92 research outputs found
Bone Healing Gone Wrong : Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors
Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor
cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly
in long bones including the tibia, clavicle, humerus and femur, this process fails in 2–10% of all
fractures, with devastating effects for the patient and the healthcare system. Underlying reasons for
this failure are manifold, from lack of biomechanical stability to impaired biological host conditions
and wound-immanent intricacies. In this review, we describe the cellular components involved in
impaired bone healing and how they interfere with the delicately orchestrated processes of bone
repair and formation. We subsequently outline and weigh the risk factors for the development of
non-unions that have been established in the literature. Therapeutic prospects are illustrated and put
into clinical perspective, before the applicability of biomarkers is finally discussed
Parathyroid hormone stimulates bone regeneration in an atrophic non-union model in aged mice
Background Non-union formation still represents a major burden in trauma and orthopedic surgery. Moreover, aged
patients are at an increased risk for bone healing failure. Parathyroid hormone (PTH) has been shown to accelerate
fracture healing in young adult animals. However, there is no information whether PTH also stimulates bone regeneration in atrophic non-unions in the aged. Therefore, the aim of the present study was to analyze the efect of PTH
on bone regeneration in an atrophic non-union model in aged CD-1 mice.
Methods After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fxation. The animals
were treated daily with either 200 mg/kg body weight PTH 1–34 (n=17) or saline (control; n=17) subcutaneously.
Bone regeneration was analyzed by means of X-ray, biomechanics, micro-computed tomography (µCT) imaging
as well as histological, immunohistochemical and Western blot analyses.
Results In PTH-treated animals bone formation was markedly improved when compared to controls. This was associated with an increased bending stifness as well as a higher number of tartrate-resistant acid phosphatase (TRAP)-
positive osteoclasts and CD31-positive microvessels within the callus tissue. Furthermore, PTH-treated aged animals showed a decreased infammatory response, characterized by a lower number of MPO-positive granulocytes
and CD68-positive macrophages within the bone defects when compared to controls. Additional Western blot
analyses demonstrated a signifcantly higher expression of cyclooxygenase (COX)-2 and phosphoinositide 3-kinase
(PI3K) in PTH-treated mice.
Conclusion Taken together, these fndings indicate that PTH is an efective pharmacological compound for the treatment of non-union formation in aged animals
A novel press-fit minimally-invasive symphysiodesis technique
Objective: Instability of the pubic symphysis often results in a poor outcome and reduced mobility of the patient.
In some cases, an arthrodesis of the pubic symphysis is required. Until today, there is no data published how many
of these procedures are performed annually and there is also no data about the outcome after this extensive
surgery.
Methods: We developed a novel surgical technique to address the arthrodesis of the pubic symphysis in a minimally
invasive approach. Therefore, we used for this purpose modified instruments and performed the transplantation of a
cylindrical bone substitute into the pubic symphysis, without an extensive approach or dissecting the anterior or
posterior symphyseal ligaments.
Results: Using this novel technique, a minimally invasive symphysiodesis was achieved in radiological findings, after
the procedure.
Conclusion: Thus, this actually minimally invasive surgical technique seems to be a promising advancement for the
arthrodesis of the pubic symphysis
Cilostazol promotes blood vessel formation and bone regeneration in a murine non-union model
Non-unions represent a major complication in trauma and orthopedic surgery. Many factors contribute to bone
regeneration, out of which an adequate vascularization has been recognized as crucial. The phosphodiesterase-3
(PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in a variety of
preclinical studies. Hence, we herein investigated the effects of cilostazol on bone regeneration in an atrophic
non-union model in mice. For this purpose, a 1.8 mm femoral segmental defect was stabilized by pin-clip fixation
and the animals were treated daily with 30 mg/kg body weight cilostazol or saline (control) per os. At 2, 5 and 10
weeks after surgery the healing of femora was analyzed by X-ray, biomechanics, photoacoustic imaging, and
micro-computed tomography (µCT). To investigate the cellular composition and the growth factor expression of
the callus tissue additional histological, immunohistochemical and Western blot analyses were performed.
