Original article
Evaluation of vitamin D status bone mineral density and dental health in children with cholestasis

https://doi.org/10.1016/j.clinre.2017.11.010Get rights and content

Summary

Background

Hepatic osteodystrophy caused by vitamin D and calcium malabsorption is thought to develop in children with cholestatic liver disease leading to secondary hyperparathyroidism and rickets or osteomalacia. The aim of this study was to evaluate the dental and bone mineral densities and the serum level of vitamin D in cholestatic infants and children and to correlate this process with clinical and laboratory parameters.

Methods

This is a cross-sectional study that include 50 patients presenting with cholestasis. Thirty age and sex matched controls recruited not complaining of liver disease. All cases were subjected to full history taking, clinical and dental examination, 25(OH)D level, ALT, AST, bilirubin, albumin, GGT, alkaline phosphatase, PT, INR, calcium, corrected calcium, phosphorus and DXA scan to those above 5 years old. Controls were subjected to measuring the serum levels of 25(OH)D, total bilirubin, direct bilirubin, ALT, GGT, AST, PT, INR, alkaline phosphatase, albumin, calcium and phosphorus.

Results

Out of the 50 cases; 23 were females (46%), with a mean age of 6.17 ± 3.9 years ranging from 1.1 to 17 years. Twenty-eight of the cases had signs of rickets (56%), 6 of them had bone fracture (12%) and 42.8% had milky teeth caries. The level of 25(OH) vitamin D was below normal range in around half of the patients. There was significant difference between cases and controls in calcium and phosphorus levels, ALT and alkaline phosphatase. Low bone mineral density (BMD) was present in 50% and 5 cases (17.9%) were diagnosed as having osteoporosis. There was a negative correlation between the Z-score, BMD of total body, BMD and bone mineral content (BMC) of spine and total and direct bilirubin. There was a positive correlation between (BMD of total body, spine and BMC of spine) and serum phosphorus, alkaline phosphatase and albumin. There was a positive correlation between the Z-score of total body and serum calcium.

Conclusion

Decreased level of 25-OH vitamin D is present in more than half of cholestatic patients, and is correlated positively to serum calcium. Decreased BMD was present in more than half of studied cholestatic patients correlated to the low serum calcium rather than the vitamin D level. The decreased BMD and the dental affection in cholestatic children is related to the level of hyperbilirubinemia.

Introduction

Cholestasis could be defined as a pathological condition of decreased bile formation or flow, in which normally excreted substances into bile are retained including conjugated bilirubin and bile salts which are the commonly measured substances [1].

Irrespective of causes, cholestasis, which is accompanied with hepatic insufficiency additionally, increases malnutrition (increased metabolism, anorexia, vomiting, diarrhea, impaired gastrointestinal absorption of lipids and vitamins A, D, E and K) [2].

Vitamin D which is necessary for bone metabolism is converted in the liver into 25-hydroxyvitamin D (25[OH] D) and then converted into 1, 25-dihydroxy vitamin D in the kidney in order to be metabolically active. So, liver and kidney play vital roles in vitamin D activation [3].

One of the most significant extrahepatic expression of chronic cholestatic liver disease is hepatic osteodystrophy and denotes the ending result of several mechanisms leading to bone fragility [4]. Hepatic osteodystrophy is caused by calcium and vitamin D malabsorption, producing secondary hyperparathyroidism and osteomalacia or rickets [5]. The etiopathogeny of hepatic osteodystrophy is not completely understood [6].

It has been indicated over years that the main bone disorder in chronic hepatic dysfunction is loss of bone mass. Some studies denoted the association of 25-hydroxyvitamin D deficiency and bone disorders in chronic cholestatic liver disease (CCLD) patients due to the significant role of the liver in vitamin D metabolism [7]. The development bone mass is impaired in cholestatic children even in the early stage of chronic cholestatic disease (CCD) [8].

Low bone mineral density, osteopenia and high incidence of fractures in children with cholestatic liver diseases have been denoted by previous finding [3]. The overall objectives of bone densitometry are to detect patients at highest risk of skeletal fragility fractures, to guide decisions concerning management, and to monitor responses to therapy. It is recommended to do skeletal assessments for children with frequent fractures, bony pain or deformities, or osteopenia on regular radiographs or to monitor treatment [9].

Dual-energy X-ray absorptiometry (DXA) has been recognized as a significant device for comprehensive skeletal assessment of children and teenagers but not yet of infants [10].

Studies revealed that a few months after liver transplantation for children with osteopaenia due to CCLD they showed an increase of bone loss; nevertheless, in the long-standing follow-up, these children present a significant increase in bone mineral density (BMD). These data denote the effect of cholestatic disorders on bone mass loss and the significance of normal hepatic function for bone mass gain in CCLD patients [11].

Opacity and hypoplasia of enamel and greenish brown hyperpigmentation of teeth caused by accumulation of biliverdin in dental tissues are odontogenic manifestations of cholestasis [2].

The development of the masticatory system, including odontogenesis is affected by systemic disorders caused by CLD leading to dental hypomineralization of the enamel [12].

In developing countries there is insufficient data regarding serum level of vitamin D and bone affection in cholestatic children and their correlation with laboratory parameters.

Section snippets

Aim of work

The aim of this study was to evaluate the dental and BMD and the serum level of vitamin D in cholestatic infants and children and to correlate this process with clinical laboratory parameters.

Patients and methods

This is a cross-sectional study that include 50 patients presenting with cholestasis. Patients were recruited from the hepatology outpatient clinic at Cairo University Pediatric Hospital and the National Hepatology and Tropical Medicine Research Institute (NHTMRI). The study also included 30 age- and sex-matched controls. The protocol was approved by the Faculty of Medicine Research Ethics Committee. Assent of the children and consent was obtained after proper orientation of the care givers

Results

Out of the 50 cholestatic cases; 23 were females (46%); the mean age of the cases was 6.17 ± 3.9 years SD ranging from 1.1 year to 17 years. Both cases and controls were age and sex matched.

Progressive familial intrahepatic cholestasis (PFIC) is the most frequent cause (40%) followed by biliary atresia operated upon by Kasai surgery unfortunately with unsuccessful one (12%). It is to be noted that we could not reach a definitive diagnosis in 12% of the studied cases.

Regarding bone and dental

Discussion

Deficiency of vitamin D is extremely predominant in children with CLD and its severity is inversely related to the levels of vitamin D [17].

In the current study the mean serum level of vitamin D was 37.9 ng/mL in cases and hypovitaminosis D was observed in 28 (56%) of cases [15 (30%) with deficient level and 13 (26%) with insufficient level]. Mohammadi et al. [18] found hypovitaminosis D in 64.5% in children with cholestatic liver diseases [10.4% with deficiency and 54.1% with insufficiency]

Conclusion

Decreased level of 25-OH vitamin D is present in more than half of cholestatic patients, and is correlated positively to serum calcium. Decreased BMD was correlated to the low serum calcium rather than the vitamin D level. The decreased BMD in cholestatic children is related to the level of hyperbilirubinemia.

Authors contribution

Shaimaa Emad El Abrak: contributed to the conception and design of the study, analysis and interpretation of data and drafting the article.

Hanaa H. EL Dash, Mona El Said EL Raziky: contributed to the conception and design of the study, analysis and interpretation of data and drafting and revising the article.

Nashwa M. Samra, Manal A. Elsheikh: contributed to the conception and design of the study, acquisition and interpretation of data and revising the article. All authors have approved the

Funding sources

This research did not receive any specific grant from any funding agencies in the public, commercial, or not-for-profit sectors.

Disclosure of interest

The authors declare that they have no competing interest.

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