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Intervention Review

Strontium ranelate for preventing and treating postmenopausal osteoporosis

  1. S O'Donnell,
  2. A Cranney,
  3. GA Wells,
  4. JD Adachi,
  5. JY Reginster

Editorial Group: Cochrane Musculoskeletal Group

Published Online: 19 JUL 2006

DOI: 10.1002/14651858.CD005326.pub2


How to Cite

O'Donnell S, Cranney A, Wells GA, Adachi JD, Reginster JY. Strontium ranelate for preventing and treating postmenopausal osteoporosis. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD005326. DOI: 10.1002/14651858.CD005326.pub2.

Author Information

*Ms Siobhan O'Donnell, Research Coordinator, Clinical Epidemiology Program, Ottawa Health Research Institute, 1053 Carling Avenue, C-414, Ottawa, ON, K1Y 4E9, CANADA. sodonnell@ohri.ca.

Publication History

  1. Publication Status: New
  2. Published Online: 19 JUL 2006

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This is not the most recent version of the article. View current version (18 OCT 2006)

 

Abstract

  1. Top of page
  2. Abstract
  3. Synopsis

Background

Strontium ranelate is a new anti-osteoporosis therapy therefore, its benefits and harms need to be known.

Objectives

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

Search strategy

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 and industry sponsors.

Selection criteria

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 and/or safety outcomes 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.

Data collection and analysis

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.

Main results

A total of four trials met our inclusion criteria, three of which investigated the effects of strontium ranelate compared to placebo in a treatment population (doses ranged from 0.5 to 2 g daily) and one, in a prevention population (doses 0.125, 0.5 and 1 g daily). In osteoporotic, postmenopausal women a 37% reduction in vertebral fractures (two trials, n = 5082, RR 0.63, 95% CI 0.56 to 0.71) and a 14% reduction in non-vertebral fractures (two trials, n = 6572, RR 0.86, 95% CI 0.75 to 0.98) was demonstrated over a three year period with 2 g of strontium ranelate daily. An increase in BMD at all sites was shown with the same dose: lumbar spine BMD (two trials, n = 1614, WMD adjusted for strontium content 5.44, 95% CI 3.41 to 7.46 and WMD not adjusted 11.29, 95% CI 10.22 to 12.37 over two years), femoral neck and total hip (two trials, n = 4230, WMD 8.25, 95% CI 7.84 to 8.66 and WMD 9.83, 95% CI 9.39 to 10.26 respectively over three years). One gram of strontium ranelate daily in postmenopausal women without osteoporosis increased BMD at all sites over a two year period: lumbar spine (one trial, n = 59, WMD adjusted for strontium content 2.39, 95% CI 0.15 to 4.63 and WMD not adjusted 6.68, 95% CI 5.16 to 8.20), femoral neck (one trial, n= 60, WMD 2.52, 95%CI 0.96 to 4.09) and total hip (one trial, n = 60, WMD 1.02, 95% CI 0.48 to 1.56). In both the treatment and prevention populations, lower doses of strontium ranelate were superior to placebo with the highest dose of strontium ranelate demonstrating the greatest reduction in vertebral fractures and increase in BMD. There is some evidence to suggest that 2 g of strontium ranelate daily compared to placebo may have a beneficial effect on health related quality of life in postmenopausal women after three years of treatment. Two grams of strontium ranelate daily increased the risk of diarrhea (RR 1.38%, 95% CI 1.02 to 1.87); however, adverse events did not affect the risk of discontinuing strontium ranelate nor did it increase the risk of serious side effects, gastritis or death. Additional data obtained suggests that the risk of vascular system disorders including venous thromboembolism (two trials, n = 6669, 2.2% versus 1.5%, OR 1.5, 95% CI 1.1 to 2.1) and pulmonary embolism (two trials, n = 6669, 0.8% versus 0.4%, OR 1.7, 95% CI 1.0 to 3.1) as well as nervous system disorders such as headaches (3.9% versus 2.9%), seizures (0.3% versus 0.1%), memory loss (2.4% versus 1.9%) and disturbance in consciousness (2.5% versus 2.0%) is slightly increased with taking 2 g of strontium ranelate daily over a 3 to 4 year period.

Authors' conclusions

There is silver level evidence to support the efficacy of strontium ranelate for the reduction of vertebral fractures (and to a lesser extent non-vertebral fractures) in postmenopausal osteoporotic women and an increase in BMD (all sites) in postmenopausal women with and without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased in the strontium ranelate group. Potential risks to the vascular and neurological system associated with taking 2 g of strontium ranelate daily need to be further explored and quantified.

 

Synopsis

  1. Top of page
  2. Abstract
  3. Synopsis

Plain language summary

Strontium ranelate for osteoporosis in women after menopause
This summary of a Cochrane review presents what we know from research about the effect of strontium ranelate for osteoporosis in women after menopause. The review shows that:

There is silver level evidence that for treatment of osteoporosis in women after menopause, 2 g of strontium ranelate daily over 3 years decreases fractures in the spine and slightly decreases fractures not in the spine. Most women do not have side effects that would cause them to stop taking strontium ranelate. However, other research shows that harms could include a chance of blood clots and seizures, memory loss and consciousness.

What is osteoporosis and how can strontium ranelate help?
Osteoporosis is a condition in which bone loss occurs. Bone loss leads to weak brittle bones that can break easily, even during everyday activities. Breaks (fractures) of the spine or non-spine (e.g. wrist and hip) are the most common type. There are many drugs and minerals that work to treat osteoporosis. Strontium ranelate is a drug that decreases the chance of fractures by slowing the loss of bone and possibly by building new bone. It is a new drug and therefore its benefits and harms need to be known.

What are the results of this review?
Women in the studies took 2 g of strontium ranelate or a placebo (fake tablets or powder). After 2 to 3 years, the number of fractures that occurred and bone mineral density was measured. Bone mineral density is a lab test to measure how dense or strong bones are in the hip, spine or neck. The higher the bone density the better.

Benefits of strontium ranelate
In women after menopause who have osteoporosis:

  • strontium ranelate decreases spine fractures
-13 out of 100 women had spine fractures taking strontium ranelate
-21 out of 100 women had spine fractures taking a placebo
  • strontium ranelate may decrease fractures that are not in the spine
-11 out of 100 women had non-spine fractures taking strontium ranelate
-13 out of 100 women had non-spine fractures taking a placebo
  • strontium ranelate increases bone mineral density
Harms of strontium ranelate
In women after menopause who have osteoporosis:
  • strontium ranelate did not cause side effects that would make them stop taking it
  • strontium ranelate did not lead to serious side effects, stomach infections, back pain or death
  • strontium ranelate increased diarrhea
-7 out of 100 women had diarrhea taking strontium ranelate
-5 out of 100 women had diarrhea taking a placebo

Other research shows that harms could include a chance of blood clots, and seizures, memory loss and consciousness. The cause of these neurological side effects are not known.

This review has several limitations which include difficulty interpreting the change in bone mineral density due to the unique aspects of strontium in bone and incomplete follow-up of some patients within the individual trials.