A three-dimensional microcomputed tomographic study of site-specific variation in trabecular microarchitecture in the human second metacarpal

J. Anat.

(2008)

213

, pp698–705 doi: 10.1111/j.1469-7580.2008.00991.x

© 2008 The AuthorsJournal compilation © 2008 Anatomical Society of Great Britain and Ireland

Blackwell Publishing Ltd

A three-dimensional microcomputed tomographic study of site-specific variation in trabecular microarchitecture in the human second metacarpal

Richard A. Lazenby,

1

Sarah Angus,

1

David M. L. Cooper

2

and Benedikt Hallgrímsson

3

1

Anthropology Program, University of Northern British Columbia, Prince George, BC, Canada

2

Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

3

Department of Anatomy and Cell Biology, University of Calgary, Calgary, Alberta, Canada

Abstract

Variation in trabecular microarchitecture is widely accepted as being regulated by both functional (mechanicalloading) and genetic parameters, although the relative influence of each is unclear. Studies reporting inter-site differences in trabecular morphology (volume, number and structure) reveal a complex interaction at thegene–environment interface. We report inter- and intra-site variation in trabecular anatomy using a novel modelof contralateral (left vs right) and ipsilateral (head vs base) comparisons for the human second metacarpal in asample of

n

= 29 historically known 19th century EuroCanadians. Measures of bone volume fraction, structuremodel index, connectivity, trabecular number, spacing and thickness as well as degree of anisotropy were obtainedfrom 5-mm volumes of interest using three-dimensional microcomputed tomography. We hypothesized that: (i)the more diverse loading environment of metacarpal heads should produce a more robust trabecular architecturethan corresponding bases within sides and (ii) the ipsilateral differences between epiphyses will be larger on the

right side than on the left side, as a function of handedness. Analysis of covariance (Side

×

Epiphysis) with Age ascovariate revealed a clear dichotomy between labile and constrained architectures within and among anatomicalsites. The predicted variation in loading was accommodated by changes in trabecular volume, whereas trabecularstructure did not vary significantly by side or by epiphysis within sides. Age was a significant covariate only forfemales. We conclude that environmental and genetic regulation of bone adaptation may act through distinctpathways and local anatomies to ensure an integrated lattice of sufficient mass to meet normal functionaldemands.

Key words

constraint; functional adaptation; site-specific variation; three-dimensional trabecular microarchitecture.

Introduction

Site-specific variation in cortical and trabecular bone pro-perties has been documented across different levels oforganization, including collagen fiber orientation (Skedros& Hunt, 2004), cortical porosity and Haversian remodeling(Thomas et al. 2006), bone mineral density (Nonaka et al.2006) and trabecular microarchitecture (Sran et al. 2007).Such studies point to a correspondence between skeletalmicroanatomy and local experience of functional loading,in keeping with the basic tenets of ‘Wolff’s Law’ (Ruff et al.2006). For example, Lazenby et al. (2008a) found significantright-biased directional asymmetry in trabecular bone

volume fraction, number and connectivity correspondingto handedness in the human second metacarpal distalepiphysis. Although mechanical function is considered theprime determinant of skeletal mass and form throughgrowth and adulthood (Tanck et al. 2001; Ryan & Krovitz,2006), the role of genetic regulation in skeletal biologyis receiving greater scrutiny (Robling et al. 2006). Forexample, variation in trabecular bone volume fraction,connectivity and anisotropy has been shown to existamong different inbred mouse strains subjected to similarmechanical environments (Bouxsein et al. 2004).

Various approaches to the question of functional vsgenetic regulation of trabecular bone properties havebeen investigated, including the documentation of site-specific variation within and among skeletal elements.Rupprecht et al. (2006) showed that the trabecular bonestructure for three separate volumes of interest (VOI)within the human calcaneus changes independently withage. The transition from plate-like to rod-like structureand reduction in bone volume fraction appear highly

Correspondence

Dr Richard A. Lazenby, Anthropology Program, University of Northern British Columbia, 3333 University Way, Prince George, BC Canada, V2N4Z9. T: 250 960 6696; F: 250 960 5545; E: [email protected]

Accepted for publication

2 September 2008

Article published online

31 October 2008

Site-specific variation in human metacarpal trabecular structure, R. A. Lazenby et al.

© 2008 The Authors Journal compilation © 2008 Anatomical Society of Great Britain and Ireland

699

localized within this element and within individuals,pointing to a primary role for mechanical loading. In anexperimental model using three genetically heterogene-ous mouse strains, Judex et al. (2004) found a high degreeof site specificity in femoral cortical and trabecular bonemass, with large differences appearing in some regionsand similar values in others (e.g. the metaphyseal trabec-ular volume was ca. 400% greater in one strain but theepiphyseal volume was almost identical). Judex et al. (2004)favored a multi-gene regulatory model to account forthese regional differences, although they admit that thisargument (p. 605) ‘seems overly complex given the greatnumber of anatomical sites within and across bones’. Suchstudies point strongly to a prominent role for function as anarbiter of trabecular mass and form. However, Bouxseinet al. (2004) examined the trabecular architecture in twomouse strains and found a complex and heterogeneousassociation of bone properties to mapped quantitativegenetic loci (19 quantitative trait loci (QTL) on 13 autosomes),a number of which were distinct from QTL previously iden-tified for femoral and vertebral bone mineral density inthe same strains. As QTL are DNA markers for the poly-genic inheritance of phenotypic traits, the association ofmultiple QTL with trabecular variation supports the multi-gene regulatory model proposed by Judex et al. (2004).

It is clear that trabecular bone is continually altered withaging, mechanical loading and pathology against aspecific genetic background, and thus the analysis of localarchitecture is essential in obtaining a fuller appreciationof the contribution of trabecular structure to mechanicalcompetence, as well as its pathophysiology (Stauber et al.2006). In the present study, we use an ipsi- and contra-lateral single element model (the human second metacarpal)to explore the relationship of site-specific variation infunctional loading and the proximate phenotype(Bouxsein et al. 2004) of local trabecular architecture.

The second metacarpal is the largest of four short tubu-lar bones defining the longitudinal and transverse archesof the palm and is of interest both phylogenetically indocumenting the shift in hand use from locomotion tomanipulation (Lazenby et al. 2008b) as well as clinically,given that nearly 10% of all skeletal fractures occur in themetacarpals and phalanges (Chin & Vedder, 2008).

Anatomically, metacarpals consist of a quadrilateral base,cortical shaft, neck and ‘cam-shaped’ head. Distally, deeptransverse ligaments bind adjacent metacarpal heads andcollateral ligaments cross the metacarpophalangeal (MCP)joint. Dorsal and volar ligamentous attachments also bindthe bases of each metacarpal to each other and with thecontiguous bones in the distal carpal row at the carpo-metacarpal (CMC) arthrosis. Although the fourth and fifthmetacarpal CMC joints are capable, respectively, of ca. 15

°

and 25

°

of motion, the second and third CMC joints arerigidly bound, having little if any independent movement.The base of the second metacarpal is further stabilized in

articulation with the trapezoid, trapezium, capitate andthird metacarpal by insertions of the extensor carpi radialislongus and flexor carpi radialis tendons. The configurationof the human index metacarpal base is unique amonghominoids (Tocheri et al. 2005, p. 582) in having moretransversely oriented facets for articulation with the tra-pezium and capitate, allowing for ‘distribution of loadbetween the second metacarpal and these two distal wristbones’. In an experimental study of the effects of trape-zoidectomy on index metacarpal stability, Wright et al.(2006) report that normal axial compressive loading acrossthe second carpometacarpal arthrosis is ca. 125 N.

Distally, the multiaxial condyloid MCP joints are capableof flexion, extension, adduction and abduction (and, incombination, circumduction). At about 70

°

of MCP jointflexion, tautness in the collateral ligaments stabilizes thefinger against radioulnar deviation, enhancing ‘powerpinch and grip’ (Chin & Vedder, 2008, p. 2). Compressivestresses at the index MCP joint during strenuous manipu-lation could reach 3.0–4.5 N mm

–2

, similar to that of weight-bearing elements in the lower limb (Tamai et al. 1988).

Thus described, the functional anatomy of the proximaland distal second metacarpal arthroses suggests thatmechanical loading will be both quantitatively and quali-tatively different between the ipsilateral head and base.The high degree of anatomical constraint characteristic ofthe CMC suggests that loading between contralateralbases will vary primarily in magnitude; the loading varia-tion between contralateral heads will reflect primarilyquantitative differences due to handedness. As such, wehypothesize that: (i) metacarpal heads should have a morerobust trabecular architecture than bases within sidesreflecting the more diverse loading environment atthe MCP joint and (ii) given the preponderance of right-handedness within human populations (Lazenby, 2002), theseipsilateral differences between epiphyses will be larger onthe right side than on the left side.

Materials and methods

A complete description of the research design is given in Lazenbyet al. (2008a). Briefly, 14 male and 15 female paired secondmetacarpals were selected from a well-studied 19th centuryEuroCanadian skeletal collection, having excellent preservationand showing no evidence of traumatic or physiological pathology.With the exception of five females, all are historically documentedindividuals. Females ranged in age from 17 to 67 years (

x

= 36.27;SD = 12.64) and males from 20 to 75 years (

x

= 50.07; SD = 20.44).The head and base of each metacarpal were removed from thediaphysis on a Struers Minitom® slow-speed saw, cleaned usingultrasonication and allowed to air-dry.

Microcomputed tomographic images of each epiphysis wereacquired with a SkyScan 1072 cone-beam micro-CT scanner(Aartselaar, Belgium) at the University of Calgary 3D MorphometricsLaboratory (Fig. 1). The protocol employed x-ray tube settings of100 kV and 98

μ

A, an exposure time of 5 s per image with three-frame averaging to improve signal-to-noise ratio and a rotation



700

step of 0.90

°

. The nominal isotropic resolution was 19

μ

m. A 1-mmaluminum filter and beam-hardening correction algorithm wereused to compensate for artifacts associated with the use of apolychromatic x-ray source. Serial 8-bit 1024

×

1024 pixel imagesequences were reconstructed using a cone-beam algorithm(SkyScan Cone Recon® software).

The VOI (5 mm

3

) were sampled from each epiphysis, comprising259 serial images. The position of the VOI was determined withregard to a scout image acquired at the time of scanning. A refer-ence slice was positioned within the epiphysis at approximatelythe midpoint of the epiphyseal trabecular mass. A median filterwas applied to the image stack to reduce image noise. Followingfiltration, the images were segmented using global thresholdingdefined with respect to the inter-peak minimum of grey-scalevalues for each VOI. Although the use of a global vs a local thresh-old has been the subject of some debate, recent studies haveshown that, at scanning and reconstruction resolutions in therange employed in this study (ca. 20

μ

m), both approaches yieldedcomparable accuracy in characterizing trabecular microarchitecture(Kim et al. 2004; Waarsing et al. 2004).

Data were collected using SkyScan’s proprietary softwareCTan®. Both volumetric [bone volume fraction (BV/TV), trabecularnumber (Tb.N) and trabecular separation (Tb.Sp)] and structural[structure model index (SMI), connectivity (Tb.Pf), thickness (Tb.Th)and degree of anisotropy (DA)] variables were assessed. The readeris referred to Lazenby et al. (2008a), Fajardo et al. (2002) andKetcham & Ryan (2004) for a complete description of thesevariables, commonly measured in micro-CT studies of trabecularbone.

We assessed reproducibility using Dahlberg’s method errorstatistic (Dahlberg, 1940):

where

d

is the difference between repeat observations and

n

thesample size, in this case five metacarpal heads. For the trabecularvariables examined, method error ranged from 1.746% for BV/TVto 0.005 mm for Tb.Th and the correlation (

r

) between measuresranged from 0.735 for SMI to 0.962 for DA, indicating very goodto excellent reproducibility for these measures.

The questions posed by this study are, simply put, in what re-spect and to what degree is site-specific variation in trabecularmicroarchitecture expressed between the second metacarpalepiphyses? The ‘global’ null hypothesis of an absence of within-element, between-site differences was tested using

ANCOVA

by sex

and side with epiphysis as factor and age as covariate, using Systat11 with

α

= 0.05. The coefficient of variation was used to evaluatesite-specific variability.

Results

Tables 1 and 2 summarize the descriptive (mean ± SD) and

ANCOVA

results, respectively. Compared with bases, meta-carpal heads had a significantly higher bone volume frac-tion in both left and right sides, and in males and femalesalike. The elevated BV/TV in the head was associated witha significantly greater Tb.N and a concomitant reductionin Tb.Sp. Tb.Th did not differ among epiphyses. Values forTb.Pf were invariably lower in the head, indicating a morewell-connected lattice structure, although significantly soonly for the female right metacarpal. No significant differ-ences occurred in the head vs base comparison for SMI.Trabeculae in the metacarpal base were significantly moreisotropic in orientation, with DA values closer to 0.0. Agewas a significant covariate only for females, influencingthe SMI in both hands and Tb.Pf and Tb.Th in the left hand.Figure 2 reports the absolute difference between ipsi-lateral epiphyseal means by side and sex. None of thedifferences were significant as determined by a

t

-test (notreported). Contrary to our second hypothesis, the head/basedifferences for the right metacarpal were not marked,favoring only bone volume fraction and connectivity infemales (although age was a significant factor for severalleft metacarpal variables, including Tb.Pf). Figure 3 illus-trates a typical pattern for all four epiphyses as presentedin a series of 5-mm cubic VOIs from a 20-year-old male.

