Skip to main content

What’s new in the management of metastatic bone disease


Metastatic bone disease is a common complication of malignant tumours. As cancer treatment improves the overall survival of patients, the number of patients with bone metastases is expected to increase. The treatments for bone metastases include surgery, radiotherapy, and bone-modifying agents, with patients with a short expected prognosis requiring less invasive treatment. Patients with metastatic bone disease show greatly varying primary tumour histology, metastases sites and numbers, and comorbidities. Therefore, randomised clinical trials are indispensable to compare treatments for these patients. This editorial reviews recent findings on the diagnosis and prognosis prediction and discusses the current treatment of patients with metastatic bone disease.

This is a preview of subscription content, access via your institution.


  1. 1.

    Sousa S, Clézardin P (2018) Bone-targeted therapies in cancer-induced bone disease. Calcif Tissue Int 102:227–250.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Campanacci M (1999) Bone and soft tissue tumors, 2nd edn. Springer-Verlag, New York, pp 755–758

    Book  Google Scholar 

  3. 3.

    Li S, Peng Y, Weinhandl ED, Blaes AH, Cetin K, Chia VM, Stryker S, Pinzone JJ, Acquavella JF, Arneson TJ (2012) Estimated number of prevalent cases of metastatic bone disease in the US adult population. Clin Epidemiol 4:87–93.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Bollen L, Dijkstra SPD, Bartels RHMA, de Graeff A, Poelma DLH, Brouwer T, Algra PR, Kuijlen JMA, Minnema MC, Nijboer C, Rolf C, Sluis T, Terheggen MAMB, van der Togt-van Leeuwen ACM, van der Linden YM, Taal W (2018) Clinical management of spinal metastases-The Dutch national guideline. Eur J Cancer 104:81–90.

    Article  PubMed  Google Scholar 

  5. 5.

    Lawrenz JM, Gordon J, George J, Haben C, Rubin BP, Ilaslan H, Mesko NW, Nystrom LM (2020) Does PET/CT aid in detecting primary carcinoma in patients with skeletal metastases of unknown primary? Clin Orthop Relat Res 478:2451–2457.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Zhu M, Liu X, Qu Y, Hu S, Zhang Y, Li W, Zhou X, Yang H, Zhou L, Wang Q, Hou Y, Chen Y, Wang Y, Wang Y, Lu Z, Luo Z, Hu X (2019) Bone metastasis pattern of cancer patients with bone metastasis but no visceral metastasis. J Bone Oncol 15:100219.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Zhang L, Wang Y, Gu Y, Hou Y, Chen Z (2019) The need for bone biopsies in the diagnosis of new bone lesions in patients with a known primary malignancy: A comparative review of 117 biopsy cases. J Bone Oncol 14:100213.

    Article  PubMed  Google Scholar 

  8. 8.

    Mutlu U, Balci A, Özsan GH, Özkal S, Şeyhanli A, Özgül HA (2020) Computed tomography characteristics of multiple myeloma and other osteolytic metastatic bone lesions. Acta Radiol.

    Article  PubMed  Google Scholar 

  9. 9.

    Li X, Wu N, Zhang W, Liu Y, Ming Y (2020) Differential diagnostic value of 18F-FDG PET/CT in osteolytic lesions. J Bone Oncol 24:100302.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Schoenfeld AJ, Le HV, Marjoua Y, Leonard DA, Belmont PJ, Bono CM, Harris MB (2016) Assessing the utility of a clinical prediction score regarding 30-day morbidity and mortality following metastatic spinal surgery: The New England Spinal Metastasis Score (NESMS). Spine J 16:482–490.

    Article  PubMed  Google Scholar 

  11. 11.

    Errani C, Mavrogenis AF, Cevolani L, Spinelli S, Piccioli A, Maccauro G, Baldini N, Donati D (2017) Treatment for long bone metastases based on a systematic literature review. Eur J Orthop Surg Traumatol 27:205–211.

    Article  PubMed  Google Scholar 

  12. 12.

    Errani C, Cosentino M, Ciani G, Ferra L, Alfaro PA, Bordini B, Donati DM (2021) C-reactive protein and tumour diagnosis predict survival in patients treated surgically for long bone metastases. Int Orthop 45:1337–1346.

