INSULIN INCREASES HISTOMORPHOMETRIC INDEXES OF BONE-FORMATION IN-VIVO

Recent clinical studies have established that bone density is related to both fat mass and circulating insulin levels. A direct action of in sulin on the osteoblast may contribute to these relationships. Osteobl ast-like cells have insulin receptors, and insulin has been shown to s timulate proliferation of these cells in vitro. However, it has not be en possible to study the effects of insulin administration on bone in vivo because of the metabolic effects of insulin, particularly hypogly cemia. A model involving the local injection of insulin over one hemic alvaria of an adult mouse overcomes these difficulties and permits the histomorphometric study of insulin's action on bone. Insulin or vehic le was injected daily for 5 days over the right hemicalvariae of adult mice, and the animals were sacrificed 1 week later. All indices of bo ne formation were significantly increased in insulin-treated hemicalva riae compared with the noninjected hemicalvariae. There was a 2.73 +/- 0.50-fold increase in osteoid area (P = 0.005), a 2.20 +/- 0.37-fold increase in osteoblast surface (P = 0.021) and a 2.04 +/- 0.29-fold in crease in osteoblast number (P = 0.012). Indices of bone resorption te nded to decline and mineralized bone area tended to increase in insuli n-treated animals. The direct action of insulin on bone may contribute to the increased bone density seen in obesity and to the osteopenia o f type I diabetes, conditions associated with insulin excess and defic iency, respectively.