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Journal of Human Evolution 54 (2008) 875e885

Articular constraint, handedness, and directional asymmetry in the human second metacarpal Richard A. Lazenby a,*, David M.L. Cooper b, Sarah Angus a, Benedikt Hallgrı´msson c a

Anthropology Program, University of Northern British Columbia, 3333 University Way, Prince George, BC, Canada V2N 4Z9 Department of Anatomy and Cell Biology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5E5 c Department of Anatomy and Cell Biology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1 b

Received 11 June 2007; accepted 6 December 2007

Abstract The hypothesis that functional adaptation of joint surfaces to mechanical loading occurs primarily through change in mass, density, and structure of subarticular trabeculae (the ‘‘articular constraint’’ model) is investigated through an analysis of directional asymmetry among three separate bone compartments in the human second metacarpal. Measures of midshaft cross-sectional geometry, osteometry of the distal epiphysis, and subarticular trabecular microarchitecture of the distal epiphysis (assessed by high-resolution microcomputed tomography) were determined for 29 paired male and female metacarpals from a well-preserved nineteenth-century Euro-Canadian historic cemetery sample. For each measure, asymmetry was quantified using both mean-difference and confidence-interval methods. Both methods found a significant right-hand bias for measures of structural strength in midshaft geometry, as has been previously noted for this sample. Articular size, however, exhibits a righthand bias only with regard to mediolateral, and not dorsopalmar, dimensions, a result that may reflect directional asymmetry in hand breadth at the distal palmar arch. The most striking asymmetries occur for subarticular trabecular microarchitecture. The right metacarpal head exhibits greater bone volume fraction, bone surface density, trabecular number, connectivity, and a more platelike rather than rodlike structure. These outcomes confer greater resistance to both axial compressive and shear strains for the metacarpal head at the metacarpophalangeal arthrosis. In all, these results confirm and extend previous research documenting structural asymmetries and limb dominance and are consistent with the concept of articular constraint. They also suggest a morphological signal through which functional asymmetry associated with handedness in fossil hominins may be investigated. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Articular constraint model; Directional asymmetry; Micro-CT; Second metacarpal

Introduction The study of directional asymmetry (DASY) in skeletal forelimb morphology, defined as a preferential bias by side in the occurrence of a trait (Van Valen, 1962), can offer significant insight into hominin ontogeny and phylogeny, as it bears upon broader questions of functional lateralization of brain and behavior, language origins, and material culture (Pobiner, 1999; Lazenby, 2002b; Corballis, 2003; Sarringhaus et al., 2005). While consensus has yet to be reached as to whether * Corresponding author. E-mail address: [email protected] (R.A. Lazenby). 0047-2484/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.jhevol.2007.12.001

‘‘handedness’’ is apomorphic for Homo, recent literature suggests that, among primates, the expression of species- or population-level hand preference is multifaceted, influenced by factors such as age, sex, and task complexity (e.g., unior bimanual tasks or degree of cognitive demand) (McGrew and Marchant, 1997, 2001; Corp and Byrne, 2004; Lonsdorf and Hopkins, 2005; O’Malley and McGrew, 2006). However, contemporary humans are demonstrably right-handed, though variably so (Harris, 1990), and behaviorally mediated departures from morphological symmetry in skeletal size and shape are well recognized (Roy et al., 1994; Hallgrı´msson, 1998, 1999; Lazenby, 1998; Auerbach and Ruff, 2006; Westcott and Cunningham, 2006). Such departures are grounded in

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our current understanding of bone functional adaptation. While debate exists regarding the predictive and/or explanatory efficacy of this paradigm (Bertram and Swartz, 1991; Lovejoy et al., 2003; Pearson and Lieberman, 2004), its primary tenetdthat bone adapts in life to achieve a form commensurate with functiondis widely acknowledged and empirically derived (Ruff et al., 2006). This paper examines asymmetry among several bone compartments in the human second metacarpal (3D trabecular microarchitecture and articular size of the distal epiphysis; midshaft cortical geometry). A key question in the analysis of bone functional adaptation concerns the differential response of cortical versus trabecular bone, and the relative stability (or constraint) of articular morphology to preferential mechanical loading (Ruff et al., 1991; Lieberman et al., 2001; Ruff, 2002). The fundamental premise of the ‘‘articular constraint’’ model is that, in order to maintain integrity of both hard and soft tissues, joint surfaces should be relatively unresponsive to mechanical loading, in contrast to anatomical sites such as the mid-diaphysis and subarticular trabecular morphology. In the latter case, the model posits that loading across joints is accommodated by adaptive modeling of trabecular bone within epiphyses. In other words, strain associated with function elicits bone-lining cells on trabecular surfaces (osteoclasts and osteoblasts) to remove and deposit, respectively, bone substance in amounts and locations necessary to preserve functional competence (for an accessible review of modeling regulation, see Robling et al., 2006). While some research suggests that articular surfaces do adjust their size in response to asymmetrical loading (Plochocki et al., 2006), others have shown that joint morphology tends to be highly canalized at the species level (Lieberman et al., 2001). Under the ‘‘articular constraint’’ model, our expectation is that directional asymmetry in trabecular microarchitecture should track that observed for diaphyseal geometry and, if present, articular size. It is important to note that the model does not require symmetry of articular morphology, but simply predicts lower, possibly nonsignificant, levels of DASY relative to more labile bone compartments. Thus, the questions posed by this study are whether directional asymmetries are present in aspects of trabecular microarchitecture specifically and to what degree are such asymmetries concordant with those present in the articular and diaphyseal compartments. Therefore, given the rightside bias among modern humans, we predict that handedness will produce not only a greater trabecular mass per unit volume in the dominant hand’s metacarpal, but a mass that is more cohesive in structure (i.e., a greater number of thicker trabeculae in a more well-connected ‘‘lattice’’), as documented in experimental models of trabecular response to functional loading (Rubin et al., 2002; Pontzer et al., 2006).

