Percutaneous Doxycycline Treatment of Aneurysmal Bone Cysts With Low Recurrence Rate: A Preliminary Report
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Aneurysmal bone cyst (ABC) has a recurrence rate of between 12% and 71% without en bloc resection or amputation. There is no percutaneous ABC treatment drug regimen demonstrating consistent evidence of bone healing with recurrence of < 12%. Doxycyline has properties that may make it appropriate for percutaneous treatment.
We therefore asked: (1) Is there reduction in ABC lytic cyst volume with injectable doxycycline? (2) Is it associated with thickening of involved bony cortex? (3) Is the recurrence rate after percutaneous treatment < 12%?
We retrospectively reviewed 20 patients who underwent percutaneous treatment of ABCs with doxycycline from 2006 to 2010. The mean age was 10 years (range, 3–18 years). There were 21 treatment locations: humerus (six), spine (five), clavicle (two), fibula (one), femur (two), ulna (two), tibia (two), and scapula (one). Twenty patients completed treatment involving 118 treatment sessions (two to 14 sessions per patient). Treatment response was evaluated radiographically by measuring the lytic component and thickness of involved cortex. Recurrence was indicated by new areas of lytic destruction after completion of treatment. The minimum followup was 24 months (mean, 38 months).
Twenty of 20 patients demonstrated reduction in lytic destruction and bony healing. All patients demonstrated cortical thickening. One patient demonstrated recurrent minimal lytic destruction after 20 months of observation.
In this series, patients undergoing percutaneous doxycycline treatment of ABCs demonstrated a healing response and a recurrence rate of 5% at more than 24 months.
Level of Evidence
Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
- Adamsbaum C, Mascard E, Guinebretiere JM, Kalifa G, Dubousset J. Intralesional Ethibloc injections in primary aneurysmal bone cysts: a efficient and safe treatment. Skeletal Radiol. 2003;32:559–566. CrossRef
- Althof PA, Ohmori K, Zhou M, Bailey JM, Bridge RS, Nelson M, Neff JR, Bridge JA. Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization. Mod Pathol. 2004;17:518–525. CrossRef
- Baruffi MR, Barbieri Neto JB, Barbieri CH, Casartelli C. Aneurysmal bone cyst with chromosomal changes involving 7q and 16p. Cancer Genet Cytogenet. 2001;129:177–180. CrossRef
- Bettany J. Tetracyclines induce apoptosis in osteoclasts. Bone. 2009;27:75–80. CrossRef
- Bjornland K, Flatmark K, Pettersen S, Aaasen A, Fodstrat Ø. Matrix metalloproteinases participate in osteosarcoma Invasion. J Surg Res. 2005;127:151–156. CrossRef
- Burrows PE, Mitri RK, Alomari A, Padua HM, Lord DJ, Sylvia MB, Fishman SJ, Mulliken JB. Percutaneous sclerotherapy of lymphatic malformations with doxycycline. Lymphat Res Biol. 2008;6:209–216. CrossRef
- Chang CY, Yamada S. Evaluation of the regenerative effect of a 25% doxycycline-loaded biodegradable membrane for guided tissue regeneration. J Periodontol. 2000;71:1086–1093. CrossRef
- Cottalorda J, Kohler R, Chotel, F, de Gauzy J, Lefort G, Louahem D, Bourelle S, Dimeglio A. Recurrence of aneurysmal bone cysts in young children: a multicentre study. J Pediatr Orthop. 2005;14:212–218. CrossRef
- Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–765. CrossRef
- Dal Cin P, Kozakewich HP, Goumnerova L, Mankin HJ, Rosenberg AE, Fletcher JA. Variant translocations involving 16q22 and 17p13 in solid variant and extraosseous forms of aneurysmal bone cyst. Genes Chromosomes Cancer. 2000;28:233–234. CrossRef
- Dormans JP, Hanna BG, Johnston DR, Khurana JS. Surgical treatment and recurrence rate of aneurysmal bone cysts in children. Clin Orthop Relat Res. 2004;421:205–211. CrossRef
- Duivenvoorden WC, Hirte HW, Singh G. Use of tetracycline as an inhibitor of matrix metalloproteinase activity secreted by human bone-metastasizing cancer cells. Invasion Metastasis. 1997:17:312–322.