    Article  PubMed  Google Scholar 

  13. 13.

    Anderson AB, Wedin R, Fabbri N, Boland P, Healey J, Forsberg JA (2020) External Validation of PATHFx Version 3.0 in Patients Treated Surgically and Nonsurgically for Symptomatic Skeletal Metastases. Clin Orthop Relat Res 478:808–818

    Article  Google Scholar 

  14. 14.

    Thio QCBS, Karhade AV, Bindels BJJ, Ogink PT, Bramer JAM, Ferrone ML, Calderón SL, Raskin KA, Schwab JH (2020) Development and internal validation of machine learning algorithms for preoperative survival prediction of extremity metastatic disease. Clin Orthop Relat Res 478:322–333.

    Article  PubMed  Google Scholar 

  15. 15.

    Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Ruatta F, Derosa L, Escudier B, Colomba E, Guida A, Baciarello G, Loriot Y, Fizazi K, Albiges L (2019) Prognosis of renal cell carcinoma with bone metastases: Experience from a large cancer centre. Eur J Cancer 107:79–85.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Tanaka A, Katagiri H, Murata H, Wasa J, Miyagi M, Honda Y, Takahashi M (2020) Surgery for femoral metastases. Bone Joint J 102:285–292

    Article  Google Scholar 

  18. 18.

    Katagiri H, Okada R, Takagi T, Takahashi M, Murata H, Harada H, Nishimura T, Asakura H, Ogawa H (2014) New prognostic factors and scoring system for patients with skeletal metastasis. Cancer Med 3:1359–1367.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Katagiri H, Takahashi M, Wakai K, Sugiura H, Kataoka T, Nakanishi K (2005) Prognostic factors and a scoring system for patients with skeletal metastasis. J Bone Joint Surg Br 87:698–703.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Philipp TC, Mikula JD, Doung YC, Gundle KR (2020) Is there an association between prophylactic femur stabilization and survival in patients with metastatic bone disease? Clin Orthop Relat Res 478:540–546.

    Article  PubMed  Google Scholar 

  21. 21.

    Erol B, Saglam F (2021) Are cemented endoprosthetic reconstructions superior to uncemented endoprostheses in terms of postoperative outcomes and complications in patients with extremity-located bone metastasis scheduled for adjuvant radiotherapy? J Arthroplasty 36:1160–1167.

    Article  PubMed  Google Scholar 

  22. 22.

    Bindels BJJ, Thio QCBS, Raskin KA, Ferrone ML, Lozano Calderón SA, Schwab JH (2020) Thirty-day postoperative complications after surgery for metastatic long bone disease are associated with higher mortality at 1 year. Clin Orthop Relat Res 478:306–318.

    Article  PubMed  Google Scholar 

  23. 23.

    Belzarena AC, Binitie O, Letson D, Joyce DM (2021) Intramedullary rod failure in metastatic breast cancer: Do triple negative cancer patients have more revision surgery? J Bone Oncol 28:100358.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Park JS, Park SJ, Lee CS (2019) Incidence and prognosis of patients with spinal metastasis as the initial manifestation of malignancy Analysis of 338 patients undergoing surgical treatment. Bone Joint J 101:1379–1384

    Article  Google Scholar 

  25. 25.

    Kanda Y, Kakutani K, Sakai Y, Yurube T, Miyazaki S, Takada T, Hoshino Y, Kuroda R (2020) Prospective cohort study of surgical outcome for spinal metastases in patients aged 70 years or older. Bone Joint J 102:1709–1716

    Article  Google Scholar 

  26. 26.

    Pranata R, Lim MA, Vania R, Bagus Mahadewa TG (2021) Minimal Invasive Surgery Instrumented Fusion versus Conventional Open Surgical Instrumented Fusion for the Treatment of Spinal metastases: A Systematic Review and Meta-analysis. World Neurosurg 148:e264–e274.

    Article  PubMed  Google Scholar 

  27. 27.

