For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
8
views
42
references
 Top references
cited by
22
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      758
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      case-report

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women.

          Pirow Bekker, Donna Holloway, Amy Rasmussen … (2004)
          The safety and bone antiresorptive effect of a single subcutaneous dose of AMG 162, a human monoclonal antibody to RANKL, was investigated in 49 postmenopausal women. AMG 162 is a potent antiresorptive agent for diseases such as osteoporosis. RANKL is an essential osteoclastic differentiation and activation factor. The bone antiresorptive activity and safety of AMG 162, a fully human monoclonal antibody to RANKL, were evaluated in postmenopausal women in this randomized, double-blind, placebo-controlled, single-dose, dose escalation study. Six cohorts of eight to nine women were randomly assigned to receive a single subcutaneous injection of either AMG 162 or placebo (3:1 ratio). AMG 162 doses were 0.01, 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg. Subjects were followed up to 6 months in all cohorts and 9 months in the three highest dose cohorts. Second morning void urinary N-telopeptide/creatinine (NTX; Osteomark), serum NTX, and serum bone-specific alkaline phosphatase (BALP, Ostase) were assessed as bone turnover markers. Forty-nine women were enrolled. A single subcutaneous dose of AMG 162 resulted in a dose-dependent, rapid (within 12 h), profound (up to 84%), and sustained (up to 6 months) decrease in urinary NTX. At 6 months, there was a mean change from baseline of -81% in the 3.0 mg/kg AMG 162 group compared with -10% in the placebo group; serum NTX changes were -56% and 2%, respectively. BALP levels did not decrease remarkably until after 1 month, indicating that the effect of AMG 162 is primarily antiresorptive. Intact parathyroid hormone (PTH) levels increased up to approximately 3-fold after 4 days in the 3.0 mg/kg dose group, but returned toward baseline with follow-up. Albumin-adjusted serum calcium did not decrease >10% on average in any group, and no subject had values below 2 mmol/liter. AMG 162 was well tolerated. No related serious adverse events occurred. No clinically meaningful laboratory changes, other than those described above, were observed. In summary, a single subcutaneous dose of AMG 162 resulted in a dose-dependent rapid and sustained decrease from baseline in bone turnover and could be an effective and convenient treatment for osteoporosis.
          Article 0 comments Cited 124 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Denosumab treatment for fibrous dysplasia.

            Alfredo Molinolo, Carol Bassim, Dan Chamberlain … (2012)
            Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)-regulating protein, α-subunit of the Gs stimulatory protein (G(s) α). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF-κB ligand (RANKL) is a cell-surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD-like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal-related events from bone metastases. We present the case of a 9-year-old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross-linked C-telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD-related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases. Copyright © 2012 American Society for Bone and Mineral Research.
            Article 0 comments Cited 75 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Aneurysmal bone cyst: concept, controversy, clinical presentation, and imaging.

              M J Kransdorf, D. Sweet (1995)
              The aneurysmal bone cyst is the result of a specific pathophysiologic change, which is probably the result of trauma or a tumor-induced anomalous vascular process. In approximately one third of cases, the preexisting lesion can be clearly identified. The most common of these is the giant cell tumor, which accounts for 19-39% of cases in which the preceding lesion is found. Other common precursor lesions include osteoblastoma, angioma, and chondroblastoma. Less common lesions include fibrous dysplasia, fibroxanthoma (nonossifying fibroma), chondromyxoid fibroma, solitary bone cyst, fibrous histiocytoma, eosinophilic granuloma, and even osteosarcoma. Interestingly, some of the controversy surrounding this lesion may be the result of a change in how the lesion was defined by Lichtenstein in 1953, when intramedullary lesions were added to the previously described juxtacortical (superficial) lesions. Members of the AFIP have suggested that many of the intramedullary lesions in which no previous lesion can be identified may represent giant cell tumors of bone. Their similarity to proved giant cell tumors in skeletally immature patients can be striking and seems more than coincidental. Appropriate treatment of an aneurysmal bone cyst requires the realization that it results from a specific pathophysiologic process, and identification of the preexisting lesion, if possible, is essential. Clearly an osteosarcoma with superimposed secondary aneurysmal bone cyst change must be treated as an osteosarcoma, and giant cell tumor with secondary features of aneurysmal bone cyst would be expected to be more likely to recur locally. The vast majority (approximately 80%) of patients presenting with aneurysmal bone cystlike findings are less than 20 years old. More than half of all such lesions occur in long bones, with approximately 12-30% of cases occurring in the spine. The pelvis accounts for about half of all flat bone lesions. Most patients present with pain and/or swelling, with symptoms usually present for less than 6 months. The imaging appearance of aneurysmal bone cyst reflects the underlying pathophysiologic change. Radiographs show an eccentric, lytic lesion with an expanded, remodeled "blown-out" or "ballooned" bony contour of the host bone, frequently with a delicate trabeculated appearance. Radiographs may rarely show flocculent densities within the lesion, which may mimic chondroid matrix. CT scanning will define the lesion and is especially valuable for those lesions located in areas in which the bony anatomy is complex, and which are not adequately evaluated by plain films. Fluid-fluid levels are common and may be seen on CT scans and MR images.(ABSTRACT TRUNCATED AT 250 WORDS)
              Article 0 comments Cited 70 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Hans Roland Dürr: +49 89 4400 76782 , hans_roland.duerr@med.uni-muenchen.de
                Ferdinand Grahneis: ferdi_grahneis@web.de
                Andrea Baur-Melnyk: andrea.baur@med.uni-muenchen.de
                Thomas Knösel: thomas.knoesel@med.uni-muenchen.de
                Christof Birkenmaier: Christof.birkenmaier@med.uni-muenchen.de
                Volkmar Jansson: volkmar.jansson@med.uni-muenchen.de
                Alexander Klein: alexander.klein@med.uni-muenchen.de
                Journal
                Journal ID (nlm-ta): BMC Musculoskelet Disord
                Journal ID (iso-abbrev): BMC Musculoskelet Disord
                Title: BMC Musculoskeletal Disorders
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2474
                Publication date (Electronic): 20 October 2019
                Publication date PMC-release: 20 October 2019
                Publication date Collection: 2019
                Volume: 20
                Electronic Location Identifier: 456
                Affiliations
                [1 ]ISNI 0000 0004 1936 973X, GRID grid.5252.0, Orthopaedic Oncology, Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital, , LMU Munich, ; Marchioninistr. 15, D-81377 Munich, Germany
                [2 ]ISNI 0000 0004 1936 973X, GRID grid.5252.0, Department of Radiology, University Hospital, , LMU Munich, ; Munich, Germany
                [3 ]ISNI 0000 0004 1936 973X, GRID grid.5252.0, Institute of Pathology, University Hospital, , LMU Munich, ; Munich, Germany
                Article
                Publisher ID: 2855
                DOI: 10.1186/s12891-019-2855-y
                PMC ID: 6802343
                PubMed ID: 31630689
                SO-VID: bfc3bff5-96ba-44a9-9310-c19a394dbd37
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 13 May 2019
                Date accepted : 27 September 2019
                Categories
                Subject: Case Report
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Orthopedics
                Keywords: aneurysmal bone cyst,denosumab,recurrence,prognosis
                Data availability:
                ScienceOpen disciplines: Orthopedics
                Keywords: aneurysmal bone cyst, denosumab, recurrence, prognosis

                Comments

                Comment on this article

                scite_

                Similar content758

                See all similar

                Cited by22

                See all cited by

                Most referenced authors525

                See all reference authors