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Osteogenesis imperfecta (OI) is a genetically heterogenous disorder most often due to heterozygosity for mutations in the type I procollagen genes, COL1A1 or COL1A2. The disorder is characterized by bone fragility leading to increased fracture incidence and long-bone deformities. Although multiple mechanisms underlie OI, endoplasmic reticulum (ER) stress as a cellular response to defective collagen trafficking is emerging as a contributor to OI pathogenesis. Herein, we used 4-phenylbutiric acid (4-PBA), an established chemical chaperone, to determine if treatment of Aga2+/- mice, a model for moderately severe OI due to a Col1a1 structural mutation, could attenuate the phenotype. In vitro, Aga2+/- osteoblasts show increased protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation protein levels, which improved upon treatment with 4-PBA. The in vivo data demonstrate that a postweaning 5-week 4-PBA treatment increased total body length and weight, decreased fracture incidence, increased femoral bone volume fraction (BV/TV), and increased cortical thickness. These findings were associated with in vivo evidence of decreased bone-derived protein levels of the ER stress markers binding immunoglobulin protein (BiP), CCAAT/-enhancer-binding protein homologous protein (CHOP), and activating transcription factor 4 (ATF4) as well as increased levels of the autophagosome marker light chain 3A/B (LC3A/B). Genetic ablation of CHOP in Aga2+/- mice resulted in increased severity of the Aga2+/- phenotype, suggesting that the reduction in CHOP observed in vitro after treatment is a consequence rather than a cause of reduced ER stress. These findings suggest the potential use of chemical chaperones as an adjunct treatment for forms of OI associated with ER stress. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Objectives Prefabrication and storage of antibiotic beads may decrease surgical time and allow for use in other settings. This study investigated the effects of sterilization technique and storage time on the bioactivity of antibiotic polymethyl methacrylate (PMMA) beads. Methods Uniform beads of PMMA containing 1 g each of tobramycin and vancomycin were sterilized using autoclave, ethylene oxide (ETO), or ultraviolet (UV) light. Beads were made in a sterile fashion as a control. Disks containing eluted antibiotics from each of the 4 groups were placed onto agar plates inoculated with Staphylococcus aureus. Zones of inhibition, a measure of bioactivity for antibiotic eluted, were determined for the experimental groups and control. Repeat testing was performed for beads stored for 1 week, 1, 3, and 6 months. Results Beads sterilized using autoclave, ETO, and UV light showed similar ZOIs after 24 hours of and 1 week of elution compared with the control group. Beads stored for up to 6 months demonstrated similar bioactivity to beads made sterile and tested immediately. Conclusion PMMA beads containing vancomycin and tobramycin made in a sterile fashion and stored for up to 6 months have the same efficacy as the current standard of beads made sterile and used immediately. The elution and bioactivity of vancomycin-tobramycin antibiotic beads are not negatively impacted by the sterilization methods of autoclaving, ETO gas, or UV light. Furthermore, nonsterile beads can be sterilized and stored up to 6 months with an expected efficacy comparable with beads made in a standard sterile fashion.

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by bone deformities and fractures caused by low bone mass and impaired bone quality. OI is a genetically heterogeneous disorder that most commonly arises from dominant mutations in genes encoding type I collagen (COL1A1 and COL1A2). In addition, OI is recessively inherited with the majority of cases resulting from mutations in prolyl-3-hydroxylation complex members, which includes cartilage-associated protein (CRTAP). OI patients are at an increased risk of fracture throughout their lifetimes. However, non-union or delayed healing has been reported in 24% of fractures and 52% of osteotomies. Additionally, refractures typically go unreported, making the frequency of refractures in OI patients unknown. Thus, there is an unmet need to better understand the mechanisms by which OI affects fracture healing. Using an open tibial fracture model, our study demonstrates delayed healing in both Col1a2 G610c/+ and Crtap -/- OI mouse models (dominant and recessive OI, respectively) that is associated with reduced callus size and predicted strength. Callus cartilage distribution and chondrocyte maturation were altered in OI, suggesting accelerated cartilage differentiation. Importantly, we determined that healed fractured tibia in female OI mice are biomechanically weaker when compared with the contralateral unfractured bone, suggesting that abnormal OI fracture healing OI may prime future refracture at the same location. We have previously shown upregulated TGF-β signaling in OI and we confirm this in the context of fracture healing. Interestingly, treatment of Crtap -/- mice with the anti-TGF-β antibody 1D11 resulted in further reduced callus size and predicted strength, highlighting the importance of investigating dose response in treatment strategies. These data provide valuable insight into the effect of the extracellular matrix (ECM) on fracture healing, a poorly understood mechanism, and support the need for prevention of primary fractures to decrease incidence of refracture and deformity in OI patients. © 2020 American Society for Bone and Mineral Research.

High-resolution computed tomography (CT) is widely used to assess bone structure under physiological and pathological conditions. Although the analytic protocols and parameters for micro-CT (μCT) analyses in mice are standardized for long bones, vertebrae, and the palms in aging mice, they have not yet been established for craniofacial bones. In this study, we conducted a morphometric assessment of craniofacial bones, in comparison with long bones, in aging mice. Although age-related changes were observed in the microarchitecture of the femur, tibia, vertebra, and basisphenoid bone, and were more pronounced in females than in males, the microarchitecture of both the interparietal bone and body of the mandible, which develop by intramembranous ossification, was less affected by age and sex. By contrast, the condyle of the mandible was more affected by aging in males compared to females. Taken together, our results indicate that mouse craniofacial bones are uniquely affected by age and sex.

Objectives Patients with dementia are at high risk for hip fractures and often have poor outcomes when a fracture is sustained. Despite this poor prognosis, little data are available on what factors should be prioritized to guide surgical decision making in these cases. We aimed to understand the decision-making process for older dementia patients hospitalized after hip fractures. Design We performed a qualitative analysis of in-depth elite interviews conducted with a clinical care team involved in management of patients with dementia after hospitalization for hip fractures. Setting Interviews were conducted with an interprofessional team involved in the care of patients with dementia after being hospitalized for hip fractures. Participants Interviewees included nine orthopaedic surgeons, three hospitalists, three geriatricians, five nurses, three occupational therapists, three physical therapists, and two clinical ethicists. Measurements Verbatim transcripts of the interviews were analyzed and coded using QSR International's NVivo 10 qualitative database management software. Results The three main themes that most interviewees discussed were pain control, functional status, and medical comorbidities. Interviewees brought up many factors related to restoring functional status including baseline functional status, rehabilitation potential, social support, and the importance of mobility. Dementia and its impact on rehabilitation potential were mentioned by all geriatricians. Conclusion Although frailty, prognosis, and life expectancy were largely absent from the responses, the emphasis on dementia, advanced directives, and involving family or caregivers by the three geriatricians indicates the importance of including geriatricians in the decision-making team for these patients.

Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon dysfunction in OI pathogenesis is largely unknown. Using the Crtap-/- mouse model of severe, recessive OI, we found that mutant Achilles and patellar tendons were thinner and weaker with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar tendons from Crtap-/- mice also had altered numbers of CD146+CD200+ and CD146-CD200+ progenitor-like cells at skeletal maturity. RNA-seq analysis of Achilles and patellar tendons from 1-month Crtap-/- mice revealed dysregulation in matrix and tendon marker gene expression concomitant with predicted alterations in TGF-β, inflammatory, and metabolic signaling. At 4-months, Crtap-/- mice showed increased αSMA, MMP2, and phospho-NFκB staining in the patellar tendon consistent with excess matrix remodeling and tissue inflammation. Finally, a series of behavioral tests showed severe motor impairments and reduced grip strength in 4-month Crtap-/- mice – a phenotype that correlates with the tendon pathology.

OBJECTIVES Multidimensional fluoroscopy is new imaging technology that generates intraoperative cross sectional imaging. Can this technology be used to assess accuracy and safety of percutaneously placed iliosacral screws intraoperatively? DESIGN Retrospective study. SETTING Level 1 academic trauma center. PATIENTS/PARTICIPANTS Fifty-two consecutive patients during a 7-month period with unstable posterior pelvic ring disruptions. INTERVENTION All patients were treated with percutaneous iliosacral and/or transsacral screw fixation by a single experienced surgeon. Traditional triplanar fluoroscopy was performed during guidepin insertion. Intraoperative multidimensional fluoroscopy was used for all patients after iliosacral screw fixation. MAIN OUTCOME MEASUREMENTS Intraoperative multidimensional fluoroscopy and postoperative computed tomography (CT) scans for each patient were retrospectively reviewed by the treating surgeon and another trauma surgeon. Screw position in relation to the sacral neuroforamen was assessed using multidimensional fluoroscopy and compared to postoperative CT scan. Screws were classified as extraforaminal, juxtaforaminal, or intraforaminal. RESULTS No screws were intraforaminally seen on intraoperative multidimensional fluoroscopy or postoperative CT scan. All iliosacral and transsacral screws were considered safe. Intraobserver and interobserver variability existed between reviewers when grading screws as extraforaminal versus juxtaforaminal. This was not clinically significant because both agreed that extraforaminal and juxtaforaminal screw positions are safe. Multidimensional fluoroscopy was used in 3 patients to assess guidepin placement before definitive screw fixation. Two patients underwent a change of fixation after reviewing multidimensional fluoroscopy. No postoperative neurological examination changes occurred. CONCLUSIONS Multidimensional fluoroscopy is a novel imaging technology that can safely be used intraoperatively to accurately determine iliosacral and transsacral screw placement. LEVELS OF EVIDENCE Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon dysfunction in OI pathogenesis is largely unknown. Using the Crtap-/- mouse model of severe, recessive OI, we found that mutant Achilles and patellar tendons were thinner and weaker with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar tendons from Crtap-/- mice also had altered numbers of CD146+CD200+ and CD146-CD200+ progenitor-like cells at skeletal maturity. RNA-seq analysis of Achilles and patellar tendons from 1-month Crtap-/- mice revealed dysregulation in matrix and tendon marker gene expression concomitant with predicted alterations in TGF-β, inflammatory, and metabolic signaling. At 4-months, Crtap-/- mice showed increased αSMA, MMP2, and phospho-NFκB staining in the patellar tendon consistent with excess matrix remodeling and tissue inflammation. Finally, a series of behavioral tests showed severe motor impairments and reduced grip strength in 4-month Crtap-/- mice – a phenotype that correlates with the tendon pathology.

Coatomer complexes function in the sorting and trafficking of proteins between subcellular organelles. Pathogenic variants in coatomer subunits or associated factors have been reported in multi-systemic disorders, i.e., coatopathies, that can affect the skeletal and central nervous systems. We have identified loss-of-function variants inCOPB2, a component of the coatomer complex I (COPI), in individuals presenting with osteoporosis, fractures and developmental delay of variable severity. Because the role of COPB2 in bone has not been characterized, we studied the effect ofCOPB2deficiency on skeletal development in mice and zebrafish.Copb2+/−mice showed low bone mass and decreased bone strength. In zebrafish, larvae carrying acopb2heterozygous frameshift variant showed delayed mineralization.copb2-null embryos showed endoplasmic reticulum (ER) and Golgi disorganization, and embryonic lethality.COPB2siRNA-treated fibroblasts showed delayed collagen trafficking with retention of type I collagen in the ER and Golgi, and altered distribution of Golgi markers. Our data suggest thatCOPB2haploinsufficiency leads to disruption of intracellular collagen trafficking and osteoporosis, which may improve with ascorbic acid supplementation. This work highlights the role of COPI complex as a critical regulator of bone mass and identifies a new form of coatopathy due toCOPB2deficiency.

Altered bone quality due to the underlying metabolic changes of type 2 diabetes (T2D) has been hypothesized to affect bone strength, leading to increased fracture risk in patients with T2D. Lumbar spine trabecular bone score (LS-TBS), an indirect measure of trabecular microarchitecture, provides information on bone quality and has been associated with T2D. However, trabecular bone score (TBS) is also affected by demographic patterns and body size, and is expected to be different in people from various ethnic or racial backgrounds. Therefore, it is important to understand associations between T2D and TBS for each ethnic or racial group separately. Although the relationship between TBS and age has been reported to be similar between non-Hispanic Caucasians and Mexican Americans (MAs), data on associations of LS-TBS with T2D in older MAs are lacking. Here, we report associations between TBS and T2D in 149 older MA men and women. Participants are part of a cohort known as the Cameron County Hispanic Cohort in Texas who have high prevalence of obesity and poor glycemic control. Bone mineral density was not altered for MA women with T2D, but was significantly higher in MA men with T2D compared with MA men without diabetes. Low LS-TBS was associated with T2D in women in our study. Although low TBS was associated with older age in men, TBS did not show any significant association with T2D for men. These results are similar to those found in other studies of non-Hispanic whites with diabetes. LS-TBS may add value in diagnosing poor bone quality in older MA women with T2D regardless of bone mineral density scoring.

