Skeletal responsiveness to parathyroid hormone in pseudohypoparathyroidism

Abstract

Background: Although there have been some case reports suggesting that bone in patients with pseudohypoparathyroidism (PHP) might respond to parathyroid hormone (PTH), no information is available as to whether serum PTH concentration is related to bone metabolic markers or to bone mineral density (BMD) in PHP. Objective: To address these relationships, by comparing intact serum PTH, bone metabolic markers and BMD in patients with PHP with those in patients with idiopathic hypoparathyroidism (IHP) and postoperative hypoparathyroidism (OHP). Methods: Intact serum PTH, bone metabolic markers (osteocalcin, tartrate-resistant acid phosphatase, pyridinoline, deoxypyridinoline) and BMD by dual-energy X-ray absorptiometry or single-photon absorptiometry were measured in patients with PHP Ia n 2 and PHP Ib n 8X The results were compared with those in patients with IHP n 5 and OHP n 14X Results: All bone metabolic markers measured were present in significantly greater amounts in patients with PHP Ib than in those with IHP+OHP. The Z score (standard deviation of average BMD at each age) of the BMD of femoral neck was significantly lower in patients with PHP Ib than in those with IHP+OHP. The Z scores of BMD of lumbar spine and radius were also lower in patients with PHP Ib than in those with IHP+OHP, but the difference was not significant. Moreover, the intact serum PTH concentrations were significantly and positively related to bone metabolic marker levels in all patients, and the intact serum PTH concentrations were significantly and negatively related to BMD of lumbar spine in PHP patients. Conclusions: These results suggest that PTH stimulates bone turnover in PHP Ib patients, resulting in a relatively lower BMD in PHP Ib patients than in IHP+OHP patients. The present study indicates that bones of most cases of PHP could respond to PTH.

A paternally inherited non‐sense variant c.424G>T (p.G142*) in the first exon of XLαs in an adult patient with hypophosphatemia and osteopetrosis

“…On the contrary, idiopathic hypoparathyroidism (IHP) cases often have reduced bone turnover and increased BMD, mainly at the trabecular, than the general population . Compared with IHP and non‐surgical hypoparathyroidism patients, PHP subjects, especially pseudohypoparathyroidism type 1b (PHP1B), tend to have lower BMD, indicating incomplete skeletal resistance to PTH may exist . However, when compared with normal controls, patients with PHP1A showed a significantly greater total body BMD .…”

Bone Mineral Density and Its Serial Changes Are Associated With PTH Levels in Pseudohypoparathyroidism Type 1B Patients

“…Specifically, one study reported that PHP1B patients had normal BMDs, whereas the other reported the BMD of the PHP1B patients in their cohort was lower than normal . Notably, both studies found evidence of bone remodeling in PHP1B patients . In addition, no longitudinal data are available from previous serial studies.…”

“…Two series studies have been conducted in PHP patients; however, these studies had small sample sizes ( n = 10 and 14) and yielded inconsistent results. Specifically, one study reported that PHP1B patients had normal BMDs, whereas the other reported the BMD of the PHP1B patients in their cohort was lower than normal . Notably, both studies found evidence of bone remodeling in PHP1B patients .…”

“…Therefore, the available data are too limited to draw definitive conclusions about whether bone tissue in these patients is responsive to PTH. Low BMDs and high levels of bone turnover markers (osteocalcin, tartrate‐resistant acid phosphatase, pyridinoline, and deoxypyridinoline) were observed in some cases; a few cases also had osteitis fibrosa . One case report by Tollin and colleagues found that, although urine N‐telopeptide type I collagen (NTX) cross‐links were elevated in PHP1B patients, the LS, femoral neck (FN), and distal radius BMDs were in the normal range before supplementing with calcium and/or vitamin D .…”

Pseudohypoparathyroidism and Graves'disease: a rare combination of two endocrinological diseases

“…Kanatani et al mentioned similar results in March 2001: significantly greater amounts of bone metabolic markers in patients with PHP Ib than, for example, in those with idiopathic hypoparathyroidism and postoperative hypoparathyroidism. The patients with PHP Ib develop skeletal disease because of longstanding secondary hyperparathyroidism (Kanatani et al, 2001;Tollin et al, 2000).…”