[Effect of acrylic bone cement mixed with calcium sulfate combined with percutaneous kyphoplasty in the treatment of osteoporotic fractures].

OBJECTIVE: To investigate the clinical efficacy of acrylic cement (PMMA) mixed with calcium sulfate combined with percutaneous kyphoplasty (PKP) in the treatment of osteoporotic fracture (OVCF). METHODS: The clinical data of 191 patients with OVCF treated with PKP from January 2020 to March 2021 were retrospectively analyzed. Among them, 82 patients with 94 vertebral bodies were treated with PMMA mixed with calcium sulfate as the observation group, and 109 patients with 125 vertebral bodies were treated with pure PMMA as the control group. Among the 82 patients in the observation group, there were 16 males and 66 females, with a mean age of (75.35±11.22) years old, including 36 thoracic vertebrae and 58 lumbar vertebrae. In the control group, there were 109 patients, 22 males and 87 females, with an average age of (74.51±9.21) years old, including 63 thoracic vertebrae and 62 lumbar vertebrae. The visual analog scale (VAS) before operation and 1 day, 3 months and 1 year after operation were calculated. The Oswestry disability index (ODI), Cobb's angle, vertebral body height and the probability of postoperative bone cement leakage were used to analyze the efficacy of the two groups. RESULTS: All the patients were followed up for more than one year. Compared with the control group, there was no significant difference in operation time, bleeding volume and bone cement injection volume between the two groups(P>0.05), while the leakage rate of bone cement was significantly lower in the observation group (P<0.05). In addition, there was no significant difference in VAS, ODI, Cobb angle, and vertebral body height between the two groups before operation, and 1 day, 3 months, and 1 year after operation (P>0.05), but each index was improved compared with that before operation (P<0.05). CONCLUSION: PMMA mixed with calcium sulfate has equivalent efficacy in treating OVCF than PMMA alone, but can effectively reduce the probability of cement leakage.

Intramedullary application of local antibiotic bullets for the treatment of long bone fracture related infection.

PURPOSE: The optimal means of local antibiotic delivery for fracture related infection is unknown. Until now, intramedullary application of calcium sulphate based local antibiotics has been challenging. We report on the use of a newly available mode of preparation and delivery: the Stimulan Bullet Mat and Introducer (Biocomposites Ltd, Staffordshire, England). METHODS: A retrospective analysis of prospectively collected data for infection cases at two separate tertiary referral institutions was performed. We included cases of long bone FRI with a retained intramedullary nail, treated with a single stage protocol of metalwork removal, debridement, local antibiotic application using the novel mould and applicator, with additional bony stabilisation and soft tissue reconstruction where required. RESULTS: All 13 patients achieved infection remission rate with an average follow-up of 19.7 months (range 12-28). All 6 patients with infection around an unhealed fracture achieved union at an average 8 months (range 4-12) from debridement. No patients developed aseptic wound leak. CONCLUSIONS: Antibiotic impregnated calcium sulphate can be used safely as part of a single stage treatment protocol for the treatment of long bone fracture related infection following intramedullary nailing. We have demonstrated high rates of infection remission and union, using a newly available intramedullary applicator.

Antibiotic-impregnated calcium sulfate for the treatment of pediatric hematogenous osteomyelitis.

BACKGROUND: Antibiotic-impregnated calcium sulfate has excellent curative efficacy in chronic osteomyelitis. However, its curative efficacy in pediatric hematogenous osteomyelitis has not been sufficiently studied. The purpose of this study was to evaluate the curative effects of antibiotic-impregnated calcium sulfate in the treatment of pediatric hematogenous osteomyelitis. METHODS: Overall, twenty-one pediatric patients with hematogenous osteomyelitis treated at our hospital between 2013 and 2018 were included for assessment. The clinical history, clinical manifestation, infection recurrence rate, sinus leakage, incision leakage, pathological fractures, bone growth and surgical procedures were analyzed. RESULTS: The infection recurrence rate was 0% (0/21) at a minimum of 31 months (range 31 to 91 months) of follow-up. Postoperative incision leakage was found in one pediatric patient. Osteolysis was found in one pediatric patient. Acceleration of bone growth occurred in one pediatric patient. Retardation of bone growth occurred in one pediatric patient. Genu valgus deformity occurred in one pediatric patient. CONCLUSIONS: Although noninfectious complications occurred, the curative effect of antibiotic-impregnated calcium sulfate in pediatric hematogenous osteomyelitis was satisfactory.

Treatment of Infected Nonunions With Bone Defects Using Autologous Bone Graft and Absorbable Antibiotic-Loaded Calcium Sulfate-Hydroxyapatite Paste.

