Primary bone tumors are rare, complex and highly heterogeneous. Its diagnostic and treatment are a challenge for the multidisciplinary team. Developments on tumor biomarkers, immunohistochemistry, histology, molecular, bioinformatics, and genetics are fundamental for an early diagnosis and identification of prognostic factors. The personalized medicine allows an effective patient tailored treatment. The bone biopsy is essential for diagnosis. Treatment may include systemic therapy and local therapy. Frequently, a limb salvage surgery includes wide resection and reconstruction with endoprosthesis, biological or composites. The risk for local recurrence and distant metastases depends on the primary tumor and treatment response.

Cancer patients are living longer and bone metastases are increasing. Bone is the third most frequently location for distant lesions. Bone metastases are associated to pain, pathological fractures, functional impairment, and neurological deficits. It impacts survival and patient quality of life. The treatment of metastatic disease is a challenge due to its complexity and heterogeneity, vascularization, reduced size and limited access. It requires a multidisciplinary treatment and depending on different factors it is palliative or curative-like treatment. For multiple bone metastases it is important to relief pain and increases function in order to provide the best quality of life and expect to prolong survival. Advances in nanotechnology, bioinformatics, and genomics, will increase biomarkers for early detection, prognosis, and targeted treatment effectiveness. We are taking the leap forward in precision medicine and personalized care.

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence.

Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated.

The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells.

Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection.

In the past decades, a huge amount of effort has been devoted to translate evidence based on standard preclinical models of bone tumours to effective tools for clinical applications. Although cancer is a genetic disease, hence the emphasis on -omics approaches, the complexity of cancer tissue, a mix of competing clones of transformed elements that react differently to microenvironmental stimuli, may hardly be reproduced by standard approaches. Cost, biological differences and ethical concerns are increasingly recognized as weaknessess of animal models. To overcome these limitations and provide reliable, reproducible, and affordable tools for predicting the effectiveness of treatments, environmental-controlled 3D cultures and co-cultures (spheroids, organoids) coupled with microfluidics and advanced imaging have recently being considered as effective instrument to increase knowledge on the pathophysiology of bone tumours and define effective therapeutic solutions.

Summary Statement

Treatment of non-union is a highly demanding field with respect to bone healing. BMP 7 is a useful, wide-ranged tool in treating non-union of the foot and benign bone tumors. It represents a low-risk procedure with a high level of reliability.

Primary bone tumours of the clavicle are rare. Currently the existing literature is limited to a single case series and case reports or cases. Information regarding the patient's demographics and tumour types is therefore limited.

The aim of this study was to investigate the and also suggest a management protocol for suspected primary bone tumours of the clavicle. We retrospectively reviewed the Scottish Bone Tumour Register from January 1971 to January 2012 and included all primary bone tumours of the clavicle.

We identified only sixteen primary bone tumours over forty one year's highlighting the rarity of these tumours. There were ten benign and six malignant tumours with a mean age of 32 years (Range 4 to 66). The average presentation to orthopaedics after onset of symptoms was two months with five patients presenting following a pathological fracture. Malignant tumour types identified were consistent with previous literature with two cases of Ewing's sarcoma and osteosarcoma and a single case of osteosarcoma post radiotherapy and a single case of chondrosarcoma. Benign tumours were treated effectively with intralesional procedures. Malignant tumours were treated with wide local excision and subtotal or total clavicle excision.

We suggest an investigatory and treatment protocol for patients with a suspected primary bone tumour of the clavicle. This is the largest series of primary bone tumours of the clavicle in the literature.

Primary bone tumours of the talus are rare. Currently the existing literature is limited to a single case series and case reports or cases described in series of foot tumours. Information regarding the patient's demographics and tumour types is therefore limited.

The aim of this study was to investigate these questions and also suggest a management protocol for suspected primary bone tumours of the talus. We retrospectively reviewed the Scottish Bone Tumour Register from January 1954 to May 2010 and included all primary bone tumours of the talus. We identified only twenty three bone tumours over fifty six years highlighting the rarity of these tumours. There were twenty benign and three malignant tumours with a mean age of twenty eight years. A delay in presentation was common with a mean time from onset of symptoms to diagnosis of ten months. Tumour types identified were consistent with previous literature. We identified cases of desmoplastic fibroma and intraosseous lipodystrophy described for the first time.

We suggest an investigatory and treatment protocol for patients with a suspected primary bone tumour of the talus. This is the largest series of primary bone tumours of the talus in the literature.