Upfront loading of oral or intravenous bisphosphonates followed by maintenance dosing may enhance the ability of these agents to reduce fracture risk compared with currently used dosing regimens, according to new research presented Monday at the 27th Annual Meeting of the American Society for Bone and Mineral Research in Nashville, Tennessee.

 

This new approach to administering bisphosphonates should help reduce costs associated with fracture prevention in high-risk patients, and be particularly beneficial for patients with established osteoporosis with high bone turnover.

 

Early and increased therapy with bisphosphonates

 

While bisphosphonates are highly effective in enhancing bone mineral density (BMD) and decreasing fracture rates, the absorption of oral bisphosphonates is usually less than 1%. Front loading doses, however, result in greater drug absorption and may enhance the fracture reduction efficacy of bisphosphonates, especially in patients with fragility fractures, according to the new research.

 

"Bisphosphonate treatment can take months to build up enough medicine to help the skeleton," lead researcher Sunil Wimalawansa, MD, PhD, FRCP, MRCPath, DSc, professor and chief of the endocrinology and metabolism division and director of the Regional Osteoporosis Center at the Robert Wood Johnson Medical School in New Brunswick, New Jersey, tells CIAOMed. "The goal is to give bisphosphonates in large enough doses early in the disease process, so enough gets to the bones and stops fracturing sooner," Dr. Wimalawansa says. "This way the efficacy comes in the first week, not in the first year." Calling the new approach "proactive," he asks, "why wait?" However, no doctors are using this novel approach yet, he says.

 

In the new study, researchers found increases of spinal BMD at 3 months, 6 months, and 1 year when patients were treated with loading doses of risedronate, alendronate, and pamidronate, compared with their standard recommended doses for osteoporosis over a 1-year period. A statistically significant increase of BMD was observed in both loading doses of oral and intravenously administered agents between 3 and 6 months, compared with 6 months of standard therapy. There was no statistical difference between the responses observed with alendronate and risedronate, the study showed.

 

Results showed that at 1 year, patients given an initial loading dose of risedronate showed 5%–6% improvement in spinal BMD, compared with a 4.3% increase among patients receiving the standard dose. At 6 months, patients in the loading dose arm had a 4% increase in spinal BMD, compared with 2.2% among those given the standard dose of risedronate. At 3 months there was a 1.5% increase in spinal BMD among patients who received a loading dose, compared with a 0.4% increase among patients receiving the standard dose.

 

Patients who received the initial loading dose of alendronate had a 5.8% increase in spinal BMD at 1 year, compared with 4.5% among those given the standard dose. At 6 months, patients in the upfront loading arm had a 3.6% increase in spinal BMD, compared with 1.1% in the standard dose arm. At 3 months, patients receiving the loading dose of alendronate had a 1.2% increase in spinal BMD, compared with 0.4% in patients given the standard dose. Moreover, biomarker changes were observed in as early as 4 weeks among patients who received loading doses of bisphosphonates.

 

Novel method may boost compliance

 

"While many of the convenience factors associated with poor compliance among patients taking bisphosphonates would still be an issue with upfront loading, patients will see improvements within 2 to 3 weeks instead of 6 months to a year; which may lead to greater adherence," Dr. Wimalawansa points out. The new dosing has been shown to be an effective approach in all 3 currently available bisphosphonates. "Loading doses differ among the available agents, he concluded. "With monthly agents, doctors can give 4 months' worth up front, then switch back to normal doses after 1 month."



Reference

  1. Wimalawansa SJ. Use of upfront loading doses of bisphosphonates: Novel method to advance the beneficial effects of bisphosphonates on enhancing fracture reduction. Presented at: 27th Annual Meeting of the American Society for Bone and Mineral Research; September 23-27, 2005; Nashville, Tennessee. Abstract M369.