Osteoporos Int (2006) 17: 150–155 DOI 10.1007/s00198-005-1920-6
CASE REPORT
Osteoporosis in HFE2 juvenile hemochromatosis. A case report and review of the literature Nicholas G. Angelopoulos Æ Anastasia K. Goula George Papanikolaou Æ George Tolis
Received: 27 November 2004 / Accepted: 31 March 2005 / Published online: 5 July 2005 Ó International Osteoporosis Foundation and National Osteoporosis Foundation 2005
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. Keywords Bone mineral density Æ Bone turnover Æ Hypogonadism Æ Juvenile hemochromatosis Æ Osteoporosis
N.G. Angelopoulos (&) Æ G. Tolis Division of Endocrinology and Metabolism, ‘‘Hippokrateion’’ Hospital of Athens, Vassilisis Sofias Avenue 108, 115 27 Athens, Greece E-mail:
[email protected] Tel.: +44-210-8668181 Fax: +44-210-7786889 E-mail:
[email protected] A.K. Goula First Division, ‘‘Ag.Sophia’’ Children University Hospital Athens, Greece E-mail:
[email protected] G. Papanikolaou First Department of Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, ‘‘Laikon’’ General Hospital, Athens, Greece E-mail:
[email protected]
Introduction Hereditary hemochromatosis (HH) is a genetically heterogeneous heritable disorder of iron metabolism commonly associated with homozygosity for the C282Y mutation in the hemochromatosis (HFE) gene on chromosome 6 [1]. Homozygosity for the C282Y mutation is found in 85–90% of patients with typical hemochromatosis of northern European origin [1]. Of the patient population, 15–20% is heterozygous for the H63D mutation, which may contribute to increased hepatic iron levels but does not result in iron overload in the absence of the C282Y mutation [2,3]. Patients under the age of 30 with hemochromatosis are considered suffering from a distinctive clinical entity called juvenile hemochromatosis (JH), with more aggressive clinical symptoms [4].
Materials and methods This is a study of the assessment of bone mass and bone turnover in a patient suffering from JH. The initial diagnosis of juvenile hemochromatosis was established by the following criteria: (1) early onset of clinical symptoms (usually in the second decade of life); (2) severity of iron overload as assessed by serum ferritin level, transferrin saturation, liver biopsy findings, and amount of iron mobilized by phlebotomies; (3) wild-type HFE genotype; and (4) linkage analysis studies of family members proving linkage to markers of chromosome 1q. There was no family history of osteoporosis. Bone mineral density (BMD) was measured by a DXA densitometer (HOLOGIC QDR 2000), both at the lumbar spine (L1–L4) in A–P projection and at the left femoral. The instrument was regularly calibrated according to the manufacturer’s instructions. Reproducibility was calculated as a coefficient of variation (CV) obtained by weekly measurements of a standard phantom on the instrument, with long-term CV of 0.5% at the spine using the Hologic Anthropometric Spine
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Phantom and with short-term in vivo CV of 1.2% and 1.5% for the spine and the hip, respectively. BMD data were expressed as grams per centimeter squared (g/cm2). Femoral BMD data were also expressed as t-scores and z-scores after been compared with BMD values of normal subjects (National Health and Examination Survey). Lumbar t-scores and z-scores were calculated after comparing BMD results with those seen in 352 healthy control males from the same geographic area. Fasting blood samples were taken for the measurement of serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), osteocalcin (BGP), bonespecific alkaline phosphatase (BAP), 25-hydroxyvitamin D [25(OH) D], 1,25-dihydroxyvitamin D [1,25(OH)2 D], osteoprotegerin (OPG), soluble receptor activator of nuclear factor (NF)-kB ligand (s-RANKL), total testosterone (T, normal range 350–1,100 ng/100 ml), free testosterone (Free T, normal range 19–41 pg/ml), estradiol (E2,normal range for men
