SUMMARYThe mode of regulation of Src kinases has been elucidated by crystallographic studies identifying conserved structured protein modules involved in an orderly set of intramolecular associations and ligand interactions. Despite these detailed insights, much of the complex behavior and diversity in the Src family remains unexplained. A key missing piece is the function of the unstructured N-terminal region. We report here the function of the N-terminal region in binding within a hydrophobic pocket in the kinase domain of a dimerization partner. Dimerization substantially enhances autophosphorylation and phosphorylation of selected substrates, and interfering with dimerization is disruptive to these functions. Dimerization and Y419 phosphorylation are codependent events creating a bistable switch. Given the versatility inherent in this intrinsically disordered region, its multisite phosphorylations, and its divergence within the family, the unique domain likely functions as a central signaling hub overseeing much of the activities and unique functions of Src family kinases.

Introduction: A fracture liaison service (FLS) is a coordinated system of care that streamlines osteoporosis management in the orthopaedic setting and can serve as an effective form of secondary preventative care in these patients. The present work reviews the available evidence regarding the impact of fracture liaison services on clinical outcomes. Methods: The literature was reviewed for studies reporting changes in the rates of bone mineral density scanning (DXA), antiresorptive therapy, new minimum trauma fractures, and mortality between cohorts with access to an FLS or not. Studies including intention to treat level data were retained. A Medline search for “fracture liaison” OR “secondary fracture prevention” produced 146 results, 98 were excluded based on the abstract, 38 were excluded based on full-text review. Ten level III studies encompassing 48,045 patients were included, of which 5 studies encompassing 7,086 were analyzed. Odds-ratios for DXA and anti-osteoporosis pharmacotherapy rates were calculated from data. Fixed and random effects analyses were performed using the Mantel-Haenszel method. Results: Four studies reported, on average, a 6-fold improvement in DXA scanning rates (Figure 1). Six studies reported, on average, a 3-fold improvement in antiresorptive therapy rates (Figure 2). Four large studies reported significant reductions in the rate of new fractures using time-dependent Cox proportional hazards models at 12 months (HR = 0.84, 0.95), 24 months (HR = 0.44, 0.65), and 36 months (HR = 0.67). Five large studies reported mortality improvements using time-dependent Cox proportional hazards models at 12 months (HR = 0.88, 0.84, 0.81) and 24 months (HR = 0.65, 0.67). Conclusions: The findings suggest that fracture liaison services improve rates of DXA scanning and antiresorptive therapy as well as reductions in the rates of new fractures and mortality among patients seen following minimum trauma fractures across many time points.

Background: Despite known surgical volume reductions in 2020 during the height of the COVID-19 pandemic, no study has fully quantified the impact of the pandemic on the number of elective inpatient total hip (THA) and total knee arthroplasty (TKA) cases. The purpose of the present study was to analyze THA and TKA case volumes in the United States during the COVID-19 pandemic. Methods: The Premier Healthcare Database was utilized to identify adults undergoing primary elective THA or TKA from January 2017 to December 2020. The National Inpatient Sample was cross-referenced to provide nationwide representative sampling weights. Patients undergoing revision total joint arthroplasty (TJA) or non-elective surgery were excluded. Two quantitative models were created from both databases to estimate TJA case volume in 2020. Descriptive statistics were utilized to report monthly changes in elective TJA utilization throughout 2020. Univariate analyses were performed to compare differences between subgroups. Results: From 2017 to 2019, it was estimated that 1,006,000 elective inpatient TJAs (64.2% TKA and 35.8% THA) were performed annually. In 2020, an estimated 526,000 to 538,000 cases (62.0% TKA and 38.0% THA) were performed, representing a 46.5% to 47.7% decrease in nationwide volume from the prior 3-year average. Moreover, the elective TJA case volume for April 2020 was 1.9% of the average for that month from 2017 through 2019. Subsequently, case volumes for May and June increased compared with the volumes for those months from 2017 through 2019. There was then a decrease in cases for July, corresponding with the "second wave" of COVID-19, followed by an additional steady monthly decline through December, corresponding with the "third wave." Finally, the elective TJA cases for December 2020 represented only 41.0% of the average case volume for that month from 2017 through 2019. continuedDisclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G959).

Background: Osteoporosis is often undiagnosed until patients experience fragility fractures. Pelvic fractures are common but underappreciated sentinel fractures. Screening patients with a pelvic fracture for osteoporosis may provide an opportunity to initiate appropriate treatments such as anti-osteoporosis therapy to prevent additional fractures. Methods: This retrospective cohort review examined the management of osteoporosis after pelvic fractures at a large tertiary care center without an established secondary fracture prevention program. Data were extracted from electronic medical records of all new patients with a pelvic fracture who were ≥50 years of age from this center and its affiliated community hospitals from 2008 to 2014. Outcome measures included the initiation of anti-osteoporosis therapy before the fracture, within the year following the fracture, >1 year following the fracture, or never and new osteoporotic fractures within 2 years after a pelvic fracture. Results: From 2008 to 2014, 947 patients presented with pelvic fractures. Of these patients, 27.1% (257 patients) were taking anti-osteoporosis medications before the fracture. Four percent of treatment-naïve patients began anti-osteoporosis therapy within 1 year of fracture, with 1.2% (11 patients) starting after 1 year. Of the treatment-naïve patients, 92.3% (637 patients) were never prescribed anti-osteoporosis therapy. Treatment rates were consistent over time. Within 2 years, 41.0% (388 patients) developed fragility fractures at secondary sites: 12.0% (114 patients) experienced a hip fracture, and 16.4% (155 patients) experienced a vertebral fracture. Conclusions: Osteoporosis screening and initiation of secondary fracture prevention after a pelvic fracture were inadequate in the study population. Of the patients in this study, 909 (96.0%) never underwent a dual x-ray absorptiometry (DXA) scan during the study period. Of the 690 treatment-naïve patients, 637 (92.3%) were never administered anti-osteoporosis medications. Within 2 years, 41.0% of all patients developed additional osteoporotic fractures. This study demonstrates an opportunity to improve bone health by screening for and treating osteoporosis in patients with a pelvic fragility fracture. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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Introduction: Osteoporosis is often not clinically recognized until after a fracture occurs. Individuals who have 1 fracture are at increased risk of future fractures. Prompt initiation of osteoporosis treatment following fracture is critical to reducing the rate of future fractures. Antiresorptives are the most widely used class of medications for the prevention and treatment of osteoporosis. Many providers are hesitant to initiate antiresorptives in the acute post-fracture period. Concerns include interference with bone remodeling necessary for successful fracture healing, which would cause increased rates of non-union, malunion, and refracture. While such concerns should not extend to anabolic medications, physicians may also hesitate to initiate anabolic osteoporosis therapies due to high cost and/or lack of familiarity. This article aims to briefly review the available data and present a digestible narrative summary to familiarize practicing orthopaedic surgeons with the essential details of the published research on this topic. Results: The results of 20 clinical studies and key pre-clinical studies related to the effect of anti-resorptive medications for osteoporosis on fracture healing are summarized in the body of this narrative review. Discussion & Conclusions: While few level I studies have examined the impact of timing of initiation of osteoporosis medications in the acute post-fracture period, the few that have been published do not support these concerns. Specifically, data from level I clinical trials indicate that initiating bisphosphonates as early as 2 weeks post-fracture does not increase rates of non-union or malunion. By reviewing the available data, we hope to give clinicians the confidence to initiate osteoporosis treatment promptly post-fracture.

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