    Zaborovskii N, Ptashnikov D, Mikaylov D, Masevnin S, Smekalenkov O (2018) Preoperative embolization and local hemostatic agents in palliative decompression surgery for spinal metastases of renal cell carcinoma. Eur J Orthop Surg Traumatol 28:1047–1052.

    Article  PubMed  Google Scholar 

  28. 28.

    Kumar N, Ramos MRD, Patel R, Tan BWL, Lopez KG, Nolan CP, Kumar A, Kumar DS, Liu G, Benneker LM (2021) The “spinal metastasis invasiveness index”: A novel scoring system to assess surgical invasiveness. Spine 46:478–485

    Article  Google Scholar 

  29. 29.

    De la Garza Ramos R, Benton JA, Gelfand Y, Echt M, Hamad MK, Kinon MD, Yanamadala V, Yassari R (2021) A novel clinical scoring system for perioperative morbidity in metastatic spinal tumor surgery: The spine oncology morbidity assessment score. Spine 46:161–166

    Article  Google Scholar 

  30. 30.

    Groot OQ, Ogink PT, Paulino Pereira NR, Ferrone ML, Harris MB, Lozano-Calderon SA, Schoenfeld AJ, Schwab JH (2019) High risk of symptomatic venous thromboembolism after surgery for spine metastatic bone lesions: A retrospective study. Clin Orthop Relat Res 477:1674–1686.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Tekin SB, Karslı B, Büyükbebeci O, Demir İH, Gökalp AY, Kılınçoğlu V (2020) How do vertebroplasty and kyphoplasty affect the quality of life of patients with multiple myeloma spinal metastasis? Eur J Orthop Surg Traumatol 30:1447–1451.

    Article  PubMed  Google Scholar 

  32. 32.

    Sun Y, Zhang H, Xu HR, Liu JZ, Pan J, Zhai HZ, Lu CY, Zhao X, Chen YQ, Zhou LL, Yu J, Han J (2019) Analgesia of percutaneous thermal ablation plus cementoplasty for cancer bone metastases. J Bone Oncol 19:100266.

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Balestrino A, Boriani S, Cecchinato R, Parafioriti A, Gambarotti M, Gasbarrini A (2020) Vertebroplasty shows no antitumoral effect on vertebral metastasis: A case-based study on anatomopathological examinations. Eur Spine J 29:3157–3162.

    Article  PubMed  Google Scholar 

  34. 34.

    Houdek MT, Ferguson PC, Abdel MP, Griffin AM, Hevesi M, Perry KI, Rose PS, Wunder JS, Lewallen DG (2020) Comparison of porous tantalum acetabular implants and Harrington reconstruction for metastatic disease of the acetabulum. J Bone Joint Surg Am 102:1239–1247.

    Article  PubMed  Google Scholar 

  35. 35.

    Gazendam A, Axelrod D, Wilson D, Ghert M (2021) Emerging concepts in the surgical management of peri-acetabular metastatic bone disease. Curr Oncol 28:2731–2740.

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Tarawneh AM, Sabou S, AlKalbani S, Pasku D, Quraishi NA (2020) Clinical outcomes of sacroplasty for metastatic sacral tumours: A systematic review and meta-analysis. Eur Spine J 29:3116–3122.

    Article  PubMed  Google Scholar 

  37. 37.

    Moser TP, Onate M, Achour K, Freire V (2019) Cementoplasty of pelvic bone metastases: Systematic assessment of lesion filling and other factors that could affect the clinical outcomes. Skelet Radiol 48:1345–1355.

    Article  Google Scholar 

  38. 38.

    Hesler MC, Buy X, Catena V, Brouste V, Kind M, Palussière J, Crombé A (2019) Assessment of risk factors for occurrence or worsening of acetabular fracture following percutaneous cementoplasty of acetabulum malignancies. Eur J Radiol 120:108694.

    Article  PubMed  Google Scholar 

  39. 39.

    Yang R, Goch A, Murphy D, Wang J, Charubhumi V, Fox J, Sen M, Hoang B, Geller D (2020) A novel tripod percutaneous reconstruction technique in periacetabular lesions caused by metastatic cancer. J Bone Joint Surg Am 102:592–599.

