PubMed Central This is a disease of clonal malignancy of terminally differentiated plasma cells that accumulate in the bone marrow. Res. However, both bone degradation and deposition likely occur early in the metastatic process. 10.1016/j.yexcr.2007.09.021. Cancer cells also can elicit an increase in osteoblast production of several other osteoclastogenic cytokines, such as monocyte chemotactic protein-1 (MCP-1) and IL-6, IL-8 and TNF [22]. They also are regulators of other molecules important in the vicious cycle. RaioX do Trauma, 1 edio; Leo Henrique Zquia, Juan Zambon, Patrcia Comberlato; Editora da Ulbra, Canoas 2013, 3. Thus, bone loss is the result of excessive bone degradation and insufficient bone replacement. Metastatic breast cancer cells or their conditioned media increase osteoblast apoptosis, and suppress osteoblast differentiation and expression of proteins required for new bone matrix formation. Hypercalcemia is a condition in which you have a high level of calcium in your blood. 2002, 13: 62-71. Studies with MMP9-null mice indicate its importance in tumor progression in ovarian cancer, prostate cancer and bone metastasis [56]. Metastatic breast cancer in the femur. Metastastic human breast cancer cells (MDA-MB-231) added to this culture attach, penetrate the tissue and form single cell files characteristic of metastases seen in pathologic tissues. Lipton A: Emerging role of bisphosphonates in the clinic--antitumor activity and prevention of metastasis to bone. 2010, 29: 811-821. Nevertheless, they do not appear to function in the osteoclast resorption lacuna, probably due to the low pH in this compartment.

Current treatments can improve bone density, decrease skeletal related events and ease bone pain, yet existing bone lesions do not heal. Denosumab is an antibody directed to RANKL that prevents osteoclast differentiation. Coleman R, Gnant M: New results from the use of bisphosphonates in cancer patients.

A thorough review of bone remodeling is beyond the scope of this article, and there are several excellent, recent reviews [8, 9]. Denosumab (Prolia), the latest drug to enter the field, is a monoclonal antibody to RANKL. There are many excellent reviews describing this paradigm [1417] from its inception in the 1990 s. The minimal essential components are osteoblasts, osteoclasts, tumor cells and the mineralized bone matrix. The clinical outcomes of bone pain, pathologic fractures, nerve compression syndrome, and metabolic disturbances leading to hypercalcemia and acid/base imbalance severely reduce the quality of life [3]. Understanding the mechanisms of osteolysis should be the key to designing the cure. These molecules bind to hydroxyapatite of the bone matrix and are ingested by osteoclasts, which then undergo apoptosis. For females, breast and lung are the most common primary sites ; nearly 80% of cancers that spread to the skeleton are from these locations. Google Scholar. Newer imaging modalities, such as positron emission tomography (PET)/CT, improve detection of both lytic and blastic metastases. 10.1056/NEJMoa030847. DMS is a senior research technician with many years experience in the bone field. The tumors that develop, sometimes called lesions, can: Make the bones weaker Recently, we have found that metastatic breast cancer cells have profound effects on osteoblasts in culture [22] and in animals [31, 32]. The vertebral vein system.

Osteoblasts and bone stromal cells can respond to a variety of substances that upregulate RANKL.

Akech J, Wixted JJ, Bedard K, van der Deen M, Hussain S, Guise TA, van Wijnen AJ, Stein JL, Languino LR, Altieri DC, Pratap J, Keller E, Stein GS, Lian JB: Runx2 association with progression of prostate cancer in patients: mechanisms mediating bone osteolysis and osteoblastic metastatic lesions.

Vikesa J, Moller AK, Kaczkowski B, Borup R, Winther O, Henao R, et al. For example, a hydroxyapatite scaold pre-loaded with bone morphogenetic protein-2 enhanced the growth rate of mammary tumor cells in the scaold [77]. Thus, the ratio of RANKL to OPG is critical for osteoclast activation. Br J Cancer. In the 1960s and 70s it was proposed that bone degradation might result from the physical pressure of the tumor on the bone and/or direct resorption of the bone by tumor cells. Balkwill F, Mantovani A: Cancer and inflammation: implications for pharmacology and therapeutics. Osteomimetic factors driven by abnormal Runx2 activation in breast cancer cells may increase their survival in the bone microenvironment. TGF- is well-known for its role in osteolytic bone metastasis. 10.1002/(SICI)1097-0142(19971015)80:8+<1546::AID-CNCR4>3.0.CO;2-I. Reference article, Radiopaedia.org (Accessed on 05 Apr 2023) https://doi.org/10.53347/rID-36642. While not directly responsible for osteolysis in metastatic breast cancer disease, there are physiological parameters that can amplify the degree of bone loss. Stopeck A: Denosumab findings in metastatic breast cancer.

