BARCELONA, Spain—Yearly treatment with zoledronic acid (Zometa®, Novartis Pharmaceuticals Corp) both reduces bone turnover and preserves bone structure and remodeling capacity, according to researchers at the EULAR 2007 meeting.

"The bone formed during treatment with zoledronate showed no evidence of marrow fibrosis, woven bone or osteomalacia, further supporting the bone safety of the new bisphosphonate."—Robert R. Recker, MD.
Pierre D. Delmas, MD, PhD, and colleagues reported that in a study of 7736 postmenopausal women, once-yearly infusion of zoledronate (5 mg) significantly reduced markers of bone resorption; this effect was maintained within premenopausal levels over the subsequent 12 months.1 "Levels, on average, returned to the premenopausal range 6 months after the infusion and increased progressively over time, reaching predose levels at year's end," Dr. Delmas, in the departments of medicine and rheumatology at University Claude Bernard Lyon, in France, said.

This analysis was based on the 3-year HORIZON-PFT (Pivotal Fracture Trial), in which patients were randomized to a single-year 15-minute IV infusion of zoledronate 5 mg or placebo at baseline, at months 12 and 24.

Investigators measured biochemical markers including bone resorption marker serum β-C-telopeptide (β -CTX), bone formation marker alkaline phosphatase (ALP), and serum bone formation marker N-terminal propeptide of type I collagen (PINP). They found that at 6 months, mean levels of β -CTX dropped from 0.39-0.42 ng/mL at baseline to 0.113 ng/mL for zoledronate-treated patients but remained at 0.367 ng/mL for placebo-treated patients.

"At month 36, patients in the zoledronate group had an approximately 55% greater rate of reduction in bone resorption as measured by serum β-CTX compared to placebo-treated patients (P <.0001)," Dr. Delmas said.

At month 36 also, bone formation as measured by mean serum bone ALP had decreased 29% more in the zoledronate-treated group than in the placebo group (P <.0001); bone formation as measured by serum bone PINP was 52% lower in zoledronate patients than in placebo patients (P <.0001). "Although an initial decrease in ALP was seen in the zoledronate group after the first 6 months, bone formation remained relatively constant in the middle of the premenopausal normal range," Dr. Delmas commented.

These changes in bone turnover did not adversely affect the quality of the new bone formed during treatment. Using data from the HORIZON-PFT study, Robert R. Recker, MD, with Creighton University in Omaha, Nebraska, and colleagues found that zoledronate reduced bone turnover by 36% while preserving the quality of trabecular bone structure in the iliac crest.2 "The bone formed during treatment with zoledronate showed no evidence of marrow fibrosis, woven bone, or osteomalacia, further supporting the bone safety of the new bisphosphonate," Dr. Recker reported.

This analysis was based on bone biopsies of 76 zoledronate patients and 67 placebo patients obtained 1 year after the last dose of zoledronate or placebo and the data analyzed using histomorphometry and microcomputed tomography.

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References

1. Delmas P, Bauer D, Black D, et al. Effect of once-yearly infusion of zoledronic acid 5 mg on biochemical markers of bone turnover: data from HORIZON-PFT. Presented at: EULAR 2007 Meeting; June 13-16, 2007; Barcelona, Spain. Abstract SAT0306.
2. Recker RR, Delmas P, Reid I, et al. Histomorphometric and micro-CT analysis of bone biopsies after three annual infusions of zoledronic acid 5mg: evidence for preservation of bone structure and remodeling capacity. Presented at: EULAR 2007 Meeting; June 13-16, 2007; Barcelona, Spain. Abstract SAT0312.