Weinans, H.H. (Harrie)

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BackgroundHigh resolution micro-CT scanning offers a wide perspec-tive of possibilities for evaluating bone tissue. It is welldescribed that bone mineral density correlates well with bonestiffness and strength and therefore this parameter is used asthe gold standard in clinical practice to evaluate bone qualityand fracture risk. The contribution of architecture to bonequality is also well recognized, however there exist manyquantitative parameters of architecture and in 2-D many ofthose are biased. In particular, the possibility to accuratelydetermine the 3-D architecture of the bone now gives theopportunity to determine the particular effects of architec-ture on bone mechanical properties independent of bonemineral density. This requires analysis of the bone architec-ture using the finite element method. When this method iscombined with mechanical testing of bone specimens thecombined data can provide additional information about theproperties of matrix tissue, independent of architecture andbone mass.Micro-CT and architectural measuresInterpretation of bone architecture from two-dimensionalbone sections requires a model of the actual structure, usu-ally the parallel plate model1. In fact, all architectural param-eters can then be derived from the area fraction and perime-ter. Using stereological principles Tb.Th., Tb.Sp. and Tb.N.can be determined. From micro-CT the complete three-dimensional architecture can be obtained in a computer andtherefore it enables to more directly determine trabecularthickness, spacing and number. In addition, many otherparameters can be obtained such as mean intercept length,structure model index, euler number, degree of anisotropy,volume orientation, fractal number, curvature etc. It is notalways clear what the relevance is of these numbers, how thedifferent parameters are related and whether they areuniquely defined. Besides, software may vary betweenresearch groups, which makes it even more difficult to com-pare the results of different studies. When the differentparameters are compared it appears that many of the param-eters are more or less related to volume fraction, therebyemphasizing the importance of bone mineral density. Only afew parameters, such as degree of anisotropy, are clearlyindependent of volume fraction. As such, these parametersare therefore more useful than others.An additional problem is related to the transfer of the rawdata from the micro-CT scan to the smoothed representationof the architecture. This transfer requires thresholding of thedata that can be executed in different ways. Different thresh-olding algorithms can make an enormous difference betweenthe quantitative outcome of the parameters, in particularwhen the resolution is above 10 microns. For example whenvolume fraction derived with micro-CT scan is comparedwith an Archimedes’ test, differences will occur. Unbiasedthresholding is a considerable problem in micro-CT scanningof bone tissue, which is not always acknowledged. Improvedthresholding methods are a prerequisite for the further appli-cations and success of micro-CT. In addition a more uniformway of deriving the three-dimensional architectural parame-ters is required to make 3-D parameters from micro-CT astandard in the sense as previously existed in sectional datausing the parallel plate model of Parfitt1,3.Micro-CT and finite element modelsWhat many studies attempt related to three-dimensionalbone architecture parameters is to elucidate somethingrelated to a status of the bone or a disease. In particular, themechanical properties or strength of the bone is importantsince osteoporosis is a major field of research in this area. Itis well recognized that volume fraction/ BMD has its short-535J Musculoskel Neuron Interact 2002; 2(6):535-537Architectural changes independentof bone mineral in osteoporosisH. WeinansDepartment of Orthopaedics, Erasmus University Rotterdam, Rotterdam, The NetherlandsKeywords: Bone Architecture, Bone Stiffness, Micro-CT, Finite Element Model, OsteoporosisPerspective Article HylonomeCorresponding author: Harrie Weinans, Ph.D., Erasmus Orthopaedic ResearchLaboratory, Erasmus University Rotterdam, Room EE1614, P.O. Box 1738,3000 DR, Rotterdam, The NetherlandsE-mail: weinans@ortho.fgg.eur.nlAccepted 1 August 2002with exactly the matrix (bulk) stiffness of the trabeculae. Itshould be emphasized that this difference can only be deter-mined as one number and thus the method can not give anyinformation about variation in bulk stiffness e.g. related tomicro-damage or mineralization variations in the individualtrabeculae. Therefore the difference between ‘FE-stiffness’and ‘tested-stiffness’ is related to what is called ‘effective-stiffness’ of the bulk material the trabeculae are made of.Such combined tests have been performed recently by a fewresearch groups2,4,5 and have shown novel information, e.g.about the strength and stiffness of trabecular bulk material(matrix). For example Day et al. have used this method toshow that the trabecular bone tissue matrix of subchondralbone from patients with mild osteoarthritis is decreased byapproximately 60%5.Future perspective of micro-CTMicro-CT has been introduced to study and to evaluatebone tissue in great detail in its 3-D architecture. Thisrequires sophisticated evaluation as well. The latest develop-ments have enabled us to apply the micro-CT scan with invivo experiments. Currently we have performed a series of invivo micro-CT scans (Skyscan, Antwerp, Belgium) in a fol-low-up study with 9-month-old rats to evaluate the effects ofOVX. We made scans of the proximal tibia with a resolutionof 20 microns and radiation dose