Emilia M D Soeiro1,2,3, Lucimary Castro4, Rejane Menezes4, Rosilene M Elias1, Luciene M Dos Reis1, Vanda Jorgetti1, Rosa M A Moysés5,6. 1. Laboratório de Investigação Médica 16, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. 2. Faculdade Pernambucana de Saúde, Recife, Brazil. 3. Instituto de Medicina Integral de Pernambuco, Recife, Brazil. 4. Hospital Pequeno Príncipe, Curitiba, Brazil. 5. Laboratório de Investigação Médica 16, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. rosa.moyses@uol.com.br. 6. LIM 16-Nephrology Department, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, 3° andar, sala 3342, São Paulo, SP, 01246-903, Brazil. rosa.moyses@uol.com.br.
Abstract
BACKGROUND: Studies investigating bone histology in children with chronic kidney disease (CKD) are scarce. METHODS: Forty-two patients, mean age 11.3 ± 4.3 years with stage 5 CKD on dialysis, underwent double tetracycline labeling bone biopsy and the relationship between clinical features, biochemical markers, and bone densitometry (DXA) was investigated. RESULTS: Low bone turnover was present in 59% of patients, abnormal mineralization in 29%, and low bone volume in 7%. Higher bone formation rate was found in non-Caucasian patients, whereas abnormal mineralization occurred in older and shorter children. We found no impact of gender and etiology of renal disease in our population. Parathormone (PTH) and alkaline phosphatase (AP) showed positive associations with bone turnover. ROC curve analysis showed a fair performance of biomarkers to predict TMV status. PTH < 2 times ULN independently associated with low bone turnover (RR 5.62, 95% CI 1.01-31.24; p = 0.049), in a model adjusted for race, calcitriol dosage, and calcium. It was also associated with abnormal mineralization (RR 1.35, 95% CI 1.04-1.75; p = 0.025), in a model adjusted for BMD scores, AP, age, and calcitriol. PTH and AP significantly predicted turnover and mineralization defect, although with low specificity and sensitivity, reaching a maximum value of 64% and 67%, respectively. CONCLUSIONS: While PTH and AP were associated with turnover and mineralization, we recognize the limitation of their performance to clearly distinguish high from low/normal bone turnover and normal from abnormal mineralization. Our results reinforce the need to expand knowledge about renal osteodystrophy in pediatric population through prospective bone biopsy studies. Graphical abstract.
BACKGROUND: Studies investigating bone histology in children with chronic kidney disease (CKD) are scarce. METHODS: Forty-two patients, mean age 11.3 ± 4.3 years with stage 5 CKD on dialysis, underwent double tetracycline labeling bone biopsy and the relationship between clinical features, biochemical markers, and bone densitometry (DXA) was investigated. RESULTS:Low bone turnover was present in 59% of patients, abnormal mineralization in 29%, and low bone volume in 7%. Higher bone formation rate was found in non-Caucasian patients, whereas abnormal mineralization occurred in older and shorter children. We found no impact of gender and etiology of renal disease in our population. Parathormone (PTH) and alkaline phosphatase (AP) showed positive associations with bone turnover. ROC curve analysis showed a fair performance of biomarkers to predict TMV status. PTH < 2 times ULN independently associated with low bone turnover (RR 5.62, 95% CI 1.01-31.24; p = 0.049), in a model adjusted for race, calcitriol dosage, and calcium. It was also associated with abnormal mineralization (RR 1.35, 95% CI 1.04-1.75; p = 0.025), in a model adjusted for BMD scores, AP, age, and calcitriol. PTH and AP significantly predicted turnover and mineralization defect, although with low specificity and sensitivity, reaching a maximum value of 64% and 67%, respectively. CONCLUSIONS: While PTH and AP were associated with turnover and mineralization, we recognize the limitation of their performance to clearly distinguish high from low/normal bone turnover and normal from abnormal mineralization. Our results reinforce the need to expand knowledge about renal osteodystrophy in pediatric population through prospective bone biopsy studies. Graphical abstract.
Entities:
Keywords:
Bone biopsy; Bone diseases; Children; Chronic kidney disease; Histomorphometry; Metabolic; Renal osteodystrophy
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