Table 1.

The relationship between vitamin K status and OA from case-control studies.

Reference	Study Design	Outcomes
Roberts et al. 1996 [24]	Patients with femoral neck fracture (n = 13): 10 women, median age 80 years; 3 men, median age 85 years. OA patients (n = 16): 10 women, median age 71 years; 6 men, median age 64 years. Healthy volunteers (n = 25): 16 women and 9 men, median age 77 years. Blood was sampled from the patients before and after surgery. Serum vitamin K1 measured by HPLC.	Vitamin K1: ↓ in patients with femoral neck fracture and OA vs. normal controls; ↓ after surgery. Carboxylated and undercarboxylated osteocalcin: ~ between case and control.
Silaghi et al. 2012 [28]	Non-inflammatory arthritis group: n = 17, median age 55 years, patients with OA or chondrocalcinosis Inflammatory arthritis group: n = 9, median age 55 years, patients with juvenile idiopathic arthritis, ankylosing spondylitis Control: n = 30, median age 42 years, no radiographic evidence of arthritis Uncarboxylated MGP measured by ELISA	Serum uncarboxylated MGP: ↑ in the controls vs. patients with arthritis; ↑ in the non-inflammatory arthritis group vs. inflammatory arthritis group. Synovial uncarboxylated MGP: ↑ in the inflammatory arthritis group vs. non-inflammatory arthritis group Synovial/serum uncarboxylated MGP ratio: ↑ in the inflammatory group vs. non-inflammatory group.
Rafael et al. 2014 [26]	OA samples from patients undergoing total knee replacement surgery. Control samples from the autopsy of subjects with no history of joint disease. Immunostaining technique.	Undercarboxylated GRP: ↑ in the OA cartilage matrix and synovial membrane vs. to carboxylated one. Carboxylated MGP: ↑ in the control cartilage matrix and synovial membrane vs. undercarboxylated ones.
Bing and Feng 2015 [27]	Case: 178 knee OA patients, aged 62.8 ± 7.4 years, 114 women: 64 men Control: 160 healthy outpatients in a hospital, aged 63.2 ± 8 years, 94 women: 66 men OA assessment: knee radiographs with KL criteria (at least ≥ 2 at one knee to be selected as cases) Uncarboxylated MGP measured using ELISA	Serum uncarboxylated MGP: ↓ in the OA patients vs. control. Synovial fluid uncarboxylated MGP level correlated negatively with the disease severity among the OA patients.
El-Brashy et al. 2016 [25]	Case: 40 knee OA patients (36 women: 10 men), age 50.4 ± 4.9 years, KL grade 2 or less Control 20 healthy individuals (85 women: 15 men), age 48.9 ± 4.6 years, Plasma phylloquinone level was measured using ELISA OA assessed using pain scale, The Western Ontario McMaster Scale (WOMAC), Thomas Grading Score and musculoskeletal ultrasound	Plasma vitamin K: ↓ in knee OA patients vs. control WOMAC score: ↑ in patients with vitamin K deficiency vs those who were sufficient. A significant positive correlation was found between plasma vitamin K level and medial cartilage thickness.

Abbreviation: ELISA, enzyme-linked immunosorbent assay; HPLC, high-performance liquid chromatography; GRP, gla-rich protein; MGP, matrix gla protein; OA, osteoarthritis; vs., versus; ↓, decrease; ↑, increase; ~, similar.