Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have measured serum osteocalcin, a vitamin K-dependent glycoprotein synthesised by osteoblasts in 62 patients, 49 with myeloma, 26 at presentation and 23 previously treated, 7 with Waldenstrom's macroglobulinaemia (WM), and 6 with monoclonal gammopathy of uncertain significance (MGUS). Osteocalcin levels were normal in WM and MGUS. High values were found in 5/26 (19%) patients with myeloma at presentation. There was no relationship between serum osteocalcin and stage of disease. Osteocalcin was normal in all patients in plateau phase, falling to low levels in relapsed patients who failed to respond to further treatment. Serum osteocalcin may be a useful indicator of bone metabolism in myeloma.
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PMID:Serum osteocalcin in the management of myeloma. 144 31

The signification of serum bone Gla protein (serum BGP, osteocalcin) has been investigated in multiple myeloma. As a first step, quantitative iliac crest bone biopsies were performed in 19 patients; the serum BGP levels strongly correlated with histologic parameters of bone formation (r = 0.72-0.84, P less than 0.001) but not with those of bone resorption (r = 0.10). These results confirm that serum BGP is a marker of bone formation in multiple myeloma, as previously described in many other bone disorders. As a second step, serum BGP was measured in 117 patients with multiple myeloma as a systemic indicator of the degree of bone formation. Twenty-one percent of the patients had abnormal serum BGP levels (25 cases). The 14 patients with increased values (mean, 13.2 +/- 2.7 ng/ml) and thus increased bone formation belonged to a subgroup characterized by a lower osteolytic potential and a more indolent disease. On the other hand, the 11 patients with decreased values (mean, 1 +/- 0.3 ng/ml) and thus reduced bone formation had an advanced disease, extensive lytic bone lesions, a hypercalcemia frequently and a poor survival (mean, 4 months; range, 1-12). The biochemical investigations of the whole patient population, including serial studies in individual patients, have shown a large scatter of serum BGP levels, suggesting major differences in the bone formation rates. However, an overall inverse correlation was found between serum BGP and osteolytic potential. These results have confirmed the important role of the inhibition of bone formation in the occurrence of bone lesions in multiple myeloma and the interest of serum BGP to select a myeloma patient subgroup with low osteolytic potential and characterized by abnormally increased levels of this marker.
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PMID:Abnormal serum bone Gla protein levels in multiple myeloma. Crucial role of bone formation and prognostic implications. 235 3

Osteocalcin, also called bone gla-protein, is a bone matrix protein synthetized specifically by osteoblasts. It circulates in blood where it can be assayed by the radioimmune method. We measured osteocalcin serum levels in 169 adult controls and 161 patients with different disseminated or localized bone diseases. The normal concentration of 6.2 +/- 0.2 ng/ml increases significantly with age. Serum osteocalcin levels are considerably increased in renal osteodystrophy (114 +/- 23 ng/ml) and to a lesser degree in primary hyperparathyroidism (15.9 +/- 2.8 ng/ml) and Paget's disease (11.4 +/- 0.9 ng/ml), all diseases characterized by increased bone turnover. High levels are also encountered in osteomalacia (9.7 +/- 0.9 ng/ml). Conversely, serum osteocalcin levels are significantly decreased in patients under long-term corticosteroid therapy (4.3 +/- 0.5 ng/ml); they remain normal in patients with bone myeloma and bone metastases under treatment. Finally, osteocalcin is normal in patients with osteoporosis, but its level reflects that of bone turnover as evaluated by iliac bone biopsy. The circulating osteocalcin therefore is the first specific and sensitive marker for bone turnover. Serum osteocalcin measurements make it possible to evaluate the osteoblastic bone formation without biopsy and should provide information on the effectiveness of drugs acting on the bone-forming process.
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PMID:[Osteocalcin (or bone gla-protein), a new biological marker for studying bone pathology]. 293 33

Osteocalcin is synthesized by osteoblasts and its concentration in serum is increased when bone metabolism is raised. Radioimmunoassay of serum from 88 healthy adults gave a mean osteocalcin value for the whole group of 4.11 +/- 1.43 ng/ml. The level rose with age. In seven patients with primary hyperparathyroidism the mean value was markedly raised to 19.37 +/- 9.2 ng/ml, in 23 with metastasizing carcinoma of the breast it was elevated to 6.57 +/- 2.98 ng/ml. Serial measurements in 14 female patients over seven months revealed different changes in osteocalcin and alkaline phosphatase in some of them. In patients with breast cancer and soft-tissue metastases or without metastases both osteocalcin and alkaline phosphatase levels were normal. Three of 17 patients with multiple myeloma had increased osteocalcin levels. These results indicate that it is clinically helpful to know osteocalcin levels in primary hyperparathyroidism. Determination of osteocalcin concentration, in addition to that of alkaline phosphatase, can be of value in the postmastectomy management of patients with breast cancer, especially in the early recognition of bone metastases. The diagnostic value of osteocalcin levels in multiple myeloma remains undecided.
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PMID:[Osteocalcin, a marker in diseases with elevated bone metabolism]. 387 69

