Background Osteoporosis is a serious complication of systemic glucocorticoid (GC) therapy. Bisphosphonate is recommended, however insufficient result have been reported in some cases. Menatetrenone (vitamin K2;VK) is a stimulator of bone formation in vitro and in vivo. We recently have reported that severity of GC-induced osteoporosis might be determined by serum basal sRANKL levels in patients with systemic autoimmune disease . In the present study, we conducted post-hoc analysis to determine whether VK influenced bone metabolism markers in these patients.
Objectives To study the efficacy of VK on serum bone metabolism markers and on bone mineral density (BMD) in patients under GC therapy.
Methods This study was approved by the Ethics Committee at Toho University Omori Hospital (No. 21-61). Detailed study design was previously shown elsewhere . Briefly, sixty patients (40 women) with systemic lupus erythematosus (n=21), vasculitis syndrome (n=19), polymyositis/dermatomyositis (n=15), and adult-onset Still’s disease (n=5) who were started to received prednisolone (30-60mg daily) were enrolled. Serum samples were obtained just before and 1 to 4 weeks after the start of GC therapy. All patients received bisphosphonate for our regimen of GC therapy. Twenty patients received VK 45 mg daily from 2 weeks after GC therapy. As bone formation markers, serum levels of osteocalcin (OC), procollagen type I N-terminal peptide (PINP), undercarboxylated OC (ucOC), and bone alkaline phosphatase (BAP) were measured. As bone resorption markers, serum levels of type I collagen cross-linked N-telopeptide (NTx) and tartrate resistant acid phosphatase isoform 5b (TRACP-5b) were measured. The BMD of lumbar spine was measured before and after (at 15 months) GC therapy.
Results Serum levels of OC and ucOC were significantly (P<0.01) decreased at 1 to 4 weeks after GC therapy. Serum PINP level was also significantly (P<0.01) decreased after GC therapy, while the serum BAP level was not changed. Serum levels of NTx and TRACP-5b did not change during 4 weeks after GC therapy. Additional use of VK restored serum OC level to the half levels of the baseline. In contrast, serum ucOC level was decreased in patients both with and without administration of VK. The percentage of BMD was not changed from baseline in the VK group, whereas it was decreased in the bisphosphonate monotherapy group.
Conclusions Additional use of VK partially restored serum OC level from the suppressed level by GC therapy. In addition, the BMD value in the VK group was not changed after GC therapy. These results suggest that VK may possibly provide some effects on bisphosphonate therapy to prevent from GC-induced osteoporosis.
Kaneko K, et al. Changes of serum soluble receptor activator for nuclear factor-κB ligand after glucocorticoid therapy reflect regulation of its expression by osteoblast. J Clin Endocrinol Metab. 2012; 97:E1909-1917.
Disclosure of Interest None Declared