March 25, 2011 (Valencia, Spain) — In postmenopausal women with osteoporosis, strontium ranelate exerts significantly greater bone-forming activity than the bisphosphonate alendronate, according to a new study presented here at the 2011 European Congress on Osteoporosis and Osteoarthritis.

This is not unexpected, the study team notes, given that alendronate is purely an antiresorptive agent, whereas strontium ranelate reduces bone resorption and increases bone formation.

What is novel in the current study, researchers say, is the use of before and after bone biopsies — the gold standard for examining the effects of osteoporosis treatment — to actually see strontium ranelate's bone-forming action.

Jean-Yves Reginster, MD, PhD, from the University of Liege, Belgium, who chaired the Congress, said: "This is a totally new study, the largest ever in osteoporosis with bone histomorphometry with bone biopsies."

"Limited" Bone Biopsy Data

There is a "large dataset" from clinical studies showing strontium ranelate's efficacy in preventing fragility fractures in osteoporotic patients, study investigator Louis-Georges Ste-Marie, MD, director of the Metabolic Bone Diseases Laboratory, Centre de recherche du CHUM, L'Hôpital Saint-Luc, Montreal, Quebec, Canada, told conference attendees.

Until now, however, there have been "very limited" data from paired bone biopsies in patients receiving strontium ranelate, he noted. He said there is a "great need" for this type of study to gain more information on specific mechanisms of action of the drug.

Study coinvestigator Roland D. Chapurlat, MD, PhD, head of the division of rheumatology and bone disease, Edouard Herriot Hospital, Lyon, France, presented the results of the double-blind multicenter international study.

Participants included women with postmenopausal osteoporosis (i.e., low bone mineral density and/or fragility fractures) and similar baseline clinical characteristics. Their average age was around 64 years. They also had similar baseline lumbar T-scores (−2.90 for strontium ranelate and −2.98 for alendronate).

The women were treated with either strontium ranelate 2 g/day or alendronate 70 mg/week. All of them also took 1000 mg calcium and 800 IU vitamin D daily. Transiliac bone biopsies to assess bone formation were obtained at baseline and after 6 and 12 months of treatment. Results were analyzed by intention to treat.

The findings are based on 268 women (179 receiving strontium ranelate and 89 receiving alendronate) with paired biopsies. The primary end point was the mean difference between the groups for "mineralizing surface (MS)," an index of bone formation expressed as a percentage of bone surface (MS/BS).

Strontium Ranelate a Better Bone Builder

After 6 and 12 months of treatment, mineralizing surfaces had improved significantly more in women treated with strontium ranelate than in those treated with alendronate, Dr. Chapurlat reported.

After 6 months, MS/BS values were 2.94% in women taking strontium ranelate and 0.20% in those taking alendronate — a significant between-group difference of 2.73% (P < .001).

The difference between groups rose to 4.65% at 12 months (P < .001), with MS/BS values of 4.91% in the strontium ranelate group and 0.28% in the alendronate group. "There was more bone formation at 12 months than at 6 months," Dr. Chapurlat noted.

"Women on alendronate had low bone formation," the researcher noted. "This is expected, because this is the way the treatment is known to work. It depresses bone turnover."

Significantly greater increases in the strontium ranelate group were also seen in 2 other bone formation parameters (the bone formation rate and the mineral apposition rate, which were secondary end points).

"The bone-forming activity seen here can be attributed to strontium ranelate's unique mechanism of action, which, unlike bisphosphonates that block bone resorption and formation, combines the dual effects of increasing or maintaining bone formation and decreasing bone resorption," Dr. Ste-Marie noted in a statement from the conference.

Both agents were well tolerated. In phase 3 studies, the overall incidence rates for adverse reactions with strontium ranelate were typically mild and transient — most commonly nausea and diarrhea. In these studies, the annual incidence of venous thromboembolism observed over the course of 5 years was roughly 0.7%, with a relative risk of 1.4 in strontium ranelate-treated patients, compared with placebo. The drug "should be used with caution" in patients at risk for venous thromboembolism, a statement from the conference reads.

Results of the open-label extension of the 2 phase 3 trials published in Osteoporosis International in 2010 concluded that strontium ranelate remains safe and well tolerated over the course of 10 years, with no unexpected adverse events.

"Osteoporosis is a major public health issue," Dr. Reginster explained. "One woman out of 2 over the age of 50 will have at least 1 fracture related to osteoporosis if we do not take care of this problem before the first fracture. Strontium ranelate, with its unique mode of action, can bring significant benefit."

The study was supported by the French Pharmaceutical Company Servier, which markets strontium ranelate, under the trade names Protos, Osseor, Bivalos, and Protaxos. Dr. Reginster and Dr. Chapurlat disclose financial relationships with several pharmaceutical companies, including Servier. Dr. Ste-Marie has disclosed no relevant financial relationships.

2011 European Congress on Osteoporosis and Osteoarthritis: Abstract OC16. Presented March 24, 2011.