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Bone Loss and Vitamin D Deficiency Are Common among People with Liver Cirrhosis

People with liver cirrhosis -- a potential outcome of chronic hepatitis B or C -- frequently experience bone loss, or reduced bone mineral density (BMD), and often have low vitamin D levels, according to an Indian study published in the July 28, 2009 issue of World Journal of Gastroenterology.

Joe George and colleagues from Mumbai sought to estimate the prevalence and identify the risk factors associated with metabolic bone disease in patients with liver cirrhosis, or scarring.

The link between chronic liver disease and fragile bones with increased risk of fractures has long been recognized, the researchers noted as background. As liver disease progresses, impairment of its normal functions can contribute to a variety of metabolic abnormalities. Metabolic bone disease involves an imbalance between bone creation and resorption, leading to osteopenia or the more severe osteoporosis (porous bones).

The study included 72 Indian patients with cirrhosis; 63 were men, 9 were women, and all were less than 50 years old. The most common cause of cirrhosis was heavy alcohol use (37 patients), followed by hepatitis B (25 patients) and hepatitis C (10 patients). About one-third (23 patients) were classified as having Child class A (least severe) cirrhosis, while 39 had class B disease, and 10 had class C (most severe) disease. Other causes of metabolic bone disease besides cirrhosis were ruled out.

The researchers constructed complete metabolic profiles for the patients. Bone mineral density was measured using dual energy X ray absorptiometry (DEXA). Low BMD was defined as a Z score below -2. Exposure to sunlight (important for vitamin D synthesis), physical activity (which promotes strong bones), and diet composition (including calcium intake) were assessed. Calcium is a major component of bones, and vitamin D is required for proper calcium absorption and metabolism.

Results

• 68% of patients were found to have low BMD.
• The lumbar spine was the most frequently and severely affected area.
• Risk factors for low BMD included minimal physical activity, decreased sunlight exposure, and low amount of lean body mass.
• Dietary composition was similar in patients with low and normal BMD.
• Calcium intake was adequate, but patients generally had unfavorable calcium-to-protein and calcium-to-phosphorus ratios.
• Most patients (92%) had evidence of vitamin D deficiency.
• 41% had evidence of hypogonadism (low level of sex hormones), but low testosterone was equally common in patients with low and normal BMD.
• Patients with normal BMD had significantly higher levels of estradiol (a form of estrogen) than those with low bone density.
• Levels of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 were below age-adjusted normal ranges in both groups.
• However, IGF-1 was significantly lower in patients with low BMD.
• 68% of participants had low serum osteocalcin, a protein that plays a role in balancing bone build-up and resorption.
• 79% had a high urinary deoxypyridinoline-to-creatinine ratio, indicating low bone formation and excess resorption.

"Patients with cirrhosis have low BMD," the study authors concluded. "Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency, and hypogonadism and low IGF-1 level."

In their discussion, they noted that there was no observed relationship between severity of liver dysfunction as indicated by Child class and incidence of low BMD, leading them to recommend that bone health should be monitored early in the course of liver disease progression.

In various international studies, prevalence of low BMD has varied from 18% to 35% for osteopenia, from 11% to 48% for osteoporosis, and from 3% to 44% for fractures, according to the researchers.

The high prevalence of bone loss in this study may in part reflect poor nutrition in the general population, as commonly seen in developing countries. The climate in India is conducive to sunlight exposure, however, and calcium intake was found to be adequate according toIndian Council of Medical Research guidelines, though low by international standards.

The study did not include a control group without cirrhosis to compare frequency of bone loss and differences in levels of vitamin D and hormones related to bone metabolism.

Department of Endocrinology & Department of Gastroenterology, Seth G.S. Medical College and KEM Hospital, Mumbai, India; Department of Gastroenterology, Jaslok Hospital, Mumbai, India.

9/01/09

Reference

J George, HK Ganesh, S Acharya, and others. Bone mineral density and disorders of mineral metabolism in chronic liver disease. World Journal of Gastroenterology 15(28):3516-3522. July 28, 2009.