# Effect of Osteoporosis on Well-Integrated Bone Implants
## 1 Introduction  
Dental implants are a successful treatment approach for dertulous patients [1, 2]. The long-term success of dental implants is directly related to their ability for early osseointegration [3]. Ossointegration is a coordinated dynamic process involving cellular and molecular events that comprise a cascade of cellular and extracellular signaling pathways in a chronological sequence of different phases of bone healing, including inflammation, angiogenesis, osteogenesis and remodeling [4, 5]. Implant osseointegration is strongly influenced by local and systemic factors, which are related either to the implant itself or to the patients' systemic status. Examples of these factors include bone quality and quantity, implant design, surface characteristics and the medical condition of the patient. For example, altered bone metabolism can negatively affect dental implant survival and function [6, 7, 8]. Indeed, the role of normal bone metabolism has been considered essential to maintaining a healthy bone structure and function around implants. The homeostasis of bone metabolism can be disrupted by an imbalance between bone resorption and formation due to bone diseases such as osteoporosis.  
Osteoporosis is a systemic skeletal disease characterized by an imbalance between bone formation and bone breakdown, resulting in a dramatic change in the bone structure [9]. The associated clinical adverse effects are mainly reported to occur in the longbones, vertebrae and the jaw bones [10]. Osteoporosis is highly prevalent among postmenopausal women as a result of estrogen deficiency [11]. Additionally, osteoporosis is seen commonly among individuals of older age, who also comprise the predominant group of patients requiring dental implant rehabilitation to enhance the retention of a full denture. Several studies using experimental animal models have demonstrated that an induced osteopororotic condition, before or during implant installation, can negatively affect the osseointegration process and significantly reduce bone-to-implant contact [12; 13; 14]. Thus, it is indispensable to fully elucidate the underlying biological mechanisms of altered bone metabolism on osseointegration, from both scientific and clinical perspectives.  
The success of implant treatment is, firstly, associated with their early osseointegration and, secondly, their long-term performance on the maintenance of this condition. Although there are several studies involving implant osseointegration in a well-established osteoporootic condition, information about the impact of altered bone metabolism on peri-implant bone tissue after the establishment of osseointegration is scarce. While it is apparent that dental implants placed in osteopororotic patients have a risk of failure of osseointegration, it can be hypothesized that such an alteration of bone metabolism developed after dental implant placement can also negatively affect osseointegration [15]. However, there is no scientific literature reporting on the effect of the distribution of bone metabolism on peri-implant bone characteristics of already-well-integrated bone implants.  
The ovariectomized (OVX) rat is one of the most reproducible models to mimic an osteopororotic condition in the trabecular bone and widely used to evaluate the bone-biomaterials response [16]. Therefore, the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and other international societies recommend this model for research on bone characteristics in response to an osteopororotic condition [17; 18]. We here aimed to evaluate, using histological and histomorphometric analysis, whether the induction of an osteopororotic condition, after the acquisition of implant osseointegration, influences peri-implant bone, i.e., bone-to-implant contact (BIC%), and peri-implant bone formation (BA%).