Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Biological Response
The implant-tissue interface is an extremely dynamic region of
interaction. This interface completely changes character as it
goes from its genesis (placement of the implant into the prepared bony site) to its maturity (healed condition). The biomechanical environment plays an immediate role in the quality
and compositional outcome of the new interface. For example,
extensive research shows that if the implant is stable in the bone
at the time of placement, then the interface is more likely to
result in osteointegration.15,20 Relative movement (or micromotion) between the implant and the bone at the time of placement is more likely to favor the development of a fibro-osseous
interface.11,18 The healing stage of the interface, however, is only
the beginning of its dynamic nature. Functional loading of the
implant brings additional biomechanical influences that greatly
affect the composition of this junction.
A topic of intense research for many years is the transduction
of loading-induced strain at the interface into a signal that can
direct the interfacial tissues to respond or remodel. It has been
proven that bone responds to both hormonal and biomechanical (functional loading) regulation. These two regulating mechanisms are often in opposition to each other. Research has
shown that even in instances in which a large demand exists for
calcium (the primary objective for hormonal regulation), functional loading can compete and maintain bone mass.21 Researchers have theorized that the actual strain (see Chapter 22) that
is perceived by the bone tissue initiates a chain of events that
results in a biological response. For tissue strain to influence
bone adaptation at the bone-implant interface, it must elicit
some sort of a chemical or biological response in a strainsensitive population. The current hypothesis is that bone cells
in conjunction with the extracellular matrix (ECM) comprise
the strain-sensitive population and that each plays a vital role
in the mediation of the interface. Based on this rationale, the
Mechanotransduction
Mechanotransduction is a multistep process that includes (1)
mechanocoupling (transduction of mechanical forces into
signals sensed by sensor cells), (2) biochemical coupling (conversion of mechanical signal into a biochemical signal to elicit
a cellular response such as gene activation), (3) transfer of a
signal from sensor to effector cells, and (4) the effector cell
response.22 Recent studies have led to the current consensus that
osteocytes embedded within lacunae in bone matrix act as
mechanosensors and help translate mechanical loads into biochemical signals.2325 Osteocytes are the most abundant cells
and inhabit an extensive lacunocanalicular network that enables
them to communicate with other osteocytes, as well as with
periosteal and endosteal osteoblasts.2426 Furthermore, osteocytes have higher sensitivity to mechanical stimulation than
osteoblasts.2729
The strains experienced at the tissue level in vivo during
normal activities (0.04%0.3%) are much less than the strain
levels (1%10%) required to elicit a cellular response.30,31 Initially, shear stress caused by fluid flow in the canalicular spaces
was believed to be the primary driver of biochemical coupling
in bone, with strain being the dominant stimulus.23,32 Later, You
etal.33 proposed a model for the amplification of physiologically induced strains to levels that would initiate intracellular
biochemical responses. The model suggested that drag forces on
the transverse tethering fibers34,35 during fluid flow through the
pericellular space (filled with matrix between osteocyte cell
membrane and canalicular wall) will produce a tensile stress,
which will in turn create a hoop strain in the intracellular actin
cytoskeleton that is two orders of magnitude higher than the
strains at the whole-bone level. This model was further modified using updated ultrastructural data on the cytoskeleton,
transverse tethering fibers, and their structural rigidity.36 Cowin37
compared and reviewed the two models by focusing on the
relationship between the bone microstructure and the mechanism by which osteocytes sense the fluid flow as the result of
mechanical loading. Possible mechanoreceptors, mechanisms
by which osteocytes sense mechanical stimuli, and intracellular
signaling pathways are discussed in several research groups.3840
Regulation of osteoblastic activity by osteocytes has been proposed to occur through gap junctions,4144 with the stimulation
of gap junctions mediated by prostaglandin E2 (PGE2).4549
Whereas loading of bone decreases osteocyte apoptosis,
disuse and supraphysiologic strains increases it followed by
