Abstract:The ability of marrow-derived osteoprogenitor cells to promote repair of critical-size tibial gaps upon autologous transplantation on a hydroxyapatite ceramic (HAC) carrier was tested in a sheep model. Conditions for in vitro expansion of sheep bone marrow stromal cells (BMSC) were established and the osteogenic potential of the expanded cells was validated. Ectopic implantation of sheep BMSC in immunocompromised mice led to extensive bone formation. When used to repair tibial gaps in sheep, cellloaded implants (n = 2) conducted a far more extensive bone formation than did cell-free HAC cylinders (n = 2) over a 2-month period. In cell-loaded implants, bone formation was found to occur both within the internal macropore space and around the HAC cylinder while in control cellfree implants, bone formation was limited mostly to the outer surface and was not observed in most of the inner pores. As tested in an indentation assay, the stiffness of the complex HAC-bone material was found to be higher in cellloaded implants compared to controls. Our pilot study on a limited number of large-sized animals suggests that the use of autologous BMSC in conjunction with HAC-based carriers results in faster bone repair compared to HAC alone. Potentially this combination could be used clinically in the treatment of extensive long bone defects.
Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse drug reaction, consisting of progressive bone destruction in the maxillofacial region of patients. ONJ can be caused by two pharmacological agents: Antiresorptive (including bisphosphonates (BPs) and receptor activator of nuclear factor kappa-B ligand inhibitors) and antiangiogenic. MRONJ pathophysiology is not completely elucidated. There are several suggested hypothesis that could explain its unique localization to the jaws: Inflammation or infection, microtrauma, altered bone remodeling or over suppression of bone resorption, angiogenesis inhibition, soft tissue BPs toxicity, peculiar biofilm of the oral cavity, terminal vascularization of the mandible, suppression of immunity, or Vitamin D deficiency. Dental screening and adequate treatment are fundamental to reduce the risk of osteonecrosis in patients under antiresorptive or antiangiogenic therapy, or before initiating the administration. The treatment of MRONJ is generally difficult and the optimal therapy strategy is still to be established. For this reason, prevention is even more important. It is suggested that a multidisciplinary team approach including a dentist, an oncologist, and a maxillofacial surgeon to evaluate and decide the best therapy for the patient. The choice between a conservative treatment and surgery is not easy, and it should be made on a case by case basis. However, the initial approach should be as conservative as possible. The most important goals of treatment for patients with established MRONJ are primarily the control of infection, bone necrosis progression, and pain. The aim of this paper is to represent the current knowledge about MRONJ, its preventive measures and management strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.