collection of nineteenth-century Euro-Canadians (Saunders et al., 1995; Lazenby, 2002a). This sample is appropriate because the bones are well preserved and show no evidence of trauma or physiologic pathology. A previous study of the full sample (n ¼ 198 individuals) demonstrated significant right-biased asymmetry for several geometric properties of midshaft cortical bone (Lazenby, 1998), though a greaterthan-expected proportion of individuals (ca. 25%) exhibited a left-side bias. Notably, variation in the degree of preferential hand use of this magnitude has been documented ethnographically (Marchant et al., 1995). Data This study contrasted data across three ‘‘compartments’’ of skeletal structure. These include (1) dimensions of the metacarpal head and shaft (dorsopalmar, or anteroposterior, depth and radioulnar, or mediolateral, width); (2) diaphyseal properties, including interarticular length, maximum midshaft diameter, total area, percent cortical area and polar moment of area at midshaft; and (3) trabecular microarchitecture of the head. Details regarding measurement of the head and diaphyseal variables are as previously reported (Lazenby, 1998, 2002a). A description of the trabecular compartment data is in order. 3D imaging

Materials and methods

Micro-CT has become a powerful tool for in vivo and in vitro analysis of trabecular microarchitecture. Several validation studies have shown a high degree of concordance of micro-CT data with data obtained by traditional histomorphometry (Fajardo et al., 2002; Cooper et al., 2004); furthermore, 3D micro-CT analyses are unencumbered by a priori assumptions regarding the structure of bone in the volume of interest (VOI) (Hildebrand and Ru¨egsegger, 1997a). All images for this study were acquired with a SkyScan 1072 cone-beam micro-CT scanner (Aartselaar, Belgium) at the University of Calgary 3D Morphometrics Laboratory. The protocol employed X-ray tube settings of 100 kV and 98 mA, an exposure time of 5 seconds per image with threeframe averaging to improve signal-to-noise ratio, and a rotation step of 0.90 degrees. Nominal isotropic resolution was 19 mm. A 1-mm aluminum filter and beam-hardening correction algorithm were used to compensate for artifacts associated with the use a polychromatic X-ray source. This protocol resulted in a total scan time of ca. 1 hour per specimen. Serial 8-bit 1024  1024 pixel image sequences were reconstructed using a cone-beam algorithm (SkyScan Cone ReconÒ software) (Fig. 1). Reconstruction time per specimen was ca. 90 minutes, though it varied depending on the number of serial slices imaged per stack (i.e., the total number of serial images selected for reconstruction).

Sample

Trabecular variables

In this study, 58 paired second metacarpals from 14 males and 15 females were selected from a large, well-studied

Cubic volumes of interest, 5 mm3, were sampled from each specimen, comprising 259 serial images. Position of the VOI

R.A. Lazenby et al. / Journal of Human Evolution 54 (2008) 875e885

Fig. 1. Three-dimensional reconstruction of a right metacarpal head.

was determined with regard to a scout image acquired at the time of scanning. A reference slice defining the midpoint of the VOI was selected at a location within the head such that the resulting VOI was fully contained within the epiphysis without encroaching on the overlying cortical shell (Fig. 2). While this approach introduced a measure of subjectivity in sampling location, quantitative trabecular analysis with micro-CT has been shown to be resilient to slight displacement of the VOI without producing significant differences (Kim et al., 2004; Na¨gele et al., 2004). A median filter was applied to the image stack to reduce image noise. Following filtration, the images were segmented using a global-thresholding algorithm. Images were initially depicted as varying in density (1e255 gray levels), and segmentation dichotomizes this information as black (bone) and

Fig. 2. Representative 5 mm3 VOI.

