Periprosthetic joint infection (PJI) is a complication of total joint arthroplasty that typically requires revision surgery for treatment. Systemic antibiotics are usually held prior to surgery to improve yield of intraoperative cultures. However, recent studies suggest that preoperative aspirations have a high concordance with intraoperative cultures, which may allow surgeons to initiate antibiotic treatment earlier. The purpose of the study was to investigate the effect of Pre-surgical systemic antibiotic therapy on the bacterial burden within the periprosthetic space and systemic immune reaction. PJI was induced with MSSA (Xen36) S. aureus in the right knee of 16-week old, female, C57BL6 mice using a previously validated murine model. Mice were randomized to three groups (n=8, each): control; Vanc, receiving systemic vancomycin (110mg/kg, SQ, twice daily); or VancRif receiving vancomycin same as in Vanc group, plus rifampin (12mg/kg dose, IV, once daily). Following 2 weeks of treatment, mice were euthanized and periprosthetic bone, soft tissue and the implant were harvested. Bacterial burden, colony forming units (CFUs), was quantified in soft tissue, tibial bone, and on the implant. Specifically, tissues were homogenized and serially plated for CFUs, while the implant was sonicated and then plated for CFUs. The host immune response was analysed through weighing inguinal and iliac lymph nodes and through measuring serum amyloid A (SAA). Non-parametric pairwise group comparisons of the three outcome measures were performed using a Mann-Whitney U test.Aim
Method
Polypropylene (PPE) synthetic mesh is increasingly used in knee arthroplasty surgery to salvage a disrupted extensor mechanism. Despite its clinical success, it is associated with a high rate of periprosthetic joint infection (PJI), which is hypothesized to be caused by bacterial biofilm. The purpose of the current study is to describe the progression of PPE-based biofilm formation over time and to determine if intraoperative antiseptic solutions could be used to effectively remove biofilm when treating PJI. Commercially available knotted monofilament PPE mesh1 was cut into 10mm circular shape, immersed in tryptic soy broth (TSB) with methicillin-sensitive staphylococcus aureus and cultured individually in 48-well plates for 10 days to elucidate the biofilm grown on mesh over time. At every 24 hours, a triplicate of samples was retrieved and biofilm on the mesh was dislodged by sonicating at 52 kHz for 15 minutes and quantified by counting colony-forming units (CFUs) after overnight growth. The biofilm growth was also verified using scanning electron microscopy. The effect of saline and antiseptic solutions was verified by exposing 1) 0.05% chlorohexidine gluconate2, 2) acetic acid-based mixture3, 3) diluted povidone-iodine (0.35%), 4) undiluted povidone-iodine (10%)4, and 5) 1:1 combination of 10% povidone-iodine & 3% hydrogen peroxide on immature and mature biofilms for 3 minutes, created by culturing with bacteria for 24 hours and 72 hours respectively. All experiments were performed in quintuples and repeated. Antiseptic treatments that produced a three-log reduction in CFU counts compared to controls were considered clinically significant.Aim
Method
To evaluate the effects of 6 and 18 months of abaloparatide (ABL) compared with placebo (PBO) on bone mineral density (BMD) in the acetabular regions of postmenopausal women with osteoporosis (OP). Acetabular bone loss, as may occur in OP, increases risk of acetabular fragility fracturesa. In total hip arthroplasty (THA), low acetabular BMD adversely affects primary stability, osseointegration, and migration of acetabular cups.c ABL is an osteoanabolic agent for the treatment of men and postmenopausal women with OP at high risk for fracture. Effects of ABL on acetabular BMD are unknown. Hip DXA scans were obtained at baseline, 6, and 18 months from a random subgroup of postmenopausal women (aged 49–86 y) from the phase 3 ACTIVE trial randomized to either ABL 80 µg/d or PBO (n=250/group). Anatomical landmarks were identified in each DXA scan to virtually place a hemispherical shell model of an acetabular cup and define regions of interest corresponding to DeLee & Charnley zones 1 (R1), 2 (R2), and 3 (R3). BMD changes compared to baseline were calculated for each zone. Statistical BMD in all zones were similar at baseline in the ABL and PBO groups. BMD significantly increased in the ABL group at 6 and 18 months compared with PBO (all ABL treatment resulted in rapid and progressive increases in BMD of all 3 acetabular zones. Increasing acetabular BMD has the potential to improve acetabular strength, which may reduce risk of acetabular fragility fractures. In bone health optimization prior to THA, increased acetabular BMD via ABL may provide better primary stability and longevity of acetabular cups in postmenopausal women with OP.
