ab2002

The femoral distal epiphysis of ovariectomized rats as a site for studies on osteoporosis: Structural and mechanical evaluations

G. Giavaresi¹, M. Fini¹, S. Gnudi², F. De Terlizzi³, A. Carpi⁴, R. Giardino^1,5

¹Department of Experimental Surgery and ²Department of Internal Medicine, Istituti Ortopedici Rizzoli, Bologna; ³IGEA SRL, Carpi - Modena; ⁴Department of Ageing and Reproduction, University of Pisa, Pisa; 5Department of Surgical Pathophysiology, University of Bologna, Bologna, Italy.

ABSTRACT
Objective
To investigate in detail the mechanical and structural characteristics of cancellous bone from the femoral distal epiphysis of normal and ovariectomized rats, and to provide reference values in order to improve experimental research on osteoporosis by characterising an alternative and complementary anatomic site.

Methods
40 female Sprague-Dawley rats (10 months old) were randomly divided into 4 groups of 10 each: baseline, ovariectomized (Ovx), sham-operated (Sham-Ovx) and sham-aged (Sham-Aged). Baseline animals were sacrificed at the beginning of the study. Ovx and Sham-Ovx animals were sacrificed 16 weeks after surgery, whereas Sham-aged rats were killed when aged 14 months. Femurs were excised and densitometric, ultrasonographic, mechanical and histomorphometric analyses were performed.

Results
When comparing the Ovx group with the others, ultrasonographic and densitometric measurements showed significant decreases (p < 0.0005) amounting to 3-5% in the amplitude dependent speed of sound (AD-SOS) and 13-20% in the BMD, respectively. Significant decreases were also seen in the femoral condyle Max. Load (28-31%; p < 0.0005) and Elastic Modulus (19-25%; p < 0.005) in the Ovx group in comparison with the Sham-Ovx and Sham-Aged groups. Histomorphometric analysis showed a significant cancellous bone loss (p < 0.0005). Densitometric (p < 0.01), histomorphometric (p < 0.01) and mechanical (p < 0.05) parameters were correlated with AD-SOS. Among the histomorphometric parameters, stepwise regression analysis showed that the trabecular bone volume (BV/TV) and Max.Load correctly predicted AD-SOS (p < 0.0005) and BMD (p < 0.0005).

Conclusion
The data from this study characterize osteopenia occurring in the rat distal femur 16 weeks after ovariectomy and provide methodology and reference values for further investigations on osteoporosis and bone-implant osteointegration in osteopenic bone.

Key words
Osteoporosis, ovariectomized rat, femur, dual X-ray absorptiometry, quantitative ultrasound.

Financial support for this research was partially provided by the Ministry of Health (Rome, Italy) special strategic project "Fratture osteoporotiche", by grants from the Istituti Ortopedici Rizzoli (ricerca corrente), and by the "Foundation of Cassa di Risparmio in Bologna" research project "Clinica e biologia delle gravi insufficienze d'organo".
Please address correspondence and reprint requests to: Gianluca Giavaresi, MD, Servizio di Chirurgia Sperimentale, Istituto di Ricerca Codivilla-Putti, IOR,
Via di Barbiano 1/10, 40136 Bologna, Italy.
E-mail: gianluca.giavaresi@ior.it