BACKGROUND: Revision surgery in the presence of infection carries high risks. We describe our results using a new technique to treat these challenging problems. We treated infected nonunions with cavitary voids with adjuvant antibiotic loaded calcium sulfate-hydroxyapatite paste composite and autologous bone graft (ABG) layer technique coupled with stable fixation. METHODS: Thirty consecutive patients who underwent revision foot and ankle surgery for an infected nonunion were prospectively studied. Following multidisciplinary team workup, surgical debridement and biopsies were undertaken. Bone voids were measured and classified according to containment and size. ABG was mixed and layered with an adjuvant antibiotic-loaded calcium sulfate-hydroxyapatite paste followed by surgical reconstruction including arthrodesis and fixation. Empirical and pathogen-specific antibiotics were instituted until intraoperative sample-specific antibiotics were identified and used. Patients were prospectively followed up for a minimum of 1 year. RESULTS: The male-female ratio was 16:14, mean age was 51.3 years, and 23.3% smoked at definitive surgery. Void volume was <1 cm3 (n=9), 1-2 cm3 (n = 13), and >2 cm3 (n=8). No patients either were lost to follow-up or had a further infective episode at a mean of 38.3 months; 86.7% united with fusion on imaging. Four patients had radiographic evidence of nonunion; 3 were asymptomatic and 1 required revision surgery (void >2 cm3). Independent ambulation was achieved at an average of 12 weeks, at 1 year mean American Orthopaedic Foot & Ankle Society score was 77.7 (SD 9.59), and the Manchester-Oxford Foot Questionnaire reached an effect size >0.5 in all domains at 1 year following surgery. The union rate was independent of smoking status and vitamin D deficiency (P = .94). CONCLUSION: Layered autologous bone grafting with adjuvant antibiotic-loaded calcium sulfate-hydroxyapatite paste has been shown to be effective and safe in revision arthrodesis, with low comorbidities in void gaps without infection recurrence.

Antibiotic-loaded calcium sulfate in clinical treatment of chronic osteomyelitis: a systematic review and meta-analysis.

BACKGROUND: Present work was aimed to gather accessible evidence on the eradication rates and related postoperative complications of antibiotic-loaded calcium sulfate (CS) as an implant in the treatment of chronic osteomyelitis (COM). METHODS: Databases including PubMed, EMBASE, Medline, Ovid and Cochrane library were searched from their dates of initiation until November 2021. Two independent authors scrutinized the relevant studies based on the effectiveness of radical debridement combined with antibiotic-loaded CS for COM; data extraction and quality assessment of the Methodological Index for Non-Randomized Studies (MINORS) criteria were also performed by the authors. In addition, clinical efficacy mainly depended on the evaluation of eradication rates and complications, and all the extracted data are pooled and analyzed by STATA 16.0. RESULTS: A total of 16 studies with 917 patients (920 locations) were recruited, with an overall eradication rate of 92%. Moreover, the overall reoperation rate, overall refracture rate, overall delayed wound healing rate, and the rate of aseptic wound leakage were 9.0%, 2.0%, 20.0%, and 12.0%, respectively. Moreover, the choice of tobramycin-loaded CS or vancomycin combined with gentamicin-loaded CS did not affect the eradication rate, and the incidence of postoperative complications in COM patients (all [Formula: see text]). The general quality of the included studies was fair. CONCLUSIONS: Our meta-analysis indicated that the overall eradication rate of COM treated with antibiotic-loaded CS was 92%. Delayed healing is the most common postoperative complication. The choice of tobramycin-loaded CS or vancomycin combined with gentamicin-loaded CS did not affect the eradication rate and the incidence of postoperative complications in COM patients.

Antibiotic calcium sulfate-loaded hybrid transport versus traditional Ilizarov bone transport in the treatment of large tibial defects after trauma.

BACKGROUND: The purpose of this study was to compare the clinical effects of antibiotic calcium sulfate-loaded hybrid transport (ACSLHT) and traditional Ilizarov bone transport (TIBT) in the treatment of large tibial defects after trauma. METHODS: Eighty-five patients with large tibial defects after trauma were selected for retrospective study. The range of tibial defects was 6-22 cm. After thorough debridement and infection controlled, bone transport technique was used to reconstruct tibial defects. Forty-four patients were treated with ACSLHT technique (the ACSLHT group), while the other 41 were treated with TIBT technique (the TIBT group). Time in external fixator was evaluated by EFI score. Enneking score was used to evaluate limb functions. SAS score was used to evaluate postoperative anxiety status. In addition, complication incidence was compared, including axis deviation, docking site nonunion, infection recurrence and so on. RESULTS: There was no significant difference in preoperative general data between ACSLHT and TIBT group. EFI score in ACSLHT and TIBT group was 0.6 ± 0.1 cm/month and 1.7 ± 0.3 cm/month, respectively (P < 0.05). Enneking score of ACSLHT and TIBT group was 86.5% and 75.1% (P < 0.05). SAS score of ACSLHT group was significantly lower than that of TIBT group (P < 0.05). Complication incidence in ACSLHT group was significantly lower than that in TIBT group (P < 0.05). CONCLUSIONS: Compared with TIBT group, ACSLHT group had shorter time in external fixator, better limb functions, lower postoperative anxiety score and lower complication incidence which is worth of clinical promotion.

Gastrocnemius muscle flap with vancomycin/gentamicin-calcium sulfate and autogenous iliac bone graft for the phase I treatment of localized osteomyelitis after tibial plateau fracture surgery.

PURPOSE: To investigate the clinical effect of gastrocnemius muscle flaps combined with vancomycin/gentamicin-calcium sulfate combined and autologous iliac bone graft in the phase I treatment of traumatic focal osteomyelitis (Cierny-Mader type III) after tibial plateau fracture surgery. METHODS: From July 2009 to January 2018, 35 patients with localized osteomyelitis (Cierny-Mader type III) who met the inclusion criteria were followed up and treated. All patients were infected after undergoing internal fracture fixation surgery. Among them, 18 cases were plate-exposed, 14 cases were due to sinus tracts, two were due to skin necrosis, and one was bone-exposed. We treated patients with several measures. All cases were then followed up. The follow-up indicators included Hospital for Special Surgery knee scores (HSS), the time of laying drainage pipe, bone healing time, infection control rate, and the incidence of nonunion and other complications. RESULTS: All patients were followed up for 24-60 months. None of them underwent amputation. For repairing soft tissue defects, 17 cases were covered with a muscle flap using the medial head of gastrocnemius alone, 15 cases were treated with the lateral head of gastrocnemius muscle, and three cases were covered with the combination of the two heads. Compared to the preoperative score, we found that the average HSS improved at the 1-year and 2-year follow-up (54 vs. 86 vs. 87). CONCLUSION: Using a gastrocnemius muscle flap combined with vancomycin/gentamicin-calcium sulfate and autogenous iliac bone was an effective method for the phase I treatment of osteomyelitis (Cierny-Mader type III) after tibial plateau fracture surgery. In the primary treatment of focal traumatic osteomyelitis, it can decrease the treatment time, number of surgeries, pain of patients, time of bone healing, postoperative exudation, and infection recurrence rate and increase the healing bone's strength.

Calcium sulfate antibiotic-impregnated bead implantation for deep surgical site infection associated with orthopedic surgery in small animals.

OBJECTIVE: To report the outcomes and complications associated with antibiotic-impregnated calcium sulfate beads for prevention and treatment of orthopedic-related surgical site infection (SSI) in companion animals. STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned cats (n = 2) and dogs (n = 14). METHODS: Medical records of 16 cases in which implantation of antibiotic-impregnated calcium sulfate beads was performed for the prevention or treatment of SSI were reviewed. Information collected included signalment, prior surgery, reason for bead placement, antibiotics used, bacterial culture results, and clinical outcomes. RESULTS: Surgical site infection resolved in six of 10 animals treated therapeutically and did not occur in six of six animals treated prophylactically. Susceptibility of the causative bacteria to the antibiotic implanted was confirmed in five of six cases with resolved SSI treated therapeutically but in only one of four cases with unresolved SSI treated therapeutically. Complications directly related to bead placement were evident in only one case in which beads extruded from external skeletal fixator pin tracts 7 days after implantation. At final follow-up, 11 of 12 animals without SSI had satisfactory limb use and no clinical, cytologic, or radiographic evidence of infection. CONCLUSION: Implantation was well tolerated. Resolution of SSI was inconsistent; however, when bacteria were susceptible to the antibiotic implanted, SSI resolved in all but one case. CLINICAL SIGNIFICANCE: Antibiotic-impregnated calcium sulfate beads could be considered for prevention or treatment of orthopedic SSI in small animals. A prospective clinical study is required to obtain additional information, including the value of preoperative bacterial culture.

Treatment of Chronic Hematogenous Osteomyelitis in Children With Antibiotic Impregnated Calcium Sulphate.

