Effects of Systemic or Local Administration of Zoledronate on Implant Osseointegration: A Preclinical Meta-Analysis

Abstract

Objective This study aims to investigate the effect of systemically administrated zoledronate on bone-implant fixation in animal models. Methods We searched MEDLINE, Embase, and EBSCO for studies that explore the role of systemic or local zoledronate delivery in implant osseointegration in animal models. The Review Manager software was used to analyze selected studies by using the weighted mean difference random-effects model. Analytical data are mainly about bone ingrowth, such as bone-to-implant contact (BIC), bone volume/total volume (BV/TV), and bone area. Results Twenty studies were selected from 182 publications. The mean quality score was 18/20 for all of the 20 studies (κ = 0.9). Despite differences in protocols, these studies showed consistent improvement of implant osseointegration with zoledronate administration. In addition, the osteoporotic animal model, systemic or local administration, sufficient drug dosage, and sample follow-up time were correlated with improved outcomes. Conclusion Systematic administration of zoledronate could improve the osseointegration of orthopedic implant in animal models. Results of this meta-analysis should be interpreted cautiously because of the inherent differences between preclinical and clinical subjects. For the local administration, there is a similar trend as well, but the results need to be confirmed and complemented with further analyses.

Histomorphometric Evaluation of Peri-Implant Bone Response to Intravenous Administration of Zoledronate (Zometa®) in an Osteoporotic Rat Model

“…In this condition, BIC% represents just the amount of bone present during implant installation. This explanation is in agreement with other studies, which suggested that a follow-up time of 6 weeks is too short, and more than 8 weeks of observation are necessary to detect a possible effect of pharmacological drugs on the interfacial implant–bone response [ 29 , 47 ].…”

“…Cardemil et al revealed that a systemic single dose of ZOL in ovariectomized animals improved bone-to-implant contact [ 31 ]. Recently, He et al [ 29 ] reviewed the literature and described 10 preclinical studies that confirmed a possible effect of systemic ZOL administration on implant osseointegration. Consequently, the conclusion seems justified that intravenous ZOL can improve implant osseointegration in osteoporotic animals.…”

“…Renal failure has been noted in patients with cancer after repetitive high-dose ZOL infusions. Moreover, osteonecrosis of the jaw after tooth extraction has been recorded as a result of the systemic administration of ZOL [ 29 ]. However, the effect of the timing of drug administration, i.e., before and/or after placing dental implants, is not clear [ 14 ].…”

Biological Effect of Single or Combined Pharmacological Therapy Using Alendronate and Simvastatin on Implant Osseointegration: An In Vivo Study in Healthy and Osteoporotic Rat Models

“…Pre-clinical studies have already been performed to study the effect of such treatments on peri-implant bone regeneration in both healthy and osteoporotic animal models [9,18,19,[33][34][35]. Despite existing evidence that single treatment with BPs or simvastatin can enhance bone formation around dental implants in healthy and osteoporotic animal models, only limited work has been dedicated toward the effect of combined administration of anti-resorptive and anabolic agents [22][23][24][25]36,37]. In addition, there is a wide variation in the route of administration of such pharmacological agents, the timing in relation to osteoporosis induction and subsequent implant placement, as well as implantation time.…”

“…These inconsistent observations can be partly explained by differences in the experimental design, type of drugs, administration route, dose, and evaluation periods. He et al [23] performed a preclinical meta-analysis to the effect of zolendronate administration on implant osseointegration, quantitatively assessing BIC% and BA%. They concluded that zolendronate administration generally increases BA%, but that for short implantation times (< eight weeks) the effect is less compared to long implantation times (> eight weeks).…”