specially designed screwshaped implants of titanium ( grade 4 ) were manufactured with tight tolerances to induce controlled bone strains .
the designs of the implants were identical to the implants in the study by halldin et  al .
the test implants comprised of a condensation portion that had an increased diameter of 0.05  mm compared to the cutting portion .
all implants had the same surface as the commercially available osseospeed implants ( dentsply implants , mlndal , sweden ) . to confirm that both implant groups had the same surface topography the implant surfaces were characterized by use of optical light interferometry ( microxam ; ade phase shift technology , inc . , tucson , az , usa ) . in brief ,
each implant was measured on three thread peaks , three valleys , and three flanks ( scan area of 264    200  m , vertical measurement range of 100  m ) .
data evaluation was performed with the mountainmaps software ( digital surf , besanon , france ) .
waviness and form were filtered with a 50    50  m gaussian filter .
the surfaces were characterized with the surface roughness parameters s 
 a ( m ) , s 
 dr ( % ) , and s 
 ds ( 1/m ) ( definition of them can be found elsewhere ( stout 2000 ; thomas 1999 ) ) .
twentyfour mature female new zealand white rabbits ( weight 34  kg ) were used in this  study .
the study was approved by the french ministre de lenseignement suprieur et de la recherche and performed at the colenationalevtrinaired'alfort ( maisonsalfort , valdemarne , france , approval number , 0039101 ) . prior to surgery ,
250  g / kg of medetomidine ( domitor , zoetis , france ) , 20  mg / kg ketamine ( imalgne 1000 , merial , sanofi , france ) , and 1  mg / kg of diazepam ( valium , roche , france ) was injected intramuscularly to provide general anesthesia .
subsequently , analgesics 30  g / kg , buprenorphine ( buprcare , animalcare , york , uk ) was injected subcutaneously and 0.2  mg / kg meloxicam ( metacam ; boehringer ingelheim vetmedica , inc . , st .
thereafter , incision of the skin was made with a # 15 blade and the muscle layers and periosteum were elevated and separated from the bone .
osteotomy was prepared in the proximal tibia by drilling with a sequence of burs , starting from a round bur , 2.8  mm drill and finally with a 3.3  mm drill , corresponding to the core diameter of the implants .
each rabbit received two test implants in one leg ( proximal and distal placement ) and two control implants on the contralateral side .
the implants were inserted with a rotation speed set to 25  revolutions / min using the w&h implant unit ( elcomed , w&h sa310 , burmoos , austria ) .
after implant insertion , the muscle layers were sutured with a resorbable suture ( vicryl3.0 ) , and the skin with a 40 nylon suture ( ethicon , auneau , france ) .
postsurgically , a patch of fentanyl ( 25  g / h , duragesic ; janssen pharmaceutica , beerse , belgium ) was applied to each animal for 3  days .
an antibiotic ( enrofloxacin , 200  mg / l , baytril ; bayer animal health , leverkusen , germany ) was administrated in the water supply for 5  days .
the rabbits were kept in separate cages and were allowed to move and eat freely . at 7 , 28 , and 84  days after implant placement ,
eights rabbits at each time point were euthanized with an overdose injection of sodium pentobarbital ( euthasol , virbac , fort worth , tx , usa ) .
each tibia was dissected and excessive soft and hard tissue around the implant square head was carefully removed .
the bone samples were firmly secured with several individual bone pins and the removal torque of the implants was measured .
the removal torque , time , and angle of rotation were recorded with a calibrated torque measurement device ( dr2112 lorenz messtechnik gmbh , alfdorf , germany ) using a constant rotational speed of 0.03  rpm .
the torque device was calibrated in the range 502000  nmm with an accuracy of 1  nmm .
the data were sampled with 100  hz and thereafter analyzed in matlab software 2013b ( mathworksinc . ,
the data were initially smoothed with a running average over a set of 50 data points and the angle of rotation was set to 0  rad when the torque reached 10  nmm .
the fracture torque [ t 
 f ] was identified as the maximum torque . in the present study ,
the magnitude of pressure at the threads was simulated by a radial displacement of the thread profile of 0.025  mm as described in the 2daxis symmetric model of halldin et  al .
the 2d simulations were performed using bilinear mature bone material properties without hardening ( table  1 ) . the reduction in prestress over time , due to relaxation and remodeling , of mature bone was simulated by use of the constitutive model , illustrated by the rheological model ( fig .  1 ) , ( halldin et  al .
