LONDON – Strontium ranelate continued to safely and effectively prevent vertebral and nonvertebral fractures in postmenopausal women with osteoporosis during 5-10 years of continuous treatment, in a "modified" case-control study that included 233 women who maintained daily 2 g/day strontium dosing for 10 years.
"Strontium ranelate should not be considered a second-line alternative to bisphosphonates or to any other [osteoporosis] treatment," Dr. Jean-Yves Reginster said at the annual European Congress of Rheumatology. Treatment with strontium ranelate "gives you a chance to bring bone turnover back to premenopausal values," said Dr. Reginster, professor of epidemiology and chairman of the department of public health at the University of Liège in Belgium.
The ability of strontium ranelate to maintain a reduced rate of both vertebral and nonvertebral fractures over 10 years of continuous use in this study marks the first reported evidence of an antiosteoporotic drug exerting an unequivocal antifracture benefit for such a prolonged period. The only other report on 10-year treatment came from the Fracture Intervention Trial Long Term Extension, which included 1,099 women randomized to alendronate or placebo for 10 years (JAMA 2006;296:2927-38). Those results showed that 5-10 years of extended alendronate treatment did not result in a reduction of all clinical fractures or nonvertebral fracture, compared with women maintained on placebo during years 5-10, but extended alendronate did reduce the clinical vertebral fracture rate, compared with placebo.
"In our study [of strontium ranelate], we had no placebo group, but we showed that you can reduce fractures over 10 years with this drug." Strontium maintained its efficacy over 10 years "probably because of its mechanism of action, a dual action," Dr. Reginster said in an interview. "With bisphosphonates you reduce bone resorption. With strontium ranelate you reduce bone resorption by 20%-25%, and you increase bone formation by 20%-25%, so you bring the bone back to what you see in younger women. I think it is a more physiologic approach" than treatment with a bisphosphonate.
In addition, "safety is most important to me when you treat for 10 years. One of the biggest advantages of strontium ranelate is that it is a very safe drug, with little risk of adverse effects over time. I think that calculating the risk/benefit ratio of a drug over time is very important."
In his report, Dr. Reginster emphasized that the women maintained on the drug for 10 years did not have a single episode of atypical fracture, osteonecrosis of the jaw or atrial fibrillation, and their adverse-event profile showed better safety than in the original, pivotal trials of strontium ranelate. He also noted that while the extension only included 233 women on the drug, registry data on about one million patients who have taken the drug also show no reported cases of atypical fracture, osteonecrosis of the jaw, or atrial fibrillation.
The 233 women followed for 10 years on continuous strontium ranelate treatment came from either of the two pivotal, 5-year trials of the drug: the Treatment of Peripheral Osteoporosis Study (TROPOS) (J. Clin. Endocrinol. Met. 2005;90:2816-22), and the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial (New. Engl. J. Med. 2004;350:459-68). They continued to receive 2 g/day strontium ranelate, and 73% of the women completed the full extension period. Their average duration of drug use was 9.8 years, and their average compliance with the regimen was 89%.
During their additional 5 years on the drug, average lumbar spine bone mineral density continued to rise, increasing from about 20% above baseline at the start of the extension to about 27% above baseline at 10 years.
To assess the efficacy of treatment for preventing vertebral and nonvertebral fractures, Dr. Reginster and his associates "rebuilt" a control population by selecting placebo patients from the TROPOS study who matched the 233 extended-treatment women based on their baseline Fracture Risk Assessment scores. The researchers matched two TROPOS placebo-group women with each women in the extension study, assembling a total of 458 controls.
The incidence of vertebral fractures during years 5-10 in the women on strontium ranelate was 21%, compared with a 28% rate in the rebuilt control group, a statistically significant difference. In addition, the 21% reduction during the 5-10 year period was statistically similar to the 19% vertebral fracture rate among women treated during 0-5 years in SOTI.
The incidence of nonvertebral fractures during years 5-10 with strontium ranelate was 14%, significantly less than the 20% rate in the derived placebo group and statistically similar to the 13% rate seen in TROPOS, Dr. Reginster reported.
The SOTI and TROPOS trials were funded by Servier, which markets strontium ranelate (Protelos). Dr. Reginster reported financial relationships with Amgen, Analis, Bristol-Myers Squibb, Ebewe, Genévrier, GlaxoSmithKline, IBSA, Eli Lilly, Merck Sharp & Dohme, Merckle, Negma, Novartis, Novo Nordisk, NPS Pharmaceuticals, Nycomed, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, Wyeth, UCB, and Zodiac.