Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis--a 2-year randomized placebo controlled trial.
The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS) trial was to investigate the efficacy and safety of different doses of SR, a novel agent in the treatment of postmenopausal osteoporosis. A randomized, multicenter, double-blind, placebo-controlled trial was undertaken in 353 osteoporotic women with at least one previous vertebral fracture and a lumbar T-score <-2.4. Patients were randomized to receive placebo, 0.5 g, 1 g, or 2 g SR/d for 2 yr. The primary efficacy endpoint was lumbar bone mineral density (BMD), assessed by dual-energy x-ray absorptiometry. Secondary outcome measures included femoral BMD, incidence of new vertebral deformities, and biochemical markers of bone metabolism. Lumbar BMD, adjusted for bone strontium content, increased in a dose-dependent manner in the intention-to-treat population: mean annual slope increased from 1.4% with 0.5 g/d SR to 3.0% with 2 g/d SR, which was significantly higher than placebo (P < 0.01). There was a significant reduction in the number of patients experiencing new vertebral deformities in the second year of treatment with 2 g/d SR [relative risk 0.56; 95% confidence interval (0.35; 0.89)]. In the 2 g/d group, there was a significant increase in serum levels of bone alkaline phosphatase, whereas urinary excretion of cross-linked N-telopeptide, a marker of bone resorption, was lower with SR than with placebo. All tested doses were well tolerated; the 2 g/d dose was considered to offer the best combination of efficacy and safety. In conclusion, SR therapy increased vertebral BMD and reduced the incidence of vertebral fractures.
Meunier
P J
PJ
Hôpital Edouard Herriot, 69437 Lyon, France. Meunier@lyon151.inserm.fr
Slosman
D O
DO
Delmas
P D
PD
Sebert
J L
JL
Brandi
M L
ML
Albanese
C
C
Lorenc
R
R
Pors-Nielsen
S
S
De Vernejoul
M C
MC
Roces
A
A
Reginster
J Y
JY
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015519:Bone Density; D001842:Bone and Bones / Q000201:enzymology; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000652:urine; D010919:Placebos; D012449:Safety; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D024042:Collagen Type I; D009942:Organometallic Compounds; D010455:Peptides; D010919:Placebos; D013876:Thiophenes; C052929:collagen type I trimeric cross-linked peptide; C081587:strontium ranelate; D003094:Collagen; D000469:Alkaline Phosphatase