# Effect of Systemic Zoledronic Acid Dosing Regimens on Bone Regeneration in Osteoporotic Rats
## 1 Introduction
This may further be influenced by factors like the large size of the defect, unfavorable healing conditions, underlying metabolic diseases, overall nutrition, and even suboptimal surgical techniques [19; 20; 22]. An important factor determining the spontaneous healing ability is the size of the bone defect. Large bone defects incapable of spontaneous healing are considered as critical-size bone defects, and these defects require adjunctive measures to achieve healing [23]. Several therapeutic strategies involving bone grafts and substitute biomaterials have been used successfully for bone augmentation and bone defect regeneration in the fields of orthopedics, oral and maxillofacial surgery, and periodonontology [24]. Depending upon their origin, bone grafts and substitutes may be classified as autografts, allografts, xenografts, or synthetic alloplasts [25; 26]. In order to be a clinically utilizable bone substitute, a material needs to fulfill requirements such as biocompatibility, ability to provide mechanical support and volume for bone regeneration, and biodegradability [27; 28]. Autografts (derived from the same individual) are considered the gold standard among substitute biomaterials for bone regeneration, because of their ability to promote osteoinduction, osteoconduction, and osteogenesis [24]. Nevertheless, their routine use is limited by inadequate availability in intraoral sites, requirement for a second surgical site for harvesting (e.g., iliac crest), and post-operative morbidity at the donor site [29; 30]. Bone allografts obtained from banked donor bone is easily available and has similar properties to those of autograft bone [20]. However, when used as a bone substitute for regeneration, allografts need to be deproteinized and are only capable of osteoconduction, in addition to carrying a significant risk of infectious disease transmission [26]. An alternative to allograft bone is xenograft bone, obtained routinely from animal sources. Xenograft bone is usually deproteinized by means of a chemical or low-heat process, which preserves the original bone micro-architecture and the inorganic bone mineral composition, but removes the organic component, thereby preventing the possibility of immunogenic reactions [24; 28]. Anorganic bovine bone graft (ABBG) or deproteinized bovine bone mineral (DBBM) have shown good biocompatibility and osteoconductivity in preclinical studies when used in conjunction with the principles of guided bone regeneration (GBR) [31]. In addition to the afore-mentioned types of bone grafts, synthetic bone-graft substitutes or alloplasts such as calcium phosphate (CaP) ceramics, bioactive glass and polymers are also used for bone defect augmentation and regeneration [32]. In spite of the availability of several biomaterials, it is still a challenge to achieve successful bone defect regeneration in patients suffering from diseases that affect bone metabolism. For example, osteoporosis is one of the most frequently occurring bone disorders and is characterized by a progressive decrease in bone mineral density [33; 34]. Bone regeneration in osteopororotic patients could be affected by inadequate mineralization, which is essential for strengthening the new bone. Both experimental and clinical data have reported that osteoporosis negatively influences the healing process of a bone defect, either in the presence or in the absence of a suitable bone substitute material [34; 35; 36]. Clinically, the mission of regenerative dentistry is restoring damaged alveolar bone in both healthy and medically compromised patients. The key step in alveolar bone regeneration is to stimulate a cascade of healing events that can promote bone quantity and quality [33]. One of the greatest challenges associated with alveolar bone augmentation is bone resorption, which is further potentiated by skeletal disorders such as osteoporosis.