whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years). RESULTS: Over 70 % of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63 % (difference 13 %, 95 % CI 0 to 27.1, P = 0.049) and good compliance -67 % (difference 15.9 %, 95 % CI 6.3 to 25.5, P = 0.001). Responders had a greater increase in spine bone density compared to nonresponders; for example 6.2 vs. 2.3 % (difference 3.9 %, 95 % CI 1.6 to 6.3, P = 0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate. CONCLUSIONS: Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD, and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.

Prophylactic oral bisphosphonate therapy in duchenne muscular dystrophy.

INTRODUCTION: We assessed prophylactic use of bisphosphonate (BP) in Duchenne muscular dystrophy (DMD) patients on glucocorticoid (GC) therapy. METHODS: Fifty-two DMD patients on daily GC were offered BP (oral risedronate). Patients were reviewed for tolerability, side effects, bone pain, and fracture frequency. Bone mineral density (BMD) was determined by annual dual energy X-ray absorptiometry. BP-treated patients were compared with 15 BP-naïve patients (untreated cohort). RESULTS: Side effects occurred in 9 patients. Thirty-six patients continued BP therapy for over 12 months (mean, 3.6 years). Five treated patients reported bone pain. Three treated patients suffered a vertebral fracture, significantly less than in the untreated cohort (5/15). Lumbar spine adjusted BMD Z-scores remained unchanged in treated patients and were significantly greater than in the untreated cohort. CONCLUSIONS: Prophylactic oral risedronate therapy was tolerated by most DMD patients. It appears to maintain BMD and may reduce fracture rate in DMD patients on GC. Muscle Nerve 54: 79-85, 2016.

Patient preference for monthly bisphosphonate versus weekly bisphosphonate in a cluster-randomized, open-label, crossover trial: Minodroate Alendronate/Risedronate Trial in Osteoporosis (MARTO).

Minodronate is a potent nitrogen-containing bisphosphonate that can be administered according to a monthly (every 4 weeks) dosing regimen. A 6-month, cluster-randomized, open-label, multicenter, crossover trial was conducted to test the preference of Japanese patients with osteoporosis for monthly bisphosphonate versus weekly bisphosphonate. One hundred and forty-seven patients (postmenopausal women and men) with primary osteoporosis were recruited at eight outpatient clinics. The clinics were randomized into two groups according to the dosing protocol-monthly minodronate followed by weekly alendronate or risedronate for a total of 24 weeks, or weekly alendronate or risedronate followed by monthly minodronate for 24 weeks. Patient preference for either the monthly or weekly bisphosphonate regimen was evaluated using a preference questionnaire. One hundred and fifteen patients (78.2 %) who completed the trial were processed for the analyses. Significantly more patients preferred the monthly bisphosphonate regimen (65.2 %) than the weekly bisphosphonate regimen (15.7 %) (P = 0.007). 'Dosing schedule fits lifestyle better' was the most common reason given for the patient preference for both the monthly (32.0 %) and weekly bisphosphonate (33.3 %) regimens. Significantly more patients found the monthly bisphosphonate regimen to be more convenient (73.0 %) than the weekly bisphosphonate regimen (13.9 %) (P < 0.0001). The safety profiles of the two regimens were similar. The present trial demonstrated a strong patient preference for and the convenience of the monthly bisphosphonate regimen over the weekly bisphosphonate regimen in Japanese patients with osteoporosis.