Additional Weight Bearing during Exercise and Estrogen in the Rat: The Effect on Bone Mass, Turnover, and Structure

Abstract

Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation. Furthermore, we expected to find changes in trabecular architecture elicited by the effects of mechanical loading and estrogen deficiency. Sixty female Wistar rats, 12 weeks old, were assigned to either the sedentary groups sham surgery (SED), ovariectomy (SED+OVX), and ovariectomy with estrogen replacement (SED+OVX+E2) or to the exercise groups EX, EX+OVX, EX+OVX+E2. Following ovariectomy, 5 microg 17beta-estradiol was given once weekly to the estrogen replacement groups. Exercise consisted of running with a backpack (load +/-20% of body weight) for 15 minutes/day, 5 days/week, for 19 weeks. Dual-energy X-ray absorptiometry (DXA) scans were performed before (T0), during (T6), and after (T19) the exercise period to obtain bone mineral content (BMC) and bone mineral density (BMD) data. After the exercise program, all rats were killed and right and left femora were dissected and prepared for micro-CT scanning and histomorphometric analysis of the proximal femoral metaphysis. After 19 weeks, increases in BMC (P = 0.010) and BMD (P = 0.031) were significant. At T19, mechanical loading had a significant effect on BMC (P = 0.025) and BMD (P = 0.010), and an interaction between mechanical loading and estrogen (P = 0.023) was observed. Bone volume and trabecular number decreased significantly after ovariectomy, while trabecular separation, mineralizing surface, bone formation rate, osteoclast surface, degree of anisotropy, and structure model index increased significantly after ovariectomy (P < 0.05). Trabecular bone turnover and structural parameters in the proximal femur were not affected by exercise. Estrogen deficiency resulted in a less dense and more oriented trabecular bone structure with increased marrow cavity and a decreased number of trabeculae. In conclusion, mechanical loading has beneficial effects on BMC and BMD of the ovariectomized rat. This indicates that the load in the backpack was high enough to elicit an osteogenic response sufficient to compensate for the ovariectomy-induced bone loss. The results confirm that estrogen suppresses both bone resorption and bone formation in the proximal metaphysis in the femoral head of our rat-with-backpack model. The effects of mechanical loading on the trabecular bone of the femoral head were not significant. This study suggests that the effect of mechanical loading in the rat-with-backpack model mainly occurs at cortical bone sites.

Treadmill training prevents bone loss by inhibition of PPARγ expression but not promoting of Runx2 expression in ovariectomized rats

“…In rat models of osteoporosis, various types of exercises including treadmill (Simões et al 2008), jump (Umemura et al 2008), whole body vibration (Sehmisch et al 2009), swim (Hart et al 2001), tower climbing (Notomi et al 2003), and resistance (Tromp et al 2006) have been examined for the influences on bone loss and demonstrated to improve their status effectively. However, the subsequent molecular events of exercise-triggered decrease in bone loss remain unclear.…”

A comparison of the microarchitecture of lower limb long bones between some animal models and humans: a review

“…Additionally, mechanical load produced by backpack loads increased bone mineral content and bone mineral density by 27% and 11% respectively, comparing to control groups (Tromp et al 2006). The same conclusion was made in experiments dealing with astronauts in zero gravity conditions and in other similar studies (Vico et al 2000;Shackelford et al 2004).…”

“…The femur is heavily loaded bone in humans, especially in the metaphyseal region; consequently cancellous bone tissue is more developed in this region compared to rats, because cancellous bone conducts mechanical forces better than cortical bone and acts like an armature and load absorber. Variations in bone tissue structure are strongly influenced by different levels of sex hormones, but intense load could preserve bone tissue volume despite low level of sex hormones (Tromp et al 2006;Mavropoulos et al 2007). …”

“…Table 4 shows data regarding cortical bone thickness in the femur in humans, rabbits and rats regarded to age, gender and anatomical location. Sex hormones have a significant impact on cortical bone thickness as well as on the bone microarchitecture (Bagi et al 1997;Tromp et al 2006). The average thickness of cortical bone located in the femoral neck region in postmenopausal women is about 10 times greater compared to ovariectiomised female rats (Bagi et al 1997).…”

“…Recently, however, great progress has been made in this field (Hert et al 1994;Bagi et al 1997;Ardizzoni 2001;Sugawara et al 2005;Tromp et al 2006;Cooper et al 2007;Mavropoulos et al 2007;Martiniakova et al 2008;Britz et al 2009;Pazzaglia et al 2010;Schneider et al 2010). Nevertheless, only a few papers comparing bone microarchitecture between animal models and humans have been published so far (Jowsey 1966;Bagi et al 1997;Pearce et al 2007).…”