Denosumab is a fully humanised monoclonal antibody to RANK ligand, inhibiting the RANK–RANKL pathway. It promotes the apoptosis of osteoclast-like giant cells, a secondary ossification and connective tissue formation.
Given its high efficacy, denosumab is the standard treatment of unresectable or metastatic giant cell tumour of bone (GCTB) requiring morbid surgery.
Neoadjuvant administration of denosumab may be justified to enable the resection of the tumour in certain cases; it should be considered, however, with caution for joint-saving surgery due to high local recurrence rates.
In cases of unresectable or metastatic GCTB, however, denosumab treatment should be administered for years or even as a lifelong therapy. This poses many yet unanswered questions concerning the frequency of denosumab treatment as well as the ratio of the adverse events in the following years.
Denosumab suppresses, not directly targets, the neoplastic stromal cells of GCTB. Ongoing in vitro studies suggest that other drugs alone or in combination (e.g. sunitinib) with denosumab may target both the neoplastic and the giant cells.
Promising results have been reported regarding the off-label use of denosumab in other giant cell-rich tumours/tumour-like lesions, i.e. aneurysmal bone cysts and central giant cell granulomas. Data are derived, however, mostly from case reports and case series. Large prospective clinical trials are needed to evaluate the role and also the side effects of denosumab in the treatment of these rare diseases.
Patients diagnosed with soft tissue sarcoma (STS) present a number of challenges for physicians, due to the vast array of subtypes and aggressive tumor biology.
There is currently no agreed-upon management strategy for these tumors, which has led to the ongoing debate surrounding how frequently surveillance scans should be performed following surgery. However, advances in multidisciplinary care have improved patient outcomes over recent years.
The early detection of local recurrence reflects a more aggressive tumor, even in association with the same histopathologic entity.
Treating the local recurrence of extremity STS is a difficult clinical challenge. The goal should be to salvage limbs when possible, with treatments such as resection and irradiation, although amputation may be necessary in some cases. Regional therapies such as high-intensity, low-dose or interleukin-1 receptor antagonist treatment are appealing options for either definitive or adjuvant therapy, depending on the location of the disease’s recurrence.
The higher survival rate following late recurrence may be explained by variations in tumor biology. Since long-term survival is, in fact, inferior in patients with high-grade STS, this necessitates the implementation of an active surveillance approach.
Catalin CirstoiuOrthopedics and Traumatology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Orthopedics and Traumatology Department, University Emergency Hospital Bucharest, Bucharest, Romania
Bogdan CretuOrthopedics and Traumatology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Orthopedics and Traumatology Department, University Emergency Hospital Bucharest, Bucharest, Romania
Sergiu IordacheOrthopedics and Traumatology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Orthopedics and Traumatology Department, University Emergency Hospital Bucharest, Bucharest, Romania
Mihnea PopaOrthopedics and Traumatology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Orthopedics and Traumatology Department, University Emergency Hospital Bucharest, Bucharest, Romania
Bogdan SerbanOrthopedics and Traumatology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Orthopedics and Traumatology Department, University Emergency Hospital Bucharest, Bucharest, Romania
Adrian CursaruOrthopedics and Traumatology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Orthopedics and Traumatology Department, University Emergency Hospital Bucharest, Bucharest, Romania
Bone metastases are difficult to treat surgically, necessitating a multidisciplinary approach that must be applied to each patient depending on the specifics of their case.
The main indications for surgical treatment are a lack of response to chemotherapy, radiation therapy, hormone therapy, immunotherapy, and bisphosphonates which is defined by persistent pain or tumor progression; the risk of imminent pathological bone fracture; and surgical treatment for single bone metastases.
An important aspect of choosing the right treatment for these patients is accurately estimating life expectancy. Improved chemotherapy, postoperative radiation therapy, and sustainable reconstructive modalities will increase the patient’s life expectancy.
The surgeon should select the best surgical strategy based on the primary tumor and its characteristics, the presence of single or multiple metastases, age, anatomical location, and the functional resources of the patient.
Preventive osteosynthesis, osteosynthesis to stabilize a fracture, resections, and reconstructions are the main surgical options for bone metastases.
Resection and reconstruction with a modular prosthesis remain the generally approved surgical option to restore functionality, increase the quality of life, and increase life expectancy.
Preoperative embolization is necessary, especially in the case of metastases of renal or thyroid origin. This procedure is extremely important to avoid complications, with a major impact on survival rates.
Venous thromboembolism (VTE) is a well-known complication following orthopaedic surgery. The incidence of this complication has decreased substantially since the introduction of routine thromboprophylaxis. However, concerns have been raised about increased bleeding complications caused by aggressive thromboprophylaxis.
Attention has grown for aspirin as a safer thromboprophylactic agent following orthopaedic surgery.
A systematic review using MEDLINE, Embase and Web of Science databases was undertaken to compare the effectiveness of aspirin prophylaxis following knee surgery with the current standard prophylactic agents (low molecular weight heparin [LMWH], vitamin K antagonists and factor Xa inhibitors).
No significant difference in effectiveness of VTE prevention was found between aspirin, LMWH and warfarin. Factor Xa inhibitors were more effective, but increased bleeding complications were reported.
As evidence is limited and of low quality with substantial heterogeneity, further research with high-quality, adequately powered trials is needed.
Cite this article: EFORT Open Rev 2021;6:892-904. DOI: 10.1302/2058-5241.6.200120
Olga SavvidouFirst Department of Orthopaedic Surgery, National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece These authors contributed equally to this manuscript
Olympia PapakonstantinouSecond Department of Radiology, National and Kapodistrian University of Athens, Medical School, Attikon University General Hospital, Athens, Greece These authors contributed equally to this manuscript
Surface bone sarcomas are rare malignant bone tumours. Osseous and cartilaginous surface bone sarcomas are the most common, with parosteal and periosteal osteosarcomas, periosteal chondrosarcomas and secondary peripheral chondrosarcomas being the most frequent.