Polymerase chain reaction (PCR) has been proposed as a method to identify bacteria in clinical samples because it is more sensitive than culture techniques and can produce results rapidly. However, PCR can detect DNA from dead cells and thus cannot distinguish between live and dead cells in a tissue sample. Killed Staphylococcus aureus cells were implanted into the femurs and knee joints of rats to determine the length of time that DNA from dead cells is detectable in a living animal under conditions similar to common orthopedic infections. In the joint infection model studied here, the DNA from the dead planktonic bacteria was detected using PCR immediately after injection or 24 h later, but was undetectable 48 and 72 h after injection. In the biofilm implanted-device model studied, the DNA from these dead biofilm cells was detected by PCR immediately after implantation and at 24 h, but not at 48 or 72 h. Thus, our results indicate that DNA from dead cells does not persist in these animal model systems for more than 2 days, which should reduce concerns about possible false positive results using molecular DNA-based techniques for the detection of pathogens.

Depression and osteoporosis are 2 common comorbidities in geriatric patients. There are concerns about the deleterious effects of selective serotonin reuptake inhibitor (SSRI) antidepressant use on bone mineral density (BMD). We examined the association between SSRI use and BMD in elderly women (≥65 yr) referred to a geriatric osteoporosis clinic for bone health evaluation. Cross-sectional analyses using the general linear model were performed on data collected retrospectively from August 2010 to April 2015. A total of 250 women were seen during the study period. Of these, 140 women had complete data on BMD measurements: 22 (15.7%) used an SSRI and 118 (84.3%) did not. The 2 groups, SSRI users and SSRI nonusers, did not differ significantly across any of the covariates tested (age, ethnicity, body mass index, and past and present osteoporosis treatment medications). After adjusting for covariates, there was no difference in the BMDs at the femoral neck (p = 0.887) or the spine (p = 0.275) between the 2 groups. Similarly, no difference was seen in the T-scores between SSRI users and nonusers at the femoral neck (p = 0.924) or at the spine level (p = 0.393). Our study did not show an association between SSRI use and BMD among elderly women referred for bone health evaluation. Other studies in the literature have been inconclusive, and therefore, robust longitudinal studies are needed to further assess the interaction between SSRI use and predictors of fracture such as BMD, bone turnover markers, and genes involved in bone turnover. Until then, clinicians should closely monitor the bone health of long-term SSRI users.

Osteogenesis imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures, and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65-kDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon, and ligaments in postnatal tissues. Furthermore, in both patients and Fkbp10 knockout mice, collagen telopeptide hydroxylysine crosslinking is dramatically reduced. To further characterize the bone specific contributions of Fkbp10, we conditionally ablated FKBP65 in Fkbp10fl/fl mice (Mus musculus; C57BL/6) using the osteoblast-specific Col1a1 2.3-kb Cre recombinase. Using μCT, histomorphometry and quantitative backscattered electron imaging, we found minimal alterations in the quantity of bone and no differences in the degree of bone matrix mineralization in this model. However, mass spectroscopy (MS) of bone collagen demonstrated a decrease in mature, hydroxylysine-aldehyde crosslinking. Furthermore, bone of mutant mice exhibits a reduction in mineral-to-matrix ratio and in crystal size as shown by Raman spectroscopy and small-angle X-ray scattering, respectively. Importantly, abnormalities in bone quality were associated with impaired bone biomechanical strength in mutant femurs compared with those of wild-type littermates. Taken together, these data suggest that the altered collagen crosslinking through Fkbp10 ablation in osteoblasts primarily leads to a qualitative defect in the skeleton. © 2017 American Society for Bone and Mineral Research.

Objective To determine whether a position screw will maintain the interfragmentary compression force obtained by a reduction clamp across an anatomically reduced cortical bone fracture and determine whether this compressive force is equivalent to that generated by a lag screw (LS). Methods Oblique fractures were created in 6 composite cortical bone models. Interfragmentary compression was measured using force sensors within the fracture after reduction with a clamp. A position screw was then placed perpendicular to the fracture, and force measurements were repeated with both the clamp and the screw. Finally, the clamp was removed, and force measurements were taken with the screw only to measure maintenance of initial compression. After these measurements, the screw was removed, and the near fragment was overdrilled to allow LS placement by technique. Compression force measurements were repeated for clamp only, clamp + screw, and screw only. Results The mean force of clamp alone across all 12 trials was 139.77 N. Application of an LS increased the compression across the fracture (P = 0.01) which was unchanged when the clamp was removed. The position screw had the opposite effect, reducing compression, and the removal of the clamp further reduced the compression (P = 0.013). Conclusions A reduction clamp will initially compress a fracture to an average of 139 N. An LS will significantly increase this interfragmentary compression. A position screw will not maintain the compression created by the clamp and in fact will significantly decrease interfragmentary compression.

Coronary artery disease (CAD) and osteoporosis, the two most frequently occurring chronic diseases of aging populations, share many risk factors including lack of estrogen, smoking, and low physical activity. CAD and low bone mineral density (BMD) are strongly associated. Statins, (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors), are used to prevent and treat CAD and have been associated with high BMD. This cross-sectional study examined associations of BMD with statin use and nonuse in elderly women with or without CAD. Multivariate regression analyses were conducted on 185 women aged ≥60 years who were referred between October 2010 and March 2015 to a geriatric osteoporosis clinic in Houston, Texas, for compromised skeletal health. Compared to the control group (without CAD and without statin use), patients with CAD and no statin use were more likely to have lower femoral neck BMD (β: -0.46, 95% confidence interval: -0.75 to -0.18). The BMD of patients taking statins, regardless of presence of CAD, was similar to that of the control group. Statins may be protective in preventing bone loss in elderly women suffering from CAD. Prospective trials are warranted to determine if continued use of statins in them would help prevent both CAD and bone loss.

Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by brittle bones that are prone to fracture. Although previous studies in animal models investigated the mechanical properties and material composition of OI bone, little work has been conducted to statistically correlate these parameters to identify key compositional contributors to the impaired bone mechanical behaviors in OI. Further, although increased TGF-β signaling has been demonstrated as a contributing mechanism to the bone pathology in OI models, the relationship between mechanical properties and bone composition after anti-TGF-β treatment in OI has not been studied. Here, we performed follow-up analyses of femurs collected in an earlier study from OI mice with and without anti-TGF-β treatment from both recessive (Crtap-/- ) and dominant (Col1a2+/P.G610C ) OI mouse models and WT mice. Mechanical properties were determined using three-point bending tests and evaluated for statistical correlation with molecular composition in bone tissue assessed by Raman spectroscopy. Statistical regression analysis was conducted to determine significant compositional determinants of mechanical integrity. Interestingly, we found differences in the relationships between bone composition and mechanical properties and in the response to anti-TGF-β treatment. Femurs of both OI models exhibited increased brittleness, which was associated with reduced collagen content and carbonate substitution. In the Col1a2+/P.G610C femurs, reduced hydroxyapatite crystallinity was also found to be associated with increased brittleness, and increased mineral-to-collagen ratio was correlated with increased ultimate strength, elastic modulus, and bone brittleness. In both models of OI, regression analysis demonstrated that collagen content was an important predictor of the increased brittleness. In summary, this work provides new insights into the relationships between bone composition and material properties in models of OI, identifies key bone compositional parameters that correlate with the impaired mechanical integrity of OI bone, and explores the effects of anti-TGF-β treatment on bone-quality parameters in these models. © 2016 American Society for Bone and Mineral Research.

Purpose: Autologous chondrocyte implantation (ACI) is a treatment option even in early osteoarthritis (OA). Surgical preparation for ACI should avoid penetration of the subchondral bone plate to prevent hemorrhage, fibrin clot formation, and subsequent activation of the inflammatory response. Hypothesis: Current surgical procedures with ring curettes preserve the integrity of the subchondral bone plate, even in patients with OA. Methods: Subchondral femoral bone plates ( n = 40) of OA knees undergoing total knee arthroplasty were prepared in vivo using standard, non–brute-force debridement for ACI. To approach regular wear/early OA, only cartilage with maximally grade 3A International Cartilage Repair Society score was prepared. Effects were analyzed by light microscopy. Results: In 87.5% of the specimens (35/40), standard debridement did not violate the tide mark, except for occasional minor openings with a smooth edge (diameter approximately 20 µm). In contrast, 5/40 samples (12.5%) showed one large area with a missing bone plate and an open bone marrow space. Twenty-eight specimens (70%) showed at least remnants of uncalcified cartilage. Conclusion: On the basis of size/fine structure, the occasional minor openings are likely due to increased vascular penetration through the tide mark in the pathologically altered bone-cartilage interface in OA. The consequences of limited hemorrhage through minor openings or selected large defects following in vivo debridement are still unknown. Thus, standard debridement appears suitable for cartilage regeneration even in OA defects.

Patients with pelvic ring displacement and instability can benefit from surgical reduction and instrumentation to stabilize the pelvis and improve functional outcomes. Current treatments include iliosacral screw or transsacral-transiliac screw, which provides greater biomechanical stability. However, controversy exists regarding the effects of placement of a screw across an uninjured sacroiliac joint for pelvis stabilization after trauma. Does transsacral-transiliac screw fixation of an uninjured sacroiliac joint increase pain and worsen functional outcomes at minimum 1-year followup compared with patients undergoing standard iliosacral screw fixation across the injured sacroiliac joint in patients who have sustained pelvic trauma? All patients between ages 18 and 84 years who sustained injuries to the pelvic ring (AO/OTA 61 A, B, C) who were surgically treated between 2011 and 2013 at an academic Level I trauma center were identified for selection. We included patients with unilateral sacroiliac disruption or sacral fractures treated with standard iliosacral screws across an injured hemipelvis and/or transsacral-transiliac screws placed in the posterior ring. Transsacral-transiliac screws were generally more likely to be used in patients with vertically unstable sacral injuries of the posterior ring as a result of previous reports of failures or in osteopenic patients. We excluded patients with bilateral posterior pelvic ring injuries, fixation with a device other than a screw, previous pelvic or acetabular fractures, associated acetabular fractures, and ankylosing spondylitis. Of the 110 patients who met study criteria, 53 (44%) were available for followup at least 12 months postinjury. Sixty patients were unable to be contacted by phone or mail and seven declined to participate in the study. Outcomes were obtained by members of the research team using the visual analog scale (VAS) pain score for both posterior sacroiliac joints, Short Musculoskeletal Functional Assessment (SMFA), and Majeed scores. Patients completed the forms by themselves when able to return to the clinic. A phone interview was performed for others after they received the outcome forms by mail or email. There were no differences between iliosacral and transsacral-transiliac in terms of VAS injured (2.9 ± 2.9 versus 3.0 ± 2.8, mean difference = 0.1 [95% confidence interval, −1.6 to 1.7], p = 0.91), VAS uninjured (1.8 ± 2.4 versus 2.0 ± 2.6, mean difference = 0.2 [−1.3 to 1.6], p = 0.82), Majeed (80.3 ± 19.9, 79.3 ± 17.5, mean difference = 1.0 [−11.6 to 9.6], p = 0.92), SMFA Function (22.8 ± 22.2, 21.0 ± 17.6, mean difference = 1.8 [−13.2 to 9.6], p = 0.29, and SMFA Bother (24.3 ± 23.8, 29.7 ± 23.4, mean difference = 5.4 [−7.8 to 18.6], p = 0.42). Placement of fixation across a contralateral, uninjured sacroiliac joint resulted in no differences in pain and function when compared with standard iliosacral screw placement across an injured hemipelvis at least 1 year after instrumentation. When needed for biomechanical stability, transsacral-transiliac fixation across an uninjured sacroiliac joint can be used without expectation of positive or negative effects on pain or functional outcomes at minimum 1-year followup. Level III, therapeutic study.

Patients with dementia are at high risk for hip fractures and often have poor outcomes when a fracture is sustained. Despite this poor prognosis, little data are available on what factors should be prioritized to guide surgical decision making in these cases. We aimed to understand the decision-making process for older dementia patients hospitalized after hip fractures.We performed a qualitative analysis of in-depth elite interviews conducted with a clinical care team involved in management of patients with dementia after hospitalization for hip fractures.Interviews were conducted with an interprofessional team involved in the care of patients with dementia after being hospitalized for hip fractures.Interviewees included nine orthopaedic surgeons, three hospitalists, three geriatricians, five nurses, three occupational therapists, three physical therapists, and two clinical ethicists.Verbatim transcripts of the interviews were analyzed and coded using QSR International's NVivo 10 qualitative database management software.The three main themes that most interviewees discussed were pain control, functional status, and medical comorbidities. Interviewees brought up many factors related to restoring functional status including baseline functional status, rehabilitation potential, social support, and the importance of mobility. Dementia and its impact on rehabilitation potential were mentioned by all geriatricians.Although frailty, prognosis, and life expectancy were largely absent from the responses, the emphasis on dementia, advanced directives, and involving family or caregivers by the three geriatricians indicates the importance of including geriatricians in the decision-making team for these patients.

