Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Osteoporosis Reports
Published in: Current Osteoporosis Reports 5/2019

01-10-2019 | Metastasis | Cancer-induced Musculoskeletal Diseases (E Keller and J Sterling, Section editors)

Breast Cancer Dormancy in Bone

Authors: Miranda E. Clements, Rachelle W. Johnson

Published in: Current Osteoporosis Reports | Issue 5/2019

Login to get access

Abstract

Purpose of Review

The goal of this review is to summarize recent experimental and clinical evidence for metastatic latency and the molecular mechanisms that regulate tumor dormancy in the bone.

Recent Findings

Tumor dormancy contributes to the progression of metastasis and thus has significant clinical implications for prognosis and treatment. Tumor-intrinsic signaling and specialized bone marrow niches play a pivotal role in determining the dormancy status of bone disseminated tumor cells. Experimental models have provided significant insight into the effects of the bone microenvironment on tumor cells; however, these models remain limited in their ability to study dormancy.

Summary

Despite recent advances in the mechanistic understanding of how tumor cells remain dormant in the bone for prolonged periods of time, the signals that trigger spontaneous dormancy escape remain unclear. This review highlights the need for further investigation of mechanisms underlying tumor dormancy using clinically relevant models.
Literature
1.
2.
Berman AT, Thukral AD, Hwang W-T, Solin LJ, Vapiwala N. Incidence and patterns of distant metastases for patients with early-stage breast cancer after breast conservation treatment. Clinical Breast Cancer. 2013;13(2):88–94.PubMed
3.
Brockton NT, Gill SJ, Laborge SL, Paterson AHG, Cook LS, Vogel HJ, et al. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer. BMC Cancer. 2015;15:512.PubMedPubMedCentral
4.
Mariotto AB, Etzioni R, Hurlbert M, Penberthy L, Mayer M. Estimation of the number of women living with metastatic breast cancer in the United States. Cancer Epidemiol Biomark Prev. 2017;26:809–815.
5.
Croucher PI, McDonald MM, Martin TJ. Bone metastasis: the importance of the neighbourhood. Nat Rev Cancer. 2016;16(6):373–86.PubMed
6.
•• Gomis RR, Gawrzak S. Tumor cell dormancy. Mol Oncol. 2017;11(1):62–78. A recent review of tumor dormancy across multiple tumor types and tissues. PubMedPubMedCentral
7.
Han HH, Lee SH, Kim BG, Lee JH, Kang S, Cho NH. Estrogen receptor status predicts late-onset skeletal recurrence in breast cancer patients. Medicine (Baltimore). 2016;95(8):e2909.
8.
Savci-Heijink CD, Halfwerk H, Hooijer GK, Horlings HM, Wesseling J, van de Vijver MJ. Retrospective analysis of metastatic behaviour of breast cancer subtypes. Breast Cancer Res Treat. 2015;150(3):547–57.PubMedPubMedCentral
9.
Macedo F, Ladeira K, Pinho F, Saraiva N, Bonito N, Pinto L, et al. Bone metastases: an overview. Oncol Rev. 2017;11(1):321.PubMedPubMedCentral
10.
Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836–46.PubMedPubMedCentral
11.
Johnson RW, Schipani E, Giaccia AJ. HIF targets in bone remodeling and metastatic disease. Pharmacol Ther. 2015;150:169–77.PubMedPubMedCentral
12.
Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27(3):165–76.PubMed
13.
Klein D. The tumor vascular endothelium as decision maker in cancer therapy. Front Oncol. 2018;8:367.
14.
Gimbrone MA Jr, Leapman SB, Cotran RS, Folkman J. Tumor dormancy in vivo by prevention of neovascularization. J Exp Med. 1972;136(2):261–76.PubMedPubMedCentral
15.
Ghajar CM, Peinado H, Mori H, Matei IR, Evason KJ, Brazier H, et al. The perivascular niche regulates breast tumour dormancy. Nat Cell Biol. 2013;15(7):807–17.PubMedPubMedCentral
16.
Straume O, Shimamura T, Lampa MJG, Carretero J, Øyan AM, Jia D, et al. Suppression of heat shock protein 27 induces long-term dormancy in human breast cancer. Proc Natl Acad Sci U S A. 2012;109(22):8699–704.PubMedPubMedCentral
