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
BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2019

Open Access 01-12-2019 | aneurysmal bone cyst | Case report

Aneurysmal bone cyst: results of an off label treatment with Denosumab

Authors: Hans Roland Dürr, Ferdinand Grahneis, Andrea Baur-Melnyk, Thomas Knösel, Christof Birkenmaier, Volkmar Jansson, Alexander Klein

Published in: BMC Musculoskeletal Disorders | Issue 1/2019

Login to get access

Abstract

Background

The treatment of aneurysmal bone cysts (ABCs) has evolved and less invasive methods have been tried. Denosumab is a monoclonal antibody which inhibits osteoclasts. It has been shown to be effective in giant cell tumour of bone (GCT) of bone and hence promises some effect also in ABC. We report on 6 patients treated with Denosumab and compare our results to the cases already published.

Methods

Data of 6 patients with ABCs and patients whose treatment included Denosumab were retrospectively analyzed. Denosumab was used at a dose of 120 mg on days 1, 8, 15 and 29, and every 4 weeks thereafter. In some of these patients the dose was reduced at the end of the treatment. Clinical and radiological responses were evaluated.

Results

In 4 female and 2 male patients with a mean age of 17 years (range: 6–30 years) the lesions were located in the sacrum (2), in distal radius, distal femur, talus and pelvis. One of the sacral lesions healed after 12 months and has stayed stable for 3 years since. The second patient received 2 years of therapy with recalcification, but recurred 1 year later and is under renewed therapy. The pelvic lesion improved but recurred. This patient has a 13-years history of intermittent therapy including surgery, two pregnancies and remains in a stable situation. The lesion of the talus did not improve with Denosumab after surgery and was complicated by destruction of the ankle joint with osteoarthritis. Recurrent lesions of the distal femur and the distal radius, previously treated by curettage and bone grafting healed under Denosumab and have remained stable for 2 and 3 years, respectively. One case of severe hypercalcemia was observed in a 7-year old child 6 months after discontinuation of Denosumab.

