The effect of zoledronic acid on serum homocysteine, folate and vitamin B12 in patients with Paget's disease of bone
Stergios Polyzos1, Athanasios Anastasilakis2, Zoe Efstathiadou1, Ioannis Litsas1, Marina Kita1, Athanasios Panagiotou1, Athanasios Papatheodorou3, Georgios Arsos4, Efstratios Moralidis4, Georgios Barmpalios5, Efthimia Zafeiriadou5 & Evangelos Terpos3
Purpose: High serum homocysteine (HCY) and indirectly deficiency of folate and/or vitamin B12 stimulate bone resorption and adversely affect collagen cross-linking. The aim of this study was the evaluation of serum levels of HCY, folate and vitamin B12 in patients with Pagets disease of bone (PDB) and the effect of zoledronic acid (ZOL) on their serum levels.
Methods: This was a prospective open-label cohort study, with a control arm at baseline. Nine consecutive patients with polyostotic PDB (median age 66 years) received a single 5 mg ZOL infusion. Blood samples for HCY, folate, vitamin B12, total serum alkaline phosphatase (TSAP), bone-specific serum alkaline phosphatase (BSAP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were obtained at baseline and 3, 6 and 12 months after ZOL infusion. Twelve age- gender- and BMI-matched healthy individuals were recruited for control group at baseline assessment. The study protocol was approved by the local ethics committee. Data are presented as median (interquartile range).
Results: Patients with PDB had significantly higher serum HCY (16.3 (13.419.0) vs 12.6 (8.914.1) μmol/l, P=0.028), folate (7.6 (7.111.2) vs 3.0 (2.34.2) ng/ml, P<0.001) and bone markers: TSAP (241 (152517) vs 71 (5690) IU/l, P<0.001; BSAP 96 (58160) vs 23.2 (18.229.6) IU/l, P<0.001; CTX 1.46 (0.832.11) vs 0.54 (0.310.80) ng/ml, (P<0.001)) compared with the control group at baseline. In the pagetic group, serum HCY significantly decreased 3 months after ZOL infusion (14.7 (10.516.2) μmol/l) and remained essentially unchanged up to the end of the study (12.4 (12.316.0) μmol/l, P=0.005 (ANOVA)). Serum vitamin B12 and folate remained unaffected throughout the study.
Conclusions: Our data suggest that serum HCY levels are increased in patients with PDB. A single ZOL infusion results in a decrease in HCY levels that might represent another mechanism for the reduction of the activity of PDB achieved by ZOL.