Monthly Minodronate Research Articles

Efficacy and Safety of Monthly Minodronate Therapy in Postmenopausal Breast Cancer Patients Receiving Aromatase Inhibitors.

Post-menopausal breast cancer (BC) patients who receive adjuvant aromatase inhibitor (AI) therapy may be at increased risk of bone loss, osteoporosis, and bone fracture. We aimed to evaluate the efficacy and safety of oral bisphosphonate minodronate in preventing bone loss complications. Patients receiving AI and 80% of those with suboptimal bone mineral density (BMD) were prescribed monthly oral minodronate 50 mg every 4 weeks for 72 weeks. BMD, bone metabolism markers, incidence of bone fractures, medication compliance, and other adverse events (AE) were examined every 24 weeks following administration. Fifty postmenopausal BC patients with a median age of 64.0 years were enrolled. The mean value of lumbar spine BMD was higher than that of the value before the minodronate administration at each observation point. Before and after the treatment, the median serum values of Tartrate-resistant Acid Phosphatase 5b (TRACP-5b) (mU/dl) and serum type I collagen cross-linked N-telopeptide (NTX) (nmolBCE/l) were decreased from 535.7 and 18.5 to 230.1 and 11.9, respectively. No adverse grade 2 or higher event was observed throughout this study. The combined administration of minodronate and AIs was safe and effective in preventing bone loss complications in postmenopausal BC patients.

Utility of monthly minodronate for osteoporosis after gastrectomy: Prospective multicenter randomized controlled trials.

AimOsteoporosis in patients after gastrectomy is increasing with the aging of gastric cancer patients. Bisphosphonates are effective treatments for osteoporosis; however, their safety or efficacy in postgastrectomy patients has not been established. The purpose of this multicenter prospective intervention study was to investigate the impact of monthly minodronate on osteoporosis after gastrectomy.MethodsOf the 261 enrolled gastric cancer patients, 164 patients were diagnosed with osteoporosis based on criteria of the Japan Society of Osteoporosis. They were randomly assigned 1:1 to groups treated with active vitamin D (VD group) or monthly minodronate (MIN group). The primary endpoint was changes in lumbar bone mineral density (L‐BMD) 12 mo after the start of administration. The secondary endpoints were changes in bone metabolism markers, adverse events (AEs), or treatment completion rates.ResultsThere was no significant difference in patient background between the VD (n = 82) and MIN (n = 82) groups. In the MIN group, the increase in L‐BMD was significantly higher than that in the VD group (4.52% vs 1.72%, P = .001), with a significant reduction in bone metabolism markers; blood NTX (−25.6% vs −1.6%, P < .01) and serum bone‐specific alkaline phosphatase (−34.3% vs −20.1%, P < .01). AEs were observed in 26.8% and 9.3% of the patients and treatment completion rates were 77.5% and 89.3% in the MIN and VD groups, respectively. Serious AEs were not observed in either group.ConclusionThis study demonstrated the safety and efficacy of monthly minodronate, suggesting that this treatment may be useful for osteoporosis after gastrectomy (UMIN000015517).

Effects of monthly minodronate with or without eldecalcitol addition in osteoporosis patients with rheumatoid arthritis: An 18-month prospective study

ObjectivesIncreasing bone mineral density (BMD) to reduce fracture risk is a primary goal of osteoporosis treatment. This prospective, observational study evaluates the effects of monthly minodronate (MIN; 50 mg) with or without eldecalcitol (ELD) addition in osteoporosis patients with rheumatoid arthritis (RA) during 18 months. MethodsThe cohort was prospectively and randomly split into the MIN monotherapy group (14 cases) and MIN plus ELD group (combination group; 14 cases) due to no reports on the effectiveness and safety of MIN therapy in relation to ELD addition for comparisons of serum tartrate-resistant acid phosphatase (TRACP)-5b, bone alkaline phosphatase (BAP), and BMD of the lumbar 1–4 vertebrae (L-BMD), bilateral total hips (H-BMD; the mean value of the right and left hips), and bilateral femoral necks (FN-BMD) at baseline and at 6, 12, and 18 months of treatment. ResultsBaseline values were comparable between the groups apart from a tendency for higher TRACP-5b in the combination group. Seven of 14 patients in the combination group had received previous bisphosphonate treatment. BAP was significantly more reduced in the monotherapy group at 6 months, with no other remarkable differences for TRACP5b, L-BMD, H-BMD, or FN-BMD during the observation period. ConclusionsThe above findings suggest that regardless of ELD addition, MIN potentially improves BMD during 18 months in osteoporosis patients with RA.