BACKGROUND: The purpose of this study was to evaluate the clinical and radiologic outcome of chronic hematogenous osteomyelitis (CHOM) in children, treated with single-stage debridement and dead space management using antibiotic impregnated calcium sulphate pellets. METHODS: The authors retrospectively evaluated a consecutive series of 34 patients who presented with CHOM from 2011 to 2017. In each case, CHOM was classified according to the Beit CURE classification. Following thorough surgical debridement, the resulting dead space in the bone was filled with the antibiotic impregnated beads before primary closure. RESULTS: Of the 31 patients available for follow up, effective regeneration of bone was confirmed in all cases, with radiographic bone healing typically observed at around 12 weeks. None of the children required reoperation for infection and none had recurrence of infection at the time of final review. The beads were completely absorbed within 3 months. No systemic adverse reactions to the local delivery of antibiotics were observed in this study. CONCLUSIONS: The authors found that single-stage debridement in conjunction with antibiotic impregnated calcium sulphate was an effective means of treating CHOM in children, with effective eradication of infection in every case. LEVEL OF EVIDENCE: Level IV-Retrospective case series. See instructions for authors for a complete description of levels of evidence.

Development and current use of local antibiotic carriers in spondylodiscitis : Pilot study on reduction of duration of systemic treatment.

BACKGROUND: The current study situation regarding the duration of systemic antibiotic treatment for spondylodiscitis is inhomogeneous and varies between 4-12 weeks. Due to the many undesirable side effects the aim is to achieve complete healing without recurrence or hematogenous scatter within the shortest possible period of time. The present pilot study investigated whether the additional application of a local antibiotic carrier to the surgically treated intervertebral disc space can contribute to a further reduction of treatment duration. MATERIAL AND METHODS: In the pilot study 20 patients with acute spondylodiscitis and indications for surgical intervention were included. Surgical treatment was carried out by dorsal instrumentation, radical debridement of the site of infection, and cage interposition in the affected disc space. The remaining disc space was filled with homologous cancellous bone and antibiotic-loaded calcium sulfate hydroxyapatite pellets. A classification into a long-term and a short-term antibiotic group was performed. Both groups initially received a 10-day parenteral antibiotic administration. This was followed by oral antibiotics for 2 or 12 weeks, depending on the group. During the 12-month follow-up inflammation parameters, the local infection situation as well as the bony fusion and antibiotic tolerance were regularly checked. RESULTS: The average age of the patients was 66.7 ± 11.2 years. Intraoperative detection of pathogens was successful in 65%. In 60% the antibiotic carrier was loaded with gentamicin, in 40% with vancomycin. At follow-up, all patients except one in the short-term antibiotic group had inflammation parameters within the normal range after 3 months. In the long-term antibiosis group, two patients still showed elevated infection values after 3 months, otherwise the values were within the normal range. After 12 months a complete cure of the infection was achieved in all patients. Antibiotic treatment intolerance occurred in 10% of the short-term antibiotic group and in 50% of the long-term group. CONCLUSION: The results of the present pilot study show that with the additional use of absorbable local antibiotic carriers in the surgical treatment of bacterial spondylodiscitis it is possible to shorten the duration of systemic antibiotic treatment to 3 weeks. This can reduce the side effects and incompatibility of treatment and still achieve similar healing results.

The effect of calcium sulfate/calcium phosphate composite for the treatment of chronic osteomyelitis compared with calcium sulfate.

BACKGROUND: Treatment of chronic osteomyelitis often requires surgical debridement in combination with bone defect reconstruction and antibiotics administration. We aimed at investigating and evaluating the effect of antibiotic-loaded absorbable calcium sulfate/calcium phosphate (CS/CP) composite as bone substitute in the treatment of chronic osteomyelitis compared with CS. METHODS: A retrospective study of 31 consecutive patients with chronic osteomyelitis from one medical center was conducted. The treatment involved thorough debridement, antibiotic loaded bone substitutes filling (group A: CS/CP, 21 patients, group B: CS, 10 patients), laboratory and radiographic examination, and culture-specific systemic antibiotic treatment guided by a multidisciplinary team. New bone formation property and resorption kinetics were analyzed through X-ray and CT scan qualitatively and quantitatively. Anti-infection effect was mainly analyzed by postoperative laboratory examination and healing of wound. RESULTS: The average follow-up in each group was 61.3 and 86.7 weeks, respectively. In group A (CS/ CP), no patient had recurrent infection at 17 months after surgery, 1 case had delayed wound healing and healed after dressing change. In group B (CS), 2 patients had recurrent infection at 18 weeks after surgery, and were managed after further surgical treatment, 3 cases had delayed wound healing and healed after dressing change. The infection in the two groups was mainly caused by staphylococcus aureus. The average percentage of new bone formation was 20.5%, 43.7%, 75.2% at 1, 3, and 6 months in group A and 15.4%, 32.2%, 49.7% at 1, 3, and 6 months in group B after operation (P=0.001 at 1 month, P=0.025 at 3 months, P=0.000 at 6 months). The average percentage of resorption was 23.7%, 56.4%, 81.2% at 1, 3, and 6 months in group A and 47.1%, 96.2%, 100% at 1, 3, and 6 months in group B after operation (P=0.000 at 1 month, P=0.000 at 3 months, P=0.000 at 6 months). There was difference in infection recurrence (P=0.034). CONCLUSIONS: Our preliminary results proved that compared with CS, this novel antibiotic-impregnated CS/CP composite acted as superior scaffold for bone formation with a lower rate of infection recurrence, when choosing bone substitutes in the treatment of chronic osteomyelitis.

