Effect of odanacatib on BMD and fractures: estimates from Bayesian univariate and bivariate meta-analyses.
BACKGROUND
Odanacatib (ODN), a selective cathepsin-K inhibitor, was found to increase bone mineral density (BMD); the effect on fractures is based on adverse event reports.


OBJECTIVE
To estimate current effects and predict future effects of ODN on BMD and fractures.


METHODS
Electronic databases (Medline, EMBASE, Cochrane Library), conference proceedings, and bibliographies.


METHODS
Trials that compared ODN 50 mg/wk to placebo for at least 1 year and reported changes in BMD or fractures. Meta-analysis: Two bone outcomes were pooled as independent and as joint outcomes in Bayesian univariate and bivariate random-effects models.


RESULTS
Of 32 potentially eligible articles, six citations describing four trials (993 patients) were included. ODN for 3 years increased mean BMD at the lumbar spine by 5.0% (95% credible interval [CrI], 2.7, 7.5), total hip by 3.6% (95% CrI, 1.6, 5.9), and femoral neck (FN) by 3.6% (95% CrI, 1.6, 5.7). In a future trial of 3-year duration, the predicted mean increase in BMD, adjusted for the effect on fractures, was 4.9% for lumbar spine (95% CrI, 2.5, 7.4), 3.4% for total hip (95% CrI, 1.7, 5.2), and 3.5% for FN (95% CrI, 1.8, 5.3). After accounting for the effect on FN BMD, ODN for 3 years was associated with a population odds ratio of 0.38 (95% CrI, 0.1, 0.8). In a future trial, the odds ratio was 0.41 (95% CrI, 0.1, 1.1). The probability of benefit on fractures was 96-99%. The estimates remained robust in sensitivity analyses.


CONCLUSIONS
Our analyses suggest that ODN will increase BMD and decrease all fractures in the fracture outcome trial; however, direct demonstration of this antifracture efficacy is needed.
Osteoporosis Program (O.G.-V., J.S., A.M.C.), University Health Network/Mt Sinai Hospital, Toronto, ON M5G 2C4, Canada; Institute of Health Policy, Management and Evaluation (G.T., A.M.C.), and Department of Medicine (G.T., R.J., A.M.C.), University of Toronto, Toronto, ON M5T 3M6, Canada; St Joseph's Healthcare and McMaster University (J.D.A.), Hamilton, ON L8N 1Y2, Canada; St Michael's Hospital (R.J.), Toronto, ON M5C 2T2, Canada; and Centre Hospitalier Universitaire de Québec Research Centre and Laval University (J.P.B.), Quebec, QC G1V 4G2, Canada.
Olga
O
Gajic-Veljanoski
George
G
Tomlinson
Jeevitha
J
Srighanthan
Jonathan D
JD
Adachi
Robert
R
Josse
Jacques P
JP
Brown
Angela M
AM
Cheung
D001499:Bayes Theorem; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects*; D056657:Cathepsin K / Q000037:antagonists & inhibitors*; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D001713:Biphenyl Compounds; C534130:CTSK protein, human; D056657:Cathepsin K; C527128:odanacatib