Raised Plasma Concentrations of Parathyroid Hormone Related Peptide in Hypercalcemic Multiple Myeloma

Horiuchi, Toshiyuki; Miyachi, Tomohiro; Arai, T; Nakamura, Takuro; Mori, Misuzu; Itô, Haruo

doi:10.1055/s-2007-979080

Cited by 10 publications

(10 citation statements)

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“…PTH does not have a primary role in MM bone disease. PTH levels of MM patients have been found to be similar to those in healthy controls, however, a few hypercalcemic MM patients were reported to have had high levels of PTH related peptide, which may cause hypercalcemia [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Biochemical markers of bone turnover in diagnosis of myeloma bone disease

Dizdar¹,

Barışta²,

Kalyoncu³

et al. 2006

American J Hematol

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This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1a (MIP-1a), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1a, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1a, and urine DPD were significantly higher in MM patients with bone disease than in controls (P < 0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P < 0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P < 0.001). The serum OPN and MIP-1a levels of the patients were significantly correlated with b2-microglobulin and lactate dehydrogenase levels (P < 0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1a needs to be further investigated. Am. J. Hematol. 82:185-191, 2007. V V C 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Biochemical markers of bone turnover in diagnosis of myeloma bone disease

Dizdar¹,

Barışta²,

Kalyoncu³

et al. 2006

American J Hematol

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“…There is supportive evidence from clinical studies that the capacity of myeloma cells demonstrated in this study to generate PTHrP is associated with the development of hypercalcaemia in vivo . Elevated circulating levels of PTHrP have been observed in a number of studies on hypercalcaemic myeloma patients7–12, and a temporal relationship has been demonstrated between elevation of the serum PTHrP level and the development of hypercalcaemia10, 11. Recent reports have also indicated that certain human myeloma cell lines produce PTHrP in vitro 18, 19.…”

Section: Discussionmentioning

confidence: 99%

“…The interpretation of studies which have sought to identify the effector of osteolysis under these conditions has been complicated by the detection of a number of different cytokines in myeloma cell culture supernatant, such as interleukin (IL)‐1β, IL‐6, tumour necrosis factor (TNF)‐α, and TNF‐β, with the capacity to promote osteolysis in this bioassay4–6. PTHrP has also been incriminated on the basis of an observed association between increased circulating PTHrP levels and the development of hypercalcaemia in some myeloma patients7–12, but the capacity of myeloma cells to produce PTHrP in vivo has not been systematically evaluated.…”

Section: Introductionmentioning

confidence: 99%

Assessment of cellular expression of parathyroid hormone‐related protein mRNA and protein in multiple myeloma

et al. 2000

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The capacity of multiple myeloma cells to generate parathyroid hormone-related protein (PTHrP) has been examined by in situ assessment of PTHrP mRNA and PTHrP protein in myeloma cells of patients in whom the disease was associated with the development of hypercalcaemia. The presence of PTHrP mRNA was evaluated by in situ hybridization using an antisense riboprobe, and PTHrP by immunohistochemistry using a monoclonal antibody, in archival bone marrow trephine specimens from 17 patients. PTHrP mRNA was detected in myeloma cells in 16 of the 17 patients, indicating a high frequency of PTHrP gene expression in myeloma cells in these subjects. PTHrP protein was, on the other hand, detected in the myeloma cells of only five of these patients. The impact of the mercury-based fixation and decalcification procedure used for processing the bone marrow trephine specimens was assessed to determine the influence of this process on the outcome of the immunohistochemical assay for PTHrP. It was shown that this preparative procedure resulted in a marked reduction of immunohistochemically detectable PTHrP, which provides a possible explanation for the lower frequency of positivity for PTHrP in myeloma cells in the bone marrow specimens. The present findings are consistent with the view that PTHrP can be generated in myeloma cells in vivo, and could contribute to osteolysis and hypercalcaemia, as in patients with cancer.

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“…Studies have reported an infrequent association between elevated serum PTHrP levels and myeloma although the frequency of elevated serum PTHrP levels is higher in myeloma patients who are hypercalcaemic than those who are not (Horiuchi et al , 1997; Firkin et al , 1998). A study of myeloma bone marrow samples provided immunohistochemical evidence of PTHrP protein production by myeloma cells and evidence of PTHLH ( PTHrP ) mRNA expression by in situ hybridization techniques.…”

Section: Hypercalcaemia In Haematological Disordersmentioning

confidence: 99%

Haematological emergencies managing hypercalcaemia in adults and children with haematological disorders

Sargent

Smith

2010

Br J Haematol

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SummaryHypercalcaemia is a common metabolic complication of malignant disease often requiring emergency intervention. Although it is more frequently associated with solid tumours, malignancy-associated hypercalcaemia (MAH) is seen in a significant number of patients with blood diseases. Its association with myeloma and adult T-cell leukaemia/lymphoma is well recognized but the incidence of hypercalcaemia in other haematological neoplasms, affecting adults and children, is less clearly defined. Haematologists need to be familiar with the clinical manifestations of, the differential diagnosis to be considered and the most effective management strategies that are currently available for MAH. The key components of management of MAH include aggressive rehydration, specific therapy to inhibit bone resorption and, crucially, treatment of the underlying malignancy. Bisphosphonates have revolutionized the management of MAH over the last 20 years, however the elucidation of molecular pathways implicated in MAH is facilitating the development of more targeted approaches to treatment.

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Raised Plasma Concentrations of Parathyroid Hormone Related Peptide in Hypercalcemic Multiple Myeloma

Cited by 10 publications

References 1 publication

Biochemical markers of bone turnover in diagnosis of myeloma bone disease

Biochemical markers of bone turnover in diagnosis of myeloma bone disease

Assessment of cellular expression of parathyroid hormone‐related protein mRNA and protein in multiple myeloma

Haematological emergencies managing hypercalcaemia in adults and children with haematological disorders

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