Calcium sulphate for control of bleeding after oral surgery in anticoagulant therapy patients.

Control of bleeding after oral surgery is mandatory in patients taking anticoagulants. There are different haemostatic measures to prevent post-surgical bleeding. The aim of the present paper is to study the use of a haemostatic agent, calcium sulphate (CaS) (P30, Ghimas, Bologna, Italy) for controlling post-surgical bleeding in a group of patients treated with warfarin therapy for thromboembolic states. Twenty teeth (12 mandibular molars, 8 maxillary molars) in 20 patients (14 male and 6 females) with a mean age of 54.3 years (±10.3 years) were included in the study. The patients were divided into 2 groups; in the study group of 10 patients calcium sulphate was used in layers to fill the socket after extraction, while for the 10 patients in the control group put a gauze with tranexamic acid was put in the extraction site immediately after extraction, and half an hour after extraction. The outcome was bleeding in subsequent days. Bleeding at post-operative day 1 was significant in 5 patients of the control group, however, in the study group treated with calcium sulfate there was no bleeding in any patient (p value 0.0055). CaS demonstrated to be a good haemostatic agent for controlling bleeding after oral surgery in patients taking anticoagulants.

Autologous Iliac Bone Graft Compared with Biphasic Hydroxyapatite and Calcium Sulfate Cement for the Treatment of Bone Defects in Tibial Plateau Fractures: A Prospective, Randomized, Open-Label, Multicenter Study.

BACKGROUND: Bone-graft substitutes are commonly used for the augmentation of traumatic bone defects in tibial plateau fractures. However, their clinical performance compared with that of autologous bone-grafting, the gold standard in bone defect reconstruction, still remains under debate. This study investigates the differences in quality of life, pain, and radiographic outcomes in the treatment of tibial plateau fracture-associated bone defects with either autologous bone grafts or a bioresorbable hydroxyapatite and calcium sulfate cement (CERAMENT BONE VOID FILLER [CBVF]; BONESUPPORT). METHODS: In this study, 135 patients with acute depression and split-depression fractures of the proximal part of the tibia (OTA/AO types 41-B2 and 41-B3) were enrolled in a prospective, controlled, randomized, multicenter trial including 20 hospitals in Germany. Patients were randomized to receive either autologous iliac bone graft or CBVF for reconstruction of the bone defect. The primary outcome measures were the Short Form (SF)-12 version 2 Physical Component Summary (PCS) score at week 26 (the study was designed to show noninferiority of the CBVF with regard to the PCS with a prespecified margin of -5 points) and the pain level at 26 weeks postoperatively measured by a visual analog scale (VAS). The secondary outcomes were the SF-12 version 2 Mental Component Summary (MCS) and SF-12 PCS scores at weeks 1, 6, and 12 and bone-healing on radiographs. RESULTS: Age, sex, fixation methods, and fracture pattern were comparable in both groups. There were no significant differences (p > 0.05) in the SF-12 PCS or VAS scores at postoperative week 26. There was a significant reduction of blood loss (p = 0.007) and pain levels (p = 0.008) at postoperative day 1 in the CBVF group. The rates of fracture-healing, defect remodeling, and articular subsidence were not significantly different (p > 0.05) in both groups. CONCLUSIONS: Bioresorbable CBVF was noninferior to autologous bone graft with regard to both patient-reported and radiographic outcomes in tibial plateau fractures of OTA/AO types 41-B2 and 41-B3. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Different Molarities and Dissolution-Precipitation Duration Affect the Formation of Carbonate-Apatite Blocks for Bone Graft Material

