Update and Reassessment of Data on the Role of Osteocalcin in Bone Properties and Glucose Homeostasis in OC-/- Mice

Osteocalcin (OC) is a small protein (49 aa) produced by the osteoblast and the most abundant noncollagenous protein in bone. Studies using the osteocalcin-depleted knock-out mouse (OC-/-) reported that osteocalcin affects bone mineral properties and bone strength. Other reports indicated osteocalcin was a hormone regulating glucose metabolism by increasing insulin secretion and sensitivity. These results were controversial. Several years ago, a couple of groups generated osteocalcin knock-out mice using different methods and failed to observe an effect of osteocalcin on bone mineral properties, bone strength or glucose metabolism. One review claimed that the previously reported results from OC-/- mouse studies were inconsistent. Within the last 2 years, additional OC-/- mouse studies have been reported, and they confirm the role of osteocalcin in glucose metabolism, bone mineral properties and strength. Some of the new data reported clears up any controversy. Published studies on the role of osteocalcin in bone and glucose metabolism using OC-/- mice will be reviewed, and results will be compared. It is shown that most of the data on the effect osteocalcin on bone properties and strength is consistent and corroborated when comparing valid data from similar techniques and similar regions of the bone. Data corroborating the role of osteocalcin in glucose metabolism will be presented, and reasons for conflicting results will be discussed. Diabetics and the elderly have reduced osteocalcin levels and are prone to bone fractures, while diabetics are glucose-intolerant. Osteocalcin may be of therapeutic use to these populations.