Histomorphometric analysis of osteoclastic bone resorption in metastatic bone disease from various primary malignomas

Ha, Kulenkampff; Dreyer, Thomas; Kersjes, W.; Delling, G.

doi:10.1007/bf00710766

Cited by 17 publications

(7 citation statements)

References 31 publications

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“…It has been suggested, on the basis of data from several experimental models and from analysis of human biopsy specimens, that osteoclasts are responsible for bone resorption at sites of osteolytic tumors (1,(3)(4)(5)(6)8,10,14,17,20,22,27). Our findings advance this concept one step further by demonstrating that osteoclasts are required for 2472 tumor-induced osteolysis to occur.…”

Section: Discussionsupporting

confidence: 59%

“…Descriptions from zn vivo expcriments with both tumors revealed that bone was destroyed at sites of tumor and that no osteoclasts were present. These observations suggest that osteoclasts may not be involved in the pathogenesis of tumor osteolysis (15J9): however, the possibility exists that osteoclasts were present before the point at which the tumor-bearing bone was collected (14). It therefore becomes important to determine when tumor osteolysis is actually occurring in the experimental model under investigation.…”

Section: Discussionmentioning

confidence: 99%

“…The precise cellular events that direct bone resorption during tumor osteolysis have not hcen fully deter-mined: however, data have been provided previously to support the hypothesis that tumor osteolysis reflects the iniluence of tumors on the formation of multinucleated osteoclasts. Support for this hypothesis has been provided from analysis of human biopsy specimens and from study of in vivn experimental models (1,(3)(4)(5)(6)8,10,14,17,20,22,27). Analysis of human biopsy specimens from sites of breast cancer (22), renal cell cancer (11, and myeloma (24) tumor indicate that the number of osteoclasts is increased at these sites.…”

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confidence: 98%

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Osteoclasts are required for bone tumors to grow and destroy bone

Clohisy

Ramnaraine

1998

Journal Orthopaedic Research

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It has been hypothesized that bone resorption during tumor osteolysis is performed by osteoclasts. Data supporting this hypothesis have been provided from analysis of human biopsy specimens obtained from sites of tumor osteolysis, as well as from experimentation with in vivo animal models. Experiments in this report take this concept one step further by testing the hypothesis that osteoclasts are required for bone tumors to grow and destroy bone. To test this hypothesis, the influence of an osteolytic sarcoma tumor, NCTC clone 2472 (2472), on bone was studied in animals that are osteoclast deficient (microphthalmic, strain B6C3Fe-a/a-Mitf(mi)) but whose osteoclast deficiency can be reversed following bone marrow transplantation. Femora of these mice and unaffected wild-type siblings were injected with 10(5) 2472 cells, and after 14 days the femora were analyzed by radiographic and histomorphometric analysis. Macroscopic tumor, tumor-induced osteolysis, and increased osteoclast number were noted in femora of normal mice but not in femora of osteoclast-deficient mice (p < 0.001). Bone marrow transplantation converted osteoclast-deficient mice to mice with femora that contained osteoclasts in 4 weeks. Femora of these mice were then injected with 10(5) 2472 tumor cells; after 14 days, in contrast to the findings in the original osteoclast-deficient mice, macroscopic tumor was present, tumor-induced osteolysis was noted on roentgenograms, and osteoclast number was increased when tumor-bearing limbs were compared with sham-injected limbs (p < 0.001). These data prove the hypothesis that osteoclasts are required for 2472 tumor-induced osteolysis, and they introduce the exciting possibility that osteoclasts are also required for tumors to grow in bone.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

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Osteoclasts are required for bone tumors to grow and destroy bone

Clohisy

Ramnaraine

1998

Journal Orthopaedic Research

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“…This could suggest that large giant multinucleated osteoclasts are able to retain some residual bone resorptive activity as an indication of partly-reduced sensitivity. Large multinucleated osteoclasts are also often seen in the context of cancer bone metastases [ 111 , 112 ]. Precisely in cancer, suppression of bone resorption is important to treat the bone disease.…”

Section: Implications For Physiology and Pathologymentioning

confidence: 99%

Osteoclast Fusion: Physiological Regulation of Multinucleation through Heterogeneity—Potential Implications for Drug Sensitivity

Søe

2020

IJMS

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Classically, osteoclast fusion consists of four basic steps: (1) attraction/migration, (2) recognition, (3) cell–cell adhesion, and (4) membrane fusion. In theory, this sounds like a straightforward simple linear process. However, it is not. Osteoclast fusion has to take place in a well-coordinated manner—something that is not simple. In vivo, the complex regulation of osteoclast formation takes place within the bone marrow—in time and space. The present review will focus on considering osteoclast fusion in the context of physiology and pathology. Special attention is given to: (1) regulation of osteoclast fusion in vivo, (2) heterogeneity of osteoclast fusion partners, (3) regulation of multi-nucleation, (4) implications for physiology and pathology, and (5) implications for drug sensitivity and side effects. The review will emphasize that more attention should be given to the human in vivo reality when interpreting the impact of in vitro and animal studies. This should be done in order to improve our understanding of human physiology and pathology, as well as to improve anti-resorptive treatment and reduce side effects.

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“…Some disagreement exists as to whether the giant cells within the tumor are actually osteoclasts that resorb bone underlying the GCTB or whether the osteoclasts seen resorbing the bone arrived by chemotaxis [11,12]. Cytokines produced in metastases to bone are known to recruit osteoclasts [13]. In the electron microscope, intervening cells, membranes, and fibrous stromal tissue usually can be seen between the GCTB and active osteoclasts on the bone [14].…”

mentioning

confidence: 98%

Cytokines Expressed in Multinucleated Cells: Paget's Disease and Giant Cell Tumors versus Normal Bone

Mills

Frausto

1997

Calcif Tissue Int

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Human osteoclasts are well characterized multinucleated cells whose function is the directed resorption of normal bone (NB). Osteoclastic bone destruction accompanies lytic solid tumors and myeloma as well as Paget's disease (PD) of bone and giant cell tumors of bone (GCTB). The mechanism of this stimulation of osteoclastic bone resorption is unknown. This study was designed to detect cytokines present in the multinucleated cells of PD and GCTB in order to determine whether cytokine abnormalities exist to account for bone lysis. Nine cytokines, representing the functions of bone resorption, angiogenesis, tumor necrosis, bone cell proliferation, and osteoblast-osteoclast coupling, were examined by immunohistochemistry using tissue samples from 15 NB, 17 PD, and 19 GCTB patients. Standard nonparametric statistical analysis showed a significant increase (P < 0.01 to 0.05) in immunostaining between osteoclasts of PD and NB for interleukin-6 (Il-6), tumor necrosis factor beta (TNFbeta), epidermal growth factor (EGF), platelet derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). There was a statistically significant decrease in immunostaining of giant cells of GCTB as compared with NB for transforming growth factor beta (TGFbeta), but no other differences from normal osteoclasts. The increase in staining of PD osteoclasts over the giant cells of GCTB was significant (P < 0.01) for Il-6, TNFbeta, PDGF, bFGF and insulin growth factor-1 (IGF-1), and (P < 0. 05) for Il-1 and EGF. It was concluded that marked cytokine differences exist in vivo between osteoclasts of NB and PD lesions consistent with stimulated resorption. Alternatively, "osteoclastoma" cells in the center of the tumor did not overexpress the cytokines associated with bone lysis, suggesting some other mechanism for stimulated resorption.

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Histomorphometric analysis of osteoclastic bone resorption in metastatic bone disease from various primary malignomas

Cited by 17 publications

References 31 publications

Osteoclasts are required for bone tumors to grow and destroy bone

Osteoclasts are required for bone tumors to grow and destroy bone

Osteoclast Fusion: Physiological Regulation of Multinucleation through Heterogeneity—Potential Implications for Drug Sensitivity

Cytokines Expressed in Multinucleated Cells: Paget's Disease and Giant Cell Tumors versus Normal Bone

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