107
108
haversian remodeling.5052 Bone disuse, even for short durations, may rapidly induce a hypoxic state of stress in osteocytes,
which when extended may lead to apoptosis. This hypoxia can
be reversed by short-term physiologic loading, which suggests
that mechanical loading at such magnitudes plays a key role in
osteocyte viability.53 This may adversely affect bone strength
independent of bone loss.54 Hypoxic osteocytes may also
mediate disuse-induced bone resorption by increasing osteopontin expression.55
6000
Pathologic
overload zone
4000
Microstrain
Overload zone
2000
Physiologic
loading zone
Frosts CGFR
Herts curve
Tension
Compression
Force
W/ rest
Cyclic
Bone formation
Max response
Threshold
Stimulus (magnitude)
Bone formation
W/ rest
Cyclic
Saturated response
Threshold
109
B
Stimulus (cycle number)
110
second messengers or intracellular mediators. In turn, these messenger molecules pass the signal on by altering the behavior of
selected cellular proteins. Some of the most widely used intracellular mediators are cyclic AMP (cAMP), Ca2+, and cyclic GMP
(cGMP).113 PGE2 and prostacyclin are paracrines that are released
by osteoblasts in response to mechanical strain.97,104108 They are
essential for bone formation by mechanical loading114119 and
are also increased by fluid shear stress120125 in a dose-dependent
manner. The anabolic effect of mechanical stimulation in vivo
has been shown to be greatly depressed by the addition of
indomethacin, a chemical that blocks the production of these
prostaglandins (PGs).109 Increase in messenger ribonucleic acid
(mRNA) of c-fos and insulin-like growth factor 1 (IGF-1) in
osteocytes immediately after mechanical stimulation led to the
study involving compressive dynamic loading of the eighth
caudal vertebrae in rats. When indomethacin and NGmonomethyllarginine (L-NMMA), inhibitors of PG and nitric
oxide (NO), respectively, were administered individually, c-fos
(a marker for mechanical responsiveness in osteocytes) was
suppressed partially, but combined administration resulted in
drastic suppression.126
This suggested that PG might be produced by NO-dependent
and NO-independent mechanisms. Rats injected with NO
donors showed increased osteogenic response only when
loaded, which suggested that NO requires other molecules such
as PG induced by mechanical loading for bone.117 Human bone
cells from patients with osteoporosis subjected to pulsating
fluid flow showed reduced long-term release of PGE2, suggesting
that long-term adaptive response of these bone cells to mechanical stimuli may have been affected.127
Harrell and Binderman99 observed that isolated osteoblasts,
grown on a polystyrene plate that had an orthodontic jackscrew
glued to its bottom, responded to continuous strain by increasing PGE2 concentrations followed in minutes by an increase in
cAMP release. Rodan etal.100 agreed that mechanical strain
affected the second-messenger cAMP and also reported changes
in cGMP and calcium ions. Yeh and Rodan97 suggested that PGs
might be involved in the transduction of mechanical strain but
did not apply physiological levels of strain to their samples.
Fluid shear experiments by Reich and Frangos101 and cyclic
biaxial strain studies by Brighton etal.98 have demonstrated that
osteoblasts respond with an increase in cellular levels of inositol
triphosphate.
Osteoblasts form bone by secreting many extracellular matrix
proteins, including type I collagen, osteopontin, osteocalcin,
osteonectin, biglycan, and decorin. Osteopontin was first purified from rat bone matrix and is considered to play an important role in the cascade of events required for the formation of
bone matrix.110 In vitro studies have revealed osteoblasts to be
more responsive to fluid forces than mechanical strain, associating increased osteopontin expression with increases in force
magnitude without any dependence on strain magnitude or
rate.128 Recently, experiments on the femoral epiphyses of
rabbits have shown that cyclic loading can influence endochondral bone formation by accelerating formation of secondary
ossification centers and increase expression of RUNX2 (an
important transcription factor of osteoblasts) and extracellular
proteins, including osteopontin, type X collagen, and decorin.129
Osteocalcin, also known as bone Gla protein, is widely used as a
marker for bone metabolism. Studies have shown that the production of osteocalcin can be stimulated by mechanical stress
both in vivo112 and in vitro.113 Experiments on bone marrow
stromal cells have revealed that shear caused by fluid flow
enhances maturation of osteoblasts by stimulating the expression of osteocalcin,130 osteopontin, and bone sialoprotein131 but
not proliferation of stromal cells.