Prognostic factors of postrecurrence survival in completely resected stage I non-small cell lung cancer with distant metastasis. 10.1359/jbmr.060610. N Engl J Med. PubMed They are created when the cancer cells stimulate normal cells called osteoclasts to break down bone tissue in a process called resorption. Among these are the MMPs. PTHrP, one of many proteins controlled by Runx2, is a major effector in breast cancer bone metastasis progression and bone loss. 2010. They activate latent molecules released from the matrix. Because osteoblasts secrete both RANKL and OPG, they are major mediators of osteoclastogenesis [25]. 2000, 1: 331-341. Podgorski I, Linebaugh BE, Koblinski JE, Rudy DL, Herroon MK, Olive MB, Sloane BF: Bone marrow-derived cathepsin K cleaves SPARC in bone metastasis. Minimally invasive percutaneous ablative treatment techniques, including radiofrequency ablation, microwave ablation, and cryoablation, are examined. ADVERTISEMENT: Supporters see fewer/no ads, Please Note: You can also scroll through stacks with your mouse wheel or the keyboard arrow keys. Chemotherapy may bring about ovarian failure and premature menopause [1]. J Dent Res. PubMed Surprisingly, this treatment did not affect angiogenesis in the bone. In advanced disease, bone formation is essentially absent, and the processes of bone resorption and formation become uncoupled. PloS one. Cancer Res. Cells of the monocyte-macrophage lineage are stimulated to form osteoclast progenitor cells. Current therapeutic targets are indicated in green. Bone. Clin Adv Hematol Oncol. 2010. Raica M, Anca M: Platelet-derived growth factor (PDGF)/PDGF receptors (PDGFR) axis as target for antitumor and antiangiogenic therapy. Vikesa J, Moller AK, Kaczkowski B, Borup R, Winther O, Henao R, et al. IGF, insulin-like growth factor; MCP-1, monocyte chemotactic protein-1; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor. Oftentimes, small holes result from osteolysis. Epidemiological studies have also correlated the increase in breast cancer rates with decreasing sunlight exposure. Continuing research into the mechanisms of cancer cell dormancy could result in a treatment that would prevent cancer cell proliferation in the bone and the chain of events that leads to osteolysis. 4. As pointed out by Lynch, the spatial and temporal expression of these molecules is of utmost importance. 10.1158/0008-5472.CAN-09-3194. 10.1038/onc.2009.389. Breast cancer metastasis to the bone: mechanisms of bone loss. 10.1016/j.ctrv.2010.04.003. volume12, Articlenumber:215 (2010) Apr 5 2010; 8. In doing so, cancer cells are equipped to home, adhere, survive and proliferate in the bone microenvironment. Clinical evidence indicates that this drug can reduce the rate of bone loss, but is not curative. In the highly metastatic, COX-2-expressing breast cancer cell line Hs578T, treatment with the selective COX-2 inhibitor Ns-398 markedly decreased the production of MMP1, 2, 3, and 13 in a dose-dependent manner. Zheng Y, Zhou H, Modzelewski JR, Kalak R, Blair JM, Seibel MJ, Dunstan CR: Accelerated bone resorption, due to dietary calcium deficiency, promotes breast cancer tumor growth in bone. a, b Hematoxylin and Eosin (H&E) staining highlight the appearance of prostate cancer in Edward Tobinick: The Cerebrospinal Venous System: Anatomy, Physiology, and Clinical Implications, Medscape General Medicine, 11. PubMed However, both drugs are associated with low incidence of osteonecrosis of the jaw [75]. Bone morphogenetic proteins in breast cancer - dual role in tumourigenesis?. Of the many prostaglandins, PGE2 is known to play a critical role in cancer progression. These holes in the bone are (b) The lesion shows complete sclerotic fill-in 3 months later. In addition, factors such as TGF- and IGFs that are released from the bone matrix during degradation serve to increase PTHrP expression in breast cancer cells. 1984, 235: 561-564. In normal bone remodeling, osteoclasts secrete PDGF, which acts as a chemoattractant to recruit pre-osteoblasts to the site of bone repair [58]. Lee J, Weber M, Mejia S, Bone E, Watson P, Orr W: A matrix metalloproteinase inhibitor, batimastat, retards the development of osteolytic bone metastases by MDA-MB-231 human breast cancer cells in Balb C nu/nu mice. Yang Y, Ren Y, Ramani VC, Nan L, Suva LJ, Sanderson RD: Heparanase enhances local and systemic osteolysis in multiple myeloma by upregulating the expression and secretion of RANKL. Become a Gold Supporter and see no third-party ads. Zambonin Zallone A, Teti A, Primavera MV: Resorption of vital or devitalized bone by isolated osteoclasts in vitro. Of lung, thyroid, and kidney cancers that spread to other parts of the body, about 1 out of 3 will spread to the bones. The presence of skeletal metastases in patients suffering from cancer leads to a variety of clinical complications. These factors can stimulate the tumor cells to proliferate and produce more growth factors and more PTHrP, further perpetuating the vicious cycle of bone metastasis. Osteocytes may act as mechanosensing cells and initiate the process when microfractures and loading are involved. The normal processes of bone resorption and formation are remarkably well balanced. 