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Keywords:

  • cartilage;
  • estrogen;
  • osteoarthritis;
  • proteoglycans

Abstract

Aims: To investigate the effects of ovariectomy and estrogen replacement therapy (ERT) on the structural integrity and proteoglycan (PG) content of articular cartilage (AC) and bone mineral density (BMD) in an ovine model of osteoarthritis (OA) induced by meniscectomy.

Method:  Thirty aged ewes were used for the study. Six had ovariectomy alone (OVX), 6 meniscectomy alone (OA) and 12 ovariectomy and meniscectomy (OVX + OA). Six of the (OVX + OA) sheep received Femtran-50 (3M) estrogen (50 µg/day) patches (OVX + OA + ERT). Six animals were used as non-operated controls (NOC). Three months post-surgery all animals were sacrificed, the stifle joints dissected through the site of lesions, and coronal sections of the lateral femoral condyle (LFC) and lateral tibial plateau (LTP) were cut which were each subdivided into inner (I), middle (M) and outer (O) zones. Toluidine blue stained sections were examined using a modified Mankin scoring system, and AC–PG content determined via computer image analysis.

Results:  There were no significant differences between lesion scores among the OA, OVX + OA and OVX + OA + ERT groups, yet all had significantly higher scores than NOC and OVX in each region (P < 0.005). Computer image analysis of PG content in stained sections showed no difference between OVX and NOC. However, in LFC-AC the loss of PG was highest in the OVX + OA group (P < 0.005) compared to the NOC or OVX groups. The bone mineral density (BMD) of the LFC averaged for all zones was higher in the OVX + OA + ERT group than the OVX + OA group (P < 0.02) with the most significant rise being in the I-zone (P < 0.002). Significantly in this same zone of the OVX + OA + ERT group the AC-PG content was higher than in the corresponding zone of the OVX + OA group (P < 0.05).

Conclusions:  While ERT did not reduce the focal AC lesions scores in the lateral compartment of this OA model it did mitigate the loss of PG from adjacent joint cartilage and increase the bone mineral density (BMD), especially in the I-zone. These findings are consistent with epidemiological studies which suggest that ERT may slow the progression of OA in postmenopausal women.