Effects of 3 years treatment with once-yearly zoledronic acid on the kinetics of bone matrix maturation in osteoporotic patients
- 470 Downloads
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
- 13.Paschalis EP, Tatakis DN, Robins S, Fratzl P, Manjubala I, Zoehrer R, Gamsjaeger S, Buchinger B, Roschger A, Phipps R, Boskey AL, Dall’Ara E, Varga P, Zysset P, Klaushofer K, Roschger P (2011) Lathyrism-induced alterations in collagen cross-links influence the mechanical properties of bone material without affecting the mineral. Bone 49:1232–1241PubMedCrossRefGoogle Scholar
- 14.Recker RR, Delmas PD, Halse J, Reid IR, Boonen S, Garcia-Hernandez PA, Supronik J, Lewiecki EM, Ochoa L, Miller P, Hu H, Mesenbrink P, Hartl F, Gasser J, Eriksen EF (2008) Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure. J Bone Miner Res 23:6–16PubMedCrossRefGoogle Scholar
- 15.Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822PubMedCrossRefGoogle Scholar
- 16.Gamsjaeger S, Buchinger B, Zwettler E, Recker R, Black D, Gasser JA, Eriksen EF, Klaushofer K, Paschalis EP (2011) Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly zoledronic acid. J Bone Miner Res 26:12–18PubMedCrossRefGoogle Scholar
- 17.Gamsjäger S, Kazanci M, Paschalis E, Fratzl P (2009) Raman spectroscopy for soft matter applications. In: Amer M (ed) Raman application in bone imaging. Wiley, Hoboken, pp 227–269Google Scholar
- 26.Bullough P (1992) Atlas of orthopaedic pathology. Gower, New YorkGoogle Scholar
- 27.Einhorn TA (1996) The bone organ system: form and function. In: Marcus R, Feldman D, Kelsey J (eds) Osteoporosis. Academic, New YorkGoogle Scholar
- 30.Boskey AL, Pleshko N, Doty SB, Mendelsohn R (1992) Applications of Fourier transform infrared (FT-IR) microscopy to the study of mineralization in bone and cartilage. Cells And Materials 2:209–220Google Scholar
- 41.Gadaleta SJ, Paschalis EP, Betts F, Mendelsohn R, Boskey AL (1996) Fourier transform infrared spectroscopy of the solution-mediated conversion of amorphous calcium phosphate to hydroxyapatite: new correlations between X-ray diffraction and infrared data. Calcif Tissue Int 58:9–16PubMedCrossRefGoogle Scholar
- 43.Rey C, Shimizu M, Collins B, Glimcher MJ (1991) Resolution-enhanced Fourier transform infrared spectroscopy study of the environment of phosphate ion in the early deposits of a solid phase of calcium phosphate in bone and enamel and their evolution with age: 2. Investigations in the nu3po4 domain. Calcif Tissue Int 49:383–388PubMedCrossRefGoogle Scholar