Bone safety with risedronate

histomorphometric studies at different dose levels and exposure

Robert R. Recker, L. G. Ste-Marie, P. Chavassieux, M. R. McClung, M. W. Lundy

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)327-337
Number of pages11
JournalOsteoporosis International
Volume26
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Safety
Bone and Bones
Bone Remodeling
Biopsy
Risedronate Sodium
Food-Drug Interactions
Physiologic Calcification
Osteomalacia
Primary Myelofibrosis
Breakfast
Diphosphonates
Tetracycline
Fluorescent Dyes
Bone Density
Biological Availability
Histology
Bone Marrow
Placebos
Therapeutics

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Bone safety with risedronate : histomorphometric studies at different dose levels and exposure. / Recker, Robert R.; Ste-Marie, L. G.; Chavassieux, P.; McClung, M. R.; Lundy, M. W.

In: Osteoporosis International, Vol. 26, No. 1, 2014, p. 327-337.

Research output: Contribution to journalArticle

Recker, Robert R. ; Ste-Marie, L. G. ; Chavassieux, P. ; McClung, M. R. ; Lundy, M. W. / Bone safety with risedronate : histomorphometric studies at different dose levels and exposure. In: Osteoporosis International. 2014 ; Vol. 26, No. 1. pp. 327-337.
@article{cbc8afebd09d42bb89fbd41555f92747,
title = "Bone safety with risedronate: histomorphometric studies at different dose levels and exposure",
abstract = "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.",
author = "Recker, {Robert R.} and Ste-Marie, {L. G.} and P. Chavassieux and McClung, {M. R.} and Lundy, {M. W.}",
year = "2014",
doi = "10.1007/s00198-014-2850-y",
language = "English",
volume = "26",
pages = "327--337",
journal = "Osteoporosis International",
issn = "0937-941X",
publisher = "Springer London",
number = "1",

}

TY - JOUR

T1 - Bone safety with risedronate

T2 - histomorphometric studies at different dose levels and exposure

AU - Recker, Robert R.

AU - Ste-Marie, L. G.

AU - Chavassieux, P.

AU - McClung, M. R.

AU - Lundy, M. W.

PY - 2014

Y1 - 2014

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.

UR - http://www.scopus.com/inward/record.url?scp=84920572956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84920572956&partnerID=8YFLogxK

U2 - 10.1007/s00198-014-2850-y

DO - 10.1007/s00198-014-2850-y

M3 - Article

VL - 26

SP - 327

EP - 337

JO - Osteoporosis International

JF - Osteoporosis International

SN - 0937-941X

IS - 1

ER -