Discussion

Although the paradigm of adaptation of bone structure toits mechanical environment has held pride of place forover a century of research in skeletal biology (Frost, 2001),there is a rapidly growing body of evidence for a promi-nent role for genetic mitigation of normal (Marshall et al.2008) and pathological bone response to mechanical

Fig. 1 Three-dimensional volumetric reconstructions of the second metacarpal head (a) and base (b). The complex morphology of the base derives from its constrained articulation with three carpals and the third metacarpal.

s i d n( ) ( )/= ∑ 2 2



701

loading (Zhang et al. 2008). There is also an increasingappreciation of the potential for modulation (up- ordown-regulation) of genetic signals for bone formationand resorption by local mechanical loading history (Zhiet al. 2008).

In our study, we found a consistent pattern of labile andconstrained morphology repeated in both left and rightsides, and males and females alike. Variables related tomass (bone volume fraction, trabecular number andspacing) show a distinct difference between head and

base, with the head having a larger bone volume fractionowing to greater trabecular number. The mechanicalsignificance of BV/TV is well appreciated. Across four sitesin the human appendicular and axial skeleton, Ulrich et al.(1999) found that BV/TV was the major contributor tomechanical aptitude, accounting for up to 82% of vari-ance in trabecular strength. Van Lenthe et al. (2006) andothers (Giesen et al. 2004) have found BV/TV to be highlypredictive of bone stiffness, whereas Bevill et al. (2006)found that a decline in BV/TV was the most significant

Table 1 Descriptive statistics by sex, side and epiphysis

Variable

Male Female

Head Base Head Base

Right BV/TV 19.10 (7.72) 11.22 (5.06) 19.32 (4.72) 10.19 (2.91)Tb.Pf 3.96 (3.35) 4.52 (1.67) 2.99 (1.95) 4.31 (0.91)SMI 0.85 (0.42) 0.88 (0.18) 0.75 (0.28) 0.84 (0.13)Tb.N 1.21 (0.33) 0.71 (0.23) 1.21 (0.24) 0.65 (0.16)Tb.Th 0.16 (0.04) 0.15 (0.03) 0.16 (0.03) 0.16 (0.02)Tb.Sp 0.57 (0.11) 0.87 (0.20) 0.61 (0.11) 0.96 (0.21)DA 0.23 (0.08) 0.16 (0.07) 0.26 (0.05) 0.18 (0.05)

Left BV/TV 18.55 (7.75) 10.72 (4.27) 17.01 (4.83) 9.91 (3.21)Tb.Pf 3.85 (3.25) 4.25 (2.00) 3.84 (1.99) 4.38 (1.06)SMI 0.82 (0.39) 0.82 (0.23) 0.86 (0.26) 0.83 (0.12)Tb.N 1.19 (0.32) 0.68 (0.20) 1.14 (0.23) 0.63 (0.14)Tb.Th 0.15 (0.04) 0.16 (0.03) 0.15 (0.03) 0.16 (0.03)Tb.Sp 0.59 (0.11) 0.98 (0.35) 0.62 (0.10) 0.98 (0.18)DA 0.24 (0.09) 0.17 (0.08) 0.27 (0.11) 0.19 (0.05)

BV/TV, bone volume fraction (%); Tb.Pf, connectivity (mm–1); SMI, structure model index; Tb.N, trabecular number (mm–1); Tb.Th, trabecular thickness (mm); Tb.Sp, trabecular separation (mm); DA, degree of anisotropy.

