title: Strontium ranelate: a new paradigm in the treatment of osteoporosis.
abstract: In vitro, strontium ranelate increases collagen and non-collagenic protein synthesis by mature osteoblast-enriched cells. The effects of strontium ranelate on bone formation were confirmed as the drug enhanced preosteoblastic cell replication. In the isolated osteoclast, a preincubation of bone slices with strontium ranelate induced a dose-dependent inhibition of the bone resorbing activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited preosteoclast differentiation. The drug was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomised study. At the conclusion of the study, the percentage variation of lumbar bone mineral density (BMD) from baseline was significantly different in the group receiving strontium ranelate 1000 mg/day as compared with placebo (+5.53 versus -0.75%, respectively). Increase in total hip and neck BMD averages were 3.2 and 2.5%, respectively. The effect of strontium ranelate in postmenopausal women with established osteoporosis was assessed during a multinational, prospective, double-blind, randomised, placebo-controlled trial. Strontium ranelate (500, 1000, 2000 mg/day) or placebo were given to 353 Caucasian women with prevalent vertebral osteoporosis. At the conclusion of this 2-year study, the annual increase in lumbar BMD of the group receiving strontium ranelate 2000 mg was 7.3% (p < 0.001). A significant increase in bone alkaline phophatase (p = 0.002) over a 6-month period and a significant decrease in N-telopeptide crosslinks (p = 0.004) throughout the 2-year period were seen in the group receiving 2000 mg of strontium ranelate. During the second year of treatment, the dose of 2000 mg was associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. Bone histomorphometry showed no mineralisation defects. The primary analysis of the SOTI study, evaluating the effect of strontium ranelate 2000 mg on vertebral fracture rates, revealed a 41% reduction in the relative risk of patients experiencing a first new vertebral fracture with strontium ranelate throughout the 3-year study. The TROPOS study showed a significant reduction in the risk of experiencing a first non-vertebral fracture in the group treated with strontium ranelate throughout the 3-year study. A reduction in the risk of experiencing a hip fracture was also demonstrated in the patients treated for > or = 18 months.
authors.affiliation: Bone and Cartilage Metabolism Research Unit, CHU Centre'Ville, Policliniques Lucien Brull, Quai Godefroid Kurth 45 (9ème étage), 4020 Liege, Belgium. jyreginster@ulg.ac.be
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Reginster
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Lecart
authors.forename: Rita
authors.initials: R
authors.lastname: Deroisy
authors.forename: Christian
authors.initials: C
authors.lastname: Lousberg
mesh_terms: D000818:Animals; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use*; D010024:Osteoporosis / Q000188:drug therapy*; D013876:Thiophenes / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate