Association of Antibiotic Alterations in Gut Microbiota With Decreased Osseointegration of an Intramedullary Nail in Mice With and Without Osteomyelitis

Treatment of osteomyelitis requires prolonged antibiotic therapy which significantly alters the gut microbiota. While the influences on bone mass and microstructure have been extensively studied, it is poorly understood what impact the changes in gut microbiota may have on the host response to osseointegration around an intramedullary nail implanted. Here, we explored the influence of gut microbiota on the bone osseointegration process around an implant under two conditions: implantation of an intramedullary nail in the bone marrow cavity and chronic osteomyelitis (CO) induced by Staphylococcus aureus infection. Body weight, hepatorenal functions, serum levels of proinflammatory cytokines were monitored. The composition of gut microbiota was assessed via 16S rRNA sequencing, and the bone condition was analyzed via micro-computed tomography, hematoxylin and eosin staining, Safranin O-fast green and Goldner’s trichrome staining. Osteoblastogenesis and osteoclastogenesis were assessed by detecting tartrate-resistant acid phosphatase and osterix expression. We found that perturbation of gut microbiota (increase in Proteobacteria and decrease in Bacteroidetes) associated with delayed osseointegration and increased levels of proinflammatory cytokines in the serum (p<0.05), lower bone mass (p<0.05), deficient endochondral ossification and bone formation, reduced osteoblastogenesis (p<0.05) and enhanced osteoclastogenesis (p<0.001). Survival rates (p=0.002) and bacterial loads (p=0.0363) in bone differed significantly between the CO and antibiotic-treated CO mice, but cytokines levels, bone mineral density, and bone formation did not differ, likely because of the severely damaged bone structure. In summary, antibiotic treatment perturbed the gut microbiota and significantly interfered with the bone osseointegration around the nail by increasing proinflammatory cytokine levels in circulation, inhibiting osteoblastogenesis, enhancing osteoclastogenesis, and thus leading to higher pathogen colonization as well as higher mortality postinfection. This report of ours is the first to demonstrate antibiotic-induced alterations in the gut microbiota affect bone osseointegration, helping us understand the role of gut microbiota disorders in osteoblastogenesis and osteoclastogenesis following implant insertion with or without infection.

Two-year results of clinical use of arthromedullary bypass for knee osteoarthritis

BACKGROUND: With the ineffectiveness of conservative therapy for the knee joints osteoarthritis (OA), arthroscopic debridement (AD) of the affected joints is a common method of surgical treatment. However, the results of studies indicate a low efficiency of the use of AD in gonarthrosis. In order to improve the results of the use of AD in the knee joints OA, it was proposed to use an original implant to communicate the bone marrow cavity and the cavity of the knee joint. In the immediate postoperative period, such arthromedullary bypass surgery revealed a rapid improvement in the condition of the affected joints, a decrease in the severity of symptoms, and a decrease in the need for pain relievers. AIM: To compare the results of arthroscopic surgery in patients with knee osteoarthritis without and with the use of arthromedullary bypass (AMB) of joint at 2 years after the intervention. MATERIALS AND METHODS: The results of a comparative study involving 147 patients aged 42 to 80 years with knee osteoarthritis were presented. In the control group (67 patients), only arthroscopic debridement was performed; in the study group (80 patients, 90 operations) AMB was additionally performed (10 patients on both knee joints) for the entry of an intraosseous content into the joint cavity. The results were evaluated 3, 6, 12, and 24 months after surgery, using the Lequesne algofunctional index and the WOMAC index and the need for the nonsteroidal antiinflammatory drugs (NSAID) was assessed. RESULTS: The positive dynamics of both indicators in both groups during the first 3 months of follow-up was maintained for 24 months, and their more significant changes, as well as a decrease in stiffness and the frequency of nocturnal joint pain, occurred in the study group (p 0.01). 24 months after surgery, 87% of patients in the study group refused to take regular NSAID, and 54% in the control group (p 0.01). During the AMB, the percentage of operations with unsatisfactory and moderate results decreased by 2.53.5 times, and the percentage of cases with good and excellent results was 28% higher compared to the control group (p 0.01). СONCLUSIONS: The proposed AMB of joints had a long-term beneficial effect and is promising for the treatment of patients with knee osteoarthritis who do not respond to conservative treatment. Its use can improve joint function, reduce joint pain and dependence on analgesics, and thus ease the severity of the disease in more patients.