Their clinical symptoms are non-specific and include pain for several months, swelling and limited range of motion of the adjacent joints.
Prompt diagnosis is important, as biological behaviour, imaging and histopathologic characteristics, treatment and prognosis differ considerably from their conventional intramedullary counterparts. Moreover, their imaging characteristics are not infrequently non-characteristic and may be misinterpreted as juxtacortical benign lesions leading to incorrect diagnosis and treatment, with life-threatening repercussions. Molecular studies and histopathological sampling are essential for accurate diagnosis.
There are still numerous issues regarding the biology, pathophysiology and treatment options of these entities due to their rarity.
Cite this article: EFORT Open Rev 2021;6:905-917. DOI: 10.1302/2058-5241.6.210064
Giant cell tumour of bone (GCT) is a relatively rare, locally aggressive benign neoplasm observed in the long bone epiphyseal-metaphyseal regions of young adults.
The optimal treatment strategy for these tumours remains controversial, and a huge amount of contradictory data regarding the functional and oncological outcomes can be found. Therefore, we performed a systematic review intended to investigate the functional and oncological outcomes after surgical treatment of GCTs arising around the knee, namely in the distal femur and proximal tibia.
A trend towards better oncological control was found using wide resections, nonetheless, curettage-based techniques achieve a highly acceptable recurrence rate with overall better knee function. A slight advantage favouring proximal tibia GCTs regarding the Musculoskeletal Tumor Society (MSTS) score was also observed.
Prospective studies comparing groups of more homogeneous patients, tumours, and treatment options should be developed to obtain more conclusive and definitive results regarding the optimal strategy for treating GCTs.
Cite this article: EFORT Open Rev 2021;6:641-650. DOI: 10.1302/2058-5241.6.200154
Olga SavvidouFirst Department of Orthopedics, National and Kapodistrian University of Athens, Medical School, ATTIKON University General Hospital, Greece These authors contributed equally to this manuscript
Olympia PapakonstantinouSecond Department of Radiology, National and Kapodistrian University of Athens, Medical School, ATTIKON University General Hospital, Athens, Greece These authors contributed equally to this manuscript
Myositis ossificans (MO) is a benign bone formation in an extra-skeletal location. The most common subtype of MO, the post-traumatic, usually develops in young males after a traumatic event or sports injury.
MO may simulate malignant bone lesions such as extra-skeletal or surface osteosarcomas, or soft tissue sarcomas such as synovial sarcoma or undifferentiated pleomorphic sarcoma. In the early phase the diagnosis of MO is challenging because imaging and histopathological findings may be non-characteristic.
Detailed medical history as well as clinical examination, follow-up imaging studies and histological assessment are crucial for a proper diagnosis. Early and accurate differential diagnosis between MO and malignant soft tissue and bone tumours is important to maximize.
Cite this article: EFORT Open Rev 2021;6:572-583. DOI: 10.1302/2058-5241.6.210002
In patients with metastatic or unresectable soft tissue and bone sarcoma of extremities and pelvis, survival is generally poor. The aim of the current systematic review was to analyse recent publications on treatment approaches in patients with inoperable and/or metastatic sarcoma.
Original articles published between 1st January 2011 and 2nd May 2020, using the search terms ‘unresectable sarcoma’, ‘inoperability AND sarcoma’, ‘inoperab* AND sarcoma’, and ‘treatment AND unresectable AND sarcoma’ in PubMed, were potentially eligible. Out of the 839 initial articles (containing 274 duplicates) obtained and 23 further articles identified by cross-reference checking, 588 were screened, of which 447 articles were removed not meeting the inclusion criteria. A further 54 articles were excluded following full-text assessment, resulting in 87 articles finally being analysed.
Of the 87 articles, 38 were retrospective (43.7%), two prospective (2.3%), six phase I or I/II trials (6.9%), 22 phase II non-randomized trials (27.6%), nine phase II randomized trials (10.3%) and eight phase III randomized trials (9.2%). Besides radio/particle therapy, isolated limb perfusion and conventional chemotherapy, novel therapeutic approaches, including immune checkpoint inhibitors and tyrosine kinase inhibitors were also identified, with partially very promising effects in advanced sarcomas.
Management of inoperable, advanced or metastatic sarcomas of the pelvis and extremities remains challenging, with the optimal treatment to be defined individually. Besides conventional chemotherapy, some novel therapeutic approaches have promising effects in both bone and soft tissue subtypes. Considering that only a small proportion of studies were randomized, the clinical evidence currently remains moderate and thus calls for further large, randomized clinical trials.
Cite this article: EFORT Open Rev 2020;5:799-814. DOI: 10.1302/2058-5241.5.200069
Diffuse-type tenosynovial giant-cell tumours of the knee (D-TGCT) have a very high complication rate.
The recurrence rate for D-TGCT is mainly dependent on an initially successful resection of the lesion.
The standard of care for this disease involves early surgery with synovectomy. Available surgical techniques may include an arthroscopic or open surgery; however, there is a lack of consensus on which technique should be used, and when.
Arthroscopic excision is effective in minimizing morbidity and surgery-related complications, while an open surgical technique provides a more successful resection with a lower incidence of local recurrence.
We could not conclude with confidence which of the surgical techniques is better at stopping a progression towards osteoarthritis and the need for a total knee arthroplasty.
Cite this article: EFORT Open Rev 2020;5:339-346. DOI: 10.1302/2058-5241.5.200005