Systemic and local zoledronic acid treatment with hydroxyapatite bone graft: A histological and histomorphometric experimental study

Abstract

In this study, the aim was to compare the relative efficacy of systemic and local zoledronic acid (ZA) on a hydroxyapatite (HA) bone graft in a rat critical-size calvarial bone defect. In total, 84 female rats were divided into four groups: Empty control (EC) group with no treatment applied; HA group, in which only HA bone graft material was used in the calvarium; and HA plus local ZA (HA+LZA) and HA plus systemic ZA (HA+SZA) groups, in which animals received ZA locally or systemically, respectively, with HA bone graft material in the calvarium. A 5-mm standardised critical-size calvarial bone defect was created with a standard trephine drill and the respective treatment was applied. Rats were sacrificed 7, 14 and 28 days later. The numbers of osteoclasts and osteoblasts, and degree of bone formation were evaluated histopathologically and histomorphometrically. Statistically significant differences were detected between the HA, HA+LZA and HA+SZA groups and the EC group for new bone formation (P<0.05). Osteoblast numbers in the HA+LZA and HA+SZA groups were significantly higher compared with those in the EC and HA groups (P<0.05). No statistically significant difference was detected between the HA+LZA and HA+SZA groups in new bone formation or osteoblast number (P>0.05). Bone formation was significantly higher in the HA group than in the EC group (P<0.05). The numbers of osteoclasts in the HA+LZA and HA+SZA groups were significantly higher than those in the groups EC and HA (P<0.05); however, there was no significant difference between groups HA+LZA and HA+SZA (P>0.05). Within the limitations of this study, systemic or local administration of ZA enhanced new bone formation with a HA bone graft in a rat critical-size calvarial defect model.

Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair

“…Günes et al 59 have shown that the administration of zoledronate, either locally using hydroxyapatite as a carrier or systemically, could enhance the osteogenic potential of graft materials, thus improving the new bone formation. Both local and systemic treatment of zoledronate resulted in enhanced regeneration of rat calvarial bone defect, which has been explained in terms of increase in the number of osteoclasts and osteoblasts at the defect site in both treatment groups.…”

“…The advantage of local delivery of zoledronate could be explained in terms of reduction in the dosage of the drug: in systemic administration, 0.1 mg/kg of zoledronate was injected into the animal model while, in local treatment, a single soak of the graft in 1 mg/ml of zoledronate solution was sufficient to accomplish similar results. 59 …”

Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

“…β-TCP, a bioactive bone substitute material, has high biocompatibility and good stability [13]. Moreover, ZOL has demonstrated to have a protective effect on bone tissue resorption by inhibiting the activity of osteoclasts at the local site [14,15]. In the present study, we further investigated if the topical co-treatment of ZOL and the rh-BMP-2/β-TCP composite is useful in the promotion as well as the maintenance of new bone formation in the bone marrow environment.…”

The Effect of Systemic Delivery of Bisphosphonates on Trabecular and Cortical Bone Mass of Ovariectomized Rats

“…This bioactive molecule interrupts osteoclastic activity by hindering farnesyl diphosphate (5). Previous investigations represented the beneficial impacts of zoledronic acid application in treating osteoporosis, myeloma, and metastatic bone cancers (6)(7)(8). Previous studies indicated that alendronate, an aminobisphosphonate, enhances BMD, reduces bone turnover, and consequently the risk of bone fractures (9).…”