Previous studies have shown that bone marrow, especially the bone microenvironment, may play an important role in the pathogenesis of multiple myeloma (MM). To elucidate the relationship between myeloma cells and bone cells, mainly osteoblasts, we have established a coculture system between two interleukin-6 (IL-6)-dependent myeloma cell lines, XG1 and XG6, and the osteosarcoma cell lines Saos-2 and MG63. Both osteosarcoma cell lines have retained major functions of normal osteoblasts; principally, the capacity to produce hematopoietic growth factors (including IL-6) and osteocalcin, a noncollagenic protein essential in the bone formation process. Because IL-6 is a critical growth factor in MM, we have examined the IL-6 osteoblastic cell production in our coculture system. XG1 cells strongly upregulate IL-6 production by MG63 and Saos-2 cells. Of major interest, the triggering of IL-6 is totally dependent on the physical contact between myeloma cells and osteoblastic cells, contact that is partly mediated by CD44, CD56, and fibronectin interactions. Osteocalcin production by MG63 and Saos-2 cells has previously been shown to be dependent on 1,25-(OH)2D3. We demonstrate that XG1 and XG6 cells reduced the amount of osteocalcin in MG63 coculture cell supernatants, a reduction that is partly mediated by a soluble factor and by cell-to-cell contact. Notably, whereas one of the myeloma cell lines, XG6, has lost its capacity to stimulate IL-6 production by osteoblastic cell lines, both XG1 and XG6 cell lines remain able to reduce the osteocalcin amount, indicating that IL-6 and osteocalcin levels are regulated by two different pathways. In conclusion, these data strongly support the concept that the bone microenvironment is directly modified by contact with myeloma cells and are consistent with the characteristics observed in vivo in patients with MM patients, ie, abnormally high IL-6 and low osteocalcin levels, respectively.
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PMID:Myeloma cells upregulate interleukin-6 secretion in osteoblastic cells through cell-to-cell contact but downregulate osteocalcin. 757 10

Collagen type I is the sole collagen type found in bones and tendons. Carboxyterminal propeptide, deriving and cleaved from procollagen type I (PICP) during collagen synthesis, is delivered into the blood, where it can be measured. According to current knowledge, PICP correlates with bone collagen synthesis and bone formation rate. Elevated serum levels of PICP in patients with Paget's disease, compared with normal subjects and correlated with serum alkaline phosphatase (Alk.Ph.), have been previously described. Thus, PICP may be a valuable marker of bone formation. PICP, serum Alk.Ph., serum bone Gla protein and 24-h urinary hydroxyproline:creatinine ratio have been measured in 47 cancer patients: 27 with predominantly osteolytic lesions (5 myeloma, 15 breast, 3 lung, 2 kidney, 1 bladder, 1 thyroid) and 20 with predominantly osteoblastic lesions (18 prostate and 2 breast). The higher levels of PICP were noted in patients with osteoblastic or mixed metastases. In the entire group of patients, a statistically significant correlation between PICP and bone Gla protein (r = 0.57; P < 0.001), PICP and Alk.Ph. (r = 0.80; P < 0.001), and bone Gla protein and Alk.Ph. (r = 0.44; P < 0.01) was noted. In those patients with osteoblastic metastases we observed a significant correlation only between PICP and Alk.Ph. (r = 0.62; P < 0.003). During chemotherapy, 13 of 20 patients with osteoblastic metastases who achieved objective response or stable disease showed a more rapid and significant decrease in PICP with respect to the other bone markers. Serum PICP level could be considered a good marker of osteoblastic activity.
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PMID:Procollagen type I carboxy-terminal propeptide as a marker of osteoblastic bone metastases. 846 47

In order to characterize the abnormalities of bone remodelling in the various stages of plasma cell disorders, we studied 60 patients (29 monoclonal gammopathies of uncertain significance (MGUS), 13 stage I myeloma, 18 stage III myeloma). We carried out histomorphometric study of bone biopsies in 34 patients and measurement of osteocalcin and the calciuria/creatinine ratio. Bone remodelling was approximately normal (BV/TV:21.2 +/- 7, ES:4.1 +/- 2, OS:16.5 +/- 10) in MGUS. Stage I myeloma was characterised by parallel increases in resorption surfaces and osteoid surfaces (BV/TV:18 +/- 5, ES/BS:7.4 +/- 3.5, OS/BS:24.8 +/- 11.5), of the ca/cr ratio and osteocalcin. In stage III myeloma, resorption surfaces and the ca/cr ratio showed an even greater increase while osteoid surfaces, osteocalcin and trabecular bone volume decreased (BV/TV 13.6 +/- 6, ES/BS:12.1 +/- 6, OS/BS:13.6 +/- 8.3). Osteocalcin and osteoid surfaces were correlated (r = 0.5). There was a positive correlation between osteocalcin and the number of plasmocytes in stage 1 myeloma (r = 0.64) and a negative correlation in stage III myeloma (r = 0.9). Bone remodeling was normal in MGUS; bone remodelling grew with a parallel increase of formation and resorption in stage I; bone resorption increased while bone formation decreased in stage III myeloma.
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PMID:Bone remodelling in monoclonal gammopathies of uncertain significance, symptomatic and nonsymptomatic myeloma. 885 67