Evaluation of new markers of bone metabolism in renal osteodystrophy in children

Serum intact parathormone (PTH 1.84) and osteocalcin levels were evaluated as early markers for secondary hyperparathyroidism in a group of pediatric patient treated with chronic hemodialysis. PTH 1.84 levels which were more closely related with alkaline phosphatase levels than PTH 53.84 levels, allowed to identify a group of children without biologic or roentgenographic evidence of hyperparathyroidism and with a normal residual hormone level. PTH 1.84 levels seem to be a reliable indicator of parathormone secretion than conventional assays and may be used as a routine test for monitoring children under chronic hemodialysis. Conversely, the plasma osteocalcin level measured by radioimmunoassay was increased in all studied patients regardless of parathyroid status and seemed to be of little value for monitoring renal osteodystrophia. Lumbar vertebral plate bone density studies disclosed abnormalities of bone mineralization in half the children with renal failure. Dialyzed or non dialyzed. Patients with decreased bone mineralization presented, in most of cases, a history of previous steroid treatment. A group of children with very severe renal failure had increased bone mineralization. The interpretation of this abnormality remains to be determined.     

Biochemical markers of bone turnover and their use

Although the clinician's ability to diagnose and monitor bone disease has improved in the past decade, there is still a need for more specific methods of assessing disturbances in bone metabolism. This article presents a review of biochemical bone markers and their practical applications in various disease states. Bone resorption and formation markers are considered to be useful in diagnosis and anticancer treatment of primary osseous tumours and metastatic bone diseases. However, better understanding of cellular and molecular events in the different phases of remodeling seems to be necessary to develop more adequate clinical diagnostic procedures and treatment for bone diseases.     

Peritoneal clearance of biochemical markers of bone turnover in children with end stage renal failure on peritoneal dialysis

Renal osteodystrophy is one of the important complications in children with end stage renal disease. Non-invasive tools for evaluation of bone metabolism have been proposed in recent years. The aim of this study was to investigate the markers of metabolic bone disease and peritoneal clearance of these markers in children treated with continuous ambulatory peritoneal dialysis (CAPD). In this study, serum osteocalcin (OC) levels were found significantly higher in patients (107.98 +/- 99.99 ng/ml) than in the healthy control group (41.94 +/- 12.94 ng/ml; p<0.05). Mean peritoneal clearance (Clp) of OC was 0.87 +/- 0.91 ml/min. There was no correlation between serum OC and Clp-osteocalcin. There was a positive correlation between serum phosphorus (P) and OC (r=0.394, p=0.031), alkaline phosphatase (ALP) and OC (r=0.520, p=0.003), and parathyroid hormone (PTH) and OC (r=0.441, p=0.017), whereas no correlation was found between OC and calcium (Ca) and OC and magnesium (Mg). There was also a significant correlation between serum ALP and PTH (r=0.714, p=0.0001). A positive correlation was found between serum PTH and Clp of PTH (r=0.471, p=0.009). In conclusion, Clp-osteocalcin is of no interest as a non-invasive marker of metabolic bone disease in children treated with CAPD. But significant correlation between serum OC and PTH, P, and ALP shows that serum OC could be used as a valuable non-invasive biochemical marker of metabolic bone disease.     

Microfocal radiography in the diagnosis of childhood renal osteodystrophy

Abstract Background: Renal osteodystrophy is common in children with chronic renal failure (CRF) and X-ray is an intensive method in the diagnosis of the disease. In this study we compared microfocal radiography with conventional method for the diagnosis of renal osteodystrophy.
Methods : The X-rays of left wrists of 21 children with CRF and chronic renal insufficiency were taken by conventional and microfocal methods.
Results : Both methods revealed osteopenia in all patients (100%), widening, fraying and cupping of ulnar and radial metaphysis in 10 (47.6%), osteosclerosis in three (14.2%) and pseudofracture in one (4.7%) patient. Microfocal radiography demonstrated osteosclerosis in one patient, pseudofracture in four and subperiosteal resorption in five patients that were not detected by conventional method.
Conclusion : Two methods were found to be significantly different in demonstrating the changes due to rickets and hyperparathyroidism and it is concluded that microfocal radiography may be preferred in the diagnosis of childhood renal osteodystrophy.     