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white (nonbone), allowing for precise discrimination of these phases at their boundary. Global thresholding applies a single gray-level to demarcate bone/nonbone over the entire image, and can be contrasted with local thresholding in which ‘‘site-specific’’ values are determined for each voxel in the reconstructed image. While the use of a global versus a local threshold has been the subject of some debate (Fajardo and Mu¨ller, 2001), recent studies have shown that, at scanning and reconstruction resolutions in the range employed in this study (ca. 20 mm), both approaches characterize trabecular microarchitecture with comparable accuracy (Kim et al., 2004; Waarsing et al., 2004). However, Waarsing et al. (2004) noted that very thin trabeculae do tend to be lost with global thresholding, even at higher resolutions, due to the partial-volume effect. Loss of the thinner trabeculae will have the effect of underestimating the mean number and connectivity of trabeculae in a VOI and overestimating mean trabecular thickness (Fajardo et al., 2002). The 3D data were collected using SkyScan’s proprietary software CTanÒ, which calculates a variety of microarchitectural properties. The following variables were selected for analysis in this study. Abbreviation of variable names follows the ABSMR convention (Parfitt et al., 1987) and current usage. (1) Bone volume fraction (BV/TV; %)dthe proportion of the total volume of the VOI occupied by trabeculae. (2) Bone specific surface (BS/BV, mm1)dthe ratio of trabecular surface area to trabecular volume. (3) Bone surface density (BS/TV, mm1)dthe ratio of trabecular surface area to the total volume of the VOI. (4) Structure model index (SMI)dSMI measures the relative proportion of platelike versus rodlike structures in the VOI (Hildebrand and Ru¨egsegger, 1997b). Values range from 0 (idealized plates) to 3 (idealized rods). (5) Trabecular thickness (Tb.Th, mm)dthe mean thickness summed over all local voxels (3D pixel elements) based on the diameters of a series of spheres fully contained within the structure (Hildebrand and Ru¨egsegger, 1997b; Fajardo and Mu¨ller, 2001). (6) Trabecular number (Tb.N, mm1)dTb.N is the ratio of bone volume fraction to trabecular thickness. (7) Trabecular separation (Tb.Sp, mm)dTb.Sp characterizes the average thickness of the spaces between trabeculae in a VOI. (8) Trabecular bone pattern factor (Tb.Pf; mm1)dTb.Pf was developed by Hahn et al. (1992) to reflect the degree of connectivity of trabeculae within a VOI based on the proportion of concave and convex surfaces. Higher Tb.Pf values denote more fragmentation and the presence of isolated nodes or struts (convexity), while lower values reflect structural integrity and greater connectivity (concave surfaces). It is possible to obtain negative values for Tb.Pf if enclosed cavities with fully concave surfaces are prevalent in the VOI. Negative values for Tb.Pf are problematic for subsequent analysis of directional asymmetry that seeks to quantify side differences, as it can have an additive effect on the magnitude of asymmetry, or in a rare

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case where values are equal but of opposite sign, produce a meaningless expression (i.e., division by zero). In the present case, only four instances of negative Tb.Pf values occurred, all with values between 0 and 0.3. The most parsimonious adjustment, and the one taken here, was to use the absolute value for Tb.Pf in subsequent analyses. (9) Degree of anisotropy (DA)dDA quantifies trabecular orientation. Anisotropic structures have a preferred orientation, while isotropic structures demonstrate symmetry of orientation in 3D space. The CTan software employs the mean intercept length (MIL) algorithm for the determination of DA (Fajardo and Mu¨ller, 2001). Anisotropy values are reported here as 1 e (minimum eigenvalue/maximum eigenvalue), which provides a dimensionless number ranging from 0 (fully isotropic) to 1.0 (fully anisotropic). Ketcham and Ryan (2004) observed that DA determined from cubic VOI may generate differentdand biaseddvalues than DA values from spherical VOI obtained from the same specimen/slices. This bias derives from ‘‘recognition error’’ associated with trabeculae at the edges and corners of the cubic VOI. In the present study, we superimposed a 5-mm spherical VOI within the original cubic VOI for calculation of DA.

reproducibility for micro-CT datadmeasured as precision error (PE) and the intraclass correlation coefficient (ICC)dfor trabecular-, cortical-, and whole-bone compartments in the mouse femur. While the trabecular compartment had somewhat higher PE values relative to cortical bone (maximum 5.24% versus 2.16%), the ICC values ranged from 0.92 to 1.00, indicating small repeat-measure variance relative to sample variance. In the present study, reproducibility was evaluated by rescanning a subset of n ¼ 5 specimens on independent occasions but employing the same scanning and reconstruction protocols. Dahlberg’s (1940) method-error statistic (often referred to as the technical error of measurement) was used to describe precision: rffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi X . ffi d 2 2n sðiÞ ¼

