Resumen de Early Healing of Hydroxyapatite-Coated Implants in Grafted Bone of Zoledronic Acid�Treated Osteoporotic Rabbits
Background: Resorption of grafted bone and delayed osseointegration of implants are main problems associated with alveolar bone augmentation in dental implantology, especially for patients with osteoporosis. The aim of this study is to investigate the early healing response of implants to systemic treatment of zoledronic acid (ZA) in autogenous grafted iliac bone of osteoporotic rabbits.
Methods: Ovariectomy (OVX) or sham operation was performed in 46 rabbits, and osteoporotic changes were verified in animals receiving OVX 3 months later. The remaining animals were divided into three groups (n = 12): sham, OVX, and OVX with ZA treatment (ZA group). Autogenous iliac bone grafting was performed in bilateral tibiae, and hydroxyapatite-coated titanium implants were simultaneously placed into the grafted bone. The animals were sacrificed 2 and 8 weeks later for examination.
Results: At both time points, systemic treatment of ZA efficiently promoted bone healing of implants in grafted bone, and all histologic and microcomputed tomography bone indices, including mineralized bone volume, implant�bone contact ratio, connectivity density, trabecular thickness, and trabecular number, were significantly increased in the ZA group compared with the OVX-only group (P <0.01); implant�bone contact rates in the ZA group were even restored to levels similar to those of sham-operated animals (P >0.05). Furthermore, biomechanical testing demonstrated that removal torque of implants was significantly increased in the ZA group compared with the OVX group (P <0.01).
Conclusion: Systemic treatment with ZA could efficiently promote early bone healing of implants in autogenous grafted bone of osteoporotic rabbits by increasing early osseointegration and fixation of implants.
Endosseous dental implants have become a promising method for rehabilitation of lost teeth in recent years.1,2 Despite the high success rate,1,2 the final outcome of dental implants is influenced by many local and systemic conditions.
Alveolar bone deficiency is a common local problem faced in implant dentistry, and many techniques, including allogeneic bone grafts, exogenous bone grafts, bone graft substitutes, and autogenous bone grafts, have been applied for augmentation of alveolar bone.3-5 Among them, autogenous bone grafting, by virtue of its being able to provide both osteogenic cells and proteins, has been considered the gold standard.4,5 Calvarial bone, mandible, and iliac crest are common donor sites.3,5,6 However, bone grafting may be affected by systemic skeletal disorders such as osteoporosis, which may increase the rate of complications such as resorption of bone graft, non-integration of bone graft, delayed healing time, and even implant failure in augmented alveolar bone.7 Osteoporosis is a common skeletal disease faced mainly by elderly people, which is also the primary population receiving dental implants.8 This skeletal disorder mainly affects long bones and vertebrae, as well as jaw bone.8 Although the devastating effect of osteoporosis on native bone has been well documented,9 its effects on grafted bones and osseointegration of dental implants in grafted bones have not been clearly elucidated. Several primary animal studies have demonstrated the negative effects of osteoporosis on healing of a variety of bone grafting materials in osteoporotic animals. These materials include autolysed antigen-extracted allogeneic bone grafts,10 synthetic particulate bone grafts,11 and bone grafts with a mixture of tooth ash and plaster of Paris.12 However, the influence of osteoporosis on healing of autogenous bone grafts and osseointegration of dental implants in them remains less understood.
Bisphosphonates, a group of pyrophosphate analogs, are effective drugs used to treat many skeletal diseases relating to excessive bone resorption, including osteoporosis, Paget disease, hypercalcemia, and many original or metastatic malignant tumors of bone.13 Although bisphosphonates are associated with osteonecrosis of the jaw, their applications for use have been increased, and more patients are being prescribed these drugs.14 Some studies also attempted to use these drugs to promote bone healing and osseointegration of implants in osteoporotic animals.15-19 Those studies showed that local delivery of zoledronic acid (ZA), pamidronate, and ibandronate using hydroxyapatite (HA)-coated implants,15,16 as well as systemic administration of alendronate, ibandronate, and ZA, could lead to more-rapid bone healing and improved osseointegration of implants in osteoporotic native bones.17-19 A previous study by the present authors further demonstrated that ZA treatment could promote implant osseointegration and fixation in grafted autogenous bone in osteoporotic rabbits.20 In that study, however, ZA�s effect was explored only at a later stage, 3 months; the response of implants to ZA at earlier stages, such as 2 or 8 weeks, was not demonstrated. The positive effect of ZA at such earlier stages may benefit early osseointegration and fixation of implants and facilitate early implant loading. Therefore, the purpose of this study is to investigate the early bone healing response of implants to systemic treatment of ZA in grafted autogenous iliac bone in osteoporotic rabbits.