17.
Baxevanis CN, Perez SA. Cancer dormancy: a regulatory role for endogenous immunity in establishing and maintaining the tumor dormant state. Vaccines (Basel). 2015;3(3):597–619.
18.
Bidwell BN, Slaney CY, Withana NP, Forster S, Cao Y, Loi S, et al. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nat Med. 2012;18(8):1224–31.PubMed
19.
Malladi S, Macalinao DG, Jin X, He L, Basnet H, Zou Y, et al. Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell. 2016;165(1):45–60.PubMedPubMedCentral
20.
Krall JA, Reinhardt F, Mercury OA, Pattabiraman DR, Brooks MW, Dougan M, et al. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Science Translational Medicine. 2018;10(436):eaan3464.PubMedPubMedCentral
21.
Dasgupta A, Lim AR, Ghajar CM. Circulating and disseminated tumor cells: harbingers or initiators of metastasis? Mol Oncol. 2017;11(1):40–61.PubMedPubMedCentral
22.
Husemann Y, Geigl JB, Schubert F, Musiani P, Meyer M, Burghart E, et al. Systemic spread is an early step in breast cancer. Cancer Cell. 2008;13(1):58–68.PubMed
23.
Sanger N, Effenberger KE, Riethdorf S, Van Haasteren V, Gauwerky J, Wiegratz I, et al. Disseminated tumor cells in the bone marrow of patients with ductal carcinoma in situ. Int J Cancer. 2011;129(10):2522–6.PubMed
24.
Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353(8):793–802.PubMed
25.
Gruber IV, Hartkopf AD, Hahn M, Taran F-A, Staebler A, Wallwiener D, et al. Relationship between hematogenous tumor cell dissemination and cellular immunity in DCIS patients. Anticancer Res. 2016;36(5):2345–51.PubMed
26.
Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Jückstock J, et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse—a European pooled analysis. Clin Cancer Res. 2011;17(9):2967–76.PubMed
27.
28.
Lee SH, Park SA, Zou Y, Seo S-U, Jun C-D, Lee WJ, et al. Real-time monitoring of cancer cells in live mouse bone marrow. Front Immunol. 2018;9:1681.PubMedPubMedCentral
29.
Jung Y, Wang J, Schneider A, Sun YX, Koh-Paige AJ, Osman NI, et al. Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing. Bone. 2006;38(4):497–508.PubMed
30.
Wang J, Loberg R, Taichman RS. The pivotal role of CXCL12 (SDF-1)/CXCR4 axis in bone metastasis. Cancer Metastasis Rev. 2006;25(4):573–87.PubMed
31.
32.
Zhang XH, Jin X, Malladi S, Zou Y, Wen YH, Brogi E, et al. Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell. 2013;154(5):1060–73.PubMedPubMedCentral
33.
Fluegen G, Avivar-Valderas A, Wang Y, Padgen MR, Williams JK, Nobre AR, et al. Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments. Nat Cell Biol. 2017;19(2):120–32.PubMedPubMedCentral
34.
Lan Q, Peyvandi S, Duffey N, Huang Y-T, Barras D, Held W, et al. Type I interferon/IRF7 axis instigates chemotherapy-induced immunological dormancy in breast cancer. Oncogene. 2019;38(15):2814–29.PubMed
35.
36.
Crane GM, Jeffery E, Morrison SJ. Adult haematopoietic stem cell niches. Nat Rev Immunol. 2017;17(9):573–90.PubMed
37.
Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J, et al. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest. 2011;121(4):1298–312.PubMedPubMedCentral
38.
Price TT, Burness ML, Sivan A, Warner MJ, Cheng R, Lee CH, et al. Dormant breast cancer micrometastases reside in specific bone marrow niches that regulate their transit to and from bone. Sci Transl Med. 2016;8(340):340ra73.PubMedPubMedCentral
39.
Bliss SA, Sinha G, Sandiford OA, Williams LM, Engelberth DJ, Guiro K, et al. Mesenchymal stem cell–derived exosomes stimulate cycling quiescence and early breast cancer dormancy in bone marrow. Cancer Res. 2016;76(19):5832–44.PubMed
40.
Wang H, Yu C, Gao X, Welte T, Muscarella AM, Tian L, et al. The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells. Cancer Cell. 2015;27(2):193–210.PubMedPubMedCentral
41.
