title: Combination therapy with risedronate and teriparatide in male osteoporosis.
abstract: Most studies of combination therapy with teriparatide and a bisphosphonate have not shown greater efficacy over monotherapy. The bisphosphonate risedronate, has not been studied in this context. The purpose of this proof-of-concept study was to assess whether combination risedronate and teriparatide increases bone mineral density (BMD) more than monotherapy with either drug alone. This was a randomized, double-blinded study of risedronate (35 mg weekly plus placebo injection), teriparatide (20 μg subcutaneously daily plus placebo tablet), or both risedronate plus teriparatide (combination) for 18 months in 29 men with low BMD. The primary endpoint was percentage change in lumbar spine (LS) BMD at 18 months. Secondary outcomes included changes in bone markers and BMD at other sites and interim time-points. All therapies increased LS BMD as compared with baseline (p < 0.05), but there were no between-group differences at 18 months. Total hip (TH) BMD increased to a greater extent in the combination group (mean ± SEM, 3.86 ± 1.1 %) versus teriparatide (0.29 ± 0.95 %) or risedronate (0.82 ± 0.95 %; p < 0.05 for both). Femoral neck (FN) BMD also increased more in the combination group (8.45 ± 1.8 %) versus risedronate (0.50 ± 1.7 %; p = 0.002), but was not different from teriparatide alone. In the combination group, P1NP and CTX increased rapidly, mirroring the teriparatide-alone arm. There were no between-group differences in adverse events. Combination teriparatide and risedronate increased BMD at the LS, TH as well as the FN and provided greater BMD increases at the TH than monotherapy. The results suggest combination risedronate and teriparatide therapy holds promise as a treatment for osteoporosis.
authors.affiliation: Metabolic Bone Diseases Unit, Division of Endocrinology, Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, PH 8W-864, New York, NY 10032, USA. mad2037@columbia.edu
authors.forename: Marcella D
authors.initials: MD
authors.lastname: Walker
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Cusano
authors.forename: James
authors.initials: J
authors.lastname: Sliney
authors.forename: Megan
authors.initials: M
authors.lastname: Romano
authors.forename: Chiyuan
authors.initials: C
authors.lastname: Zhang
authors.forename: Donald J
authors.initials: DJ
authors.lastname: McMahon
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005272:Femur Neck; D006801:Humans; D007279:Injections, Subcutaneous; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy*; D010919:Placebos; D000068296:Risedronic Acid; D019379:Teriparatide / Q000008:administration & dosage*
chemical_list: D050071:Bone Density Conservation Agents; D010919:Placebos; D019379:Teriparatide; D000068296:Risedronic Acid; D012968:Etidronic Acid