Skeletal Health
Skeletal health is important at every age and stage of life. Our bones allow us to walk, ride a bike, and hold a child. The skeleton serves six major functions:
• Support: provides the framework which supports the body and maintains its shape
• Movement: forms joints between bones allow for a wider range of movement (e.g. the ball and socket joint in the hip)
• Protection: helps protect our vital organs (e.g. rib cage protects the lungs and heart)
• Blood cell production: development of blood cells takes place in the bone marrow
• Storage: the bone matrix can store calcium and the bone marrow can store iron
• Endocrine regulation: bone cells can release a hormone called osteocalcin which helps regulate blood sugar and fat deposition
In the last 15 years, bone research has provided insight into the way the skeleton works, grows, rebuilds, weakens, and breaks. We know that diet and exercise can grow strong, healthy bones in children and help maintain them as we age. But we also know that lifestyle factors such as smoking and obesity can negatively affect bone health.
Aging
What we have learned about bone health is especially important as individuals around the world are living longer. By 2050, there will be approximately 1.5 billion people who will be 65 years of age or older. Skeletal pain tends to increase with age as the mass, quality and strength of the human skeleton peaks at 25–30 years of age in both males and females. The age-related bone loss results primarily from decreased bone formation relative to bone resorption.
Loss of bone strength can lead to osteoporosis, a disorder in which bones become very fragile and more likely to break. Older adults with osteoporosis are most vulnerable to breaks in the wrist, hip, and spine. These fractures often never heal, permanently limiting mobility and independence. Therefore, as the lifespan of individuals in both the developing and developed world continues to increase and with the rise of lifestyle factors such as obesity and reduction in daily physical activity, both of which reduce skeletal health, the burden that skeletal pain will exact on individuals and society is expected to increase markedly in the coming decades
Currently, there is a significant unmet clinical need to develop new therapies that relieve skeletal pain due to fracture, osteoarthritis, orthopedic procedures, etc. and enhance bone and joint tissue repair following injury and aging. Our lab works to address these issues by working at the interface between neurobiology, bone biology, and stem cell biology. Our efforts have the potential to halt or reverse changes that occur in the human skeleton as a result of aging, injury or genetic disorders.
Cancer
There was an estimated 13.4 million people living with cancer in the United States in 2011, with a projected 1.66 million new cases of cancer developing in 2014. Lung, breast, prostate, myeloma, and other cancers show a propensity to metastasize to bone. With this metastasis comes intractable pain that often affects a patient’s quality of life. Unfortunately, the current treatments used to treat cancer-induced pain are largely inadequate. To address this, our lab has established mouse models that emulate metastasized cancer pain in the femur. These models have provided valuable insight into the relationship between nerves and cancer as well as serve as a platform to test the efficacy of therapeutics.
Our laboratory focuses on the effects of new treatments on cancer-induced bone pain, and the effect of those treatments on cancer disease progression. Cancer induced nerve sprouting has long been appreciated, but the function of this sprouting is just starting to be understood. This synergistic interaction between both nerves and cancer has been, and continues to be, a focus of the Mantyh laboratory.
We not only study the biology of cancer and nerves, but also utilize our cancer models to test novel therapeutics. Collaborations with industry partners have provided insight into the effects of growth factors, neuropeptides, nerve sprouting, bone loss, as well as other key players on bone cancer-induced pain. We strive to maintain these partnerships and are open to establishing new ones.