Highlights of the 28th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR)

September 15-19, 2006; Philadelphia, Pennsylvania

Ego Seeman, MD


January 11, 2007

In This Article

Strontium Ranelate: An Anabolic Agent for Cortical Bone?

The efficacy of strontium ranelate in the treatment of postmenopausal osteoporosis is based on data from 2 ongoing, prospective, 5-year, phase 3 RCTs.[19,20] In contrast to other therapies for osteoporosis; strontium ranelate appears to produce dissociation in bone remodeling, allowing bone formation at the tissue level to continue while suppressing bone resorption at the tissue level. Another interpretation of the data is that there is more surface undergoing bone formation than surface undergoing bone resorption because the time course of the bone formation component of the remodeling cycle is longer than the time course of the resorptive phase of bone remodeling. Data demonstrating dissociation between bone formation and resorption at the cellular (basic multicellular unit [BMU]) level are not available.

Using cultured primary human osteoblasts, Brennan and colleagues[21] demonstrated that strontium ranelate increased osteoblast replication, increased osteoprotegerin mRNA expression, and decreased receptor activator of NF-kappaB ligand (RANKL) expression, and thus decreased promotion of osteoclastogenesis.

Two animal studies, however, contradict the hypothesis that strontium is an anabolic agent for cortical bone. In a study of ovariectomized rats treated with a low-calcium or normal-calcium diet, Fuchs and colleagues[22] found that periosteal bone formation indices were lower in animals treated with strontium, and that there were no differences in endocortical bone formation among groups. Likewise, Allen and colleagues[23] reported that strontium ranelate given to ovariectomized rats 4 weeks postovarectomy produced a higher vertebral BMD, but reduced mineralizing surface with no effect on mineral apposition rate. Bone formation rate and bone surface were reduced.

Overall, there is compelling evidence that strontium ranelate reduces the risk of vertebral and nonvertebral fractures. However, at this time it remains unclear as to what mechanisms are responsible for the reduction in progression of fracture risk. Although data suggesting differing effects of this treatment on bone formation and resorption exist, clear evidence that the drug has a dual action remains to be demonstrated. Further research is ongoing to address the possible mode of action of this drug.


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