Raman Spectroscopic Investigation of Osteoclastic Activity under the Influence of Bisphosphonate

Abstract

The bone resorption inhibitor bisphosphonate (BP) is used to prevent fractures in patients with osteoporosis and bone metastases caused by cancer. However, BP induces apoptosis of osteoclasts and excessively suppresses bone turnover, so that side effects such as jawbone necrosis have become a problem. In the super-aging society that Japan is facing, it is expected that jawbone necrosis (Medication-related osteonecrosis of the jaw: MRONJ) will increase as the number of osteoporosis patients increases. There are many unclear points about the pathophysiology of jawbone necrosis, and there have been attempts to clarify it. Most of the research on osteoclasts so far has comprised destructive and invasive analyses, such as TRAP staining and PCR by culturing osteoclasts on a plastic plate, which is the original physiological function of osteoclasts. “Bone resorption” cannot be analyzed in real time. In this study, Raman spectroscopy is used to show the state of bone resorption of osteoclasts cultured on ivory sections or octacalcium phosphate plates noninvasively and without the need for colorimetric assays. This makes it possible to clarify the effect of BP on osteoclast metabolism in an environment closer to that of a living body. If this method is established, then we aim to elucidate the pathophysiology of bone pathologies and medical treatments that directly affect osteoclasts, such as medication-related osteonecrosis, and establish a diagnostic method.