• Tulotta C, Lefley DV, Freeman K, Gregory WM, Hanby AM, Heath PR, et al. Endogenous production of IL1B by breast cancer cells drives metastasis and colonization of the bone microenvironment. Clinical Cancer Research. 2019;25(9):2769–82 Found that interaction of breast cancer cells with osteoblasts within the endosteal niche results in the enhanced secretion of IL-1B, expansion of the metastatic niche, and proliferation of tumor cells. PubMed
42.
Adam AP, George A, Schewe D, Bragado P, Iglesias BV, Ranganathan AC, et al. Computational identification of a p38SAPK-regulated transcription factor network required for tumor cell quiescence. Cancer Res. 2009;69(14):5664–72.PubMedPubMedCentral
43.
Yu-Lee LY, Yu G, Lee YC, Lin SC, Pan J, Pan T, et al. Osteoblast-secreted factors mediate dormancy of metastatic prostate cancer in the bone via activation of the TGFbetaRIII-p38MAPK-pS249/T252RB pathway. Cancer Res. 2018;78(11):2911–24.PubMedPubMedCentral
44.
Bragado P, Estrada Y, Parikh F, Krause S, Capobianco C, Farina HG, et al. TGF-beta2 dictates disseminated tumour cell fate in target organs through TGF-beta-RIII and p38alpha/beta signalling. Nat Cell Biol. 2013;15(11):1351–61.PubMedPubMedCentral
45.
Aguirre-Ghiso JA, Liu D, Mignatti A, Kovalski K, Ossowski L, Hunter T. Urokinase receptor and fibronectin regulate the ERKMAPK to p38MAPK activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol Biol Cell. 2001;12(4):863–79.PubMedPubMedCentral
46.
Kobayashi A, Okuda H, Xing F, Pandey PR, Watabe M, Hirota S, et al. Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med. 2011;208(13):2641–55.PubMedPubMedCentral
47.
Sosa MS, Bragado P, Aguirre-Ghiso JA. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer. 2014;14(9):611–22.PubMedPubMedCentral
48.
•• Gawrzak S, Rinaldi L, Gregorio S, Arenas EJ, Salvador F, Urosevic J, et al. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer. Nat Cell Biol. 2018;20(2):211–21 Identified MSK1 as a critical regulator of luminal cell differentiation and ER+ tumor dormancy. PubMed
49.
Kim RS, Avivar-Valderas A, Estrada Y, Bragado P, Sosa MS, Aguirre-Ghiso JA, et al. Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer. PLoS One. 2012;7(4):e35569.PubMedPubMedCentral
50.
Sosa MS, Parikh F, Maia AG, Estrada Y, Bosch A, Bragado P, et al. NR2F1 controls tumour cell dormancy via SOX9- and RARbeta-driven quiescence programmes. Nat Commun. 2015;6:6170.PubMed
51.
Borgen E, Rypdal MC, Sosa MS, Renolen A, Schlichting E, Lønning PE, et al. NR2F1 stratifies dormant disseminated tumor cells in breast cancer patients. Breast Cancer Res. 2018;20(1):120.PubMedPubMedCentral
52.
• Vera-Ramirez L, Vodnala SK, Nini R, Hunter KW, Green JE. Autophagy promotes the survival of dormant breast cancer cells and metastatic tumour recurrence. Nature Communications. 2018;9(1):1944 Identified autophagy as a major pathway that drives the survival and dormancy of bone-disseminated breast cancer cells.
53.
Sosa MS, Bragado P, Debnath J, Aguirre-Ghiso JA. Regulation of tumor cell dormancy by tissue microenvironments and autophagy. Adv Exp Med Biol. 2013;734:73–89.PubMedPubMedCentral
54.
55.
Msaki A, Pastò A, Curtarello M, Arigoni M, Barutello G, Calogero RA, et al. A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model. Oncotarget. 2016;7(22):33081–95.PubMedPubMedCentral
56.
Johnson RW, Finger EC, Olcina MM, Vilalta M, Aguilera T, Miao Y, et al. Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow. Nat Cell Biol. 2016;18(10):1078–89.PubMedPubMedCentral
57.
Chen D, Sun Y, Wei Y, Zhang P, Rezaeian AH, Teruya-Feldstein J, et al. LIFR is a breast cancer metastasis suppressor upstream of the hippo-YAP pathway and a prognostic marker. Nat Med. 2012;18(10):1511–7.PubMedPubMedCentral
58.
Laderoute KR, Alarcon RM, Brody MD, Calaoagan JM, Chen EY, Knapp AM, et al. Opposing effects of hypoxia on expression of the angiogenic inhibitor thrombospondin 1 and the angiogenic inducer vascular endothelial growth factor. Clin Cancer Res. 2000;6(7):2941–50.PubMed
