PMID- 24184313
OWN - NLM
STAT- MEDLINE
DCOM- 20140909
LR  - 20221207
IS  - 1873-2763 (Electronic)
IS  - 1873-2763 (Linking)
VI  - 59
DP  - 2014 Feb
TI  - Efficacy, tolerability and safety of once-monthly administration of 75mg 
      risedronate in Japanese patients with involutional osteoporosis: a comparison 
      with a 2.5mg once-daily dosage regimen.
PG  - 44-52
LID - S8756-3282(13)00427-4 [pii]
LID - 10.1016/j.bone.2013.10.017 [doi]
AB  - Oral risedronate has been shown to be effective in the treatment of osteoporosis 
      when administered once-daily or once-weekly in Japan. This randomized, 
      double-blind, multicenter 12-month study was conducted to compare the efficacy 
      and tolerability of oral risedronate 75mg once-monthly with 2.5mg once-daily in 
      Japanese patients with involutional osteoporosis. Bone mineral density (BMD), 
      biochemical markers of bone metabolism, fractures, and adverse events (AEs) were 
      evaluated. At the end of the study (Month 12, last observation carried forward 
      [M12, LOCF]), mean percent change (SD) from baseline in lumbar spine (L2-L4) BMD, 
      measured by dual energy X-ray absorptiometry (primary endpoint), was increased by 
      5.69 (4.00)% in the 2.5mg once-daily group (n=428), and 5.98 (4.54)% in the 75mg 
      once-monthly group (n=422). In the non-inferiority t-test (non-inferiority margin 
      Delta=1.5%), the 75mg once-monthly group was non-inferior to the 2.5mg once-daily 
      group (p<0.0001). The difference between treatment groups was 0.28% (95% CI, 
      -0.31% to 0.88%). Changes in biochemical markers of bone metabolism were 
      generally comparable in the two groups, although decreases in the percent change 
      from baseline in urinary NTX/CRN and CTX/CRN were statistically greater in the 
      2.5mg once-daily group than the 75mg once-monthly group. The frequency of new 
      vertebral fractures (including aggravation of prevalent fractures) at the end of 
      the study (M12, LOCF) was also similar in the two groups: 1.2% in the 2.5mg 
      once-daily group and 1.3% in the 75mg once-monthly group. The incidence of 
      mild/moderate/severe AEs was 75.5%/6.3%/0.5% in the 2.5mg once-daily group and 
      77.7%/8.1%/0.7% in the 75mg once-monthly group. AEs associated with 
      gastrointestinal symptoms occurred in approximately 30% of subjects in each group 
      but with no severe cases. AEs potentially associated with acute phase reaction 
      (including symptoms of influenza-like illness or pyrexia starting within 3days of 
      the first dose of the study drug and with a duration of 7days or less) only 
      occurred in the 75mg once-monthly group (2.1%, 9/422 subjects; influenza-like 
      symptoms in 1 subject and pyrexia in 8 subjects), although the incidence was low 
      without any severe cases. In conclusion, risedronate 75mg once-monthly (a dosage 
      which is 30 times higher than risedronate 2.5mg once-daily) had non-inferior 
      efficacy in terms of BMD and was similarly well tolerated compared to the 
      once-daily regimen in Japanese patients with involutional osteoporosis. 
      Consistent with the once-daily and once-weekly dosage, the once-monthly dosage of 
      risedronate 75mg was half that used outside Japan (150mg).
CI  - (c) 2013. Published by Elsevier Inc. All rights reserved.
FAU - Hagino, Hiroshi
AU  - Hagino H
AD  - School of Health Science and Rehabilitation Division, Tottori University, 
      Nishicho 86, Yonago, Tottori, Japan. Electronic address: 
      hagino@med.tottori-u.ac.jp.
FAU - Kishimoto, Hideaki
AU  - Kishimoto H
AD  - Department of Orthopedics, Nojima Hospital, Tottori, Japan.
FAU - Ohishi, Hiroaki
AU  - Ohishi H
AD  - Clinical Development Dept., Ajinomoto Pharmaceuticals Company Limited, Tokyo, 
      Japan.
FAU - Horii, Sayako
AU  - Horii S
AD  - Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, 
      Japan.
FAU - Nakamura, Toshitaka
AU  - Nakamura T
AD  - National Center for Global Health and Medicine, Tokyo, Japan.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20131029
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Biomarkers)
RN  - 0 (Bone Density Conservation Agents)
RN  - KM2Z91756Z (Risedronic Acid)
RN  - M2F465ROXU (Etidronic Acid)
SB  - IM
MH  - Aged
MH  - *Asian People
MH  - Biomarkers/metabolism
MH  - Bone Density/drug effects
MH  - Bone Density Conservation Agents/*administration & dosage/adverse 
      effects/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Etidronic Acid/administration & dosage/adverse effects/*analogs & 
      derivatives/therapeutic use
MH  - Female
MH  - Humans
MH  - Japan/epidemiology
MH  - Lumbar Vertebrae/drug effects/pathology
MH  - Male
MH  - Osteoporosis/*drug therapy
MH  - Risedronic Acid
MH  - Spinal Fractures/epidemiology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Bisphosphonates
OT  - Bone mineral density
OT  - Involutional osteoporosis
OT  - Lumbar spine
OT  - Risedronate
EDAT- 2013/11/05 06:00
MHDA- 2014/09/10 06:00
CRDT- 2013/11/05 06:00
PHST- 2013/05/25 00:00 [received]
PHST- 2013/10/18 00:00 [revised]
PHST- 2013/10/23 00:00 [accepted]
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2014/09/10 06:00 [medline]
AID - S8756-3282(13)00427-4 [pii]
AID - 10.1016/j.bone.2013.10.017 [doi]
PST - ppublish
SO  - Bone. 2014 Feb;59:44-52. doi: 10.1016/j.bone.2013.10.017. Epub 2013 Oct 29.