Decreased bone mineral density after therapy with alpha interferon in combination with ribavirin for chronic hepatitis C

doi:10.1016/S0168-8278(00)80314-1

Journal of Hepatology

Volume 33, Issue 5, November 2000, Pages 812-817

https://doi.org/10.1016/S0168-8278(00)80314-1 Get rights and content

Abstract

Background/Aims: Several thousand patients with chronic hepatitis C have been treated with interferon plus ribavirin. After observing a male patient who developed severe bone loss during this treatment, we studied skeletal status and bone mineral metabolism in patients on therapy with interferon plus ribavirin.

Methods: Bone mineral density and biochemical bone markers were studied in 32 male patients (31–58 years old) treated for 12 months with either interferon alone (group 1; n=13) or interferon plus ribavirin (group 2; n=19).

Results: Bone mineral density was significantly lower in group 2 (0.877±0.07 g/cm²) than in group 1 (1.108±0.08 g/cm², p<0.001). Likewise, T- and Z-score values were also decreased in group 2 (T: −1.95±0.6. Z: −1.76±0.51) compared with group 1 (T: 0.19±0.6; p<0.001. Z: 0.26±0.6; p<0.001). Serum and urine biochemical bone markers were normal in both groups. However, urinary calcium excretion was decreased in patients on combined therapy.

Conclusion: Treatment of chronic hepatitis C with interferon plus ribavirin may induce bone loss. This secondary effect should be investigated during the followup of these patients, since they may require therapies aimed at prevention or amelioration of these defects.

Section snippets

Case Report

A 55-year-old male physician with chronic hepatitis C was referred to our hospital to be included in a trial of combination therapy with IFN and ribavirin. In 1984, high levels of serum aminotransferases were found in a routine blood test. There was no history of alcohol intake, intravenous drugs, tobacco or medication, but, due to his profession as a health care worker, he had been exposed to needlestick on several occasions. He felt well and remained asymptomatic for the next 11 years. In

Patients and Methods

Thirty-two patients with chronic hepatitis C without cirrhosis treated with IFN for 12 months were studied All were males ranging from 31 to 48 years (mean age, 40 6±6 8 years). We excluded men over 50 years old and women to avoid the effect of age and estrogen deficiency on the bone mineral metabolism. Thirteen patients had been treated with IFN alone (3 MU tiw) (Group 1), and 19 patients with IFN (3 MU tiw) plus ribavirin (1000 to 1200 mg/day) (Group 2). All patients were asymptomatic and

Bone mineral density (BMD)

The T-score values were in the normal range in group 1 (0.19±0.6) None of them had T-scores under −1.0. By contrast, T-score was significantly decreased (−1.94±0.6) in group 2 treated with IFN plus ribavirin (p<0.001). Four of the 19 patients treated with this combination had T-score values below −2.5, that is, in the range of osteoporosis. None of them presented symptoms of bone fractures. The remaining 15 patients showed T-score values between −1.0 and −2.5, that is, in the range of

Discussion

Although a few patients have so far been reported to develop bone fractures or back pain during therapy with ribavirin plus IFN (11), little attention has been paid to such events and no study has been published concerning the effect of this therapy on bone mineral metabolism. In this paper, we report the case of a male patient treated with IFN plus ribavirin who presented several episodes of back pain. A bone densitometry of the lumbar spine demonstrated T-scores and Z-scores in the range of

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In some other studies results relative to BMD are more in accordance to those reported here. A normal BMD, but an increased bone loss with therapy, was reported by Solís-Herruzo et al. [33]. Luchi et al. [20], in 60 patients affected by HCV infection, found a total of 34 affected by osteopenia, and 7 (12%) affected by osteoporosis.
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Decreased bone mineral density after therapy with alpha interferon in combination with ribavirin for chronic hepatitis C

Abstract

Section snippets

Case Report

Patients and Methods

Bone mineral density (BMD)

Discussion

J Hepatol

Broad-spectrum antiviral activity of virazole 1-beta-D-ribofuranosyl-1,2,4 triazole-3-carboxamide

Science

Molecular action of ribavirin

Rev Infect Dis

viral RNA titers in serum prior to, during, and after oral treatment with ribavirin for chronic hepatitis C

J Med Virol

Ribavirin as therapy for chronic hepatitis C

Ann Intern Med

Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C A multicenter trial

Hepatology

Interferon alpha 2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C

N Engl J Med