The more specific characterizations of trabecular microarchitecture (e.g., Tb.N, Tb.Th, Tb.Pf, Tb.Sp, SMI) will be significantly correlated (either positively or negatively) with trabecular ‘‘mass’’ (BV/TV) (Recker et al., 2005). Indeed, BV/TV and DA have been viewed as the most significant contributors to mechanical aptitude of trabecular bone (Odgaard, 1997). For example, in a micro-CT and finite-element analysis of trabecular bone from four anatomical locations, Ulrich et al. (1999) found that these two parameters alone could account for 82% of the variance in trabecular strength (elastic constants); additional microarchitectural variables (e.g., Tb.Th) provided a further though modest increase in explanatory power. However, in spite of its high correlation with bone strength and stiffness, BV/TV does not accurately describe microarchitecture per se, and the analysis of these specific properties has become standard practice within this emerging field. Stauber et al. (2006) recently argued that, because trabeculae are continually altered with aging, mechanical loading, and pathology, analysis of local architecture is essential in obtaining a fuller appreciation of the contribution of trabecular structure to mechanical competence, as well as the response of bone to pharmacologic treatment in the clinical context.

Statistical analysis

Reproducibility Reproducibility can be defined as the agreement between results obtained by independent tests, and it offers a measure of precision between observers, instruments, labs, etc. Although it is well characterized for the osteometric and geometric data investigated here (on the order of 2e4%; Lazenby, 1998), as well as for studies of bone mass and density (IidaKlein et al., 2003), it is less appreciated for micro-CT analyses of trabecular microarchitecture. Kohler et al. (2005) examined

where d is the difference between repeat observations and n is the sample size. For the trabecular variables examined, method error ranged from 1.746% for BV/TV to 0.005 mm for Tb.Th, and the correlation (r) between measures ranged from 0.735 for SMI to 0.962 for DA, indicating very good to excellent reproducibility for these measures.

Directional asymmetry was determined in two ways. First, we calculated relative asymmetry using a method exemplified by Plochocki (2004) in an analysis of humeral articular asymmetry. Plochocki (2004: 330) applied the following formula, which ‘‘standardizes the asymmetry to within-individual percentages’’ and is designed to accommodate body size variation:   2ðR  LÞ DASY ¼  1000 RþL This approach takes into consideration samples composed of both males and females for which reliable estimates of body mass permitting size-adjustment of data are unavailable. Compensation for the absence of size-adjustment is an important consideration, as significant sexual dimorphism in upperlimb asymmetry has been recorded across a number of human populations (Auerbach and Ruff, 2006; Sla´dek et al., 2007). Positive DASY values indicate a right-side bias and negative values a left-side bias. For this determination, significance was evaluated with a one-sample t-test against a hypothesized value of 0, with Bonferroni adjustment of p-values. Our second approach follows Richtsmeier et al. (2005), who proposed a bootstrap method to provide confidence intervals for the mean difference in DASY, R  L. In this case, DASY is considered significant in the sample when the confidence interval excludes zero. For this analysis, 1000 iterations of resampling with replacement were performed. We also examined concordance and magnitude of DASY among compartments within individuals, posing the question, e.g., if trabecular bone volume fraction is greater on the right

R.A. Lazenby et al. / Journal of Human Evolution 54 (2008) 875e885

side in an individual, is it also the case for polar moment of area at midshaft or radioulnar head width in that individual, and is the expression of similar magnitude? Concordance for directionality was examined using a tetrachoric correlation, converting the calculated DASY values to a binary expression of either zero (left bias) or one (right bias). Spearman’s rankorder correlation coefficient (rho) was used to examine agreement in magnitude of expression of DASY among compartments. Normality of the data was confirmed with the Wilk-Shapiro normal test. All analyses were carried out using Systat 11.0, with a ¼ 0.05. Results Descriptive statistics for left and right second metacarpal heads are reported in Table 1. In the trabecular compartment, the majority of variables favor the right side, either in terms of mass, size, or structural integrity. For example, values for bone volume fraction (BV/TV), surface density (BS/TV), and trabecular number (Tb.N) indicate a right bias; likewise, connectivity (Tb.Pf) values suggest greater integrity in the right rather than left metacarpal head. As indicated by the structure model index (SMI), the right metacarpal head possesses a somewhat more platelike (broad, flat) trabecular network. The fact that the left side is somewhat more rodlike in SMI is reflected in a left-side bias for greater bone specific surface (BS/BV). Trabecular spacing, trabecular thickness, and degree of anisotropy all failed to demonstrate a definitive asymmetry. In the articular and diaphyseal compartments, a right bias is evident in the majority of dimensions, with the exception of bone length (IAL) and percent cortical area (PCA). Table 2 gives the results for the directional-asymmetry analyses. In the trabecular compartment, bone volume and bone surface variables (BV/TV, BS/BV, and BS/TV) were all significantly asymmetric by both measures of DASY, while trabecular number, trabecular pattern factor and the SMI

