Peptide and steroid hormones help regulate fracture healing. Growth hormone, insulin, thyroid hormone, cortisol, and gonadal steroids all have important functions throughout the process of fracture healing; each of these hormones has cell membrane or nuclear receptors in the tissues involved in the regenerative response. Vitamin D and its active metabolites as well as parathyroid hormone are essential for normal mineralization of bone in the later stages of fracture healing.

Vitamin C is vital in fracture healing and in post-translational modification of collage, the most abundant matrix component in both soft and hard callus. An adequate supply of amino acids, carbohydrates, fats, and trace elements is also critical for normal fracture healing.

Physical factors such as microenvironment and weight bearing are essential in the production of a normal inductive callus and are therefore essential in the promotion of bone healing.

FACTORS THAT DELAY BONE HEALING

Numerous factors are known to retard or inhibit bone repair. Glucocorticoid excess, for example, can lead to severe osteopenia, imperiling fracture healing; juvenile diabetes has the same potential effect. A deficiency of gonadal steroids in either men or women can also result in profound osteopenia, which slows the regenerative response after a fracture. Severe anemia can alter oxygen tensions at the fracture site. Deficiencies of vitamin D or its metabolites cause abnormal mineralization of the fracture callus, delaying fracture healing or causing nonunion.

The regenerative response is interrupted by large bone gaps due to the interposition of soft tissue and by devitalization of bone by irradiation, vascular loss, injury, loss of soft tissue, or denervation. Infections and neoplasm can retard fracture healing by some unknown mechanisms. The regenerative response can also be interrupted by components in the synovial fluid bathing the fragments of an intra-articular fracture, resulting in delayed union or nonunion. Severe osteoporosis from any cause, as well as metabolic diseases such as hyperparathyroidism, osteomalacia, Paget disease of bone, or fibrous dysplasia, can retard the regenerative response to a fracture.

Fractures heal more slowly in older persons than in children and young adults. Poor general nutrition and lack of vitamin C can have a direct inhibitory effect on the production of extracellular matrix, which can disrupt the formation of both soft and hard callus. Although movement can stimulate fracture healing, too little or too much movement disrupts endochondral callus formation, which may have important implications for fracture healing. Cigarette smoke has a negative effect on bone healing and increases the risk of nonunion. Nonsteroidal anti-inflammatory drugs have a negative impact on bone healing and should be avoided if possible during fracture healing as well.