Short-Term Effects of High-Dose Zoledronic Acid Treatment on Bone Mineralization Density Distribution After Orthotopic Liver Transplantation

Abstract

Patients with "hepatic" bone disease exhibit increased fracture incidence. The effects on bone material properties, their changes due to orthotopic liver transplantation (OLT), as well as zolendronate (ZOL) treatment have not yet been investigated. We studied bone mineralization density distribution (BMDD) in paired transiliacal biopsies (at and 6 months after OLT) from patients (control CON n = 18, treatment group ZOL n = 21, the latter treated with i.v. ZOL at doses of 4 mg/month) for how bone at the material level was affected by the "hepatic" disease in general, as well as by OLT and ZOL in particular. (1) BMDD parameters at baseline reflected disturbed bone matrix mineralization in "hepatic" bone disease combined with low turnover. Trabecular bone displayed a decrease in mean and most frequent calcium concentration (Ca(MEAN) -2.9% and Ca(PEAK) -2.8%, respectively; both P < 0.001), increased heterogeneity of mineralization (Ca(WIDTH) +12.2%, P = 0.01), and increased percentage of bone areas with low mineralization (Ca(LOW) +32.4%, P = 0.02) compared to normal; however, there were no differences compared to cortical bone. (2) Six months after OLT, ZOL-treated trabecular bone displayed reduced Ca(LOW) (-32.0%, P = 0.047), cortical bone increased Ca(MEAN) (+4.2%, P = 0.009), increased Ca(PEAK) (+3.3%, P = 0.040), and decreased Ca(LOW) (-55.7, P = 0.038) compared to CON and increased Ca(MEAN) compared to baseline (+1.9, P = 0.032) without any signs of hyper- or defective mineralization. These changes as consequence of the antiresorptive action of ZOL visible already after 6 months result in beneficial effects on bone matrix mineralization, likely contributing to the significant decrease in fracture incidence observed in these patients 2 years post transplantation.