Odanacatib, a cathepsin-K inhibitor for osteoporosis

A two-year study in postmenopausal women with low bone density

Henry G. Bone, Michael R. McClung, Christian Roux, Robert R. Recker, John A. Eisman, Nadia Verbruggen, Carolyn M. Hustad, Carolyn DaSilva, Arthur C. Santora, B. Avery Ince

Research output: Contribution to journalArticle

257 Citations (Scopus)

Abstract

Cathepsin K, a cysteine protease expressed in osteoclasts, degrades type 1 collagen. Odanacatib selectively and reversibly inhibited cathepsin K and rapidly decreased bone resorption in preclinical and phase I studies. A 1-year dose-finding trial with a 1-year extension on the same treatment assignment was performed in postmenopausal women with low bone mineral density (BMD) to evaluate the safety and efficacy of weekly doses of placebo or 3, 10, 25, or 50mg of odanacatib on BMD and biomarkers of skeletal remodeling. Women with BMD T-scores of -2.0 or less but not less than -3.5 at the lumbar spine or femoral sites were randomly assigned to receive placebo or one of four doses of odanacatib; all received vitamin D with calcium supplementation as needed. The primary endpoint was percentage change from baseline lumbar spine BMD. Other endpoints included percentage change in BMD at hip and forearm sites, as well as changes in biomarkers of skeletal remodeling. Twenty-four months of treatment produced progressive dose-related increases in BMD. With the 50-mg dose of odanacatib, lumbar spine and total-hip BMD increased 5.5% and 3.2%, respectively, whereas BMD at these sites was essentially unchanged with placebo (-0.2% and -0.9%). Biochemical markers of bone turnover exhibited dose-related changes. The safety and tolerability of odanacatib generally were similar to those of placebo, with no dose-related trends in any adverse experiences. In summary, 2 years of weekly odanacatib treatment was generally well-tolerated and increased lumbar spine and total-hip BMD in a dose-related manner in postmenopausal women with low BMD.

Original languageEnglish
Pages (from-to)937-947
Number of pages11
JournalJournal of Bone and Mineral Research
Volume25
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

Cathepsin K
Bone Density
Osteoporosis
Spine
Placebos
Pelvic Bones
Biomarkers
odanacatib
Safety
Cysteine Proteases
Bone Remodeling
Osteoclasts
Bone Resorption
Collagen Type I
Thigh
Forearm
Vitamin D
Hip
Therapeutics

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Odanacatib, a cathepsin-K inhibitor for osteoporosis : A two-year study in postmenopausal women with low bone density. / Bone, Henry G.; McClung, Michael R.; Roux, Christian; Recker, Robert R.; Eisman, John A.; Verbruggen, Nadia; Hustad, Carolyn M.; DaSilva, Carolyn; Santora, Arthur C.; Ince, B. Avery.

In: Journal of Bone and Mineral Research, Vol. 25, No. 5, 05.2010, p. 937-947.

Research output: Contribution to journalArticle

Bone, HG, McClung, MR, Roux, C, Recker, RR, Eisman, JA, Verbruggen, N, Hustad, CM, DaSilva, C, Santora, AC & Ince, BA 2010, 'Odanacatib, a cathepsin-K inhibitor for osteoporosis: A two-year study in postmenopausal women with low bone density', Journal of Bone and Mineral Research, vol. 25, no. 5, pp. 937-947. https://doi.org/10.1359/jbmr.091035
Bone, Henry G. ; McClung, Michael R. ; Roux, Christian ; Recker, Robert R. ; Eisman, John A. ; Verbruggen, Nadia ; Hustad, Carolyn M. ; DaSilva, Carolyn ; Santora, Arthur C. ; Ince, B. Avery. / Odanacatib, a cathepsin-K inhibitor for osteoporosis : A two-year study in postmenopausal women with low bone density. In: Journal of Bone and Mineral Research. 2010 ; Vol. 25, No. 5. pp. 937-947.
@article{9f8c8ea8f2924c2e8c52b2d76254e98a,
title = "Odanacatib, a cathepsin-K inhibitor for osteoporosis: A two-year study in postmenopausal women with low bone density",
abstract = "Cathepsin K, a cysteine protease expressed in osteoclasts, degrades type 1 collagen. Odanacatib selectively and reversibly inhibited cathepsin K and rapidly decreased bone resorption in preclinical and phase I studies. A 1-year dose-finding trial with a 1-year extension on the same treatment assignment was performed in postmenopausal women with low bone mineral density (BMD) to evaluate the safety and efficacy of weekly doses of placebo or 3, 10, 25, or 50mg of odanacatib on BMD and biomarkers of skeletal remodeling. Women with BMD T-scores of -2.0 or less but not less than -3.5 at the lumbar spine or femoral sites were randomly assigned to receive placebo or one of four doses of odanacatib; all received vitamin D with calcium supplementation as needed. The primary endpoint was percentage change from baseline lumbar spine BMD. Other endpoints included percentage change in BMD at hip and forearm sites, as well as changes in biomarkers of skeletal remodeling. Twenty-four months of treatment produced progressive dose-related increases in BMD. With the 50-mg dose of odanacatib, lumbar spine and total-hip BMD increased 5.5{\%} and 3.2{\%}, respectively, whereas BMD at these sites was essentially unchanged with placebo (-0.2{\%} and -0.9{\%}). Biochemical markers of bone turnover exhibited dose-related changes. The safety and tolerability of odanacatib generally were similar to those of placebo, with no dose-related trends in any adverse experiences. In summary, 2 years of weekly odanacatib treatment was generally well-tolerated and increased lumbar spine and total-hip BMD in a dose-related manner in postmenopausal women with low BMD.",
author = "Bone, {Henry G.} and McClung, {Michael R.} and Christian Roux and Recker, {Robert R.} and Eisman, {John A.} and Nadia Verbruggen and Hustad, {Carolyn M.} and Carolyn DaSilva and Santora, {Arthur C.} and Ince, {B. Avery}",
year = "2010",
month = "5",
doi = "10.1359/jbmr.091035",
language = "English",
volume = "25",
pages = "937--947",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Odanacatib, a cathepsin-K inhibitor for osteoporosis

