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Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study



We compared the effects of oral alendronate, ibandronate and risedronate on the central and peripheral skeleton over 2 years. We report differences in effect on the central skeleton but not on the peripheral skeleton. Greater effects were observed for ibandronate (and alendronate) than risedronate at the spine but not the hip.


Generally, comparative clinical trials of bisphosphonates have examined changes in bone within central skeletal regions. We have examined the effects of bisphosphonate treatment on the peripheral skeleton.


We conducted a 2-year, open-label, parallel randomised control trial of three orally administered bisphosphonates, at their licensed dose, to examine and compare their effects on the peripheral skeleton using multiple modes of measurement. We studied 172 postmenopausal women (53–84 years) who had either a bone mineral density (BMD) T-score of  ≤ −2.5 at the spine and/or total hip or  < −1.0 at either site plus a previous low trauma fracture. Participants were randomised to receive either (i) ibandronate 150 mg/month, (ii) alendronate 70 mg/week or (iii) risedronate 35 mg/week, plus calcium (1,200 mg/day) and vitamin D (800 IU/day), for 2 years. Premenopausal women (33–40 years, n = 226) were studied to monitor device stability.


We measured central BMD of the lumbar spine, total hip, total body and forearm using dual-energy X-ray absorptiometry. We measured calcaneus BMD (using dual-energy X-ray absorptiometry plus laser), radius and tibia BMD (using peripheral quantitative computed tomography), finger BMD (using radiographic absorptiometry), and phalangeal and calcaneal ultrasound variables (using quantitative ultrasound). Mixed effects regression models were used to evaluate effects of time and treatment allocation on BMD change. By 2 years, there were significant increases (p < 0.05) in central BMD sites (lumbar spine, total hip). In the peripheral skeleton, only significant changes in calcaneus BMD, 33 % total radius BMD and quantitative ultrasound (QUS)-2 broadband ultrasound attenuation (BUA) were evident for women receiving oral bisphosphonates.


The increases in lumbar spine and total body BMD were greater with ibandronate and alendronate than with risedronate. Treatment effects on peripheral measurements did not differ between the three bisphosphonates.

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This study was funded by Warner Chilcott. Professor Richard Eastell (Academic Unit of Bone Metabolism, The University of Sheffield) is a National Institute for Health Research (NIHR) Senior Investigator. The authors approved the manuscript for publication and vouch for the completeness and accuracy of the data. The funder was involved in the design, but not in the conduct, analysis or reporting of the study. We are grateful to Professor Robert E. Coleman (Academic Unit of Clinical Oncology, The University of Sheffield) and Professor Richard J. Ross (Academic Unit of Diabetes, The University of Sheffield) and Mike Bradburn (Clinical Trials Research Unit, School of Health and Related Research (ScHARR), The University of Sheffield) for acting as the data safety monitoring board, Neil Shephard (Clinical Trials Research Unit, School of Health and Related Research (ScHARR), The University of Sheffield) for conducting the statistical analyses according to the statistical analysis plan, Tim Chater and Saleema Rex (Clinical Trials Research Unit, School of Health and Related Research (ScHARR) for data management, all the staff of the Academic Unit of Bone Metabolism and all-out study participants.

Conflicts of interest

Dr Margaret Paggiosi has no disclosures; Dr Nicola Peel has received speaker’s honoraria and funding/support to attend educational events from Warner-Chilcott, Lilly Servier, Prostraken, Merck and Roche; consultancy fees from Internis Pharma and lecture fees from Warner Chilcott, Lilly, GSK and Prostrakan; Professor Eugene McCloskey has received speaker’s honoraria and/or research funding and/or advisory board funding from Warner-Chilcott, Merck, Amgen, GSK, Bayer, Consilient, Roche, Hologic, Lilly, Novartis, Pfizer, Servier and Wyeth; Dr Jennifer Walsh has received a donation of drug and placebo from Prostraken for a clinical trial and speaker fees from Lilly; and Professor Richard Eastell (relevant to this manuscript) has received grant funding from Warner-Chilcott and the National Institute for Health Research (NIHR) and has received consultancy funding from Warner-Chilcott and Merck.

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Correspondence to M. A. Paggiosi.

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Paggiosi, M.A., Peel, N., McCloskey, E. et al. Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study. Osteoporos Int 25, 2729–2741 (2014).

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  • Densitometry
  • Oral bisphosphonates
  • Peripheral skeleton
  • Postmenopausal osteoporosis
  • Treatment effects
  • TRIO study