Short- to Mid-Term Effects of Ovariectomy on Bone Turnover, Bone Mass and Bone Strength in Rats

Abstract

Osteoporosis (OP) that is associated with ovarian hormone deficiency following menopause is by far the most common cause of age-related bone loss. Postmenopausal osteoporosis (POP) has become a major problem with significant morbidity and mortality.1) Bone loss induced by ovariectomy in rats has been widely used as a model of POP and has been validated as a clinically relevant model of this condition in human.Peripheral quantitative computed tomography (pQCT) and dual energy X-ray absorptiometry (DEXA) are non-invasive bone densitometry methods used in clinical settings for assessment of bone density as well as the efficacy of treatment for osteoporosis. 2,3) pQCT provides measurement of volumetric bone densities (vBMD, total and cortical bone mineral density) as well as a set of geometric variables including cross-sectional area; while DEXA provides measurements of bone mineral content (BMC) and the area of the scanned region and areal bone mineral density. Although DEXA is one of the most commonly used clinical methods for measurement of bone mass, it is not ideal for use in animal studies and clinical trials due to its inability to distinguish between cancellous and cortical bone 4) and provide limited information regarding bone architecture. 5) In contrast, pQCT is now the method of choice as it can provide vBMD, differentiate cortical and trabecular bone compartments and perform in vivo measurement of histomorphometric parameters like endosteal and periosteal circumferences, total and cross-sectional bone areas. 6)As an alternative to four-point bending testing, three-point bending testing has become more widely used for the evaluation of whole bone strength. Although the two testing modalities are complementary to some extent, when describing the mechanical characteristics of bone, it appears that four-point bending testing has some disadvantages, which requires that the force at each loading point be equal. This requirement is simple to achieve in regularly shaped specimens but difficult to achieve in whole bone tests. 7) Therefore, three-point bending is used more often for measuring the mechanical properties of bones from rodents.The differential responses of bone properties to the mid-to long-term effects of ovariectomy in rats has been widely studied, [8][9][10][11][12][13] and simultaneously efficacy testing of potential chemicals for anti-POP in ovariectomized (OVX) rats was also conducted in a duration of mid-to long time. Previous studies showed that the earliest statistically significant time of cancellous bone loss of rats in the proximal tibial metaphysis (PTM), lumbar vertebral body (LVB) and femoral neck (FN) occurring at 14, 60 and 30 d post ovariectomy, respectively, and the time of 50% bone loss for the PTM was 30-60 d, 8,9) and for LVB and FN was 180-270 d. 10,11) While the earliest changes in cortical bone width and medullary cavity size to be between 90-120 d and to reach a steady state often 180 d or more.12,13) These suggested that influence of ovariectomy on bones showed site-and tim...

Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats

“…We employed a three-point bending test on the femoral midshaft to evaluate the biomechanical characteristics of cortical bone (21). Consistent with previous literature (64), femoral strength deficits were not observed within 4 wk of GX, which may indicate that mechanical loading is sufficient to maintain cortical bone mass and femoral strength in the near absence of circulating sex hormones, at least during the relatively short duration of this study (43). However, studies of longer duration have demonstrated that GX produces biomechanical deficits in bone, indicating that sex hormone-mediated skeletal regulation is necessary for bone maintenance (13,14).…”

Effect of Host Sex and Sex Hormones on Muscle-Derived Stem Cell-Mediated Bone Formation and Defect Healing

“…[22][23][24] With regard to native bone maintenance and turnover, ovariectomy is also known to decrease bone volume and quality in both rats and mice (including the C57BL strain of mice used in this study). [25][26][27][28][29] Normal skeletal bone formation, growth, and maintenance are all known to be influenced by sex steroid hormones. [30][31][32] However, MDSC-mediated bone formation appeared not to be influenced by ovariectomy or castration, which could be promising for translation to clinical therapies.…”

Effects of Ovariectomy on Bone Metabolism and Bone Mineral Density in Spontaneously Diabetic Torii-Leprfa Rats

“…2B). OVX induces greater bone loss more prominently in cancellous bone than in cortical bone [18]. Since the lumbar vertebral body contains abundant cancellous bone, it is considered that OVX caused greater bone loss in the L5 vertebral body than in the whole tibia of control rats ( Fig.…”