Altered bone quality, caused by underlying metabolic changes of type 2 diabetes (T2D), has been hypothesized to cause altered bone strength and turnover leading to increased fracture risk in T2D patients. Current understanding about changes in bone turnover markers in T2D patients is mainly based on studies focused on Caucasian men and women. However, Hispanic populations have the highest prevalence of both T2D and osteoporosis in the US. We investigated associations of glycemic control (in terms of glycated hemoglobin [HbA1c]) and bone turnover rate in 69 older (≥50 years) Mexican American Cameron County Hispanic Cohort (CCHC) participants with T2D. Multivariable analyses were conducted to assess the associations between HbA1c (%), serum osteocalcin (OC), and serum sclerostin. In agreement with published reports from other racial/ethnic populations, our study found that lower bone turnover (indicated by lower serum OC) occurred in Mexican American men with T2D who had poorer glycemic control. For the women in our study, we found no significant association between glycemic control and OC. In contrast, HbA1c was positively associated with sclerostin for women, with near significance (p=0.07), while no association was found in men. We recommend screening Mexican American individuals with T2D, specifically those with poor glycemic control, for bone loss and fracture risk.

Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders.

Although an understanding of bone material properties is crucial for interpreting and predicting fracture patterns due to injury or defining the effects of disease on bone strength, information about infant bone properties is scant in the literature. In this study we present the mechanical testing results from 47 tibia and 52 rib specimens taken from 53 infant decedents in order to further our understanding of infant bone strength. Bone specimens were imaged using microCT and tested in three-point bending until failure. Extrinsic and intrinsic properties demonstrated an increase in strength and stiffness over the first year of life, while ductility measures remained largely unchanged. Donor race had no effect on the material properties, but tibia bone specimens showed significant sex differences, with the elastic modulus from females being larger than males. When compared to properties from adolescent and adult donors, infant bone is less strong, less stiff, and more ductile.

Greater bone mineral density was observed after treating hypertension using angiotensin-converting enzyme inhibitor (ACEi). We report decreased rate of bone loss in hypertensive black men using ACEi for 9 years. There may be a gender- and race-specific effect of ACEi in the prevention of age-associated bone loss. There is evidence of bone mass preservation in patients receiving ACEis, commonly used to treat hypertension. However, limitations of previous studies include being cross-sectional or only including a short-term follow-up of patients using ACEi and including patients with diabetes, which affects bone metabolism. None of the previous studies described effects of ACEi stratified by race. The objective of this study was to investigate differences in changes in bone mineral density (BMD) in older adults who suffer from hypertension and had reported ACEi use during each study visit for at least 9 years during the study, stratified by gender and race. We used data from the Dynamics of Health, Aging and Body Composition (HABC) study, which enrolled 3075 community-dwelling older white and black individuals. We compared changes in femoral neck, total hip, and whole-body BMD after either no use of ACEi (n = 580) or long-term use (at least 9 years) of ACEi (n = 239) in HABC participants with hypertension and no known diagnosis of diabetes mellitus. Overall, BMD values significantly decreased for all subgroups over time. In the stratified multivariate analysis, long-term use of ACEi was associated with a reduced rate of decline for all three BMD measures among black men, but no significant effect was observed in the other subgroups. Our findings show a gender- and race-specific effect of ACEi in the prevention of age-associated bone loss that warrants further evaluation.

Mutations in COMP (cartilage oligomeric matrix protein) cause severe long bone shortening in mice and humans. Previously, we showed that massive accumulation of misfolded COMP in the ER of growth plate chondrocytes in our MT-COMP mouse model of pseudoachondroplasia (PSACH) causes premature chondrocyte death and loss of linear growth. Premature chondrocyte death results from activation of oxidative stress and inflammation through the CHOP-ER pathway and is reduced by removing CHOP or by anti-inflammatory or antioxidant therapies. Although the mutant COMP chondrocyte pathologic mechanism is now recognized, the effect of mutant COMP on bone quality and joint health (laxity) is largely unknown. Applying multiple analytic approaches, we describe a novel mechanism by which the deleterious consequences of mutant COMP retention results in upregulation of miR-223 disturbing the adipogenesis - osteogenesis balance. This results in reduction in bone mineral density, bone quality, mechanical strength and subchondral bone thickness. These, in addition to abnormal patterns of ossification at the ends of the femoral bones likely contribute to precocious osteoarthritis (OA) of the hips and knees in the MT-COMP mouse and PSACH. Moreover, joint laxity is compromised by abnormally thin ligaments. Altogether, these novel findings align with the PSACH phenotype of delayed ossification and bone age, extreme joint laxity and joint erosion, and extend our understanding of the underlying processes that affect bone in PSACH. These results introduce a novel finding that miR-223 is involved in the ossification defect in MT-COMP mice making it a therapeutic target.

Trabecular bone score (TBS) is a texture parameter that measures the grayscale variation within dual-energy X-ray absorptiometry (DXA) images, and has been shown to significantly correlate with the 3-dimensional bone microarchitecture. The objective of this study was to determine whether TBS is a better clinical tool than traditionally used bone mineral density (BMD) to detect the skeletal deterioration seen in patients with diabetes (DM), patients undergoing oral glucocorticoid (GC) therapy, and patients who are both diabetic and taking steroids (GC + DM). We performed retrospective, cross-sectional study using DXA images of patients who visited UTHealth Department of Internal Medicine DXA clinic in Houston, TX, from May 30, 2014 to May 30, 2016. A total of 477 men and women, who were 55 years or older, were included in the study. Lumbar spine (LS) BMD and TBS were collected. Electronic medical records were reviewed to collect clinical information for each patient. When both men and women were analyzed as a single group, LS-BMD was significantly higher in the diabetic group than in the control group (1.14 vs 1.10, p = 0.038), whereas mean TBS of L1-L4 was significantly lower in the diabetic group (1.21 vs 1.26, p = 0.004). LS-TBS was also significantly lower in diabetic women than in nondiabetic women (1.20 vs 1.26, p = 0.002). Receiver operating characteristic curves and areas under the curve indicated that LS-TBS provided better ability than LS-BMD to discriminate between control subjects and those in the DM, GC, or GC + DM groups (areas under the curve between 0.645 and 0.697, p

