TY - JOUR
T1 - Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis
AU - Schnitzer, T.
AU - Bone, H. G.
AU - Crepaldi, G.
AU - Adami, S.
AU - McClung, M.
AU - Kiel, D.
AU - Felsenberg, D.
AU - Recker, R. R.
AU - Tonino, R. P.
AU - Roux, C.
AU - Pinchera, A.
AU - Foldes, A. J.
AU - Greenspan, S. L.
AU - Levine, M. A.
AU - Emkey, R.
AU - Santora, A. C.
AU - Kaur, A.
AU - Thompson, D. E.
AU - Yates, J.
AU - Orloff, J. J.
N1 - Funding Information:
Clinical Centers Australia: C. Gilfillin, Monash Medical Centre, Melbourne Belgium: J. J. Body, Institut Jules Bordet, Bruxelles; S. Boonen, U.Z. Gasthuiberg, Leuven Finland: M. Valimaki, Helsinki Medical Center, Helsinki France: C. Roux, Centre d’Evaluation des Maladies Osseuses, Clinique de Rhumatologie-Hôpital Cochin, Paris; Germany: D. Felsenberg, Abtlg. Radiologische Diagnostik Freie Universitat Berlin Klinikum, Berlin; P. Donhauser, Poliklinik F. Physikalische Medizia und Rehabilitation Klinikum Innenstadt der LMU, München Israel: M. Popovtzer/ J. Foldes, The Jerusalem Osteoporosis Center Hadassah University Hospital, Jerusalem; R. Pollak, Department of Medicine Hadassah University Hospital, Jerusalem Italy: S. Adami, Cattedra di Reumatologia, Università degli Studi di Verona, Valeggio; G. Crepaldi, Istituto di Medicina Interna, Clinica Medica I, Università degli Studi di Padova, Padova; A. Pinchera, Is-tituto di Endocrinologia, Università degli Studi di Pisa, Pisa New Zealand: I. Reid, School of Medicine, University of Auckland, Auckland; N. Gilchrist, Older Persons Health Princess Margaret Hospital, Christchurch; J. Singh, Department of Geriatrics, North Shore Hospital, Auckland Norway: J. Halse, Betanien Medical Lab, Oslo, U. Syversen, Endokrinolo-gisk Seksjon Regionsykehuset, Trandheim; J. Stakkestad, Cecor AS, Haugesund; A. Huiseth, Sentrum Rontgeninstitutt, Oslo; S. Hem-minghytt, Specialistsenteret, Bodo Portugal: M. Gomes, Hospital Militar Principal Servicio de Reumatologia, Lisboa South Africa: P. Davis, Little Company of Mary Medical Centre, Pretoria; J.A. de Weerd, Pretoria East Private Hospital, Pretoria; S. Lips-chitz, Barney Hurwitz Hospital, Johannesburg; T. De Villiers, Panorama Medi-Clinic, Capetown Switzerland: R. Rizzoli, Hôpital Cantonal, Geneva; P. Jaeger, Medizinsche Universitatspoliklinki Inselspital, Bern United Kingdom: I. Smith, The Edgebright Partnership Medical Research Unit, Wrightington Hospital, Wigan Lancs United States: California: S.R. Weiss, San Diego Endocrine & Medical Clinic, San Diego, S. Harris, University of California, San Francisco; M. Greenwald, Osteoporosis Medical Center, Palm Springs; R. Marcus, VA Palo Alto Health Care System, Palo Alto Colorado: P. Miller, Colorado Center for Bone Research, Lakewood; D.A. Podlecki, Longmont Clinic, PC, Longmont Connecticut: K.L. Insogna, Yale University School of Medicine, New Haven Florida: M. Ettinger, Clinical Research Center of South Florida, Stuart; H. McIlwain, Tampa Medical Group, Tampa Georgia:
Funding Information:
We are greatly indebted to M. Daley and C. Peverly for their outstanding contributions in overseeing the conduct of this trial; to D. Tracey and A. Dynder for expert data coordination and statistical programming support; and to A. Barash and E. Pechillo for excellent administrative support. This study was supported by funding from Merck Research Laboratories, Rahway, New Jersey, USA.