Known risk factors for early periprosthetic femur fracture (PFF) following total hip arthroplasty (THA) include poor bone quality, surgical approach and cementless implants. The association between femoral component size and alignment and the risk of early PFF is not well described. We evaluated radiographic parameters of femoral component sizing and alignment as risk factors for early PFF. From 16,065 primary cementless THA, we identified 66 cases (0.41%) of early PFF (<90 days from index THA) at a single institution between 2016–2020. The stem was unstable and revised in all cases. We matched 60 cases of early PFFs (2:1) to 120 controls based on femoral component model, offset, surgical approach, age, BMI, and sex. Mean age was 67 years; 60% were female. Radiographic assessment of preoperative bone morphology and postoperative femoral component parameters including stem alignment, metaphyseal fill, and medial congruence with the calcar. A multivariable logistic regression was built to identify radiographic risk factors associated with early PPF. Markers of poor preoperative bone quality including canal calcar ratio (p=0.003), canal flare index (p<0.001), anteroposterior canal bone ratio (CBR) (p<0.001) and lateral CBR (p<0.001) were statistically associated with PFF. Valgus alignment (23% versus 12%) (p<0.001) was more prevalent in the PFF group compared to controls, as well as varus alignment of the implant (57% versus 43%). Distance between the medial aspect of the implant and the calcar was greater in cases of PFF (2.5 mm versus 1.4 mm) (p<0.001). Multivariate analysis demonstrated that valgus implant alignment (Odds Ratio (OR) 5) and medial implant-calcar incongruity (OR 2) increased the risk of early PFF. Medial implant-calcar incongruity and valgus alignment of the femoral component were risk factors for early PFF following cementless THA after controlling for age, sex, BMI, approach, proximal femoral morphology, and implant design.
A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis.Aims
Methods
Due to the opioid epidemic, our service developed a cultural change highlighted by decreasing discharge opioids after lower extremity arthroplasty. However, concern of potentially increasing refill requests exists. As such, the goal of this study was to analyze whether decreased discharge opioids led to increased postoperative opioid refills. We retrospectively reviewed 19,428 patients undergoing a primary hip or knee arthroplasty at a single institution from 2016–2019. Patients that underwent secondary procedures within that timeframe were excluded. Two-thousand two-hundred and forty-one patients (12%) were on narcotics preoperatively or had chronic pain syndrome. Two reductions in routine discharge narcotics were performed over this timeframe. First, 8,898 patients routinely received 750 morphine milligram equivalents (MMEs). After the first reduction, 4,842 patients routinely received 520 MMEs. After a second reduction, 5,688 patients routinely received 320 MMEs. We analyzed refill rates, refill MMEs, and whether discharge MMEs were associated with refill MMEs in a multivariate model.Introduction
Methods
Current treatments of prosthetic joint infection (PJI) are minimally effective against The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load.Aims
Methods
Poor osseointegration of cementless implants is the leading clinical cause of implant loosening, subsidence, and replacement failure, which require costly and technically challenging revision surgery. The mechanism of osseointegration requires further elucidation. We have recently developed a novel titanium implant for the mouse tibia that maintains in vivo knee joint function and allows us to study osseointegration in an intra-articular, load-bearing environment. Vascular endothelial growth factor (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. It also plays critical roles in skeletal development and bone repair and regeneration. A specialized subset of vascular endothelium, CD31hiEMCNhi cells displaying high cell surface expression of CD31 and Endomucin, has been reported to promote osteoblast maturation and may be responsible for bone formation during development and fracture healing. Because of their potential role in osseointegration, the aim of this study was to use our mouse implant model to investigate the role of VEGF and CD31hiEMCNhi endothelium in osseointegration. Under an IACUC-approved protocol, the implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (N = 38). The mice were then randomized into 2 groups: Control group (N=19) and Anti-VEGFR group (N=19). A cocktail of VEGFR-1 antibody (25mg/kg) and VEGFR-2 antibody (25mg/kg) was given to the mice in the Anti-VEGFR group by intraperitoneal injection every third day starting immediately after surgery until euthanasia. An equivalent amount of an isotype control antibody was given to the control group. Flow cytometric (N = 4/group) and immunofluorescencent (N = 3/group) analyses were performed at 2 weeks post-implantation to detect the distribution and density of CD31hiEMCNhi endothelium in the peri-implant bone. Pull-out testing was used at 4 weeks post-implantation to determine the strength of the bone-implant interface.Introduction
Methods
Trunnionosis is an important failure mechanism of total hip arthroplasties as has recently been reported by the England and Wales national joint registry. Adverse local tissue reaction has also recently been associated with total hip arthroplasty (THA) with metal on polyethylene and ceramic on polyethylene articulations. The contributing factors in the mechanism of this failure pattern have not been elucidated, however they are likely multifactorial to include corrosion, fretting, taper design, implantation time, metal particulate debris, and wear at the metal on metal interface. Furthermore, dissimilar metallic combinations have been shown to exacerbate tribocorrosion. Authors have also reported on the use of ceramic heads to reduce trunniononis, however, tribocorrosion is still present. The majority of the literature regarding modular head neck taper fretting and corrosion involves cobalt chrome (CoCr) alloy. Little is known about head neck fretting corrosion with Oxinium femoral heads. To measure fretting, corrosion, and wear on the female tapers of retrieved Oxinium femoral heads and to determine how demographic and device factors affect these measurements. Ninety-two (92) retrieved 12/14 Oxinium heads were graded using the modified Goldberg score for subjectively grading corrosion and fretting on the taper surface. A novel silicone molding technique was validated, then applied to the female tapers of the retrievals and of two pristine Oxinium femoral heads, sizes 32+0 and 32+4. The molds were scanned using a Konica Minolta 3D laser scanner for reconstruction of the topography, dimensions, and surface features of the tapers. Geomagic software was used to align the retrieved to the pristine 3D models, allowing measurement of surface deviations (from wear) that had occurred while the heads were implanted. Patient demographic and implant data were correlated with Goldberg scores and wear deviations. The mean Goldberg score was 1.6. Goldberg scores of 1 (minimal), 2 (mild), and 3 (moderate) were present in 41 of the 92 heads (45%), 43 heads (47%), and 8 heads (8%) respectively. No implants received a score of 4 (severe). A positive significant correlation was found between length of implantation and increased female taper fretting ( Similar to previous work analyzing ceramic heads, Oxinium heads demonstrated predominately mild tribocorrosion grades, however do not eliminate tribocorrosion. Tribocorrosion was increased with large heads and increased offsets. This finding is consistent perhaps with greater mechanical burden that larger implants with increased offsets experience. Further investigation is needed to elucidate if Oxinium femoral heads reduce fretting and corrosion when compared to CoCr femoral heads.
Proximal femoral replacements are commonly used in oncologic limb salvage procedures. Recently, these megaprostheses have been utilized in complex revision arthroplasties where proximal femoral bone is compromised. The purpose of this study is to evaluate the clinical and radiographic survivorship of proximal femoral replacements as a salvage treatment for bone loss after hip arthroplasty. We retrospectively reviewed the clinical and radiographic outcomes of 31 proximal femoral replacements of a single design between 2004 and 2013 at a single institution. The mean age at time of index surgery was 62 years, 58% were female, and mean BMI was 28.1 Kg/m2. The indications and complications associated with megaprosthesis implantation were collected. Average follow-up was 60 months (range 24–120 months). Kaplan-Meier survivorship assessed clinical and radiographic survivorship. Indication for revision, use of a constrained liner and construct length were assessed as risk factors for construct failure. The indications for proximal femoral replacement were periprosthetic infection (n=12, 38.7%), aseptic loosening (n=10, 32.3%), periprosthetic fracture (n=6, 19.3%), and non-union (n=3, 9.7%). A constrained liner was used in 22 hips (71%). The average length of bone resection was 148 cm (range 81–240 cm). There were nine revisions (29.2%): 3 for infection (9.7%) 2 for dislocation (6.5%), 2 for aseptic loosening (6.5%), and 2 for periprosthetic fracture (6.5%). Two of the 3 infections were in patients treated for infection. Overall survivorship was at 70.8%. There was no relation between the length of the bone resection, indication for revision and failure rate. Proximal femoral replacement in non-oncologic revision hip arthroplasty demonstrated a high failure rate at 2–10 year follow-up. Despite the high failure rate, the benefits of this salvage construct are that they allow full weight-bearing and allow rapid mobilization with minimal morbidity.
Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.
To test the hypothesis that: CERAMENT[™]|G (C-G) would improve new bone growth and decrease infection rate after debridement as compared with 1) CERAMENT|BONE VOID FILLER (CBVF) and 2) no void filler in a rat osteomyelitis model. 72 Sprague Dawley rats were injected with 1.5 × 10∧6 CFU of S. aureus into a drill hole in the right tibia. After 3 weeks, the osteomyelitic defect was debrided, and filled with either: 1) C-G (n=32), 2) CBVF (n=20), or 3) nothing (n=20). 6 weeks after the second surgery, 20 rats from each group were sacrificed and the right tibias were harvested. A long-term group (n=12) of C-G treated rats were also sacrificed at 6 months after the second surgery. The tissues were sonicated and the colony forming units in the sonicate were quantified by serial dilutions and culture. MicroCT was used to quantify the new bone growth (BV/TV) in the debrided osteomyelitic void. Histological samples were analyzed for the presence of a neutrophil response by a blinded pathologist. (*: p<0.05) Positive cultures in:
○ 30% of animals treated with CBVF ○ 25% of animals treated with no void filler ○ 0% of animals treated with C-G (*) Neutrophil reaction in:
○ 35% of animals treated with CBVF ○ 50% of animals treated with no void filler ○ 0% of animals treated with C-G (*) The BV/TV in:
○ C-G treated rats was 24% greater than CBVF treated rats (*) ○ C-G treated rats was 94% greater than rats treated with no void filler (*) ○ CBVF treated rats was 56% greater than rats treated with no void filler (*) Animals sacrificed at 6 months which were treated with C-G did not have any evidence of infection by culture or histology. The bone mass of the implanted limb was higher than the contralateral (non-operated) side. CERAMENT|G decreased the rate of infection and increased new bone growth as compared with both CBVF and no void filler in a debrided osteomyelitic environment. Animals treated with C-G at 6 months showed no evidence of infection and retained a higher bone mass relative to the contralateral (non-operated) side. This study supports the use of CERAMENT|G as a readily available void filler which could be used in osteomyelitic environments after debridement.
