ARTHRITIS & RHEUMATISMVol. 56, No. 11, November 2007, pp 3872–3880© 2007, American College of Rheumatology

LETTERS

DOI 10.1002/art.23031

Does knee malalignment predispose to osteoarthritis?Comment on the articles by Brouwer et al and Hunteret al and the editorial by Sharma

To the Editor:The Osteoarthritis section of the April 2007 issue of

Arthritis & Rheumatism included reports of studies by Brouweret al (1) and Hunter et al (2), concerning knee malalignmentand the risk of subsequent development of osteoarthritis, thatappear to be contradictory. The accompanying editorial bySharma (3) did not resolve the contradiction.

Since these studies addressed an important topic onwhich there is little or no previous literature, used differentmethodologies, and led to different conclusions, it would behelpful if Dr. Sharma or the authors of the studies could addbrief commentary to assist those readers who are not research-ers in this field.

Paul Monach, MD, PhDBrigham and Women’s HospitalBoston, MA

1. Brouwer GM, van Tol AW, Bergink AP, Belo JN, Bernsen RM,Reijman M, et al. Association between valgus and varus alignmentand the development and progression of radiographic osteoarthritisof the knee. Arthritis Rheum 2007;56:1204–11.

2. Hunter DJ, Niu J, Felson DT, Harvey WF, Gross KD, McCree P, etal. Knee alignment does not predict indicent osteoarthritis: theFramingham Osteoarthritis Study. Arthritis Rheum 2007;56:1212–8.

3. Sharma L.The role of varus and valgus alignment in knee osteoar-thritis [editorial]. Arthritis Rheum 2007;56:1044–7.

DOI 10.1002/art.23029

Reply

To the Editor:Two interesting and timely studies dealing with mal-

alignment and its relationship to incident (1,2) and progressive(2) radiographic knee osteoarthritis (OA) appeared in a recentissue of Arthritis & Rheumatism. The study by Brouwer andcolleagues (2) (discussed in 3) showed that malalignmentincreased the risk of incident knee OA, whereas the study byHunter et al (1) did not. While the latter study has numerousstrengths including a careful assessment of alignment, arethere elements that could help to explain why a relationshipwas not detected? As a smaller case–control study consideringquartiles of alignment, did the study by Hunter and colleagueshave less power than the study by Brouwer et al? Is thereference group in the presentation of primary results in thereport by Hunter et al (Table 2), i.e., subjects with the mostvalgus knees, a group that is itself at greater risk for incidentOA than are persons with more neutrally aligned knees? Arethe cut points for alignment quartiles (5–10 valgus, 3–4 valgus,0–2 valgus, 1–7 varus) meaningful divisions? Since the medialjoint space is narrower than the lateral in the majority ofhealthy knees, does the definition of medial tibiofemoral OAused for the secondary analyses, i.e., medial greater thanlateral joint space narrowing, truly distinguish knees with

medial OA, especially when the Kellgren/Lawrence grade (4)is 2?

The alternative posed by Hunter and colleagues—thatmalalignment may simply be a marker of increasing diseaseseverity as opposed to a risk factor for incident disease—isamong several possibilities that should be considered. The riskfactor profiles for incident and progressive knee OA are notidentical; it is possible for a factor to have no impact on the riskof incident OA and still accelerate progression, perhaps re-lated to a more vulnerable joint organ milieu in the alreadydiseased knee. As pointed out in each of the articles (1–3),biomechanical studies reveal that malalignment influencesload distribution; evidence of its impact on the joint comesboth from animal studies and from natural history studies ofhumans with knee OA, and most recently, from the study byBrouwer et al (2). Whether or not malalignment precedes thedevelopment of knee OA, there is strong evidence that itinfluences the subsequent disease course. Results from addi-tional studies will further advance knowledge of the influenceof malalignment on the risk of incident knee OA.

Leena Sharma, MDNorthwestern UniversityChicago, IL

1. Hunter DJ, Niu J, Felson DT, Harvey WF, Gross KD, McCree P, etal. Knee alignment does not predict indicent osteoarthritis: theFramingham Osteoarthritis Study. Arthritis Rheum 2007;56:1212–18.

2. Brouwer GM, van Tol AW, Bergink AP, Belo JN, Bernsen RM,Reijman M, et al. Association between valgus and varus alignmentand the development and progression of radiographic osteoarthritisof the knee. Arthritis Rheum 2007;56:1204–11.

3. Sharma L.The role of varus and valgus alignment in knee osteoar-thritis [editorial]. Arthritis Rheum 2007;56:1044–7.

4. Kellgren JH, Lawrence JS, editors. The epidemiology of chronicrheumatism: atlas of standard radiographs. Oxford: Blackwell Sci-entific; 1963.

Editor’s note. Readers sometimes find it curious that aneditorial addresses only one of two or more papers on the sametopic in the same issue of the journal. When this happens, it is notbecause the editors have deliberately chosen to slight one of thepapers. Manuscripts are accepted at very different times and areassigned to a specific month of publication only when the galleyshave been returned and all necessary permissions have beensigned and submitted—times that vary from a few days to manymonths after acceptance. Editorials, on the other hand, aresolicited at the time of acceptance of a paper. The table ofcontents of a specific issue is finalized approximately 2 monthsbefore the publication date.

In the case of the papers and editorial described in theabove letters, the editorial was solicited and accepted before thesecond paper was accepted. By happenstance, the completeddocuments for all the papers arrived sufficiently closely in time topermit their inclusion in the same issue. To have asked theeditorial writer to rewrite the already accepted, edited, andproofread editorial would have unduly delayed the publication ofall three papers.

Michael D. Lockshin, MDEditor, Arthritis & Rheumatism

3872