Femoral neck strength of mouse in two loading configurations

Abstract

We evaluated the mechanical strength of murine femoral neck in two loading configurations. The mechanical strength of the left femora of 25 male mice (weight 39±4 g) were measured in an axial configuration simulating one-legged stance in a human, and the right femora were tested in a configuration simulating a fall to the lateral side, on the trochanter. The reproducibility of the mechanical testing was 1.6% in the axial configuration and 3.7% in the fall configuration. The femoral neck was slightly stronger in the fall configuration. Typically, a load in the fall direction associated with a basicervical fracture, while axial loading resulted in both mid- and basicervical fractures. The linear bivariate correlation coefficient between the mechanical strengths in the two loading configurations was 0.83. Total bone mineral content (BMC), cortical bone mineral content (CtBMC), volumetric cortical bone mineral density (vCtBMD), and cross-sectional cortical area (CSA), measured at the femoral neck by peripheral quantitative computed tomography (pQCT), had a significant relationship with the femoral neck strength in the axial configuration. The coefficient of variation of the pQCT measurements was 9.1, 5.5, 2.3 and 5.5% for BMC, CtBMC, vCtBMD and CSA, respectively. We conclude that the precision of pQCT is moderate in evaluating the femoral neck of the mouse, and vCtBMD is the most reproducible parameter. The mechanical strength of the murine femoral neck can be measured with high precision by the two mechanical testing configurations presented here.

Introduction

Biomechanical testing is an important tool in the evaluation of bone strength, which is associated with susceptibility to fractures. Rat has been employed as a standard rodent model in biomechanical skeletal studies (Ferretti et al., 1993; FDA 1994; Kimmel 1996; Peng et al., 1994; Raab et al., 1990; Tuukkanen et al., 1994), while mouse has been used far less often. According to some earlier studies, genetic variation between different inbred mouse strains results in notable differences in bone density, bone geometry, and mechanical properties (Beamer et al., 1996; Bonadio et al., 1990; Di Masso et al., 1997; Kimmel, 1996; Kuro-o et al., 1997; Mikic et al., 1995; Simske et al., 1994). Transgenic mouse can be considered a suitable animal model for experimental studies of osteoporosis and aging (Kimmel, 1996; Kuro-o et al., 1997).

In the previous biomechanical studies of murine bones, diaphyseal bending strength (Ammann et al., 1997; Anderson et al., 1993; Bonadio et al., 1990; Di Masso et al., 1997; Hiltunen et al., 1993; Jämsä et al., 1998; Simske et al., 1994) and torsion strength (Mikic et al., 1995; Yang et al., 1993) have been measured. However, the femoral neck is clinically a more interesting measuring site than the diaphysis. The studies on rat and rabbit bones have shown that the evaluation of femoral neck strength is a good indicator of bone fragility (Peng et al., 1994; Søgaard et al., 1994; Turner et al., 1996; Tuukkanen et al., 1994). In these studies, the femoral neck has been loaded in a direction parallel to the femoral shaft axis. This simulates one-legged stance in humans. Simulating a fall to the lateral side, on the greater trochanter, is clinically more relevant, because approximately 90% of hip fractures are associated with a fall (Cummings et al., 1990; Grisso et al., 1991). Femoral neck studies on human cadavers have often applied this simulation (Backman, 1957; Cheng et al., 1997; Courtney et al., 1995; Lang et al., 1997; Lotz and Hayes, 1990; Pinilla et al., 1996). The weight-bearing and locomotion of mouse result in different in vivo loads compared to human. However, these clinically relevant loading configurations should be evaluated when developing sensitive experimental skeletal models.

Quantitative computed tomography (QCT) has proven to be an effective tool in evaluating the densitometric and geometric properties of human femoral neck (Augat et al., 1996; Cheng et al., 1997; Esses et al., 1989; Lang et al., 1997; Lotz and Hayes, 1990). Peripheral QCT (pQCT) has been used in experimental studies on the diaphyseal bones of rat (Breen et al., 1996; Ferretti et al., 1995; Ferretti et al., 1996; Gasser, 1995; Österman et al., 1997; Rosen et al., 1995aRosen et al., 1995b; Sato et al., 1995; Vanderschueren et al., 1997). Beamer et al. (1996)applied pQCT to analyses of genetic variability in femoral, vertebral and phalangeal bone density among inbred strains of mice. We have found pQCT fairly precise in evaluating the bending strength of murine femoral and tibial shafts (Jämsä et al., 1998). As far as we know, there have been no earlier attempts to evaluate the properties of the femoral neck of rodents by pQCT.

The purpose of the present study was to evaluate the mechanical testing of the femoral neck strength of mouse in two loading configurations, in the axial direction and in the falling direction, and to assess the usefulness of pQCT in evaluating the mechanical strength of the murine femoral neck in vitro.