Efficacy of complementary treatment with autologous platelet concentrates and/or mesenchymal stem cells in chemical osteonecrosis of the jaw. Systematic review of the literature.

The aim of this systematic review was to establish the current status of the subject and find out what scientific evidence we have on the use of autologous plasma concentrates (APCs) and mesenchymal stem cells (MSCs) as complementary therapies at the management of Medication-related Osteonecrosis of the jaw (MRONJ). We performed a literature search of articles published between December 2019 to January 2020 in electronic databases, in accordance to PRISMA system. The variables analyzed were: the number of patients, age, sex, medical history, origin of MRONJ, imaging studies, treatment performed, and evolution of MRONJ. The articles included in the review were grouped into two groups (Group A "Therapy with APCs" and Group B "Therapy with APCs and MSCs"). Newcastle-Ottawa scale (NOS) was used to assess the quality of the articles. Fisher's exact test was used to evaluate eventual differences between groups. Of the 306 patients who were included, 297 belonged to Group A and 9 to Group B. In our sample, women predominated against men and no significant differences in age were observed. Osteoporosis was the most frequent underlying disease in both groups. The most common origin of MRONJ was oral surgery in group A. Conservative surgery was performed in all patients, but complementary treatment was applied in different ways in each group. The resolution of the pathology was achieved in 90% of cases in both groups without significant differences between them. The mean score of the reviewed studies at NOS was 4. There are currently no published scientific data that can sufficiently support the use of APCs and MSCs for the treatment of established MRONJs.

The effect of aging on the bone healing properties of blood plasma.

OBJECTIVES: Age-related changes in blood composition have been found to affect overall health. Thus, this study aimed to understand the effect of these changes on bone healing by assessing how plasma derived from young and old rats affect bone healing using a rat model. METHODS: . Blood plasma was collected from 6-month and 24-month old rats. Differences in elemental composition and metabolome were assessed using optical emission spectrometry and liquid mass spectrometry, respectively. Bilateral tibial bone defects were created in eight rats. Young plasma was randomly applied to one defect, while aged plasma was applied to the contralateral one. Rats were euthanized after two weeks, and their tibiae were analyzed using micro-CT and histology. The proteome of bone marrow was analyzed in an additional group of three rats. RESULTS: Bone-defects treated with aged-plasma were significantly bigger in size and presented lower bone volume/tissue volume compared to defects treated with young-plasma. Histomorphometric analysis showed fewer mast cells, macrophages, and lymphocytes in defects treated with old versus young plasma. The proteome analysis showed that young plasma upregulated pathways required for bone healing (e.g. RUNX2, platelet signaling, and crosslinking of collagen fibrils) whereas old plasma upregulated pathways, involved in disease and inflammation (e.g. IL-7, IL-15, IL-20, and GM-CSF signaling). Plasma derived from old rats presented higher concentrations of iron, phosphorous, and nucleotide metabolites as well as lower concentrations of platelets, citric acid cycle, and pentose phosphate pathway metabolites compared to plasma derived from young rats. CONCLUSION: bone defects treated with plasma-derived from young rats showed better healing compared to defects treated with plasma-derived from old rats. The application of young and old plasmas has different effects on the proteome of bone defects.

Treatment of von Willebrand Disease.

The general goal of therapy in von Willebrand disease is to correct the two defects that are related to the bleeding tendency of these patients, i.e., the abnormal primary hemostasis expressed by a prolonged bleeding time (BT) and the abnormal intrinsic coagulation due to low factor VIII (FVIII) levels. There are two main treatments in von Willebrand disease, i.e., desmopressin and transfusional therapy with blood products. Desmopressin is most effective in patients with type 1, who account for about 80 per cent of all patients. The remaining patients with type 2 and type 3 von Willebrand disease do not respond consistently to desmopressin and need the infusion of blood products containing FVIII and von Willebrand factor. Virally-inactivated concentrates that are currently on the market are preferable to fresh-frozen plasma and cryoprecipate, that still carry a small risk of transmitting blood-borne infections. In rare instance, particularly for hemorrhoages in mucosal tracts such as gastrointestinal bleeding, platelet concentrates are useful adjuncts to plasma concentrates when patients do not respond to the latters. The role of purified von Willebrand factor and of recombinant products is still unclear.