Vertebral antifracture efficacy of strontium rane

Authors: J Collette O Bruyère J M Kaufman R Lorenc D Felsenberg T D Spector M Diaz Curiel S Boonen JY Reginster

Publish Date: 2009/05/13

Volume: 21, Issue: 2, Pages: 233-241

PDF Link

Abstract

Osteoporotic postmenopausal women patients in two randomised trials comparing the antifracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption The vertebral antifracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levelsBone turnover BTO levels vary among women at risk of osteoporotic fracture Strontium ranelate is an antiosteoporotic treatment increasing bone formation and reducing bone resorption It was hypothesised that its antifracture efficacy would be independent of baseline BTO levelsPostmenopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers bonespecific alkaline phosphatase bALP n = 4995 and serum Ctelopeptide crosslinks sCTX n = 4891 Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placeboIn the placebo group relative risk of vertebral fractures increased with BTO tertiles by 32 and 24 for patients in the highest tertile for bALP and CTX respectively compared to those in the lowest tertile In the strontium ranelate group incidences of vertebral fracture did not differ significantly across BTO tertiles Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers with relative risk reductions of 31 to 47 relative to placebo Risk reduction did not differ among tertiles bALP p = 0513 sCTX p = 0290Osteoporosis is a complex disease and many factors may contribute to the skeletal fragility that underlies osteoporotic fractures 1 Two processes are thought to be particularly important in postmenopausal osteoporosis First during adult life in both men and women resorption of bone tends to exceed bone formation at each of the basic multicellular units that are responsible for bone remodelling Secondly relative oestrogen deficiency in women after the menopause increases the rate of bone remodelling accelerating the net loss of bone 2 3 During longterm treatment antiresorptive antiosteoporotic agents act primarily by decreasing the rate of bone remodelling 4 For example during treatment with the bisphosphonate alendronate some biochemical markers of bone resorption show a rapid decrease of 50 to 65 within 1 month of treatment However this is accompanied by a delayed decrease in markers of bone formation of approximately 50 which reaches a nadir between 6 and 12 months 5 It might be predicted that baseline bone turnover rates could influence the effects of treatment with antiresorptive and other antiosteoporotic agents For example antiresorptive agents might be expected to be of greatest benefit to women with high levels of bone turnover while bone formation agents might be most effective in women with low rates of bone formationStudies of the effects of antiresorptive agents on bone mineral density BMD have generally shown larger treatment effects in women with high pretreatment levels of bone turnover 6 7 8 9 10 However results for osteoporotic fracture risk have been less consistent 11 12 The effects of teriparatide an agent that increases bone formation on BMD were also greater in women with high bone turnover 13 but the reduction in the relative risk of osteoporotic fracture was independent of the pretreatment bone turnover level 14Strontium ranelate is an oral antiosteoporotic agent that reduces the risk of vertebral 15 nonvertebral and hip 16 fractures in postmenopausal osteoporotic women Experiments in vitro and in animals 17 18 as well as measurements of biochemical markers of bone turnover in osteoporotic women in a clinical trial 15 have shown that strontium ranelate simultaneously stimulates bone formation and reduces bone resorption although individual effects are less pronounced than those induced by PTH or bisphosphonates Two previous analyses have demonstrated that strontium ranelate reduces the risk to have a new vertebral fracture in patients with a wide range of osteoporosis severity in osteopenic patients with and without previous fractures in osteoporotic patients without prevalent vertebral fractures and in severe osteoporotic patients at least two prevalent vertebral fractures 19 20 The purpose of the present study was to determine whether the efficacy of strontium ranelate in increasing lumbar BMD and reducing vertebral fracture risk in postmenopausal women is influenced by the pretreatment level of biochemical markers of bone turnover using data obtained over 3 years in two large placebocontrolled clinical trials the Spinal Osteoporosis Therapeutic Intervention SOTI study 15 and the Treatment of Peripheral Osteoporosis TROPOS study 16 Given the specific effects on bone turnover and its wide efficacy profile to date we hypothesise that its efficacy would be independent of pretreatment bone turnover levels

Keywords: