Value of SPECT/CT in the assessment of necrotic bone fragments in patients with delayed bone healing or non-union after traumatic fractures

Objective: To evaluate the value of single-photon emission computed tomography / computed tomography (SPECT/CT) compared with planar bone scintigraphy (BS) in the assessment of necrotic bone fragments in patients with delayed bone healing or non-union after traumatic fractures. Methods: Retrospective evaluation of patients with traumatic fractures and suspected delayed healing or non-union and/or persistent pain or suspected infection who had undergone planar late phase BS and SPECT/CT between 2011 and 2018. On the BS and SPECT/CT images, a necrotic fragment was considered if there was an area of absent radiotracer uptake (photopenia) related to bone at the fracture site. Histology served as a reference standard (presence or absence of necrotic bone fragments). If histology was not available, intraoperative findings and combined clinical and imaging follow-up served as reference standards. Results: In 37 consecutive patients with traumatic fractures (femur (n = 18), tibia (11), humerus (6), radius (1), jaw (1)), necrotic bone fragments were suspected in 11 fractures (29.7%) on BS and in 16 fractures (43.2%) on SPECT/CT. 35 fractures (94.6%) had metallic implants. Histology showed necrotic fragments in 10/11 (90.9%) patients. For the detection of necrotic bone fragments, SPECT/CT showed sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 95%, 94%, 100%, and 97%, respectively, and BS 67%, 95%, 91%, 81%, and 83%, respectively. SPECT/CT significantly outperformed BS with better area under curve (AUC) for SPECT/CT (0.9773) compared to planar imaging (0.8106) (p-value < 0.01). Conclusions: SPECT/CT is an accurate tool in the assessment of necrotic bone fragments in patients with delayed bone healing or non-union after traumatic bone fractures and is superior to conventional planar BS. Advances in knowledge: SPECT/CT is accurate and superior to planar BS in identification of necrotic bone fragments, responsible for delayed bone healing/non-union after fractures.

Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model

Background Delayed bone healing, especially in long bones poses one of the biggest problems in orthopeadic and reconstructive surgery and causes tremendous costs every year. There is a need for exploring the causes in order to find an adequate therapy. Earlier investigations of human scaphoid non-union revealed an elevated osteoclast activity, accompanied by upregulated levels of TGF-beta and RANKL. Interestingly, scaphoid non-union seemed to be well vascularized. Methods In the current study, we used a murine femur-defect model to study atrophic non unions over a time-course of 10 weeks. Different time points were chosen, to gather insights into the dynamic processes of non-union establishment. Results Histological analyses as well as western blots and qRT-PCR indicated enhanced osteoclast activity throughout the observation period, paralleled by elevated levels of TGF-beta, TNF-alpha, MMP9, MMP13 and RANKL, especially during the early phases of non-union establishment. Interestingly, elevated levels of these mediators decreased markedly over a period of 10 weeks, as inflammatory reaction during non-union establishment seemed to wear out. To our surprise, osteoblastogenesis seemed to be unaffected during early stages of non-union establishment. Conclusion Taken together, we gained first insights into the establishment process of atrophic non unions, in which inflammatory processes accompanied by highly elevated osteoclast activity seem to play a leading role.

Surgical Bone Drilling: A Review

Bone drilling is an important step in orthopedic surgeries for the reconstruction and repair of fractured bones. The main concern in bone drilling is to create holes without causing minimum damage to the bone tissues. It is well reported that high temperature and high force in drilling cause bone thermal necrosis leading to the delayed bone healing and implant failure. In the past, a significant amount of research has been conducted to understand and mitigate the issues in bone drilling. However, the current practice in bone drilling is that medical surgeons still rely on their own experience and feeling, which often causes unwanted damage to the bone. The present paper aims to provide a comprehensive review of surgical bone drilling and impending factors affecting drilling and biological performance of the bone. Current protocols and practices in tackling issues around drilling are discussed and assessed in terms of results obtained in both experimental and computational domains. This pragmatic discussion will signify the importance and challenges ahead in empowering medical surgeons to enable improved surgical outcome. Furthermore, the findings of this extensive review are expected to drive further exploration of new opportunities for developing advanced bone drilling system integrated with intelligent sensors and control technology.

Cefazolin Irreversibly Inhibits Proliferation and Migration of Human Mesenchymal Stromal Cells

Drugs may have a significant effect on postoperative bone healing by reducing the function of human mesenchymal stromal cells (hMSC) or mature osteoblasts. Although cefazolin is one of the most commonly used antibiotic drugs in arthroplasty to prevent infection worldwide, there is a lack of information regarding how cefazolin affects hMSC and therefore may have an effect on early bone healing. We studied the proliferation and migration capacity of primary hMSC during cefazolin treatment at various doses for up to 3 days, as well as the reversibility of the effects during the subsequent 3 days of culture without the drug. We found a time- and dose-dependent reduction of the proliferation rate and the migratory potential. Tests of whether these effects were reversible revealed that doses ≥250 μg/mL or treatments longer than 24 h irreversibly affected the cells. We are the first to show that application of cefazolin irreversibly inhibits the potential of hMSC for migration to the trauma site and local proliferation. Cefazolin should be administered only at the required dosage and time to prevent periprosthetic infection. If long-term administration is required and delayed bone healing is present, cefazolin application must be considered as a cause of delayed bone healing.