Revisiting the Beighton Criteria: Does Ligamentous Laxity Testing Correlate With Shoulder Range of Motion Norms in a North American, Pediatric Population?

BACKGROUND: Ligamentous laxity testing using the Beighton score is frequently used as part of the pediatric shoulder examination. However, the relationship between generalized ligamentous laxity (GLL) and shoulder range of motion (ROM) remains unexamined in children, and normative data for these clinical tests have not been well established. In this study, we establish normative data for shoulder range of motion and GLL in a healthy, diverse pediatric population and investigate whether Beighton testing correlates with shoulder ROM in children. METHODS: Healthy subjects age 2 to 18 years with isolated lower extremity complaints were recruited. Passive shoulder ROM measurements for forward flexion (FF), abduction (ABD), internal rotation (IR), external rotation (ER), and extension (EXT) were obtained using a long-armed goniometer. The Beighton score was obtained, with a positive test defined as ≥5. Descriptive statistics were used to stratify data on the basis of age and sex. Interclass correlation coefficients (ICCs) were calculated. Spearman's r was calculated to determine correlations between the Beighton score and shoulder ROM. Predictive indices of a positive Beighton test to identify patients with high shoulder mobility (ROM in the top 15 percentile, or 1 SD above the mean) were calculated. RESULTS: A total of 202 subjects were enrolled and evaluated. Passive ROM norms by age and sex were determined. Intraclass correlation coefficients for all shoulder ROM measurements were substantial to excellent. Female individuals had greater ROM than age-matched male individuals, but this trend was largely statistically insignificant. Pearson's correlation between age and shoulder ROM was significant for FF, ABD, EXT, and ER (r=-0.52 to -0.20, P<0.001). Based on a Beighton score of ≥5, the prevalence of GLL was 10% in male and 15% in female individuals. Spearman's correlation between Beighton score and shoulder ROM was significant for 3 of 5 ROM measurements: FF, ER, and EXT (r=0.30 to 0.39, P<0.001). CONCLUSIONS: Normative pediatric shoulder ROM and joint laxity data have been established in a healthy, diverse population of children. Beighton testing exhibits only a weak to moderate correlation, despite statistical significance, with shoulder ROM and is poorly predictive for high ROM in children. LEVEL OF EVIDENCE: Level I- Diagnostic.

Abstract Submission and Acceptance Rates for Men and Women in Academic Pediatric Orthopaedic Surgery: An Analysis of POSNA Annual Meeting Abstract Submissions 2012-2015.

BACKGROUND: It has recently been demonstrated that women members of the Pediatric Orthopaedic Society of North America (POSNA) participate at the Annual Meeting at disproportionately lower rates than men members, as defined by accepted abstract(s). We hypothesize that this discrepancy is associated with lower abstract submission rates by women members. METHODS: POSNA membership directories for the years 2012-2015 were used to record the name, sex, membership category, and years of membership for each member. Final programs for Annual Meetings and abstract submission records for the same time period were used to record the number of accepted and rejected abstracts for each member. General estimating equations with a binomial model and logit link were used to compare the proportion of abstract acceptances between sexes across years. RESULTS: During the period 2012-2015, active members included 534 men (83.8%) and 103 women (16.2%), whereas candidate members included 207 men (64.7%) and 113 women (35.3%). When active and candidate members were considered collectively, men were significantly more likely to have an accepted abstract (P=0.009) and this significant difference did not change over the 4-year period (P=0.627). However, men submitted significantly more abstracts per member per year than women (means: 1.5 abstracts/man/y; 0.8 abstracts/woman/y; P<0.001). This held true for both candidate members (early career) (P=0.001) as well as active members (mid-career) (P<0.001). When the total number of abstract submissions per year per member was taken into account, the percentage of abstract acceptances was similar for men and women (men=42%, women=40%; P=0.847). CONCLUSIONS: Abstract acceptance rates were similar for women and men members of POSNA for the 2012-2015 Annual Meetings. However, men had a significantly greater number of abstract submissions per member than women, and consequently, men presented a higher proportion of abstracts relative to their membership numbers. This supports our hypothesis that the disproportionately lower rate of active participation amongst women members at POSNA Annual Meetings, defined as abstract acceptance, is due to lower rates of abstract submissions, rather than to lower rates of acceptances. LEVEL OF EVIDENCE: It is not applicable as it is not a clinical or basic science study.

