Androgen Deprivation Therapy Induces Vitamin K Loss in Men with Prostate Cancer

Hisashi Matsushima

Bone strength is determined by bone mineral density (BMD) and bone quality. Bone fractures are serious adverse events in men receiving androgen deprivation therapy (ADT) for prostate cancer. Although it is established that ADT reduces BMD, it is unclear how ADT alters bone quality. Vitamin K is a bone quality marker which aids to carboxylates osteocalcin to form bone matrix. Serum undercarboxylated osteocalcin (ucOC) is accumulated in vitamin K deficiency, which is used as a surrogate for vitamin K status. As little is known as to the impact of ADT on serum ucOC, we investigated the changes of serum ucOC in PC patients during ADT. Fifty consecutive hormone naïve PC patients were enrolled. Serum ucOC, serum osteocalcin (OC), serum Nteloptide of type 1 collagen (NTx) and hip bone mineral density (BMD) were measured at baseline, 6 month and 12 months since the start of ADT. Serum ucOC levels at 6 and 12 months (3.86 ± 2.28 and 4.32 ± 1.76 ng/ml) were significantly higher than those at baseline (2.46 ± 1.46 ng/ml). Serum OC levels at 12 months (7.82 ± 2.65 ng/ml) were significantly higher than those at baseline (5.26 ± 1.86 ng/ml). Furthermore, the ratio of ucOC/OC at 1 year (0.54 ± 0.15) were significantly higher than at baseline (0.42 ± 0.18). Both serum NTx levels and hip BMDs at 6 and 12 months were also significantly higher than those at baseline. Our results first demonstrated that ADT induced vitamin K loss in men with prostate cancer. Further investigations are required to determine whether vitamin K supplement is useful to prevent bone fractures in men on ADT.