Principles of Bone Healing

Iain H. Kalfas, MD, FACS Department of Neurosurgery, Section of Spinal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio

Neurosurg Focus. 2001;10(4) 

In This Article

Regulators of Bone Metabolism

Bone metabolism is under constant regulation by a host of hormonal and local factors. Three of the calcitropic hormones that most affect bone metabolism are parathyroid hormone, vitamin D, and calcitonin. Parathyroid hormone increases the flow of calcium into the calcium pool and maintains the body's extracelluar calcium levels at a relatively constant level. Osteoblasts are the only bone cells that have parathyroid hormone receptors. This hormone can induce cytoskeletal changes in osteoblasts. Vitamin D stimulates intestinal and renal calcium-binding proteins and facilitates active calcium transport. Calcitonin is secreted by the parafollicular cells of the thyroid gland in response to an acutely rising plasma calcium level. Calcitonin serves to inhibit calcium-dependent cellular metabolic activity.

Bone metabolism is also affected by a series of proteins, or growth factors, released from platelets, macrophages, and fibroblasts. These proteins cause healing bone to vascularize, solidify, incorporate, and function mechanically. They can induce mesenchymal-derived cells, such as monocytes and fibroblasts, to migrate, proliferate, and differentiate into bone cells. The proteins that enhance bone healing include the BMPs, insulin-like growth factors, transforming growth factors, platelet derived growth factor, and fibroblast growth factor among others.[18,32]

The most well known of these proteins are the BMPs, a family of glycoproteins derived from bone matrix. Bone morphogenetic proteins induce mesenchymal cells to differentiate into bone cells. Although typically present in only minute quantities in the body, several BMPs have been synthesized using recombinant DNA technology and are currently undergoing clinical trials to assess their potential to facilitate bone fusion in humans.[26,27,28]

Other proteins influence bone healing in different ways. Transforming growth factor-regulates angiogenesis, bone formation, extracellular matrix synthesis, and controls cell-mediated activities. Osteonectin, fibronectin, osteonectin, and osteocalcin promote cell attachment, facilitate cell migration, and activate cells.[15,20,22]

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