Parathyroid hormone (PTH) has been found to play a vital
role in bone adaptation to mechanical stimuli. Rats with thyroparathyroidectomy did not show any osteogenic response
caused by mechanical loading of vertebrae,132 but the response
could be restored by a single PTH injection before loading.
However, the restoration did not occur when PTH was injected
3 days after mechanical stimulation. Expression of c-fos was
observed only in loaded rats injected with PTH,132 further highlighting the importance of PTH in mechanical adaptation of
bone. In vitro studies on mouse osteoblasts provided further
insights into the interactive effects of PTH and pulsating fluid
flow on PGE2 and NO production. Although fluid flow stimulated a twofold rise in PGE2 and NO production, PTH induced
a similar effect on PGE2 but reduced NO production by degrading the enzyme activity of NO synthase. When applied together,
the stimulatory effects of fluid flow were nullified. According to
the authors, the results suggested that PTH enhances
NO-independent PGE2 production but inhibits stressinduced NO production by degrading NO synthase, in turn
reducing NO-dependent PGE2 production.133 PTH may also
regulate mechanotransduction by influencing the influx of
extracellular calcium in hypotonic osteocytes.134
111
112
Actin
-Actinin
Vinculin
Paxillin
Talin
Plasma membrane
Intracellular
Integrin
Extracellular
Matrix proteins
Subunits
Subunits
Culture Dish
FIGURE 6-4. Diagram illustrating cytoskeletal components at point of attachment with extracellular
matrix in vitro. (Adapted from Duncan RL, Turner CH: Mechanotransduction and the functional response of
bone to mechanical strain, Calcif Tissue Int 57:344-358, 1995.)
fluid flow applying physiological strain levels on human osteoblasts rapidly induced ERK phosphorylation and clustering of
v3 integrins in vitro,176 the mechanism behind the regulation
of osteocyte apoptosis by mechanical stimulation involves and
requires the activation of an integrincytoskeletonSrcERK
pathway.179 These results have led researchers to suggest that
both mechanical (e.g., fluid flow, cyclic stretching) and chemical
(e.g., hormones, growth factors) stimuli may act through the
same intracellular signaling pathways.176,179
Numerous subunits have been characterized, and different
combinations of and subunits function as receptors for a
variety of extracellular proteins.180,181 The 1-integrin subunit is
often expressed in bone cells both in vitro and in vivo.181
Carvalho etal.155 demonstrated that changes in the organization of the 1-subunit were induced by the application of strain
as early as 4 hours from its onset. They compared the expression
of the 1-integrin subunit mRNA from strained cultures with
unstrained controls.
113
Biomechanical Response
A compelling argument has been presented for strain-induced
biological response of bone to mechanical load. The question
remains: What controls the magnitude of strain imparted to the
dental implantbone interface?
Strain has been generically defined in relation to deformation and applied stress. The discussion of strain must be necessarily extended for biological structures. The mechanical
properties of the trabecular and cortical bone found within the
oral environment exhibit a high degree of variation as a function of load direction, rate, and duration. In addition, the structural density of the bone has a significant influence on its
stiffness (modulus of elasticity) and ultimate strength. As such,
the mechanical strain exhibited in bone is ultimately a function
of the bone density.
114
E2
E2
E1
E3
E3
E1
115
0.016
= 1500/sec
o
xe
= 300/sec
Stress (MPa)
xe
o
= 1/sec
x e = 0.1/sec
o
x e = 0.01/sec
200
xe
100
= 0.001/sec
Strain (mm/mm)
xe
300
0.020
p 60 MPa
0.012
0.008
0.004
0
0.004
0.008
0.012
Strain
0.016
10,000
20,000
Time (seconds)
FIGURE 6-7. Creep curve for adult human cortical bone at constant stress of 60MPa. (From Carter DR, Caler WE: Cycle dependent
and time dependent bone fracture with repeated loading, J Biomech
Eng 105:166, 1983. Used by permission.)
