Introduction
Eldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in ...glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of alfacalcidol in GIO patients.
Materials and methods
A randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75 μg eldecalcitol compared with 1.0 μg alfacalcidol in GIO patients.
Results
Lumbar spine BMD increased with eldecalcitol, but decreased with alfacalcidol at 12 and 24 months (between group difference 1.29%,
p <
0.01, and 1.10%,
p <
0.05, respectively). Total hip and femoral neck BMD were maintained until 24 months by eldecalcitol, but decreased by alfacalcidol (between group difference 0.97%,
p <
0.05 and 1.22%,
p <
0.05, respectively). Both bone formation and resorption markers were more strongly suppressed by eldecalcitol than by alfacalcidol. Eldecalcitol showed better effect on BMD than alfacalcidol in patients with no prevalent fracture and BMD > 70% of the young adult mean, and with ≤ 3 months of previous glucocorticoid treatment. No significant difference in the incidence of vertebral fracture was found, and the incidence of adverse events was similar between the two groups.
Conclusions
Eldecalcitol was more effective than alfacalcidol in maintaining BMD in GIO patients. Because eldecalcitol was effective in patients with no or short-term previous glucocorticoid treatment, as well as those without prevalent fracture or low BMD, eldecalcitol can be a good candidate for primary prevention of GIO.
Clinical trial registration number
UMIN000011700.
Context:
Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral, nonvertebral, and hip fracture in predominantly Caucasian ...postmenopausal women with osteoporosis.
Objective:
The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo.
Design and Setting:
A randomized, double-blind, placebo-controlled trial with an open-label active comparator as a referential arm was conducted.
Patients:
Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older, who had one to four prevalent vertebral fractures.
Intervention:
Subjects were randomly assigned to receive denosumab 60 mg sc every 6 months (n = 500), placebo for denosumab (n = 511), or oral alendronate 35 mg weekly (n = 251). All subjects received daily supplements of calcium and vitamin D.
Main Outcome Measure:
The primary endpoint was the 24-month incidence of new or worsening vertebral fracture for denosumab vs placebo.
Results:
Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7%, with incidences of 3.6% in denosumab and 10.3% in placebo at 24 months (hazard ratio 0.343; 95% confidence interval 0.194–0.606, P = .0001). No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study.
Conclusion:
These results provide evidence of the efficacy and safety of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis.
Introduction
This study compared the clinical usefulness of minodronate (50 mg/4 weeks) plus alfacalcidol (1 μg/day) (Group M) with that of alfacalcidol alone (1 μg/day) (Group A) for treating ...glucocorticoid-induced osteoporosis.
Materials and methods
The primary endpoints were the changes from baseline in lumbar spine (LS) bone mineral density (BMD) and the cumulative incidence of vertebral fracture at 24 months; secondary endpoints included the changes from baseline in total hip (TH) BMD and bone turnover markers.
Results
Of 164 patients enrolled, 152 (Group M,
n
= 75; Group A,
n
= 77) were included in the analysis of efficacy. At each time point and at 24 months, LS BMD and TH BMD were significantly higher in Group M than in Group A. The 152 patients were divided into two subgroups that were previously treated with glucocorticoids for ≤ 3 months or > 3 months. In both subgroups, the changes from baseline in LS BMD and TH BMD from baseline at 24 months had increased more in Group M than in Group A. There were no differences found in the incidence of vertebral fracture between the groups, because the number of enrolled patients was lesser than that initially expected. In Group M, both bone formation and resorption markers significantly decreased from baseline at 3 months and maintained at 6, 12, and 24 months.
Conclusions
Minodronate plus alfacalcidol was more effective than alfacalcidol alone in increasing BMD and was effective in increasing BMD for both prevention and treatment. Therefore, minodronate can be a good candidate drug for the treatment of glucocorticoid-induced osteoporosis.
Polyinosinic-polycytidylic acid (PIC), a double-stranded RNA that induces innate immunity in mammals, is a candidate immunopotentiator for pharmaceuticals. The potency and adverse effects of PIC are ...strongly correlated with the nucleotide length, and the inability to precisely control the length in PIC production limits its practical use. Length extension during the annealing process is the major factor underlying the lack of control, but tuning the annealing conditions is insufficient to resolve this issue. In this study, we developed a novel method to produce accurate nucleotide length PIC at an industrial scale. The length extension was significantly suppressed by the assembly of multiple short polyinosinic acid molecules with one long polycytidylic acid molecule. A newly developed PIC, uPIC100-400, demonstrated a reproducible length and better storage stability than that of corresponding evenly structured PIC. Human dsRNA receptors exhibited equivalent responsiveness to uPIC100-400 and the evenly structured PIC with the same length.
