RESUMO
The present study aimed to investigate the effect of orally administered simvastatin on lumbar vertebral bone mass and intervertebral disc (IVD) degeneration in ovariectomized (OVX) rats. A total of 30 female Sprague-Dawley (SD) rats were subjected to either bilateral ovariectomy (n=20) or sham surgery (n=10). After 12 weeks, the OVX rats were orally administered either saline vehicle (OVX + V group; n=10), or 5 mg/kg/day simvastatin (OVX + SIM group; n=10). Following 12 weeks of treatment, necropsy was conducted and bone mineral density (BMD) was determined in the L5-6 vertebrae. Furthermore, the microstructure and biomechanical properties of the L3 vertebrae were detected by micro-computed tomography and compression testing, respectively. The L5-6 vertebrae were analyzed by measurement of IVD height, observation of histological changes by van Gieson staining, and evaluation of collagen-II (col-II), aggrecan (AGG) and collagen I (col-I) expression by immunohistochemical analysis. Rats in the OVX+V group had lower BMD, bone volume/trabecular volume ratio, maximum load and elastic modulus than the sham group. Rats in the OVX + SIM group had higher BMD and biomechanical strength values than the rats in the OVX+V group. Histological analysis showed that the OVX + V and OVX + SIM groups exhibited significantly higher disc degeneration scores and significantly lower IVD height than the sham group. Immunohistochemical analysis revealed lower expression levels of col-II and AGG, but higher levels of col-I in the annulus fibrosis and endplate in OVX+V rats compared with the sham group. The OVX + SIM group exhibited levels of col-II, AGG and col-I expression comparable with those of OVX+V rats, with the exception of an upregulation of col-II expression in the annulus fibrosis. These data demonstrate that simvastatin treatment partially prevented bone loss and the deterioration of biomechanical properties of lumbar vertebrae, but not the progression of IVD degeneration in OVX rats.
RESUMO
Osteoarthritis (OA) is a chronic degenerative disease involving multiple physiopathological mechanisms. The increased prevalence of OA after menopause and the presence of estrogen receptors in joint tissues suggest that estrogen could help prevent development of OA. This review summarizes OA research with a focus on the effects of estrogen and selective estrogen receptor modulators (SERMs). Preclinical studies and clinical trials of estrogen therapy have reported inconsistent results. However, almost all studies assessing SERM treatment have obtained more consistent and favorable effects in OA with a relatively safety and tolerability profiles. At present, some SERMs including raloxifene and bazedoxifene have been approved for the treatment of osteoporosis. In summary, estrogen-related agents may exert both a direct effect on subchondral bone and direct and/or indirect effects upon the surrounding tissues, including the articular cartilage, synovium, and muscle, to name a few. Estrogen and SERMs may be particularly favorable for postmenopausal patients with early-stage OA or osteoporotic OA, a phenotype defined by reduced bone mineral density related to high remodeling in subchondral bone. At present, no single drug exists that can prevent OA progression. Although estrogen-related drugs provide insight into the continued work in the field of OA drug administration, further research is required before SERMs can become therapeutic alternatives for OA treatment.