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Bisphosphonates: from bone anti-resorptive to anti-cancer drugs.

Mohammed Helmy Faris Shalayel, Saeed Ali Alsareii, Abdulhadi Mohamed Elbashir, Mohammed Ayed Huneif

Bisphosphonates, analogues of pyrophosphates, are utilized as efficient drugs against bone resorption in bone disorders like, osteoporosis, Paget's disease, multiple myeloma, cancerinduced hypercalcemia, and bony metastases. They suppress osteoclastic bone resorption by incorporating with hydroxyapatite binding sites on bony surfaces that undergo active resorption with due interference with various biochemical processes in bone-resorbing osteoclasts, impairing the ability of the osteoclasts and enhancing osteoclast apoptosis. The clinical utilization of bisphosphonates has dramatically expanded during the past 3 decades or more especially for osteoporosis to diminish the frequency of skeletal-related events in patients with breast cancer and myeloma. Some preclinical studies had reported that bisphosphonates exhibit direct and indirect anticancer activities in patients with early breast cancer or symptomatic multiple myeloma exhibiting disease-free survival and overall survival benefits. Moreover, some epidemiological and clinically applied studies concluded that current use of bisphosphonates in healthy postmenopausal women to manage osteoporosis was correlated with a 30% reduction in the risk of breast and colon cancers and ladies who use bisphosphonates had about one half the risk of getting endometrial cancer compared with those who did not use them. Recently, it was reported that addition of bisphosphonates to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) could enhance the antitumor effect of EGFR-TKIs in patients with EGFR-mutant non-small-cell lung cancer and bone metastasis.