The growing field of osteoimmunology seeks to unravel the complex interdependence of the skeletal and immune systems. Notably, we and others have demonstrated that complement signaling influences the differentiation of osteoblasts and osteoclasts, the two primary cell types responsible for maintaining bone homeostasis. However, the net effect of complement on bone homeostasis in vivo was unknown. Our published in vitro mechanistic work led us to hypothesize that absence of complement component 3 (C3), a central protein in the complement activation cascade, protects against bone loss in the ovariectomy-based model of postmenopausal osteoporosis. Indeed, we report here that, when compared to their C57BL/6J (WT) counterparts, ovariectomized C3 deficient mice experienced reduced bone loss at multiple sites and increased stiffness at the femoral neck, the latter potentially improving mechanical function. WT and B6;129S4-C3tm1Crr /J (C3-/- ) mice were either ovariectomized or sham-operated at 6 weeks of age and euthanized at 12 weeks. MicroCT on harvested bones revealed that the trabecular bone volume fraction in the metaphyses of both the proximal tibiae and distal femora of ovariectomized C3-/- mice is significantly greater than that of their WT counterparts. Lumbar vertebrae showed significantly greater osteoid content and mineral apposition rates. Mechanical testing demonstrated significantly greater stiffness in the femoral necks of ovariectomized C3-/- mice. These results demonstrate that C3 deficiency reduces bone loss at ovariectomy and may improve mechanical properties. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:118-128, 2018.

Mutations in WNT1 cause osteogenesis imperfecta (OI) and early-onset osteoporosis, identifying it as a key Wnt ligand in human bone homeostasis. However, how and where WNT1 acts in bone are unclear. To address this mechanism, we generated late-osteoblast-specific and osteocyte-specific WNT1 loss- and gain-of-function mouse models. Deletion of Wnt1 in osteocytes resulted in low bone mass with spontaneous fractures similar to that observed in OI patients. Conversely, Wnt1 overexpression from osteocytes stimulated bone formation by increasing osteoblast number and activity, which was due in part to activation of mTORC1 signaling. While antiresorptive therapy is the mainstay of OI treatment, it has limited efficacy in WNT1-related OI. In this study, anti-sclerostin antibody (Scl-Ab) treatment effectively improved bone mass and dramatically decreased fracture rate in swaying mice, a model of global Wnt1 loss. Collectively, our data suggest that WNT1-related OI and osteoporosis are caused in part by decreased mTORC1-dependent osteoblast function resulting from loss of WNT1 signaling in osteocytes. As such, this work identifies an anabolic function of osteocytes as a source of Wnt in bone development and homoeostasis, complementing their known function as targets of Wnt signaling in regulating osteoclastogenesis. Finally, this study suggests that Scl-Ab is an effective genotype-specific treatment option for WNT1-related OI and osteoporosis.

Background Prevention of infection associated with uncemented orthopaedic implants could lead to improved implant stability and better patient outcomes. We hypothesized that coating porous metal implants with antibiotic-containing microspheres would prevent infections in grossly contaminated wounds. Methods Bioresorbable polymer microspheres containing tobramycin were manufactured and pressed into porous metal cylinders that were then implanted into radial defects in rabbits. Control implants that did not contain antibiotic microspheres were also implanted into the contralateral limbs. Each implant was then contaminated with Staphylococcus aureus prior to closure of the wound. The animal was euthanized after clinical signs of infection appeared, or at two weeks after surgery. Periprosthetic tissue was cultured for the presence of S. aureus, and integration of the implant with the surrounding bone was measured. Results The antibiotic microspheres successfully prevented infection in 100% of the eleven limbs with treated implants, which represented a significant improvement (p = 0.004) compared with the infection rate of 64% (seven of eleven) for the limbs with control implants. Implant integration averaged 38.87% ± 12.69% in the fifteen uninfected limbs, which was significantly better (p = 0.012) than the average of 19.46% ± 14.49% in the seven infected limbs. Conclusions The antibiotic delivery system successfully prevented infection in 100% of the cases studied, resulting in an increase in implant integration. Clinical relevance Antibiotic delivery utilizing the system described here may be effective in preventing implant-associated infections after orthopaedic surgery and increasing the longevity of orthopaedic implants.

Objectives The purpose of this study is to compare open reduction and internal fixation of the patella with a locking plate and tension-band construct (PF) versus cannulated screws and tension-band fixation (SF). The hypothesis is that both constructs will have similar failure loads with simulated extension loading. Methods Transverse patellar fractures were created in 10 cadaveric pairs of legs and were fixed with either PF or SF. Dual-energy X-ray Absorptiometry (DXA) scans of all calcanei measured bone mineral density (BMD). Using an MTS 810 servohydraulic testing machine, each leg cycled to full extension 10 times before loading to failure. A differential variable reluctance transducer measured the distraction of the patella. Data were analyzed using paired t test analysis and bivariate analysis for Pearson correlation coefficients. Results There was no difference in the BMD between the PF and the SF groups (P = 0.367). No measurable differences occurred during the 10 cycles, and load at clinical failure was not significantly different between the 2 fixation groups (P = 0.38). Stiffness during the final loading cycle was significantly higher for the SF group (P = 0.008). Ultimate strength of fixation was significantly higher in PF group (P = 0.048). BMD was not correlated to the ultimate strength of SF (P = 0.112), but was correlated for PF (P = 0.025). Conclusions Based on our results, PF provides comparable strength to SF, and it seems to be a safe and effective alternative to the current gold standard.

TGF-β is abundantly produced in the skeletal system and plays a crucial role in skeletal homeostasis. E-selectin ligand-1 (ESL-1), a Golgi apparatus-localized protein, acts as a negative regulator of TGF-β bioavailability by attenuating maturation of pro–TGF-β during cartilage homeostasis. However, whether regulation of intracellular TGF-β maturation by ESL-1 is also crucial during bone homeostasis has not been well defined. Here, we show that Esl-1 −/− mice exhibit a severe osteopenia with elevated bone resorption and decreased bone mineralization. In primary culture, Esl-1 −/− osteoclast progenitors show no difference in osteoclastogenesis. However, Esl-1 −/− osteoblasts show delayed differentiation and mineralization and stimulate osteoclastogenesis more potently in the osteoblast–osteoclast coculture, suggesting that ESL-1 primarily acts in osteoblasts to regulate bone homeostasis. In addition, Esl-1 −/− calvaria exhibit an elevated mature TGF-β/pro–TGF-β ratio, with increased expression of TGF-β downstream targets (plasminogen activator inhibitor-1, parathyroid hormone-related peptide, connective tissue growth factor, and matrix metallopeptidase 13, etc.) and a key regulator of osteoclastogenesis (receptor activator of nuclear factor κB ligand). Moreover, in vivo treatment with 1D11, a pan–TGF-β antibody, significantly improved the low bone mass of Esl-1 −/− mice, suggesting that elevated TGF-β signaling is the major cause of osteopenia in Esl-1 −/− mice. In summary, our study identifies ESL-1 as an important regulator of bone remodeling and demonstrates that the modulation of TGF-β maturation is pivotal in the maintenance of a homeostatic bone microenvironment and for proper osteoblast–osteoclast coupling.

