WNT11, a new gene associated with early-onset osteoporosis, is required for osteoblastogenesis.

Monogenic early-onset osteoporosis (EOOP) is a rare disease defined by low bone mineral density (BMD) that results in increased risk of fracture in children and young adults. Although several causative genes have been identified, some of the EOOP causation remains unresolved. Whole-exome sequencing revealed a de novo heterozygous loss-of-function mutation in WNT11 (NM_004626.2:c.677_678dup p.Leu227Glyfs*22) in a 4-year-old boy with low BMD and fractures. We identified two heterozygous WNT11 missense variants (NM_004626.2:c.217G > A p.Ala73Thr) and (NM_004626.2:c.865G > A p.Val289Met) in a 51-year-old woman and in a 61-year-old woman respectively, both with bone fragility. U2OS cells with heterozygous WNT11 mutation (NM_004626.2:c.690_721delfs*40) generated by CRISPR-Cas9 showed reduced cell proliferation (30%) and osteoblast differentiation (80%) as compared with wild-type U2OS cells. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells, but recombinant WNT11 treatment rescued the expression of Wnt pathway target genes. Furthermore, the expression of RSPO2, a WNT11 target involved in bone cell differentiation, and its receptor LGR5, was decreased in WNT11 mutant cells. Treatment with WNT5A and WNT11 recombinant proteins reversed LGR5 expression, but WNT3A recombinant protein treatment had no effect on LGR5 expression in mutant cells. Moreover, treatment with recombinant RSPO2 but not WNT11 or WNT3A activated the canonical pathway in mutant cells. In conclusion, we have identified WNT11 as a new gene responsible for EOOP, with loss-of-function variant inhibiting bone formation via Wnt canonical and non-canonical pathways. WNT11 may activate Wnt signaling by inducing the RSPO2-LGR5 complex via the non-canonical Wnt pathway

Familial hypocalciuric hypercalcemia associated with crystal deposition disease.

International audienceChondrocalcinosis is a common disease occasionally associated with hypercalcemia in case of primary hyperparathyroidism. Familial Hypocalciuric Hypercalcemia (FHH) is a rare and almost always asymptomatic condition, due to an autosomal dominant mutation of the calcium-sensing receptor gene. We report the case of a 61-year-old female with chronic hypercalcemia and joint pain. Clinical and biological data revealed chondrocalcinosis associated with FHH. Since primary hyperparathyroidism may mimic FHH, calcium to creatinine clearance ratio should be calculated in every case to avoid a wrong diagnosis and useless parathyroid surgery. The paucity of FFH complications, including chondrocalcinosis, makes their study difficult: additional studies are needed to clearly evaluate the link between FHH and chondrocalcinosis

Enquête alimentaire sur la consommation calcique au C.H.U. de Rennes parmi le personnel médical, paramédical et administratif

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Analyse de textures appliquée au tissu osseux

RENNES1-BU Santé (352382103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Traitement de l'ostéoporose/Osteoporosis treatment

International audienc

Ostéoporose postménopausique et sa prise en charge à l'officine (enquête)

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Dosage du taux sérique de 25 hydroxyvitamine D chez les patients admis en service de médecine physique et de réadaptation à Rennes (étude prospective multicentrique)

La vitamine D jouerait un rôle d'hormone, intervenant au niveau osseux mais également extra-osseux. Les patients admis en médecine physique et de réadaptation (MPR) présentent des facteurs de risque d'ostéoporose; leurs pathologies nécessiteraient le taux de 25 hydroxyvitamine D [25(OH)D] optimaux. Nous avons étudié de manière prospective sur 3 mois le statut vitaminique D des patients admis en unité de MPR à Rennes. 161 patients n'étaient pas supplémentés en vitamine D; leur taux de 25(OH)D était de 14,1+-8,5 ng/ml. Parmi eux, seuls 3 patients (1,8 %) avaient un taux optimal. Le taux de 25(OH)D était lié à l'existence de chutes dans l'année précédant l'admission. Il semblerait indiqué de doser systématiquement le taux de 25(OH)D, particulièrement chez les patients chuteurs ou atteints de sclérose en plaques. D'autres études doivent être conduites, dans des populations plus spécifiques, couplées à l'analyse de l'efficience de la supplémentation en vitamine D.RENNES1-BU Santé (352382103) / SudocSudocFranceF

Miscellaneous non-inflammatory musculoskeletal conditions. Rare thesaurismosis and xanthomatosis.

International audienceThe focus will be on xanthomatosis, a tissue danger signal which needs to be recognized by the clinician, and its relationship with monogenetic lipoprotein disorders (cholesterol, triglycerides), bile acid and sterol metabolism, particularly on metabolic pathways and genetics as well as on musculoskeletal and cardiovascular involvement, and their implications for clinical management. The critical question is to assess coronary heart disease risk, requiring correct identification of the pattern of lipoprotein disorders and of the causes (primary or secondary). Familial hypercholesterolemia must be suspected in adults and children with raised total cholesterol, especially when there is a personal or a family history of premature coronary heart disease, usually requiring potent statins to achieve adequate LDL-cholesterol lowering, even if we do not know safety of long-term therapy and whether treatments of dyslipidemia early in life prevent cardiovascular diseases in adulthood. Cerebrotendinous xanthomatosis is a treatable disease and must be suspected if there is a history of infantile chronic diarrhea and/or juvenile cataracts, even in the absence of tendon xanthomas. Current evidence for the prevention and screening, diagnosis, and treatment of dyslipidemia are available for the clinicians

Miscellaneous non-inflammatory musculoskeletal conditions. Haemochromatosis: the bone and the joint.

International audienceGenetic haemochromatosis is a hereditary disease characterised by tissue iron overload. In Caucasians it is most often due to homozygous C282Y HFE gene mutation, but other genes may be involved. Without treatment by venesections, patients can develop life-threatening visceral damage such as liver cirrhosis and carcinoma, diabetes or heart failure. This treatment has been remarkably successful in preventing these complications, but patients survive with other symptoms of the disease susceptible to impair, sometimes seriously, their quality of life. This is the case of arthropathy and osteoporosis complicating haemochromatosis. In this chapter, focus has been placed on the rheumatological complications of genetic haemochromatosis