Variable1

Right Mean

Trabecular

Left SD

Mean

SD

BV/TV BS/BV BS/TV Tb.Th Tb.N Tb.Pf Tb.Sp SMI DA

19.21 28.51 5.07 0.16 1.21 3.46 0.59 0.80 0.25

6.23 7.67 0.83 0.04 0.28 2.71 0.11 0.35 0.07

17.75 30.02 4.88 0.15 1.16 3.84 0.60 0.84 0.26

6.34 7.98 0.85 0.03 0.28 2.63 0.10 0.32 0.10

Articular

MLW DPW

15.32 14.24

1.28 1.29

14.95 14.07

1.36 1.18

Diaphyseal

IAL MSD TA PCA J

63.21 9.33 56.67 74.59 500.28

4.04 0.96 9.79 7.77 170.21

63.25 9.05 54.26 74.86 460.96

3.94 0.92 9.80 6.52 163.59

1

See text for units of measurement.

were significantly asymmetric by the 95% CI method alone. As anticipated from the descriptive statistics, trabecular thickness (Tb.Th), spacing (Tb.Sp), and anisotropy (DA) failed to demonstrate significant asymmetry. A strong right-side bias is evident in aspects of volume (e.g., BV/TV), size/density (e.g., Tb.N), and organization (e.g., Tb.Pf and SMI). For the articular compartment, the metacarpal head was asymmetric with a right-side bias in the mediolateral, but not in the dorsopalmar, plane. Among the diaphyseal measures, those variables associated with midshaft size and structural strengthdtotal area, polar moment of area, and maximum midshaft diameterdexhibited significant right-side asymmetry. There was no significant asymmetry in either midshaft mass (PCA) or in bone length (IAL). Intra-individual agreement in direction and magnitude of DASY among trabecular, articular, and cortical compartments was examined using a variable from each compartment that had exhibited significant DASY for the sample as a whole based on the above analyses. These were trabecular bone volume fraction (BV/TV), mediolateral articular head width (MLW), and midshaft torsional strength (J). No significant correlations were found for either direction (tetrachoric) or magnitude (Spearman’s rho) of DASY. Discussion Directional asymmetry in osteometric and geometric bone properties is well documented in anthropological, clinical, and experimental research, invariably within a paradigm of adaptation to asymmetric functional loading (i.e., limb dominance) (Garn et al., 1976; Plato and Norris, 1980; Fresia et al., 1990; Helmkamp and Falk, 1990; Kimura, 1990; Lazenby, 1994, 2002b; Roy et al., 1994; Trinkaus et al., 1994; Albert and Greene, 1999; Mays, 2000; Ducher et al., 2004; Plochocki, 2004; Sarringhaus et al., 2005; Auerbach and Ruff, 2006; Westcott and Cunningham, 2006). However, Table 2 Directional asymmetry (DASY) by bone compartment1

Table 1 Descriptive statistics by bone compartment Compartment

879

Compartment

Variable

Mean DASY

t

Trabecular

BV/TV BS/BV BS/TV Tb.Th Tb.N Tb.Pf Tb.Sp SMI DA

89.78 51.27 39.00 4.71 74.87 164.39 19.03 71.50 14.86

Articular

MLW DPW

Diaphyseal

IAL TA PCA J MSD

1

CLlower

CLupper

2.605* 2.232* 2.101* 0.140 1.571 1.698 0.974 1.662 0.226

30.841 86.241 10.723 58.822 6.129 328.977 50.713 142.302 130.446

146.447 16.444 69.098 51.393 156.367 13.042 10.401 5.551 84.118

24.97 11.92

4.292* 1.556

15.289 0.278

33.746 23.849

0.79 44.89 5.45 88.35 31.32

0.298 4.198* 0.561 4.361* 4.129*

4.939 27.751 20.874 57.164 18.933

3.553 61.783 9.809 121.462 42.962

The t-values are from a one-sample t-test; asterisk (*) indicates significance at p < 0.05. Confidence intervals are from bootstrap analysis; bolded values indicate presence of DASY.