Conclusion

Denosumab provides a treatment option for ABCs in anatomically critical locations. Adjuvant application might reduce the rate of local recurrence. In young patients, severe rebound hypercalcemia months after discontinuation of Denosumab may occur.
Literature
1.
Jaffe HL, Lichtenstein L. Solitary unicameral bone cyst: with emphasis on the roentgen picture, the pathologic appearence and the pathogenesis. Arch Surg. 1942;44:1004–25.CrossRef
2.
Martinez V, Sissons HA. Aneurysmal bone cyst. A review of 123 cases including primary lesions and those secondary to other bone pathology. Cancer. 1988;61(11):2291–304.PubMedCrossRef
3.
Vergel De Dios AM, Bond JR, Shives TC, McLeod RA, Unni KK. Aneurysmal bone cyst. A clinicopathologic study of 238 cases. Cancer. 1992;69(12):2921–31.PubMedCrossRef
4.
Sciot R, Dorfman H, Brys P, Dal Cin P, De Wever I, Fletcher CD, Jonson K, Mandahl N, Mertens F, Mitelman F, et al. Cytogenetic-morphologic correlations in aneurysmal bone cyst, giant cell tumor of bone and combined lesions. A report from the CHAMP study group. Mod Pathol. 2000;13(11):1206–10.PubMedCrossRef
5.
Clough JR, Price CH. Aneurysmal bone cyst: pathogenesis and long term results of treatment. Clin Orthop Relat Res. 1973;97:52–63.CrossRef
6.
Kransdorf MJ, Sweet DE. Aneurysmal bone cyst: concept, controversy, clinical presentation, and imaging. AJR Am J Roentgenol. 1995;164(3):573–80.PubMedCrossRef
7.
Panoutsakopoulos G, Pandis N, Kyriazoglou I, Gustafson P, Mertens F, Mandahl N. Recurrent t(16;17)(q22;p13) in aneurysmal bone cysts. Genes Chromosomes Cancer. 1999;26(3):265–6.PubMedCrossRef
8.
Baumhoer D, Amary F, Flanagan AM. An update of molecular pathology of bone tumors. Lessons learned from investigating samples by next generation sequencing. Genes Chromosomes Cancer. 2019;58(2):88–99.PubMedCrossRef
9.
Ye Y, Pringle LM, Lau AW, Riquelme DN, Wang H, Jiang T, Lev D, Welman A, Blobel GA, Oliveira AM, et al. TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB. Oncogene. 2010;29(25):3619–29.PubMedPubMedCentralCrossRef
10.
Lau AW, Pringle LM, Quick L, Riquelme DN, Ye Y, Oliveira AM, Chou MM. TRE17/ubiquitin-specific protease 6 (USP6) oncogene translocated in aneurysmal bone cyst blocks osteoblastic maturation via an autocrine mechanism involving bone morphogenetic protein dysregulation. J Biol Chem. 2010;285(47):37111–20.PubMedPubMedCentralCrossRef
11.
Park HY, Yang SK, Sheppard WL, Hegde V, Zoller SD, Nelson SD, Federman N, Bernthal NM. Current management of aneurysmal bone cysts. Curr Rev Musculo Med. 2016;9(4):435–44.CrossRef
12.
13.
Rossi G, Mavrogenis AF, Facchini G, Bartalena T, Rimondi E, Renzulli M, Andreone A, Durante S, Angelini A, Errani C. How effective is embolization with N-2-butyl-cyanoacrylate for aneurysmal bone cysts? Int Orthop. 2017;41(8):1685–92.PubMedCrossRef
14.
Terzi S, Gasbarrini A, Fuiano M, Barbanti Brodano G, Ghermandi R, Bandiera S, Boriani S. Efficacy and safety of selective arterial embolization in the treatment of aneurysmal bone cyst of the Mobile spine: a retrospective observational study. Spine (Phila Pa 1976). 2017;42(15):1130–8.CrossRef
15.
Batisse F, Schmitt A, Vendeuvre T, Herbreteau D, Bonnard C. Aneurysmal bone cyst: a 19-case series managed by percutaneous sclerotherapy. Orthop Traumatol Surg Res. 2016;102(2):213–6.PubMedCrossRef
16.
Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, Holmes GB, Dunstan CR, DePaoli AM. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19(7):1059–66.PubMedCrossRef
17.
18.
Palmerini E, Ruggieri P, Angelini A, Boriani S, Campanacci D, Milano GM, Cesari M, Paioli A, Longhi A, Abate ME, et al. Denosumab in patients with aneurysmal bone cysts: a case series with preliminary results. Tumori. 2018;104(5):344–51.PubMedPubMedCentralCrossRef
19.
20.
Lange T, Stehling C, Frohlich B, Klingenhofer M, Kunkel P, Schneppenheim R, Escherich G, Gosheger G, Hardes J, Jurgens H, et al. Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts. Eur Spine J. 2013;22(6):1417–22.PubMedPubMedCentralCrossRef
21.
Pauli C, Fuchs B, Pfirrmann C, Bridge JA, Hofer S, Bode B. Response of an aggressive periosteal aneurysmal bone cyst (ABC) of the radius to denosumab therapy. World J Surg Oncol. 2014;12:17.PubMedPubMedCentralCrossRef
22.
Dubory A, Missenard G, Domont J, Court C. Interest of Denosumab for the treatment of Giant-cells tumors and aneurysmal bone cysts of the spine. About Nine Cases. Spine (Phila Pa 1976). 2016;41(11):E654–60.CrossRef
23.
Fontenot PB, Jesurajan J, Bui M, Reed D, Binitie O. Recurrent aneurysmal bone cyst of the distal fibula treated with Denosumab and curettage. Case Rep Oncol Med. 2018;2018:1574343.PubMedPubMedCentral
24.
Asi KW, Abdelmeguid A, Bell D, Hanna EY. Massive aneurysmal bone cyst of the skull base treated with denosumab. Head Neck. 2018;40(12):E107–e113.PubMedCrossRef
25.
Ghermandi R, Terzi S, Gasbarrini A, Boriani S. Denosumab: non-surgical treatment option for selective arterial embolization resistant aneurysmal bone cyst of the spine and sacrum. Case report. Eur Rev Med Pharmacol Sci. 2016;20(17):3692–5.PubMed
