الفهرس 
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Abstract
Bone is composed of organic matrix and specific type of mineral which removed by bone cells. Bone cells classified into osteoblast which are the main synthetic cells of bone and derived from precursors in the stromal cell system and converted to osteocytes and osteoclasts which are derived from precursors in the hematopoietic system and responsible for bone resorption and osteocytes which derived from osteoblast and its function is unknown while bone matrix is composed of collagen, non collagen protein and proteoglycans.
Remodelling of bone is continuous all over the life in normal sequence of 4 steps, firstly activation of osteoclast by osteoblast cells, secondly bone resorption by osteoclast, thirdly reversal from bone resorption to formation and last step is the formation of new bone by osteoblast and mineralization.
Remodelling occurs normally in 10% of bone surface and regulated by circulating hormones and local factors.
The factors affecting the rate of remodelling include: calcium and phosphate balance, parathyroid hormone, vitamin D, calcitonin and other hormones like corticosteroid, thyroxin, growth hormone, sex hormone and gonadotropins. The role of locally acting cytokines like TNF, GF, interleukins, interferons and colony-stimulating factor are unknown.
The IGF-I and IGF-II are peptide hormones which synthesized in liver and other tissue are important for cellular proliferation, differentiation and specific function of many cells.
IGFs regulated by GH and nutrient and 99% of IGFs circulating in plasma in a complex with binding proteins called IGFBP (from 1-6) and at least 95% are bound to IGFBP-3.
The liver is the major source of IGFBP-1 and 3 and probably 2 so decrease of IGF-1 has suggested to be the early marker of liver dysfunction.
Low levels of IGF-1 correlate with histomorphic evidence of reduced bone formation while low levels of IGFBP-3 has been reported in osteoporotic men and women.
Systemic administration of low dose of IGF-1 increase markers of bone formation while higher dose increase markers of formation and resorption.
Complex metabolic changes in liver disease result in alterations in bone metabolism.
Osteoporosis is a systemic disease of the skeleton characterized by low bone mass and classified into primary osteoporosis including type I(post menopausal), type II(senile osteoporosis) and secondary osteoporosis due to disorders as nutrition, endocrine, metabolic, drugs and others.
Incidence of osteoporosis and fracturing varies widely with CLD depending on patient population, underlying liver disease and its severity.
Osteomalacia is characterized by impaired mineralization of bone matrix mostly due to vitamin D deficiency which accompanies symptomatic cholestatic liver disease. The CLD which affect metabolic bone diseases may be classified into:
1- Primary hepatocellular damage (autoimmune chronic hepatitis, chronic viral hepatitis B, and alcoholic liver disease).
2- Cholestatic disease (PBC and PSC).
The main bone abnormality in CLD is osteoporosis but osteomalecia is very rare.
The mechanism by which CLD affect osteoblast is unclear but may be due to GFs, toxic substances as copper, aluminium and iron and bilirubin may contribute.
Cholestatic CLD associated with osteoporosis more than other types of CLD. The additional risk factors for osteoporosis in CLD include:
Genetic, nutritional, hormonal and other factors like corticosteroids.
Chronic cholestasis and liver cirrhosis are well accepted risk factor for osteopenia and bone loss.
Leptin is a peptide hormone circulate in free and bound forms.
Its functions: firstly as satiety factor inhibiting food intake, a stimulator of energy expenditure, a signal to the reproductive system and finally as a factor in haematopoiesis.
Leptin affects bone metabolism via a central neuroendocrineal pathway and its high level in patients with liver cirrhosis is unknown.
Screening is done by measuring BMD using non invasive methods based on radiology as SPA and DXA.
Osteoporosis in CLD is observed mainly in trabecular bone, there for bone loss detected by BMD is prominent at femoral neck and at the lumbar spine.
Screening for osteopenia is indicated for all patients with:
- All patients with chronic cholestasis
- All patients with cirrhosis
- Precirrhotic patients with additional risk factors
- All potential liver transplant candidates.
The factors contribute to bone loss after transplantation include glucocorticoid therapy, vitamin D deficiency, secondary hyper parathyrodism, malnutrition, hypogonadisim, preexisting bone disease, cyclosporin and other immunosuppressive drugs.
Management of post transplantation osteoporosis depends on bone health prior to transplant and prophylaxis against bone loss following transplantation. Oral or parenteral vitamin D is given if blood test detect vitamin D deficiency. Hormone replacement therapy may be considered in cases of hypogonadism. Biphosphonate is effective in reducing bone loss in addition to some measures about life style. Prevention of post transplantation bone loss include modification of immunosuppressive regimen and administration of anti resorptive agent.