1 3 J Bone Miner Metab DOI 10.1007/s00774-016-0785-4 ORIGINAL ARTICLE Vitamin K homologs as potential biomarkers for disease activity in patients with rheumatoid arthritis Hani M. Khojah 1 · Sameh Ahmed 2 · Mahran S. Abdel-Rahman 3,4 · Khaled M. Alkhalil 5 · Al-Badr Hamza 5 Received: 11 May 2016 / Accepted: 5 September 2016 © The Japanese Society for Bone and Mineral Research and Springer Japan 2016 the levels of menaquinone-4 (MK-4) and menaquinone-7 (MK-7) were moderately to strongly inversely correlated with the clinical articular features in RA patients, whereas phylloquinone (PK) levels were weakly correlated. Serum levels of MK-4, MK-7 and PK were strongly inversely correlated with ucOC, MMP-3 and DAS28-ESR in RA patients. In contrast, serum levels of MK-4, MK-7 and PK were weakly correlated with CRP, RF and anti-CCP. These results suggest that serum levels of vitamin K homologs may be considered as potential biomarkers for disease activity. In addition, the results confirm the role of vitamin K deficiency in the etiology of RA. Keywords Vitamin K homologs · Rheumatoid arthritis · Biomarkers · DAS28-ESR · Matrix metalloproteinase Introduction Naturally occurring vitamin K includes phylloquinone (PK, vitamin K 1 ) and menaquinone series (vitamin K 2 ). These vitamin K compounds share a common chemical struc- ture consisting of a naphthoquinone nucleus [1]. Based on the differences of the structure of the side chain, vitamin K 2 divides into a series of chemically related compounds known as menaquinones (MKs; MK 1 –MK 10 ). PK is consid- ered as the major dietary form of vitamin K, which occurs in green and leafy vegetables. In contrast, MKs are found in fermented foods (e.g., fermented soybeans) and in the colon, where they are synthesized by the intestinal microflora [2]. In addition to the effect of vitamin K on blood coagu- lation, several studies have indicated the important role of vitamin K in bone metabolism and bone protection [3–5]. Osteocalcin, a vitamin K-dependent protein, is a major component of organic bone matrix and is produced by Abstract The aim of this study was to evaluate the possi- ble role of vitamin K homologs as potential biomarkers for disease activity in patients with rheumatoid arthritis (RA). In this study, 42 patients with RA and 40 healthy controls were enrolled. Serum levels of vitamin K homologs were measured using a high-performance liquid chromatogra- phy-fluorescence method. Different biochemical and clini- cal markers for disease activity were measured and corre- lated with serum levels of vitamin K homologs. There were no significant differences between RA patients and healthy subjects in demographic data. Patients with RA showed sig- nificantly higher levels of biochemical markers compared with healthy subjects (p < 0.001). These markers included rheumatoid factor (RF), anticyclic citrullinated polypeptide (anti-CCP), undercarboxylated osteocalcin (ucOC), matrix metalloproteinase (MMP-3), C-reactive protein (CRP), and disease activity score assessing 28 joints with erythrocyte sedimentation rate (DAS28-ESR). In addition, serum levels of vitamin K homologs were reduced in RA patients, and * Hani M. Khojah hkhojah@taibahu.edu.sa 1 Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Al Madinah AlMunawarah, Saudi Arabia 2 Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al Madinah AlMunawarah, Saudi Arabia 3 Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al Madinah AlMunawarah, Saudi Arabia 4 Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt 5 Department of Rheumatology, King Fahd Hospital, Al Madinah AlMunawarah, Saudi Arabia