Aetiology of nutritional rickets in rural Bangladeshi children

Abstract

Objectives: A high prevalence of rickets of unknown aetiology has been reported in Chakaria, Bangladesh. Classically, rickets is caused by vitamin D deficiency but increasing evidence from Africa and Asia points towards other nutritional deficiencies or excessive exposure to some metals. The aim of this study was to investigate the aetiology of rickets in rural Bangladeshi children.

Methods: 64 cases with rickets-like deformities were recruited at first presentation together with age-sex-village matched controls. Data and sample acquisition included anthropometry, radiographs, fasted plasma and urinary samples, 24 h weighed dietary intake together with a 24 h urine collection, and ¹³C-breath tests to detect Helicobacter (H.) pylori infection.

Results: One child had active rickets and frank hypovitaminosis D (F, n = 1) and one had deformities with radiological features of Blount disease (M, n = 1). The remaining cases were grouped into those with active rickets, defined as a radiographic Thacher score ≥1.5 (Group A, n = 24, 12M, 12F) and rickets-like bone deformities but not active rickets (Group B, n = 38, 28M, 10F). All children had a low dietary calcium intake, but this was lower in Group A than their controls (mean (SD): 156 (80) versus 323 (249) mg/day, p = 0.005). Plasma 25-hydroxyvitamin D (25OHD) was lower in Group A compared to controls; 63% of Group A and 8% of controls had a concentration <25 nmol/L (p ≤ 0.0001). There was, however, no evidence of differences in skin sunshine exposure. Group A had lower plasma calcium and phosphate and higher 1,25-dihydroxyvitamin D (1,25(OH)₂D) and parathyroid hormone (PTH). 88% of Group A and 0% of controls had undetectable plasma intact fibroblast growth factor (iFGF23), with c-terminal FGF23 (cFGF23) concentrations in the normal range. Urinary phosphate and daily outputs of environmental metals relative to creatinine were higher and tubular maximal phosphate reabsorption per unit glomerular filtration rate (TmP/GFR) was lower in Group A compared to controls. Although less pronounced than Group A, Group B had higher alkaline phosphatase, 1,25(OH)₂D and PTH concentrations than controls but similar calcium intake, TmP/GFR, iFGF23 and cFGF23 concentrations. Mean 25OHD concentrations were also similar to controls and there was no significant difference in the percentage <25 nmol/L (Group B: 13%, controls: 5%, p = 0.2) No group differences were seen in prevalence of anaemia, iron deficiency or H. pylori infection.

Conclusion: Nutritional rickets in this region is likely to be predominantly due to low calcium intake in the context of poor vitamin D status and exposure to environmental metals, but not H. pylori infection, anaemia or iron deficiency.

Keywords: Bangladesh; Calcium; Fibroblast growth factor 23; Phosphate; Rickets; Vitamin D.