Influence on the bone mineral density and bone metabolism marker after the interruption and reinitiation of monthly minodronate therapy in postmenopausal women with osteoporosis

ObjectivesThe purpose of this study was to investigate the influences of interruption and reinitiation of monthly minodronate therapy on the bone mineral density (BMD) and bone metabolism markers in postmenopausal women with osteoporosis. MethodsStudy patients were included if they had been administered monthly minodronate therapy for ≥6 months, interrupted the therapy, and reinitiated the therapy for ≥12 months. The BMD and bone metabolism markers were assessed at 4 time points: initiation, interruption, reinitiation and 1 year after reinitiation of therapy. ResultsA total of 23 patients were enrolled. The mean monthly minodronate treatment period was 23.8 ± 12.9 months following a mean interruption period of 11.9 ± 5.4 months. Once increased by monthly minodronate treatment for 2 years on average, the BMD of lumbar spine and radius did not significantly decrease even after an interruption for 1 year on average. However, the BMD of the femoral neck did decrease after interruption. The BMD of the lumbar spine and radius increased further after 1 year of monthly minodronate retreatment. The BMD of the femoral neck did not change. Once decreased after the treatment for an average of 2 years followed by an interruption for 1 year, bone metabolism markers increased gradually but did not recover to baseline levels. A potent suppressive effect on bone resorption was noted. The change rate was greater for the bone formation marker procollagen 1 N-terminal propeptide. ConclusionsMonthly minodronate treatment increases BMD and reduces bone metabolism markers. The effect lessens after treatment interruptions, and can be restored by retreatment.

Serum homocysteine levels are affected by renal function during a 3-year period of minodronate therapy in female osteoporotic patients.

Serum homocysteine is a possible marker to indicate bone quality. However, it is not clear whether changes are seen in serum homocysteine levels with long-term bisphosphonate therapy. We aimed to investigate the factors affecting serum homocysteine levels during a 3-year period of monthly minodronate therapy in osteoporotic women, and to examine if the serum homocysteine levels could reflect some aspects of bone metabolism. The study included 43 patients (age 72.3 ± 7.0years) undergoing treatment for osteoporosis for the first time (New group) and 35 patients (age 74.4 ± 8.2years) who switched from alendronate or risedronate to minodronate (Switch group). Minodronate (50mg/every 4weeks) was administered for 36months. Lumbar, femoral neck, and total hip bone mineral densities (BMD), and serum homocysteine levels were monitored at baseline and after 9, 18, 27, and 36months of treatment. Lumbar BMD increased significantly in both groups (New group 11.4%, Switch group 6.2%). However, femoral neck and total hip BMDs increased only in the New group (femoral neck 3.6%, total hip 4.1%). Serum homocysteine levels increased significantly at 18 and 27months in all subjects. Multiple linear regression analysis revealed that changes in homocysteine levels during 18, 27, and 36months significantly correlated with changes in creatinine clearance during the same corresponding periods (18months: B = - 0.472, p = 0.003; 27months: B = - 0.375, p = 0.021; 36months: B = - 0.445, p = 0.012). Thus, serum homocysteine levels possibly reflect renal function instead of bone metabolism during minodronate therapy.

The effects of minodronate and activated vitamin D on bone mineral density and muscle mass in postmenopausal women with osteoporosis.

Introduction Osteoporosis and sarcopenia are said to be similar disorders. However, few reports have described the effects of anti-osteoporosis drugs on muscle mass in clinical practice. Methods We selected 150 postmenopausal women with osteoporosis treated by minodronate (osteoporosis medication [OM] group) and 50 postmenopausal women without osteoporosis who did not receive treatment (no osteoporosis [NO] group). The OM group was further divided into two treatment subgroups: a combination of monthly minodronate and daily activated vitamin D vs. monthly minodronate alone. We measured lumbar spine and femoral neck bone mineral density (BMD) with dual-energy X-ray absorptiometry and muscle mass of the upper limbs, lower limbs, and trunk with bioelectrical impedance analysis at baseline and after 6 months. Results The OM and NO groups contained 130 and 37 patients, respectively (mean age: 73.9 ± 8.3 and 74.1 ± 10.0 years, respectively). In the OM group, lumbar spine BMD significantly increased after 6 months, while lower limb muscle mass significantly decreased. In the NO group, lumbar spine BMD and lower limb muscle mass did not significantly change after 6 months. In the OM group, BMD of the lumbar spine significantly increased but the lower limb muscle mass significantly decreased after 6 months relative to the NO group. In the combination therapy subgroup of the OM group muscle mass decreased significantly less than in the minodronate-alone subgroup. Conclusions In postmenopausal women with osteoporosis, minodronate can increase BMD but cannot increase muscle mass. However, simultaneous use of activated vitamin D can suppress muscle mass decrease. The combination of activated vitamin D and minodronate may be useful for treating osteoporosis in postmenopausal women.

