We studied two radiographic grading criteria: Kellgren–Lawrence grading and joint space width. These two methods for evaluating the degree of OA are widely used. In the present study they were significantly related to each other: the Kellgren–Lawrence grade varied inversely with joint space width. We also used the concept of GOA as a means of radiographic grading of OA [10
]. Several disease subsets in OA are recognized clinically. These subsets of OA fall into two broad groups: those causing biomechanical loading or instability at a specific joint, and those influencing generalized and systemic susceptibility to the process at multiple joints. The concept of generalized and systemic susceptibility is supported by studies indicating a subset of patients with polyarticular disease known as GOA. Earlier GOA is characterized by hand OA as a generalized nodal OA, which is a familial disease affecting mostly women and characterized by the development of Heberden nodes and a specific pattern of OA showing multiple joint involvement. Because levels of serum biochemical markers for arthritis depend on the circulating concentrations of molecules derived from the affected joints, the marker level is expected to be higher in patients with multiple joint involvement than in patients with a specific joint site. Therefore, in this study, to ascertain the ability of joint markers we used two OA populations: a knee OA group and a GOA group. The results obtained showed that CRP, pyridinoline, YKL-40 and MMP-3 were significantly greater in the GOA group than in the non-GOA group. In contrast, there was no significant difference in joint space width between the GOA and non-GOA groups.
There are two major categories of substances that are currently being investigated as potential biochemical markers for arthritis. One includes constituents of the extracellular matrix of the joint tissues; the other includes enzymes or cytokines that metabolize the molecules of the joint tissues. Among the biochemical markers investigated in the present study, pyridinoline is a major crosslink of collagen in the joint tissues, which is abundant both in cartilage and bone, and belongs to the former group. MMPs and TIMP are proteolytic enzymes that belong to the latter group [11
]. We do not know which group YKL-40 belongs to, because the function and origin of this substance is still not clear [12
]. Although the function of YKL-40 is not yet known, several studies have suggested that YKL-40 might be a useful new marker for patients with OA and rheumatoid arthritis [13
]. However, the biochemical markers of bone metabolism are also proposed as indicators of disease progress of OA [14
]. Spector and colleagues demonstrated that bone resorption is increased in patients with progressive knee OA and is not increased in those with nonprogressive knee OA. Altered bone turnover might be a diagnostic or therapeutic target in patients with progressive OA [16
Urinary pyridinoline has the most consistent relationship with radiographic grades of OA among the biochemical markers studied here. Pyridinium crosslinks consist of two major molecules, namely pyridinoline and its analogue deoxypyridinoline. Although both crosslinks are located in several tissues, deoxypyridinoline is more specifically located in bone, whereas pyridinoline is most abundant in cartilage and bone. Urinary excretion of deoxypyridinoline is therefore used clinically as a marker of bone metabolism, whereas urinary excretion of pyridinoline is considered to be a biochemical marker for cartilage destruction and metabolism as well as bone metabolism [17
]. However, because pyridinoline locates in several tissues of the joint in a significant amount [18
], urinary pyridinoline might be affected by the synthesis of osteophytes, sclerosis of subchondral bone and synovial degeneration as well as cartilage degeneration in the joints of OA.