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 < 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 < 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 < 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.