Therapeutic Approach of Primary Bone Tumours by Bisphosphonates

Abstract

Bone tumours can be dissociated in two main categories: i) primary bone tumours (benign or malignant) including mainly osteosarcoma and other sarcomas.ii)and giant cell tumour and bone metastases originate from others cancer (Breast, prostate, kidney cancer, etc). These tumours are able to destroy or/and induce a new calcified matrix. However, the first step of bone tumour development is associated with an induction of bone resorption and the establishment of a vicious cycle between the osteoclasts and the tumour growth. Indeed, bone resorption contributes to the pathogenesis of bone tumour by the release of cytokines (IL6, TNFα) which govern the bone tumour's development and which are trapped into the bone matrix. Bisphosphonates (BPs) are chemical compounds of P-C-P structure with a high affinity for bone hydroxyapatite crystals. Thus, they have been used as a carrier for radio nucleotides to develop novel approaches of bone imaging. BPs exert also indirect anti-tumour activities in vivo. Indeed, BPs directly interfere with the bone microenvironment and target osteoclasts, endothelial cells and immune cells (tumour-associated macrophages, γ9δ2 T cells). BPs induce tumour cell death in vitro and same activity is suspected in vivo. The present review summarizes the mechanisms of actions of BPs as well as their clinical interests in bone primary tumours.

Preclinical evidence of potential craniofacial adverse effect of zoledronic acid in pediatric patients with bone malignancies

“…High doses of ZOL have been proposed as adjuvant therapy for the treatment of malignant primary bone tumors (osteosarcoma and Ewing sarcoma; 4, 13) that mainly affect children and young adults [25,26]. The principal objectives of high doses zoledronic acid protocol were not only to protect bone from the tumor-induced osteolysis but also to target tumor cells [27], ZOL being a powerful inhibitor of the mevalonate pathway [28]. Our previous studies have evidenced that high doses of ZOL in mouse, similar to the human pediatric treatment, induced a transient arrest of the axial and appendicular skeleton growth of long bones [20].…”

Anti-inflammatory effects of Panax notoginseng saponins ameliorate acute lung injury induced by oleic acid and lipopolysaccharide in rats

“…Furthermore, they observed that the activity of TNF-α was effectively inhibited in the aqueous phase of lung fluids of patients with ARDS. TNF-α has also been suggested to induce the release of IL-6 by endothelial cells and macrophages (42).…”

Effect of zoledronic acid and amputation on bone invasion and lung metastasis of canine osteosarcoma in nude mice

“…We used the nitrogen-containing bisphosphonate, Zol, which has been shown to be a potent inhibitor of osteoclasts and tumor growth in a variety of solid tumors [14, 32–35]. Nitrogen-containing bisphosphonates, such as Zol interfere with the mevalonate pathway by inhibiting farnesyl pyrophosphate synthase [36].…”