Quadriceps weakness may be present in patients who have osteoarthritis but do not have knee pain or muscle atrophy; this suggests that the weakness may be due to muscle dysfunction. The data are consistent with the possibility that quadriceps weakness is a primary risk factor for knee pain, disability, and progression of joint damage in persons with osteoarthritis of the knee.

A CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions.

Objective. Quadriceps weakness is a risk factor for incident knee osteoarthritis (OA). We describe a randomized controlled trial of effects of lower-extremity strength training on incidence and progression of knee OA. Methods. A total of 221 older adults (mean age 69 years) were stratified by sex, presence of radiographic knee OA, and severity of knee pain, and were randomized to strength training (ST) or range-of-motion (ROM) exercises. Subjects exercised 3 times per week (twice at a fitness facility, once at home) for 12 weeks, followed by transition to home-based exercise after 12 months. Assessments of isokinetic lower-extremity strength and highly standardized knee radiographs were obtained at baseline and 30 months. Results. Subjects in both groups lost lower-extremity strength over 30 months; however, the rate of loss was slower with ST than with ROM. Compared with ROM, ST decreased the mean rate of joint space narrowing (JSN) in osteoarthritic knees by 26% (P ‫؍‬ not significant). However, the difference between ST and ROM groups with respect to frequency of knee OA progression in JSN consensus ratings was marginally significant (18% versus 28%; P ‫؍‬ 0.094). In knees that were radiographically normal at baseline, JSN >0.50 mm was more common in ST than in ROM (34% versus 19%; P ‫؍‬ 0.038). Incident JSN was unrelated to exercise adherence or changes in quadriceps strength or knee pain. Conclusion. The ST group retained more strength and exhibited less frequent progressive JSN over 30 months than the ROM group. The increase in incident JSN >0.50 mm in ST is unexplained and requires confirmation.

Objective. To confirm preclinical data suggesting that doxycycline can slow the progression of osteoarthritis (OA). The primary outcome measure was joint space narrowing (JSN) in the medial tibiofemoral compartment.Methods. In this placebo-controlled trial, obese women (n ‫؍‬ 431) ages 45-64 years with unilateral radiographic knee OA were randomly assigned to receive 30 months of treatment with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured manually in fluoroscopically standardized radiographic examinations performed at baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6-month intervals.Results. Seventy-one percent of all randomized subjects completed the trial. Radiographs were obtained from 85% of all randomized subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects who completed the study per protocol. After 16 months of treatment, the mean ؎ SD loss of joint space width in the index knee in the doxycycline group was 40% less than that in the placebo group (0.15 ؎ 0.42 mm versus 0.24 ؎ 0.54 mm); after 30 months, it was 33% less (0.30 ؎ 0.60 mm versus 0.45 ؎ 0.70 mm). Doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, suggesting the presence of a floor effect. However, the frequency of followup visits at which the subject reported a >20% increase in pain in the index knee, relative to the previous visit, was reduced among those receiving doxycycline. In contrast, doxycycline did not have an effect on either JSN or pain in the contralateral knee. In both treatment groups, subjects who reported a >20% increase in knee pain at the majority of their followup visits had more rapid JSN than those whose pain did not increase.Conclusion. Doxycycline slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in the contralateral knee suggests that pathogenetic mechanisms in that joint were different from those in the index knee.In the present report, we describe the results of a randomized, placebo-controlled, double-blind trial of the tetracycline antibiotic, doxycycline, in subjects with knee osteoarthritis (OA). Selection of doxycycline as a potential disease-modifying OA drug was based not on the premise that OA is an infectious disease, but rather on results of in vitro studies showing 1) that doxycycline inhibited the degradation of type XI collagen, one of the minor collagens of articular cartilage, by 72-kd gelati-

Objective. To determine whether baseline lower extremity muscle weakness is a risk factor for incident radiographic osteoarthritis (OA) of the knee.Methods. This prospective study involved 342 elderly community-dwelling subjects (178 women, 164 men) from central Indiana, for whom baseline and followup (mean interval 31.3 months) knee radiographs were available. Lower extremity muscle strength was measured by isokinetic dynamometry and lean tissue (Le., muscle) mass in the lower extremities by dual x-ray absorptiometry.Results. Knee OA was associated with an increase in body weight in women (P = 0.0014), but not in men.In both sexes, lower extremity muscle mass exhibited a strong positive correlation with body weight. In women, after adjustment for body weight, knee extensor strength was 18% lower at baseline among subjects who developed incident knee OA than among the controls (P = 0.053), whereas after adjustment for lower extremity muscle mass, knee extensor strength was 15% lower than in the controls (P not significant). In men, in contrast, adjusted knee extensor strength at baseline was comparable to that in the controls. Among the 13 women who developed incident OA, there was a strong, highly significant negative correlation between body weight and extensor strength (r = -0.740, P = 0.003),

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Objective. To evaluate progression of joint space narrowing in radiographs of osteoarthritic (OA) knees imaged in both the standing anteroposterior (AP) and the Lyon schuss positions, using alternative methods to measure joint space width (JSW). The aim of treatment of patients with osteoarthritis (OA) is to improve pain and function and, ideally, to prevent progression of structural damage. Therapeutic agents that prevent the development, or slow the progression, of structural changes of OA have been designated disease-modifying OA drugs (DMOADs).

qMRI and LS radiography detected significant change in KLG3 participants at high risk of progression, but not in KLG2 participants, and only small changes in controls. At 12 and 24 months, LS displayed greater, and FF less, sensitivity to change in KLG3 participants than qMRI.