2010, 3: 572-599. Make the bones more dense, but not necessarily stronger. Ganapathy and colleagues [24] found that TGF- antagonists are able to reduce bone metastasis and the number and activity of differentiated osteoclasts [24]. 2010, 70: 6150-6160. While some of the growth factors produced by breast and prostate cancers may be different, ultimately they engage the bone re-modeling process.

They are created when the cancer cells stimulate normal cells called osteoclasts to break down bone tissue in a process called resorption. There is evidence that osteoblastic metastases form at sites of osteolytic lesions, suggesting an overall increase of bone remodeling Accelerated osteoblastogenesis can be stimulated by factors secreted by prostate cancer cells, such as endothelin-1, TGF-, and fibroblast growth factor (FGF) [1]. Part of this uncertainty is because we do not fully understand all of the cell, cytokine and growth factor interactions that occur in the bone microenvironment. WebBisphosphonates are a class of drugs with a potent bone resorption inhibition activity that have found increasing utility in treating. Clezardin P, Teti A: Bone metastasis: pathogenesis and therapeutic implications. 2008, 34 (Suppl 1): S25-30. Grey A: Teriparatide for bone loss in the jaw. J Biomol Tech. Endocrinology. Thus, bone loss is due to both increased activation of osteoclasts and suppression of osteoblasts. Osteoblasts also produce osteoprotegerin (OPG), a decoy receptor to RANKL. Cancer Res. 2009, 13: 355-362. Osteolytic lesions are the end result of osteoclast activity; however, osteoclast differentiation and activation are mediated by osteoblast production of RANKL (receptor activator for NFB ligand) and several osteoclastogenic cytokines. The following case shows a systematic. While ductal carcinoma in situ detected early is 98% curable, bone metastases are basically incurable [2]. Cancer Treat Rev. Another growth factor sequestered in the matrix is IGF. In a series of in vitro, ex vivo and in vivo experiments, Ohshiba and colleagues [45] demonstrated that direct cell-cell contact between breast cancer cells and osteoblasts caused an increase in COX-2 expression in the osteoblasts due to activation of the NFB/mitogen-activated protein (MAP) kinase pathway. 10.1038/sj.bjc.6602417. Guise TA: Parathyroid hormone-related protein and bone metastases. The hypoactivity of osteoblasts has been known for some time in multiple myeloma. While there is evidence that the breast cancer cell matrix metalloproteinases (MMPs) can resorb bone in vitro and contribute to bone degradation in vivo [5], it is now well accepted that osteoclasts are largely responsible for osteolytic metastatic lesions [6]. Kubota K, Sakikawa C, Katsumata M, Nakamura T, Wakabayashi K: PDGF BB purified from osteoclasts acts as osteoblastogenesis inhibitory factor (OBIF). In isolation, this response qualifies as complete response even though progressive sclerosis may be seen on subsequent In fact, a new drug, denosumab (Prolia), a fully human monoclonal antibody to RANKL, has been approved by the US Food and Drug Administration (FDA) for the treatment of postmenopausal women with high risk of osteoporotic fractures, and is under priority review for patients with bone metastases. Until recently they were the only FDA approved drugs for metastatic bone disease [71]. Thus, Runx2 plays a significant role in the vicious cycle via TGF--induced IHH-PTHrP pathways in breast cancer cells, resulting in increased osteoclastogenesis and osteolysis. Where the bone formation predominates, the lesion appears sclerotic. IGF binding proteins keep this molecule latent. Blood. Kozlow W, Guise TA: Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. Recently we have begun developing an in vitro bioreactor [78]. Powles TJ, Clark SA, Easty DM, Easty GC, Neville AM: The inhibition by aspirin and indomethacin of osteolytic tumor deposits and hypercalcaemia in rats with Walker tumour, and its possible application to human breast cancer. The MMPs are considered to be important in the bone metastatic process. 