Changes of bone mineral density and serum pentosidine during a 27-month follow-up of monthly minodronate in osteoporotic patients

ABSTRACTPurpose: Monthly regimen of minodronate for osteoporosis more than two years has not been reported yet. The aim of this study is to elucidate the effect of monthly minodronate (M-MIN) on bone mineral density (BMD) and serum pentosidine (Pen) during 27 months. Materials and methods: The study consisted of 52 newly treated patients (73.3 ± 8.8 years) (new group) and 47 patients (75.9 ± 9.5 years) who were switched from either alendronate or risedronate (switch group). Monthly minodronate (50 mg/every 4 weeks) was administered for 27 months. Lumbar, femoral neck, and total hip BMDs and serum pentosidine were monitored at baseline and after 9, 18, and 27 months of treatment. Results: In the new condition, lumbar, neck, and total hip BMDs increased significantly by 9.07%, 3.15%, and 3.06%, respectively. Only the lumbar BMD significantly increased in the switch condition. Serum Pen increased in both groups in a time-dependent manner. In the group switch, multivariate logistic regression analysis revealed that the initial change in serum intact procollagen type I N-terminal propeptide (P1NP) at 9 months was an independent predictor of changes in neck and total hip BMDs at 27 months (OR = 1.039, 95% CI 1.003–1.077, p = 0.032 for neck and OR = 1.055, 95% CI 1.009–1.104, p = 0.020 for total hip). Conclusions: Monthly minodronate treatment increased BMDs in newly treated patients over 27 months. Serum Pen increased with M-MIN therapy, possibly indicating prolonged bone turnover. The initial 9-month changes in serum P1NP predicted the 27-month changes in hip BMDs when M-MIN replaced alendronate or risedronate.

Monthly minodronate inhibits bone resorption to a greater extent than does monthly risedronate

As a bisphosphonate, minodronate (MIN) is one of the strongest inhibitors of bone resorption. However, there have been no reports directly comparing the antiresorptive effects of monthly MIN with those of monthly risedronate (RIS). We enrolled 30 cases of osteoporosis (OP; 16 in the MIN group [mean age: 68.2 years] and 14 in the RIS group [mean age: 68.1 years]) to investigate the early effects of treatment by monthly MIN or RIS over a 4-month period using bone turnover marker values. Only female patients were enrolled to avoid gender bias. Urinary cross-linked N-telopeptide of type I collagen (NTX) before treatment and at 1, 2, and 4 months of therapy, as well as serum bone alkaline phosphatase and alkaline phosphatase before treatment and at 4 months afterwards, were evaluated. All bone turnover marker values were significantly decreased at 4 months in both groups. The changes in urinary NTX at the study end point for RIS and MIN were −30.1% and −63.1%, respectively. From 2 months of treatment, the antiresorptive effects on urinary NTX by MIN were significantly higher than those by RIS, indicating that MIN more immediately and strongly inhibited bone absorption. Thus, monthly MIN seems to suppress bone resorption faster and more strongly than RIS in OP treatment.

Initiation of Monthly Minodronate Therapy at an Early Stage After Hip Fracture

The incidence of second hip fractures occurring within a year of initial fractures is 20%–45%. The high incidence of second hip fractures in this period can be attributed to the rapid bone loss that occurs during this time. Restoring bone mass at an early stage after hip fractures is critical for preventing subsequent fractures. The aim of this study was to investigate the efficacy of monthly minodronate therapy (50 mg/4 wk) for preventing bone loss over a 9-mo period following hip fractures. Minodronate was administered monthly to 51 patients (44 females), beginning within 3 mo after hip fracture surgery. The mean (±standard deviation) age of the patients was 82.0 ± 0.9 yr. Demographics, mobility status, bone turnover makers, and bone mineral density (BMD) in the lumbar spine and proximal femur (including femoral neck and total hip BMD) were examined prior to and after 9 mo of treatment. Lumbar BMD was increased by 2.7% ± 4.4% (p < 0.001) compared to the baseline values. However, femoral neck and total hip BMD did not significantly change. Bone formation and resorption markers both decreased by approximately 70% during treatment. Monthly treatment with minodronate did not adversely affect the healing process on the fracture site or the patients' laboratory results. The patients who were independently mobile prior to injury exhibited greater recovery of BMD in the femoral neck during the 9-mo treatment period. Monthly minodronate therapy during the early stages after hip fractures has favorable effects on restoring overall lumbar BMD and contralateral femoral neck BMD in patients with independent mobility prior to fractures.