Precise control method for poly I:C nucleotide length
Intranasal inactivated influenza vaccines can elicit mucosal immune responses that protect against virus infection. For the development of intranasal inactivated influenza vaccines, effective ...adjuvants inducing minimal adverse reactions are required. Generally, however, lower toxicity adjuvants have lower adjuvanticity. In this research, we fabricated nanoparticle-based adjuvants to enhance its adjuvanticity. Herein, we focused on low-molecular-weight polyinosinic-polycytidylic acid, referred to as uPIC(40:400), as a weak and less toxic RNA adjuvant. We conjugated uPIC(40:400) with different shaped gold nanoparticles (AuNPs) electrostatically. Conjugation with gold nanorods, but not spherical AuNPs, markedly enhanced the adjuvanticity of uPIC(40:400), leading to the suppression of viral infection in mice. Notably, conjugation with gold nanorods did not increase the inflammatory cytokine production in dendritic cells. These data indicated that gold nanorods can provide a good platform for enhancing the weak adjuvanticity of uPIC(40:400) while maintaining low inflammatory cytokine production toward the development of intranasal inactivated influenza vaccines.
The aim of this study was to compare the efficacy of elcatonin injections and oral nonsteroidal anti-inflammatory drugs (NSAIDs) for patients with osteoporosis who have acute lumbar pain after ...experiencing new vertebral compression fractures. Two hundred twenty-eight Japanese female patients (mean age 77.3 years) with acute lumbar pain from osteoporotic vertebral fractures were randomly divided into two groups. Patients in one group were given an NSAID (NSAIDs group) and patients in the other group were given weekly intramuscular injections of 20 units of elcatonin (elcatonin group). All patients underwent follow-up examinations up to 6 weeks from the start of the trial. Outcome measures were the level of functional impairment according to the Japan Questionnaire for Osteoporotic Pain (JQ22), the Roland–Morris Disability Questionnaire (RDQ), and a visual analog scale (VAS) of pain intensity. Statistical analyses focused on (1) the time course of pain and functional level using linear mixed effects models to analyze the longitudinal data and (2) the effectiveness of elcatonin injection with mean difference values and 95 % confidence intervals. Significant differences were seen over time between the initial values and the postintervention values (4 and 6 weeks) in JQ22, RDQ, and VAS scores (effect size
d
> 0.4) in each group. The mean differences between the elcatonin group and the NSAIDs group in each measure at 4 and 6 weeks were −4.8 and −8.3 for the JQ22, −1.3 and −2.6 for the RDQ, and −11.3 and −11.5 for the VAS, shifted to elcatonin. Once weekly elcatonin injection was more effective than NSAIDs for treating acute lumbar pain and improving mobility in Japanese women with osteoporotic vertebral fractures.
Background and Objectives: Reports on the mortality and its contributing factors after vertebral fracture (VFx) has been scarce, and limited to prevalent VFx. In this paper, we have studied the ...factors influencing mortality after freshly diagnosed VFx.
Methods and Study Design: 759 subjects aged 78.8+-8.5 years old with back or lumbar pain, and diagnosed as fresh VFx by MRI were studied for their age, gender, number of prevalent fracture (s), survival or the date of death, circulating concentrations of Hb, albumin, C reactive protein, and estimated glomerular filtration rate (eGFR). Cox's proportional hazard analysis was performed to assess the significant predictors for mortality. The cut-off concentrations of the variables for mortality were analyzed using the receiver operator characteristic (ROC) curve.
Results: The median observation duration was 3.8 years, and 3-year survival rate was 78.8%. Cox's proportional hazard analysis has shown that serum albumin concentration (hazard ratio (HR) =0.355) and eGFR (HR=0.993) were significant predictors for mortality. The cut-off concentrations were 3.6 g/dL and 60 mL/min/1.73m2, respectively. Kaplan-Meier curves revealed that survival rates were significantly decreased in patients with both serum albumin concentration and eGFR below these cut-off concentrations.
Conclusions: The present study has revealed that malnutrition and impaired renal function were significant predictors for mortality after VFx.
