Context:​ Knee osteoarthritis (OA) is a leading cause of disability in older persons. Few risk factors for disease progression or functional decline have been identified. Hip-knee-ankle alignment influences load distribution at the knee;​ varus and valgus alignment increase medial and lateral load, respectively.

Objective:​ To test the hypotheses that (1) varus alignment increases risk of medial knee OA progression during the subsequent 18 months, (2) valgus alignment increases risk of subsequent lateral knee OA progression, (3) greater severity of malalignment is associated with greater subsequent loss of joint space, and (4) greater burden of malalignment is associated with greater subsequent decline in physical function.

Design and Setting:​ Prospective longitudinal cohort study conducted March 1997 to March 2000 at an academic medical center in Chicago, Ill.

Participants:​ A total of 237 persons recruited from the community with primary knee OA, defined by presence of definite tibiofemoral osteophytes and at least some difficulty with knee-requiring activity;​ 230 (97%) completed the study.

Main Outcome Measures:​ Progression of OA, defined as a 1-grade increase in severity of joint space narrowing on semiflexed, fluoroscopically confirmed knee radiographs;​ change in narrowest joint space width;​ and change in physical function between baseline and 18 months, compared by knee alignment at baseline.

Results:​ Varus alignment at baseline was associated with a 4-fold increase in the odds of medial progression, adjusting for age, sex, and body mass index (adjusted odds ratio [OR], 4.09;​ 95% confidence interval [CI], 2.20-7.62). Valgus alignment at baseline was associated with a nearly 5-fold increase in the odds of lateral progression (adjusted OR, 4.89;​ 95% CI, 2.13-11.20). Severity of varus correlated with greater medial joint space loss during the subsequent 18 months (R = 0.52;​ 95% CI, 0.40-0.62 in dominant knees), and severity of valgus correlated with greater subsequent lateral joint space loss (R = 0.35;​ 95% CI, 0.21-0.47 in dominant knees). Having alignment of more than 5° (in either direction) in both knees at baseline was associated with significantly greater functional deterioration during the 18 months than having alignment of 5° or less in both knees, after adjusting for age, sex, body mass index, and pain.

Conclusion:​ This is, to our knowledge, the first demonstration that in primary knee OA varus alignment increases risk of medial OA progression, that valgus alignment increases risk of lateral OA progression, that burden of malalignment predicts decline in physical function, and that these effects can be detected after as little as 18 months of observation.