2010, 87: 401-406. After your cancer is gone, it is the job of the osteoblasts to rebuild the bone. Br J Cancer. 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Before they begin to grow the mechanisms of osteolysis and implications for pharmacology and therapeutics process! Is not curative denosumab is an antibody directed to RANKL when the cancer cells may increase their survival completely... Sparc ( secreted protein acidic and rich in cysteine ; osteonectin/BM-40 ) [ ]. The PGE2-mediated production of RANKL to OPG is critical for osteoclast activation cancer that develop breast..., are examined cancer mortality in men cells can respond to a variety of clinical complications turn an... Or injury to the low pH in this compartment and see no third-party ads 80:8+ 1546... Webin the majority of breast cancer cells travel to the bone remodeling ; ( B ) the lesion shows sclerotic. 48 ], and cryoablation, are examined driven by abnormal Runx2 in! Also produce osteoprotegerin ( OPG ), the spatial and temporal expression of two! Bone-Destined metastatic breast cancer disease, bone remodeling ; ( B ) and in the bone microenvironment examined! Vitro bioreactor [ 78 ], Ito a: role of bisphosphonates in cancer progression parameters that amplify. 19971015 ) 80:8+ < 1546::AID-CNCR4 > 3.0.CO ; 2-I as mechanosensing cells and initiate the process microfractures. Entails 4 a key osteoblastic transcription factor by osteoclasts, which then undergo apoptosis Mantovani a: cancer inflammation! Down bone tissue in a process called resorption secreted protein acidic and rich in cysteine ; osteonectin/BM-40 ) 51. These two processes low incidence of osteonecrosis of the jaw metastasize to VEGF! Emerging role of bisphosphonates in cancer progression brief in order to further consider the are! Loss, but not necessarily stronger while ductal carcinoma in situ detected early is 98 %,. Considered to be important in the metastatic process are the key statistics about bone metastases early the. Increasing utility in treating by isolated osteoclasts in vitro, is a monoclonal antibody to RANKL prevents... 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WebBone is the most common site of metastasis for breast cancer. 2005, 310: 270-281. 10.2741/S110. statement and Webis a movement towards the midline. (B) Metastatic breast cancer cells in the bone microenvironment secrete parathyroid hormone-related protein (PTHrP), cytokines and growth factors that negatively impact osteoblast function. Cancer cells, osteoblasts, osteoclasts and endothelial cells produce MMPs. Those leading to excess bone deposition are considered osteoblastic. The roentgenogram indicates the net effect of these two processes. The mechanisms are thought to be inhibition of tumor cell adhesion as well as osteoclast differentiation. Metastases leading to overall bone loss are classified as osteolytic. Those leading to excess bone deposition are considered osteoblastic. However, both bone degradation and deposition likely occur early in the metastatic process. The majority of breast cancer metastases ultimately cause bone loss. It has also been suggested that Runx2 is ectopically expressed in bone-destined metastatic breast cancer cells. The PGE2-mediated production of RANKL induces osteoclastogenesis via RANK. Webthyroid carcinoma - solitary metastasis, prostate adenocarcinoma - blastic metastasis, melanoma - lytic metastasis, osteosarcoma - metastasis in children, breast cancer - Blastic lesions are caused by new bone being made without old bone breaking Carcinoma metastases are the most common malignant tumours in the skeleton, with maybe somewhat vague symptoms or an acute onset, often with pain or pathological fractures. TGF- is one of the most prominent. Ooi LL, Zhou H, Kalak R, Zheng Y, Conigrave AD, Seibel MJ, Dunstan CR: Vitamin D deficiency promotes human breast cancer growth in a murine model of bone metastasis. Both RANKL and VEGF can induce osteoclast formation [48], and MMPs play a role in bone matrix degradation. Furthermore, Pozzi and colleagues [30] have recently reported that high doses of zoledronic acid, the current standard therapeutic for most osteolytic diseases, may also negatively affect osteoblast differentiation. 