- Duivenvoorden WC, Popovi SV, Lhoták S, Seidlitz E, Hirte HW, Tozer RG, Singh G. Doxycycline decreases tumor burden in a bone metastasis model of human breast cancer. Cancer Res. 2002;62:1588–1591.
- Feldman JP, Goldwasser R, Mark S, Schwartz J, Orion I. A mathematical model for tumor volume evaluation using two-dimensions. J Appl Quant Methods. 2009;4:455–462.
- Fife R, Rougraff B, Proctor C, Sledge G. Inhibition of proliferation and induction of apoptosis by doxycycline in cultured human osteosarcoma cells. J Lab Clin Med. 2009;130:530–534. CrossRef
- Freiberg AA, Loder RT, Heidelberger KP, Hensinger RN. Aneurysmal bone cysts in young children. J Pediatr Orthop. 1994;14:86–91. CrossRef
- Gibbs CP Jr, Hefele MC, Peabody TD, Montag AG, Aithal V, Simon MA. Aneurysmal bone cyst of the extremities: Factors related to local recurrence after curettage with a high-speed burr. J Bone Joint Surg Am. 1999;81:1671–1678.
- Gilbertson-Beadling S, Powers EA, Stamp-Cole M, Scott PS, Wallace TL, Copeland J, Petzold G, Mitchell M, Ledbetter S, Poorman R, Wilks JW, Fisher C. The tetracycline analogs minocycline and doxycycline inhibit angiogenesis in vitro by a non-metalloproteinase-dependent mechanism. Cancer Chemother Pharmacol. 1995;36:418–424. CrossRef
- Holmes SG, Still K, Buttle DJ, Bishop NJ, Grabowski PS. Chemically modified tetracyclines act through multiple mechanisms directly on osteoclast precursors. Bone. 2004;35:471–478. CrossRef
- Kirse D, Stern S, Suen J, Rudnicki S, Roberson P, Schaefer R. Neurotoxic effects of doxycycline sclerotherapy. Otolaryngol Head Neck Surg. 1998;118:356–362. CrossRef
- Kirse DJ, Suen JY, Stern SJ. Phrenic nerve paralysis after doxycycline sclerotherapy for chylous fistula. Otolaryngol Head Neck Surg. 1997;116:680–683. CrossRef
- Kirse DJ, Suen JY, Stern SJ, Schaefer RF, Roberson PK. Histologic effect of doxycycline sclerotherapy on rat femoral nerve. Head Neck. 1996;18:506–511. CrossRef
- Kumta SM, Huang L, Cheng YY, Chow LT, Lee KM, Zheng MH. Expression of VEGF and MMP-9 in giant cell tumor of bone and other osteolytic lesions. Life Sci. 2003;73:1427–1436. CrossRef
- Lau AW, Pringle AM, 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 morphogenic protein dysregulation. J Biol Chem. 2010;285:37111–37120. CrossRef
- Lin PP, Brown C, Raymond AK, Deavers MT, Yasko AW. Aneurysmal bone cysts recur at juxtaphyseal locations in skeletally immature patients. Clin Orthop Relat Res. 2008;466:722–728. CrossRef
- Liu B, Yu SF, Li TJ. Multinucleated giant cells in various forms of giant cell containing lesions of the jaws express features of osteoclasts. J Oral Pathol Med. 2003;6:367–375. CrossRef
- Lokeshwar BL. Chemically modified non-antimicrobial tetracyclines are multifunctional drugs against advanced cancers. Pharmacol Res. 2011;63:146–150. CrossRef
- Mankin HJ, Hornicek FJ, Ortiz-Cruz E, Villafuerte J, Gebhardt MC. Aneurysmal bone cyst: a review of 150 patients. J Clin Oncol. 2005;23:6756–6762. CrossRef
- Marler JJ, Fishman SJ, Kilroy SM, Fang J, Upton J, Mulliken JB, Burrows PE, Zurakowski D, Folkman J, Moses MA. Increased expression of urinary matrix metalloproteinases parallels the extent and activity of vascular anomalies. Pediatrics. 2005;116:38–45. CrossRef
- Oliveira AM, Perez-Atayde AR, Dal Cin P, Gebhardt MC, Chen CJ, Neff JR, Demetri GD, Rosenberg AE, Bridge JA, Fletcher JA. Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZFN9, COL1A1, TRAP150, and OMD genes. Oncogene. 2005;24:3419–3426. CrossRef
- Oliveira AM, Perez-Atayde AR, Inwards CY, Medeiros F, Derr V, His BL, Gebhardt MC, Rosenberg AE, Fletcher JA. USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Am J Pathol. 2004;165:1773–1780. CrossRef
- 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;26:265–266. CrossRef
- Peeters SP, Van der Geest IC, de Rooy JW, Veth RP, Schreuder HW. Aneurysmal bone cyst: the role of cryosurgery as local adjuvant treatment. J Surg Oncol. 2009;100:719–724. CrossRef
- Ramirez AR, Stanton, RP. Aneurysmal bone cyst in 29 children. J Pediatr Orthop. 2002;22:533–539.
