OBJECTIVE: To determine whether oral administration of doxycycline in clinically relevant doses will suppress activities of collagenase and gelatinase in extracts of human osteoarthritic (OA) cartilage. METHODS: Femoral heads were obtained from 21 patients undergoing arthroplasty for endstage hip OA. Activities of collagenase and gelatinase were measured in extracts of the OA cartilage from patients who received doxycycline, 100 mg bid or qam for 5 days before surgery (n = 5 and n = 6, respectively), 200 mg as a single dose 3 days before surgery (n = 4); or no doxycycline (n = 6). RESULTS: Five days of doxycycline treatment, in a dose of either 100 mg bid or 100 mg qam, inhibited gelatinase activity in the cartilage extracts (p = 0.003, 0.008, respectively). The bid dose also inhibited collagenase activity (p = 0.002), but inhibition of collagenase with 100 mg qam did not quite reach statistical significance (p = 0.055), in comparison with the values for the untreated OA controls. The single 200 mg dose, given 3 days before procurement of the cartilage, was ineffective in inhibiting metalloproteinase activity. CONCLUSION: Oral administration of doxycycline significantly inhibited collagenase and gelatinase activity in human OA cartilage. The effective dose is likely to be well tolerated during chronic administration, e.g., in a clinical trial to assess the potential of the drug to modify cartilage breakdown in OA.
OBJECTIVE: To determine whether oral administration of doxycycline in clinically relevant doses will suppress activities of collagenase and gelatinase in extracts of humanosteoarthritic (OA) cartilage. METHODS: Femoral heads were obtained from 21 patients undergoing arthroplasty for endstage hip OA. Activities of collagenase and gelatinase were measured in extracts of the OA cartilage from patients who received doxycycline, 100 mg bid or qam for 5 days before surgery (n = 5 and n = 6, respectively), 200 mg as a single dose 3 days before surgery (n = 4); or no doxycycline (n = 6). RESULTS: Five days of doxycycline treatment, in a dose of either 100 mg bid or 100 mg qam, inhibited gelatinase activity in the cartilage extracts (p = 0.003, 0.008, respectively). The bid dose also inhibited collagenase activity (p = 0.002), but inhibition of collagenase with 100 mg qam did not quite reach statistical significance (p = 0.055), in comparison with the values for the untreated OA controls. The single 200 mg dose, given 3 days before procurement of the cartilage, was ineffective in inhibiting metalloproteinase activity. CONCLUSION: Oral administration of doxycycline significantly inhibited collagenase and gelatinase activity in human OA cartilage. The effective dose is likely to be well tolerated during chronic administration, e.g., in a clinical trial to assess the potential of the drug to modify cartilage breakdown in OA.
Authors: David M Thompson; Hsi-Ming Lee; Julie A Stoner; Lorne M Golub; Pirkka V Nummikoski; Jeffrey B Payne Journal: J Periodontal Res Date: 2019-04-29 Impact factor: 4.419