Abstract Objective: To determine diametral tensile strength and water absorption ability of Carbonate-apatite blocks fabricated from gypsum precursors (CaSO4) through a dissolution-precipitation method, with different solution molarities and immersion times. Material and Methods: Thirty-six CaSO4 gypsum specimens with 6 mm diameter; 3 mm height (Group A for diametral tensile strength) and 36 specimens of 6 mm diameter; 3 mm thickness (Group B for water absorption ability) were used. Each group was divided into 4 group treatments of: 1) dissolution-precipitation in solution of 0.5mol / L Na2CO3 + 0.5mol / L Na3PO4 for 48 hours and 72 hours; 1mol / L Na2CO3 + 1mol / L Na3PO4 for 48 hours and 72 hours. The C-Ap blocks were then tested using ATR-FTIR spectrometer to identify the formation of C-Ap functional groups. Furthermore, Group A specimens were tested for diametral tensile strength using Universal Testing Machine, and Group B specimens were tested for water adsorption ability using an analytical balance by measuring initial and final weight after immersion in saline solution at 37oC for 24 hours. Results: The formation of carbonate-apatite (C-Ap) in groups with solution molarity of 1 mol/L for 48 hours and 72 hours resulted in a lower diametral tensile strength and water absorption ability than the groups with a 0.5 mol/L solution. Conclusion: Solution with different molarities and dissolution-precipitation duration affect the formation of carbonate-apatite blocks.

Strontium­containing α­calcium sulfate hemihydrate promotes bone repair via the TGF­ß/Smad signaling pathway.

Calcium phosphate­based bone substitutes have been widely used for bone repair, augmentation and reconstruction in bone implant surgery. While some of these substitutes have shown excellent biological efficacy, there remains a need to improve the performance of the current calcium phosphate­based bone substitutes. Strontium ions (Sr) can promote new osteogenesis, inhibit osteoclast formation and increase osteoconductivity. However, the therapeutic effect and mechanism of strontium­containing α­calcium sulfate hemihydrate (Sr­CaS) remains unclear. The present study created bone injuries in rats and treated the injuries with Sr­CaS. Then Cell Counting Kit­8, soft agar colony formation, flow cytometry, Transwell and Alizarin Red staining assays were performed to assess the bone cells for their proliferation, growth, apoptosis, invasion, and osteogenic differentiation abilities. The bone reconstructive states were measured by the microCT method, hematoxylin and eosin staining and Masson staining. Bone­related factors were analyzed by the reverse transcription­quantitative PCR assay; transforming growth factor (TGF)­ß, mothers against decapentaplegic homolog (Smad)2/3 and ß­catenin expression was measured by western blot analysis and osteocalcin (OCN) expression was assessed by immunohistochemistry. Sr­CaS did not significantly affect the proliferation and apoptosis of bone marrow stem cells (BMSCs), but did accelerate the migration and osteogenic differentiation of BMSCs in vitro. Sr­CaS promoted bone repair and significantly increased the values for bone mineral density, bone volume fraction, and trabecular thickness, but decreased trabecular spacing in vivo in a concentration­-dependent manner. In addition, Sr­CaS dramatically upregulated the expression levels of genes associated with osteogenic differentiation (Runt­related transcription factor 2, Osterix, ALP, OCN and bone sialoprotein) both in vitro and in vivo. Sr­CaS also increased Smad2/3, TGF­ß and phosphorylated­ß­catenin protein expression in vitro and in vivo. These results indicated that materials that contain 5 or 10% Sr can improve bone defects by regulating the TGF­ß/Smad signaling pathway.

Is Hypercalcemia a Frequent Complication following Local Use of Calcium Sulfate with Antibiotics for the Treatment of Extremity Posttraumatic Osteomyelitis? A Preliminary Study.

BACKGROUND: Previous study had reported hypercalcemia as a frequent complication (20%) following local use of antibiotic-eluting calcium sulfate (CS) during treatment of periprosthetic joint infections (PJIs). However, whether this complication may occur in patients who receive local CS implantation for management of posttraumatic osteomyelitis (OM) remains unclear. METHODS: Between April 2016 and May 2017, we included 55 patients with extremity posttraumatic OM who received local antibiotic-loaded CS therapy. Serum calcium levels were detected preoperatively and on the 1st, 3rd, and 7th postoperative days (PODs). Comparisons were performed regarding serum calcium levels among the four time points and between two different CS volume groups (≤ 20 cc group and > 20 cc group). Additionally, potential associations were examined regarding CS volume and preoperative calcium level with postoperative calcium levels, respectively. RESULTS: Altogether 46 males and 9 females were included, with a median CS volume of 20 cc. Outcomes showed that prevalence of asymptomatic hypocalcemia was more frequent, with 16.4% before surgery and 60%, 53.8%, and 25% on the 1st, 3rd, and 7th PODs, respectively. Hypercalcemia was not found in any patients, at any time point. In addition, significant differences were identified regarding serum calcium levels among different time points, suggesting significantly decreased calcium levels on the 1st (P < 0.001) and 3rd PODs (P < 0.001) and back to near preoperative level on the 7th POD (P = 0.334). However, no statistical differences were observed regarding serum calcium levels between the two CS volume groups at any time points (P > 0.05). Moreover, no significant links were identified between CS volume and postoperative calcium levels (P > 0.05). Serum calcium levels on the 3rd (P = 0.019) and 7th PODs (P = 0.036) were significantly associated with the preoperative calcium level. CONCLUSIONS: In contrast to what had occurred in PJI patients, asymptomatic hypocalcemia appeared to be more frequent in this cohort with posttraumatic OM. Hypercalcemia may be an infrequent complication before and after local CS use for the treatment of extremity posttraumatic OM.

