Recommendations for the registration of agents to be used in the prevention and treatment of glucocorticoid-induced osteoporosis: updated recommendations from the Group for the Respect of Ethics and Excellence in Science.
OBJECTIVE
The Group for the Respect and Excellence in Science (GREES) has reviewed and updated their recommendations for clinical trials to evaluate the efficacy and safety of new chemical entities to be used in the treatment and prevention of glucocorticoid-induced osteoporosis (GIOP).


METHODS
Consensus discussion of the committee.


RESULTS
With the exception of steroid use posttransplantation, there is no need to differentiate between underlying diseases. Prevention and treatment for GIOP are dependent on exposure to glucocorticoids rather than T-scores as in postmenopausal osteoporosis (PMO). If fracture data are obtained for PMO, it need not be repeated for GIOP, relying instead on bone mineral density (BMD) trials of at least 1 year. GREES recommends several changes in the previous guidance for GIOP. The committee saw no need to repeat preclinical studies if those have been previously done to assure bone quality in PMO. Similarly, phase I and phase II trials, if careful dose selection has been done for PMO, should not be repeated. The "prevention" and "treatment" claims should remain. Since the most recent evidence suggests significant increase in fracture risk for daily doses of prednisone of 5 mg/day or equivalent, clinical trials should concentrate on patients receiving at least this daily dosage. The emergence of bisphosphonates as the reference treatment, together with the rapid bone loss and high fracture incidence in glucocorticoid users, necessitates recommending a noninferiority trial design with lumbar spine BMD as the primary endpoint after 1 year.


CONCLUSIONS
Registration of new chemical entities to be used in the management of GIOP should be granted, based on a 1-year noninferiority trial, using BMD as primary outcome and alendronate or risedronate as comparator. Demonstration of antifracture efficacy should have been previously demonstrated in PMO.
Abadie
Eric C
EC
Department of Public Health, Epidemiology, and Health Economics, University of Liège, Liège, Belgium.
Devogealer
Jean-Pierre
JP
Ringe
Johann D
JD
Ethgen
Dominique J
DJ
Bouvenot
Gilles M
GM
Kreutz
Gottfried
G
Laslop
Andrea
A
Orloff
John J
JJ
Vanderauwera
Philippe M
PM
Delmas
Pierre D
PD
Dere
Willard H
WH
Branco
Jaime
J
Altman
Roy D
RD
Avouac
Bernard P
BP
Menkes
Charles J
CJ
Vanhaelst
Luc
L
Mitlak
Bruce H
BH
Tsouderos
Yannis
Y
Reginster
Jean-Yves L
JY
D002986:Clinical Trials as Topic; D005938:Glucocorticoids / Q000009:adverse effects*; D006287:Health Planning Guidelines; D006801:Humans; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D012216:Rheumatic Diseases / Q000188:drug therapy*
D005938:Glucocorticoids