26.
Patel RS, Dhamne CA, Gopinathan A, Kumar N, Kumar N. Denosumab: a potential treatment option for aneurysmal bone cyst of the atlas. Eur Spine J. 2018;27(Suppl 3):494–500.PubMedCrossRef
27.
Ntalos D, Priemel M, Schlickewei C, Thiesen DM, Rueger JM, Spiro AS. Therapeutic Management of a Substantial Pelvic Aneurysmatic Bone Cyst Including the off-label use of Denosumab in a 35-year-old female patient. Case Rep Ortho. 2017;2017:9125493.
28.
Skubitz KM, Peltola JC, Santos ER, Cheng EY. Response of aneurysmal bone cyst to Denosumab. Spine (Phila Pa 1976). 2015;40(22):E1201–4.CrossRef
29.
Pelle DW, Ringler JW, Peacock JD, Kampfschulte K, Scholten DJ 2nd, Davis MM, Mitchell DS, Steensma MR. Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res. 2014;164(2):139–48.PubMedCrossRef
30.
Thomas D, Henshaw R, Skubitz K, Chawla S, Staddon A, Blay JY, Roudier M, Smith J, Ye Z, Sohn W, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11(3):275–80.PubMedCrossRef
31.
Topouchian V, Mazda K, Hamze B, Laredo JD, Pennecot GF. Aneurysmal bone cysts in children: complications of fibrosing agent injection. Radiology. 2004;232(2):522–6.PubMedCrossRef
32.
Varshney MK, Rastogi S, Khan SA, Trikha V. Is sclerotherapy better than intralesional excision for treating aneurysmal bone cysts? Clin Orthop Relat Res. 2010;468(6):1649–59.PubMedCrossRef
33.
Shiels WE 2nd, Beebe AC, Mayerson JL. Percutaneous doxycycline treatment of Juxtaphyseal aneurysmal bone cysts. J Pediatr Orthop. 2016;36(2):205–12.PubMedCrossRef
34.
35.
Wu PF, Tang JY, Li KH. RANK pathway in giant cell tumor of bone: pathogenesis and therapeutic aspects. Tumour Biol. 2015;36(2):495–501.PubMedCrossRef
36.
Won KY, Kalil RK, Kim YW, Park YK. RANK signalling in bone lesions with osteoclast-like giant cells. Pathology. 2011;43(4):318–21.PubMedCrossRef
37.
Savvidou OD, Bolia IK, Chloros GD, Papanastasiou J, Koutsouradis P, Papagelopoulos PJ. Denosumab: current use in the treatment of primary bone tumors. Orthopedics. 2017;40(4):204–10.PubMedCrossRef
38.
Luengo-Alonso G, Mellado-Romero M, Shemesh S, Ramos-Pascua L, Pretell-Mazzini J. Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature. Arch Orthop Trauma Surg. 2019;139(10):1339–49.PubMedCrossRef
39.
40.
Wang HD, Boyce AM, Tsai JY, Gafni RI, Farley FA, Kasa-Vubu JZ, Molinolo AA, Collins MT. Effects of denosumab treatment and discontinuation on human growth plates. J Clin Endocrinol Metab. 2014;99(3):891–7.PubMedPubMedCentralCrossRef
41.
Boyce AM, Chong WH, Yao J, Gafni RI, Kelly MH, Chamberlain CE, Bassim C, Cherman N, Ellsworth M, Kasa-Vubu JZ, et al. Denosumab treatment for fibrous dysplasia. J Bone Miner Res. 2012;27(7):1462–70.PubMedCrossRef
42.
Hernandez M, Phulpin B, Mansuy L, Droz D. Use of new targeted cancer therapies in children: effects on dental development and risk of jaw osteonecrosis: a review. J Oral Pathol Med. 2017;46(5):321–6.PubMedCrossRef
43.
Semler O, Netzer C, Hoyer-Kuhn H, Becker J, Eysel P, Schoenau E. First use of the RANKL antibody denosumab in osteogenesis imperfecta type VI. J Musculoskelet Neuronal Interact. 2012;12(3):183–8.PubMed
44.
Gossai N, Hilgers MV, Polgreen LE, Greengard EG. Critical hypercalcemia following discontinuation of denosumab therapy for metastatic giant cell tumor of bone. Pediatr Blood Cancer. 2015;62(6):1078–80.PubMedCrossRef
45.
Roux S, Massicotte MH, Huot Daneault A, Brazeau-Lamontagne L, Dufresne J. Acute hypercalcemia and excessive bone resorption following anti-RANKL withdrawal: case report and brief literature review. Bone. 2019;120:482–6.PubMedCrossRef
Metadata
Title
Aneurysmal bone cyst: results of an off label treatment with Denosumab
Authors
Hans Roland Dürr
Ferdinand Grahneis
Andrea Baur-Melnyk
Thomas Knösel
Christof Birkenmaier
Volkmar Jansson
Alexander Klein
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2019
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-019-2855-y

Other articles of this Issue 1/2019

BMC Musculoskeletal Disorders 1/2019 Go to the issue

Research article

Increased lactic acid content associated with extracellular matrix depletion in a porcine disc degeneration induced by superficial annular lesion

Research article

Technology-assisted rehabilitation following total knee or hip replacement for people with osteoarthritis: a systematic review and meta-analysis

Research article

Musculoskeletal ultrasound in symptomatic thumb-base osteoarthritis: clinical, functional, radiological and muscle strength associations

Research article

Effect of lordosis on adjacent levels after lumbar interbody fusion, before and after removal of the spinal fixator: a finite element analysis

Research article

The efficacy and safety of tranexamic acid for reducing blood loss following simultaneous bilateral total knee arthroplasty: a multicenter retrospective study

Research article

Real-time detection of antibiotics cytotoxicity in rabbit periosteal cells using microfluidic devices with comparison to conventional culture assays