Background: Disruption of the distal tibia and fibula articulation or syndesmosis can occur without fracture, and isolated syndesmotic disruption is often treated operatively. Following syndesmotic screw removal, a period of protected weight-bearing usually follows to allow the screw holes to heal. Our hypothesis was that supplementing transsyndesmotic fixation with a one-third tubular plate would potentially increase the torsional stiffness about the ankle, thus reducing the risk of fracture after screw removal and potentially allowing a faster return to weight-bearing and sport. Methods: Ten pairs of fresh frozen cadaveric specimens were divided into 2 groups. In group 1 (7 pairs), each left extremity underwent the placement, and subsequent removal, of a 4.5-mm transsyndesmotic screw in a tricortical fashion. The matching right extremity underwent the same procedure but with the addition of a one-third tubular plate, which remained in situ after screw removal. In group 2 (3 pairs), the left specimens had a screw placed and removed while the right limbs remained intact. All specimens were tested under an axial preload and a torsional load until failure. Results: In group 1, the results demonstrated an increase in torsional stiffness in 5 of 7 specimens with supplemental fixation of a one-third tubular plate. In group 2, the presence of the screw hole alone reduced the torsional stiffness in all specimens tested when compared with intact specimens. However, neither of these differences were statistically significant. Conclusion: From this study, we can conclude that the use of supplementary one-third tubular plate fixation demonstrated a trend toward increasing the torsional stiffness following transsyndesmotic screw removal. Clinical Relevance: We believe the trend toward improved stiffness justifies the continued use of our technique, although further studies are necessary to confirm it.

The growing field of osteoimmunology seeks to unravel the complex interdependence of the skeletal and immune systems. Notably, we and others have demonstrated that complement signaling influences the differentiation of osteoblasts and osteoclasts, the two primary cell types responsible for maintaining bone homeostasis. However, the net effect of complement on bone homeostasis in vivo was unknown. Our published in vitro mechanistic work led us to hypothesize that absence of complement component 3 (C3), a central protein in the complement activation cascade, protects against bone loss in the ovariectomy-based model of postmenopausal osteoporosis. Indeed, we report here that, when compared to their C57BL/6J (WT) counterparts, ovariectomized C3 deficient mice experienced reduced bone loss at multiple sites and increased stiffness at the femoral neck, the latter potentially improving mechanical function. WT and B6;129S4‐C3tm1Crr/J (C3−/−) mice were either ovariectomized or sham-operated at 6 weeks of age and euthanized at 12 weeks. MicroCT on harvested bones revealed that the trabecular bone volume fraction in the metaphyses of both the proximal tibiae and distal femora of ovariectomized C3−/− mice is significantly greater than that of their WT counterparts. Lumbar vertebrae showed significantly greater osteoid content and mineral apposition rates. Mechanical testing demonstrated significantly greater stiffness in the femoral necks of ovariectomized C3−/− mice. These results demonstrate that C3 deficiency reduces bone loss at ovariectomy and may improve mechanical properties.

Osteogenesis Imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65KDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon and ligaments in postnatal tissues. Furthermore, in both patients and Fkbp10 knockout mice, collagen telopeptide hydroxylysine crosslinking is dramatically reduced. To further characterize the bone specific contributions of Fkbp10, we conditionally ablated FKBP65 in Fkbp10fl/fl mice (Mus musculus; C57BL/6) using the osteoblast specific Col1a1 2.3kb Cre recombinase. Using μCT, histomorphometry and quantitative backscattered electron imaging, we found minimal alterations in the quantity of bone and no differences in the degree of bone matrix mineralization in this model. However, mass spectroscopy of bone collagen demonstrated a decrease in mature, hydroxylysine-aldehyde crosslinking. Furthermore, bone of mutant mice exhibits a reduction in mineral-to-matrix ratio and in crystal size as shown by Raman spectroscopy and small angle x-ray scattering, respectively. Importantly, abnormalities in bone quality were associated with impaired bone biomechanical strength in mutant femurs compared with those of wild type littermates. Taken together, these data suggest that the altered collagen crosslinking through Fkbp10 ablation in osteoblasts primarily leads to a qualitative defect in the skeleton.

Sepsis from bacteremia occurs in 250,000 cases annually in the United States, has a mortality rate as high as 60%, and is associated with a poorer prognosis than localized infection. Because of these high figures, empiric antibiotic administration for patients with systemic inflammatory response syndrome (SIRS) and suspected infection is the second most common indication for antibiotic administration in intensive care units (ICU)s. However, overuse of empiric antibiotics contributes to the development of opportunistic infections, antibiotic resistance, and the increase in multi-drug-resistant bacterial strains. The current method of diagnosing and ruling out bacteremia is via blood culture (BC) and Gram stain (GS) analysis.Conventional and molecular methods for diagnosing bacteremia were reviewed and compared. The clinical implications, use, and current clinical trials of polymerase chain reaction (PCR)-based methods to detect bacterial pathogens in the blood stream were detailed.BC/GS has several disadvantages. These include: some bacteria do not grow in culture media; others do not GS appropriately; and cultures can require up to 5 d to guide or discontinue antibiotic treatment. PCR-based methods can be potentially applied to detect rapidly, accurately, and directly microbes in human blood samples.Compared with the conventional BC/GS, particular advantages to molecular methods (specifically, PCR-based methods) include faster results, leading to possible improved antibiotic stewardship when bacteremia is not present.