Fibrocartilaginous Mesenchymoma of the Spine: A Case Report.

CASE: A healthy, 19-year-old woman was incidentally found to have a large, destructive tumor of T11 without neurologic symptoms. Biopsy demonstrated fibrocartilaginous mesenchymoma (FCM). The patient was treated with resection including subtotal corpectomy and T8-L1 fusion with use of cage and allograft strut construct. The patient remained without recurrence over 3 years of follow-up. CONCLUSION: FCM arising from the spine is a rare tumor, of which this is the sixth report. FCM affects primarily young adults and is benign but locally aggressive, requiring complete excision to prevent recurrence.

Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model.

Introduction: Diabetes mellitus (DM) impairs fracture healing and is associated with susceptibility to infection, which further inhibits fracture healing. While intermittent parathyroid hormone (1-34) (iPTH) effectively improves fracture healing, it is unknown whether infection-associated impaired fracture healing can be rescued with PTH (teriparatide). Methods: A chronic diet-induced type 2 diabetic mouse model was used to yield mice with decreased glucose tolerance and increased blood glucose levels compared to lean-fed controls. Methicillin-resistant Staphylococcus aureus (MRSA) was inoculated in a surgical tibia fracture model to simulate infected fracture, after which mice were treated with a combination of antibiotics and adjunctive teriparatide treatment. Fracture healing was assessed by Radiographic Union Scale in Tibial Fractures (RUST), micro-computed tomography (µCT), biomechanical testing, and histology. Results: RUST score was significantly poorer in diabetic mice compared to their lean nondiabetic counterparts. There were concomitant reductions in micro-computed tomography (µCT) parameters of callus architecture including bone volume/total volume, trabecular thickness, and total mineral density in type 2 diabetes mellitus (T2DM) mice. Biomechanicaltesting of fractured femora demonstrated diminished torsional rigidity, stiffness, and toughness to max torque. Adjuvant teriparatide treatment with systemic antibiotic therapy improved numerous parameters of bone microarchitecture bone volume, increased connectivity density, and increased trabecular number in both the lean and T2DM group. Despite the observation that poor fracture healing in T2DM mice was further impaired by MRSA infection, adjuvant iPTH treatment significantly improved fracture healing compared to antibiotic treatment alone in infected T2DM fractures. Discussion: Our results suggest that teriparatide may constitute a viable adjuvant therapeutic agent to improve bony union and bone microarchitecture to prevent the development of septic nonunion under diabetic conditions.

The rate and predictors of healing of repaired lesser tuberosity osteotomy in reverse total shoulder arthroplasty.

