TY - JOUR
T1 - Bone safety with risedronate
T2 - histomorphometric studies at different dose levels and exposure
AU - Recker, R. R.
AU - Ste-Marie, L. G.
AU - Chavassieux, P.
AU - McClung, M. R.
AU - Lundy, M. W.
N1 - Funding Information:
The study, as well as writing and editorial support, was funded by Warner Chilcott (US) LLC and Sanofi. The authors had full access to the data and were involved in the preparation of the manuscript. The authors played a significant role in writing this manuscript, critically reviewed all versions of the manuscript, and take full responsibility for all content and the decision to submit the manuscript. None of the authors received any form of compensation related to the development of this manuscript. This manuscript was prepared conforming to the guidelines of the International Committee of Medical Journal Editors. The authors would like to thank Tam Vo, PhD, from Excerpta Medica for providing editorial and writing assistance in the preparation of this manuscript.
Publisher Copyright:
© 2014, International Osteoporosis Foundation and National Osteoporosis Foundation.
PY - 2014/1
Y1 - 2014/1
N2 - Methods: Bridging studies, with bone mineral density as the primary endpoint, demonstrated non-inferiority of risedronate 35 mg and 50 mg once a week, risedronate 150 mg once a month, and a risedronate 75-mg dose on two consecutive days a month versus risedronate 5 mg daily. The low oral bioavailability and known dosing limitations due to food interactions of bisphosphonates have led to development of an oral delayed-release dose form of risedronate 35 mg to be taken weekly, before or after breakfast. Bone biopsies were collected at 24 months in studies involving these risedronate dosing regimens; bone safety and histomorphometric data were evaluated.Results: Qualitative bone histology showed normal mineralization of newly formed bone without evidence of pathological findings, such as osteomalacia, bone marrow dyscrasia, or bone marrow fibrosis. Importantly, ongoing bone remodeling, based on fluorochrome labeling, was observed in all patients regardless of dose and exposure. Key histomorphometric variables were comparable to those observed with the risedronate 5 mg daily dose and were within the range seen in healthy pre- and post-menopausal women.Conclusions: Overall, the results are reassuring with respect to bone safety and histomorphometric data, and do not suggest oversuppression of bone remodeling during treatment with these established risedronate regimens.Summary: This report describes bone safety and histomorphometric data across different dose levels and dosing frequencies of risedronate. Normal bone structure and histomorphometric data were observed, with ongoing bone remodeling and mineralization regardless of dose. These data are reassuring and do not suggest compromised bone remodeling during treatment with established risedronate regimens.Introduction: The efficacy and bone safety of risedronate 5 mg daily were established in pivotal phase III randomized, placebo-controlled clinical studies. Histomorphometric analysis of paired biopsies demonstrated bone safety as reflected by presence of fluorescent tetracycline double-labels in all evaluable biopsies. This report describes bone safety and histomorphometric data across studies of various dose regimens of risedronate.
AB - Methods: Bridging studies, with bone mineral density as the primary endpoint, demonstrated non-inferiority of risedronate 35 mg and 50 mg once a week, risedronate 150 mg once a month, and a risedronate 75-mg dose on two consecutive days a month versus risedronate 5 mg daily. The low oral bioavailability and known dosing limitations due to food interactions of bisphosphonates have led to development of an oral delayed-release dose form of risedronate 35 mg to be taken weekly, before or after breakfast. Bone biopsies were collected at 24 months in studies involving these risedronate dosing regimens; bone safety and histomorphometric data were evaluated.Results: Qualitative bone histology showed normal mineralization of newly formed bone without evidence of pathological findings, such as osteomalacia, bone marrow dyscrasia, or bone marrow fibrosis. Importantly, ongoing bone remodeling, based on fluorochrome labeling, was observed in all patients regardless of dose and exposure. Key histomorphometric variables were comparable to those observed with the risedronate 5 mg daily dose and were within the range seen in healthy pre- and post-menopausal women.Conclusions: Overall, the results are reassuring with respect to bone safety and histomorphometric data, and do not suggest oversuppression of bone remodeling during treatment with these established risedronate regimens.Summary: This report describes bone safety and histomorphometric data across different dose levels and dosing frequencies of risedronate. Normal bone structure and histomorphometric data were observed, with ongoing bone remodeling and mineralization regardless of dose. These data are reassuring and do not suggest compromised bone remodeling during treatment with established risedronate regimens.Introduction: The efficacy and bone safety of risedronate 5 mg daily were established in pivotal phase III randomized, placebo-controlled clinical studies. Histomorphometric analysis of paired biopsies demonstrated bone safety as reflected by presence of fluorescent tetracycline double-labels in all evaluable biopsies. This report describes bone safety and histomorphometric data across studies of various dose regimens of risedronate.
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U2 - 10.1007/s00198-014-2850-y
DO - 10.1007/s00198-014-2850-y
M3 - Article
C2 - 25304456
AN - SCOPUS:84920572956
VL - 26
SP - 327
EP - 337
JO - Osteoporosis International
JF - Osteoporosis International
SN - 0937-941X
IS - 1
ER -