Calcified Tissue International

, Volume 79, Issue 6, pp 404–415 | Cite as

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

  • A. M. Tromp
  • N. Bravenboer
  • E. Tanck
  • A. Oostlander
  • P. J. Holzmann
  • P. J. Kostense
  • J. C. Roos
  • E. H. Burger
  • R. Huiskes
  • P. LipsEmail author


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 μg 17ß-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.


Bone structure Bone mass Estrogen Ovariectomy Mechanical loading Micro-computed tomography Histomorphometry Dual-energy X-ray absorptiometry 



The authors thank the members of the animal laboratory for their great support and hospitality, the endocrinology laboratory for the estradiol measurements, Toos Boekhoven for the line drawing of the rat with backpack, and Peggy Tjou Tam Sin, Mia Engelbregt, Huib van Essen, Ab Geldof, and Astrid Bakker for their help with training the rats. This study was funded by The Netherlands Organization for Scientific Research (grant 903–41–193).


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • A. M. Tromp
    • 1
  • N. Bravenboer
    • 1
  • E. Tanck
    • 2
  • A. Oostlander
    • 1
  • P. J. Holzmann
    • 1
  • P. J. Kostense
    • 3
  • J. C. Roos
    • 4
  • E. H. Burger
    • 5
  • R. Huiskes
    • 6
  • P. Lips
    • 1
    Email author
  1. 1.Department of EndocrinologyVrije Universiteit Medical CenterAmsterdamThe Netherlands
  2. 2.Orthopedic Research LabUniversity Medical Center NijmegenNijmegenThe Netherlands
  3. 3.Department of Clinical Epidemiology and BiostatisticsVrije Universiteit Medical CenterAmsterdamThe Netherlands
  4. 4.Department of Nuclear MedicineVrije Universiteit Medical CenterAmsterdamThe Netherlands
  5. 5.Department of Oral Cell BiologyACTA, VU Medical CenterAmsterdamThe Netherlands
  6. 6.Department of Biomedical EngineeringUniversity of Technology, Bone & Orthopedic BiomechanicsEindhovenThe Netherlands

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