Anchorage of orthopedic implants depends on the interfacial bonding between the implant and the host bone as well as on the mass and microstructure of peri-implant bone, with all these factors being continuously regulated by the biological process of bone (re)modeling. In osteoporotic bone, implant integration may be jeopardized not only by lower peri-implant bone quality but also by reduced intrinsic regeneration ability. The first aim of this review is to provide a critical overview of the influence of osteoporosis on bone regeneration post-implantation. Mechanical stimulation can trigger bone formation and inhibit bone resorption; thus, judicious administration of mechanical loading can be used as an effective non-pharmacological treatment to enhance implant anchorage. Our second aim is to report recent achievements on the application of external mechanical stimulation to improve the quantity of periimplant bone. The review focuses on peri-implant bone changes in osteoporotic conditions and following mechanical loading, prevalently using small animals and in vivo monitoring approaches. We intend to demonstrate the necessity to reveal new biological information on peri-implant bone mechanobiology to better target implant anchorage and fracture fixation in osteoporotic conditions. ß

Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.

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.royalsocietypublishing.org/journal/rsif J. R. Soc. Interface 16: 20180667