Osteoporosis in HFE2 juvenile hemochromatosis. A case report and review of the literature

Abstract

Juvenile hemochromatosis (JH) is a severe form of hemochromatosis, which involves rapid iron overload and leads to organ damage, typically before the age of 30. We report a single case of a 25-year-old man suffering from juvenile hemochromatosis, with aggressive clinical manifestations, typically characterized by transaminasemia and progressive erectile dysfunction, due to hypogonadotropic hypogonadism. The clinical case appears interesting, as the patient also had secondary osteoporosis accompanied by increased bone resorption, which prevalently affected trabecular bone. Approximately 6 months after normalization of serum ferritin levels was achieved by frequent phlebotomies, he became eugonadal and bone mineral density of the lumbar spine increased. Our observations suggest that osteoporosis might occur in the state of JH even at a young age, mainly due to the deprivation of sex steroids and the direct tissue toxicity of iron.

Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin

“…Several reports described low bone density, osteoporosis and/or osteopenia in patients with different forms of hemochromatosis [8][9][10][11]. Supporting this notion, both pharmacological and genetic provocation of iron overload was shown to be associated with bone abnormalities in rodent models of hemochromatosis.…”

“…Excess iron accumulates in the bones of individuals with hemochromatosis [35], and there is a long-known association between hemochromatosis and low bone mineral density [8][9][10][11]. In a study of iliac crest biopsies from 21 individuals with severe osteoporosis iron bone concentration was evaluated and a significant increase in iron content in cortical bone was found in osteoporotic patients vs. 12 controls [36].…”

Association between iron overload and osteoporosis in patients with hereditary hemochromatosis

“…However, non-HFE related HHC represent a genetically heterogeneous disease, and it is likely that specific subgroups are at higher risk for OP. In particular, due to the early occurrence and severity of iron overload and of hypogonadism, patients with the rare juvenile hemochromatosis may be nearly always affected [14]. Indeed, the two patients included here with juvenile hemochromatosis had OP.…”

“…The last mechanism seems to play a major role in OP associated with juvenile hemochromatosis, due to the very early onset of pituitary malfunction [14]. However, no data are available on the role of HFE gene mutations vs. other causes of iron overload in determining the risk of OP, and few observations are available on the role of acquired factors influencing iron absorption, such as sex and menopausal status, chronic hepatitis C and alcohol intake.…”

Bone status in a mouse model of genetic hemochromatosis

“…Other mutations in the hemojuvelin gene, which lead to the development of a juvenile form of hemochromatosis, have been associated with osteoporosis in hemochromatosis. However, a severe hypogonadism [13] is reported in this type of hemochromatosis. Thalassemia, which is associated with the development of secondary iron overload and hypogonadism favors the development of osteoporosis [14], thus supporting either a direct role of iron on bone or an endocrinological complication of the disease.…”