In vitro osteolytic activity of human myeloma plasma cells and the clinical evaluation of myeloma osteoclastic bone lesions

Jf, Rossi; Bataille, Régis

doi:10.1038/bjc.1984.147

Cited by 15 publications

(3 citation statements)

References 12 publications

(15 reference statements)

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“…We have previously published a series of nine cases presenting B-cell malignancy other than MM, but with bone changes mimicking MM (Rossi et al, 1987). In these cases we have demonstrated the production by the tumour cells of a bone resorbing activity in vitro, as observed in MM (Mundy et al, 1974: Rossi & Bataille, 1984. Furthermore, two of these patients when quantitative histology was available, showed an abnormal bone remodelling, as noted on quantitative bone biopsies.…”

Section: Discljssionsupporting

confidence: 66%

Micro‐osteoclast resorption as a characteristic feature of B‐cell malignancies other than multiple myeloma

Chappard²,

Marcelli

et al. 1990

Br J Haematol

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Multiple myeloma (MM) is characterized by the presence of lytic bone lesion and frequent hypercalcaemia. These are due to an excessive osteoclastic resorption in association with a low bone formation, as demonstrated by bone histomorphometry. Conversely, B-cell malignancies other than MM are rarely associated with lytic bone lesion and/or hypercalcaemia. In this study we have analysed quantitative bone histology in 65 patients with B-cell malignancies other than MM at diagnosis: chronic lymphocytic leukaemia (CLL, n = 20), non-Hodgkin's lymphoma (NHL, n = 25), Waldenström's disease (WD, n = 14), hairy cell leukaemia (HCL, n = 6). Fifty patients presented no clinical evidence of increased bone resorption, including no lytic bone lesions radiologically detectable and/or no hypercalcaemia. 80% of these patients (40/50) had increased bone resorption parameter using quantitative bone histology, including 19/29 (65.5%) patients with CLL or WD and 21/21 (100%) patients with NHL or HCL (P less than 0.01). As a control group, seven patients lacking bone marrow involvement on bone sample presented no excessive bone resorption. However, eight patients presented lytic bone lesions and/or hypercalcaemia. All of these patients had increased resorption parameters with high numbers of osteoclasts per surface trabecular bone (mean = 35.3), as opposed to the patients lacking lytic bone lesions and/or hypercalcaemia (mean = 6.6, n = 28) and to normal individuals (mean +/- SD = 3.8 +/- 1.7 and 6.3 +/- 2.6, respectively before and after 60 years). In all the cases, excessive histologic bone resorption was mediated by mononuclear small osteoclasts (mean osteoclast length +/- SD = 27.3 +/- 4.1 as compared to normal range = 35.0 +/- 1.0, P less than 0.001). In different in vitro models, these small mononuclear osteoclasts are considered as progenitors. These data suggest an abnormal osteoclast differentiation in B-cell malignancies other than MM, probably due to differences in the production of local factors acting on bone remodelling.

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Section: Discljssionsupporting

confidence: 66%

Micro‐osteoclast resorption as a characteristic feature of B‐cell malignancies other than multiple myeloma

Chappard²,

Marcelli

et al. 1990

Br J Haematol

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“…This could be explained by a higher production of osteoclastic factors, as emphasized by Durie et al (1981). Similar observations were made by ourselves (Rossi & Bataille 1984;and unpublished data). The number of osteoclasts (mm-2) was another interesting parameter of active OR (Valentin-Opran et al, 1982).…”

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confidence: 74%

Importance of quantitative histology of bone changes in monoclonal gammopathy

Bataille¹,

Chappard²,

Alexandre³

et al. 1986

Br J Cancer

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Quantitative histology of bone changes, using undecalcified transiliac bone biopsies (UTBB), was performed blindly in 46 individuals with monoclonal gammopathy (MG), including 17 with MG of undetermined significance (MGUS) and 29 with overt multiple myeloma (MM). Three MGUS presented an excess of osteoclastic resorption (OR) in the vicinity of clusters of tumour cells and developed overt B cell malignancies, chronic lymphocytic leukaemia, WaldenstrÃ¶m's disease and MM respectively. On the other hand, MGUS with normal OR remained stable (median follow-up = 28 months), with one exception who developed a systemic amyloidosis. In MM, excessive OR was only observed in areas invaded by myeloma cells. OR was frequently normal in active MM lacking myeloma cells in UTBB. Active MM without lesions on radiography had excessive OR. IgA and pure Bence Jones MM appeared more osteoclastic than IgG cases (P less than 0.05). Of major interest was the finding that one third of MM presented histological bone changes similar to osteoporosis, osteosclerosis or osteoblastic metastasis. Two major findings must be emphasized from the current data: UTBB could be of major interest for the early detection of a B cell malignancy; heterogeneity of myeloma bone condition is unexpected. If some changes appear directly related to the tumour (i.e. excessive OR or osteoblastic dysfunction), some others are probably accidentally associated with it (i.e. osteoporosis), both needing treatment other than chemotherapy.

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“…Bone involvement is related to an excessive bone resorption encountered in the close vicinity of myeloma cells (3)(4)(5)(6). This increased resorption is due to the local stimulation of osteoclasts by soluble factors released by myeloma cells and environmental cells, such as IL-1 and tumor necrosis factor (TNF) (3,(7)(8)(9)(10)(11)(12)(13). The severity of lytic bone lesions is actually correlated with the presence of a marked uncoupling process in patients with advanced MM: increased bone resorption with decreased bone formation (14).…”

Section: Introductionmentioning

confidence: 99%

Recruitment of new osteoblasts and osteoclasts is the earliest critical event in the pathogenesis of human multiple myeloma.

Bataille

Chappard²,

Marcelli³

et al. 1991

J. Clin. Invest.

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233

163

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Considering the special relation of human multiple myeloma (MM) to bones, it is of importance to clarify the early steps of bone involvement in this disease. In this work, using bone histomorphometry (including histoenzymologic and kinetic studies for the first time), we have evaluated the bone remodeling (i.e., bone resorption and bone formation rates) of 16 individuals with early MM in comparison with that of 10 with benign monoclonal gammopathy (BMG) and that of 17 patients with previously untreated overt MM. A significantly increased osteoblastic recruitment was observed in the individuals with early MM when compared with those with BMG (P < 0.01). A significant (P < 0.01) increased bone resorption (i.e., eroded surfaces, osteoclast numbers and surfaces) was observed from the early stage of MM in comparison with the BMG status where bone resorption remained within the normal range. At the tissue level, there was no difference in terms of bone resorption between early and overt MM. On the other hand, osteoblast activity was significantly reduced in patients with overt MM (P < 0.05 by comparison with those with early MM).A significant enhancement of osteoblastic recruitment with an increased generation of new osteoclasts is an early critical event in the pathogenesis of human MM. Of particular importance is the early stimulation of osteoblasts, since these cells produce high amounts of IL-6, a potent myeloma cell growth factor and a critical cytokine for the formation of osteoclasts in the bone marrow. (J. Clin. Invest. 1991. 88:62-66.)

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In vitro osteolytic activity of human myeloma plasma cells and the clinical evaluation of myeloma osteoclastic bone lesions

Cited by 15 publications

References 12 publications

Micro‐osteoclast resorption as a characteristic feature of B‐cell malignancies other than multiple myeloma

Micro‐osteoclast resorption as a characteristic feature of B‐cell malignancies other than multiple myeloma

Importance of quantitative histology of bone changes in monoclonal gammopathy

Recruitment of new osteoblasts and osteoclasts is the earliest critical event in the pathogenesis of human multiple myeloma.

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