Background: Evidence is building that a functional subscapularis improves function-specifically internal rotation tasks-following reverse total shoulder arthroplasty (rTSA). However, the optimal method for subscapularis repair during rTSA remains unknown with variable healing rates reported. This study aims to investigate the rate of and predictors for healing a lesser tuberosity osteotomy (LTO) following rTSA. Methods: Following local institutional review board approval, patients with at least one-year follow-up for rTSA managed with an LTO and subsequent repair between March, 2017 and March, 2020 were retrospectively identified. Shoulders were selected for LTO repair based upon preoperative imaging and intraoperative assessment of subscapularis quality. All patients were implanted with a system consisting of a 150° or 155° (constrained) humeral neck-shaft angle and 2.5 to 4.5 millimeters (mm) of glenoid lateralization (Trabecular Metal Reverse Shoulder System; Zimmer Biomet, Warsaw, IN, USA). At a minimum of six months, radiographs were reviewed for an assessment of LTO healing by three independent reviewers. Healing was classified as displaced, fibrous union, or ossified union. For assessing predictors, the repair was considered intact if the LTO fragment was not displaced (fibrous union or ossified union). Results: Sixty-five rTSA with LTO repair were performed in 64 patients. These patients had an average age of 67.2 years (range, 31-81) and 36 (55.4%; 36/65) were female. At an average follow-up of 15.2 months (range, 8-38), 50 cases (76.9%; 50/65) were classified as having an ossified union. The radiographic healing could not be assessed in a single case. Of the 14 cases without ossific union, 8 (12.3%; 8/65) were displaced and 6 (9.2%; 6/65) were classified as a fibrous union. In logistic regression, only combined humeral liner height predicted LTO displacement (odds ratio = 1.4 [95% confidence interval = 1.1-1.8]; P = .01). Humeral loosening was not found in any cases following LTO. Conclusion: This analysis demonstrates that radiographic healing of LTO repair is more favorable than published rates of healing after subscapularis tenotomy or peel in the setting of rTSA. Subscapularis management with LTO provides the ability to monitor repair integrity with plain radiographs and a predictable radiographic healing rate. The integrity of subscapularis repair may be influenced by the use of thicker humeral liners. Further investigation is needed to determine the functional impact of a healed subscapularis following rTSA.

Enhancement of Impaired MRSA-Infected Fracture Healing by Combinatorial Antibiotics and Modulation of Sustained Inflammation.

Fracture healing is impaired in the setting of infection, which begets protracted inflammation. The most problematic causative agent of musculoskeletal infection is methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that modulation of excessive inflammation combined with cell-penetrating antibiotic treatments facilitates fracture healing in a murine MRSA-infected femoral fracture model. Sterile and MRSA-contaminated open transverse femoral osteotomies were induced in 10-week-old male C57BL/6 mice and fixed via intramedullary nailing. In the initial therapeutic cohort, empty, vancomycin (V), rifampin (R), vancomycin-rifampin (VR), or vancomycin-rifampin-trametinib (VRT) hydrogels were applied to the fracture site intraoperatively. Rifampin was included because of its ability to penetrate eukaryotic cells to target intracellular bacteria. Unbiased screening demonstrated ERK activation was upregulated in the setting of MRSA infection. As such, the FDA-approved mitogen-activated protein kinase kinase (MEK)1-pERK1/2 inhibitor trametinib was evaluated as an adjunctive therapeutic agent to selectively mitigate excessive inflammation after infected fracture. Two additional cohorts were created mimicking immediate and delayed postoperative antibiotic administration. Systemic vancomycin or VR was administered for 2 weeks, followed by 2 weeks of VRT hydrogel or oral trametinib therapy. Hematologic, histological, and cytokine analyses were performed using serum and tissue isolates obtained at distinct postoperative intervals. Radiography and micro-computed tomography (µCT) were employed to assess fracture healing. Pro-inflammatory cytokine levels remained elevated in MRSA-infected mice with antibiotic treatment alone, but increasingly normalized with trametinib therapy. Impaired callus formation and malunion were consistently observed in the MRSA-infected groups and was partially salvaged with systemic antibiotic treatment alone. Mice that received VR alongside adjuvant MEK1-pERK1/2 inhibition displayed the greatest restoration of bone and osseous union. A combinatorial approach involving adjuvant cell-penetrating antibiotic treatments alongside mitigation of excessive inflammation enhanced healing of infected fractures. © 2022 American Society for Bone and Mineral Research (ASBMR).

Concurrent targeting of glycolysis in bacteria and host cell inflammation in septic arthritis.