2014a ) with model parameter values according to table 6 . in brief : the parameters values obtained for simulation ( halldin et  al .
2014a ) of the crowninshield & pope ( 1974 ) experiment were used but recalibrated to represent rabbit bone .
1a ) were adjusted to 5008 , 2166 and 776  mpa , respectively , to represent young 's modulus of mature rabbit cortical bone ( 7950  mpa ) ( isaksson et  al .
hence , by changing the spring stiffness values the viscosity was consequently adjusted to fit the relaxation behavior ( halldin et  al .
thereafter , the initial strain was increased to achieve a pressure similar to the theoretical thread pressure , simulated in the 2d finite element method , of the test implant .
finally , the remodeling parameter was set to result in no pressure at 30  days which represents the expected theoretical time point when the initially induced bone strainshave vanished ( halldin et  al .
. the theoretical interfacial shear strength of the moderately rough surface was simulated using the finite element model described in halldin et  al .
a representative patch of the implant surface was selected and a finite element model was developed according to fig . 
the implant was moved until bone failure occurred which was assumed to represent the interfacial shear strength . in the current investigation
the interfacial shear strength of a bone condensation implant was simulated with adding an external pressure ( fig . 
the pressure was reduced by use of the constitutive model ( halldin et  al .
the theoretical interfacial shear strength was simulated both with mechanical properties of healing bone and mature bone ( halldin et  al .
mechanical properties of bone during healing derived from mineralization level during healing bone and the relationship between mineralization level and mechanical properties halldin et  al .
( 2014a , b ) ( a ) rheological model and the model parameters for the constitutive model developed by halldin et  al .
( b ) fea model to simulate the interfacial shear strength of a rough surface exposed to a pressure .
pairwise differences in removal torque measurements between test and control implants that were assumed to be normally distributed were analyzed with student 's ttest .
pairwise differences in measurements between test and control that were not assumed to be normally distributed were analyzed using sign test for median .
pairwise ratios ( test / control ) for different healing times were analyzed using mood median test to test the equality of medians from two populations .
specially designed screwshaped implants of titanium ( grade 4 ) were manufactured with tight tolerances to induce controlled bone strains .
the designs of the implants were identical to the implants in the study by halldin et  al .
the test implants comprised of a condensation portion that had an increased diameter of 0.05  mm compared to the cutting portion .
all implants had the same surface as the commercially available osseospeed implants ( dentsply implants , mlndal , sweden ) .
to confirm that both implant groups had the same surface topography the implant surfaces were characterized by use of optical light interferometry ( microxam ; ade phase shift technology , inc . ,
tucson , az , usa ) . in brief , six randomly selected implants ( three controls and three tests ) were selected .
each implant was measured on three thread peaks , three valleys , and three flanks ( scan area of 264    200  m , vertical measurement range of 100  m ) .
data evaluation was performed with the mountainmaps software ( digital surf , besanon , france ) .
waviness and form were filtered with a 50    50  m gaussian filter .
the surfaces were characterized with the surface roughness parameters s 
 a ( m ) , s 
 dr ( % ) , and s 
 ds ( 1/m ) ( definition of them can be found elsewhere ( stout 2000 ; thomas 1999 ) ) .
twentyfour mature female new zealand white rabbits ( weight 34  kg ) were used in this  study .
the study was approved by the french ministre de lenseignement suprieur et de la recherche and performed at the colenationalevtrinaired'alfort ( maisonsalfort , valdemarne , france , approval number , 0039101 ) . prior to surgery , 250  g / kg of medetomidine ( domitor , zoetis , france ) , 20  mg / kg ketamine ( imalgne 1000 , merial , sanofi , france ) , and 1  mg / kg of diazepam ( valium , roche , france )
subsequently , analgesics 30  g / kg , buprenorphine ( buprcare , animalcare , york , uk ) was injected subcutaneously and 0.2  mg / kg meloxicam ( metacam ; boehringer ingelheim vetmedica , inc . , st .