Table 2 ANCOVA results for ipsilateral differences by side and sex

Side Variable

Male Female

H – B Effect F P = Cov F P = H – B Effect F P = Cov F P =

Right BV/TV 7.878 9.822 0.004 0.032 0.859 9.126 40.243 0 0.746 0.395Tb.Pf –0.554 0.302 0.588 0.489 0.491 –1.319 5.923 0.022 2.408 0.132SMI –0.025 0.041 0.840 0.915 0.348 –0.086 1.341 0.257 5.048 0.033Tb.N 0.497 21.333 0 0.657 0.425 0.558 55.034 0 0.239 0.629Tb.Th 0.002 0.018 0.895 2.561 0.122 0.005 0.286 0.597 3.838 0.061Tb.Sp –0.308 29.019 0 3.660 0.067 –0.355 35.961 0 2.189 0.151DA 0.070 6.338 0.019 0.014 0.907 0.083 21.561 0 3.088 0.090

Left BV/TV 8.725 10.550 0.003 0.005 0.943 7.103 24.009 0 2.881 0.101Tb.Pf –0.396 0.149 0.702 0.833 0.370 –0.537 1.019 0.322 6.480 0.017SMI –0.005 0.002 0.963 1.651 0.211 0.029 0.215 0.646 11.125 0.002Tb.N 0.505 24.223 0 0.778 0.386 0.504 51.373 0 0.247 0.623Tb.Th –0.003 0.056 0.815 1.851 0.186 –0.007 0.556 0.462 5.515 0.026Tb.Sp –0.391 17.777 0 3.094 0.091 –0.364 50.196 0 2.151 0.154DA 0.072 5.353 0.029 0.191 0.666 0.082 7.115 0.013 2.620 0.117

H – B, head – base; effect, epiphysis; covariate (Cov), age.BV/TV, bone volume fraction (%); Tb.Pf, connectivity (mm–1); SMI, structure model index; Tb.N, trabecular number (mm–1); Tb.Th, trabecular thickness (mm); Tb.Sp, trabecular separation (mm); DA, degree of anisotropy.



702

predictor of reduction in strength under large-deformationloads.

With respect to DA, in all cases the metacarpal headwas found to be significantly more anisotropic relative tothe base in our sample, indicating that distal epiphysealtrabecular orientation was adapted to a more uniformloading history. This was a somewhat surprising outcome,given that the MCP joint experiences more varied loadingthan occurs at the CMC articulation. One possible explana-tion is that the greater isotropy (absence of preferredorientation) found in the base is determined by proximalmetacarpal articular shape. As noted above, the basecontacts three elements in the distal carpal row, as well asthe third metacarpal. Although movement is highlyconstrained among these joints, load transfer across thecomplex CMC may translate as isotropy within the trabe-cular mass beneath the external cortical shell.

Of equal interest are those features of trabecular archi-tecture that did not differ between ipsilateral epiphyses inspite of the very different functional contexts to which

they are exposed (left and right; male and female) andwhich may suggest mitigation through greater geneticconstraint. With Tb.Pf in the female right metacarpal asthe only exception, those variables indicative of structure(connectivity, SMI and trabecular thickness) did not differsignificantly between the head and base (although thedistal epiphysis tends to have a better connected, plate-like lattice; Fig. 3). The nearly uniform trabecular thicknessamong the ipsi- and contralateral epiphyses is consistentwith the model of ‘constant trabecular size’ proposed bySwartz et al. (1998) in their theoretical and empirical studyof inter-specific variation in cancellous bone architecturein mammals across five orders of magnitude of body sizevariation. They proposed that trabecular bone adapts tochange in functional demand primarily through the addi-tion of more trabeculae and that the demands of calciummetabolism place an upper threshold on trabecular size.Applied to the present study, this adaptive response wouldaccount for the greater trabecular number and BV/TV inthe metacarpal head noted above. Bouxsein et al. (2004)observed no difference for trabecular thickness betweenC57BL/6J and C3H/HeJ mouse strains in their comparativestudy of trabecular microarchitecture, although other volumeand structural measures differed significantly. Giesenet al. (2004) found no differences for trabecular thicknessin specimens excised from the manidibular condyles ofhuman dentate and edentate subjects, although the lattersubjects (in which the level of loading was presumablylower given a lack of rooted teeth) did have a lower BV/TVand a more rod-like structure.

Not unexpectedly, for some variables age was asignificant covariate within females, the sample of which

Fig. 2 Absolute differences between ipsilateral epiphyseal means by side and sex. BV/TV, bone volume fraction; Tb.Pf, connectivity; SMI, structure model index; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation; DA, degree of anisotropy.

Fig. 3 The typical pattern of findings for all four epiphyses as presented in a series of 5-mm cubic volumes of interest (VOI) from a 20-year-old male. Note variation in both volumetric measures and structural properties (e.g. plates vs rods).