Magnetic resonance imaging of renal osteodystrophy in children

Background. Improved life expectancy of children with chronic renal failure (CRF) has increased the number of patients with renal osteodystrophy and has brought to light novel and severe forms of the disease. These factors have contributed to the need to evaluate new, noninvasive imaging modalities for the detection of bone involvement. Objectives. To evaluate the potential of MRI in the detection of the bone changes of renal osteodystrophy as compared to conventional X-rays. Materials and methods. Fourteen children with CRF were examined with a 0.5-T MR unit using TI-weighted and STIR sequences and conventional radiographs. The following features were reviewed in a nonblinded study: skeletal deformities, thickening of cortical bone, trabecular pattern, intraosseous soft-tissue masses, osteonecrosis, extraskeletal calcifications and bone marrow signal changes. Results. MRI adequately demonstrated skeletal deformities, cortical thickening and irregular trabecular pattern. It showed osteonecrosis and intraosseous soft-tissue masses more conspicuously than X-ray. In addition, it revealed diffuse nonspecific signal changes in the bone marrow. Conclusion. MRI is a potentially useful tool for evaluating the bone changes of renal osteodystrophy. Received: 28 February 1997 Accepted: 23 June 1997     

Correlation among markers of renal osteodystrophy in pediatric hemodialysis patients

Serum levels of parathyroid hormone (PTH), alkaline phosphatase (AP), and calcium (Ca2+) have been used to evaluate renal osteodystrophy (RO) in adult patients undergoing dialysis. Osteocalcin (BGP) is a bone protein which also serves as a marker for bone turnover. Serum BGP levels correlate positively with rates of bone turnover and serum concentrations of PTH, AP, and Ca2+ in various studies of adult end-stage renal disease (ESRD) patients, whereas other studies reveal BGP to be a poor indicator of bone turnover in ESRD. RO is a significant problem in pediatric ESRD patients; however, there have been few studies evaluating the correlation of markers for RO in children with ESRD. We measured serum PTH, AP, Ca2+, and BGP levels in a group (n=23) of pediatric patients with ESRD and assessed the correlation among the markers. There was a positive correlation between serum PTH and AP (r=0.658, p<0.001). In contrast, there was no correlation between either serum Ca2+ or BGP, and either PTH or AP. The correlation between Ca2+, BGP and either PTH or AP was unaffected by growth in our patient population. Finally, neither age nor pubertal stage improved the correlation between either Ca2+ or BGP, and either PTH or AP. We conclude that serum PTH and AP are useful markers for RO, whereas calcium and BGP levels should not be used to evaluate RO in pediatric ESRD patients.     

Biochemical markers of bone metabolism: application to understanding bone remodeling in children and adolescents

Markers of bone remodeling have been developed that provide biochemical indices that reflect changes in the rates of bone formation, resorption, and mineralization. These processes are important determinants of bone metabolism, and indicators that correspond to these processes can provide clinically relevant information. Until recently, the best way to measure parameters of bone metabolism was to perform a bone biopsy after administration of two courses of tetracycline. Bone markers offer significant potential advantages over bone biopsy. Some of these markers are protein fragments that are generated during metabolism of type I collagen, the major structural protein of bone, and are formed as this collagen is synthesized or degraded. Other markers, such as osteocalcin and alkaline phosphatase, are released from osteoblasts during bone formation. Although these markers have found significant utility in the evaluation of adults with metabolic bone diseases, their application in children has been limited due to great variability in normal ranges that reflect the changes in skeletal metabolism induced by age, growth rate, gender, and pubertal state.     

Assessment of bone mineral density and markers of bone turnover in children under long-term oral anticoagulant therapy

Oral anticoagulants antagonize vitamin K action and potentially impair the carboxylation of osteocalcin, a protein essential for normal bone matrix formation. In the present study, bone mineral density (BMD) and bone turnover markers were evaluated in 23 children under long-term oral anticoagulant therapy. BMD of the lumbar spine was assessed (Dual Energy x-ray Absorptiometry) and reported as z score. Osteoblast [bone alkaline phosphatase, osteocalcin (Gla-Oc), amino-terminal procollagen 1 extension peptide] and osteoclast (urinary calcium and deoxypyridinoline, serum cross-linked C telopeptide) activity markers were measured. Vitamin D {[25(OH) D], parathormone, calcium, phosphorus, magnesium} and vitamin K status [factors II, VII, IX, X, protein C, protein S, undercarboxylated osteocalcin (Glu-Oc)] were determined. The above parameters were also evaluated in 25 healthy controls. Patients presented with higher levels in Glu-Oc, parathormone, and bone resorption markers, lower levels in bone formation markers and 25(OH) D, whereas 52% of them showed signs of osteopenia (-1>BMD z score>-2.5). Statistical analysis demonstrated that anticoagulant therapy was an independent predictor of alterations in Glu-Oc, Gla-Oc, bone alkaline phosphatase, amino-terminal procollagen 1 extension peptide, and serum cross-linked C telopeptide levels. It seems that long-term use of coumarin derivatives may cause osteopenia in children with the risk of developing osteoporosis later in life.     

