Daniel D. Bikle, MD, PhD
Staff Physician, Medical Service, SFVAHCS
Professor of Medicine and Dermatology, UCSF
Preventing Bone Loss and Investigating Skin Cancer
Skeletal unloading-when no stress is placed on the skeleton-occurs during prolonged bed rest, immobilization, and paralysis. It often leads to bone loss and resultant fractures. Dr. Bikle and his fellow researchers determined a likely cause of this bone loss: selective resistance to a growth factor called insulin-like growth factor (IGF-I), which is critical for normal bone growth and remodeling. They demonstrated that this resistance is linked, in turn, to a loss of expression of a major class of proteins, the integrins, which link the matrix of bone in which bone cells reside to the internal workings of those cells. They believe that efforts to restore or maintain the expression of these integrins should prevent the loss of IGF-I responsiveness during skeletal unloading. This would prevent bone loss during periods of bed rest or immobilization, and protect our affected veteran population from fractures.
Dr. Bikle is also investigating the role of IGF1 during bone formation and fracture repair. Fracture repair undergoes a process in which the initial step is to stimulate chondrocytes to form the initial mending with what is called the soft callus comprised of cartilage. Th ecartilage being replaced by bone is the same sequence of events that takes place in the growth plates of growing bone. IGF1 regulates this process by inducing signaling molecules that enable cells involved to talke to each other in a coordinated fashion to ensure both notmal growth and fracture repair.
Dr. Bikle also investigates skin cancer. This is the most common form of cancer, and represents a failure of the differentiation process in skin cells. Dr. Bikle found that both calcium and vitamin D regulate the development of major skin cells, and that furthermore, regulation of these substances within the skin cell may guard against the development of cancer. Dr. Bikle and his associates anticipate that their studies may result in new methods to prevent the development of skin cancer in predisposed individuals, including those with excessive sun exposure, such as veterans returning from the Middle East.
In addition to examining the role of calcium and vitamin D in skin cancer, Dr. Bikle is exploring the role of calcium and vitamin D in wound healing. As in skin cancer, lack of calcium and vitamin D receptors in the skin cells decreases their ability to heal wounds of the skin. This appears to be due at least in part to a loss of stem cell number and activation required for the healing process. These findings are expected to help patients with chronic wounds, the basis of which may include both vitamin D and calcium deficiency.
To see Dr. Bikle on Pub Med, click here.