59.
Bienes-Martínez R, Ordóñez A, Feijoo-Cuaresma M, Corral-Escariz M, Mateo G, Stenina O, et al. Autocrine stimulation of clear-cell renal carcinoma cell migration in hypoxia via HIF-independent suppression of thrombospondin-1. Sci Rep. 2012;2:788.PubMedPubMedCentral
60.
Firlej V, Mathieu JRR, Gilbert C, Lemonnier L, Nakhlé J, Gallou-Kabani C, et al. Thrombospondin-1 triggers cell migration and development of advanced prostate tumors. Cancer Res. 2011;71(24):7649–58.PubMed
61.
Kumar R, Mickael C, Kassa B, Gebreab L, Robinson JC, Koyanagi DE, et al. TGF-β activation by bone marrow-derived thrombospondin-1 causes schistosoma- and hypoxia-induced pulmonary hypertension. Nat Commun. 2017;8:15494.PubMedPubMedCentral
62.
Labrousse-Arias D, Castillo-González R, Rogers NM, Torres-Capelli M, Barreira B, Aragonés J, et al. HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction. Cardiovasc Res. 2016;109(1):115–30.PubMed
63.
Shimizu H, Takeishi S, Nakatsumi H, Nakayama KI. Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells. JCI Insight. 2019;4(4):e125138.
64.
El-Shennawy L, Dubrovskyi O, Kastrati I, Danes JM, Zhang Y, Whiteley HE, et al. Coactivation of estrogen receptor and IKKβ induces a dormant metastatic phenotype in ER-positive breast cancer. Cancer Res. 2018;78(4):974–84.PubMed
65.
Johnson RW, Sun Y, Ho PWM, Chan ASM, Johnson JA, Pavlos NJ, et al. Parathyroid hormone-related protein negatively regulates tumor cell dormancy genes in a PTHR1/cyclic AMP-independent manner. Front Endocrinol. 2018;9:241.
66.
Thomas RJ, Guise TA, Yin JJ, Elliott J, Horwood NJ, Martin TJ, et al. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology. 1999;140(10):4451–8.PubMed
67.
Wang H, Tian L, Liu J, Goldstein A, Bado I, Zhang W, et al. The osteogenic niche is a calcium reservoir of bone micrometastases and confers unexpected therapeutic vulnerability. Cancer Cell. 2018;34(5):823–39.e7.PubMedPubMedCentral
68.
Marlow R, Honeth G, Lombardi S, Cariati M, Hessey S, Pipili A, et al. A novel model of dormancy for bone metastatic breast cancer cells. Cancer Res. 2013;73(23):6886–99.PubMed
69.
McGrath J, Panzica L, Ransom R, Withers HG, Gelman IH. Identification of genes regulating breast cancer dormancy in 3D bone endosteal niche cultures. Mol Cancer Res. 2019;17(4):860–9.PubMedPubMedCentral
70.
Buschhaus JM, Luker KE, Luker GD. A facile, in vitro 384-well plate system to model disseminated tumor cells in the bone marrow microenvironment. Methods Mol Biol. 1686;2018:201–13.
71.
• Sowder ME, Johnson RW. Enrichment and detection of bone disseminated tumor cells in models of low tumor burden. Scientific Reports. 2018;8(1):14299 Established highly sensitive methods to detect rare DTCs in the bone marrow in novel models of prolonged latency and low tumor burden.
72.
Capietto AH, Chan SR, Ricci B, Allen JA, Su X, Novack DV, et al. Novel ERalpha positive breast cancer model with estrogen independent growth in the bone microenvironment. Oncotarget. 2016;7(31):49751–64.PubMedPubMedCentral
73.
Lawson DA, Bhakta NR, Kessenbrock K, Prummel KD, Yu Y, Takai K, et al. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature. 2015;526(7571):131–5.PubMedPubMedCentral
74.
Harper KL, Sosa MS, Entenberg D, Hosseini H, Cheung JF, Nobre R, et al. Mechanism of early dissemination and metastasis in Her2(+) mammary cancer. Nature. 2016;540:588–92.PubMedPubMedCentral
75.
Hosseini H, Obradovic MM, Hoffmann M, Harper KL, Sosa MS, Werner-Klein M, et al. Early dissemination seeds metastasis in breast cancer. Nature. 2016;540(7634):552–558.PubMedPubMedCentral
76.
Wright LE, Ottewell PD, Rucci N, Peyruchaud O, Pagnotti GM, Chiechi A, et al. Murine models of breast cancer bone metastasis. Bonekey Rep. 2016;5:804.PubMedPubMedCentral
