The Constant Destruction and Regeneration of BoneThe "bones" that support our bodies may appear at first glance to be merely rigid structures. However, when we explore their interior using the latest scientific technology, it becomes clear that dynamic and complex life activities far exceeding our imagination are taking place within them. Bones are not simply supportive tissue but vital organs that govern overall health, and their roles are diverse.Bones are not static structures that remain unchanged once formed. Throughout our lives, they continuously undergo destruction and regeneration. This process is called "remodeling" and is essential for maintaining our health. Remodeling primarily involves two types of cells.Types of Cells That Break Down BoneOsteoclasts are responsible for dissolving bone tissue and absorbing old bone. They attach to the bone surface and secrete acids and enzymes to break down hydroxyapatite (hard crystals primarily composed of calcium phosphate, the main component of bone) and collagen (the protein responsible for bone flexibility). Through this action, old portions of bone are constantly removed, creating space for new bone.Osteoblasts create new bone tissue and maintain bone strength. They appear after bone resorption and secrete collagen and other proteins, then deposit calcium and phosphate to form bone. Through the action of osteoblasts, bone structure is reconstructed and microscopic damage is repaired.When the balance between destruction and regeneration collapses, serious impacts on bone health occur. For example, when bone destruction exceeds regeneration, bone density decreases and the risk of osteoporosis increases. In Japan, approximately 13 million people are estimated to suffer from osteoporosis, particularly common among postmenopausal women. Data shows that about one in three women over 50 has osteoporosis. With osteoporosis, bones become susceptible to fracture even from minor impacts, significantly reducing quality of life. The incidence of proximal femoral fractures reaches approximately 1.2% annually among women in their 80s, and the subsequent risk of transitioning to a state requiring nursing care is reported to be high.The Close Relationship Between Bones and the Immune SystemBones also play an extremely important role in the body's immune system. The bone marrow existing inside bones is the birthplace of all blood cells—red blood cells, white blood cells, and platelets. White blood cells in particular form the core of immune cells and work on the front lines of defense mechanisms that protect the body from pathogens.Bone marrow serves as an "educational ground" where immature immune cells mature and differentiate into functional cells. For example, B lymphocytes mature in the bone marrow and protect the body from bacteria and viruses by producing antibodies. Antibodies are proteins that recognize specific pathogens and help eliminate them.The thymus, while not directly related to bones, is also an important organ in terms of immune cell education. T lymphocytes born in the bone marrow migrate to the thymus, where they receive "education" to distinguish between self cells and foreign substances. If this process does not proceed normally, the risk of developing autoimmune diseases (illnesses where one's own immune system attacks the body, such as rheumatoid arthritis) increases.Healthy bone marrow function is essential for maintaining a robust immune system. The importance of bone marrow can be understood from the fact that blood cancers such as leukemia and multiple myeloma originate in the bone marrow. These diseases impair normal hematopoietic function through abnormal blood cell proliferation, causing decreased immunity and anemia.Why Cancer Cells Gather in Bones"Cancer," one of humanity's greatest enemies, is also deeply connected to bones. Many cancers, as they progress, metastasize to other organs, but breast cancer, prostate cancer, lung cancer, and others are known to frequently metastasize to bones. Reports indicate that approximately 70% of breast cancer patients and about 85% of prostate cancer patients develop bone metastases.Bones are blessed with abundant blood vessels, providing an environment where cancer cells can easily obtain nutrients and oxygen. Factors that promote angiogenesis and bone formation exist abundantly, providing a niche (in the ecological sense, the optimal place or environment for a specific organism to live) suitable for cancer cell proliferation.Bones are locations where growth factors and proliferation factors are abundantly stored. For example, cytokines (proteins responsible for intercellular communication) such as TGF-β (transforming growth factor beta) and IGF-1 (insulin-like growth factor 1), which are stored bound to hydroxyapatite, the main component of bone, are released during the bone destruction process and may help cancer cell proliferation and survival.The active cellular metabolism of bone remodeling creates an optimal proliferation environment for cancer cells. As bone destruction by osteoclasts progresses, growth factors are released from the bone, and it has become clear that this creates a "vicious cycle" that further stimulates cancer cell proliferation.Bone metastases cause serious complications such as severe pain, pathological fractures (fractures occurring from weak forces that would not normally cause fractures, due to bones weakened by cancer cells), and spinal cord compression (a condition where bone metastases compress the spinal cord, causing