703

includes a number of subjects who would be peri- or post-menopausal. Interestingly, age appears to impact onlystructural and not volumetric variables. This is perhapsunderstandable if, as we suggest, volumetric propertiessuch as BV/TV and Tb.N are more responsive to mechanicalregulation and would be maintained through functionalloading. Indeed, this would account for the fact thatthe influence of age is felt more on the left rather thanthe right metacarpal given the human propensity for aright-hand bias (handedness).

Our argument that there are measurable differencesbetween functionally labile and constrained trabeculararchitectures not only between but within anatomicalsites begs the following question: why would structuralproperties such as trabecular connectivity and SMI appearto be relatively isolated from mechanical input in com-parison to a variable such as bone volume fraction? Thisquestion is complicated by clinical and experimental studiesthat point to sensitivity of structural properties to inter-ventions, either prophylactic and/or exercise (increasedloading or unloading). For example, Fox et al. (2005) reportedincreases in bone volume fraction, connectivity and a shiftto more plate-like structure in iliac crest biopsies inpostmenopausal women following 18 months of para-thyroid hormone 1–84 administration, whereas Chen et al.(2008) found that alfacalcidol, a vitamin D metabolite,inhibited bone loss and increased bone formation (bonevolume fraction and trabecular thickness) in the lumbarvertebrae of bipedal and sedentary female rats. Examiningthe effect of unloading on trabecular and cortical architec-ture in male BALB and C3H mice strains, Squire et al. (2004)found that both strains showed a similar level of responseto loss of mechanical loading, with reductions in metaphy-seal and epiphyseal BV/TV, Tb.N and Tb.Th. Interestingly,these results for male mice differed from those found forfemales of the same strains subjected to the same proto-cols (Judex et al. 2004), suggesting a complex gender/gene/anatomical site interaction. Clinically, mechanicalunloading due to spinal cord injury resulted in reducedbone volume and structure (thickness) (Modlesky et al.2004), although notably Tb.Th declined only in the distalfemur and not in the proximal tibia. Similarly, increasedloading due to targeted exercise (gymnastics) increasedapparent bone mineral content, bone volume and trabe-cular number but not trabecular thickness in the proximaltibia of female college athletes (Modlesky et al. 2008).

The degree to which the intervention research appliesto the current study is somewhat of an open question, asour subjects were drawn from a mostly urban, non-sedentary 19th century population unencumbered withthe ‘conveniences’ of modern living (motorized transport,processed foods, a diverse array of over-the-counter andprescribed medications). However, and importantly,the clinical and experimental data do suggest that theprimary response to either drug or exercise intervention

occurs through altered bone volume mediated throughan increase/decrease in Tb.N and, to a lesser and morevariable degree, through changes in Tb.Th and connectivity.This pattern broadly agrees with our results for the contra-and ipsilateral second metacarpal epiphyses. It seems likelytherefore that a fundamental objective of adaptivebone regulation is to maintain the integrity of the latticestructure through conservation of connectivity, thicknessand the SMI while maintaining responsiveness to fluctua-tions (increase or decrease) in loading via volume and number.

There are several limitations to the present study.Among these is our presumption that the right metacarpalwould experience a more diverse loading history as a func-tion of handedness. Although reasonable at the popula-tion level, in fact, we do not know the hand preferenceof these particular individuals, derived from an historicarchaeological sample. Previous research with this sampleclearly points to a strong directional asymmetry consistentwith right-handedness in both trabecular (Lazenby et al.2008a) and cortical (Lazenby, 1998) structure. We also donot know whether these individuals suffered any meta-bolic or endocrine disorders that may have affected bonephysiology. However, as noted earlier, no manifestationsof disorders known to be grossly or histologically evidentin skeletal remains (e.g. hyperparathyroidism, vitamin Ddeficiency) were observed. It is also the case that ourrelatively small sample of males and females covers abroad age range. It would be of interest to know whateffect, if any, a more comprehensive sampling of adultsacross the lifespan would be revealed with regard to ageand trabecular physiology.

Conclusions

Characterization of trabecular microarchitecture in proxi-mal and distal epiphyses in the human second metacarpalreveals patterns of variation partitioned between afunctionally responsive and conserved morphology. Theunique combination of anatomy at the CMC and MCParthroses in a context of human functional laterality affordsthe opportunity to investigate the impact of varied load-ing environments in ipsilateral and contralateral epiphyses.As hypothesized, the second metacarpal head reveals amore robust architecture in keeping with a more diversemechanical loading environment. However, this is trueonly with regard to volumetric measures, including bonevolume fraction and trabecular number, and in terms ofgreater anisotropy for trabecular orientation. In contrast,structural measures, such as connectivity, thickness andrelative ‘plateness’ appear to be relatively protected fromvariation in mechanical loading. The existence of function-ally constrained properties within a diverse loading environ-ment suggests mitigation of mechanical input throughgenetic regulation, although our study design does notpermit a direct test of that hypothesis.