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DASY in the microarchitecture of trabecular bone is less well appreciated, as quantification of such differences has proven more intractable. The recent application of micro-CT 3D imaging provides a relatively quick, precise, and noninvasive approach to investigating variation in trabecular microarchitecture (Uchiyama et al., 1997), including DASY in the subarticular compartment. In the present study a significant right-side bias was found for several trabecular bone variables, most evident in aspects of volume and structure. As noted by others (Day et al., 2000; Ammann and Rizzoli, 2003), BV/TV exhibits a strong influence on a number of microarchitectural variables. In the present study, a higher bone volume fraction is associated with greater connectivity and a preponderance of plates versus rods (Fig. 3). Figure 4 illustrates the greater bone volume fraction, platelike structure, and degree of connectivity in the right versus left metacarpal head. Such differences are concordant with DASY in midshaft metacarpal cross-sectional geometry in both this sample and in a larger sample from the same historical context (Lazenby, 1998), including a number of strength measures not included in the present analysis (e.g., maximum and minimum bending moments). Although only two orthogonal dimensions were evaluated for articular size, these capture the principal motions at the metacarpophalangeal joint (Tamai et al., 1988). In agreement with the trabecular and diaphyseal measures, the right metacarpal head was larger than the left, but significantly so only for mediolateral width. The mechanical aptitude of epiphyses (and other skeletal sites in which trabecular bone predominates; e.g., vertebrae, tarsals, and carpals) to resist deformation and failure is determined by the element’s microarchitecture as much as by its density (BMD) (Ammann and Rizzoli, 2003; Rupprecht et al., 2006). Architecturally, bone volume fraction and the structure model index appear to be most reflective of that aptitude. Sran et al. (2007) reported BV/TV to be positively correlated with anteroposterior failure load in thoracic vertebrae. Similarly, van Lenthe et al. (2006) found BV/TV to be highly predictive of directly measured bone stiffness (Young’s modulus R2 ¼ 0.88), particularly at lower values (i.e., <10%). In an in vitro study investigating failure mechanisms in human trabecular bone, Bevill et al. (2006) found that bone volume fraction and the structure model index were the most significant predictors of reductions in strength under large-deformation loads. Mechanical loading has also been demonstrated to have a morphogenic effect on trabecular bone volume fraction and microarchitecture during growth. Using a swine model, Tanck et al. (2001) showed that the initial response to functional loading during development occurs through a rapid increase in bone volume fraction and stiffness, followed subsequently by a reorientation of trabeculae (increasing anisotropy). More recently, Ryan and Krovitz (2006) documented the reorganization of trabecular structure within the human proximal femur with the adoption of ‘‘unassisted walking’’ in infants and children from prenatal age to nine years, noting that, by three years of age, adult levels of bone volume fraction were achieved. While not addressing asymmetry per se, such

Fig. 3. Scatter plots of the structural model index (SMI) and connectivity (Tb.Pf) against bone volume fraction. Note that lower values for SMI indicate a more platelike architecture and for Tb.Pf, greater connectivity.

reports reinforce the ‘‘articular constraint’’ model for trabecular plasticity under loading. Such plasticity has been observed in experimental regimes with adult sheep (Judex et al., 2003). Interestingly, in their growth study, Ryan and Krovitz (2006) sampled two adjacent VOIs within the femoral neck and noted that the major distinction between sites within individuals older than six months was an increase in degree of anisotropy in the inferior VOI associated with development of the primary compressive trabecular arcade. However, BV/TV, Tb.Th, and Tb.N remained relatively unchanged. In the present study, significant directional asymmetry was found in the metacarpal head for BV/TV and SMI but not for anisotropy. These differences support the argument that trabecular orientation is more responsive to qualitative aspects of loading

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Fig. 4. Paired VOIs from a 35-year-old female showing platelike (right) versus rodlike (left) trabecular architecture.

within an element (in the case of the femoral neck [Ryan and Krovitz, 2006] associated with changes in VOI location), while mass and structure respond to variation in quantitative aspects of loading (magnitude and/or frequency) among elements, as seen in the present study examining comparable VOIs in opposing hands. The ‘‘articular constraint’’ model proposes that the necessity to maintain joint integrity limits the degree to which articular morphology can adaptively respond to functional loading. Lieberman et al. (2001) found no significant change in articular surface area in exercised vs. sedentary sheep across three age groups (juvenile to adult) and over several limb joints. However, cross-sectional geometric properties showed significant increases in the exercised individuals. Rafferty and Ruff (1994) examined articular morphology (area and mass) and subarticular trabecular structure in the proximal humerus and femur of Papio, Hylobates, and Colobus and found that, adjusted for body size, articular dimensions were related to joint mobility, while trabecular density (assessed by radiograph) was related to mechanical load-bearing and force transmission. Siamangs, for example, had larger humeral and femoral areas associated with high joint excursion during brachiation and climbing but lower trabecular density than either baboons or colobines, species adapted for quadrupedal walking or running with attendant high load-bearing and compressive forces. At the same time, variation in functional loading effects on limb-bone articular-surface asymmetry has been noted by others (Ruff et al., 1991; Plochocki, 2004), suggesting that adaptation to differential loading can occur within this compartment as well. However, changes at the articular level are seen to be modest compared to those that occur in other compartments, a finding that is consistent with the relative degrees of asymmetry evident in trabecular microarchitecture versus articular size seen in the present study. Recently, Plochocki et al. (2006) examined chondral, articular, and trabecular adaptation to loading in young, growing mice allowed to run at will on a calibrated wheel. Compared to nonrunning controls, all three compartments in their study showed

