Clinical Drug Investigation

, Volume 26, Issue 2, pp 63–74 | Cite as

Alendronic Acid Produces Greater Effects than Risedronic Acid on Bone Density and Turnover in Postmenopausal Women with Osteoporosis

Results of FACTS-International
  • David M. Reid
  • David Hosking
  • David Kendler
  • Maria L. Brandi
  • John D. Wark
  • Georges Weryha
  • João F. Marques-Neto
  • Keavy A. Gaines
  • Nadia Verbruggen
  • Mary E. Melton
Original Research Article

Abstract

Background: The objective of the study was to evaluate the effects of alendronic acid once weekly relative to risedronic acid once weekly on bone mineral density (BMD), markers of bone turnover and tolerability in the treatment of osteoporosis in postmenopausal women.

Methods: This was a randomised, double-masked, double-dummy multicentre international study (75 centres in 27 countries in Europe, the Americas and Asia-Pacific). A total of 1303 women were screened and 936 with low bone density (T-score ≤−2.0 at the spine, hip trochanter, total hip or femoral neck) were randomised; 91% (n = 854) completed the study. Patients were randomised to treatment with either active alendronic acid 70mg weekly (Fosamax®) and placebo identical to risedronic acid weekly or active risedronic acid 35mg weekly (Actonel®) and placebo identical to alendronic acid weekly for 12 months. The primary efficacy endpoint was the percentage change from baseline in hip trochanter BMD at 12 months. Secondary endpoints included the percentage change from baseline in lumbar spine, total hip and femoral neck BMD; biochemical markers of bone turnover (including serum bone-specific alkaline phosphatase [BSAP] and urinary type I collagen N-telopeptides [NTx]); and safety and tolerability as assessed by reporting of adverse experiences.

Results: Alendronic acid produced greater increases in BMD than did risedronic acid at 12 months at all sites measured. Mean percentage increases from baseline in hip trochanter BMD at month 12 were 3.56% and 2.71% in the alendronic acid and risedronic acid groups, respectively (treatment difference [95% CI]: 0.83% [0.22, 1.45; p = 0.008]). Mean percentage increases from baseline were greater with alendronic acid than risedronic acid at the lumbar spine, total hip and femoral neck BMD at month 12 (p = 0.002, p < 0.001, p = 0.039, respectively). Increases in BMD with alendronic acid compared with risedronic acid were also significantly greater at 6 months at the trochanter and total hip. There was a greater reduction in bone turnover with alendronic acid compared with risedronic acid: NTx decreased 58% with alendronic acid compared with 47% with risedronic acid at 12 months (p < 0.001); and BSAP decreased 45% with alendronic acid compared with 34% with risedronic acid at 12 months (p < 0.001). Overall tolerability and upper gastrointestinal tolerability were similar for both agents.

Conclusions: Alendronic acid once weekly produced greater BMD increases at both hip and spine sites and greater reductions in bone turnover relative to risedronic acid once weekly. Both agents were well tolerated with no significant difference in upper gastrointestinal adverse experiences. Clinicians should consider these results when making treatment decisions for postmenopausal women with osteoporosis.

Notes

Acknowledgements

This clinical trial was funded by Merck & Co., Inc.; no funding was received for manuscript development. D.M. Reid, D. Hosking, D. Kendler, M.L. Brandi and J.D. Wark have served as paid consultants and/or speakers for Merck & Co., Inc. M.L. Brandi has served as a paid speaker for Procter and Gamble Pharmaceuticals. K. Gaines, N. Verbruggen and M.E. Melton are employees of Merck & Co., Inc. and potentially own stock and/or hold stock options in the company.

The authors would like to recognise the valuable contributions of Christine Sisk to the writing of earlier versions of this manuscript and the expert review and comments to the manuscript provided by Philip Ross, PhD, both of Merck. The authors would also like to recognise the efforts of the study staff at the investigative sites, including the following lead investigators: Australia: J. Eden, J. Graham, M. Hooper, E. Seeman, J. Wark, C. White; Belgium: S. Boonen, Y. Boutsen, J. Kaufman, M. Malaise, J.-Y. Reginster. Brazil: J.F.M. Neto, J.R. Provenza; Canada: J. Brown, D. Kendler, A. Khan; Chile: A. Brizzolara, L. Villanueva; Costa Rica: A. Cob, W. Rios; Dominican Republic: J.V. de Camps, C. Velazco; Ecuador: C. Bracho; Finland: M. Valimaki; France: C.-L. Benhamou, F. Blotman, P. Delmas, L. Euller-Ziegler, P. Fardellone, Y. Maugars, C. Ribot, T. Thomas, G. Weryha; Greece: A. Avramides; Hungary: L. Koranyi, P. Lakatos; Italy: M.L. Brandi, C.E. Fiore, Q. Mela, R. Nuti; Jordan: B. Masri; Latvia: A. Lejnieks, I. Rasa; Lebanon: H. Awada, G. Maalouf, C. Saab; Lithuania: V. Alekna, M. Tamulaitiene, L. Valius; Malaysia: S.P. Chan; Peru: L. Danckers, R. Olavide, R. Salinas; Poland: R. Lorenc, S. Mackiewicz, T. Pertyński; Portugal: A. Faustino, J.M. Gomes; Slovenia: A. Kocijančič; Spain: J.J. Gomez-Reino, C. Lozano-Tonkin, J.L. Perez-Castrillon, M. Rodriguez-Perez, J. Roman-Ivorra; Taiwan: J.-F. Chen, S.-M. Hou; Thailand: B. Ongphiphadhanakul, K. Wilawan; UK: M. Davie, D. Hosking, R. Keen, D. Reid, O. Sahota, P. Selby, M. Stone; Venezuela: T. López.

[ClinicalTrials.gov registry number: 00092040]

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Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • David M. Reid
    • 1
  • David Hosking
    • 2
  • David Kendler
    • 3
  • Maria L. Brandi
    • 4
  • John D. Wark
    • 5
  • Georges Weryha
    • 6
  • João F. Marques-Neto
    • 7
  • Keavy A. Gaines
    • 8
  • Nadia Verbruggen
    • 8
  • Mary E. Melton
    • 8
  1. 1.Department of Medicine and Therapeutics, Medical School BuildingsUniversity of AberdeenForesterhillUK
  2. 2.Department of Bone and Mineral MetabolismNottingham City HospitalNottinghamUK
  3. 3.Clinical Research CentreSt Vincent’s HospitalVancouverCanada
  4. 4.Department of MedicineUniversity of FlorenceFlorenceItaly
  5. 5.Department of Medicine, Royal Melbourne HospitalUniversity of MelbourneParkvilleAustralia
  6. 6.Service d’EndocrinologieHôpital de BraboisNancyFrance
  7. 7.Department of RheumatologyState University (Unicamp)CampinasBrazil
  8. 8.Merck & Co., Inc.Whitehouse StationUSA

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