Skip navigation

Prognostic factors for progression of OA knee

Clinical bottom line

Generalised OA and level of hyaluronic acid in serum are the only factors for which there is strong evidence that they are markers of progression of knee osteoarthritis.


JN Belo et al. Prognostic factors of progression of osteoarthritis of the knee: a systematic review of observational studies. Arthritis & Rheumatism 2007 57: 13-26.


It is always useful to know if one or more features of an illness predict the speed at which it gets worse. The trouble is that small observational studies may find some statistical significance just by the random play of chance, or because of some feature of the way they were conducted. Systematic review is needed to pull together the evidence and look at its quality, validity, size, and consistency.


This was a systematic review looking for observational studies published up to the end of 2003. The methodological quality of the studies found was measured, and an evidence synthesis performed on the basis of the level of evidence defined as:

Studies were judged of high quality when scoring 9 or more on a 13 point scale. Only statistically significant associations were examined for the evidence synthesis.


Thirty-seven articles were examined, all with a prospective design, and all used recognised diagnostic criteria for osteoarthritis. Follow up was at least 12 months, and often much longer. The main results are in Table 1.

Table 1: Factors associated with or not associated with progression of osteoarthritis

Strength of evidence
Strong evidence Level of hyaluronic acid in serum
generalised OA
Limited evidence Synovial fluid volume, nodal warmth, medial bone marrow oedema lesions, adducton moment, joint alignment, low serum levels or dietary intake of vitamin D, low dietary vitamin C, use of walking aids, use of NSAIDs
Not associated
Strong evidence Sex, knee injury, quadriceps strength, regular sports activity, knee pain at baseline, radiological severity of OA
Limited evidence Oestrogen, uric acid, localised OA, other markers of bone turnover, lateral bone marrow oesema lesions, meniscectomy, chondrocalcinosis, running, miacin, folate, smoking, low intake of beta-carotene, vitamins E1, B1 and B6
Conflicting evidence Age, bone density, IGF-1, heberden's node, keratan sulphate, COMP, duration of symptoms, clinica severity, CRP at baseline, BMI


This is a good and useful example of how evidence of progression can be examined in systematic review. It is a difficult area.