Abstract
In addition to the well-documented hyporesponsiveness of the kidney, resistance to parathyroid hormone (PTH) has been postulated for bone in pseudohypoparathyroidism type I (PHP). In some of these patients reduced bone density and even frank osteitis fibrosa suggest osteoclastic overactivity. To address the possibility that the skeletal system of patients with PHP may be affected by their increased PTH secretion we measured intact serum PTH and three biochemical markers of bone turnover in a large number of patients with PHP (n=20). The results were compared with subjects with low (hypoparathyroidism, HP, n=29), normal (controls, n=31) and high (primary hyperparathyroidism, 1°HPT, n=13) PTH secretion. Both markers of osteoblastic bone formation, alkaline phosphatase activity and osteocalcin concentration in serum, and one index of osteoclastic bone degradation, the urinary hydroxyproline/creatinine ratio (OH-P/Cr), were decreased in HP and increased in 1°HPT, whereas only OH-P/Cr was elevated in patients with PHP. Although intact serum PTH was significantly more increased in PHP than in 1°HPT, the markers of bone turnover were not significantly different in these two groups, suggesting some bone resistance in the patients with PHP. In these subjects intact serum PTH was elevated even at normocalcaemia during vitamin D treatment with a negative correlation with the respective serum calcium concentration (r=−0.69, P<0.001), indicating an elevated set-point for the suppression of their parathyroid glands. OH-P/Cr was negatively related to serum calcium in PHP, it normalized in most patients during normocalcaemia induced by vitamin D treatment. The urinary calcium excretion remained normal in the patients with PHP but was markedly elevated in patients with HP after the serum calcium levels had normalized during vitamin D therapy. In conclusion, the present and other studies suggest that the resistance to PTH in patients with PHP is mainly limited to the proximal kidney tubule and that the tendency to increased bone degradation implies either some response of the remodelling bone system to PTH or the result of marked secondary hyperparathyroidism overcoming a partial resistance of bone cells. The aim of vitamin D treatment in patients with PHP should therefore be an elevation of the serum calcium concentration into the high normal-range in order to suppress PTH secretion and thus bone degradation. In these patients the parathyroid glands are less sensitive to circulating calcium levels.
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Abbreviations
- AHO:
-
Albright's hereditary osteodystrophy
- AMP:
-
adenosine monophosphate
- AP:
-
alkaline phosphatase activity
- Ca:
-
calcium
- Ca/Cr:
-
urinary calcium/creatinine ratio
- Cr:
-
creatinine
- HP:
-
hypoparathyroidism
- 1°HPT:
-
primary hyperparathyroidism
- OH-P/Cr:
-
urinary hydroxyproline/creatinine ratio
- PHP:
-
pseudohypoparathyroidism
- PTH:
-
parathyroid hormone
- SDS:
-
standard deviation score
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Kruse, K., Kracht, U., Wohlfart, K. et al. Biochemical markers of bone turnover, intact serum parathyroid hormone and renal calcium excretion in patients with pseudohypoparathyroidism and hypoparathyroidism before and during vitamin D treatment. Eur J Pediatr 148, 535–539 (1989). https://doi.org/10.1007/BF00441552
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DOI: https://doi.org/10.1007/BF00441552