Intracellular infiltration of bacteria into host cells complicates medical and surgical treatment of bacterial joint infections. Unlike soft tissue infections, septic arthritis and infection-associated inflammation destroy cartilage that does not regenerate once damaged. Herein, we show that glycolytic pathways are shared by methicillin-resistant Staphylococcus aureus (MRSA) proliferation and host inflammatory machinery in septic arthritis. MRSA readily penetrates host cells and induces proinflammatory cascades that persist after conventional antibiotic treatment. The glycolysis-targeting drug dimethyl fumarate (DMF) showed both bacteriostatic and anti-inflammatory effects by hindering the proliferation of intracellular MRSA and dampening excessive intraarticular inflammation. Combinatorial treatment with DMF and vancomycin further reduced the proliferation and re-emergence of intracellular MRSA. Combinatorial adjuvant administration of DMF with antibiotics alleviated clinical symptoms of septic arthritis by suppressing bacterial burden and curbing inflammation to protect cartilage and bone. Our results provide mechanistic insight into the regulation of glycolysis in the context of infection and host inflammation toward development of a novel therapeutic paradigm to ameliorate joint bioburden and destruction in septic arthritis.

Clinical assessment of generalized ligamentous laxity using a single test: is thumb-to-forearm apposition enough?

The complete Beighton criteria, commonly used to establish the diagnosis of generalized ligamentous laxity (GLL), include nine discrete examination maneuvers. However, busy examiners may perform only a single maneuver (e.g. passive apposition of the thumb to the forearm) as a rapid method of assessment. We hypothesize that the use of a single-joint hypermobility test does not reliably identify the presence of GLL. Healthy patients 2-18 years old presenting to a general pediatric orthopaedic clinic were screened for participation. Exclusion criteria included the presence of a systemic illness, neuromuscular disease, and inability to complete the examination. Subjects were assessed for GLL according to the Beighton criteria, using a cutoff score of 5. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio were calculated for the thumb-to-forearm apposition test with the composite Beighton score used as the gold standard. Two hundred and four patients were included in the study, 111 females and 93 males, with an average age of 10.7 years. The prevalence of GLL was 13.3%. When thumb-to-forearm apposition was performed unilaterally, the PPV was poor (34%). Conversely, the NPV was excellent (99%). Sensitivity of thumb-to-forearm motion was extremely high (99%), although the specificity of this test was modest (67%). The likelihood ratio was fair (+3.3). Performing the test bilaterally did not significantly change its utility. Thumb-to-forearm apposition testing was equally effective in identifying the presence of GLL in males and females. When performed in isolation, assessment of thumb-to-forearm apposition has a poor PPV, excellent NPV, and modest likelihood ratio. It is an extremely sensitive test, with only fair specificity. Other upper extremity tests of GLL perform similarly. Therefore, while single tests like thumb-to-forearm apposition may be helpful for 'ruling out' GLL, they are less reliable at identifying it correctly. When single tests are used to identify GLL in either clinical or research settings, the results should be interpreted with caution. Level of evidence Level I (diagnostic).

Locally delivered adjuvant biofilm-penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection.

Infection is a devastating complication following an open fracture. We investigated whether local rifampin-loaded hydrogel can combat infection and improve healing in a murine model of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. A transverse fracture was made at the tibia midshaft of C57BL/6J mice aged 10-12 weeks and stabilized with an intramedullary pin. A total of 1 × 106 colony-forming units (CFU) of MRSA was inoculated. A collagen-based hydrogel containing low-dose (60 µg) and high-dose (300 µg) rifampin was applied before closure. Postoperative treatment response was assessed through bacterial CFU counts from tissue and hardware, tibial radiographs and microcomputed tomography (µCT), immunohistochemistry, and histological analyses. All untreated MRSA-infected fractures progressed to nonunion by 28 days with profuse MRSA colonization. Infected fractures demonstrated decreased soft callus formation on safranin O stain compared to controls. Areas of dense interleukin-1ß stain were associated with poor callus formation. High-dose rifampin hydrogels reduced the average MRSA load in tissue (p < 0.0001) and implants (p = 0.041). Low-dose rifampin hydrogels reduced tissue bacterial load by 50% (p = 0.021). Among sterile models, 88% achieved union compared to 0% of those infected. Mean radiographic union scale in tibia scores improved from 6 to 8.7 with high-dose rifampin hydrogel (p = 0.024) and to 10 with combination local/systemic rifampin therapy (p < 0.0001). µCT demonstrated reactive bone formation in MRSA infection. Histology demonstrated restored fracture healing with bacterial elimination. Rifampin-loaded hydrogels suppressed osteomyelitis, prevented implant colonization, and improved healing. Systemic rifampin was more effective at eliminating infection and improving fracture healing. Further investigation into rifampin-loaded hydrogels is required to correlate these findings with clinical efficacy.

