Osteoporosis in an elderly man as interplay of multiple diseases

Abstract

Osteoporosis continues to be overlooked in men. In this population, osteoporosis is often related to corticosteroid use, alcohol abuse and hypogonadism. Osteoporosis-related fractures often result in long-term hospitalization with a consequent decline in quality of life. Bone mass density (BMD) in the aging male population is positively associated with endogenous androgen and estrogen levels, and testosterone treatment improves bone mineralization in hypogonadal men. Type 1 hereditary hemochromatosis (HH), is an autosomal recessive disorder associated with a mutation of the HFE (high iron Fe, hemochromatosis) gene, leading to a progressive iron overload which impairs the function of many organs. HH is an unusual cause of hypogonadotropic hypogonadism. In addition, hemochromatosis per se causes significant bone loss that cannot be solely explained by hypogonadism. A 71-year-old man was referred to our endocrinology unit from the Center of Metabolic Bone Diseases of our hospital for the finding of undetectable testosterone levels during screening for osteoporosis 1 year earlier. His family history was unremarkable; by contrast, the patient’s anamnesis was remarkable for type 2 diabetes mellitus, which had been satisfactorily treated with insulin therapy during the last 10 years, and longstanding (~50 years) epilepsy, treated with phenobarbital 150 mg/day. In addition, the patient reported phlebotomies and chelation therapies for “high iron levels” 20 years earlier, which had been withdrawn for poor compliance and tolerance. Over the last 2 years, the patient had been complaining of asthenia and worsening back pain; the latter was treated with analgesics. Targeted anamnesis ascertained no libido or erections and absence of sexual intercourses dating back many years. Previous examinations included computed tomography (CT) of the spine which showed osteoarthritis and thinning of the lumbar vertebrae secondary to osteoporosis, and dual-energy X-ray absorptiometry (DXA) scan which evidenced markedly reduced BMD both in the lumbar spine (0.8 g/cm, T-score -3.6) and in the proximal femur neck (0.57 g/cm, T-score -4). Secondary hyperparathyroidism characterized by increased parathyroid hormone levels, normal calcium levels (corrected for albumin) of 9.3 mg/dL (normal range 8.5–10.5) and 25-OH vitamin D deficiency (Table 1), and undetectable testosterone levels had been ascertained. Current therapy included alendronate 70 mg/week, colecalciferol 7500 IU/week and analgesics. On physical evaluation, the patient looked pale, had no axillary or pubic hair, and markedly decreased testis volume. Further laboratory evaluations were undertaken and abnormal values are shown in Table 1. Severe hypogonadotropic hypogonadism, normochromic normocytic anemia and increased iron levels were found. No testosterone response was observed after human chorionic gonadotropin (hCG; 2000 IU i.m.) testing. Dual-energy X-ray absorptiometry scan showed an improvement in BMD only in the lumbar spine (0.84 g/cm, T-score -3.3, +3.4% vs baseline). Contrast-enhanced magnetic resonance imaging (MRI) of the pituitary gland was unremarkable. Testosterone gel 50 mg/day was started; this normalized testosterone levels (5–6 ng/mL) over months, improved libido and sexual capability, and reduced asthenia. Lipids and liver function did not change over time and anemia reversed. DXA scan performed 1 year later (during which time also bisphosphonate and vitamin D therapy were continued) showed a significant BMD increase at both lumbar (+11.4% increase vs baseline) and femur (+5.9% increase vs baseline) levels. Owing to the clinical history, the patient was referred to the Center for Iron Overload Diseases of our hospital. Markedly increased ferritin and increased percent of transferrin saturation levels were found (Table 1). Genetic testing of the HFE gene showed the homozygous p.C282Y (Cys282Tyr) mutation. The final diagnosis was type 1 HH. Measurement of liver Geriatr Gerontol Int 2011; 11: 123–126