Measurements of bone turnover markers in premature infants

We determined the levels of circulating bone turnover markers in preterm infants during the first weeks of life. Twenty premature infants (mean gestational age 27+/-2.2 weeks, mean birth weight 894+/-231 g) hospitalized in the neonatal intensive care unit (NICU) at the Meir General Hospital, Israel, participated in the study. Measurements of bone turnover markers were performed at birth, and every week thereafter for an average follow-up of 11.2+/-0.7 weeks. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of serum levels of the carboxy-terminal cross-links telopeptide of type I collagen (ICTP). All three markers of osteoblastic activity increased markedly and significantly during the first three weeks of life, and then continued to increase gradually until week 10 (p<0.01). Circulating ICTP levels increased in the first week of life and then decreased gradually throughout the follow-up (p<0.01). The study participants were divided into premature infants born at extremely low birth weight (ELBW: <1000 g, n=12) and very low birth weight (VLBW: 1000-1250 g, n=8). Osteocalcin (in weeks 2-5 of life), PICP (weeks 3-5), and ICTP levels (weeks 2-3) were significantly higher in VLBW preterms. These results suggest increased bone formation in premature infants in the first three months of life. The increased bone turnover in VLBW compared to ELBW premature infants may be the result of a generally higher morbidity in ELBW preterm infants in early stages of life.     

慢性肾衰竭患儿肾性骨病及贫血的治疗

1肾性骨营养不良肾性骨营养不良(renalosteodystrophy,ROD,简称肾性骨病)是由于肾功能衰竭时钙、磷、甲状旁腺激素(PTH)和维生素D的代谢异常而导致的一系列临床表现。儿童时期的ROD早期表现不特异且常被忽略,可表现为:(1)生长迟缓,虽然与甲状旁腺功能亢进(HPT)有关,但单纯纠正HPT并不能纠正生长迟缓;(2)骨痛,常发生于低转化性骨病者,易发生骨折或骨骺脱位,特别是骨软化症;(3)骨骼变形,4岁以下患儿类似于维生素D缺乏性佝偻病的表现。ROD总的治疗原则为应在早期即开始治疗,控制血磷、纠正低钙、给予维生素D以及预防和治疗HPT,尽可能…     

Biochemical bone markers in the assessment and pamidronate treatment of children and adolescents with osteogenesis imperfecta

Aim: To assess the role of biochemical bone markers in classification of children with osteogenesis imperfecta (OI), their possible association with vertebral compression fractures in milder forms of OI and their role in monitoring of intravenous pamidronate (APD) treatment. Methods: Serum total alkaline phosphatase (ALP), bone ALP isoforms (in a subgroup), osteocalcin, type I procollagen carboxy‐terminal propeptide, carboxy‐terminal telopeptide of type I collagen, and urine deoxypyridinoline (DPD) were measured in a cross‐sectional study of 130 untreated individuals, 0.25–20.9 years (median 6.7), with OI types I, III and IV. Of those, sixty‐nine were also assessed longitudinally during monthly APD treatment. Bone mineral density (BMD) was measured by dual‐energy X‐ray absorptiometry. Results: Significant differences in bone markers, however not sufficient for individual clinical use, were found in the larger untreated group but not between subgroups with or without vertebral compressions. All bone markers decreased during treatment for 1.0–12.5 years, but with different relative amounts. Changes were not correlated to the improvement in BMD, mobility or pain. Conclusion: Bone markers are, despite significant differences, not useful for the classification of OI type in the individual child and are not associated with vertebral compressions. Serum ALP and urinary DPD are sensitive in monitoring bisphosphonate treatment.     

短期吸入小剂量糖皮质激素对哮喘患儿骨转换指标影响的研究

目的研究短期吸入小剂量糖皮质激素对哮喘儿童骨转换指标的影响。方法对８例无激素治疗史哮喘儿童持续吸入二丙酸倍氯米松（ＢＤＰ）２００～３００μｇ／ｄ,疗程１～２个月。疗程开始与结束时分别检测血清钙、磷、碱性磷酸酶、骨钙素及尿羟脯氨酸／肌酐比值。结果吸入ＢＤＰ１～２个月后患儿血清骨钙素水平下降了２０５６％,Ｐ＜００５,而血钙、磷、碱性磷酸酶水平和尿羟脯氨酸／肌酐比值无明显改变。结论短期内吸入ＢＤＰ２００～３００μｇ／ｄ有可能发生骨生成抑制。有必要对血清骨钙素水平进行长期动态观察     

Biochemical markers of bone turnover,intact serum parathyroid hormone and renal calcium excretion in patients with pseudohypoparathyroidism and hypoparathyroidism before and during vitamin D treatment

