Contribution of Trabecular Microarchitecture and its Heterogeneity

to Biomechanical Behavior of Human L3 Vertebrae

+1 2

Wegrzyn, J; 1Roux, J P;

1Arlot, M E;

1Boutroy, S;

1 Vilayphiou, N;

2Guyen, O;

1Delmas, P D;

3Bouxsein, M L

+1INSERM U 831, Université de Lyon, Lyon, France,

2Department of Orthopedic Surgery, Pavillon T, Hôpital E. Herriot, Lyon, France,

3Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA

Senior author mbouxsei@bidmc.harvard.edu

INTRODUCTION: Low bone mineral density (BMD) is a strong risk factor for

vertebral fracture in osteoporosis. However, BMD explains only

40 to 70% of the variation in trabecular bone strength [1]. In

addition, many fractures occur in people with normal BMD [2].

Besides BMD, trabecular microarchitecture improves prediction

of bone mechanical behavior [3, 4]. Trabecular microarchitecture

heterogeneity has been previously described [5, 6], however

there is limited information about its contribution to vertebral

fragility.

The aim of this study was to assess the contribution of

trabecular microarchitecture and its heterogeneity to mechanical

behavior of human lumbar vertebrae.

METHODS: L3 vertebrae taken from 21 fresh donors (11 males and 10

females, respectively aged 75±10 years and 76±10 years) were

analyzed and destructively tested in uniaxial compression.

Lateral-BMD (g/cm²) was measured using dual energy X-ray

absorptiometry (DXA; Delphi W®, Hologic, MA, USA). 3D

trabecular microachitecture (bone volume per tissue volume

(BV/TV), structural model index (SMI), trabecular separation

(Tb.Sp*), trabecular thickness (Tb.Th*) and trabecular number

(Tb.N*)) was assessed without model assumption using high-

resolution peripheral quantitative computed tomography (HR-

pQCT; X-Trem CT®, Scanco Medical, Switzerland) with a

nominal isotropic voxel size of 82 µm.

Trabecular microarchitecture heterogeneity was assessed

using two 8.2 mm diameter virtual biopsies (one anterior and one

posterior vertically cored in 3 zones: superior, middle and

inferior) and on the whole vertebral trabecular area (Figure 1.).

Heterogeneity of trabecular microarchitecture was evaluated by:

1) the ratio of antero-posterior BV/TV (BV/TVratio); 2) the

coefficient of variation of the vertical 3 zones parameters

(BV/TVcv); and 3) the distribution expressed by the standard

deviation of Tb.Sp* on virtual biopsies (Tb.Sp*SDant) and on the

whole trabecular area (Tb.Sp*SD).

Vertebral stiffness (N/mm), failure load (N) and work to

failure (N.mm) were measured on the whole vertebral body

using a servohydraulic testing machine (Schenck RSA-250®,

Germany) under displacement control at 0.5 mm/s until failure.

All parameters had normal distribution, after log

transformation for work to failure and BV/TVratio. Parametric

tests (Student t-test, ANOVA, Pearson's correlation coefficient,

stepwise and multiple regression analyses) were performed using

SPSS 12.0® software.

RESULTS: Mean values for L3 vertebral biomechanics, as well as

trabecular architectural parameters are given in Table 1.

Microarchitectureal features differed significantly between

the anterior and posterior virtual biopsies for all parameters (p=

0.007 to 0.04), except for SMI and Tb.Th*. Vertebral failure

load was mainly explained by microarchitectural parameters of

the anterior region as assessed by stepwise regression analysis

(ie.; in the equations, failure load = anterior and posterior

microarchitectural parameter, the second one was always out of

model). As a result, we studied vertical heterogeneity on the

anterior biopsy. Significant vertical heterogeneity was found for

BV/TV and SMI (respectively, p-value = 0.0001 and 0.021,

ANOVA).

Although all parameters reflecting trabecular

microarchitecture of the whole vertebral body (i.e.; BV/TV,

SMI, Tb.Sp*, Tb.Th* and Tb.N*) were correlated with

mechanical indices (r = -0.81 to 0.44, p-values = 0.0001 to

0.047, Pearson test), SMI seemed to be the most pertinent one,

with r = -0.81 (stepwise regression analysis).

Trabecular bone heterogeneity (BV/TVratio and Tb.Sp*SDant)

was significantly correlated with mechanical behavior (r = -0.53

to -0.57, p = 0.01 to 0.007). No correlation was found with

Tb.Sp*SD.

The combination of one parameter of bone mass (BMD) and

one parameter of heterogeneity (BV/TVcv) significantly

improved the prediction of both failure load and stiffness as

indicated by stepwise multiple regression analyses (respectively,

R = 0.83 and 0.74; p<0.0001 and p=0.0008), compared to: r =

0.82 and 0.69; p<0.0001 and p=0.0006 with BMD alone). In

addition, the correlations between failure load or stiffness with

BV/TVcv remain significant after adjustment with BMD

(respectively p=0.001 and 0.005; partial correlation).

Figure 1. L3 vertebra whole trabecular area and 2 virtual

biopsies (82 µm isotropic voxel size)

Whole

Vertebrae

Anterior

Core

Posterior

Core

Failure load (N) 2615 (1136)

Stiffness (N/mm) 2938 (1585)

Work (N.mm) 1730 (1129

BMD (g/cm²) 0.62 (0.12)

BV/TV (%) 13.5 (5.9) 11.4 (6.1)* 13.5 (6.7)

SMI (#) 2.61 (0.53) 2.75 (0.65) 2.76 (0.50)

Tb.Sp* (µm) 1363 (332) 1368 (382)* 1209 (319)

Tb.Th* (%m) 308 (43) 288 (64) 293 (42)

Tb.N* (#/mm) 0.76 (0.16) 0.76 (0.17)* 0.86 (0.20)

BV/TVratio 1.41 (0.70)

BV/TVcv 0.28 (0.16) 0.31 (0.13)

Tb.Sp*SD 0.53 (0.16) 0.43 (0.13) 0.45 (0.18)

Table 1. L3 vertebrae bone trabecular architectural parameters –

(mean, (SD)). * p < 0.05 posterior core vs anterior core.

DISCUSSION: Consistent with previous studies, we found heterogeneity of

vertebral trabecular microarchitecture [3]. Importantly, bone

mass parameters (i.e.; BMD or BV/TV) in combination with

trabecular microarchitecture heterogeneity (i.e.; BV/TVratio,

BV/TVcv and Tb.Sp*SDant) were independent predictors of

vertebral mechanical behavior, together explaining up to 74% of

the variability in the prediction of vertebral fragility. Our data

imply that the measurement of trabecular microarchitecture

heterogeneity may enhance prediction of vertebral fracture risk.

REFERENCES: [1] McDonnell, P. et al., Ann Biomed Eng, 2007; [2]

Delmas, P.D. et al., J Bone Miner Res 2005; [3] Hulme, P.A. et

al., Bone 2007; [4] Buckley, J.M. et al., Bone 2007; [5] Banse,

X. et al., Bone 2001; [6] Boutroy, S. et al., J Clin Endocrinol

Metab 2005.

This study was supported in part by a research grant from Eli-

Lilly® to INSERM.

superior

inferior

middle

posterior

anterior

Poster No. 715 • 55th Annual Meeting of the Orthopaedic Research Society