Clinical Gastroenterology and Hepatology
Volume 7, Issue 8 , Pages 814-815, August 2009

Tone the Bones of Your Chronic Liver Disease Patients

published online 27 April 2009.

Article Outline

 

Bone is a specialized support tissue which acts as a calcium deposit, an acid-base buffer, and because of its rigidity and hardness gives form to the body and protects internal organs. Osteoporosis is an asymptomatic disease characterized by low bone mineral density (BMD) with microarchitectural disruption, and increased risk of fracture.

It is estimated that over 200 million people worldwide have osteoporosis and 30% of these are postmenopausal women in the US and Europe.1 At least 40% of these women and 15%–30% of men will sustain 1 or more fragility fractures in their remaining lifetime.2, 3 The aging of populations worldwide will increase the incidence of osteoporosis in postmenopausal women.4 Women who have sustained a hip fracture have a 10%–20% higher mortality than would be expected for their age.5 By 2050, the worldwide incidence of hip fracture is projected to increase by 240% in women and 310% in men,6 and the estimated number of hip fractures will rise from 1.66 million in 1990 to 6.26 million in 2050.7

The most common fractures associated with osteoporosis occur at the spine, hip, and wrist, and the incidence of these fractures increases with age in both women and men. Vertebral fractures can result in loss of height, intense back pain, and deformity, while a hip fracture often requires a surgery and may result in significant morbidity and mortality. Osteoporosis-related fractures create a heavy economic burden, causing more than 432,000 hospital admissions, almost 2.5 million medical office visits, and about 180,000 nursing home admissions annually in the United States.8 The cost to the US healthcare system associated with osteoporosis-related fractures has been estimated at $17 billion for 2005; hip fractures account for 14% of incident fractures and 72% of fracture costs.9

Hepatic osteodystrophy is a metabolic bone disease due to reduced bone formation and increased resorption and presents as low BMD and fractures. The major risk factors for hepatic osteodystrophy are chronic cholestasis and advanced cirrhosis. Low BMD occurs in up to 60% of these patients, and approximately 20% have atraumatic fractures.10 Possible pathogenetic mechanisms for hepatic osteodystrophy are: abnormalities of calcium, vitamin D, vitamin K, and bilirubin metabolism, hypogonadism, treatment with glucocorticoids, insulin-like growth factor-1 deficiency, and alterations in receptor activator of nuclear factor kB ligand and osteoprotegerin (RANKL/OPG) system. Lifestyle factors such as decreased intake of calcium and vitamin D, sedentary life style, smoking, alcoholism, and low body mass index also contribute.10

In this issue of Clinical Gastroenterology and Hepatology, Nanda et al studied the effect of chronic hepatitis C virus (HCV) infection on metabolic bone disease in a cohort of postmenopausal Irish women who were exposed to contaminated anti-D immunoglobulin from a single donor source.11 After randomly selecting 100 women, their final analysis included 20 postmenopausal, treatment naïve, chronic HCV infected women, and 21 postmenopausal women who consistently tested negative for HCV RNA. These groups were compared with 23 healthy, randomly selected, age-matched, postmenopausal women with no risks for liver disease. None of these patients had taken hormone replacement therapy, vitamin D, corticosteroids, bisphosphonates, or calcitonin in the 12 months prior to the study. They found no significant differences in the baseline characteristics, risk factors for osteoporosis, life events associated with estrogen exposure, and biochemical markers of bone turnover and bone mineral density. However, they observed an increased frequency of fractures in the polymerase chain reaction (PCR) positive group, where 6 patients had fractures, compared with the PCR negative group, where no fractures were reported (P = .007). Although they did not find any significant correlation between chronic HCV infection and low BMD, postmenopausal status was a risk factor for low BMD and osteoporosis.

While Nanda et al did not find a relationship between low BMD and liver disease, patients with chronic liver diseases and other gastrointestinal pathologies like those resulting in malabsorption of fat soluble vitamins (vitamin D), irrespective of their menopausal status are at a risk for low BMD and fragility fractures. Luchi et al studied a group of male patients with chronic HCV infection and found that 56% of the patients had low BMD, and the prevalence of low BMD increased as the histological score of the disease increased. They also found that there is increased bone remodeling in these individuals mainly due to osteoclastic resorption.12 Carey et al studied BMD and fracture rates in patients with cirrhosis due to HCV, alcohol abuse (ALD), and from HCV in conjunction with ALD (HCV + ALD) and found that the baseline mean T-score was lower in the HCV group than in the ALD group. Patients with both HCV and ALD had intermediate T-scores. Fractures occurred in 17% of these patients in the first year after liver transplantation, the majority being vertebral compression fractures.13

