Abstract Objective To investigate the dose-dependent effects of neonatal-onset phosphate deficiency on bone growth and mineralization and assess whether supraphysiological vitamin D3 or calcitriol can rescue skeletal defects. Methods Newborn Sprague-Dawley rats were randomly assigned to seven diets: phosphate-free (0P), low phosphate (1/2P), normal phosphate (NP), calcium-free (0Ca), phosphate/vitamin D-free (0P/D), and 0P/D supplemented with either supraphysiological vitamin D3 (0P/D+D3) or calcitriol (0P/D+calcitriol). Longitudinal radiographic assessments were performed before euthanasia at 6 to 8 weeks. Serum analyses measured phosphate (sP), calcium (sCa), phosphotropic hormones, and bone turnover markers. Tibial growth plates were examined by hematoxylin and eosin (H vitamin D showed dual effects on bone turnover. Conclusions Phosphate sufficiency during the early postnatal period is critical for bone mineralization and growth in neonatal rats. Isolated calcium deficiency caused a distinct osteomalacic phenotype with preserved growth. Supraphysiological-dose vitamin D metabolites corrected hypophosphatemia but failed to rescue—and may have exacerbated—skeletal defects, cautioning against vitamin D monotherapy without concurrent phosphate supplementation.
Wang et al. (Wed,) studied this question.