Change in arterial stiffness associated with monthly bisphosphonate treatment in women with postmenopausal osteoporosis

Osteoporosis and atherosclerosis are the two most common diseases in postmenopausal women. In most cases, they are simultaneously present in the same individual and commonly lead to bone fracture or cardiovascular disease (CVD). Bisphosphonates (BPs) are frequently used in the treatment of osteoporosis and have the ability to increase lumbar spine bone mineral density (L-BMD). BPs may also protect against CVD. A single monthly 50-mg dose of minodronate (monthly minodronate) is now common practice and is highly anticipated to reduce the incidence of both bone fracture and CVD. A useful approach to independently predicting CVD is brachial-ankle pulse wave velocity (baPWV). Here, we directly compared the effects of monthly minodronate with those of a standard single weekly 35-mg dose of alendronate (weekly alendronate) on L-BMD and baPWV in postmenopausal women with osteoporosis across a 12-month period. Thirty-eight postmenopausal women with osteoporosis were randomized into two treatment groups (group 1, weekly alendronate, n = 19; group 2, monthly minodronate, n = 19). L-BMD and baPWV were assessed at baseline and 12-month follow-up. At the end of the 12-month period, increases in L-BMD were similar between group 1 (7.6%) and group 2 (8.5%), but baPWV was significantly reduced in group 2 compared with group 1. The change in baPWV during the study period showed a significant negative correlation with the change in L-BMD. Changes in L-BMD in the monthly minodronate and weekly alendronate groups are generally comparable. Good control of changes in L-BMD in the postmenopausal phase might be associated with regression of CVD. Monthly minodronate is a promising new BP and potential first-line drug for the treatment of osteoporosis in postmenopausal women.

Erratum to: Clinical efficacy and treatment persistence of monthly minodronate for osteoporotic patients unsatisfied with, and shifted from, daily or weekly bisphosphonates: the BP-MUSASHI study

Erratum to: Clinical efficacy and treatment persistence of monthly minodronate for osteoporotic patients unsatisfied with, and shifted from, daily or weekly bisphosphonates: the BP-MUSASHI study

Clinical efficacy and treatment persistence of monthly minodronate for osteoporotic patients unsatisfied with, and shifted from, daily or weekly bisphosphonates: the BP-MUSASHI study.

SummaryThis multi-center, prospective, open-label, observational study evaluated the effects of once-monthly minodronate (50 mg) on treatment persistence, bone turnover markers, bone mineral density, low back pain, and upper gastrointestinal symptoms in outpatients with osteoporosis previously treated with daily or weekly bisphosphonate products.IntroductionThe purposes of this study were to investigate the effects of once-monthly oral minodronate (MIN 50 mg) on bone turnover markers and bone mineral density, low back pain, and upper gastrointestinal symptoms, as well as preference for and treatment persistence of MIN 50 mg among Japanese osteoporosis patients currently treated with daily or weekly bisphosphonates.MethodsStudy patients were allocated based on their preference to either the Switch group (patients willing to switch over to MIN 50 mg) or the Continue group (patients wanting to continue their current therapies). Patients’ treatment persistence and satisfaction levels with the therapies were assessed using a self-administered questionnaire. The study endpoints were serum TRACP-5b, serum P1NP, bone mineral density, upper gastrointestinal symptoms, and low back pain.ResultsIn total, 264 and 133 patients were allocated into the Switch and Continue groups, respectively. Approximately, 65 % of patients were willing to switch to MIN 50 mg, with the predominant reason being “less frequent dosing more convenient.” Treatment persistence was significantly higher in the Switch group (MIN 50 mg) than the Continue group. Almost all patients with abnormal bone metabolism markers demonstrated normalization after switchover. MIN 50 mg alleviated low back pain and upper gastrointestinal symptoms induced by prior bisphosphonate use.ConclusionsMIN 50 mg alleviates low back pain, reduces bone turnover markers and increases bone density, and induces fewer upper gastrointestinal symptoms after switchover from prior bisphosphonate products, and therefore, it may provide patients with a more convenient treatment option and enhance long-term treatment persistence.