thereafter , incision of the skin was made with a # 15 blade and the muscle layers and periosteum were elevated and separated from the bone .
osteotomy was prepared in the proximal tibia by drilling with a sequence of burs , starting from a round bur , 2.8  mm drill and finally with a 3.3  mm drill , corresponding to the core diameter of the implants .
each rabbit received two test implants in one leg ( proximal and distal placement ) and two control implants on the contralateral side .
the implants were inserted with a rotation speed set to 25  revolutions / min using the w&h implant unit ( elcomed , w&h sa310 , burmoos , austria ) .
after implant insertion , the muscle layers were sutured with a resorbable suture ( vicryl3.0 ) , and the skin with a 40 nylon suture ( ethicon , auneau , france ) .
postsurgically , a patch of fentanyl ( 25  g / h , duragesic ; janssen pharmaceutica , beerse , belgium ) was applied to each animal for 3  days .
an antibiotic ( enrofloxacin , 200  mg / l , baytril ; bayer animal health , leverkusen , germany ) was administrated in the water supply for 5  days .
the rabbits were kept in separate cages and were allowed to move and eat freely . at 7 , 28 , and 84  days after implant placement ,
eights rabbits at each time point were euthanized with an overdose injection of sodium pentobarbital ( euthasol , virbac , fort worth , tx , usa ) .
each tibia was dissected and excessive soft and hard tissue around the implant square head was carefully removed .
the bone samples were firmly secured with several individual bone pins and the removal torque of the implants was measured .
the removal torque , time , and angle of rotation were recorded with a calibrated torque measurement device ( dr2112 lorenz messtechnik gmbh , alfdorf , germany ) using a constant rotational speed of 0.03  rpm .
the torque device was calibrated in the range 502000  nmm with an accuracy of 1  nmm .
the data were sampled with 100  hz and thereafter analyzed in matlab software 2013b ( mathworksinc . ,
the data were initially smoothed with a running average over a set of 50 data points and the angle of rotation was set to 0  rad when the torque reached 10  nmm .
in the present study , the test implant induced a pressure at the threads in the condensation region .
the magnitude of pressure at the threads was simulated by a radial displacement of the thread profile of 0.025  mm as described in the 2daxis symmetric model of halldin et  al .
the 2d simulations were performed using bilinear mature bone material properties without hardening ( table  1 ) . the reduction in prestress over time , due to relaxation and remodeling , of mature bone was simulated by use of the constitutive model , illustrated by the rheological model ( fig .  1 ) , ( halldin et  al .
2014a ) with model parameter values according to table 6 . in brief : the parameters values obtained for simulation ( halldin et  al .
2014a ) of the crowninshield & pope ( 1974 ) experiment were used but recalibrated to represent rabbit bone .
1a ) were adjusted to 5008 , 2166 and 776  mpa , respectively , to represent young 's modulus of mature rabbit cortical bone ( 7950  mpa ) ( isaksson et  al .
hence , by changing the spring stiffness values the viscosity was consequently adjusted to fit the relaxation behavior ( halldin et  al .
thereafter , the initial strain was increased to achieve a pressure similar to the theoretical thread pressure , simulated in the 2d finite element method , of the test implant .
finally , the remodeling parameter was set to result in no pressure at 30  days which represents the expected theoretical time point when the initially induced bone strainshave vanished ( halldin et  al .
the theoretical interfacial shear strength of the moderately rough surface was simulated using the finite element model described in halldin et  al .
( 2015 ) . in brief , a representative patch of the implant surface was selected and a finite element model was developed according to fig . 
the implant was moved until bone failure occurred which was assumed to represent the interfacial shear strength . in the current investigation
the interfacial shear strength of a bone condensation implant was simulated with adding an external pressure ( fig . 
the pressure was reduced by use of the constitutive model ( halldin et  al .
the theoretical interfacial shear strength was simulated both with mechanical properties of healing bone and mature bone ( halldin et  al .
mechanical properties of bone during healing derived from mineralization level during healing bone and the relationship between mineralization level and mechanical properties halldin et  al .
( 2014a , b ) ( a ) rheological model and the model parameters for the constitutive model developed by halldin et  al .
( b ) fea model to simulate the interfacial shear strength of a rough surface exposed to a pressure .
pairwise differences in removal torque measurements between test and control implants that were assumed to be normally distributed were analyzed with student 's ttest .
pairwise differences in measurements between test and control that were not assumed to be normally distributed were analyzed using sign test for median .
pairwise ratios ( test / control ) for different healing times were analyzed using mood median test to test the equality of medians from two populations .
there was no difference ( p  =  0.287 ) in s 
 a value of test implants ( mean 1.55  m ; std 0.21 ) compared to control implants ( mean 1.49  m ; std 0.19 ) .
there was no difference ( p  =  0.441 ) in s 
 dr value of test implants ( mean 109% ; std44 ) compared to control ( mean 103% ; std 49 ) and no difference ( p  =  0.337 ) in s 
 ds value of test implants ( mean 0.061/m ; std 0.005 ) compared to control implants ( mean 0.061/m 0.007 ) .
the results of the removal torque measurement ( nmm ) , for the three different implantation times ( 7 , 28 , and 84  days ) are presented in a boxplot ( fig . 
one sample ( tibia proximal 28  days of healing ) was unfortunately lost during carefully removing the excessive soft and hard tissue .
the ratios between test and control , placed distally , of the present study ( at 7 , 28 , and 84  days ) .
( b ) removal torque ratios of the present study and the study by halldin et  al .
mean and median of removal torque values and the statistical analysis between the pairwise differences of test and control and the corresponding ratios subscription is commonly used to differentiate between different statistical methods . by use of the 2d axisymmetric model a theoretical average normal pressure on the thread profile of 39.5 
parameter values the relaxation behavior of mature rabbit bone is captured quite well ( fig . 
3a ) . using the constitutive model , with an initial strain to obtain an initial pressure of 39.5  mpa and a tuned remodeling parameter value that eliminated the pressure after 30  days ,
the decrease in pressure on the implant surface during healing was simulated ( fig . 
the parameter values used in the constitutive model to simulate the decrease in pressure over time are presented in table  3 .
the theoretical interfacial shear strength , with mechanical properties of healing bone together with no pressure over time ( represents control implants , simulation c ) , is presented in fig . 
the theoretical interfacial shear strengths , with mechanical properties of healing bone together with decreased pressure over time ( represents test implants , simulation b ) and mature bone mechanical properties together with decreased pressure over time ( represents test implants , simulation a ) , are presented in fig  4a .
the ratios between test and control of the in  vivo study and the corresponding theoretical ratios are presented in fig . 
( a ) simulated behavior of mature bone with calibrated model parameters to fit the relaxation behavior described in halldin et  al .
( b ) simulated behavior of increased initial strain to generate a pressure of 39.5  mpa ( which represents the theoretical thread pressure of the test implant ) and the tuned remodeling parameter value that eliminates the pressure after 30  days .
( 2014a , b ) to simulate the change of pressure over time ( a ) simulation of the interfacial shear strength for the test implants with constant mechanical properties of mature bone during healing time and mechanical properties of bone during healing time .
simulation of the interfacial shear strength for the control implants was performed with mechanical properties of bone during healing time .
( b ) the ratios of the present in  vivo study and of the simulations .
there was no difference ( p  =  0.287 ) in s 
 a value of test implants ( mean 1.55  m ; std 0.21 ) compared to control implants ( mean 1.49  m ; std 0.19 ) .
there was no difference ( p  =  0.441 ) in s 
 dr value of test implants ( mean 109% ; std44 ) compared to control ( mean 103% ; std 49 ) and no difference ( p  =  0.337 ) in s 
 ds value of test implants ( mean 0.061/m ; std 0.005 ) compared to control implants ( mean 0.061/m 0.007 ) .
the results of the removal torque measurement ( nmm ) , for the three different implantation times ( 7 , 28 , and 84  days ) are presented in a boxplot ( fig . 
one sample ( tibia proximal 28  days of healing ) was unfortunately lost during carefully removing the excessive soft and hard tissue .
the ratios between test and control , placed distally , of the present study ( at 7 , 28 , and 84  days ) .
( b ) removal torque ratios of the present study and the study by halldin et  al .
mean and median of removal torque values and the statistical analysis between the pairwise differences of test and control and the corresponding ratios subscription is commonly used to differentiate between different statistical methods .
by use of the 2d axisymmetric model a theoretical average normal pressure on the thread profile of 39.5  mpa was obtained . by applying appropriate
parameter values the relaxation behavior of mature rabbit bone is captured quite well ( fig . 
3a ) . using the constitutive model , with an initial strain to obtain an initial pressure of 39.5  mpa and a tuned remodeling parameter value that eliminated the pressure after 30  days ,
the decrease in pressure on the implant surface during healing was simulated ( fig . 
the parameter values used in the constitutive model to simulate the decrease in pressure over time are presented in table  3 .
the theoretical interfacial shear strength , with mechanical properties of healing bone together with no pressure over time ( represents control implants , simulation c ) , is presented in fig . 
the theoretical interfacial shear strengths , with mechanical properties of healing bone together with decreased pressure over time ( represents test implants , simulation b ) and mature bone mechanical properties together with decreased pressure over time ( represents test implants , simulation a ) , are presented in fig  4a .
the ratios between test and control of the in  vivo study and the corresponding theoretical ratios are presented in fig
( a ) simulated behavior of mature bone with calibrated model parameters to fit the relaxation behavior described in halldin et  al .
( b ) simulated behavior of increased initial strain to generate a pressure of 39.5  mpa ( which represents the theoretical thread pressure of the test implant ) and the tuned remodeling parameter value that eliminates the pressure after 30  days .
( 2014a , b ) to simulate the change of pressure over time ( a ) simulation of the interfacial shear strength for the test implants with constant mechanical properties of mature bone during healing time and mechanical properties of bone during healing time .
simulation of the interfacial shear strength for the control implants was performed with mechanical properties of bone during healing time .
( b ) the ratios of the present in  vivo study and of the simulations .
an in  vivo study was conducted to investigate how the implant stability was affected by a moderately rough implant that induced moderate bone strains of 0.015 at the time of implant installation .
the implants were allowed to heal in the rabbit tibiae for 7 , 28 , and 84  days .
it was hypothesized that bone condensation implants will enhance the mechanical stability initially and that the moderately rough surface will further contribute to the secondary stability by enhanced osseointegration .
the bone condensation implants ( i.e. test implants ) presented an increased removal torque at 7  days of healing compared to the noncondensation implants ( i.e. control implant ) , whereas at 28 and 84  days of healing no difference in removal torque between bone condensation implants and nonbone condensation implants ( fig . 
2b ) was observed . in the previous in  vivo studies by halldin et  al .
( 2011 , 2014b ) turned implants with the same moderate bone condensation level were used .
the turned implants had a healing time of 3 , 13 , and 24  days and the removal torque values were measured with a removal torque device different to that of the one utilized in the current study . in the previous studies ,
the test ( moderate bone condensation ) implants presented significantly increased removal torque compared to control implants .
the removal torque values of the two different removal torque devices can not directly be compared . however ,
if the removal torque ratios ( test / control ) are calculated respectively for study , they may be compared .
interestingly , there was a similar trend of decreased ratio over time regardless of the surface micro roughness ( turned or moderately roughened ) ( fig . 
the ratios were considerably higher than 1 ( or 100% ) during the early healing times , which , in turn , means higher removal torque values for the tests implants compared to the control implants .
this suggests that the moderate bone condensation implants ( test ) enhances implant stability during the initial critical phases of healing .
when the osseointegration consolidates ( at 28 and 84  days ) the ratios between test and control tend to reach the value 1 ( fig . 
it is interesting to observe that the ratio was higher of turned implants at 3  days compared to the ratio of the moderately rough implants at 7  days .
this might be related to the fact that the controlled condensation is particularly effective for the retention the first few days of healing ( 3  days vs. 7  days ) regardless of surface structure .
the absolute removal torque values of moderately rough surface were increased during healing for both test and control implants , which attests to the favorable bone formation around all implants with a moderately rough surface structure .
an interesting reflection from the previous studies of turned implants is that the removal torque decreased over time for the test implants .
this might reflect that the decreased pressure , due to relaxation and remodeling , had a more pronounced effect on removal torque than the interlocking of a turned surface structure . in the present study
therefore , it might be speculated that the increased interlocking capacity of the moderately rough surface had a more pronounced effect on the removal torque than the reduction in pressure , due to relaxation and remodeling , over time .
it should be noted that the removal torque values , especially for the longer healing times , might be affected by bone growth into the cutting feature affecting the results .
in addition , the potential grinding effect a structured surface has on the bone might influence the result .
the present study used a rabbit model which comprises of a dense cortical bone layer of 34  mm and it does not incorporate the implant stability of a potential trabecular bone .
the ratios of the present in  vivo study were compared to the theoretical interfacial shear strength ratios simulated by the use of the 3d finite element model .
interestingly , it was found that the simulated ratios are in line with the in  vivo ratios . in the 3d simulation
the strength of the interfacial bone was increased over time , reflecting healing bone and increased mineralization , that increased the interlocking capacity ( halldin et  al .
the interfacial shear strength was simulated both with constant mechanical properties of mature bone and mechanical properties representing healing bone .
therefore the simulated shear strength of mature bone was assumed to provide the highest interlocking capacity that can be achieved during healing , thus reflecting only how a decreased pressure affects the interfacial shear strength . in the 3d finite element model the decreased pressure on the surface over time was obtained by use of the constitutive model simulating the relaxation and remodeling behavior of cortical bone ( halldin et  al .
the characteristics of the actual mechanical properties of the in  vivo bone during healing are unknown .
therefore , the simulation was based on the estimated mechanical properties of the interfacial bone obtained in the study by halldin et  al .
( 2015 ) . in the present study , the parameters of the constitutive model described in halldin et  al .
( 2014a ) were recalibrated to fit the viscoelastic relaxation and remodeling behavior of rabbit mature bone .
it is assumed that when analyzing the ratios these assumptions might have a limited impact . despite these assumptions , regarding the healing bone mechanical properties and the relaxation and remodeling behavior of rabbit bone ( fig . 
3a , b ) , the simulated ratios had the same trend as the ratios obtained the in  vivo experiment ( fig . 
this implies that finite element analysis , with appropriate material models , may be used to evaluate differences in structural interlocking capacity between two surfaces .
in addition , it seems to be a more rapid decrease in ratios during the initial healing which is in line with the findings of perren et  al .
the results of the study suggest that modification of the implant macro geometry in relationship to the osteotomy preparation , to induce moderate bone strain levels of 0.015 during implant insertion does not result in reduction in stability of moderately rough implants .
it is interesting to note that the ratios using finite element method were in line with the in  vivo ratios .
this is an indication that when the condensation level is controlled in  vivo , the biological outcomes may be predicted , which could optimize implant design .
 abstractobjectiveswhen implants are inserted , the initial implant stability is dependent on the mechanical stability . to increase the initial stability , 
 it was hypothesized that bone condensation implants will enhance the mechanical stability initially and that the moderately rough surface will further contribute to the secondary stability by enhanced osseointegration . 
 it was further hypothesized that as the healing progresses the difference in removal torque will diminish . 
 in addition , a 3d model was developed to simulate the interfacial shear strength . 
 this was converted to a theoretical removal torque that was compared to the removal torque obtained in  vivo.material and methodscondensation implants , inducing bone strains of 0.015 , were installed into the left tibia of 24 rabbits . 
 noncondensation implants were installed into the right tibia . 
 all implants had a moderately rough surface . 
 the implants had an implantation time of 7 , 28 , or 84  days before the removal torque was measured . 
 the interfacial shear strength at different healing time was estimated by the means of finite element method.resultsat 7  days of healing , the condensation implant had an increased removal torque compared to the nonbonecondensation implant . at 28 and 84  days of healing 
 , there was no difference in removal torque . 
 the simulated interfacial shear strength ratios of bone condensation implants at different implantation time were in line with the in  vivo data.conclusionsmoderately rough implants that initially induce bone strain during installation have increased stability during the early healing period . in addition , the finite element method may be used to evaluate differences in interlocking capacity . 
Material and methods
Implant design
Interferometry
Animal study
Removal torque measurement
Theoretical interfacial shear strength
Statistical analysis
Results
Interferometry
Animal study
Theoretical interfacial shear strength
Discussion
Conflicts of interests