Osteoarthritis (OA) occurs naturally in cynomolgus macaques. The purposes of the present study were to: 1) develop histological measurement schemes to measure the cross-sectional area of axial and abaxial osteophytes in the proximal tibia; 2) determine the effects of long-term estrogen replacement therapy (ERT) on osteophyte prevalence and area; and 3) assess relationships between osteophyte size and risk factors of OA (age and body weight) and concurrent bone and cartilage lesions. Adult female cynomolgus macaques (n = 180) were bilaterally ovariectomized (OVX) and were treated for 3 years with ERT, soy phytoestrogens (SPE), or no hormones (OVX controls). At necropsy, the prevalence and cross-sectional area of periarticular tibial osteophytes were evaluated histologically. Treatment effects on osteophyte prevalence and area were evaluated using Chi-square analyses and Kruskal-Wallis test, respectively; other comparisons were evaluated using regression analyses. The prevalence of abaxial osteophytes in the medial tibial plateau was not significantly affected by treatment group; however, the prevalence of abaxial osteophytes in the lateral tibial plateau was significantly lower in ERT group than SPE group (p < 0.01). The total number of abaxial osteophytes (sum of lateral and medial) was significantly lower in ERT group compared to OVX and SPE groups. Neither the prevalence of axial osteophytes nor the sum of lateral and medial axial osteophytes was significantly affected by treatment in either tibial plateau. There were no significant treatment effects on axial or abaxial osteophyte cross-sectional area in either tibial plateau. There was a significant positive correlation between abaxial osteophyte area and SCB thickness in the medial tibial plateau (p = 0.048); however, there were no significant correlations between abaxial osteophyte area (medial or lateral) and age or body weight. In this model of naturally occurring OA, long-term ERT does not consistently reduce the prevalence, and has no significant effects on cross-sectional area, of periarticular tibial osteophytes.
Bibliographical noteFunding Information:
The authors thank Josh Parker, Anne Undersander, and Drs. Kim Ham and Laura Eikmeier for technical assistance. We also thank Dr. Thomas Clarkson for providing the knee joints for this study, Dr. Mary Anthony for providing the details of the clinical trial, and Jean Gardin for assistance with tissue collection. This study was supported by the National Institutes of Health Grants RR14099 and RR18719.
- Animal models
- Bone histomorphometry