This study reports a post-hoc analysis of the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study. 407 females, between the ages of 50 and 60, at high risk of developing knee osteoarthritis (OA) were included. Patients were randomized using a 2x2 factorial design into 4 groups, that received either glucosamine sulfate (1500mg orally per day) and a tailored diet and exercise program, glucosamine sulfate alone, a diet and exercise program and placebo, or just a placebo. The purpose of this study was to conduct an exploratory analysis of the incidence of joint space narrowing (progression of >1.0 mm) at 2.5 years to delineate the preventative effects of glucosamine sulfate, diet, and exercise. The results identified a significantly lower incidence of joint space narrowing in patients who received glucosamine sulfate compared to individuals that did not. No differences were noted between the patients receiving diet and exercise and those not receiving diet and exercise, although there was low compliance overall, to the program.