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Liver disease is a major burden on society. In fact, in the U.S. alone, more than 17,000 people are currently waiting for a liver transplant. Moreover, over 5,000 liver transplants occur yearly. Liver disease is so common that the liver is the second most commonly transplanted major organ. Only the kidney is transplanted more than the liver. The major liver diseases requiring liver transplants are chronic active hepatitis and alcohol-induced cirrhosis in adults and billary atresia, the incomplete development of the bile duct, in children.
Common complications following liver transplantation include: allograft nonfunction, rejection, viral reinfection of the transplanted liver by the host, recurrent hepatic malignancy and posttransplantation lymphoproliferative disease (PTLD). Furthermore, osteolysis due to bone disease from liver transplant can also occur.
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What is osteolysis and why does it occur following liver transplantation?
Low bone density is associated with dysfunction of either osteoblasts or osteclasts. While bone loss is associated with advanced liver disease, osteolysis after liver transplant is also common. Metabolic bone disease, primarily osteoporosis, is common among liver disease patients undergoing liver transplantation. In fact, 20-100% of chronic liver disease patients suffer from bone loss duw to osteoporosis. Moreover, the incidence of bone pain and fractures, with an underlying cause of osteoporosis, is a major source of morbidity following liver transplantation.
Certain factors can elevate the risk of osteolysis due to bone disease from liver transplant. These factors include:
- Reduced synthesis of collagen matrix
- Low rate of bone mineralization.
- Osteoblast dysfunction.
- Hypogonadism (Chronic liver disease accelerates the development of hypogonadism)
- A decline in circulating estrogen
- Vitamin D deficiency
Corticosteroid therapy, the primary therapy for autoimmune hepatitis and immunosuppression after liver transplantation has been shown to enhance osteoclast function and suppress osteoblast function. Moreover, corticosteroids alter intestinal calcium absorption, increase urinary calcium and precipitate hypogonadism.
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What are the signs and symptoms of osteolysis?
While many patients will never develop symptoms following liver transplantation, others with develop severe and sudden pain or develop aching bone pain and deformities. The most common symptom of osteolysis is unexplained bone fractures with little or no force. The main reason for these fractures is due to a decrease in bone density with allows bones to collapse and fracture. Fractures normally occur at the ends of the long bones found in the arms and legs. Rarely will these fractures be present in the middle of the bone. Moreover, the vertebrae of the middle to lower back at risk of fracturing. Bones in other parts of the body may also fracture. These fractures are often caused by minor falls or bumps that would normally not result in a bone fracture. Furthermore, these fractures tend to take a longer period of time to heal.
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How is osteolysis treated?
While many liver transplant patients suffer osteolysis, bone loss can be prevented. The first step is to eliminate reversible factors that may responsible for bone loss. These factors include: tobacco and alcohol consumption, ingestion of caffeine containing substances such as coffee or soft drinks and diuretic and corticosteroidal therapies. Moreover, maintaining a healthy body weight via exercise or eating healthy can help maintain skeletal in integrity and thus decrease the rate of osteolysis. Consumption of adequate levels of calcium can also reduce bone loss in liver disease patients. Following liver transplantation, physiotherapy may be recommended to maintain bone integrity.
Malnutrition is a major cause of bone loss in chronic liver disease patients and in patients following liver transplantation. Patients with liver disease have been shown to suffering from calcium malaborption. This may be due to malnutrition, vitamin D deficiency or the use of certain medications. It is recommended that liver transplant patients receive calcium supplements as a protective agent against bone loss. Calcium carbonate and calcium citrate are generally the supplements given to patients because they are well tolerated and absorbed.
While the benefits of treating liver transplant patients for vitamin D deficiency is still controversial, studies have demonstrated that treatment with vitamin D supplements has shown to improve bone density in alcohol-induced liver disease and osteoporosis patients. Thus, if liver transplant patients are shown to suffer from vitamin D deficiency, it may be recommended that their diet be supplemented with extra vitamin D.
Pharmacotherapies have also been shown to help reduce osteolysis due to bone disease from liver transplant. Studies have demonstrated that therapeutic doses of calcitriol can improve calcium absorption and stabilize bone mineral density. However, this drug has yet to demonstrate a benefit in reducing the incidence of bone fractures. Moreover, a low-dose of prednisone in combination with both calcium and vitamin D supplements has demonstrated an increased bone mineral density. Another medication, alendronate, combined with calcium and vitamin D almost completely prevented further bone loss in the first 4 months following liver transplantation.
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Rouillard S., Lane NE. Bone Loss in Liver Disease. Hepatic osteodystrophy. Hepatology. 2001;33.
eMedicineHealth - http://www.emedicinehealth.com/liver_transplant/article_em.htm
Merck manuals - http://www.merck.com/mmhe/sec05/ch060/ch060a.html