Abstract
A majority of patients with orofacial cleft deformity requires cleft repair through a bone graft. However, elevated amount of bone resorption and subsequent bone graft failure remains a significant clinical challenge. Bisphosphonates (BPs), a class of anti-resorptive drugs, may offer great promise in enhancing the clinical success of bone grafting. In this study, we compared the effects of systemic and local delivery of BPs in an intraoral bone graft model in rats. We randomly divided 34 female 20-week-old Fischer F344 Inbred rats into four groups to repair an intraoral critical-sized defect (CSD): (1) Control: CSD without graft (n = 4); (2) Graft/Saline: bone graft with systemic administration of saline 1 week post-operatively (n = 10); (3) Graft/Systemic: bone graft with systemic administration of zoledronic acid 1 week post-operatively (n = 10); and (4) Graft/Local: bone graft pre-treated with zoledronic acid (n = 10). At 6-weeks post-operatively, microCT volumetric analysis showed a significant increase in bone fraction volume (BV/TV) in the Graft/Systemic (62.99 ±14.31%) and Graft/Local (69.35 ±13.18%) groups compared to the Graft/Saline (39.18±10.18%). Similarly, histological analysis demonstrated a significant increase in bone volume in the Graft/Systemic (78.76 ±18.00%) and Graft/Local (89.95 ±4.93%) groups compared to the Graft/Saline (19.74±18.89%). The local delivery approach resulted in the clinical success of bone grafts, with reduced graft resorption and enhanced osteogenesis and bony integration with defect margins while avoiding the effects of BPs on peripheral osteoclastic function. In addition, local delivery of BPs may be superior to systemic delivery with its ease of procedure as it involves simple soaking of bone graft materials in BP solution prior to graft placement into the defect. This new approach may provide convenient and promising clinical applications towards effectively managing cleft patients.
Highlights
Orofacial cleft anomalies are the most common craniofacial congenital aberrations to occur worldwide [1] and these clefts may manifest as part of a syndrome or more commonly, as isolated cases [2]
To evaluate bone graft retention and bone regeneration in the intraoral critical-sized defect (CSD), high-resolution microCT was used for 3D qualitative and quantitative analysis. 3D reconstructed images of the defect area confirmed that the Control group defect was a non-healing CSD (BV/tissue volume (TV) = 8.71±2.21%)
Bone mineral density (BMD) analysis showed a significant increase in Graft/Systemic (0.59 ± 0.12g/cm3) and Graft/Local (0.63 ± 0.12g/cm3) groups compared to the Graft/Saline group (0.41 ± 0.09g/cm3) (Fig 2C)
Summary
Orofacial cleft anomalies are the most common craniofacial congenital aberrations to occur worldwide [1] and these clefts may manifest as part of a syndrome or more commonly, as isolated cases [2]. A multitude of clinical problems are associated with cleft patients, including deficient facial growth, malocclusion, and respiratory, feeding, and speech complications [4], requiring a comprehensive and multi-disciplinary approach for their care. Bone graft surgery is an essential step in the comprehensive treatment of cleft patients. Bone grafting provides: 1) stabilization of the maxilla, thereby helping maintain palatal width and preventing collapse following expansion, 2) a scaffold for tooth eruption or future implant placement, 3) effective closure of oronasal fistulas, 4) support for the alar base of the nose and lip, and 5) improvement of esthetic results and overall facial symmetry [5,6,7]. Insufficient bone volume in the cleft region due to a high amount of bone resorption has been a major clinical challenge in cleft patient care
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