Nationwide one-decade survey of hip fractures in Japan Hagino, Hiroshi; Sakamoto, Keizo; Harada, Atsushi ...
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association,
11/2010, Letnik:
15, Številka:
6
Journal Article
Recenzirano
To elucidate the characteristics of hip fractures and the current status of their treatment in Japan, the Japanese Orthopaedic Association (JOA) conducted a nationwide hip fracture survey from 1998 ...to the present. The aim of the current report was to present the changes in patient distribution by age and fracture type, cause of fracture, treatment selection, and duration of hospitalization for a study period of one decade.
A tally of all hip fractures that occurred in patients between 2001 and 2008 was conducted in JOA-authorized hospitals and in Japanese Clinical Orthopaedic Association (JCOA) hospitals. Registration forms were sent to these hospitals each year, and registration was performed based on their hospital records.
The mean response rate was 51.8%, and the total number of patients aged ≥35 with new hip fractures between 2001 and 2008 was 402 760. A drastic increase in the number of patients, especially those aged ≥90 was observed over the course of the decade. More trochanteric fractures occurred than neck fractures during the observational period; however, the neck/trochanter ratio increased over time. Simple falls were the most common cause of fracture. About 94% patients were treated surgically with about a 5-day presurgical hospital stay, and the mean hospitalization period was 40.7 days in 2008.
This one-decade survey demonstrated a drastic increase in the number of patients over the course of the decade in Japan. Appropriate treatment and prevention of hip fractures, including the treatment of osteoporosis and more effective interventions for preventing falls, are important issues to address to reduce the burden of this fracture.
We examined response to bone mineral density (BMD) gains in the MOVER study following treatment with intravenous (IV) ibandronate 1 mg/month, and investigated the characteristics of a non-responder ...group. At 1 year, responder rates for patients with BMD increases >0 % were similar with IV ibandronate 0.5 or 1 mg/month and oral risedronate 2.5 mg/day. However, after 3 years, responder rates with BMD increases ≥3 % were highest with ibandronate 1 mg at all bone sites (>80 % at the lumbar spine L2–L4 and >50 % at all femur sites, which was significantly higher than with risedronate). Non-responders were defined by BMD increases ≤3 % at L2–L4 or ≤0 % at total hip, and ≤50 % reduction in creatinine-corrected urinary collagen type 1 cross-linked C-telopeptide (uCTX) from baseline to 1 year. There were a small number of non-responders in the ibandronate 1 mg group: 3.3 % (10/299) with ≤0 % total hip BMD increase and ≤50 % uCTX reduction from baseline. These non-responders had lower 25-hydroxyvitamin D (25OHD) levels than responders, but no differences in kidney function, L2–L4 BMD or bone turnover marker baseline values. Throughout the study, non-responders failed to show any increases in BMD. Our analysis demonstrates significantly higher responder rates with IV ibandronate 1 mg/month than with risedronate at 3 years. A small number of non-responders in the ibandronate group had lower 25(OH)D baseline levels than responders, suggesting that 25(OH)D levels could be a useful indicator of BMD response to therapy.
The objective of this study was to determine the safety and efficacy of long-term minodronate treatment in women with postmenopausal osteoporosis based on re-analysis of a phase III 2-year clinical ...trial with a 1-year extension. Women aged 55–80 years old with fragility fractures were enrolled and randomized to take 1 mg minodronate or placebo once a day in the original 2-year study. The subjects who completed the 2-year study were invited to participate in an additional 1-year extension in which all subjects were to receive minodronate. Finally, a total 380 subjects completed the extension study (186 from the placebo group and 194 from the minodronate group). Fracture results observed in the extension study were consistent with those observed in the first 2 years in minodronate group. In contrast, the placebo/minodronate group showed a decreased incidence of new vertebral fractures during year 3 compared to that in year 2. In the patients who received minodronate in the original 2-year study, lumbar bone mineral density (BMD) increased consistently during year 3 and bone turnover markers decreased within the first 6 months and remained constant thereafter over 3 years. Similar positive effects of minodronate on BMD and bone turnover markers occurred when therapy was initiated in the placebo/minodronate group. No new safety concerns observed during the extension period compared to the safety observations made during the 2-year study. It was concluded that daily administration of 1 mg oral minodronate is safe and well tolerated, and that the efficacy of this dose in reducing vertebral fracture risk in postmenopausal women over 2 years is sustained with continuing treatment.
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