Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly Zoledronic acid

Abstract

Zoledronic acid (ZOL), a third-generation aminobisphosphonate, showed pronounced antifracture efficacy in a phase III clinical trial [Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT)] when administered yearly (5-mg infusions of ZOL), producing significant reductions in morphometric vertebral, clinical vertebral, hip, and nonvertebral fractures by 70%, 77%, 41%, and 25%, respectively, over a 3-year period. The purpose of this study was to analyze the biopsies obtained during the HORIZON clinical trial (152 patients, 82 ZOL and 70 placebo) by means of Raman microspectroscopy (a vibrational spectroscopic technique capable of analyzing undecalcified bone tissue with a spatial resolution of approximately 0.6 mm) to determine the effect of ZOL therapy on bone material properties (in particular mineral/matrix ratio, lamellar organization, carbonate and proteoglycan (based on spectral identification of glycosaminoglycan) content, and mineral maturity/crystallinity) at similar tissue age (based on the presence of tetracycline double labels). The results indicated that while ZOL administration increased the mineral/ matrix ratio compared with placebo, it also resulted in mineral crystallites with a quality profile (based on carbonate content and maturity/crystallinity characteristics) of younger (with respect to tissue age) bone. Since the comparisons between ZOL-and placebotreated patients were performed at similar tissue age at actively forming bone surfaces, these results suggest that ZOL may be exerting an effect on bone matrix formation in addition to its well-established antiresorptive effect, thereby contributing to its antifracture efficacy. ß

Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: A three-year study

“…(25,34) The analysis of iliac crest bone biopsies performed in a subset of HORIZON trial patients by mCT identified significantly better preservation of trabecular structure with ZOL than with PLB (26) and microspectroscopy analysis of these biopsies showed an increased mineral/matrix ratio with a larger proportion of younger bone tissue with ZOL compared with PLB. (36) These findings suggest that ZOL may exert its fracture risk reduction effects by increasing bone mass and by preserving bone quality in terms of bone microarchitecture and bone material properties. These findings are consistent with the improvements in TBS versus baseline observed with ZOL but not with PLB over 3 years.…”

Protective effects of resveratrol on osteoporosis via activation of the SIRT1‑NF‑κB signaling pathway in rats

“…As one of the diseases predominantly presenting in the elderly, an increasing number of individuals suffer from osteoporosis and osteoporotic fractures as a result of the increase in the elderly population (21). Osteoporosis has already become a problem for healthcare in the aging population; however, it has yet to attract sufficient research attention (22).…”

Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces

“…(11,25) In the present study, areas adjacent to fluorescent tetracycline labels were analyzed, ensuring that tissue of similar age was analyzed, thus rendering the results bone turnoverindependent. (14) Mineral/matrix ratio is a measure of bone density, which unlike BMD expresses the amount of mineral per amount of matrix (mainly type I collagen) per volume analyzed (25) and reflects bone ash weight. (41) In a recent report it was shown to be a better predictor of bending stiffness than BMD.…”

“…For the biopsies in which only one label was discernible, casting doubt as to whether it was the first or the second one, we analyzed areas that had around 10 mm distance between the label and the mineralizing front. (14) In these cases, spectra were recorded 2 mm from the label, in the area between the label and the mineralizing front.…”