Dual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis.

Bacterial infections involving joints and vital organs represent a challenging clinical problem because of the two concurrent therapeutic goals of bacterial eradication and tissue preservation. In the case of septic arthritis, permanent destruction of articular cartilage by intense host inflammation is commonly seen even after successful treatment of bacterial infection. Here, we provide scientific evidence of a novel treatment modality that can protect articular cartilage and enhanced eradication of causative bacteria in septic arthritis. Locally delivered cell-penetrating antibiotics such as rifampicin effectively eradicate intracellular reservoirs of methicillin-resistant Staphylococcus aureus within joint cells. Furthermore, mitigation of intra-articular inflammation by targeting the NLRP3 (nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3) inflammasome protects articular cartilage from damage in a murine model of knee septic arthritis. Together, concurrent mitigation of intra-articular inflammation and local adjuvant targeting of intracellular bacteria represents a promising new therapeutic strategy for septic arthritis.

Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains.

Smokers are at a higher risk of delayed union or nonunion after fracture repair. Few specific interventions are available for prevention because the molecular mechanisms that result in these negative sequelae are poorly understood. Murine models that mimic fracture healing in smokers are crucial in further understanding the local cellular and molecular alterations during fracture healing caused by smoking. We exposed three murine strains, C57BL/6J, 129X1/SvJ, and BALB/cJ, to cigarette smoke for 3 months before the induction of a midshaft transverse femoral osteotomy. We evaluated fracture healing 4 weeks after the osteotomy using radiography, micro-computed tomography (µCT), and biomechanical testing. Radiographic analysis demonstrated a significant decrease in the fracture healing capacity of smoking 129X1/SvJ mice. µCT results showed delayed remodeling of fracture calluses in all three strains after cigarette smoke exposure. Biomechanical testing indicated the most significant impairment in the functional properties of 129X1/SvJ in comparison with C57BL/6J and BALB/cJ mice after cigarette smoke exposure. Thus, the 129X1/SvJ strain is most suitable in simulating smoking-induced impaired fracture healing. Furthermore, in smoking 129X1/SvJ murine models, we investigated the molecular and cellular alterations in fracture healing caused by cigarette smoking using histology, flow cytometry, and multiplex cytokine/chemokine analysis. Histological analysis showed impaired chondrogenesis in cigarette smoking. In addition, the important reparative cell populations, including skeletal stem cells and their downstream progenitors, demonstrated decreased expansion after injury as a result of cigarette smoking. Moreover, significantly increased pro-inflammatory mediators and the recruitment of immune cells in fracture hematomas were demonstrated in smoking mice. Collectively, our findings demonstrate the significant cellular and molecular alterations during fracture healing impaired by smoking, including disrupted chondrogenesis, aberrant skeletal stem and progenitor cell activity, and a pronounced initial inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR).