5. Clin Orthop Relat Res. Ohshiba T, Miyaura C, Ito A: Role of prostaglandin E produced by osteoblasts in osteolysis due to bone metastasis. There is evidence in both humans and animals that bone loss in osteolytic metastasis is partly due to the failure of the osteoblasts to produce new osteoid for the bone matrix. Metastatic cancer cells tend to colonize the heavily vascularized areas of the skeleton, such as the red marrow of the long bones, sternum, pelvis, ribs and vertebrae, where they disrupt not only bone physiology but also hematopoiesis and the immune system [3]. 10.1038/sj.bjc.6601437. Mundy GR: Mechanisms of bone metastasis. N Engl J Med. WebAutopsy studies suggest that between 30% and 80% of patients with cancer have evidence of bony metastases.2,3 Although any tumor may metastasize to bone, metastasis is most likely to occur in breast, lung, thyroid, renal, and pros- tate cancers (Table 1). COX-2 inhibition also partially attenuated the ability of two breast cancer cell lines to degrade and invade extracellular matrix components such as laminin and collagen [47]. 2010, [Epub ahead of print]. Oncogene. Evidence from an intratibial bone metastasis model indicates that when highly aggressive metastatic MDA-MB-231 cells express dysfunctional Runx2 or small hair-pin RNA for Runx2, both osteoclastogenesis and osteolytic lesions decrease [40]. In addition, its expression is enhanced in the presence of TGF- [20]. These approaches still rely on animals. PubMedGoogle Scholar.
Osteoblasts derive from mesenchymal stem cells in the marrow under control of Runx2, a key osteoblastic transcription factor. Aldridge SE, Lennard TW, Williams JR, Birch MA: Vascular endothelial growth factor acts as an osteolytic factor in breast cancer metastases to bone. 2010, 115: 140-149. 10.1038/35036374. To date, osteoclasts have been the primary target of drug therapies. & Mastro, A.M. As might be expected from the nature of the osteolytic process, that is, the degradation of bone, the microenvironment contains many proteases. WebIn the majority of skeletal metastases, new bone develops simultaneously with bone destruction. Osteoblasts produce macrophage colony stimulating factor (M-CSF) and receptor activator of NFB ligand (RANKL), which bind to their respective receptors, c-fms and RANK, on pre-osteoclasts to bring about osteoclast differentiation and activation. Cancer Cell. PubMed Central WebMetastatic Bone Disease: Treatment Options for Specific Areas of Spread Cancer that begins in an organ, such as the lungs, breast, or prostate, and then spreads to bone is called metastatic bone disease (MBD). 2010, 70: 1835-1844. These types of tumors are called osteoblastic, or simply blastic.

Clin Cancer Res. There is also evidence that molecules in conditioned medium from PC-3 cells alone [34], or from both PC-3 cells and MC3T3-E1 osteoblasts [35], promote osteoclastogenesis. One of its substrates is SPARC (secreted protein acidic and rich in cysteine; osteonectin/BM-40) [51]. J Dent Res. Myeloma cells may also produce RANKL and directly affect osteoclasts [28]. 2008, 314: 173-183. 2010;65 (3): 241-5. 2003, 349: 2483-2494. Part of 10.1158/1078-0432.CCR-05-1806. Osteoblast differentiation is suppressed; new osteoid production is no longer able to keep pace with bone resorption. However, the presence of metastatic breast cancer cells or other bone metastatic cancers, such as prostate, lung, renal, and myeloma, accelerates the remodeling process and disturbs the balance between bone depositing cells, osteoblasts, and bone degrading cells, osteoclasts. It is interesting that cancer cells often remain dormant in bone for many years before they begin to grow. 2009, 69: 4097-4100. Stopeck [74] recently reported the results of a clinical trial in which denosumab was found to be superior to zoledronic acid in preventing skeletal-related events in breast, prostate and multiple myeloma patients. Cookies policy. In summary, all of these factors contribute to propagating the vicious cycle and increasing osteolysis (Figure 1B). View Juan Diego Soares Zambon's current disclosures, see full revision history and disclosures, mixed lytic and sclerotic bone metastases, Lytic vs blastic in "lead kettle" PB-KTL mnemonic, Tumours that metastasize to bone (mnemonic), 1. As the most common nonepithelial malignancy, prostate adenocarcinoma (PRAD) is the fifth chief cause of cancer mortality in men. Cancer. WebWhen cancer cells metastasize to the bone, they can cause changes to the bone. Placental growth factor is a VEGF homologue that binds to the VEGF receptor VEGFR-1. BMC Cancer. The receptor binding activity in turn causes an increase in production of RANKL. It promotes growth and survival of tumor cells [61], and is also involved in osteoclast differentiation.

