Longitudinal evaluation of hepatic osteodystrophy in children and adolescents with chronic cholestatic liver disease

Taveira, A. T. A.; Pereira, Fernanda Aparecida Castro; Fernandes, Maria Inez Machado; Sawamura, Regina; Nogueira-Barbosa, Marcello Henrique; Paula, Francisco José Albuquerque de

doi:10.1590/s0100-879x2010007500118

Cited by 8 publications

(8 citation statements)

References 37 publications

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“…In a previous cross-sectional study, we demonstrated that children with congenital cholestasis had low bone mass 10. In another longitudinal study, we documented impairment of bone mass acquisition 11. In these studies, the serum levels of PTH and 25-hydroxyvitamin D were normal, whereas decreased IGF-I was an early biochemical change in cholestasis 10, 11.…”

Section: Discussionmentioning

confidence: 78%

“…In another longitudinal study, we documented impairment of bone mass acquisition 11. In these studies, the serum levels of PTH and 25-hydroxyvitamin D were normal, whereas decreased IGF-I was an early biochemical change in cholestasis 10, 11. Bone loss was an early event in hepatic cholestasis, as 85% of the children were classified as Child-Pugh A and the other 15% were classified as Child-Pugh B.…”

Section: Discussionmentioning

confidence: 91%

“…Bone loss was an early event in hepatic cholestasis, as 85% of the children were classified as Child-Pugh A and the other 15% were classified as Child-Pugh B. After 3 years, more consistent incremental increases in the serum levels of osteocalcin were observed in the control group (76%) than in children with cholestasis (31%) 11. Moreover, Klein et al (2002) reported decreased serum levels of osteocalcin and type I collagen telopeptide (ICTP) in children showing advanced cholestatic liver disease 6.…”

Section: Discussionmentioning

confidence: 97%

“…Cross-sectional 10 and longitudinal 11 clinical studies have shown that cholestasis impairs bone mass development in children and adolescents with non-severe cholestatic disease. In these studies, the serum levels of endocrine IGF-I were reduced.…”

Section: Introductionmentioning

confidence: 99%

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Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

Spirlandeli¹,

Dick-de-Paula²,

Zamarioli³

et al. 2017

Clinics

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OBJECTIVES:The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated.METHODS:The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression.RESULTS:CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice.CONCLUSION:Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

Spirlandeli¹,

Dick-de-Paula²,

Zamarioli³

et al. 2017

Clinics

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“…Multiple factors contribute to bone loss in CCLD and all can be easily recognized at the end stage of chronic liver disease (malnutrition, hypogonadism, vitamin D deficiency, insulin-like growth factor-I (IGF-I) deficiency, and cholestasis) (2). However, decreased production of endocrine IGF-I by the liver (3,4), as well as paracrine/autocrine IGF-I expression in the bone microenvironment (5), has been shown to be an early crucial determinant of bone impairment in CCLD.…”

Section: Introductionmentioning

confidence: 99%

Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

Pereira

Mattar

Facincani

et al. 2012

Braz J Med Biol Res

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Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

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Reduced Serum IGF-1 Associated With Hepatic Osteodystrophy Is a Main Determinant of Low Cortical but Not Trabecular Bone Mass

Liu

Han

Werner

et al. 2017

Journal of Bone and Mineral Research

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Hepatic osteodystrophy is multifactorial in its pathogenesis. Numerous studies have shown that impairments of the hepatic growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) are common in patients with non-alcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and chronic cholestatic liver disease. Moreover, these conditions are also associated with low bone mineral density (BMD) and greater fracture risk, particularly in cortical bone sites. Hence, we addressed whether disruptions in the GH/IGF-1 axis were causally related to the low bone mass in states of chronic liver disease using a mouse model of liver-specific GH-receptor (GHR) gene deletion (Li-GHRKO). These mice exhibit chronic hepatic steatosis, local inflammation, and reduced BMD. We then employed a crossing strategy to restore liver production of IGF-1 via hepatic IGF-1 transgene (HIT). The resultant Li-GHRKO-HIT mouse model allowed us to dissect the roles of liver-derived IGF-1 in the pathogenesis of osteodystrophy during liver disease. We found that hepatic IGF-1 restored cortical bone acquisition, microarchitecture, and mechanical properties during growth in Li-GHRKO-HIT mice, which was maintained during aging. However, trabecular bone volume was not restored in the Li-GHRKO-HIT mice. We found increased bone resorption indices in vivo as well as increased basal reactive oxygen species and increased mitochondrial stress in osteoblast cultures from Li-GHRKO and the Li-GHRKO-HIT compared with control mice. Changes in systemic markers such as inflammatory cytokines, osteoprotegerin, osteopontin, parathyroid hormone, osteocalcin, or carboxy-terminal collagen cross-links could not fully account for the diminished trabecular bone in the Li-GHRKO-HIT mice. Thus, the reduced serum IGF-1 associated with hepatic osteodystrophy is a main determinant of low cortical but not trabecular bone mass.

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Longitudinal evaluation of hepatic osteodystrophy in children and adolescents with chronic cholestatic liver disease

Cited by 8 publications

References 37 publications

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

Reduced Serum IGF-1 Associated With Hepatic Osteodystrophy Is a Main Determinant of Low Cortical but Not Trabecular Bone Mass

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