Effect of Glucosamine on Joint Structure and Quality of Life (JOG)

Inclusion Criteria: * Female or male (female only for skin sub-study) * 35-65 years of age (40 -65 for skin sub-study) * Willingness to provide informed consent * Willingness to be randomized to glucosamine or placebo * Knee pain on more days than not for at least one month in past year * Sum of WOMAC pain subscales between 300 and 500 inclusive * Ability to read and understand English * Ability to understand study procedures * Dry skin for sub-study Exclusion Criteria: * Plans for elective surgery in the next 12 months Plans to move out of the area in the next 12 months * Concurrent medical/arthritic disease that could confound or interfere with evaluation of pain or efficacy including inflammatory arthritis * Spine or hip pain of sufficient magnitude to interfere with the evaluation of the knee * Isolated patellofemoral disease manifested by primarily anterior knee pain in the absence of tibiofemoral radiographic finding * History of arthroscopy of the affected knee within 6 months prior to study entry * Allergy to,or history of significant clinical or laboratory adverse experience associated with acetaminophen or glucosamine * Inability to undergo a MRI of knee * Inability to walk without a cane or other assistive device * Liver or kidney disease * Diabetes mellitus * Women who are currently pregnant or nursing, pregnant within the previous six months, or planning on becoming pregnant within the next 6 months * Unwilling to use double barrier method of contraception * Alcohol use in excess of 3 mixed drinks/day * Corticosteroid treatment * Sustained use of NSAIDS including aspirin in anti-inflammatory doses may be used for treatment of pain other than knee pain, if such use is intermittent * Topical analgesics * Other medical therapy for arthritis within one month prior to entry * Participation in another clinical study with an investigational agent within the last 4 weeks * Have taken glucosamine in past 3 months, chondroitin, Sam-E, MSM or other dietary supplements for knee pain within the past 6 months * Have taken a bisphosphonate medication that affects bone turnover in the past 6 months * Initiation of physical therapy or muscle conditioning program within 2 months prior to study entry * Intra-articular injection of hyaluronic acid or congeners into the knee within past 12 months. * Concurrent use of tetracycline, anticoagulants, dietary supplements or other complementary or alternative regimens for joint pain * History of knee or hip replacement * Weight exceeds 285 in men or 250 in women. * Have had any of the following cancers: Acute Leukemia, Brain, Chronic Leukemia, Esophagus, Liver,Lung, Lymphoma, Multiple Myeloma, Pancreas, Skin Melanoma, and Stomach. * Have taken any of the following doctor prescribed medications for arthritis: Methotrexate, Plaquenil, Hydroxychloroquine, Enbrel, Etanercept, Remicade, Infliximab, Arava, Leflunomide, Gold shots or pills, Prednisone pills, steroid pills, or glucocorticoid pills taken by mouth, Sulfasalazine, Kineret, Anakinra, Humira, and Adalimumab. * Kellgren-Lawrence score of 4 (severe) in both knees based on x-ray. * Anterior knee pain only with normal x-ray results.