Endocrine Abstracts

JOINT3271

Background: Refractory rickets, though rare, significantly contributes to bone health-related morbidity in both children and adults. Non-invasive biochemical markers can offer insights into bone remodelling, but their use in children with resistant rickets remains largely unexplored.

Objective: To assess the bone metabolism in children with refractory rickets using bone turnover markers.

Methods: In this single-center, cross-sectional study, children (≤18 years) with refractory rickets were enrolled. Refractory rickets was defined as failure to achieve radiological healing after 12 weeks, despite a cumulative dose of 300,000 IU of vitamin D. Exclusions included nutritional rickets, chronic kidney disease, and use of glucocorticoids or anticonvulsants. Diagnosis was confirmed either biochemically or via clinical exome sequencing. Patients were categorized into hypophosphatemic rickets (HPR), vitamin D–dependent rickets (VDDR), and renal tubular acidosis (RTA). Rickets severity was assessed using the Rickets Severity Score (RSS). Non-compliance was defined as worsening of RSS with non-adherence to prescribed therapy for 3 months over past year. Age- and gender-matched normal controls were also included. Bone turnover markers, C-telopeptides of type I collagen (CTX, resorption) and procollagen I N-propeptide (P1NP, formation) were assessed early morning after overnight fasting.

Results: Thirty-nine children [53% female, 9.69 (4.39) years and 64% compliant] were included, with genetic confirmation in 29 (75%) cases (HPR: 62%, VDDR: 20%, RTA: 18%) along with 39 controls. Bone resorption marker CTX was 2077 pg/ml (1532–2886), and bone formation marker P1NP was 690 ng/ml (586–1080) in our patient cohort, with no significant intergroup differences [CTX: P = 0.289, P1NP: P = 0.465]. However, both markers were significantly higher in patients than controls [CTX: 1561 (1250–1860) pg/mL, P = 0.004; P1NP: 450 (400–484) ng/mL, P<0.001]. A significant positive correlation was found between serum CTX with P1NP (r=0.405, P = 0.016), and between CTX with RSS (r=0.400, P= 0.026). Notably, P1NP was significantly elevated in the compliant group as compared to the control group [753.1(293.7) versus 449.8 (57.7) ng/ml, P<0.001] while no significant difference was noted in CTX [1818.4 (610.2) versus 1542.8 (380.1) pg/ml, P = 0.09]. In contrast, both CTX and P1NP were significantly elevated in the non-compliant group compared to controls [CTX 3482.5 (1340.9) versus 1542.8 (380.1) pg/ml, P<0.001; P1NP 939.6 (359.3) versus 449.8 (57.7) ng/ml, P<0.001].

Conclusions: To conclude, children with refractory rickets exhibit higher bone turnover compared to controls. Treatment adherence disproportionately reduces bone degradation relative to bone formation. This can contribute to improved bone health on follow up.