Familial hypophosphatemic rickets is characterized by defective skeletal mineralization resulting in abnormal growth and development. The pathologic and radiologic correlates of this syndrome have been given some investigation, but the effect of this mineralization defect on bone mineral density has not been adequately assessed. We measured axial and appendicular bone mineral in 17 children (mean age 5.59 +/- 4.87) with familial hypophosphatemia at baseline and at 6-month intervals after initiation of therapy with vitamin D3 (calcitriol) and phosphate supplementation. Noninvasive quantitative techniques included single photon absorptiometry (SPA) of the radius, combined cortical thickness (CCT) of the second metacarpal, and quantitative computed tomography (QCT) of vertebral trabecular bone. Thoraco-lumbar and hand/wrist radiographs were qualitatively assessed for the prevalence and severity of osteosclerosis, rickets, and other parameters indicative of metabolic bone disease as well as skeletal age. Quantitative determinations of bone mineral by each technique were compared with normal values for age and sex, and individual standardized scores (z-scores) were calculated at each measurement interval. Standard scores were also calculated for bone age-adjusted mineral values. At baseline, spinal trabecular bone by QCT was not significantly different from normal values; however, measurements of peripheral cortical bone by either SPA or CCT were significantly lower than values for normal children of the same age and sex (P = 0.05 and P = 0.01, respectively). Following therapy with calcitriol and phosphate, peripheral bone mass was not shown to improve significantly when contiguous standard scores were compared even when values were adjusted for bone age.(ABSTRACT TRUNCATED AT 250 WORDS)