PY - 2000/2
Y1 - 2000/2
N2 - Dosing convenience is a key element in the effective management of any chronic disease, and is particularly important in the long-term management of osteoporosis. Less frequent dosing with any medication may enhance compliance, thereby maximizing the effectiveness of therapy. Animal data support the rationale that once-weekly dosing with alendronate 70 mg (7 times the daily oral treatment dose) could provide similar efficacy to daily dosing with alendronate 10 mg due to its long duration of effect in bone. In addition, dog studies suggest that the potential for esophageal irritation, observed with daily oral bisphosphonates, may be substantially reduced with once-weekly dosing. This dosing regimen would provide patients with increased convenience and would be likely to enhance patient compliance. We compared the efficacy and safety of treatment with oral once-weekly alendronate 70 mg (N=519), twice-weekly alendronate 35 mg (N=369), and daily alendronate 10 mg (N=370) in a one-year, double-blind, multicenter study of postmenopausal women (ages 42 to 95) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak premenopausal mean, or prior vertebral or hip fracture). The primary efficacy endpoint was the comparability of increases in lumbar spine BMD, using strict pre-defined equivalence criteria. Secondary endpoints included changes in BMD at the hip and total body and rate of bone turnover, as assessed by biochemical markers. Both of the new regimens fully satisfied the equivalence criteria relative to daily therapy. Mean increases in lumbar spine BMD at 12 months were: 5.1% (95% CI 4.8, 5.4) in the 70 mg once-weekly group, 5.2% (4.9, 5.6) in the 35 mg twice-weekly group, and 5.4% (5.0, 5.8) in the 10 mg daily treatment group. Increases in BMD at the total hip, femoral neck, trochanter, and total body were similar for the three dosing regimens. All three treatment groups similarly reduced biochemical markers of bone resorption (urinary N- telopeptides of type I collagen) and bone formation (serum bone-specific alkaline phosphatase) into the middle of the premenopausal reference range. All treatment regimens were well tolerated with a similar incidence of upper GI adverse experiences. There were fewer serious upper GI adverse experiences and a trend toward a lower incidence of esophageal events in the once-weekly dosing group compared to the daily dosing group. These data are consistent with preclinical animal models, and suggest that once-weekly dosing has the potential for improved upper GI tolerability. Clinical fractures, captured as adverse experiences, were similar among the groups. We conclude that the alendronate 70 mg once-weekly dosing regimen will provide patients with a more convenient, therapeutically equivalent alternative to daily dosing, and may enhance compliance and long-term persistence with therapy. (C) 2000, Editrice Kurtis.
AB - Dosing convenience is a key element in the effective management of any chronic disease, and is particularly important in the long-term management of osteoporosis. Less frequent dosing with any medication may enhance compliance, thereby maximizing the effectiveness of therapy. Animal data support the rationale that once-weekly dosing with alendronate 70 mg (7 times the daily oral treatment dose) could provide similar efficacy to daily dosing with alendronate 10 mg due to its long duration of effect in bone. In addition, dog studies suggest that the potential for esophageal irritation, observed with daily oral bisphosphonates, may be substantially reduced with once-weekly dosing. This dosing regimen would provide patients with increased convenience and would be likely to enhance patient compliance. We compared the efficacy and safety of treatment with oral once-weekly alendronate 70 mg (N=519), twice-weekly alendronate 35 mg (N=369), and daily alendronate 10 mg (N=370) in a one-year, double-blind, multicenter study of postmenopausal women (ages 42 to 95) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak premenopausal mean, or prior vertebral or hip fracture). The primary efficacy endpoint was the comparability of increases in lumbar spine BMD, using strict pre-defined equivalence criteria. Secondary endpoints included changes in BMD at the hip and total body and rate of bone turnover, as assessed by biochemical markers. Both of the new regimens fully satisfied the equivalence criteria relative to daily therapy. Mean increases in lumbar spine BMD at 12 months were: 5.1% (95% CI 4.8, 5.4) in the 70 mg once-weekly group, 5.2% (4.9, 5.6) in the 35 mg twice-weekly group, and 5.4% (5.0, 5.8) in the 10 mg daily treatment group. Increases in BMD at the total hip, femoral neck, trochanter, and total body were similar for the three dosing regimens. All three treatment groups similarly reduced biochemical markers of bone resorption (urinary N- telopeptides of type I collagen) and bone formation (serum bone-specific alkaline phosphatase) into the middle of the premenopausal reference range. All treatment regimens were well tolerated with a similar incidence of upper GI adverse experiences. There were fewer serious upper GI adverse experiences and a trend toward a lower incidence of esophageal events in the once-weekly dosing group compared to the daily dosing group. These data are consistent with preclinical animal models, and suggest that once-weekly dosing has the potential for improved upper GI tolerability. Clinical fractures, captured as adverse experiences, were similar among the groups. We conclude that the alendronate 70 mg once-weekly dosing regimen will provide patients with a more convenient, therapeutically equivalent alternative to daily dosing, and may enhance compliance and long-term persistence with therapy. (C) 2000, Editrice Kurtis.
UR - http://www.scopus.com/inward/record.url?scp=0034097152&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034097152&partnerID=8YFLogxK
U2 - 10.1007/bf03339822
DO - 10.1007/bf03339822
M3 - Article
C2 - 10746426
AN - SCOPUS:0034097152
VL - 12
SP - 1
EP - 12
JO - Aging
JF - Aging
SN - 1594-0667
IS - 1
ER -