Cilostazol-treated animals showed increased bone formation within the callus, resulting in an enhanced bending
stiffness when compared to controls. This was associated with a more pronounced expression of vascular
endothelial growth factor (VEGF), a higher number of CD31-positive microvessels and an increased oxygen
saturation within the callus tissue. Furthermore, cilostazol induced higher numbers of tartrate-resistant acidic
phosphate (TRAP)-positive osteoclasts and CD68-positive macrophages. Taken together, these findings demonstrate that cilostazol is a promising drug candidate for the adjuvant treatment of atrophic non-unions in clinical
practice
Managing periprosthetic fractures: perspectives on periprosthetic pelvic fractures
Periacetabular periprosthetic fractures are rare but potentially disastrous for the longevity of the adjacent implants, leading to multiple revision surgeries. It is of paramount importance to identify and treat intraoperative fractures, which will lead to satisfactory results. Postoperative fractures may be managed operatively or nonoperatively depending on the patient's pain and function, the fracture pattern, and the stability of the acetabular component
Radiographic, Biomechanical and Histological Characterization of Femoral Fracture Healing in Aged CD-1 Mice
With a gradually increasing elderly population, the treatment of geriatric patients represents
a major challenge for trauma and reconstructive surgery. Although, it is well established that aging
affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we
investigated fracture healing in young adult (3–4 months) and aged (16–18 months) CD-1 mice using
a stable closed femoral fracture model. Bone healing was analyzed by radiographic, biomechanical
and histological analysis at 1, 2, 3, 4 and 5 weeks after fracture. Our results demonstrated an increased
callus diameter to femoral diameter ratio in aged animals at later time points of fracture healing
when compared to young adult mice. Moreover, our biomechanical analysis revealed a significantly
decreased bending stiffness at 3 and 4 weeks after fracture in aged animals. In contrast, at 5 weeks
after fracture, the analysis showed no significant difference in bending stiffness between the two study
groups. Additional histological analysis showed a delayed endochondral ossification in aged animals
as well as a higher amounts of fibrous tissue at early healing time points. These findings indicate a
delayed process of callus remodeling in aged CD-1 mice, resulting in a delayed fracture healing when
compared to young adult animals. However, the overall healing capacity of the fractured femora was
not affected by aging
Effects on Bone and Muscle upon Treadmill Interval Training in Hypogonadal Male Rats
Testosterone deficiency in males is linked to various pathological conditions, including
muscle and bone loss. This study evaluated the potential of different training modalities to counteract
these losses in hypogonadal male rats. A total of 54 male Wistar rats underwent either castration
(ORX, n = 18) or sham castration (n = 18), with 18 castrated rats engaging in uphill, level, or downhill
interval treadmill training. Analyses were conducted at 4, 8, and 12 weeks postsurgery. Muscle force
of the soleus muscle, muscle tissue samples, and bone characteristics were analyzed. No significant
differences were observed in cortical bone characteristics. Castrated rats experienced decreased
trabecular bone mineral density compared to sham-operated rats. However, 12 weeks of training
increased trabecular bone mineral density, with no significant differences among groups. Muscle force
measurements revealed decreased tetanic force in castrated rats at week 12, while uphill and downhill
interval training restored force to sham group levels and led to muscle hypertrophy compared to
ORX animals. Linear regression analyses showed a positive correlation between bone biomechanical
characteristics and muscle force. The findings suggest that running exercise can prevent bone loss in
osteoporosis, with similar bone restoration effects observed across different training modalities
Pantoprazole impairs fracture healing in aged mice
Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2Â weeks and decreased at 5Â weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation
Awareness of predatory journals and open access publishing among orthopaedic and trauma surgeons – results from an online survey in Germany
Background
Along with emerging open access journals (OAJ) predatory journals increasingly appear. As they harm accurate and good scientific research, we aimed to examine the awareness of predatory journals and open access publishing among orthopaedic and trauma surgeons.
Methods
In an online survey between August and December 2019 the knowledge on predatory journals and OAJ was tested with a hyperlink made available to the participants via the German Society for Orthopaedics and Trauma Surgery (DGOU) email distributor.
Results
Three hundred fifty orthopaedic and trauma surgeons participated, of which 291 complete responses (231 males (79.4%), 54 females (18.6%) and 5 N/A (2.0%)) were obtained. 39.9% were aware of predatory journals. However, 21.0% knew about the “Directory of Open Access Journals” (DOAJ) as a register for non-predatory open access journals. The level of profession (e.g. clinic director, consultant) (p = 0.018) influenced the awareness of predatory journals. Interestingly, participants aware of predatory journals had more often been listed as corresponding authors (p < 0.001) and were well published as first or last author (p < 0.001). Awareness of OAJ was masked when journal selection options did not to provide any information on the editorial board, the peer review process or the publication costs.
Conclusion
The impending hazard of predatory journals is unknown to many orthopaedic and trauma surgeons. Early stage clinical researchers must be trained to differentiate between predatory and scientifically accurate journals
Profiling microRNA expression in murine bone healing and non-union formation: Role of miR-140 during the early stage of bone healing
Although cellular and molecular mechanisms during the course of bone healing have been
thoroughly investigated, the regulation of gene expression by microRNA during bone regen eration is still poorly understood. We hypothesized that nonunion formation is associated
with different microRNA expression patterns and that target proteins of these microRNAs
are differently expressed in callus tissue of nonunions compared to physiologically healing
bones. In a well-established femoral osteotomy model in CD-1 mice osteotomies were
induced which result either in healing or in nonunion formation. MicroRNA and target protein
expression was evaluated by microarray, quantitative real-time polymerase chain reaction
(qrt-PCR) and Western blot. Microarray analyses demonstrated 44 microRNAs to be rele vant for nonunion formation compared to physiological bone healing. In nonunions qrt-PCR
could validate a higher expression of microRNA-140-3p and microRNA-140-5p. This was
associated with a reduced expression of Dnpep and stromal cell-derived factor (SDF)-1α,
which are both known to be target proteins of microRNA-140 and also to be involved in the
process of bone healing. These data suggest that an increased expression of microRNA 140-3p and microRNA-140-5p markedly contributes to the development of nonunions, most
probably by affecting bone morphogenetic protein (BMP)-2 function during the early stage
of healing due to a reduced SDF-1α expression
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