Effects of 3 years treatment with once-yearly zoledronic acid on the kinetics of bone matrix maturation in osteoporotic patients
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Once-yearly administration of intravenous zoledronic acid for 3 years in humans affects the kinetics of matrix filling in by mineral, independent of bone turnover.
Yearly 5-mg infusions of zoledronic acid (ZOL) for 3 years have shown pronounced antifracture efficacy. The purpose of the present study was to test whether ZOL affects the kinetics of forming bone material properties maturation.
Iliac crest biopsies from the HORIZON-PFT clinical trial were analyzed by Raman microspectroscopy in actively bone-forming surfaces as a function of tissue age in trabecular and osteonal bone, to determine ZOL’s effect on bone material quality indices maturation kinetics.
Mineral/matrix ratio increased in both groups as a function of tissue age, at both osteonal- and trabecular-forming surfaces; ZOL exhibiting the greatest increase in the trabecular surfaces only. The proteoglycan content showed a dependency on tissue age in both trabecular and osteonal surfaces, with ZOL exhibiting lower values in the tissue age 8–22 days in the trabecular surfaces. Mineral crystallinity (crystallite length and thickness) showed a dependence on tissue age, with ZOL exhibiting lower crystallite length compared with placebo only in the 8- to 22-day-old tissue at trabecular surfaces, while crystal thickness was lower in the 1- to 5-day-old tissue at both osteonal and trabecular surfaces.
The results of the present study suggest that once-yearly administration of intravenous ZOL for 3 years in humans does not exert any adverse effects on the evolution of bone material properties at actively forming osteonal and trabecular surfaces, while it may have a beneficial effect on the progression of the mineral-to-matrix ratio and mineral maturity bone quality indices.
KeywordsBisphosphonate Bone maturation Osteoporosis Raman spectroscopy Zoledronic acid
The authors thank Novartis Pharma AG, Basel, Switzerland, for provision of the biopsy samples. This study was supported by the Allgemeine Unfallversicherungsanstalt (AUVA), research funds of the Austrian Workers' Compensation Board, the Wiener Gebietskrankenkasse (WGKK), Viennese Sickness Insurance Funds, and the Fonds zur Foederung der wissenschaftlichen Forschung (FWF project number P20646-B11).
Conflicts of interest
Dr. Recker consults for and/or receives research grants from Amgen, Eli Lilly, GlaxoSmithKline, Merck, Novartis, NPS Allelix, Procter & Gamble, Roche, and Sanofi-aventis. Dr. Eriksen consults and speaks for Novartis, Amgen, and Eli Lilly. Dr. Gasser is an employee of the Novartis Institute for BioMedical Research. Drs. Gamsjaeger, Hofstetter, Zwettler, Klaushofer, and Paschalis have no conflicts of interest.
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