77.
Zheng H, Bae Y, Kasimir-Bauer S, Tang R, Chen J, Ren G, et al. Therapeutic antibody targeting tumor- and osteoblastic niche-derived Jagged1 sensitizes bone metastasis to chemotherapy. Cancer Cell. 2017;32(6):731–47.e6.PubMedPubMedCentral
78.
Yu C, Wang H, Muscarella A, Goldstein A, Zeng H-C, Bae Y, et al. Intra-iliac artery injection for efficient and selective modeling of microscopic bone metastasis. J Vis Exp. 2016;115:53982.
79.
Kuchimaru T, Kataoka N, Nakagawa K, Isozaki T, Miyabara H, Minegishi M, et al. A reliable murine model of bone metastasis by injecting cancer cells through caudal arteries. Nat Commun. 2018;9(1):2981.PubMedPubMedCentral
80.
Peyruchaud O, Winding B, Pécheur I, Serre C-M, Delmas P, Clézardin P. Early detection of bone metastases in a murine model using fluorescent human breast cancer cells: application to the use of the bisphosphonate zoledronic acid in the treatment of osteolytic lesions. J Bone Miner Res. 2001;16(11):2027–34.PubMed
81.
Ottewell PD, Deux B, Mönkkönen H, Cross S, Coleman RE, Clezardin P, et al. Differential effect of doxorubicin and zoledronic acid on intraosseous versus extraosseous breast tumor growth in vivo. Clin Cancer Res. 2008;14(14):4658–66.PubMed
82.
Campbell JP, Merkel AR, Masood-Campbell SK, Elefteriou F, Sterling JA. Models of bone metastasis. J Vis Exp. 2012;67:e4260.
83.
Barkan D, Kleinman H, Simmons JL, Asmussen H, Kamaraju AK, Hoenorhoff MJ, et al. Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton. Cancer Res. 2008;68(15):6241–50.PubMedPubMedCentral
84.
Dall G, Vieusseux J, Unsworth A, Anderson R, Britt K. Low dose, low cost estradiol pellets can support MCF-7 tumour growth in nude mice without bladder symptoms. J Cancer. 2015;6(12):1331–6.PubMedPubMedCentral
85.
Gakhar G, Wight-Carter M, Andrews G, Olson S, Nguyen TA. Hydronephrosis and urine retention in estrogen-implanted athymic nude mice. Vet Pathol. 2009;46(3):505–8.PubMed
86.
Holen I, Speirs V, Morrissey B, Blyth K. In vivo models in breast cancer research: progress, challenges and future directions. Dis Model Mech. 2017;10(4):359–71.PubMedPubMedCentral
87.
Eyre R, Alférez DG, Spence K, Kamal M, Shaw FL, Simões BM, et al. Patient-derived mammosphere and xenograft tumour initiation correlates with progression to metastasis. J Mammary Gland Biol Neoplasia. 2016;21(3–4):99–109.PubMedPubMedCentral
88.
Whittle JR, Lewis MT, Lindeman GJ, Visvader JE. Patient-derived xenograft models of breast cancer and their predictive power. Breast Cancer Res. 2015;17(1):17.PubMedPubMedCentral
Metadata
Title
Breast Cancer Dormancy in Bone
Authors
Miranda E. Clements
Rachelle W. Johnson
Publication date
01-10-2019
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 5/2019
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-019-00532-y

Other articles of this Issue 5/2019

Current Osteoporosis Reports 5/2019 Go to the issue

Skeletal Biology and Regulation (M Forwood and A Robling, Section Editors)

Cellular Processes by Which Osteoblasts and Osteocytes Control Bone Mineral Deposition and Maturation Revealed by Stage-Specific EphrinB2 Knockdown

Cancer-induced Musculoskeletal Diseases (E Keller and J Sterling, Section editors)

Osteosarcoma in the Post Genome Era: Preclinical Models and Approaches to Identify Tractable Therapeutic Targets

Bone and Diabetes (A Schwartz and P Vestergaard, Section Editors)

Peripheral Neuropathy as a Component of Skeletal Disease in Diabetes

Osteocytes (J Klein-Nulend, Section editor)

Physicochemical Niche Conditions and Mechanosensing by Osteocytes and Myocytes

Kidney and Bone (I Salusky and T Nickolas, Section Editors)

Controversies in the Management of Secondary Hyperparathyroidism in Chronic Kidney Disease

Bone and Diabetes (A Schwartz and P Vestergaard, Section Editors)

Osteoglycin and Bone—a Systematic Review