Increased serum OPG in atrophic nonunion shaft fractures

Abstract

BackgroundBone repair alteration is hypothesized for nonunion fracture pathogenesis. Since it is involved in osteoclast regulation, the RANK/RANKL/OPG system (receptor activator of nuclear factor kB/its ligand/osteoprotegerin) may play a role.Materials and methodsSerum OPG, free RANKL, bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline (DPD) were determined in 16 male patients (20–39 years) with long bone atrophic nonunion fractures. Serum markers were also measured in 18 age-matched male controls who healed from the same type of fractures within six months, and in 14 age-matched male controls who were healing from the same fractures one month after injury. One-way ANOVA and Bonferroni’s test were used for statistical analysis.ResultsOnly OPG was significantly higher (0.56 sd 0.11 ng/ml) in the patients compared to healed (0.26 sd 0.04 ng/ml; P < 0.001) and healing (0.29 sd 0.09 ng/ml; P < 0.001) controls. The patients’ DPD levels were normal. No correlations were found between bone markers and the characteristics of the subjects in all groups.ConclusionsA normal steady state of bone metabolism seems to be present in patients with atrophic nonunion fractures, despite the high serum OPG. The reason for the inability of the patients’ OPG to inhibit osteoclastic activity is unknown. Osteoblast activity also appears normal, so another cellular source of OPG can be hypothesized.

Plasma and drainage fluid levels of soluble receptor activator of nuclear factor-kB (sRANK), soluble receptor activator of nuclear factor-kB ligand (sRANKL) and osteoprotegerin (OPG) during proximal humerus fracture healing

“…There are few reports about the modes of action of RANKL, OPG and none about RANK during fracture healing in humans. In these studies, following patients with fractures at different anatomical sites, no differences have been shown in these biological measurements between upper and lower limb [14,15]. Our study represents one of the first investigations to define the involvement of RANK, RANKL and OPG in fracture healing and their possible roles as biomarkers to monitor this process.…”

Bone turnover markers for early detection of fracture healing disturbances: A review of the scientific literature

“…In the first study, lower OC concentrations were reported in the group of patients whose fractures evolved into delayed union than in the group showing normal bone union, from the first days after treatment and throughout the entire study period, while in the second study there was a lag in the rise of OC concentration during the first 2 months amongst the group of patients that underwent a delayed union. Nevertheless, Emami et al (1999) and Marchelli et al (2009) found that serum OC concentration was unable to differentiate between a delayed union and a normal bone union. These studies present some limitations that could call into question the comparability of the results from the different study groups, results which are mainly related to the small number of patients included in each group.…”

“…With regard to molecules that regulate the function of osteoclasts, a preliminary clinical study was conducted in which differences were observed in serum OPG levels between patients who had developed an atrophic non-union and those that had progressed towards normal fracture healing (Marchelli et al 2009). However, in a more recent study, it was noticed that in patients with a normal bone-union, serum OPG, RANK and RANKL levels were not affected by the fracture healing process, since these levels remained unchanged (2005) verified that the serological variation of TGF-β1 could contribute to an early detection of an impaired fracture healing process.…”

“…Patients with atrophic nonunion process of diaphyseal long bone fractures presented higher serum levels than control groups: subjects that have already healed from the same type of fracture (p<0.001) and subjects that were healing from the same type of fracture (p<0.001). RANK Ligand Marchelli et al (2009) No significant differences between the groups.…”

Multivalent Presentation of Peptide Targeting Groups Alters Polymer Biodistribution to Target Tissues

“…20 There is clear motivation to increase drug delivery to bone, as approximately 6 million bone fractures occur annually in the United States, of which nearly 20% result in non-unions or delayed unions. 21 Impaired healing is due to dysfunctions in bone remodeling, including poor vascularization, 22–24 overactive osteoclasts, 25 and deficient osteoblasts. 26–28 A variety of drugs have great potential for overcoming these deficiencies.…”