a response to loading. Although the largest effect was reported for trabecular mass, both the chondral and articular phases showed significant adaptive responses to exercise. Their study suggests that, during the active growth phase, mechanical loading can exert a modeling influence on overall joint morphology. It is not clear, however, whether the pattern of aging in mice mitigates the response differentially among the compartments studied, such that (for example) the trabecular phase remains labile and responsive into the adult age range, while chondral and articular compartments become quiescent. Ruff et al. (1991) for example, found no adaptive response in femoral articular size to change in body weight in humans over the adult lifespan. These findings suggest that different bone compartments follow independent developmental pathways. In their examination of directional asymmetry in limb-bone lengths, diaphyseal and epiphyseal breadths, and articular diameters, Auerbach and Ruff (2006) reported graded degrees of asymmetry. Within and between populations, upper-limb DASY was greatest for diaphyseal breadths, less for bone lengths, and least for articular dimensions (very little asymmetry was observed for the lower limb). Auerbach and Ruff suggested that these ‘‘modules’’ are perhaps differentially canalized with varying degrees of genetically determined ‘‘mechanical sensitivity.’’ Canalization refers to the tendency of structures to achieve particular end-point morphologies irrespective of environmental perturbations (Hallgrı´msson et al., 2002); the more canalized a structure, the greater the degree of genetic constraint. Recent studies with inbred mice (Turner et al., 2000; Bouxsein et al., 2004; Judex et al., 2004) have demonstrated significant differences between strains, and between bone compartments within strains, that are consistent with site-specific genetic determination of both bone mass (i.e., BMD) and trabecular microarchitecture. Bouxsein et al. (2004), for example, compared B6 with C3H strains using micro-CT imaging of the fifth lumbar vertebral body and found that the C3H mice had much reduced bone volume fraction and trabecular number than B6 mice. In contrast, Judex et al. (2004), in their study of the distal femur in

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the same strains, reported that BV/TV was higher in the metaphysis of C3H mice compared with the B6 strain. While such studies have yet to examine canalization of articular dimensions, they strongly suggest that the genetic regulation of bone quantity and quality is both highly site-specific and complex. The independence of compartments is also supported by the lack of significance obtained in the intra-individual correlation analyses. In the directional analysis, trabecular mass had only small and nonsignificant relationships with both articular size (MLW rtet ¼ 0.279) and cortical rigidity (J rtet ¼ 0.372). The former result is consistent with the ‘‘articular constraint’’ model. While both the trabecular and articular compartments are right-biased for the sample as a whole, it is not uncommon for an individual with a larger BV/TV in the right side to have greater articular breadth on the left. Indeed, disagreement in direction was found for 11 of 29 cases. This finding and the fact that DASY on average was almost four times greater for BV/TV than MLW (Table 2) suggest that greater credence be given to trabecular data than to articular morphology in the search for functional asymmetry. The inverse relationship for bone volume fraction and torsional rigidity noted above is also interesting, as it suggests that these two compartments (cortical and trabecular) within hands are responding differently to functional loading. A differential cortical versus trabecular response has been noted by others in both natural (Ducher et al., 2004) and experimental (Turner et al., 2000) models. The loading environment of the head and shaft are also qualitatively different (primarily compression at the head, bending at the midshaft), which also mitigates the tissue response, a factor also underlying the lack of agreement for magnitude of response (Spearman’s rho). The fact that platelike trabeculae predominate in both sides (see Table 1) is noteworthy, given that increasing age has been observed to transform trabecular microarchitecture from plates to rods (Mu¨ller et al., 1998). However, Ding and Hvid (2000) studied trabecular thickness and the SMI in human proximal tibiae and found that these parameters were relatively age-stable until the later decades of life. Trabeculae do become thinner and more rodlike in the elderly, but these changes do not become significant until age 80 and beyond. In animal models, a more platelike architecture (e.g., lower SMI values) has been shown to be the most significant determinant of ultimate bone strength (Mittra et al., 2005) and to be inversely related to microcrack density under both shear and compressive loading (Wang and Niebur, 2006). Tamai et al. (1988) estimated that compressive loads at the index metacarpophalangeal joint during strenuous manipulation could reach 3.0e4.5 N/mm2, comparable to that of weight-bearing elements in the lower limb. However, strenuous activity would not be a prerequisite for adaptive modeling of subarticular trabecular architecture. Judex et al. (2003) exposed adult female sheep to low-intensity, high-frequency loading over one year, producing significant increases in tissue stiffness and reduction in strain magnitude. Therefore, a right-biased DASY for a platelike architecture (and the concomitant increase in bone volume fraction) is arguably adaptive for the dominant hand invoking both fine and coarse motor skills.