Anatomical parameters of and differences in the proximal femoral cavity in adult patients with developmental hip dysplasia

Objective: To explore the anatomical parameters proximal femoral cavity and developmental dysplasia of the hip. Methods: The retrospective study was conducted at Peking University Third Hospital, Beijing, China, and comprised data of adult patients of either gender who underwent total hip arthroplasty from January 2009 to August 2015. Paients with a diagnosis of primary osteoarthrosis or aseptic necrosis of the femoral head were taken as the control group A, while patients with developmental dysplasia of the hip in group B were graded into subgroups I-IV using the Crowe classification. For each patient, the inner diameter of the proximal femoral medullary cavity was measured on preoperative radiographs using Noble’s technique. Data was analysed using SPSS 20. Results: Of the 835 hips, 571(68.4%) were in group A and 264(31.6%) in group B. The mean age of the patients at the time of surgery was 58.3 ± 12.3 years. Overall, there were 404(48.4%) hips of male patients; 59(22.3%) in group B. There were 431(51.6%) hips of female patients; 205(77.7%) in group B. In group B, 186(70.5%) hips were graded I, 38(14.4%)grade II, 22(8.3%)grade III, and 18(6.8%) hips were graded IV. There were significant differences in femoral offset, height of the femoral head, and canal flare index of the metaphysis between groups A and B (p<0.05). There was no significant difference in the morphology of the marrow cavity between subgroups II and III.

Long-Term Use of Glucocorticoid Exacerbates Bone Lesions in Postmenopausal Women With Rheumatoid Arthritis

Background Glucocorticoid-induced osteoporosis is osteoporosis arising due to long-term use of glucocorticoids. Current despite decades of intense research, the effects of long-term use of glucocorticoids in humans on bone cells and bone structural changes remain unclear. Methods We performed postmortem histomorphometric analysis of bone from two female patients with rheumatoid arthritis aged 64y and 85y. Our two patients had been treated with glucocorticoids for 19 years and 14 years, respectively. Results In case 1, all markers of cancellous bone volume were markedly decreased compared with the age-matched reference range. Connectivity of cancellous bone trabecula was absent. Only a few island bones were noted. There was prominent thinning of the cortical bone, and extension of the bone marrow cavity into the cortical bone with prominent cortical porosis. Cortical nodes between the endocortical surface and the trabecula disappeared due to endocortical resorption. Stoppage of lamellar structure was observed because the bone resorption by osteoclasts surpassed bone formation by osteoblasts. Empty lacunae characterized by disappearance of osteocytes were visible. In case 2, all volume markers of cancellous bone were decreased to the same extent as case 1. However, cortical porosis was more prominent than case 1. Conclusion These two cases suggest that use of glucocorticoid therapy &gt; 10 y can induce severe osteoporosis in elderly RA women with higher disease activity, and that the disappearance of cancellous bone is the common characteristic. The 85 year-old woman was characterized by cortical porosis.

Effect of Zoledronic Acid Combined With Metformin on Bone of Db/db Mice

Background Diabetic Osteoporosis (DO) is a complication of diabetes. As a first-line medication for diabetes, metformin combined with the anti-osteoporosis drug zoledronic acid is still unclear whether it is effective in treating DO. In this work, we explored the effect of metformin combined with zoledronic acid in the treatment of DO.Methods 12-week-old db/db mice were randomly divided into db/db group, ZA (zoledronic acid) group, MET (metformin) group, CMT (combination therapy group) group, Set WT (wild-type) mice of the same strain and age as the blank control group. Body weight and blood glucose were measured every 2 weeks. After 10 weeks, samples were taken for pathology and imaging related tests.Results (1) The body weight of db/db mice treated with metformin was stable and blood glucose was decreased. (2) After HE staining, db/db mice treated with metformin showed decreased adipocytes, increased blood cells and blood vessels in bone marrow cavity; db/db mice treated with zoledronic acid showed increased trabeculae. The number of bone trabeculae and blood vessels in the bone increased after the combined use of the two drugs. (3) By OPG staining and semi-quantitative analysis, db/db mice had the lowest osteoblastic activity. db/db mice treated with metformin had higher osteoblastic activity than those treated with zoledronic acid, and the osteoblastic activity of CMT was higher than that treated with ZA group or MET group. (4) After TE staining, semi-quantitative analysis showed that the number of bone lacunae in WT group was the least, the number of bone lacunae in ZA group and CMT group was significantly lower than that in db/db group, but the number of bone lacunae in MET group was not significant. (5) The bone morphological analysis of db/db mice in the CMT group was significantly better than that of MET or ZA alone by micro-CT scanning and bone tissue parameters determination.Conclusion ZA combined with MET has better anti-bone loss effect than zoledronic acid or metformin alone in db/db mice.

Osteopetrosis in a Domestic Shorthair Cat

The purpose of this case report was to describe a cat with generalized bone dysplasia, resembling osteopetrosis and Albers-Schönberg disease in humans. A 1-year-3-month-old, intact male, domestic shorthair cat had a 9-month history of multiple bone fractures without known trauma. Most fractures were treated conservatively and two by osteosynthesis. Bone healing occurred but recurring fractures eventually led to euthanasia. Radiographs, computed tomographic imaging, postmortem analysis and histopathologic examination revealed a generalized increase in bone density and mass with preservation of bone shape, obliteration of the bone marrow cavity and persistence of cartilage and primary trabeculae. Abuse and secondary bone diseases were excluded. History, diagnostic bloodwork, radiographs, computed tomographic imaging and histopathologic examination supported the diagnosis of inherited osteopetrosis and strongly resembled Albers-Schönberg disease in humans. The presence of osteoclasts suggested that the underlying pathology might be found in osteoclast dysfunction, deficient number of osteoclasts, inadequate recruitment of osteoclasts, or other micro environmental changes. In (young) cats that are presented with recurring fractures and the possible suspicion of abuse, inherited osteopetrosis should be considered as a differential diagnosis.