T2 - A two-year study in postmenopausal women with low bone density

AU - Bone, Henry G.

AU - McClung, Michael R.

AU - Roux, Christian

AU - Recker, Robert R.

AU - Eisman, John A.

AU - Verbruggen, Nadia

AU - Hustad, Carolyn M.

AU - DaSilva, Carolyn

AU - Santora, Arthur C.

AU - Ince, B. Avery

PY - 2010/5

Y1 - 2010/5

N2 - Cathepsin K, a cysteine protease expressed in osteoclasts, degrades type 1 collagen. Odanacatib selectively and reversibly inhibited cathepsin K and rapidly decreased bone resorption in preclinical and phase I studies. A 1-year dose-finding trial with a 1-year extension on the same treatment assignment was performed in postmenopausal women with low bone mineral density (BMD) to evaluate the safety and efficacy of weekly doses of placebo or 3, 10, 25, or 50mg of odanacatib on BMD and biomarkers of skeletal remodeling. Women with BMD T-scores of -2.0 or less but not less than -3.5 at the lumbar spine or femoral sites were randomly assigned to receive placebo or one of four doses of odanacatib; all received vitamin D with calcium supplementation as needed. The primary endpoint was percentage change from baseline lumbar spine BMD. Other endpoints included percentage change in BMD at hip and forearm sites, as well as changes in biomarkers of skeletal remodeling. Twenty-four months of treatment produced progressive dose-related increases in BMD. With the 50-mg dose of odanacatib, lumbar spine and total-hip BMD increased 5.5% and 3.2%, respectively, whereas BMD at these sites was essentially unchanged with placebo (-0.2% and -0.9%). Biochemical markers of bone turnover exhibited dose-related changes. The safety and tolerability of odanacatib generally were similar to those of placebo, with no dose-related trends in any adverse experiences. In summary, 2 years of weekly odanacatib treatment was generally well-tolerated and increased lumbar spine and total-hip BMD in a dose-related manner in postmenopausal women with low BMD.

AB - Cathepsin K, a cysteine protease expressed in osteoclasts, degrades type 1 collagen. Odanacatib selectively and reversibly inhibited cathepsin K and rapidly decreased bone resorption in preclinical and phase I studies. A 1-year dose-finding trial with a 1-year extension on the same treatment assignment was performed in postmenopausal women with low bone mineral density (BMD) to evaluate the safety and efficacy of weekly doses of placebo or 3, 10, 25, or 50mg of odanacatib on BMD and biomarkers of skeletal remodeling. Women with BMD T-scores of -2.0 or less but not less than -3.5 at the lumbar spine or femoral sites were randomly assigned to receive placebo or one of four doses of odanacatib; all received vitamin D with calcium supplementation as needed. The primary endpoint was percentage change from baseline lumbar spine BMD. Other endpoints included percentage change in BMD at hip and forearm sites, as well as changes in biomarkers of skeletal remodeling. Twenty-four months of treatment produced progressive dose-related increases in BMD. With the 50-mg dose of odanacatib, lumbar spine and total-hip BMD increased 5.5% and 3.2%, respectively, whereas BMD at these sites was essentially unchanged with placebo (-0.2% and -0.9%). Biochemical markers of bone turnover exhibited dose-related changes. The safety and tolerability of odanacatib generally were similar to those of placebo, with no dose-related trends in any adverse experiences. In summary, 2 years of weekly odanacatib treatment was generally well-tolerated and increased lumbar spine and total-hip BMD in a dose-related manner in postmenopausal women with low BMD.

UR - http://www.scopus.com/inward/record.url?scp=77953510486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953510486&partnerID=8YFLogxK

U2 - 10.1359/jbmr.091035

DO - 10.1359/jbmr.091035

M3 - Article

VL - 25

SP - 937

EP - 947

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 5

ER -