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Evidence for bone remodeling but lack of calcium mobilization response to parathyroid hormone in pseudohypoparathyroidism.

Twenty-eight patients with hypoparathyroidism were classified into PTH-deficient (HP; n = 14) or PTH-resistant [pseudohypoparathyroid (PHP); n = 14] groups on the basis of serum PTH level and urinary cAMP response to PTH infusion. Bone density (BD; bone mineral content/bone width) was determined by 125I photon absorptiometry in the distal third of the radius of each patient. After 3 days of equilibration on a constant diet, fasting serum Ca, 1,25-dihydroxyvitamin D [1,25-(OH)2D] and 24-h urinary hydroxyproline (OHP) were measured during 4 control days and 4 treatment days [Lilly Parathyroid Extract (PTE); 100 U, im, every 6 h]. In HP, the mean BD was 0.772 +/- 0.016 (+/- SE) g/cm2, which was similar to the value obtained in a normal control group matched for age, sex, and race. In PHP, the mean BD was 0.633 +/- 0.017 g/cm2, which was 15 +/- 2% less than the normal value (P less than 0.005). Diminished BD was present in all patients with PHP, even in the absence of radiographic changes. Mean basal OHP excretion in PHP was more than twice that in HP (34.9 +/- 5.5 vs. 13.8 +/- 1.3 mg/day; P less than 0.005). Both groups had significant and comparable increases in urinary OHP excretion in response to PTE (9.1 +/- 2.1 mg/day for HP; 8.1 +/- 2.2 mg/day for PHP; P less than 0.005 for each). However, unlike the patients with HP, those with PHP did not have increases in serum 1,25-(OH)2D or a normal calcemic response to PTE. Thus, the bone-remodeling response to PTH remains intact in the majority of patients with PHP, but the mineral mobilization response, which may require 1,25-(OH)2D, is defective.