Comparing Tolerability and Efficacy of Generic versus Brand Alendronate: A Randomized Clinical Study in Postmenopausal Women with a Recent Fracture.

J.P. van den Bergh; M.E. Bouts; E. van der Veer; R.Y. van der Velde; M.J. Janssen; P.P. Geusens; B. Winkens; N.J. Oldenhof; T.A. van Geel

doi:10.1371/journal.pone.0078153

Comparing Tolerability and Efficacy of Generic versus Brand Alendronate: A Randomized Clinical Study in Postmenopausal Women with a Recent Fracture.

J.P. van den Bergh, M.E. Bouts, E. van der Veer, R.Y. van der Velde, M.J. Janssen, P.P. Geusens, B. Winkens, N.J. Oldenhof, T.A. van Geel^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Introduction: An increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate.

Methods: In a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4+/-6.4 years) with osteoporosis were treated with generic and branded alendronate during 24 (2x12) weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS) and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). No wash out period was allowed (ethical reasons). Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models.

Results: There were no significant differences in overall tolerance (GSRS) between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B): 0.40; 95% CI: 0.05 to 0.74, p = 0.024). The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p <0.001). Mean level of CTX was significantly lower with branded at week 4 (B: 121.3; 95% CI: 52.0 to 190.5), but not at week 12 (B: 53.6; 95% CI:-3.7 to 110.9). No significant differences were found for PINP at week 4 or 12.

Conclusions: Bone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients with a recent fracture.

Trial Registration: Dutch Trial Register NTR number 1867 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1867

Original language	English
Article number	78153
Number of pages	9
Journal	PLOS ONE
Volume	8
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0078153
Publication status	Published - 21 Oct 2013

Keywords

BONE TURNOVER MARKERS
LIAISON SERVICES
SODIUM TABLETS
OSTEOPOROSIS
DISINTEGRATION
IMPLEMENTATION
SUBSTITUTION
COPIES
SCALE

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Cite this

van den Bergh, J. P., Bouts, M. E., van der Veer, E., van der Velde, R. Y., Janssen, M. J., Geusens, P. P., Winkens, B., Oldenhof, N. J., & van Geel, T. A. (2013). Comparing Tolerability and Efficacy of Generic versus Brand Alendronate: A Randomized Clinical Study in Postmenopausal Women with a Recent Fracture. PLOS ONE, 8(10), Article 78153. https://doi.org/10.1371/journal.pone.0078153

@article{abb1807e9e6544ef82a78e94732c8a59,

title = "Comparing Tolerability and Efficacy of Generic versus Brand Alendronate: A Randomized Clinical Study in Postmenopausal Women with a Recent Fracture.",

abstract = "Introduction: An increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate.Methods: In a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4+/-6.4 years) with osteoporosis were treated with generic and branded alendronate during 24 (2x12) weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS) and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). No wash out period was allowed (ethical reasons). Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models.Results: There were no significant differences in overall tolerance (GSRS) between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B): 0.40; 95% CI: 0.05 to 0.74, p = 0.024). The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p <0.001). Mean level of CTX was significantly lower with branded at week 4 (B: 121.3; 95% CI: 52.0 to 190.5), but not at week 12 (B: 53.6; 95% CI:-3.7 to 110.9). No significant differences were found for PINP at week 4 or 12.Conclusions: Bone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients with a recent fracture.Trial Registration: Dutch Trial Register NTR number 1867 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1867",

keywords = "BONE TURNOVER MARKERS, LIAISON SERVICES, SODIUM TABLETS, OSTEOPOROSIS, DISINTEGRATION, IMPLEMENTATION, SUBSTITUTION, COPIES, SCALE",

author = "{van den Bergh}, J.P. and M.E. Bouts and {van der Veer}, E. and {van der Velde}, R.Y. and M.J. Janssen and P.P. Geusens and B. Winkens and N.J. Oldenhof and {van Geel}, T.A.",

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month = oct,

day = "21",

doi = "10.1371/journal.pone.0078153",

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T1 - Comparing Tolerability and Efficacy of Generic versus Brand Alendronate: A Randomized Clinical Study in Postmenopausal Women with a Recent Fracture.

AU - van den Bergh, J.P.

AU - Bouts, M.E.

AU - van der Veer, E.

AU - van der Velde, R.Y.

AU - Janssen, M.J.

AU - Geusens, P.P.

AU - Winkens, B.

AU - Oldenhof, N.J.

AU - van Geel, T.A.

PY - 2013/10/21

Y1 - 2013/10/21

N2 - Introduction: An increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate.Methods: In a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4+/-6.4 years) with osteoporosis were treated with generic and branded alendronate during 24 (2x12) weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS) and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). No wash out period was allowed (ethical reasons). Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models.Results: There were no significant differences in overall tolerance (GSRS) between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B): 0.40; 95% CI: 0.05 to 0.74, p = 0.024). The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p <0.001). Mean level of CTX was significantly lower with branded at week 4 (B: 121.3; 95% CI: 52.0 to 190.5), but not at week 12 (B: 53.6; 95% CI:-3.7 to 110.9). No significant differences were found for PINP at week 4 or 12.Conclusions: Bone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients with a recent fracture.Trial Registration: Dutch Trial Register NTR number 1867 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1867

AB - Introduction: An increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate.Methods: In a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4+/-6.4 years) with osteoporosis were treated with generic and branded alendronate during 24 (2x12) weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS) and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). No wash out period was allowed (ethical reasons). Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models.Results: There were no significant differences in overall tolerance (GSRS) between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B): 0.40; 95% CI: 0.05 to 0.74, p = 0.024). The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p <0.001). Mean level of CTX was significantly lower with branded at week 4 (B: 121.3; 95% CI: 52.0 to 190.5), but not at week 12 (B: 53.6; 95% CI:-3.7 to 110.9). No significant differences were found for PINP at week 4 or 12.Conclusions: Bone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients with a recent fracture.Trial Registration: Dutch Trial Register NTR number 1867 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1867

KW - BONE TURNOVER MARKERS

KW - LIAISON SERVICES

KW - SODIUM TABLETS

KW - OSTEOPOROSIS

KW - DISINTEGRATION

KW - IMPLEMENTATION

KW - SUBSTITUTION

KW - COPIES

KW - SCALE

U2 - 10.1371/journal.pone.0078153

DO - 10.1371/journal.pone.0078153

M3 - Article

SN - 1932-6203

VL - 8

JO - PLOS ONE

JF - PLOS ONE

IS - 10

M1 - 78153

ER -