Our results have direct implications for the inference of hominin behavior from the fossil record. Lieberman (1997) discussed the pitfalls associated with inferring behavior and phylogeny in consideration of the effects of mechanical loading. He noted that the multifactorial determination of bone morphology (genetic, epigenetic, and environmental) needs to be considered in evaluating the significance of specific featuresdthose aspects of form with a higher genetic input have more relevance taxonomically, while those features that are more responsive to environmental influences speak directly to behavior. Lieberman (and others, e.g., Trinkaus et al., 1994; Lieberman et al., 2004; Demes, 2007) considered the interpretation of cortical-bone morphology, such as crosssectional geometry, as a behavioral indicator, but we would argue that the value of trabecular bone has been understated. Trabecular bone has been shown to be highly responsive to its loading environment (Pontzer et al., 2006), and has effectively no functional responsibilities beyond transferring load by modifying strength and stiffness through the arrangement of its architecturedprimarily mass and orientation. Diaphyseal bone and articular surfaces are compromised in this regard: soft tissues must maintain functional attachment to periosteal surfaces of cortical bone, and joint integrity must be maintained by constraint of epiphyseal form. The advent of 3D imaging technology has focused increasing attention on the contribution of trabecular bone to behavioral modeling (Ryan and Ketcham, 2005; Maga et al., 2006). Maga et al. (2006), for example, demonstrated a ‘‘signal for bipedality’’ in a comparison of calcaneal trabecular morphology in Homo, Pan, and Gorilla. Our emphasis in the present study is manipulation and the advent of lateralized behavior (functional asymmetry). Diverse manipulative skills would have been required in the evolution of the human hand in performing tasks such as stone-tool manufacture involving, for example, the three-jaw-chuck precision grip or spherical power grip (Marzke and Marzke, 2000). Studies of functional asymmetry in the hominin record are relatively few and confined principally to late Pleistocene samples (e.g., the Neandertal humerus; see discussion in [Auerbach and Ruff, 2006]), though all demonstrate a significant right-limb bias. Behavioral inferences from fossil hominin hand remains are even rarer. Tocheri et al. (2003) compared the trapezia of nonhuman primates, modern Homo, Australopithecus afarensis (A.L. 333-80), and Homo habilis (OH 7-NNQ) using 3D imaging and concluded that the shift to a modern trapezial morphology likely occurred within Homo erectus (though no samples for this species were available for study), associated with the development of more complex bifacial technologies and production methods. Technological shifts have also been implicated in comprehending differences in carpometacarpal articular morphology among Near Eastern Neandertals and anatomically modern humans (Niewoehner, 2001), possibly associated with the adaptive significance of the manufacture and use of composite (hafted) tools and a palmar morphology adapted for employing oblique rather than transverse power grips (Churchill, 2001). However, these latter studies of hominin carpals and metacarpals have been limited to examining morphological

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variation in articular facets (areas, angles, etc.) and have not broached the question of lateralized behavior, in part due to the rarity of well-preserved paired elements. Specimen A.L. 438-1, attributed to A. afarensis, is an important exception in this regard (Drapeau et al., 2005), as it includes intact left and right second metacarpals. A significant outcome of the present study is the identification of a putative signal for handedness that could be applied to unpaired fossil remains. For example, the identification of a predominately rodlike architecture in an unpaired left metacarpal, such as that attributed to Homo antecessor (Lorenzo et al., 1999), would be strongly suggestive of right-hand dominance. However, in order to confidently interpret such results, studies of trabecular architectural asymmetry in both humans of known handedness, as well as in nonhuman primates of differing locomotor habits, should be carried out. Conclusions Directional asymmetry has been well characterized for a variety of skeletal morphologies, most especially in terms of diaphyseal breadths and cross-sectional geometries, but less so for articular dimensions. To our knowledge, this is the first study to characterize DASY in the subarticular trabecular compartment suggestive of lateralized functional loading. A strong right-hand bias exists within the second metacarpal head for bone volume fraction, as well as for more distinctive attributes such as connectivity density and a predominance of platelike versus rodlike trabeculae, in both males and females and young and old alike. This architecture is associated with greater ultimate strength and resistance to both compressive and shear strains. The right-bias in trabecular asymmetry is also reflected in aspects of diaphyseal size (e.g., width and cortical area), but less so in articular dimensions. This result is consistent with a model of articular constraint, in which contiguous joint morphologies are less responsive (and more highly canalized during and subsequent to development) to environmental signals such as those imparted by mechanical strain. The trabecular signal observed in this study may be applicable to investigations into the origins of handedness in the hominin fossil record, though should be refined through studies of nonhuman primates and other human samples. Acknowledgements Support for the research was provided by grants from the Natural Sciences and Engineering Research Council (RAL, BH); the Canadian Foundation for Innovation, Alberta Innovation and Science, and the Alberta Heritage Fund, Genome Canada, and Genome Alberta (BH). We thank the editor and reviewers for their well-considered and thoughtful suggestions for improving the manuscript. References Albert, A.M., Greene, D.L., 1999. Bilateral asymmetry in skeletal growth and maturation as an indicator of environmental stress. Am. J. Phys. Anthropol. 110, 341e349.

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