- Rapp TB, Ward JP, Alaia MJ. Aneurysmal bone cyst. J Am Acad Orthop Surg. 2012;20:233–241. CrossRef
- Rastogi S, Varshney MK, Trikha V, Khan SA, Choudhury B, Safaya R. Treatment of aneurysmal bone cysts with percutaneous sclerotherapy using polidocanol. A review of 72 cases with long-term follow-up. J Bone Joint Surg Br. 2006;88:1212–1216.
- Richardson M, Wong D, Lacroix S, Stanisz J, Singh G. Inhibition by doxycycline of angiogenesis in the chicken chorioallantoic membrane (CAM). Cancer Chemother Pharmacol. 2005;56:1–9. CrossRef
- Sciot R, Dorfman H, Brys P, Dal Cin, P, De Wever I, Fletcher CD, Jonson K, Mandahl N, Mertens F, Mitelman F, Rosai J, Rydholm A, Samson I, Tallini G, Van den Berghe H, Vanni R, Willén H. 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;13:1206–1210. CrossRef
- Shiels WE, Kang D, Murakami J, Hogan M, Wiet G. Percutaneous treatment of lymphatic malformations. Otolaryngol Head Neck Surg. 2009;141:219–224. CrossRef
- Shiels WE, Kenney B, Caniano D, Besner G. Definitive percutaneous treatment of lymphatic malformations of the trunk and extremities. J Pediatr Surg. 2008;43:136–140. CrossRef
- Topouchian V, Mazda K, Hamze B, Laredo JD, Pennecot GF. Aneurysmal bone cysts in children; complications of fibrosing agent injection. Radiology. 2004;232:522–526. CrossRef
- Vergel De Dios AM, Bond JR, Shives TC, McLeod RA, Unni KK. Aneurysmal bone cyst: a clinicopathologic study of 238 cases. Cancer. 1992;69:2921–2931. CrossRef
- Ye Y, Pringle LM, Lau AW, Riquelme DN, Wang H, Jiang T, Lev D, Welman A, Blobel GA, Oliveira AM, Chou MM. TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-xB. Oncogene. 2010;29:3619–3629. CrossRef
- Zenonos G, Jamil O, Governale L, Jernigan S, Hedequist D, Proctor MR. Surgical treatement for primary spinal aneurysmal bone cysts: experience from Children’s Hospital Boston. J Neurosurg Pediatr. 2012;9:305–315. CrossRef
- Percutaneous Doxycycline Treatment of Aneurysmal Bone Cysts With Low Recurrence Rate: A Preliminary Report
Clinical Orthopaedics and Related Research®
Volume 471, Issue 8 , pp 2675-2683
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Department of Radiology, The Ohio State University Medical Center and Nationwide Children’s Hospital, 700 Children’s Drive, Room K140, Columbus, OH, 43205, USA
- 2. Department of Orthopedic Surgery, The Ohio State University Medical Center and Nationwide Children’s Hospital, Columbus, OH, USA