704

Acknowledgements

Support for the research was provided by grants from the NaturalSciences and Engineering Research Council (R.A.L. and B.H.),the Canadian Foundation for Innovation, Alberta Innovation andScience and the Alberta Heritage Fund, Genome Canada andGenome Alberta (B.H.).

References

Bevill G, Eswaran SK, Gupta A, Papadopoulos P, Keaveny TM

(2006) Influence of bone volume fraction and architecture oncomputed large-deformation failure mechanisms in humantrabecular bone.

Bone

39

, 1218–1225.

Bouxsein M, Uchiyama T, Rosen C, et al.

(2004) Mapping quanti-tative trait loci for vertebral trabecular bone volume fractionand microarchitecture in mice.

J Bone Min Res

19

, 587–599.

Chen H, Tian X, Liu X, Setterberg R, Li M, Jee W

(2008) Alfacalcidol-stimulated focal bone formation on the cancellous surface andincreased bone formation on the periosteal surface of the lum-bar vertebrae of adult female rats.

Calcif Tissue Int

82

, 127–136.

Chin S, Vedder N

(2008) MOC-PSSM CME article: metacarpal frac-tures.

Plast Reconstruct Surg

121

(1 Suppl), 1–13.

Dahlberg G

(1940)

Statistical Methods for Medical and BiologicalStudents

. New York: Interscience Publications.

Fajardo RJ, Ryan T, Kappelman J

(2002) Assessing the accuracy ofhigh-resolution X-ray computed tomography of primate trabecularbone by comparisons with histological sections.

Am J PhysAnthropol

118

, 1–10.

Fox J, Miller M, Recker R, Bare S, Smith S, Moreau I

(2005) Treat-ment of postmenopausal osteoporotic women with parathyroidhormone 1–84 for 18 months increases cancellous bone forma-tion and improves cancellous architecture: a study of iliac crestbiopsies using hisomorphometry and microcomputed tomography.

J Musculoskelet Neuronal Interact

5

, 356–357.

Frost H

(2001) From Wolff’s law to the Utah paradigm: insightsabout bone physiology and its clinical applications.

Anat Rec

262

, 398–419.

Giesen EBW, Ding M, Dalstra M, van Eijden TMGJ

(2004) Changedmorphology and mechanical properties of cancellous bone in themandibular condyles of edentate people.

J Dent Res

83

, 255–259.

Judex S, Garman R, Squire M, Donahue L-R, Rubin C

(2004)Genetically based influences on the site-specific regulation oftrabecular and cortical bone morphology.

J Bone Min Res

19

,600–606.

Ketcham R, Ryan T

(2004) Quantification and visualization ofanisotropy in trabecular bone.

J Microsc

213

, 158–171.

Kim D-G, Christopherson GT, Dong XN, Fyhrie DP, Yeni YN

(2004)The effect of microcomputed tomography scanning and re-construction voxel size on the accuracy of stereological measure-ments in human cancellous bone.

Bone

35

, 1375–1382.

Lazenby R

(1998) Second metacarpal midshaft geometry in anhistoric cemetery sample.

Am J Phys Anthropol

106

, 157–167.

Lazenby R, Cooper D, Angus S, Hallgrimsson B

(2008a) Articularconstraint, handedness, and directional asymmetry in the humansecond metacarpal.

J Hum Evol

54

, 875–885.

Lazenby R, Skinner M, Hublin J-J, Cooper D, Hallgrimsson B

(2008b)A comparative 3D micro-CT study of trabecular architecture inthe second metacarpal of

Homo

and Pan.

Am J Phys Anthropol

Supp. 46, 138.

Lazenby RA

(2002) Skeletal biology, functional asymmetry and theorigins of ‘handedness’.

J Theor Biol

218

, 129–138.

Marshall LM, Zmuda JM, Chan BKS, et al.

(2008) Race and ethnicvariation in proximal femur structure and BMD among oldermen.

J Bone Min Res

23

, 121–130.

Modlesky CM, Majumdar S, Dudley GA

(2008) Trabecular bonemicroarchitecture in female collegiate gymnasts.

OsteoporosisInt

, DOI 10.1007/s00198-007-0522-x.