below 0.4 Gy, enabling usto do follow-up studies with individual rats. So far we have a14-week follow-up of control and OVX treated rats. Sincewe have multiple scans of one animal the consecutive scanscan be overlaid (registration or matching) on top of eachother to determine architectural changes in time in individ-ual rats. Precision and reproducibility have been tested.Using this method we can accurately determine architectur-al changes at the level of individual trabeculae in living ani-mals. Preliminary results show a novel finding of additionalgrowth and architectural changes in OVX rats relative tosham operated rats (Figure). These new developments of invivo micro-CT scanning will greatly contribute to experi-mental studies in small animals concerning orthopaedic orpharmacological intervention and transgenic mouse models.Overlaid identical cross-sections of registered data-sets ofepi- and metaphysial parts of tibia of the OVX rat. At theright detail of lateral metaphysis of OVX rat showing growthof approximately 150 microns at the growth plate 14 weeksafter OVX in a 9-month-old rat.H. Weinans: Architecture of bone536comings, however it is not clear what additional informationwe need to perfectly predict bone strength from architectur-al information. According to the definition of osteoporosis,fragility and architecture are important, but it is not clearhow to quantify it. For architecture however there is a clearsolution. Strength is a well-defined mechanical parameter,however the criterion on how the material fails is debatable.Different strength criteria are therefore defined, e.g. basedon deformation or energy. For bone we are able to estimatestiffness quite well and we know that stiffness correlates wellwith strength. Under the assumption that the bone matrixproperties (also called bulk properties as opposed to appar-ent properties) are uniform and isotropic we can fully calcu-late the stiffness of a piece of bone, even with a very complexarchitecture.When a beam or a long bone bends, the stiffness dependson the bulk properties of the material (cortex) and the geom-etry of the cross-section. Therefore cross-section or momentof inertia is measured when the stiffness or strength of thebeam is determined. For cancellous bone exactly the samecan be done. However, the geometry of cancellous bone ismuch more complex and a finite element (FE) model isrequired to do the ‘beam’ analyses. Such FE-analyses havebeen done2,3 and the finite element result should be inter-preted with caution. The basic assumption is that the bulkproperty of cancellous bone is uniform and isotropic and wealready know that this is not true in reality. However theresult can also be interpreted in another way. The input forthe finite element code is no more then the architecture ofstructure. There is no further information concerning matrixtissue properties or whatsoever. Hence, the input is no morethan required for any other 3-D architectural parameter.The output, in this case the calculated stiffness or FE-stiff-ness of the specimen, is a number representing somethingwhich is only related to architecture! In that sense it can beinterpreted as an alternative architecture parameter, similarto any other 3-D parameter. Though it is a nice one, since itrepresents the stiffness of the specimen exclusively as a con-sequence of the 3-D architecture, free of matrix (bulk) prop-erties. However, it should not be interpreted as the truestiffness as measured from an experimental compression testwith the true specimen. The difference being precisely relat-ed to the matrix bulk properties only!Micro-CT and mechanical testsIt appears obvious that the bone matrix properties areimportant as well. Bone quantity is of course only importantas long as the quality of the material itself is beneficial. Thisis the reason that, when diaphyseal bone is tested, it shouldbe corrected for cross-sectional geometry. Again, we can dothe same for a test with a piece of cancellous bone. The finiteelement model functions as the correction factor because itcan provide us with the stiffness as a result of architectureonly. The difference between a true stiffness from a mechan-ical test and the finite element model thus can provide usH. Weinans: Architecture of bone537AcknowledgmentPart of the work presented in this manuscript was funded by the Euro-pean Union under FP5, project MIAB, QLRT-1999-02024.References1. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, MallucheH, Meunier PJ, Ott SM, Recker RR. Bone histomorphome-try: standardization of nomenclature, symbols, and units.Report of the ASBMR Histomorphometry, NomenclatureCommittee.  J Bone Miner Res 1987; 2:595-610.2. Van Rietbergen B, Odgaard A, Kabel J, Huiskes R.Relationships between bone morphology and bone elasticproperties can be accurately quantified using high-resolutioncomputer reconstructions. J Orthop Res 1998; 16:23-28.3. Day JS, Ding M, Odgaard A, Sumner DR, Hvid I, Weinans H.Parallel plate model for trabecular bone exhibits volume frac-tion-dependent bias. Bone 2000; 27:715-720.4. Niebur GL, Feldstein MJ, Yuen JC, Chen TJ, Keaveny TM.High-resolution finite element models with tissue strengthasymmetry accurately predict failure of trabecular bone. JBiomech 2000; 33:1575-1583.5. Day JS, Ding M, van der Linden JC, Hvid I, Sumner DR,Weinans H. A decreased subchondral trabecular bone tissueelastic modulus is associated with pre-arthritic cartilage dam-age. J Orthop Res 2001; 19:914-918

Architectural changes independent of bone mineral in osteoporosis

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Architectural changes independent of bone mineral in osteoporosis

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