The impact of medication on osseointegration and implant anchorage in bone determined using removal torque-A review

Abstract

Permanently anchored metal implants are frequently used in dental, craniomaxillofacial, and orthopaedic rehabilitation. The success of such therapies is owed to the phenomenon of osseointegration-the direct connection between the living bone and the implant. The extent of biomechanical anchorage (i.e., physical interlocking between the implant and bone) can be assessed with removal torque (RTQ) measurement. Implant anchorage is strongly influenced by underlying bone quality, involving physicochemical and biological properties such as composition and structural organisation of extracellular matrix, extent of micro-damage, and bone turnover. In this review, we evaluated the impact of various pharmacological agents on osseointegration, from animal experiments conducting RTQ measurements. In addition to substances whose antiresorptive and/or anti-catabolic effects on bone are well-documented (e.g., alendronate, zoledronate, ibandronate, raloxifene, human parathyroid hormone, odanacatib, and the sclerostin monoclonal antibody), positive effects on RTQ have been reported for substances that do not primarily target bone (e.g., aminoguanidine, insulin, losartan, simvastatin, bone morphogenetic protein, alpha-tocopherol, and the combination of silk fibroin powder and platelet-rich fibrin). On the contrary, several substances (e.g., prednisolone, cyclosporin A, cisplatin, and enamel matrix derivative) tend to adversely impact RTQ. While morphometric parameters such as bone-implant contact appear to influence the biomechanical anchorage, increased or decreased RTQ is not always accompanied by corresponding fluctuations in bone-implant contact. This further confirms that factors such as bone quality underpin biomechanical anchorage of metal implants. Several fundamental questions on drug metabolism and bioavailability, drug dosage, animal-to-human translation, and the consequences of treatment interruption remain yet unanswered.

Keywords: Bisphosphonates; Bone; Drug delivery; Implant; In vivo; Osseointegration; Removal torque.

Graphical abstract

Figure 1

Removal torque (RTQ) and bone-implant contact (BIC). (A) Typical RTQ load-displacement curve. The peak/maximum torque value represents the point of failure (also referred to as the “break-point”) of the bone-implant interface. (B) BIC is one of several key factors contributing to the recorded RTQ.

Figure 2

Systemic administration of antiresorptive agents. Green bars: Rattus norvegicus (rat) models. Blue bars: Oryctolagus cuniculus (rabbit) models. Down arrow: implant placement when different to initiation of therapy. Circle: study endpoint(s). ALN ​= ​Alendronate. hPTH ​= ​Human parathyroid hormone. SOSTab ​= ​Sclerostin monoclonal antibody. IBN ​= ​Ibandronate. ZLN ​= ​Zoledronate. ODN ​= ​Odanacatib. RLX ​= ​Raloxifene. EST ​= ​17 β-estradiol.

Figure 3

Local administration of antiresorptive agents. Green bars: Rattus norvegicus (rat) models. Blue bars: Oryctolagus cuniculus (rabbit) models. Circle: study endpoint(s). IBN ​= ​Ibandronate. ZLN ​= ​Zoledronate. ALN ​= ​Alendronate. RLX ​= ​Raloxifene.

Figure 4

Studies in Rattus norvegicus (rat) models. Down arrow: implant placement when different to initiation of therapy. Circle: study endpoint(s). COL-CS = Collagen-Chondroitin sulphate. SMV-Chi = Simvastatin-Chitosan. ASU = Avocado-Soybean unsaponifiables.

Figure 5

Studies in Oryctolagus cuniculus (rabbit) and Canis lupus familiaris (dog) models. Down arrow: implant placement when different to initiation of therapy. Circle: study endpoint(s). SF-PRF = Silk fibroin powder and platelet-rich fibrin. hGH = Human growth hormone. rhFGF-4 = Recombinant human fibroblast growth factor-4. BMP = Bone morphogenetic protein. rhBMP-2 = Recombinant human bone morphogenetic protein-2.

Figure 6

Prevalence of the use of individual antiresorptives included in this review, based on 19 published studies. Four studies have tested at least two antiresorptive agents. The outer ring represents success rates of individual antiresorptives based on the proportion of studies reporting significantly increased RTQ values. One study has used a combination of ibandronate and pamidronate.