Systemic Parathyroid Hormone Enhances Fracture Healing in Multiple Murine Models of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a multisystemic disease that afflicts more than 415 million people globally-the incidence and prevalence of T2DM continues to rise. It is well-known that T2DM has detrimental effects on bone quality that increase skeletal fragility, which predisposes subjects to an increased risk of fracture and fracture healing that results in non- or malunion. Diabetics have been found to have perturbations in metabolism, hormone production, and calcium homeostasis-particularly PTH expression-that contribute to the increased risk of fracture and decreased fracture healing. Given the perturbations in PTH expression and the establishment of hPTH (1-34) for use in age-related osteoporosis, it was determined logical to attempt to ameliorate the bone phenotype found in T2DM using hPTH (1-34). Therefore, the present study had two aims: (i) to establish a suitable murine model of the skeletal fragility present in T2DM because no current consensus model exists; and (ii) to determine the effects of hPTH (1-34) on bone fractures in T2DM. The results of the present study suggest that the polygenic mouse of T2DM, TALLYHO/JngJ, most accurately recapitulates the diabetic osteoporotic phenotype seen in humans and that the intermittent systemic administration of hPTH (1-34) increases fracture healing in T2DM murine models by increasing the proliferation of mesenchymal stem cells. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Intracellular Staphylococcus aureus in bone and joint infections: A mechanism of disease recurrence, inflammation, and bone and cartilage destruction.

Bone and joint infections are devastating afflictions. Although medical interventions and advents have improved their care, bone and joint infections still portend dismal outcomes. Indeed, bone and joint infections are associated with extremely high mortality and morbidity rates and, generally, occur secondary to the aggressive pathogen Staphylococcus aureus. The consequences of bone and joint infections are further compounded by the fact that although they are aggressively treated, they frequently recur and result in massive bone and articular cartilage loss. Here, we review the literature and chronicle the fact that the fundamental cellular components of the musculoskeletal system can be internally infected with Staphylococcus aureus, which explains the ready recurrence of bone and joint infections even after extensive administration of antibiotic therapy and debridement and offer potential treatment solutions for further study. Moreover, we review the ramifications of intracellular infection and expound that the massive bone and articular cartilage loss is caused by the sustained proinflammatory state induced by infection and offer potential combination therapies for further study to protect bone and cartilage.

Re-appraising the potential of naringin for natural, novel orthopedic biotherapies.

Naringin is a naturally occurring flavonoid found in plants of the Citrus genus that has historically been used in traditional Chinese medical regimens for the treatment of osteoporosis. Naringin modulates signaling through numerous molecular pathways critical to musculoskeletal development, cellular differentiation, and inflammation. Administration of naringin increases in vitro expression of bone morphogenetic proteins (BMPs) and activation of the Wnt/ß-catenin and extracellular signal-related kinase (Erk) pathways, thereby promoting osteoblastic proliferation and differentiation from stem cell precursors for bone formation. Naringin also inhibits osteoclastogenesis by both modifying RANK/RANKL interactions and inducing apoptosis in osteoclasts in vitro. In addition, naringin acts on the estrogen receptor in bone to mimic the native bone-preserving effects of estrogen, with few systemic side effects on other estrogen-sensitive tissues. The efficacy of naringin therapy in reducing the osteolysis characteristic of common musculoskeletal pathologies such as osteoporosis, degenerative joint disease, and osteomyelitis, as well as inflammatory conditions affecting bone such as diabetes mellitus, has been extensively demonstrated in vitro and in animal models. Naringin thus represents a naturally abundant, cost-efficient agent whose potential for use in novel musculoskeletal biotherapies warrants re-visiting and further exploration through human studies. Here, we review the cellular mechanisms of action that have been elucidated regarding the action of naringin on bone resident cells and the bone microenvironment, in vivo evidence of naringin's osteostimulative and chondroprotective properties in the setting of osteolytic bone disease, and current limitations in the development of naringin-containing translational therapies for common musculoskeletal conditions.

Rotational Tibio-Pelvic Constrained Hip Arthroplasty: A Surgical Technique: A Case Report.

CASE: A 25-year-old man presented with chronic bone and soft tissue infection of the right thigh following resection and radiation of epithelioid sarcoma. Multiple revisions and debridement procedures had failed to control the infection and left him unable to ambulate. We describe a modified Van Nes rotationplasty using a constrained, prosthetic hip between the tibia and pelvis following femur resection. With 18 months of follow-up, the patient was able to walk with a prosthetic device without evidence of recurrent infection. CONCLUSIONS: We report this rotationplasty as a potential approach to avoid hip disarticulation in cases requiring extensive debridement for incurable infection.