116
0.25
ea,p (103)
0.20
a 50 MPa
m (MPa)
25
0.15
0.10
10
0.05
10
25
0.00
100
104
102
106
Unconstrained modulus
Constrained modulus
140
Elastic modulus (MPa)
117
120
100
107.36
96.23
83.86
80
60
80.98
67.48
55.98
47.30
35.55
40
20
0
Region 2
(N = 18)
Region 3
(N = 16)
when constrained by the surrounding trabecular bone compared with comparable unconstrained tests.
Dental implant patients exhibit variation in the integrity of
the buccal and lingual cortical plates. In some instances, one or
both plates are completely absent. Treatment planning for such
patients should incorporate consideration of the significantly
compromised mechanical stiffness (and likely, strength) of the
trabecular bone in such anatomical sites.
118
TABLE 6-1
Compressive Strength
Pooled sample
Region 1
Region 2
Region 3
10
8
6
4
5.38
3.94
2.57
1.70
0
Pooled sample Region 1
(N = 76)
(N = 42)
Region 2
(N = 18)
Region 3
(N = 16)
FIGURE 6-10. Elastic modulus for constrained and unconstrained test conditions in human mandibular trabecular bone.
Regional differences were noted in the human mandibular
trabecular bone elastic modulus and ultimate compressive
strength, exhibiting up to 47% to 68% higher mean values in
the anterior (region 1) compared with the posterior region of
the mandible (Table 6-1). No differences were observed in
elastic modulus and ultimate compressive strength in the region
between the premolars and molars (regions 2 and 3) (Figure
6-10). The compressive strength was correlated at a high level
of significance (r = 0.88, p < 0.0001) with the trabecular apparent density for a best-fit cubic relationship.
Based on clinical experience with varying densities of available trabecular bone, Misch285 defined two types of trabecular
bone in his clinical classification scheme for the mandible and
maxilla: (1) coarse (division 2 [D2]) in the anterior mandible
and (2) fine trabecular bone in the posterior mandible (division
3 [D3]). Qu264 found a significant difference between apparent
density in region 1 (anterior mandible) and in regions 2 and 3
(posterior mandible). No significant difference was noted
between region 2 and region 3. The results of the study by Qu
thus provide quantitative validation of Mischs classification
scheme for trabecular bone in the oral environment.
References
1. Dattilo DJ, Misch CM, Arena S: Interface analysis of
hydroxylapatite-coated implants in a human vascularized iliac
bone graft, Int J Oral Maxillofac Implants 10:405409, 1995.
119
120
121
122
156. Ponik SM, Triplett JW, Pavalko FM: Osteoblasts and osteocytes
respond differently to oscillatory and uni-directional fluid flow
profiles, J Cell Biochem 100:794807, 2007.
157. Ingber D: Integrins as mechanochemical transducers, Curr Opin
Cell Biol 3:841848, 1991.
158. Alberts B, Bray D, Lewis J, et al: Extracellular matrix receptors on
animals cells: the integrins. In Alberts B, Bray D, Lewis J, et al,
editors: Molecular biology of the cell, New York, 1994, Garland.
159. Salter DM, Robb JE, Wright MO: Electrophysiological responses
of human bone cells to mechanical stimulation: evidence for
specific integrin function in mechanotransduction, J Bone Miner
Res 12:11331141, 1997.
160. Meazzini MC, Toma CD, Schaffer JL, et al: Osteoblast
cytoskeletal modulation in response to mechanical strain in
vitro, J Orthop Res 16:170180, 1998.
161. Pavalko FM, Chen NX, Turner CH, et al: Fluid shear-induced
mechanical signaling in MC3T3-E1 osteoblasts requires
cytoskeleton-integrin interactions, Am J Physiol 275(6 pt
1):C1591C1601, 1998.
162. Sastry SK, Horwitz AF: Integrin cytoplasmic domains:
mediators of cytoskeletal linkages and extra- and intercellular
initiated transmembrane signaling, Curr Opin Cell Biol 5:831
853, 1993.