A study of treatment of osteoporosis in this population by Arase et al evaluated the effect of cyclic etidronate on the predictive factors and cumulative incidence of bone fracture in postmenopausal women with osteoporosis and chronic liver disease and found that tenth year cumulative appearance rates of bone fracture were 4.9% in the etidronate group and 13.8% in the control group.14 Cohen et al studied the safety of primary total hip arthroplasty and total knee arthroplasty in cirrhotic patients and found significant adverse outcomes in 20.7% of cirrhotic patients compared with 3.23% of control subjects. However, 80% of the cirrhotic patients undergoing emergent total hip arthroplasty secondary to fracture had major complications, with a 60% mortality rate.15

The American Gastroenterological Association (AGA) published recommendations on management of osteoporosis in hepatic and other gastrointestinal disorders in 2003.16 According to AGA, vitamin D levels and BMD should be assessed in all patients with cirrhosis. A normal initial BMD should be retested after 2–3 years to exclude significant interval bone loss. There is a paucity of randomized clinical trials aimed at bone health and fracture prevention in hepatic diseases. The AGA, because of level D evidence of use of pharmacological agents for osteoporosis in hepatic diseases, recommends the involvement of a bone disease specialist in the management of such patients.

The National Osteoporosis Foundation (NOF) recommends that adequate calcium intake should be at least 1200 mg/day, vitamin D intake 800–1000 IU/day, and a desirable level of serum 25-hydroxyvitamin D should be 30–60 ng/mL.17 These recommendations seem prudent for individuals with hepatic cirrhosis and gastrointestinal diseases though alterations may be needed for malabsorption. Patients should be educated regarding physical activity, fall preventions, avoidance of smoking, and excess alcohol.

According to the National Osteoporosis Foundation, patients are still not being given appropriate information about screening, prevention, diagnosis, and Food and Drug Administration-approved, effective therapies for osteoporosis.17 Osteoporosis is a treatable condition and with appropriate screening, combination of life style changes, and pharmacological treatment, many fractures can be avoided in premenopausal as well as postmenopausal patients with hepatic cirrhosis and other gastrointestinal pathologies.

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References 

  1. Cooper C, Campion G, Melton LJ. Hip fractures in the elderly: a world-wide projection. Osteoporosis Int. 1992;2:285–289
  2. Melton LJ, Chrischilles EA, Cooper C, et al. Perspective: How many women have osteoporosis?. J Bone Miner Res. 1992;7:1005–1010
  3. Randell A, Sambrook PN, Nguyen TV, et al. Direct clinical and welfare costs of osteoporotic fractures in elderly men and women. Osteoporosis Int. 1995;5:427–432
  4. Reginster JY, Burlet N. Osteoporosis: a still increasing prevalence. Bone. 2006;38:S4–S9
  5. Cummings SR, Melton JR. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359:1761–1767
  6. Gullberg B, Johnell O, Kanis JA. Worldwide projections for hip fracture. Osteoporosis Int. 1997;7:407–413
  7. Sambrook P, Cooper C. Osteoporosis. Lancet. 2006;367:2010–2018
  8. US Department of Health and Human Services. Bone health and osteoporosis: a report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004;
  9. Burge RT, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporotic fractures in the United States, 2005–2025. J Bone Min Res. 2007;22:465–475
  10. Gasser RW. Cholestasis and metabolic bone disease — a clinical review. Wien Med Wochenschr. 2008;158:553–557
  11. Nanda K, Ryan E, Murray B, et al. The effect of chronic hepatitis C virus infection on bone disease in postmenopausal women. Clin Gastroenterol Hepatol. 2009;7:894–899
  12. Luchi S, Fiorini I, Meini M, et al. Alterations of bone metabolism in patients with chronic C virus hepatitis. [in Italian] Infez Med. 2005;13:23–27
  13. Carey EJ, Balan V, Kremers WK, et al. Osteopenia and osteoporosis in patients with end-stage liver disease caused by hepatitis C and alcoholic liver disease: not just a cholestatic problem. Liver Transpl. 2003;9:1166–1173
  14. Arase Y, Suzuki F, Suzuki Y, et al. Prolonged-efficacy of bisphosphonates in postmenopausal women with osteoporosis and chronic liver disease. [erratum in: 2008;80:1868] J Med Virol. 2008;80:1302–1307
  15. Cohen SM, Te HS, Levitsky J. Operative risk of total hip and knee arthroplasty in cirrhotic patients. J Arthroplasty. 2005;20:460–466
  16. American Gastroenterological Association. American Gastroenterological Association medical position statement: osteoporosis in hepatic disorders. Gastroenterology. 2003;125:937–940
  17. National Osteoporosis Foundation. Clinician's guide to prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation; 2008;

 Conflicts of interest The authors disclose no conflicts.

PII: S1542-3565(09)00373-5

doi:10.1016/j.cgh.2009.04.013

Clinical Gastroenterology and Hepatology
Volume 7, Issue 8 , Pages 814-815, August 2009