paralysis or numbness), significantly reducing patients' quality of life. Elucidating the mechanisms of bone metastasis is an extremely important challenge in developing cancer treatment strategies.The Evolutionary History of Human BonesThe story of when and how the "bones" in our bodies came to their present form is a grand tale of evolution. Since the birth of life on Earth, over the tremendous span of approximately 3.8 billion years, the prototype of bone has gradually formed.After life originated in the ocean, the first appearance of hard tissue is thought to date back to the Cambrian explosion approximately 540 million years ago. During this period, organisms with exoskeletons began to appear among invertebrates. For example, arthropods like trilobites had hard shells to protect their bodies. These were mainly made of chitin, but later evolved into harder structures incorporating inorganic materials such as calcium carbonate.The development of endoskeletons in vertebrates is thought to have begun approximately 500 million years ago during the Ordovician period of the Paleozoic era. Early vertebrates were mainly those with cartilaginous skeletons like cartilaginous fish. Cartilage has the advantages of flexibility and relatively rapid growth, but has limitations in strength to resist gravity on land.Hard bone—skeletal structures primarily composed of calcium phosphate—began to develop in earnest approximately 400 million years ago during the Devonian period of the Paleozoic era, when fish diversified. Around this time, bony fish appeared and developed hard, durable skeletons for more efficient swimming and defense against predators. This is thought to be because the substance calcium phosphate was extremely advantageous for supporting the body while resisting gravity in water and enabling rapid movement.Approximately 360 million years ago during the Carboniferous period of the Paleozoic era, amphibians evolved from fish and advanced onto land. In this "terrestrial migration," skeletal strength played a decisive role. In terrestrial environments without the buoyancy of water, a strong skeleton to support one's own body weight became absolutely essential. With the appearance of tetrapods, the shape and structure of bones also changed significantly to withstand gravity and enable efficient movement.The human skeleton has undergone further unique adaptations in the evolutionary process. The acquisition of bipedalism brought major structural changes to the pelvis, spine, and lower limb bones. For example, the human spine evolved to absorb impacts in an upright posture and maintain balance by forming an S-curve. Additionally, with brain enlargement, the shape of the skull also changed significantly, taking on the role of protecting the complex brain.Thus, the evolutionary history of bone is closely connected to the process by which life adapts to environments and acquires diverse lifestyles. Bones have evolved into multifunctional organs that support the fundamentals of life activities, not only supporting the body but also storing calcium phosphate, producing immune cells, and even secreting hormones.Cutting-Edge Research on BonesResearch on "invisible bones" is evolving daily. In recent years, it has become clear that bones function not only as calcium reservoirs or immune cell sources but also as endocrine organs. For example, osteocalcin, a hormone secreted by osteoblasts, has been shown to promote insulin secretion from the pancreas and regulate blood glucose levels. Research using mice has also suggested that osteocalcin may enhance muscle function and improve exercise capacity.Let us consider the importance of these "invisible bones" through an episode. An elderly woman suffered a serious proximal femoral neck fracture from a fall. Although the surgery was successful, her recovery took longer than expected, and returning to daily life was difficult. This case suggests that not only the physical problem of a broken bone was involved, but also bone fragility from osteoporosis, accompanying muscle mass decline, and possibly slight immune function decline combined to have an impact. If her bones had been undergoing active remodeling internally despite appearances, supplying appropriate immune cells, and furthermore if systemic metabolism had been properly regulated by bone-derived hormones, recovery might have been faster.Furthermore, detailed research is being conducted on how the network of nerves and blood vessels in bones affects bone remodeling, immune function, and even cancer metastasis. In addition to advances in diagnostic imaging technologies such as X-ray CT and MRI, the development of molecular biological methods and live imaging technologies (techniques for observing the activities of living cells and tissues in real time) that enable more detailed cellular-level analysis is accelerating the elucidation of "invisible bones."These research findings are leading to the development of new treatments for intractable diseases such as osteoporosis and bone metastases from cancer, and are expected to greatly contribute to extending healthy life expectancy in the future. Bones contain life activities that are far deeper and more complex than we imagine. Unraveling the hidden world of these "invisible bones" is a frontier of life sciences and an important key to shaping our future.Sources"Invisible Bones" by Masaru Ishii "The Hard and Soft 'Complex System': The Mysteries of Bone - More Than Just Supporting the Body, Unknown Functions" by Masaru Ishii