163. Schwartz MA, Ingber DE: Integrating with integrins, Mol Biol Cell
5:389393, 1994.
164. Davies PF, Robotewskyj A, Griem ML: Quantitative studies of
endothelial cell adhesion: directional remodeling of focal
adhesion sites in response to flow forces, J Clin Invest 93:2031
2038, 1994.
165. Wang N, Butler JP, Ingber DE: Mechanotransduction across the
cell surface and through the cytoskeleton, Science 260:1124
1127, 1993.
166. Toma CD, Ashkar S, Gray ML, et al: Signal transduction of
mechanical stimuli is dependent on microfilament integrity:
identification of osteopontin as a mechanically induced gene in
osteoblasts, J Bone Miner Res 12:16261636, 1997.
167. Carvalho RS, Schaffer JL, Gerstenfeld LC: Osteoblasts induce
osteopontin expression in response to attachment on
fibronectin: demonstration of a common role for integrin
receptors in the signal transduction processes of cell attachment
and mechanical stimulation, J Cell Biochem 70:376390, 1998.
168. Carvalho RS, Bumann A, Schaffer JL, et al: Predominant integrin
ligands expressed by osteoblasts show preferential regulation in
response to both cell adhesion and mechanical perturbation,
J Cell Biochem 84:497508, 2002.
169. Damsky CH, Werb Z: Signal transduction by integrin receptors
for extracellular matrix: cooperative processing of extracellular
information, Curr Opin Cell Biol 5:772781, 1992.
170. Jaiswal RK, Jaiswal N, Bruder SP, et al: Adult human
mesenchymal stem cell differentiation to the osteogenic or
adipogenic lineage is regulated by mitogen-activated protein
kinase, J Biol Chem 275:96459652, 2000.
171. Lai CF, Chaudhary L, Fausto A, et al: ERK is essential for growth,
differentiation, integrin expression, and cell function in human
osteoblastic cells, J Biol Chem 276:1444314450, 2001.
172. Ogata T: Fluid flow-induced tyrosine phosphorylation and
participation of growth factor signaling pathway in osteoblastlike cells, J Cell Biochem 76:529538, 2000.
173. You J, Reilly GC, Zhen X, et al: Osteopontin gene regulation by
oscillatory fluid flow via intracellular calcium mobilization and
activation of mitogen-activated protein kinase in MC3T3-E1
osteoblasts, J Biol Chem 276:1336513671, 2001.
174. Wadhwa S, Godwin SL, Peterson DR, et al: Fluid flow induction
of cyclo-oxygenase 2 gene expression in osteoblasts is
dependent on an extracellular signal-regulated kinase signaling
pathway, J Bone Miner Res 17:266274, 2002.
175. Ziros PG, Gil AP, Georgakopoulos T, et al: The bone-specific
transcriptional regulator Cbfa1 is a target of mechanical signals
in osteoblastic cells, J Biol Chem 277:2393423941, 2002.
176. Weyts FA, Li YS, van Leeuwen J, et al: ERK activation and alpha v
beta 3 integrin signaling through Shc recruitment in response to
mechanical stimulation in human osteoblasts, J Cell Biochem
87:8592, 2002.
177. Kapur S, Baylink DJ, Lau KH: Fluid flow shear stress stimulates
human osteoblast proliferation and differentiation through
multiple interacting and competing signal transduction
pathways, Bone 32:241251, 2003.
178. Boutahar N, Guignandon A, Vico L, et al: Mechanical strain on
osteoblasts activates autophosphorylation of focal adhesion
kinase and proline-rich tyrosine kinase 2 tyrosine sites involved
in ERK activation, J Biol Chem 279:3058830599, 2004.
179. Plotkin LI, Mathov I, Aguirre JI, et al: Mechanical stimulation
prevents osteocyte apoptosis: requirement of integrins, Src
kinases, and ERKs, Am J Physiol Cell Physiol 289:C633C643,
2005.
180. Hynes RO: Integrins: versatility, modulation and signaling in cell
adhesion, Cell 69:1125, 1992.
