Celiac disease is an autoimmune disorder characterized by atrophy of the intestine villi triggered by ingestion of gluten in genetically susceptible individuals. The association between celiac disease and low BMD has been recognized, but the mechanisms of disturbance are poorly understood. We show imbalance of cytokines relevant to bone metabolism in celiac patients' sera and the direct effect of these sera on in vitro bone cell activity.Introduction: Celiac disease is associated with mineral metabolism derangement and low BMD. We investigated whether imbalance of serum factors in celiac patients could affect human bone cell activity in vitro. Materials and Methods:We studied two groups of celiac patients-one on a gluten-free diet and another before the diet-both with decreased bone mass. Patients were investigated for bone turnover markers, and their sera were used for culturing bone cells from healthy donors and evaluate changes in cell activity. Results:The N-terminal telopeptide of procollagen type I and interleukin (IL)-6 were higher than normal in patients not on the gluten-free diet. IL-1␤ and TNF-␣/␤ were normal in all patients. IL-12 was reduced in all patients, whereas IL-18 was reduced only in patients on the diet. The RANKL/Osteoprotegerin (OPG) ratio was increased in patients not on the gluten-free diet. Persistently increased osteoclast numbers were obtained from peripheral blood mononuclear cells of healthy donors on incubation with sera of patients not on the gluten-free diet versus control sera and sera from patients on the diet. In human osteoblasts from healthy individuals, IL-18 was reduced on incubation with sera from all patients, whereas OPG expression was lower when sera from patients not on the diet were used. Proliferation, alkaline phosphatase, and nodule mineralization were increased in osteoblast cultures containing sera from all celiac patients, either on or not on the gluten-free diet. Conclusions: We conclude that bone loss in celiac disease might also be caused by a cytokine imbalance directly affecting osteoclastogenesis and osteoblast activity.

This is a report of a 34-year-old male lacking of bone development in the frontal and orbital part of the skull due to a surgical removal of a right orbital-front osteoma at the age of 5. The integrity of the craniofacial district was important for the young patient also for social acceptance and self-esteem. Based on computed tomography patient images, a skull model was reconstructed, both digitally and on 3-dimensional real model, to best design the needed bone graft. Defect wide extension and surface curvature called for the use of the puzzle technique, where the whole graft is composed by several elements, mechanically slotting into each other. The realization was made possible thanks to the use of a composite xenohybrid bone substitute specifically developed for reconstructive surgery (SmartBone, by Industrie Biomediche Insubri SA). SmartBone technology allowed the realization of custom-made grafts which perfectly joined each other and fitted the bone defect thanks to mechanical strength, also at low thicknesses and wide extensions. The postoperative course was uneventful and computed tomography scans showed new bone formation and complete calvaria continuity already 10 months after surgery, with no signs of inflammation over the entire follow-up. This case study represents a proof of concept that SmartBone on Demand custom-made bone grafts, together with puzzle technique, are effective, easy to handle and provide final excellent functional and aesthetic results.

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The case is reported to emphasize the need for careful radiological investigation in case of condylar fractures and the effectiveness of the extracranial route to surgically treat these rare complications.

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