The modulation of both quantity and quality of peri-implant bone with either PTH or loading may be viable options to improve implant fixation and patient outcomes. A strong bone-implant interface is essential for successful joint replacement surgery. This study investigated the differences in bone surrounding and within a porous titanium implant after single or combined treatment with two anabolic bone therapies: intermittent parathyroid hormone (teriparatide) and mechanical loading. Porous titanium implants were inserted bilaterally on the distal lateral femurs of rabbits. The right implant was loaded daily (1 MPa, 50 cycles/day) while the left implant was not. Rabbits received daily PTH injections (20 ug/kg) or saline vehicle. Periprosthetic cancellous bone 0.5, 1.0, and 2.0 mm below the implant surface, bone at the 0.25 mm bone-implant interface and total bone within each implant were examined using tissue-level analyses (quantitative backscattered electron microscopy), cellular analyses (immunohistochemistry staining of osteoblasts with procollagen-1 and TRAP staining of osteoclasts), and shear testing (implant-bone interface). Statistical significance was determined using GEE models (p<0.05). For tissue located 0.5 mm below the implant, significant increases in bone area per total area (BA/TA) were observed with PTH treatment (56%) and with loading (27%). Further, an 18% increase in mineralization density with PTH treatment and a 20% increase in mineralization density with loading was found. Loading effects were not present beyond the 0.5 mm periprosthetic region, but PTH significantly increased BA/TA 2.0 mm below and mineralization density 1.0 mm below the implant. Tissue-level changes were supported by increases in osteoblast activity 0.5 mm below the implant with PTH (79%) and loading (34%), as well as by minimal osteoclast changes. At the 0.25 mm implant-bone interface PTH and loading increased BA/TA (16% and 23%, respectively), but only loading increased mineralization density (7%). Further, total integrated bone area was increased 35% with PTH. Both PTH and loading enhanced the mechanical integrity of the implant-bone; shear strength increased 34% and 60%, respectively. Although combined treatment was not synergistic, both PTH and loading individually enhanced the amount and mineralization density of bone at the implant interface and immediately below the interface, thereby increasing the mechanical strength of the metal-bone interface. This research suggests that modulation of both quantity and quality of peri-implant bone may be viable options to improve implant fixation and patient outcomes.Summary Statement
The influence of controlled mechanical loading on osseointegration was investigated using an in vivo device implanted in the distal lateral femur of five male rabbits. Compressive loads (1 MPa, 1 Hz, 50 cycles/day, 4 weeks) were applied to a porous coated titanium cylindrical implant (5mm diameter, 2mm width, 75% porosity, 350ìm average pore diameter) and the underlying cancellous bone.. The contralateral limb served as an unloaded control. MicroCT scans at 28 μm resolution were taken of a 4 × 4mm cylindrical region of interest that included cancellous bone below the implant. A scanning electron microscope with a backscattered electron (BSE) detector was used to quantify the percent bone ingrowth and periprosthetic bone in undecalcified sections through the same region of interest. A mixed effects model was used to account for the correlation of the outcome measures within rabbits.. The percent bone ingrowth was significantly greater in the loaded limb (19 +/− 4%) compared to the unloaded control limb (16 +/− 4%, p=0.016) as measured by BSE imaging. The underlying cancellous periprosthetic tissue bone volume fraction was not different between the loaded (0.26 +/− 0.06) and unloaded control limb (0.27 +/− 0.07, p=0.81) by microCT. BSE imaging also showed no difference in the percent area of periprosthetic bone (27 +/− 10% loaded vs. 23 +/− 10% unloaded, p=0.25). Cyclic mechanical loading significantly enhanced bone ingrowth into a titanium porous coated surface compared to the unloaded controls.
Objective: to analyze influence of propranolol, a beta-blocker, on fracture healing in a mouse model.