Morphological Analysis of Medullary Cavity for Designing Personalized Femoral Stem

To improve the quality and efficiency of femoral stem prosthesis design, a Monte Carlo method based on femoral bone marrow cavity analysis is proposed to measure morphological parameters using anatomical semantics. The region of interest is the femur, which includes the medullary cavity and cortical region. After this region is extracted, the size of the cavity and region is simulated using the Monte Carlo method. Finally, based on clinical needs, the morphological parameters are calculated and analyzed based on the size of the region of interest. From the perspective of the probability model, the non-random problem of solving the cross-section area of the femoral marrow cavity is transformed into one having a random nature so that a probability model can be used. The experimental results show that this method is simple, flexible, and efficient. It provides a new and reasonable scientific method for comprehensively understanding the anatomical morphological changes of the femoral marrow cavity. The measurement and analysis of the morphological parameters of the femoral bone marrow cavity in this paper provide the necessary scientific theoretical support for improved morphologic research, design, and clinical selection of femoral stem prostheses and has important significance and application value in clinical practice.

Anti-Osteoporotic Effects of Commiphora Myrrha and Its Poly-Saccharide via Osteoclastogenesis Inhibition

In traditional oriental medicines, Commiphora myrrha and its resinous exudate (i.e., myrrh) are used as herbal remedies to treat various inflammatory and metabolic disorders. Until now, C. myrrha-derived herbal products are considered useful source for bioactive compounds to manage numerous human diseases. This study investigated the effects of water extract of C. myrrha resin (WCM) and its polysaccharide (WCM-PE) on modulatory effects of osteoclast differentiation and/or ovariectomized-induced bone loss. Oral administration of WCM (200 and 500 mg/kg/day for four weeks) notably decreased trabecular bone loss and lipid accumulation in the bone marrow cavity. WCM and WCM-PE dose-dependently inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and suppressed RANKL-mediated overexpression of c-Fos and nuclear factor of activated T cells, cytoplasmic 1, thereby downregulating osteoclast-specific gene (Atp6v0d2, DC-STAMP and cathepsin K) expression. Thus, our results suggest that WCM and WCM-PE are promising nutraceutical candidates for the management of osteoporosis in postmenopausal women.

Experimental Study On Antibacterial Properties of Iodine-Coated Implant in Acute Osteomyelitis Model

Purpose We have developed a iodine-coated implant and evaluated its antibacterial properties against Gram-negative bacteria by constructing an experimental osteomyelitis model.Methods In this study, 16 titanium Kirschner-wires were selected, of which 8 titanium K-wires were treated with iodine on the surface by electrophoretic deposition with PVP-I solution. In our study, the standard strain of Escherichia coli (ATCC 25922) was selected, and 16 New Zealand rabbits were selected. There were 8 rabbits in the iodine-coated group and 8 rabbits in the non-iodine-coated group. All animals were drilled in the left proximal tibia after successful anesthesia.After that,the iodine-coated group was implanted with iodine-coated titanium K-wires.Then, 25ul of 2×108CFU/ml bacterial suspension was injected into the bone marrow cavity with pipette gun, and the bone hole was sealed with bone wax.They were reared in cages for 1 week after operation, and evaluated and analyzed by microbiology, histopathology, scanning electron microscopy, etc.Results The results of gross wound score and microbiology showed that the wound infection of the iodine-coated group was less severe than that of the non-iodine-coated group, which was confirmed by the histopathological results. Scanning electron microscopy and confocal microscopy showed that the amount of bacteria on the surface of iodine-coated K-wires was significantly lower than that non-iodine-coated K-wires. Conclusions In this study, we have verified that the iodine-coated titanium implant could effectively inhibit E. coli infection in the early stage of infection by constructing an acute osteomyelitis model.

Epiphyseal enchondroma masking as osteoid osteoma: a case report

Background Enchondromas originating in the epiphyses of long bones are rare and epiphyseal osteoid osteomas are also uncommon. Diagnosis can become elusive when enchondromas or osteoid osteomas occur in atypical locations and present with nonspecific clinical and imaging characteristics. Case presentation We report a case of epiphyseal enchondroma of the left proximal femur in a 15-year-old girl with a 2-month history of left lower extremity pain. Preoperative CT displayed thickened cortex in the anterior surface of the left proximal femur with specks of calcification and inhomogeneity of the adjacent bone marrow cavity. She was diagnosed with osteoid osteoma. Postoperative pathological examination of surgically excised specimens revealed a diagnosis of enchondromas. Conclusions Our case highlights that enchondroma should be considered in lesions of the epiphysis.