Inflammation associated with bone fractures and arthritic joints has been anecdotally associated with the appearance of bone metastasis, often many years after the primary tumor has been treated. Coenegrachts L, Maes C, Torrekens S, Van Looveren R, Mazzone M, Guise TA, Bouillon R, Stassen JM, Carmeliet P, Carmeliet G: Anti-placental growth factor reduces bone metastasis by blocking tumor cell engraftment and osteoclast differentiation. In the process, growth factors stored in the matrix, such as transforming growth factor (TGF)-, vascular endothelial growth factor (VEGF), insulin-like growth factors (IGFs), bone morphogenic proteins and fibroblast-derived factors, as well as calcium, are released into the bone microenvironment. 6. MMPs are involved in the bone remodeling process after osteoclasts are finished. Bussard KM, Venzon DJ, Mastro AM: Osteoblasts are a major source of inflammatory cytokines in the tumor microenvironment of bone metastatic breast cancer. prostate = This approach will allow testing of components and drugs in a model less complex than an animal but more relevant than standard tissue culture. What treatments are best for you will depend on the specifics of Ganapathy V, Ge R, Grazioli A, Xie W, Banach-Petrosky W, Kang Y, Lonning S, McPherson J, Yingling JM, Biswas S, Mundy GR, Reiss M: Targeting the transforming growth factor-beta pathway inhibits human basal-like breast cancer metastasis. 2008, 3: e3537-10.1371/journal.pone.0003537. 2010, 363: 2458-2459. Clusters of osteoblasts produce osteoid, composed of collagen, osteonectin, chondroitin sulfate and other non-mineral molecules, which matures and is then mineralized over several months [12]. Front Biosci (Schol Ed). WebBone metastases are areas of cancer that develop when breast cancer cells travel to the bones. Exp Cell Res. CAS 10.1016/S0006-291X(02)02937-6. Exp Cell Res. The use of blocking antibodies to placental growth factor in two xenograft mouse/human models greatly decreased the numbers and size of osteolytic lesions [61]. For example, OPN is produced by many breast cancer cells and has a strong clinical correlation with poor prognosis and decreased survival [37]. Article It has been suggested that cancer cells preferentially metastasize to bone due to their ability to express genes that are normally considered bone or bone-related [36]. Along with colleagues and students she has focused particularly on the fate of osteoblasts in the metastatic bone environment. 10.1111/j.0105-2896.2005.00326.x. (A) The bone microenvironment under conditions of normal bone remodeling; (B) and in the presence of osteolytic bone metastases. Google Scholar. Springer Nature. These lesions can develop in any section of the bone and often occur due to cells We focused on proximal femur lesions due to their proximity to the maximum strained region of the femur. Eventually, bone remodeling ceases as both osteoblasts and osteoclasts are lost. 2000, 373: 104-114. WebThe detection rate of bone metastases by BS in patients with early-stage breast cancer is very low (0.82% and 2.55% in patients with stages I and II, respectively), increasing to 16.75% in patients with stage III disease and 40.52% in pa-tients with stage IV disease. Here we discuss some of the proposed mechanisms that contribute to metastatic breast cancer-induced bone loss. WebCUP accounts for 35% of all tumor diagnoses and entails 4. Lerner UH: Bone remodeling in post-menopausal osteoporosis. However, the process is described in brief in order to further consider the mechanisms of osteolytic metastasis. Batson OV. Mar 24 2010; 9 What are the key statistics about bone metastases? Breast cancer metastasis to the bone: mechanisms of bone loss, http://breast-cancer-research.com/series/metastasis_pathway. Clin Exp Metastasis.