    Article  PubMed  Google Scholar 

  40. 40.

    Harrington KD (1981) The management of acetabular insufficiency secondary to metastatic malignant disease. J Bone Joint Surg Am 63:653–664.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Roux C, Tselikas L, Yevich S, Sandes Solha R, Hakime A, Teriitehau C, Gravel G, de Baere T, Deschamps F (2019) Fluoroscopy and cone-beam CT-guided fixation by internal cemented screw for pathologic pelvic fractures. Radiology 290:418–425.

    Article  PubMed  Google Scholar 

  42. 42.

    van de Ven S, van den Bongard D, Pielkenrood B, Kasperts N, Eppinga W, Peters M, Verkooijen H, van der Velden J (2020) Patient-reported outcomes of oligometastatic patients after conventional or stereotactic radiation therapy to bone metastases: An analysis of the PRESENT cohort. Int J Radiat Oncol Biol Phys 107:39–47.

    Article  PubMed  Google Scholar 

  43. 43.

    Kim TH, Park S, Rim CH, Choi C, Seong J (2021) Improved oncologic outcomes by ablative radiotherapy in patients with bone metastasis from hepatocellular carcinoma. J Cancer Res Clin Oncol 147:2693–2700.

    Article  PubMed  Google Scholar 

  44. 44.

    Chen-Xu S, Martel-Villagrán J, Bueno-Horcajadas Á (2021) Percutaneous management of bone metastases: State of the art. Radiol (Engl Ed) 63:345–357.

    CAS  Article  Google Scholar 

  45. 45.

    Jiang L, Cui X, Ma H, Tang X (2021) Comparison of denosumab and zoledronic acid for the treatment of solid tumors and multiple myeloma with bone metastasis: A systematic review and meta-analysis based on randomized controlled trials. J Orthop Surg Res 16:400.

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Okuma S, Matsuda Y, Nariai Y, Karino M, Suzuki R, Kanno T (2020) A retrospective observational study of risk factors for denosumab-related osteonecrosis of the jaw in patients with bone metastases from solid cancers. Cancers Basel 12:E1209.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Ikesue H, Mouri M, Tomita H, Hirabatake M, Ikemura M, Muroi N, Yamamoto S, Takenobu T, Tomii K, Kawakita M, Katoh H, Ishikawa T, Yasui H, Hashida T (2021) Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases. Support Care Cancer 29:4763–4772.

    Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Belehradek M, Domenge C, Luboinski B, Orlowski S, Belehradek J, Mir LM (1993) Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial Cancer 72:3694–3700.;2-2

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Horiuchi A, Nikaido T, Mitsushita J, Toki T, Konishi I, Fujii S (2000) Enhancement of antitumor effect of bleomycin by low-voltage in vivo electroporation: A study of human uterine leiomyosarcomas in nude mice. Int J Cancer 88:640–644.;2-k

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Kotnik T, Pucihar G, Miklavcic D (2010) Induced transmembrane voltage and its correlation with electroporation-mediated molecular transport. J Membr Biol 236:3–13.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Campanacci L, Bianchi G, Cevolani L, Errani C, Ciani G, Facchini G, Spinnato P, Tognù A, Massari L, Cornelis FH, Mosconi M, Screpis D, Benazzo F, Rossi B, Bonicoli E, Fazioli F, Nicolosi M, Boffano M, Piana R, De Terlizzi F, Cadossi M, Donati DM (2021) Operating procedures for electrochemotherapy in bone metastases: Results from a multicenter prospective study on 102 patients. Eur J Surg Oncol S0748–7983:00480–00487.

    Article  Google Scholar 

Download references


The authors did not receive support from any organization for the submitted work.

Author information




ST and AFM performed the literature search and wrote the manuscript. CE and AK revised the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Shinji Tsukamoto.

Ethics declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tsukamoto, S., Errani, C., Kido, A. et al. What’s new in the management of metastatic bone disease. Eur J Orthop Surg Traumatol 31, 1547–1555 (2021).

Download citation


  • Metastatic bone disease
  • Prognosis
  • Cancer
  • Cementoplasty
  • Radiotherapy
  • Electrochemotherapy