In addition to the well-documented hyporesponsiveness of the kidney, resistance to parathyroid hormone (PTH) has been postulated for bone in pseudohypoparathyroidism type I (PHP). In some of these patients reduced bone density and even frank osteitis fibrosa suggest osteoclastic overactivity. To address the possibility that the skeletal system of patients with PHP may be affected by their increased PTH secretion we measured intact serum PTH and three biochemical markers of bone turnover in a large number of patients with PHP (n=20). The results were compared with subjects with low (hypoparathyroidism, HP, n=29), normal (controls, n=31) and high (primary hyperparathyroidism, 1°HPT, n=13) PTH secretion. Both markers of osteoblastic bone formation, alkaline phosphatase activity and osteocalcin concentration in serum, and one index of osteoclastic bone degradation, the urinary hydroxyproline/creatinine ratio (OH-P/Cr), were decreased in HP and increased in 1°HPT, whereas only OH-P/Cr was elevated in patients with PHP. Although intact serum PTH was significantly more increased in PHP than in 1°HPT, the markers of bone turnover were not significantly different in these two groups, suggesting some bone resistance in the patients with PHP. In these subjects intact serum PTH was elevated even at normocalcaemia during vitamin D treatment with a negative correlation with the respective serum calcium concentration (r=–0.69, P<0.001), indicating an elevated set-point for the suppression of their parathyroid glands. OH-P/Cr was negatively related to serum calcium in PHP, it normalized in most patients during normocalcaemia induced by vitamin D treatment. The urinary calcium excretion remained normal in the patients with PHP but was markedly elevated in patients with HP after the serum calcium levels had normalized during vitamin D therapy. In conclusion, the present and other studies suggest that the resistance to PTH in patients with PHP is mainly limited to the proximal kidney tubule and that the tendency to increased bone degradation implies either some response of the remodelling bone system to PTH or the result of marked secondary hyperparathyroidism overcoming a partial resistance of bone cells. The aim of vitamin D treatment in patients with PHP should therefore be an elevation of the serum calcium concentration into the high normal-range in order to suppress PTH secretion and thus bone degradation. In these patients the parathyroid glands are less sensitive to circulating calcium levels.Abbreviations AHO Albright's hereditary osteodystrophy - AMP adenosine monophosphate - AP alkaline phosphatase activity - Ca calcium - Ca/Cr urinary calcium/creatinine ratio - Cr creatinine - HP hypoparathyroidism - 1°HPT primary hyperparathyroidism - OH-P/Cr urinary hydroxyproline/creatinine ratio - PHP pseudohypoparathyroidism - PTH parathyroid hormone - SDS standard deviation score     

新生儿骨转换生化标志物的研究进展

骨代谢是骨形成和骨吸收的动态平衡过程,骨代谢过程中产生的一些代谢产物,叫做骨转换生化标志物.包括骨形成生化标志物和骨吸收生化标志物.骨形成生化标志物代表成骨细胞活动及骨形成时的代谢产物,骨吸收生化标志物代表破骨细胞活动及骨吸收时的代谢产物.现就新生儿骨转换生化标志物的研究进行综述.     

Spectrum of renal osteodystrophy in children on continuous ambulatory peritoneal dialysis

BACKGROUND: The prevalence of different types of bone disease in chronic renal failure (CRF) has changed significantly during the last decade. The aim of the present study is to evaluate the spectrum of bone disease in children with CRF undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Seventeen children with CRF on CAPD aged 7-20 years were evaluated. All patients had received regular vitamin D and calcium carbonate therapy during the 6 months preceding the bone biopsy. Serum calcium, phosphate, alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) levels were measured and hand X-rays were performed. Transiliac bone biopsies were analyzed for histologic diagnosis. RESULTS: High turnover renal osteodystrophy (ROD) was the most common bone disease, present in eight patients (47%). Five patients (29%) had low turnover bone disease, and four (24%) had mixed ROD. The mean age of the high turnover ROD group was higher than that of the low turnover group (14 +/- 3 vs. 11 +/- 3 years, P < 0.05). Seven of the nine patients who had tubulo-interstitial nephritis were found to have high turnover bone disease. In contrast, none of the patients with glomerulonephritis exhibited high turnover bone lesions. Mean serum calcium levels were found to be significantly higher in the low turnover group compared with the patients with high turnover bone disease (P < 0.001). A serum iPTH level > 200 pg/mL was 100% sensitive and 66% specific in identifying patients with high turnover ROD. CONCLUSION: The spectrum of bone disease of the children with CRF undergoing CAPD seems to depend on the rate of CRF and primary disease. The risk of developing overt hyperparathyroid bone disease is high in children with slowly progressing forms of renal pathology and especially in those with tubulo-interstitial disease. In contrast, children with glomerular diseases who had a more rapidly progressive course may have a lesser risk of developing high turnover bone disease. The results of the present study indicate that even routinely prescribed regular vitamin D therapy early in the course of disease may lead to low turnover bone lesion in small children who have CRF due to rapidly progressive forms of renal pathology.