Modlesky CM, Majumdar S, Narasimhan A, Dudley GA

(2004)Trabecular bone microarchitecture is deteriorated in men withspinal cord injury.

J Bone Min Res

19

, 48–55.

Nonaka K, Fukuda S, Aoki K, Yoshida T, Ohya K

(2006) Regionaldistinctions in cortical bone mineral density measured by pQCTcan predict alterations in material property at the tibial diaphysisof the Cynomolgus monkey.

Bone

38

, 265–272.

Robling A, Castillo A, Turner C

(2006) Biomechanical and molecularregulation of bone remodeling.

Ann Rev Biomed Eng

8

, 455–498.

Ruff CB, Holt B, Trinkaus E

(2006) Who’s afraid of the big badWolff? ‘Wolff’s Law’ and bone functional adaptation.

Am J PhysAnthropol

129

, 484–498.

Rupprecht M, Pogoda P, Mumme M, Rueger J, Püschel K, Amling M

(2006) Bone microarchitecture of the calcaneus and its changesin aging: a histomorphometric analysis of 60 human specimens.

J Orthop Res

24

, 664–674.

Ryan T, Krovitz G (2006) Trabecular bone ontogeny in the proximalhuman femur. J Hum Evol 51, 591–602.

Skedros JG, Hunt KJ (2004) Does the degree of laminarity correlatewith site-specific differences in collagen fibre orientation inprimary bone? An evaluation in the turkey ulna diaphysis. J Anat205, 121–134.

Squire M, Donahue L-R, Rubin C, Judex S (2004) Genetic variationsthat regulate bone morphology in the male mouse skeleton donot define its susceptibility to mechanical loading. Bone 35,1353–1360.

Sran MM, Boyd SK, Cooper DML, Khan KM, Zernicke RF, Oxland TR(2007) Regional trabecular morphology assessed by micro-CT iscorrelated with failure of aged thoracic vertebrae under aposteroanterior load and may determine the site of fracture.Bone 40, 751–757.

Stauber M, Rapillard L, van Lenthe G, PZ, Müller R (2006) Impor-tance of individual rods and plates in the assessment of bonequality and their contribution to bone stiffness. J Bone Min Res21, 586–595.

Swartz SM, Parker A, Huo C (1998) Theoretical and empiricalscaling patterns and topological homology in bone trabeculae.J Exp Biol 201, 573–590.

Tamai K, Ryu J, An KN, Linscheid RL, Cooney WP, Chao EYS (1988)Three-dimensional geometric analysis of the metacarpophalan-geal joint. J Hand Surg 13A, 521–529.

Tanck E, Homminga J, Van Lenthe GH, Huiskes R (2001) Increase inbone volume fraction precedes architectural adaptation in grow-ing bone. Bone 28, 650–654.

Thomas CDL, Feik SA, Clement JG (2006) Increase in pore area, andnot pore density, is the main determinant in the developmentof porosity in human cortical bone. J Anat 209, 219–230.

Tocheri M, Razdan A, Williams R, Marzke M (2005) A 3D quantita-tive comparison of trapezium and trapezoid relative articularand nonarticular facet areas in modern humans and great apes.J Hum Evol 49, 570–586.

Ulrich D, van Rietbergen B, Laib A, Rüegsegger P (1999) The abilityof three-dimensional structural indices to reflect mechanicalaspects of trabecular bone. Bone 25, 55–60.

Van Lenthe GH, Stauber M, Muller R (2006) Specimen-specificbeam models for fast and accurate prediction of human trabe-cular bone mechanical properties. Bone 39, 1182–1189.

10.1007/s00198-007-0522-x



705

Waarsing J, Day J, Weinans (2004) An improved segmentationmethod for in vivo μCT imaging. J Bone Min Res 19, 1640–1650.

Wright T, Thompson J, Conrad B (2006) Loading of the indexmetacarpal after trapezial and partial versus complete trape-zoid resection. J Hand Surg 31A, 58–62.

Zhang F, Xiao P, Yang F, et al. (2008) A whole genome linkage scan

for QTLs underlying peak bone mineral density. Osteoporos Int19, 303–310.

Zhi J, Xu G, Rubin C, Hadjiargyrou M (2008) The lipogenic geneSpot 14 is activated in bone by disuse yet remains unaffected bya mechanical signal anabolic to the skeleton. Calcif Tissue Int 82,148–154.

A three-dimensional microcomputed tomographic study of site-specific variation in trabecular microarchitecture in the human second metacarpal

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