A potentially dual-acting new osteoporosis medication, strontium ranelate,* may safely decrease bone resorption while increasing bone formation, rebalancing bone turnover toward formation, according to new research presented at the 27th Annual Meeting of the American Society for Bone and Mineral Research in Nashville, Tennessee. But exactly how this agent works to reduce the risk of fractures is not yet known, experts tell CIAOMed.

Two large clinical trials (SOTI [Spinal Osteoporosis Therapeutic Intervention] and TROPOS [Treatment of Peripheral Osteoporosis]) had previously shown that 2 g/day of oral strontium ranelate reduced spinal fracture risk in postmenopausal osteoporotic women by 41% and reduced hip fracture risk in osteoporotic women aged 74 years and older by 36% over 3 years, according to Pierre D. Delmas, MD, lead study investigator and professor of medicine and rheumatology at Université Claude Bernard in Lyon, France.

The new study gathered transiliac bone biopsies from patients enrolled in three studies (SOTI, TROPOS, and STRATOS [Strontium Administration for Treatment of Osteoporosis]) during the first 5 years of treatment with either strontium ranelate (2 g/day) or placebo. All patients received calcium and vitamin D supplementation. In the active drug arm, results showed statistically significant evidence of increased osteoblast activity and a tendency toward decreased osteoclast activity. Moreover, the positive effects of strontium ranelate on bone formation were confirmed by a significantly higher number of osteoblastic surfaces in treated as compared to untreated patients and a significantly higher mineral apposition rate (MAR) in cancellous and cortical bone. Specifically, the number of osteoblastic surfaces in treated women was 38% higher, with a higher MAR indicated by an 8% increase in cancellous bone and 11% increase in cortical bone. There was no significant change in activation frequency at the tissue level, researchers reported.

Safety shown in new trial

"The drug is very safe for bone," Dr. Delmas tells CIAOMed. "There were no abnormalities in the texture of bone and no mineral defects in patients taking the new drug for 1 to 5 years." Noting that the study was very reassuring in terms of determining the safety of strontium ranelate, Dr. Delmas indicated the need for additional studies to understand the mechanisms by which the drug reduces the risk of fractures.

"The data presented in this abstract are highly significant because they represent the first direct biopsy evidence that the tightly linked processes of bone formation and resorption can be dissociated in a manner that can benefit the skeleton by lowering the risk of fracture," ASBMR President-Elect Elizabeth Shane, MD, professor of clinical medicine at Columbia University College of Physicians and Surgeons in New York City, said in a press release, adding that "strontium should prove to be a useful addition to the group of drugs used to treat osteoporosis."

However, Felicia Cosman, MD, medical director of the Clinical Research Center at Helen Hayes Hospital in West Haverstraw, New York, and clinical director of the National Osteoporosis Foundation in Washington, DC, said that she is not sold on the new agent just yet. "There doesn't seem to be a clear-cut mechanism of action by which this drug makes bones stronger," she tells CIAOMed. "We are in a quandary as to how this drug makes bone stronger or reduces fracture risk, so I am not tremendously enthusiastic at this point about [strontium ranelate]."

*Strontium ranelate (ProtelosR) is currently only available in Europe.

Reference

Arlot ME, Delmas P, Burt-Pichat B, Roux JP, Portero N, Meunier PJ. The effects of strontium ranelate on bone remodeling and bone safety assessed by histomorphometry in patients with postmenopausal osteoporosis. Presented at: 27th Annual Meeting of the American Society for Bone and Mineral Research; September 23–27, 2005; Nashville, Tenn. Abstract 1084.