Do Systemic Factors Influence the Fate of Nonunions to Become Atrophic? A Retrospective Analysis of 162 Cases

Abstract

Introduction. Nonunions are a challenge for orthopedic surgeons. In hypertrophic nonunions, improvement of mechanical stability usually is the satisfactory treatment, whereas in atrophic nonunions improvement of the biological environment is most important. However, scientific evidence revealed that “avital” nonunions are not avascular and fibrous tissue contains cells with osteogenic potential. To find out if systemic factors suppress this intrinsic potential in atrophic nonunions, this study compares characteristics of hypertrophic with atrophic nonunion patients. Methods. We analyzed medical records of 162 surgically treated patients suffering from aseptic long bone nonunions. Atrophic and hypertrophic nonunions were distinguished by absence or presence of callus and calcification in the fracture gap. Mechanical implant loosening and patient characteristics such as age, gender, and body mass index were assessed. Fracture classification according to AO/OTA, open and closed fractures, and osteosynthesis were recorded. In addition, comorbidities and allergies between both groups were compared. Results. A higher number of hypertrophic nonunion patients were male with often allergies. Hypertrophic nonunion occurred more often after intramedullary nailing compared to atrophic nonunions. Atrophic nonunion patients being nonallergic were significantly older than nonallergic patients suffering from hypertrophic nonunions. In both atrophic and hypertrophic nonunion patients, age was lower in patients with accompanying injuries compared with age of patients with isolated fractures. Conclusion. Systemic factors influence development of nonunion types. In nonallergic patients, atrophic nonunions occur more often in the elderly. This manuscript is a first step to identify different factors which might influence the nature of nonunion. To enable nonunion treatment which is tailored to individual patient characteristics, further prospective studies with more sophisticated research methods are necessary.

Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union

“…Furthermore, proteomic analysis of serum showed that complement C6, C3 and C4, which their strongly activating phenotype is less favourable for MSC-related immunosuppression 85 , were up-regulated in the serum of NU patients compared to healthy controls 101 . Altogether, the systemic changes of various serum mediators could explain the lower proliferative and osteogenic potential as well as the altered immunomodulatory potential of the MSC pool in BM that we noted in our study and by others for NU fracture patients 103 .…”

Existence of multilineage mesenchymal progenitor cells in human atrophic nonunion tissue

“…While the pool of BMSCs in nonunion patients was decreased compared to healthy subjects, we inferred that the NCs were the BMSCs in nonunion patients. In atrophic nonunion, it is also an important factor to improve the biological environment [36]. The purpose of using bone morphogenetic proteins is stimulating osteogenic activity at the nonunion site [37].…”

Differences in fracture healing between female and male C57BL/6J mice

“…Clinical studies analysing differences in fracture healing between male and female fracture patients are rather rare and results are di cult to interpret, because other in uencing factors, including fracture type, degree of tissue trauma, body weight and clinical manifestation of osteoporosis, frequently differ between men and women. It was shown for some types of fractures that male patients displayed more rapid fracture healing and women had an increased risk for atrophic non-unions rather than hypertrophic non-unions in males [14,15]. One clinical study reported signi cantly increased blood levels of the Wnt/βcatenin-signalling inhibitor Sclerostin in male geriatric hip fracture patients compared to female agematched patients, whereas the concentrations of another Wnt/β-catenin-signalling inhibitor, Dickkopf-1 were reduced [31].…”

“…However, it is known that sex hormones like oestrogen have considerable effects on bone healing [11][12][13]. There are also clinical indications that male patients display more rapid fracture healing and that women may have an increased risk for atrophic non-unions rather than hypertrophic non-unions as observed in males [14,15]. By contrast, there are also clinical studies reporting no in uence of sex on fracture healing in speci c fracture types [16][17][18].…”