Treatment with Vancomycin Loaded Calcium Sulphate and Autogenous Bone in an Improved Rabbit Model of Bone Infection.

Bone infection results from bacterial invasion, which is extremely difficult to treat in clinical, orthopedic, and traumatic surgery. The bone infection may result in sustained inflammation, osteomyelitis, and eventual bone non-union. Establishment of a feasible, reproducible animal model is important to bone infection research and antibiotic treatment. As an in vivo model, the rabbit model is widely used in bone infection research. However, previous studies on rabbit bone infection models showed that the infection status was inconsistent, as the amount of bacteria was variable. This study presents an improved surgical method for inducing bone infection on a rabbit, by blocking the bacteria in the bone marrow. Then, multi-level evaluations can be carried out to verify the modelling method. In general, debriding necrotic tissue and implantation of vancomycin-loaded calcium sulphate (VCS) are predominant in antibiotic treatment. Although calcium sulphate in VCS benefits osteocyte crawling and new bone growth, massive bone defects occur after debriding. Autogenous bone (AB) is an appealing strategy to overcome bone defects for the treatment of massive bone defects after debriding necrotic bone. In this study, we used the tail bone as an autogenous bone implanted in the bone defect. Bone repair was measured using micro-computed-tomography (micro-CT) and histological analysis after animal sacrifice. As a result, in the VCS group, bone non-union was consistently obtained. In contrast, the bone defect areas in the VCS-AB group were decreased significantly. The present modeling method described a reproducible, feasible, stable method to prepare a bone infection model. The VCS-AB treatment resulted in lower bone non-union rates after antibiotic treatment. The improved bone infection model and the combination treatment of VCS and autogenous bone could be helpful in studying the underlying mechanisms in bone infection and bone regeneration pertinent to traumatology orthopedic applications.

Aplicación profiláctica de sulfato de calcio medicado en prótesis total de cadera no cementada / Prophylactic application of medicated calcium sulphate in uncemented total hip prosthesis

Resumen: El incremento en la cirugía de artroplastía total de cadera es motivado por muchos factores, como el aumento en la expectativa de vida, mejoría continua en la técnica quirúrgica e innovaciones en el diseño y los materiales de los implantes que, sumados, han convertido a este procedimiento en una solución efectiva a la degeneración articular, con excelentes resultados. Sin embargo, a pesar de los avances tecnológicos, la infección periprotésica se ha mantenido como una de las complicaciones más devastadoras. Este estudio evalúa la aplicación profiláctica de perlas de sulfato de calcio medicadas en el canal femoral y superficie acetabular para prevenir infecciones periprotésicas en pacientes que fueron sometidos a una artroplastía total de cadera primaria no cementada contra un grupo control mediante la medición de reactantes de fase aguda y cultivo de líquido sinovial. Se sometieron al estudio 146 individuos: 67 a quienes se les aplicaron perlas de sulfato de calcio medicado y 79 a quienes se les aplicó antibiótico profiláctico intravenoso de Septiembre de 2013 a Agosto de 2016. Como método diagnóstico de infección periprotésica temprana se evaluaron la proteína C reactiva asociada a velocidad de sedimentación globular aumentada, una fístula que comunicara con la prótesis, cultivo positivo de dos o más sitios periprotésicos de líquido sinovial o tejido. Los resultados clínicos demostraron que hubo una disminución en los valores de los reactantes de fase aguda en los sujetos a quienes se les aplicaron las perlas de sulfato de calcio medicado. Se encontró que 14 personas presentaron infección en el grupo con profilaxis parenteral, comparado con tres del grupo con profilaxis local con perlas de sulfato de calcio medicado; ambos grupos con ceftriaxona. Se consideró que el uso profiláctico de perlas de sulfato de calcio dentro de canal medular y la superficie acetabular es una buena opción para prevenir infecciones periprotésicas en quienes han sido sometidos a una artroplastía total de cadera primaria no cementada; sin embargo el estudio amerita seguimiento con más pacientes para tener significancia estadística.