181. Clover J, Dodds RA, Gowen M: Integrin subunit expression by
human osteoblasts and osteoclasts in situ and in culture, J Cell
Sci 103:267271, 1992.
182. Buckley MJ, Banes AJ, Levin LG, et al: Osteoblasts increase their
rate of division and align in response to cyclic, mechanical
tension in vitro, Bone Miner 4:225236, 1988.
183. Harter LV, Hruska KA, Duncan RL: Human osteoblast-like cells
respond to mechanical strain with increased bone matrix protein
production independent of hormonal regulation, Endocrinology
136:528535, 1995.
184. Zaman G, Dallas SL, Lanyon LE: Cultured embryonic bone
shafts show osteogenic responses to mechanical loading, Calcif
Tissue Int 51:132136, 1992.
185. Nagatomi J, Arulanandam BP, Metzger DW, et al: Cyclic pressure
affects osteoblast functions pertinent to osteogenesis, Ann
Biomed Eng 31:917923, 2003.
186. Tang LL, Wang YL, Pan J, et al: The effect of step-wise increased
stretching on rat calvarial osteoblast collagen production,
J Biomech 37:157161, 2004.
187. Stanford CM, Keller JC: The concept of osseointegration and
bone matrix expression, Crit Rev Oral Biol Med 2:83101, 1991.
188. Pavlin D, Dove SB, Zadro R, et al: Mechanical loading stimulates
differentiation of periodontal osteoblasts in a mouse
osteoinduction model: effect on type I collagen and alkaline
phosphatase genes, Calcif Tissue Int 67:163172, 2000.
189. Pavlin D, Zadro R, Gluhak-Heinrich J: Temporal pattern of
stimulation of osteoblast-associated genes during mechanically
induced osteogenesis in vivo: early responses of osteocalcin and
type I collagen, Connect Tissue Res 42:135148, 2001.
190. Reich A, Jaffe N, Tong A, et al: Weight loading young chicks
inhibits bone elongation and promotes growth plate ossification
and vascularization, J Appl Physiol 98:23812389, 2005.
191. Hankenson KD, Ausk BJ, Bain SD, et al: Mice lacking
thrombospondin 2 show an atypical pattern of endocortical and
periosteal bone formation in response to mechanical loading,
Bone 38:310316, 2006.
192. Rigsby DF: Analysis of the metabolic and morphologic response of
osteoblasts cultured on Ti-6A1-4V to dynamic, uniaxial stress
[doctoral thesis], Birmingham, AL, 1997, University of Alabama.
193. Reilly DT, Burstein AH: The elastic and ultimate properties of
compact bone tissue, J Biomech 8:393, 1975.
194. Yoon HS, Katz JL: Ultrasonic wave propagation in human
cortical bone, II: Measurements of elastic properties and
micro-hardness, J Biomech 9:459, 1976.
195. Knets I, Malmeister A: Deformability and strength of human
compact bone tissue. In Brankov G, editor: Mechanics of biological
solids 1977. Proceedings of the Euromechanic Colloquium 68,
Sofia, 1977, Bulgarian Academy of Sciences.
196. Ashman RB, Cowin SC, Van Buskirk WC, et al: A continuous
wave technique for the measurement of the elastic properties of
bone, J Biomech 17:349361, 1984.
123
124
244. Pattin CA, Carter DR, Caler WE: Cortical bone modulus
reduction in tensile and compressive fatigue. In Transactions of
the 36th Annual Meeting of the Orthopaedic Research Society, New
Orleans, 1990.
245. Fleck C, Eifler D: Deformation behaviour and damage
accumulation of cortical bone specimens from the equine tibia
under cyclic loading, J Biomech 36:179189, 2003.
246. Zioupos P, Currey JD: The extent of microcracking and the
morphology of microcracks in damaged bone, J Mater Sci
29:978986, 1994.
247. Schaffler MB, Choi K, Milgrom C: Microcracks and aging
in human femoral compact bone, J Orthop Res 19:190,
1994.
248. Boyce TM, Fyhrie DP, Glotkowski MC, et al: Damage type and
strain mode associations in human compact bone bending
fatigue, J Orthop Res 16:322329, 1998.
