Osteitis fibrosa is mediated by Platelet-Derived Growth Factor-A via a phosphoinositide 3-kinase-dependent signaling pathway in a rat model for chronic hyperparathyroidism.

Abnormal secretion of PTH by the parathyroid glands contributes to a variety of common skeletal disorders. Prior studies implicate platelet-derived growth factor-A (PDGF-A) as an important mediator of selective PTH actions on bone. The present studies used targeted gene profiling and small-molecule antagonists directed against candidate gene products to elucidate the roles of specific PTH-regulated genes and signaling pathways. A group of 29 genes in rats continuously infused with PTH and cotreated with the PDGF receptor antagonist trapidil were differentially expressed compared with PTH treatment alone. Several of the identified genes were functionally clustered as regulators of fibroblast differentiation and extracellular matrix modeling, including the matrix cross-linking enzyme lysyl oxidase (LOX). Treatment with beta-aminopropionitrile, an irreversible inhibitor of LOX activity, dramatically reduced diffuse mineralization but had no effect on PTH-induced fibrosis. In contrast, the receptor tyrosine kinase inhibitor Gleevec and the phosphoinositide 3-kinase inhibitor wortmannin each reduced bone marrow fibrosis. In summary, the present studies support the hypotheses that PTH-induced bone marrow fibrosis is mediated by PDGF-A via a phosphoinositide 3-kinase-dependent signaling pathway and that increased LOX gene expression plays a key role in abnormal mineralization, a hallmark of chronic hyperparathyroidism.

[Brown tumors of upper and lower jaws in Recklinghausen neurofibromatosis. A case report]. / Tumori brune ale maxilarului si mandibulei in neurofibromatoza Recklinghausen. Observatii pe marginea unui caz.

We report the case of a 41-year-old patient who presented multiple cafe au lait spots and exophytic tumors of the upper jaw, causing facial asymmetry and masticatory impairment. Physical examination and paraclinical investigations established the diagnosis of NF1 (type 1 neurofibromatosis) associated with brown tumors in jaws and left nasal bone, caused by a primary hyperparathyroidism (Oxyphilic adenoma). The parathyroidectomy determines brown tumors regression and sclerosis with no dependence on their localization.

[Early appearing neurofibromatosis (author's transl)]. / Neurofibromatosis de aparición precoz. Nuestra casuística

Six cases of neurofibromatosis in children under seven years of age with other members of the family affected are reported. Mental retardation was observed in five patients, and one had convulsive crises. Growth and bone maturation retardation, without HGH deficiency after glucagon stimulation were observed.