Abstract: The increase in total hip arthroplasty occurs by many factors, such as increasing life expectancy, improving surgical technique as well as innovating the design and implant material. However, despite technological advances, peri-prosthetic infection has remained one of the most devastating complications. This study evaluates the prophylactic application of calcium sulfate pearls medicated in the femoral canal and acetabular surface to prevent peri-prosthetic infections in patients who underwent total uncemented primary hip arthroplasty against a control group by measuring acute phase reactants. 146 patients, 67 were applied calcium sulfate pearls medicated and 79 prophylactic antibiotic intravenous in the period from 2013 to 2016. To perform the diagnosis of peri-prosthetic infection was assessed PCR associated with VSG, communication between fistula and prostheses and positive culture in 2 or more different sites. There was a decrease in the values of acute-phase reactants in patients who were given calcium sulfate pearls. 14 patients presented infection in the control group and 3 in the study group. The prophylactic use of calcium sulphate pearls within the medullary canal and acetabular surface is an option for the prophylaxis of peri-prosthetic infections, however the study deserves follow-up with more patients.

Guided tissue engineering for healing of cancellous and cortical bone using a combination of biomaterial based scaffolding and local bone active molecule delivery.

A metaphyseal bone defect due to infection, tumor or fracture leads to loss of cancellous and cortical bone. An animal model separating the cancellous and cortical healing was used with a combination of a macroporous gelatin-calcium sulphate-hydroxyapatite (Gel-CaS-HA) biomaterial as a cancellous defect filler, and a thin collagen membrane (CM) guiding cortical bone regeneration. The membrane was immobilized with bone morphogenic protein-2 (rhBMP-2) to enhance the osteoinductive properties. The Gel-CaS-HA cancellous defect filler contained both rhBMP-2 and a bisphosphonate, (zoledronate = ZA) to prevent premature callus resorption induced by the pro-osteoclast effect of rhBMP-2 alone. In the first part of the study, the CM delivering both rhBMP-2 and ZA was tested in a muscle pouch model in rats and the co-delivery of rhBMP-2 and ZA via the CM resulted in higher amounts of bone compared to rhBMP-2 alone. Secondly, an established tibia defect model in rats was used to study cortical and cancellous bone regeneration. The defect was left empty, filled with Gel-CaS-HA alone, Gel-CaS-HA immobilized with ZA or Gel-CaS-HA immobilized with rhBMP-2+ZA. Functionalization of the Gel-CaS-HA scaffold with bioactive molecules produced significantly more bone in the cancellous defect and its surroundings but cortical defect healing was delayed likely due to the protrusion of the Gel-CaS-HA into the cortical bone. To guide cortical regeneration, the cortical defect was sealed endosteally by a CM with or without rhBMP-2. Subsequently, the cancellous defect was filled with Gel-CaS-HA containing ZA and rhBMP-2+ZA. In the groups where the CM was doped with rhBMP-2, significantly higher number of cortices bridged. The approach to guide cancellous as well as cortical bone regeneration separately in a metaphyseal defect using two bioactive molecule immobilized biomaterials is promising and could improve the clinical care of patients with metaphyseal defects.

Ephedra sinica Stapf and Gypsum Attenuates Heat-Induced Hypothalamic Inflammation in Mice.

Ephedra sinica Stapf (EH) exert toxic effects, such as excitability, cardiac arrhythmia, and others. On the contrary, in traditional herbal medicine, EH and gypsum (GF) are used most often to treat symptoms caused by external stressors. The hypothalamus plays a crucial role in thermal homeostasis. Inflammatory response in the hypothalamus by thermal stressors may affect thermal and energy homeostasis. This study investigates the effect of EH and GF against heat-induced mouse model. Mice were divided into four groups: saline, saline plus heat, EH plus heat, and GF plus heat treated groups. Heat stress was fixed at 43 °C for 15 min once daily for 3 days. Weight and ear and rectal temperature measurements were made after terminating heat stress. Hypothalamus tissue was collected to evaluate the HSP70, nuclear factor kappa-Β (NF-kB), and interleukin (IL)-1ß protein expression levels. EH and GF treatment suppressed the increased body temperature. EH significantly ameliorated heat-induced body weight loss, compared to gypsum. Regulatory effects of EH and GF for body temperature and weight against heat stress were mediated by IL-1ß reduction. EH showed significant HSP70 and NF-kB inhibition against heat stress. EH and GF contribute to the inhibition of heat-induced proinflammatory factors and the promotion of hypothalamic homeostasis.