97 - Effect of Estrogen Replacement Therapy on Healing of a Femoral Articular Cartilage Defect in a Rat Model: A Pilot Study

Poster Board Number: 97
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Odd poster #s – first hour
Even poster #s – second hour

Abstract Body : Introduction and Objective: Declines in circulating estrogen and knee trauma are known risk factors for developing knee osteoarthritis (OA), and postmenopausal women have a higher incidence and severity of this disease. To better understand the relationship between estrogen levels and joint damage repair we used an ovariectomized (OVX) rat model to create a standardized, cylindrical defect in the knee articular cartilage. The objective of this study was to determine the effect of estrogen replacement therapy (ERT) on healing of femoral articular cartilage in OVX rats.

Materials and Methods: Female Lewis rats were randomly divided into 3 groups: OVX rats with 60-day estrogen supplement (n = 5, OVX+ERT group), OVX rats without hormonal intervention (n = 5, OVX group), and non-OVX rats without hormonal intervention (n = 5, control group). Estrogen supplementation was given on day 1 of the study as a 0.025-mg 17β-estradiol subcutaneous pellet. A focal knee cartilage defect was made unilaterally on day 14 of the study. The surgery involved an incision through the skin, lateral reflection of the patellar tendon, and introduction of a cylindrical defect to the medial femoral condyle through the articular cartilage using a drill with a 0.75-mm drill bit. Rats were regularly weighed and sacrificed on day 60. Rat knees were stained with Safranin O to visualize the articular cartilage. The defect was analyzed histologically and measured. Blood was collected at 3 time intervals for 17β-estradiol serum analyses. A 2-way ANOVA repeated measure in 1 domain (time) was used to assess differences in defect size, weight, and estrogen concentration between groups. Significance was set at .05.

Results: Rats in both OVX groups had greater average body weight than the controls, 368 g in the OVX+ ERT group and 376 g in the OVX group vs. 263 g in the control group. Body weight did not change significantly throughout the experiment in the OVX and control groups. In the OVX+ERT group, weights started declining after pellet insertion, reaching a minimum of 334 g at 3 weeks postsurgery (significant), after which they started increasing and caught up with the ERT group by the end of the experiment. The average defect size was 0.473 mm in the OVX+ERT group, 0.664 mm in the OVX group, and 0.876 mm in the control group. Defect size was significantly smaller in the OVX+ERT group than in the ERT or control groups. There was no difference in defect size between the OVX and control groups. The OVX+ERT group had higher serum estrogen levels after pellet insertion, but after 3 weeks and throughout the rest of the experiment, estrogen levels were not different among the 3 groups. Serum estrogen levels in the control group were not different from the OVX group.

Conclusion: A significant decrease in defect size in the OVX+ERT group compared with the OVX and control groups indicated that estrogen supplementation promoted the healing of articular cartilage.

Significance/Implication: Severe joint damage in the control group may indicate that only a marked increase in circulating levels of estrogen (as in the OVX+ERT group) can stimulate cartilage repair. Future studies should use other methods of estrogen supplementation with regular monitoring of serum estrogen levels to better understand the correlation between joint defect healing and circulating estrogen levels.