249. Jepsen KJ, Davy DT, Krzypow DJ: The role of the lamellar
interface during torsional yielding of human cortical bone,
J Biomech 32:303310, 1999.
250. OBrien FJ, Taylor D, Lee TC: Microcrack accumulation at
different intervals during fatigue testing of compact bone,
J Biomech 36:973980, 2003.
251. Hazenberg JG, Taylor D, Clive Lee T: Mechanisms of short crack
growth at constant stress in bone, Biomaterials 27:21142122,
2006.
252. Mohsin S, OBrien FJ, Lee TC: Osteonal crack barriers in ovine
compact bone, J Anat 208:8189, 2006.
253. Forwood MR, Parker AW: Microdamage in response to repetitive
torsional loading in the rat tibia, Calcif Tissue Int 45:4753,
1989.
254. OBrien FJ, Taylor D, Clive Lee T: The effect of bone
microstructure on the initiation and growth of microcracks,
J Orthop Res 23:475480, 2005.
255. Guo XE, McMahon TA, Keaveny TM, et al: Finite element
modeling of damage accumulation in trabecular bone under
cyclic loading, J Biomech 27:145155, 1994.
256. Schaffner G, Guo XE, Silva MJ, et al: Modeling fatigue damage
accumulation in two-dimensional Voronoi honey-combs, Int
J Med Sci 42:645656, 2000.
257. Makiyama AM, Vajjala S, Gibson LJ: Analysis of crack growth in
a 3D Voronoi structure: a model for fatigue in low density
trabecular bone, J Biomech Eng 124:512520, 2002.
258. Moore TL, Gibson LJ: Fatigue of bovine trabecular bone,
J Biomech Eng 125:761768, 2003.
259. Moore TL, Gibson LJ: Fatigue microdamage in bovine trabecular
bone, J Biomech Eng 125:769776, 2003.
260. Moore TL, Gibson LJ: Microdamage accumulation in bovine
trabecular bone in uniaxial compression, J Biomech Eng
124:6371, 2002.
261. Igarashi K, Miyoshi K, Shinoda H, et al: Diurnal variation in
tooth movement in response to orthodontic force in rats, Am J
Orthod Dentofacial Orthop 114:814, 1998.
262. Miyoshi K, Igarashi K, Saeki S, et al: Tooth movement and
changes in periodontal tissue in response to orthodontic force in
rats vary depending on the time of day the force is applied, Eur J
Orthod 23:329338, 2001.
263. Yamada S, Saeki S, Takahashi I, et al: Diurnal variation in the
response of the mandible to orthopedic force, J Dent Res
81:711715, 2002.
264. Qu Z: Mechanical properties of trabecular bone in the human
mandible [masters thesis], Birmingham, AL, 1994, University of
Alabama.
265. Martens M, Van Audekercke R, Delport P, et al: The mechanical
characteristics of cancellous bone at the upper femoral region,
J Biomech 16:971983, 1983.
266. Morgan EF, Keaveny TM: Dependence of yield strain of human
trabecular bone on anatomic site, J Biomech 34:569577, 2001.
267. Hildebrand T, Laib A, Muller R, et al: Direct three-dimensional
morphometric analysis of human cancellous bone:
125
296. Rice JC, Cowin SC, Bowan JA: On the dependence of the
elasticity and strength of cancellous bone on apparent density,
J Biomech 21:155, 1988.
297. Nicholson PH, Cheng XG, Lowet G, et al: Structural and
material mechanical properties of human vertebral cancellous
bone, Med Eng Phys 19:729737, 1997.
298. Kopperdahl DL, Keaveny TM: Yield strain behavior of trabecular
bone, J Biomech 31:601608, 1998.
299. Keaveny TM, Wachtel EF, Ford CM, et al: Differences between the
tensile and compressive strengths of bovine tibial trabecular
bone depend on modulus, J Biomech 27:11371146, 1994.
300. Rohl L, Larsen E, Linde F, et al: Tensile and compressive
properties of cancellous bone, J Biomech 24:11431149, 1991.