Bone safety with risedronate: histomorphometric studies at different dose levels and exposure View Full Text


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Article Info

DATE

2014-10-11

AUTHORS

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

ABSTRACT

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.IntroductionThe 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.MethodsBridging 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.ResultsQualitative 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.ConclusionsOverall, 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. More... »

PAGES

327-337

References to SciGraph publications

  • 2004-10-14. Five Years of Treatment with Risedronate and its Effects on Bone Safety in Women with Postmenopausal Osteoporosis in CALCIFIED TISSUE INTERNATIONAL
  • 2000-01. Randomized Trial of the Effects of Risedronate on Vertebral Fractures in Women with Established Postmenopausal Osteoporosis in OSTEOPOROSIS INTERNATIONAL
  • 1969-12. Tetracycline-based histological analysis of bone remodeling in CALCIFIED TISSUE RESEARCH
  • 2003-04. ECTS Program in CALCIFIED TISSUE INTERNATIONAL
  • 2003-01. Bisphosphonate mechanism of action in CURRENT RHEUMATOLOGY REPORTS
  • 1970-12. The influence of pyrophosphate, condensed phosphates, phosphonates and other phosphate compounds on the dissolution of hydroxyapatitein vitro and on bone resorption induced by parathyroid hormone in tissue culture and in thyroparathyroidectomised rats in CALCIFIED TISSUE RESEARCH
  • 2012-11-13. A Novel Monthly Dosing Regimen of Risedronate for the Treatment of Postmenopausal Osteoporosis: 2-Year Data in CALCIFIED TISSUE INTERNATIONAL
  • 2004-01-16. Histomorphometric evaluation of daily and intermittent oral ibandronate in women with postmenopausal osteoporosis: results from the BONE study in OSTEOPOROSIS INTERNATIONAL
  • 2012-06-30. Efficacy and safety of risedronate 150-mg once a month in the treatment of postmenopausal osteoporosis: 2-year data in OSTEOPOROSIS INTERNATIONAL
  • 2003-08-29. Remodeling and skeletal fragility in OSTEOPOROSIS INTERNATIONAL
  • 2011-09-27. Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet in OSTEOPOROSIS INTERNATIONAL
  • Identifiers

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    http://scigraph.springernature.com/pub.10.1007/s00198-014-2850-y

    DOI

    http://dx.doi.org/10.1007/s00198-014-2850-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1044416054

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25304456


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