Differences in bone and vitamin D metabolism between primary hyperparathyroidism and malignancy-associated hypercalcemia.

Abstract

Bone and vitamin D metabolism are examined in patients with primary hyperparathyroidism (1 degree HPT), humoral hypercalcemia of malignancy (HHM), and local osteolytic hypercalcemia (LOH) with normal renal function. Among the bone resorption markers, T scores of total deoxypyridinoline (Dpyd) were highest in HHM and were significantly higher than those in 1 degree HPT. Among the formation markers, T scores of osteocalcin (OC) were highest in 1 degree HPT but were negative in HHM. The elevation in total Dpyd was associated with an increase in OC in 1 degree HPT, and the ratios of total Dpyd/OC were similar to those in controls. In contrast, many patients with HHM and LOH exhibited elevated total Dpyd and suppressed OC with increased total Dpyd/OC ratios, but the ratios varied widely. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was elevated in 1 degrees HPT but was suppressed in HHM and LOH at any serum Ca levels. These results demonstrate that increased bone resorption is associated with enhanced bone formation in 1 degrees HPT but are uncoupled in many of the HHM and LOH patients, and that total Dpyd/OC ratio can be a useful index to estimate the coupling state of bone. It is suggested that the reduction in serum 1,25(OH)2D cannot be explained by an elevation in serum Ca in HHM and LOH, and that the differences in bone and vitamin D metabolism in HHM and LOH from those in 1 degree HPT may be caused by a common mechanism such as the secretion of some cytokines from tumors.

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

“…Secondly, while both syndromes have marked increases in osteoclastic bone resorption, many patients with HHM do not have the normally coupled increase in osteoblastic activity that those with 1 HPT experience. Studies using either serum markers of bone turnover (Nakayama et al 1996) or quantitative bone histomorphometry (Stewart et al 1982) have demonstrated this uncoupling of bone resorption from bone formation. Finally, unlike the metabolic acidosis seen in patients with 1 HPT, patients with HHM often have a metabolic alkalosis with a low plasma chloride and high plasma bicarbonate concentration.…”

Thyroid Follicular Adenoma Producing Parathyroid Hormone-related Protein with a Normal Serum Calcium Level

“…The normal physiologic role of PTHrP is not thoroughly understood, but it is considered to be involved in normal calcium homeostasis (18), regulation of smooth muscle (19), and regulation of tissue and organ development, differentiation, and proliferation (1-3, 20, 21 , , , and (27). In the patients with HHB, the serum 1,25-dihydroxy vitamin D3 concentration was reported to be low or normal (6,10,12 …”

Parathyroid Hormone-Related Protein Induced Coupled Increases in Bone Formation and Resorption Markers for 7 Years in a Patient With Malignant Islet Cell Tumors

“…Bone metabolic markers were examined in the same laboratory as previously reported (5) with a high-performance liquid chromatography (HPLC) method for urinary total deoxypyridinoline and pyridinoline, (10) an immunoassay using Osteomark NTx (Mochida Pharmaceutical Co., Tokyo, Japan) for urinary N-telopeptide of type I collagen (NTx), an immunoradiometric assay using a Mitsubishi bone-gla protein (BGP)-IRMA kit (Mitsubishi Kagaku) for serum osteocalcin (5) and an immunoassay using Alkphase-B kit (Quidel, San Diego, CA, USA) for serum bone-type alkaline phosphatase. For bone resorption markers, urinary excretions of deoxypyridinoline (74 pmol/mol of creatinine [2.2-6.1]) and pyridinoline (333 pmol/mol of creatinine [17.7-41.9]) were elevated at the time of diagnosis, and that of NTx was higher (87.7 nmol of bone collagen equivalents [BCE]/mmol of creatinine [Ͻ55]) 7 years after diagnosis even in the midst of regular infusions of incadronate.…”

“…Serum 1,25-dihydroxyvitamin D is suppressed usually in HHM patients, whereas its level is elevated in primary hyperparathyroidism. (1,5) Bone resorption and formation are well balanced in primary hyperparathyroidism, whereas bone resorption is enhanced but bone formation is severely suppressed in HHM. (5,6) It is not clarified whether there are any systemic effects of PTHrP that are different from those of PTH or there are other humoral factors than PTHrP in HHM.…”

“…(1,5) Bone resorption and formation are well balanced in primary hyperparathyroidism, whereas bone resorption is enhanced but bone formation is severely suppressed in HHM. (5,6) It is not clarified whether there are any systemic effects of PTHrP that are different from those of PTH or there are other humoral factors than PTHrP in HHM. Although systemic administration of hPTHrP fragments in animals (7) and humans (8) for short periods could reproduce the same effects as those of PTH, chronic and systemic effects of PTHrP in humans are difficult to evaluate because its systemic administration that evokes prolonged hypercalcemia is not allowed in humans because of an ethical problem.…”