Dataset Information

Local vs. systemic administration of bisphosphonates in rat cleft bone graft: A comparative study.

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.

SUBMITTER: Hong C

PROVIDER: S-EPMC5755940 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundBisphosphonates limit resorption by inhibiting osteoclast formation and activation. They are removed during preparation of demineralized bone matrix (DBM) particles, but it is not known if osteogenesis and incorporation of mineralized bone allografts from patients treated with oral bisphosphonates are affected in vivo.MethodsHuman block allografts from 3 bisphosphonate-treated donors and 3 age and sex-matched control donors who had not received bisphosphonates were obtained (Musculoskeletal Transplant Foundation); one-half from each donor was demineralized. In the first study, 3 × 2-mm mineralized and demineralized cylindrical grafts were implanted bilaterally in the femoral metaphysis of 56 rats. In the second study, samples from each group were pooled, prepared as particles, and implanted bilaterally in the femoral marrow canal of 24 rats. Osseointegration, defined as native bone in contact with allograft, was assessed at 10 weeks by micro-computed tomography (CT) and histomorphometry.ResultsMicro-CT showed greater bone volume in sites treated with demineralized samples compared with the control mineralized and bisphosphonate-exposed mineralized samples. More new bone was generated along the cortical-endosteal interface compared with mineralized samples. Histology showed significantly less new bone in contact with the mineralized bisphosphonate-exposed allograft (10.4%) compared with mineralized samples that did not receive bisphosphonates (22.8%) and demineralized samples (31.7% and 42.8%). A gap was observed between native bone and allograft in the bisphosphonate-exposed mineralized samples (0.50 mm 2 ). The gap area was significantly greater compared with mineralized samples that did not receive bisphosphonates (0.16 mm 2 ) and demineralized samples (0.10 and 0.03 mm 2 ).ConclusionsMineralized allografts were osseointegrated, but not remodeled or replaced by living bone, preventing full regeneration of the bone defect. Prior treatment of the donor with bisphosphonates affected osteogenesis, preventing osteointegration and remodeling of the allograft into the regenerating bone.Clinical relevanceClinical use of mineralized allografts from patients who had received bisphosphonate therapy needs to be evaluated; in this animal model, such grafts were not integrated into the host bone or remodeled, and full regeneration of the bone defects was prevented.

Project description:BackgroundSystemic administration of sclerostin neutralizing antibody has led to increased bone formation in animal models of osteoporosis. The purpose of this study was to determine if systemic administration of sclerostin neutralizing antibody could increase the healing response in a critical-sized femoral defect in rats.MethodsCritical-sized femoral defects were created in Lewis rats, and the rats were randomized into four groups. The sclerostin antibody (Scl-Ab) treatment groups included the continuous Scl-Ab group (twenty-one animals), the early Scl-Ab group (fifteen animals), and the delayed Scl-Ab group (fifteen animals), which received sclerostin antibody (25 mg/kg) twice weekly for weeks 0 through 12; weeks 0 through 2; and weeks 2 through 4; respectively. Twenty-one animals in the control group received vehicle from weeks 0 through 12. In a subsequent study, bone turnover markers were measured at zero, two, six, and twelve weeks after surgery in rats receiving vehicle or sclerostin neutralizing antibody for twelve weeks (fifteen rats per group). The quality of bone formed was evaluated with radiographs, microcomputed tomography, biomechanical testing, and histologic and histomorphometric analysis.ResultsIn the primary study, four of fifteen defects in the continuous (zero to twelve-week) Scl-Ab group, three of fifteen defects in the early (zero to two-week) Scl-Ab group, and four of fifteen defects in the delayed (two to four-week) Scl-Ab group healed at twelve weeks, while none of the defects healed in the control group. In both studies, treatment with sclerostin antibody for twelve weeks demonstrated a significant increase in new bone formation (p < 0.05) compared with the control group. The three treatment groups did not differ significantly with respect to the healing rates and the quality of new bone formed in the defect. The serum markers of bone formation were significantly elevated in the animals in the continuous Scl-Ab group (p < 0.05) compared with the controls.ConclusionsAdministration of sclerostin neutralizing antibody led to increased bone formation, resulting in complete healing of femoral defects in a small subset of rats, with a majority of the animals not healing the defect by twelve weeks.

Project description:Background and objectives: Bisphosphonates represent selective inhibitors of excess osteoblastic bone resorption that characterizes all osteopathies, targeting osteoclasts and their precursors. Their long-term administration in postmenopausal women suffering from osteoporosis has resulted in neural adverse effects. The current study focuses on the research of possible alterations in the femoral nerve, caused by bisphosphonates. We hypothesized that bisphosphonates, taken orally (per os), may produce degenerative changes to the femoral nerve, affecting lower-limb posture and walking neuronal commands. Materials and Methods: In order to support our hypothesis, femoral nerve specimens were extracted from ten female 12-month-old Wistar rats given 0.05 milligrams (mg) per kilogram (kg) of body weight (b.w.) per week alendronate per os for 13 weeks and from ten female 12-month-old Wistar rats given normal saline that were used as a control group. Specimens were studied using immunohistochemistry for selected antibodies NeuN (Neuronal Nuclear Protein), a protein located within mature, postmitotic neural nucleus, and cytosol and Sox10 (Sex-determining Region Y (SRY) - High-Motility Group (HMG) - box 10). The latter marker is fundamental for myelination of peripheral nerves. Obtained slides were examined under a light microscope. Results: Samples extracted from rats given alendronate were more Sox10 positive compared to samples of the control group, where the marker's expression was not so intense. Both groups were equally NeuN positive. Our results are in agreement with previous studies conducted under a transmission electron microscope. Conclusions: The suggested pathophysiological mechanism linked to histological alterations described above is possibly related to toxic drug effects on Schwann and neuronal cells. Our hypothesis enhances the existing scientific evidence of degenerative changes present on femoral nerve following bisphosphonates administration, indicating a possible relationship between alendronate use and neuronal function.

Dataset Information

Local vs. systemic administration of bisphosphonates in rat cleft bone graft: A comparative study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets