title: The potential role of doxycycline in the treatment of osteoarthritis of the temporomandibular joint.
abstract: Collagenase and gelatinase are matrix metalloproteinases (MMPs) which play an important role in tissue destruction in arthritic joints. Studies have demonstrated that tetracyclines can inhibit MMPs and prevent tissue destruction independent of their antimicrobial activity. The purpose of this pilot study is to assess the potential therapeutic role of Doxycycline in patients with advanced osteoarthritis of the temporomandibular joint (TMJ). This ongoing investigation includes patients with a diagnosis of osteoarthritis of the TMJ based on clinical and diagnostic imaging findings, symptoms (localized TMJ pain, limited mobility, dysfunction) for a minimum of 36 months, and failure of previous non-surgical and surgical modalities to alleviate the symptoms. A synovial fluid sample is collected by a saline injection and aspiration technique, followed by diagnostic arthroscopy. Patients are placed on Doxycycline 50 mg BID for three months and then undergo repeat diagnostic arthroscopy and synovial fluid collection. The samples are stored at -80 degrees C. Collagenase activity is determined by a combination of SDS-polyacrylamide gel electrophoresis and fluorography and calculated based on the percentage of collagen alpha chains that are degraded into alphaA breakdown products. Three patients have completed the three-month course of Doxycycline thus far, and 5 joints with osteoarthritis have been analyzed. All patients were female (mean age = 35, mean duration of symptoms = 132 months) and had undergone previous bilateral arthroscopies. One patient had undergone unilateral arthroplasty. The mean collagenase activity showed 55% collagen lysis prior to Doxycycline treatment and 19% after three months of therapy. The mean gelatinase activity was 28% prior to Doxycycline treatment and 7% after three months of therapy. The mean interincisal opening was 33 mm initially and 41 mm after three months of Doxycycline. Subjectively, two of the three patients reported significant improvement in their overall symptoms, which they had not experienced over the previous three years. One patient did not experience any change in symptoms, in spite of a marked reduction in collagenase activity from 86.4% to 9.6%. Because of the very small numbers of patients enrolled in this pilot study so far, no statistically significant differences could be appreciated. However, the dramatic reduction in collagenase activity in these patients, with a long history of TMJ symptoms from osteoarthritis, suggests the potential promising role of Doxycycline in the management of osteoarthritis, and further investigation is warranted.
authors.affiliation: Columbia University, New York, New York, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Israel
authors.forename: N S
authors.initials: NS
authors.lastname: Ramamurthy
authors.forename: R
authors.initials: R
authors.lastname: Greenwald
authors.forename: L
authors.initials: L
authors.lastname: Golub
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017364:Collagenases / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D010003:Osteoarthritis / Q000188:drug therapy* / Q000201:enzymology; D010865:Pilot Projects; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013582:Synovial Fluid / Q000201:enzymology; D013705:Temporomandibular Joint Disorders / Q000188:drug therapy* / Q000201:enzymology