Patient case (clinical description): A 47-year-old woman comes to the office complaining of pain in the calf and knee when she bends down. The pain limits her activity. Her medical history is significant for osteoarthritis, for which she uses nonsteroidal anti-inflammatory drugs (NSAIDs) for the past two years. She is living with her husband and has 3 children. She doesn't smoke but drinks alcohol occasionally. Her vital signs are normal. On physical examination, there is a small effusion in the right knee. The effusion grew a little larger and she developed a tender swelling in the popliteal fossa and calf. Both the pain and swelling worsened as she bent and straightened her knee.

Patient's own account: I'm a 47-year-old woman, married with 3 kids. I don't smoke and I drink occasionally. I went to the doctor because of pain in my calf and knee when I was bending down. This has been limiting my daily activities. I have been diagnosed with osteoarthritis for which I have taken anti-inflammatory drugs for the past 2 years. The doctor saw a small fluid buildup in my right knee. This buildup became a bit bigger and I have a swollen calf. The pain is worse when I bend and straighten my knee.

Clinical trial: Doxycycline and OA Progression

Eligibility criteria:
Inclusion Criteria:

          -  Women 45-64 years of age.

          -  Upper tertile of sex-, age- and race-adjusted norms for body mass index.

          -  Unilateral knee OA at baseline.

          -  Postmenopausal status or otherwise incapable of childbearing.

          -  Ability to ambulate (move about) independently without assistive devices.

          -  Ability to read and write in English or Spanish and give informed consent.

        Exclusion Criteria:

          -  Premenopausal status (unless subject has had a hysterectomy).

          -  Current use of any investigational drug.

          -  Significant hematologic, renal, hepatic or cardiovascular disease (but not including
             mild/moderate hypertension) or any other serious medical condition that might preclude
             the subject's ability to participate fully in the project, keep clinic appointments,
             etc.

          -  Prior surgery (including arthroscopy) of the contralateral knee.

          -  Significantly abnormal laboratory values at the time of enrollment.

          -  Pigmented villonodular synovitis of the knee.

          -  Synovial chondromatosis.

          -  Charcot arthropathy.

          -  A known "secondary" cause of OA, including acute or chronic infectious OA;
             crystal-induced arthritis; systemic inflammatory connective tissue disease (e.g.,
             rheumatoid arthritis, systemic lupus erythematosus); osteonecrosis; Paget's disease;
             or metabolic diseases, such as hemochromatosis, Wilson's disease, or ochronosis.
             Chondrocalcinosis, however, will not be an exclusion criterion.

          -  Conditions other than knee OA which limit lower extremity function and mobility and/or
             would confound the evaluation of knee pain and function (e.g., clinically significant
             spinal or hip arthritis, painful or dysfunctional feet, peripheral vascular disease,
             lumbar radiculopathy, stroke, etc.).

          -  Steroid injection into either knee within past 3 months.

          -  A history of photosensitivity (sensitivity to light) or any other adverse reaction to
             a tetracycline.

          -  Failure to pass a "faintness-of-heart" test (pre-randomization compliance test).

          -  Prior chronic use of tetracycline (e.g., for severe acne).

          -  Severe OA (Kellgren and Lawrence Grade IV) of the index knee.

          -  Salicylate use, with a mean dose >2g/d.

          -  Institutionalization.
Female
No healthy subjects accepted to join the trial.
Subject must be at least 45 Years old.
Subject must be at most 64 Years

Eligibility (NLI label): Entailment