Recent Advances in the Use of Serological Bone Formation Markers to Monitor Callus Development and Fracture Healing

Abstract

The failure of an osseous fracture to heal, or the development of a nonunion, is common; however, current diagnostic measures lack the capability of early and reliable detection of such events. Analyses of radiographic imaging and clinical examination, in combination, remain the gold standard for diagnosis; however, these methods are not reliable for early detection. Delayed diagnosis of a nonunion is costly from both the patient and treatment standpoints. In response, repeated efforts have been made to identify bone metabolic markers as diagnostic or prognostic tools for monitoring bone healing. Thus far, the evidence regarding a correlation between the kinetics of most bone metabolic markers and nonunion is very limited. With the aim of classifying the role of biological pathways of bone metabolism and of understanding bone conditions in the development of osteoporosis, advances have been made in our knowledge of the molecular basis of bone remodeling, fracture healing, and its failure. Procollagen type I amino-terminal propeptide has been shown to be a reliable bone formation marker in osteoporosis therapy and its kinetics during fracture healing has been recently described. In this article, we suggest that procollagen type I amino-terminal propeptide presents a good opportunity for early detection of nonunion. We also review the role and potential of serum PINP, as well as other markers, as indications of fracture healing.

Smoking Modulates Gene Expression of Type I Collagen, Bone Sialoprotein, and Osteocalcin in Human Alveolar Bone

“…18,19 In addition, the TGF family is linked to osteoblastic proliferation, differentiation, and COL-I synthesis, which also are related to bone formation activity. 18,20 Other essential bone biomarkers are OCN, a bone matrix protein manufactured by osteoblasts that has an important impact on bone metabolism, and ALP, an enzyme produced by activated osteoblasts that have a role in calcium hydroxyapatite deposition on bone. 18,20 Conversely, TNF-a is a proinflammatory cytokine acting as a potent activator of bone resorption and inhibitor of bone formation by stimulating osteoclast differentiation, [21][22][23] preventing osteoclast apoptosis, 24 increasing osteoclast activation, 25 and inhibiting osteoblast differentiation.…”

“…18,20 Other essential bone biomarkers are OCN, a bone matrix protein manufactured by osteoblasts that has an important impact on bone metabolism, and ALP, an enzyme produced by activated osteoblasts that have a role in calcium hydroxyapatite deposition on bone. 18,20 Conversely, TNF-a is a proinflammatory cytokine acting as a potent activator of bone resorption and inhibitor of bone formation by stimulating osteoclast differentiation, [21][22][23] preventing osteoclast apoptosis, 24 increasing osteoclast activation, 25 and inhibiting osteoblast differentiation. 26 A better understanding of the profile of these bonerelated factors, as proposed in the present investigation, could elucidate possible molecular mechanisms through which smoking interferes with bone tissue repair around implants.…”

Changes of Bone Turnover Markers in Long Bone Nonunions Treated with a Regenerative Approach

“…During the callus remodeling, an increase of markers of bone resorption is expected [33]. As a marker, we selected CTX that derives from the digestion of type 1 collagen mediated by cathepsin K produced by osteoclasts [32, 40].…”

Teriparatide as a nonoperative treatment for tibial and femoral fracture nonunion

“…[12] However, measurement of the specific molecular markers of osteoblasts and osteoclasts could improve the evaluation of fracture healing and detect the risk of nonunion. [13] P1NP may be a promising marker of nonunion, with 1 previous study showing that it decreased to normal levels during union. [14] In that same study, the changing rate of bone collagen synthesis was closely related to the changing rate of bone formation during fracture healing.…”