Strontium ranelate for preventing and treating postmenopausal osteoporosis.
BACKGROUND
Strontium ranelate is a new treatment for osteoporosis therefore, its benefits and harms need to be known.


OBJECTIVE
To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis.


METHODS
We searched MEDLINE (1996 to March 2005), EMBASE (1996 to week 9 2005), the Cochrane Library (1996 to Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors.


METHODS
We included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate versus placebo reporting fracture incidence, bone mineral density (BMD), health related quality of life or safety in postmenopausal women. Treatment (versus prevention) population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T score < -2.5 SD.


METHODS
Two reviewers independently determined study eligibility, assessed trial quality and extracted the relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose of strontium ranelate and treatment duration. Where possible, meta-analysis was conducted using the random effects model.


RESULTS
Four trials met the inclusion criteria. Three included a treatment population (0.5 to 2 g of strontium ranelate daily) and one a prevention population (0.125 g, 0.5 g and 1 g daily). A 37% reduction in vertebral fractures (RR 0.63, 95% CI 0.56, 0.71) and a 14% reduction in non-vertebral fractures (RR 0.86, 95% CI 0.75, 0.98) were demonstrated over three years with 2 g of strontium ranelate daily in a treatment population. An increase in BMD was shown at all BMD sites after two to three years in both populations. Lower doses of strontium ranelate were superior to placebo and the highest dose demonstrated the greatest reduction in vertebral fractures and increase in BMD. An increased risk of diarrhea with 2 g of strontium ranelate was found; however, adverse events did not affect the risk of discontinuing treatment nor did it increase the risk of serious side effects, gastritis or death. Additional data suggests that the risk of vascular and nervous system side-effects is slightly increased with taking 2 g of strontium ranelate daily over three to four years.


CONCLUSIONS
There is silver level evidence (www.cochranemsk.org) to support the efficacy of strontium ranelate for the reduction of fractures (vertebral and to a lesser extent non-vertebral) in postmenopausal osteoporotic women and an increase in BMD in postmenopausal women with/without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased with taking 2 g of strontium ranelate daily. Potential vascular and neurological side-effects need to be further explored.
O'Donnell
S
S
Ottawa Hospital, Division of Rheumatology, 1053 Carling Ave, Ottawa, Ontario, Canada.
Cranney
A
A
Wells
G A
GA
Adachi
J D
JD
Reginster
J Y
JY
D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D016103:Spinal Fractures; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*
D050071:Bone Density Conservation Agents; D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate