Mechanical regulation of bone formation and resorption around implants in a mouse model of osteopenic bone

Although mechanical stimulation is considered a promising approach to accelerate implant integration, our understanding of load-driven bone formation and resorption around implants is still limited. This lack of knowledge may delay the development of effective loading protocols to prevent implant loosening, especially in osteoporosis. In healthy bone, formation and resorption are mechanoregulated processes. In the intricate context of peri-implant bone regeneration, it is not clear whether bone (re)modelling can still be load-driven. Here, we investigated the mechanical control of peri-implant bone (re)modelling with a well-controlled mechanobiological experiment. We applied cyclic mechanical loading after implant insertion in tail vertebrae of oestrogen depleted mice and we monitored peri-implant bone response by in vivo micro-CT. Experimental data were combined with micro-finite element simulations to estimate local tissue strains in (re)modelling locations. We demonstrated that a substantial increase in bone mass around the implant could be obtained by loading the entire bone. This augmentation could be attributed to a large reduction in bone resorption rather than to an increase in bone formation. We also showed that following implantation, mechanical regulation of bone (re)modelling was transiently lost. Our findings should help to clarify the role of mechanical stimulation on the maintenance of peri-implant bone mass.

[1]  K. Ip,et al.  The Effect of Material Heterogeneity, Element Type, and Down-Sampling on Trabecular Stiffness in Micro Finite Element Models , 2018, Annals of Biomedical Engineering.

[2]  Joseph M. Wallace,et al.  Incorporating tissue anisotropy and heterogeneity in finite element models of trabecular bone altered predicted local stress distributions , 2018, Biomechanics and modeling in mechanobiology.

[3]  C. Hellmich,et al.  A mathematical multiscale model of bone remodeling, accounting for pore space-specific mechanosensation. , 2018, Bone.

[4]  R. Buck,et al.  In Vivo Monitoring , 2018 .

[5]  S. Fritton,et al.  Microstructural changes associated with osteoporosis negatively affect loading-induced fluid flow around osteocytes in cortical bone. , 2018, Journal of biomechanics.

[6]  Marco Viceconti,et al.  Longitudinal effects of Parathyroid Hormone treatment on morphological, densitometric and mechanical properties of mouse tibia. , 2017, Journal of the mechanical behavior of biomedical materials.

[7]  Mia M. Thi,et al.  Osteocyte calcium signals encode strain magnitude and loading frequency in vivo , 2017, Proceedings of the National Academy of Sciences.

[8]  Ralph Müller,et al.  Bone remodeling and mechanobiology around implants: Insights from small animal imaging , 2017, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[9]  Davide Ruffoni,et al.  Re-entrant inclusions in cellular solids: From defects to reinforcements , 2017 .

[10]  R. Müller,et al.  Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography , 2017, PloS one.

[11]  Evan P. Roush,et al.  Time course of peri‐implant bone regeneration around loaded and unloaded implants in a rat model , 2017, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[12]  Georg N Duda,et al.  The Periosteal Bone Surface is Less Mechano-Responsive than the Endocortical , 2016, Scientific Reports.

[13]  C. Hernandez,et al.  Spatial relationships between bone formation and mechanical stress within cancellous bone. , 2016, Journal of biomechanics.

[14]  R. Müller,et al.  In vivo monitoring of bone architecture and remodeling after implant insertion: The different responses of cortical and trabecular bone. , 2015, Bone.

[15]  Georg N Duda,et al.  Aging Leads to a Dysregulation in Mechanically Driven Bone Formation and Resorption , 2015, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  Ralph Müller,et al.  Does mechanical stimulation really protect the architecture of trabecular bone? A simulation study , 2014, Biomechanics and Modeling in Mechanobiology.

[17]  C. Hellmich,et al.  Poromicromechanics reveals that physiological bone strains induce osteocyte-stimulating lacunar pressure , 2015, Biomechanics and modeling in mechanobiology.

[18]  Glen L Niebur,et al.  Development of an in vivo rabbit ulnar loading model. , 2015, Bone.

[19]  Georg N Duda,et al.  Monitoring in vivo (re)modeling: a computational approach using 4D microCT data to quantify bone surface movements. , 2015, Bone.

[20]  Ralph Müller,et al.  Bone adaptation to cyclic loading in murine caudal vertebrae is maintained with age and directly correlated to the local micromechanical environment. , 2015, Journal of biomechanics.

[21]  Françoise Peyrin,et al.  Synchrotron X-ray phase nano-tomography-based analysis of the lacunar–canalicular network morphology and its relation to the strains experienced by osteocytes in situ as predicted by case-specific finite element analysis , 2014, Biomechanics and Modeling in Mechanobiology.

[22]  Stephen J Ferguson,et al.  Computational analysis of primary implant stability in trabecular bone. , 2015, Journal of biomechanics.

[23]  Q. Yuan,et al.  Effect of estrogen deficiency on the fixation of titanium implants in chronic kidney disease mice , 2015, Osteoporosis International.

[24]  D. Pioletti,et al.  Does locally delivered Zoledronate influence peri-implant bone formation? - Spatio-temporal monitoring of bone remodeling in vivo. , 2014, Biomaterials.

[25]  B. van Rietbergen,et al.  Bone remodelling in humans is load-driven but not lazy , 2014, Nature Communications.

[26]  Georg N Duda,et al.  Mineralizing surface is the main target of mechanical stimulation independent of age: 3D dynamic in vivo morphometry. , 2014, Bone.

[27]  Davide Ruffoni,et al.  The role of the renal ammonia transporter Rhcg in metabolic responses to dietary protein. , 2014, Journal of the American Society of Nephrology : JASN.

[28]  L. Claes,et al.  Distinct frequency dependent effects of whole‐body vibration on non‐fractured bone and fracture healing in mice , 2014, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[29]  Ralph Müller,et al.  The Clinical Biomechanics Award 2012 - presented by the European Society of Biomechanics: large scale simulations of trabecular bone adaptation to loading and treatment. , 2014, Clinical biomechanics.

[30]  Ralph Müller,et al.  Image interpolation allows accurate quantitative bone morphometry in registered micro-computed tomography scans , 2014, Computer methods in biomechanics and biomedical engineering.

[31]  C. Schem,et al.  Three-dimensional Image Registration Improves the Long-term Precision of In Vivo Micro-Computed Tomographic Measurements in Anabolic and Catabolic Mouse Models , 2014, Calcified Tissue International.

[32]  L. Deng,et al.  Repair of Microdamage in Osteonal Cortical Bone Adjacent to Bone Screw , 2014, PloS one.

[33]  C. Hellmich,et al.  Intravoxel bone micromechanics for microCT-based finite element simulations. , 2013, Journal of biomechanics.

[34]  S. Boyd,et al.  In vivo monitoring of bone–implant bond strength by microCT and finite element modelling , 2013, Computer methods in biomechanics and biomedical engineering.

[35]  Ralph Müller,et al.  Mineralization kinetics in murine trabecular bone quantified by time-lapsed in vivo micro-computed tomography. , 2013, Bone.

[36]  Ralph Müller,et al.  Trabecular bone adapts to long-term cyclic loading by increasing stiffness and normalization of dynamic morphometric rates. , 2013, Bone.

[37]  D. Ruffoni,et al.  High-throughput quantification of the mechanical competence of murine femora--a highly automated approach for large-scale genetic studies. , 2013, Bone.

[38]  D. R. Sumner,et al.  Implant placement increases bone remodeling transiently in a rat model , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[39]  Ralph Müller,et al.  Local Mechanical Stimuli Regulate Bone Formation and Resorption in Mice at the Tissue Level , 2013, PloS one.

[40]  H. Kido,et al.  Peri-implant bone density in senile osteoporosis-changes from implant placement to osseointegration. , 2013, Clinical implant dentistry and related research.

[41]  Stefaan W Verbruggen,et al.  Strain amplification in bone mechanobiology: a computational investigation of the in vivo mechanics of osteocytes , 2012, Journal of The Royal Society Interface.

[42]  Ignace Naert,et al.  In vivo assessment of the effect of controlled high- and low-frequency mechanical loading on peri-implant bone healing , 2012, Journal of The Royal Society Interface.

[43]  O. Kennedy,et al.  Osteocyte Signaling in Bone , 2012, Current Osteoporosis Reports.

[44]  Ralph Müller,et al.  The different contributions of cortical and trabecular bone to implant anchorage in a human vertebra. , 2012, Bone.

[45]  R. Müller,et al.  Bone morphology allows estimation of loading history in a murine model of bone adaptation , 2012, Biomechanics and modeling in mechanobiology.

[46]  R. Müller,et al.  Mechanisms of reduced implant stability in osteoporotic bone , 2012, Biomechanics and modeling in mechanobiology.

[47]  R. Müller,et al.  Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis , 2012, Calcified Tissue International.

[48]  Cyril Flaig,et al.  A scalable memory efficient multigrid solver for micro-finite element analyses based on CT images , 2011, Parallel Comput..

[49]  Ralph Müller,et al.  Mouse tail vertebrae adapt to cyclic mechanical loading by increasing bone formation rate and decreasing bone resorption rate as shown by time-lapsed in vivo imaging of dynamic bone morphometry. , 2011, Bone.

[50]  J. Dunlop,et al.  Trabecular bone remodelling simulated by a stochastic exchange of discrete bone packets from the surface. , 2011, Journal of the mechanical behavior of biomedical materials.

[51]  Ralph Müller,et al.  In vivo micro-computed tomography allows direct three-dimensional quantification of both bone formation and bone resorption parameters using time-lapsed imaging. , 2011, Bone.

[52]  I. Naert,et al.  The effect of whole-body vibration on peri-implant bone healing in rats. , 2011, Clinical oral implants research.

[53]  T. van Eijden,et al.  Mineral heterogeneity affects predictions of intratrabecular stress and strain. , 2011, Journal of biomechanics.

[54]  Ralph Müller,et al.  Guidelines for assessment of bone microstructure in rodents using micro–computed tomography , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[55]  Richard Weinkamer,et al.  Effect of minimal defects in periodic cellular solids , 2010 .

[56]  R. Müller,et al.  Mechanical loading of mouse caudal vertebrae increases trabecular and cortical bone mass-dependence on dose and genotype , 2010, Biomechanics and modeling in mechanobiology.

[57]  Matthew J Silva,et al.  Skeletal effects of whole‐body vibration in adult and aged mice , 2010, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[58]  J. W. C. Dunlop,et al.  New Suggestions for the Mechanical Control of Bone Remodeling , 2009, Calcified Tissue International.

[59]  C. Hellmich,et al.  Multiporoelasticity of Hierarchically Structured Materials: Micromechanical Foundations and Application to Bone , 2009 .

[60]  P. Prendergast,et al.  Loss of trabeculae by mechano-biological means may explain rapid bone loss in osteoporosis , 2008, Journal of The Royal Society Interface.

[61]  Ralph Müller,et al.  A novel in vivo mouse model for mechanically stimulated bone adaptation – a combined experimental and computational validation study , 2008, Computer methods in biomechanics and biomedical engineering.

[62]  C. Hellmich,et al.  Micromechanics-Based Conversion of CT Data into Anisotropic Elasticity Tensors, Applied to FE Simulations of a Mandible , 2008, Annals of Biomedical Engineering.

[63]  D. Pioletti,et al.  Microstimulation at the bone-implant interface upregulates osteoclast activation pathways. , 2008, Bone.

[64]  Ralph Müller,et al.  Automated compartmental analysis for high-throughput skeletal phenotyping in femora of genetic mouse models. , 2007, Bone.

[65]  Ralph Müller,et al.  Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography. , 2006, Bone.

[66]  Felix Eckstein,et al.  Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. , 2005, Bone.

[67]  T. Adachi,et al.  Directional dependence of osteoblastic calcium response to mechanical stimuli , 2003, Biomechanics and modeling in mechanobiology.

[68]  Niklaus P Lang,et al.  De novo alveolar bone formation adjacent to endosseous implants. , 2003, Clinical oral implants research.

[69]  Taiji Adachi,et al.  Functional adaptation of cancellous bone in human proximal femur predicted by trabecular surface remodeling simulation toward uniform stress state. , 2002, Journal of biomechanics.

[70]  F. Eckstein,et al.  Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. , 2002, Bone.

[71]  X. Guo,et al.  Quantification of a rat tail vertebra model for trabecular bone adaptation studies. , 2002, Journal of biomechanics.

[72]  R. Giardino,et al.  Osteointegration of hydroxyapatite-coated and uncoated titanium screws in long-term ovariectomized sheep. , 2002, Biomaterials.

[73]  H Weinans,et al.  Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution. , 2001, Journal of biomechanics.

[74]  H J Donahue,et al.  Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow. , 2000, Journal of biomechanical engineering.

[75]  Rik Huiskes,et al.  Effects of mechanical forces on maintenance and adaptation of form in trabecular bone , 2000, Nature.

[76]  D. Puleo,et al.  Understanding and controlling the bone-implant interface. , 1999, Biomaterials.

[77]  G. Niebur,et al.  Convergence behavior of high-resolution finite element models of trabecular bone. , 1999, Journal of biomechanical engineering.

[78]  R E Guldberg,et al.  The accuracy of digital image-based finite element models. , 1998, Journal of biomechanical engineering.

[79]  M. Nagumo,et al.  Osseointegration of dental implants in rabbit bone with low mineral density. , 1997, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[80]  C. Bünger,et al.  Tissue ingrowth into titanium and hydroxyapatite‐coated implants during stable and unstable mechanical conditions , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[81]  D. Ruffoni,et al.  3.10 Finite Element Analysis in Bone Research: A Computational Method Relating Structure to Mechanical Function☆ , 2017 .

[82]  Philipp Schneider,et al.  Inverse finite element modeling for characterization of local elastic properties in image-guided failure assessment of human trabecular bone. , 2015, Journal of biomechanical engineering.

[83]  Maria A. Fiatarone Singh Exercise and Bone Health , 2015 .

[84]  Stefaan W Verbruggen,et al.  Fluid flow in the osteocyte mechanical environment: a fluid–structure interaction approach , 2013, Biomechanics and Modeling in Mechanobiology.

[85]  R. Miron,et al.  Effect of decreased implant healing time on bone (re)modeling adjacent to plateaued implants under functional loading in a dog model , 2013, Clinical Oral Investigations.

[86]  Ralph Müller,et al.  Strain-adaptive in silico modeling of bone adaptation--a computer simulation validated by in vivo micro-computed tomography data. , 2013, Bone.

[87]  D. Ruffoni,et al.  Finite Element Analysis in Bone Research: A Computational Method Relating Structure to Mechanical Function , 2011 .

[88]  C. Cooper,et al.  Osteoporosis: trends in epidemiology, pathogenesis and treatment , 2006 .

[89]  Katarina T. Borer,et al.  Physical Activity in the Prevention and Amelioration of Osteoporosis in Women , 2005, Sports medicine.