Nathalie Saidenberg-Kermanac’h

Vitamin D and inflammation.

Calcitriol, or 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D3) is a well-known endocrine regulator of calcium homeostasis. More recently, local calcitriol production by immune cells was shown to exert autocrine or paracrine immunomodulating effects. Immune cells that produce calcitriol also express the vitamin D receptor (VDR) and the enzymes needed to metabolize vitamin D3 (1α-, 25-, and 24-hydroxylases). Studies of animal models and cell cultures showed both direct and indirect immunomodulating effects involving the T cells, B cells, and antigen-presenting cells (dendritic cells and macrophages) and affecting both innate and adaptive immune responses. The overall effect is a switch from the Th1/Th17 response to the Th2/Treg profile. The immunomodulating effects of vitamin D may explain the reported epidemiological associations between vitamin D status and a large number of autoimmune and inflammatory diseases. Such associations have been suggested by observational studies not only in rheumatoid arthritis, lupus, inflammatory bowel disease, and type 1 diabetes; but also in infections, malignancies, transplant rejection, and cardiovascular disease. In animal models for these diseases, vitamin D supplementation has been found to produce therapeutic effects. Thus, vitamin D is a key focus for public health efforts and may hold promise for the treatment of dysimmune diseases.

Role for osteoprotegerin in rheumatoid inflammation

Osteoprotegerin (OPG), a member of the TNF-receptor family expressed by osteoblasts, has documented effects on the regulation of bone metabolism. OPG inhibits bone resorption and binds with strong affinity to its ligand RANKL, thereby preventing RANKL from binding to its receptor RANK. This system is regulated by calcium-modifying hormones. OPG may also be pivotal in modulating the immune system. RANKL-deficient mice exhibit both severe immunological abnormalities and osteopetrosis, and activated T cells express RANKL mRNA. RANKL secretion by activated T cells may induce osteoclastogenesis via a mechanism enhanced by several cytokines (TNF-alpha, IL-1, and IL-17) that promote both inflammation and bone resorption. Conversely, this mechanism is inhibited by OPG, IL-4, and IL-10, which have antiinflammatory effects and inhibit osteoclast formation. Activated T cells in the rheumatoid synovium express RANKL. Synoviocytes can differentiate to osteoclast-like cells under specific conditions, particularly when they are cultured with M-CSF and RANKL. Thus, the bony erosions seen in RA may result from RANKL/RANK system activation by activated T cells. This raises the possibility that OPG therapy to block this mechanism might prove beneficial in patients with RA.

Spinal epidural lipomatosis revealing endogenous Cushing's syndrome.

Spinal epidural lipomatosis is defined as accumulation of nonencapsulated fat within the spinal canal. It occurs chiefly in patients on long-term glucocorticoid therapy or in obese patients without any other detectable cause. We report the second case of spinal epidural lipomatosis revealing endogenous Cushings syndrome.

Normal plasma FGF23 levels kinetic in tenofovir-related hypophosphatemic osteomalacia in an HIV-infected patient with von Recklinghausen disease

The antiretroviral agent tenofovir can cause hypophosphatemic osteomalacia due to renal phosphate wasting. The potential role for Fibroblast Growth Factor 23 (FGF23), a phosphaturic hormone is unknown. We evaluated FGF23 plasma concentrations in an HIV-positive patient with neurofibromatosis in whom hypophosphatemia developed during tenofovir therapy. This patient presented with diffuse pain, hypophosphatemia and tubular dysfunction with inadequate phosphate reabsorption. The full recovery after tenofovir discontinuation indicates that the hypophosphatemia was related to tenofovir and not to von Recklinghausen disease. Our data argue against a role for FGF23 in tenofovir-induced hypophosphatemia nor in the regulation of hypophosphatemia in this situation.

Vitamin D supplementation in patients treated for sarcoidosis: Controversy or consensus?

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 3 mai 2017

Lipomatose épidurale révélatrice d’un syndrome de Cushing endogène

Resume La lipomatose epidurale, definie par le depot de graisse non encapsulee dans l’espace epidural, s’observe le plus souvent au cours des corticotherapies prolongees mais aussi sans cause apparente chez des sujets obeses. Nous rapportons le 2e cas de lipomatose epidurale revelateur d’une tumeur surrenalienne responsable d’un syndrome de Cushing endogene.