Etiological Spectrum, Clinical Characteristics, and Six-Month Treatment Outcomes of Refractory Rickets in Children: A...

Refractory rickets comprises a heterogeneous group of inherited and acquired disorders characterized by persistent clinical, biochemical, and radiological evidence of rickets despite adequate vitamin D and calcium therapy. Owing to limited data from Eastern India, this study aimed to characterize the etiological spectrum of refractory rickets, compare the clinical, biochemical, and radiological characteristics across different etiologies, and evaluate treatment outcomes following six months of etiology-specific therapy.

This hospital-based prospective observational cohort study included 32 consecutive children with refractory rickets attending a tertiary pediatric endocrine centre in Eastern India. Demographic, clinical, biochemical, radiological, and genetic data (where available) were collected. Children were classified into distal renal tubular acidosis (DRTA), proximal renal tubular acidosis (PRTA), hypophosphatemic rickets (HPR), and vitamin D-dependent rickets (VDDR). All participants received etiology-specific treatment and were followed for six months. Treatment outcomes included radiological healing, biochemical response, and height gain.

DRTA was the commonest etiology (43.8%), followed by HPR (28.1%), VDDR (18.8%), and PRTA (9.4%). Short stature was universal, while failure to thrive (75.0%), delayed motor development (78.1%), and skeletal deformities (93.8%) were common across all groups. Metabolic acidosis was confined to DRTA and PRTA, hyperparathyroidism predominated in VDDR, and reduced tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR) was significantly associated with HPR and PRTA (all p<0.001). Radiological healing was achieved in all children after six months; however, complete biochemical healing occurred in only 18.8%, while 46.9% had persistent biochemical abnormalities. Median height gain was greatest in DRTA (2.7 cm). Baseline serum alkaline phosphatase (ALP) correlated with six-month ALP (ρ=0.776, p<0.001), and baseline parathyroid hormone independently predicted biochemical response (β=1.276, R²=0.412, p<0.05).

DRTA was the predominant cause of refractory rickets in this cohort. Although clinical manifestations overlapped, characteristic biochemical abnormalities enabled accurate etiological differentiation. Etiology-specific therapy resulted in universal radiological healing but variable biochemical recovery, highlighting the importance of early diagnosis and individualized management.