Fracture non-unions and bone re-fracture are common challenges for post-fracture management. To achieve better prognosis and treatment evaluation, it is important to be able to assess the quality of callus over the time course of healing. This study evaluated the potential of spatially offset Raman spectroscopy for assessing the fracture healing process in situ. We investigated a rat model of fracture healing at two weeks and 4 weeks post fracture with a fractured femur and a contralateral control in each animal. Raman spectra were collected from the depilated thighs on both sides transcutaneously in situ with various source/detection offsets. Bone signals were recovered from SORS spectra, and then compared with those collected from bare bones. The relative intensity of mineral from fractured bone was markedly decreased compared to the control. The fractured bones demonstrated lower mineral and carbonate level and higher collagen content in the callus at the early time point. Compared to week 2, collagen mineralization and mineral carbonation increased at 4 weeks post fracture. Similarly, the material properties of callus determined by reference point indentation also increased in the 4-week group, indicating improved callus quality with time. The results from Raman analysis are in agreement with radiographic and material testing, indicating the potential of this technique in assessing fracture healing in vivo.

Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by brittle bones that are prone to fracture. Although previous studies in animal models investigated the mechanical properties and material composition of OI bone, little work has been conducted to statistically correlate these parameters to identify key compositional contributors to the impaired bone mechanical behaviors in OI. Further, although increased TGF-β signaling has been demonstrated as a contributing mechanism to the bone pathology in OI models, the relationship between mechanical properties and bone composition after anti-TGF-β treatment in OI has not been studied. Here, we performed follow-up analyses of femurs collected in an earlier study from OI mice with and without anti-TGF-β treatment from both recessive (Crtap(−/−)) and dominant (Col1a2(+/P.G610C)) OI mouse models and WT mice. Mechanical properties were determined using three-point bending tests and evaluated for statistical correlation with molecular composition in bone tissue assessed by Raman spectroscopy. Statistical regression analysis was conducted to determine significant compositional determinants of mechanical integrity. Interestingly, we found differences in the relationships between bone composition and mechanical properties and in the response to anti-TGF-β treatment. Femurs of both OI models exhibited increased brittleness, which was associated with reduced collagen content and carbonate substitution. In the Col1a2(+/P.G610C) femurs, reduced hydroxyapatite crystallinity was also found to be associated with increased brittleness, and increased mineral-to-collagen ratio was correlated with increased ultimate strength, elastic modulus, and bone brittleness. In both models of OI, regression analysis demonstrated that collagen content was an important predictor of the increased brittleness. In summary, this work provides new insights into the relationships between bone composition and material properties in models of OI, identifies key bone compositional parameters that correlate with the impaired mechanical integrity of OI bone, and explores the effects of anti-TGF-β treatment on bone-quality parameters in these models.

Purpose and Methods: Previous in vitro experiments have demonstrated that the addition of bisphosphonate groups to a fullerene (C60) molecule may lead to a drug delivery system targeted to bone. To determine the safety and the efficacy of the C60 bisphosphonated compound, a rat model of osteoporosis has been employed. Results: Two different doses were studied and the results demonstrated that the C60 compound is safe in the rat model: no significant behavior changes occurred, weight gains were normal, and no significant pathology was noted in the kidney, liver or esophagi of the animals when the test compound was administered orally over the course of eight weeks. The test compound also resulted in positive changes in the bone architecture of the treated ovariectomized animals. Conclusion: This indicates that the compound was delivered to bone and that it was bioactive.

Objectives Iliosacral screw pathways in the first (S1) and second (S2) sacral segments are commonly used for adult pelvic ring stabilization. We hypothesize that radiographically "safe" pathways exist in pediatric patients. Setting Academic level I Trauma Center. Patients All patients between ages 2 and 16 years with a computed tomography scan including the pelvis obtained over a 6-week period (174 children, mean age 10.8 ± 3.9 years; 90 boys, 84 girls). Intervention The width and height at the "constriction point" in 3 safe screw pathways were measured bilaterally by 3 orthopaedists (resident, trauma fellow, trauma attending). Pathways corresponding to: (1) an "iliosacral" screw at S1, a "trans-sacral trans-iliac" (TSTI) screw at S1, and a TSTI screw at S2. Main outcome measurements (1) Mean width and height of pathways, (2) interrater reliability coefficient, (3) availability of pathways greater than 7 mm, (4) growth of pathways with age, (5) sacral morphology. Results The interrater reliability coefficient was above 0.917 for all measurements. Radiographically safe pathways were available for 99%, 51%, and 89% of children for iliosacral screws at S1 (width 16.4 ± 2.8 mm, height 15.1 ± 3.3 mm), TSTI screws at S1 (width 7.2 ± 4.9 mm, height 8.3 ± 5.6 mm), and TSTI at S2 (width 9.3 ± 2.2 mm, height 11.5 ± 2.7 mm), respectively. Conclusions Contrary to our hypothesis, almost all children aged 2-16 had a radiographically safe screw pathway for an iliosacral screw at S1, and most of the children had an available pathway for a TSTI screw at S2. However, only 51% had a pathway for a TSTI screw at S1.

Purpose: To compare the loop and knot security of arthroscopic square knots with other arthroscopic and open knots with the use of 2 commonly used suture types. Methods: Five knot configurations were tested 12 times each. The arthroscopic square knot was compared with the open square knot, arthroscopic and open half hitches with alternating posts, and the Duncan loop. Load-to-failure testing was performed at a rate of 1.25 mm/sec, and cyclic testing was performed between 7 N and 30 N at a rate of 1 N/sec for 50 cycles. Two suture types were tested: No. 2 Ethibond suture and No. 2 FiberWire. Results: Among the No. 2 Ethibond sutures, the arthroscopic Duncan loop had the highest load-to-failure at 165 N. The remaining knot types failed at between 142 N and 148 N. The load at 3 mm of lengthening was between 100 N and 120 N for all knots. The No. 2 FiberWire failed at higher loads than the No. 2 Ethibond suture for all knot types except the Duncan loop. The arthroscopic half hitches, arthroscopic square knots, and open half hitches all failed at between 220 N and 264 N. The open square knot failed at 188 N, and the Duncan loop failed at 147 N. The load at 3 mm of lengthening was between 130 N and 165 N for all knots except the Duncan loop, which failed at 95 N. With cyclic testing, arthroscopic square knots performed better than all knot types, but the differences were clinically insignificant. Conclusions: Arthroscopic square knots have the same or greater strength when compared with other arthroscopic or open knots tied with the same suture type, and they perform as well or better in the face of cyclic loads. Good knot security can be attained with all of the knots tested, regardless of suture type. Equivalent knots tied with No. 2 FiberWire fail at higher loads, except for those tied with the Duncan loop. Clinical Relevance: Arthroscopic square knots can be used in the clinical setting with no compromise in function when compared with open square knots.