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

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 degree 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 degree 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 degree 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium metabolism in the jansen type of metaphyseal dysplasia

“…Hydoxyproline (OH-P), cyclic adenosine-3"-5"-monophosphate (cAMP) in spontaneously voided morning urine samples, osteocalcin and intact parathyroid hormone (PTH 1-84) were assayed as previoulsy described [12,13]. Calcium, phosphate, creatinine, and AP were measured with standard automatic analyser techniques.…”

Transient Increased Calcium and Calcitriol Requirements After Discontinuation of Human Synthetic Parathyroid Hormone 1-34 (hPTH 1-34) Replacement Therapy in Hypoparathyroidism

“…Patients with hypoparathyroidism experience hypocalcemia, hyperphosphatemia, and inappropriately normal or frankly elevated urinary calcium excretion. (1) In the adult skeleton, hypoparathyroidism results in a low-turnover state with low or low-normal bone turnover markers, (2) decreased tetracycline uptake and increased bone volume on iliac crest bone biopsies, (3,4) and variable changes in bone mineral density (BMD) on dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). (5)(6)(7) Human synthetic PTH 1-34 (hPTH 1-34) hormone replacement therapy has been shown to be effective for the management of hypocalcemia in hypoparathyroidism, (8,9) while at the same time converting bone to a high bone turnover state.…”

Bone disease in hypoparathyroidism

“…This disorder is characterized by markedly reduced bone remodeling due to the absence or markedly reduced presence of PTH (3)(4)(5). Chronically reduced bone turnover in patients with hypoparathyroidism typically leads to increased bone mass compared to that in ageand sex-matched controls (6)(7)(8)(9)(10)(11).…”