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BACKGROUND: Proximal humerus fractures (PHFs) are common fractures, especially in older female patients. These fractures are commonly treated surgically, but the consensus on the best treatment is still lacking. METHODS AND FINDINGS: The primary aim of this multicenter, randomized 3-arm superiority, open-label trial was to assess the results of nonoperative treatment and operative treatment either with locking plate (LP) or hemiarthroplasty (HA) of 3- and 4-part PHF with the primary outcome of Disabilities of the Arm, Shoulder, and Hand (DASH) at 2-year follow-up. Between February 2011 and December 2019, 160 patients 60 years and older with 3- and 4-part PHFs were randomly assigned in 1:1:1 fashion in block size of 10 to undergo nonoperative treatment (control) or operative intervention with LP or HA. In total, 54 patients were assigned to the nonoperative group, 52 to the LP group, and 54 to the HA group. Five patients assigned to the LP group were reassigned to the HA group perioperatively due to high comminution, and all of these patients had 4-part fractures. In the intention-to-treat analysis, there were 42 patients in the nonoperative group, 44 in the LP group, and 37 in the HA group. The outcome assessors were blinded to the study group. The mean DASH score at 2-year follow-up was 30.4 (standard error (SE) 3.25), 31.4 (SE 3.11), and 26.6 (SE 3.23) points for the nonoperative, LP, and HA groups, respectively. At 2 years, the between-group differences were 1.07 points (95% CI [-9.5,11.7]; p = 0.97) between nonoperative and LP, 3.78 points (95% CI [-7.0,14.6]; p = 0.69) between nonoperative and HA, and 4.84 points (95% CI [-5.7,15.4]; p = 0.53) between LP and HA. No significant differences in primary or secondary outcomes were seen in stratified age groups (60 to 70 years and 71 years and over). At 2 years, we found 30 complications (3/52, 5.8% in nonoperative; 22/49, 45% in LP; and 5/49, 10% in HA group, p = 0.0004) and 16 severe pain-related adverse events. Th

OBJECTIVES: To compare the recently developed Hansson Pinloc system, which features 3 cylindrical parallel pins with hooks connected through a fixed-angle interlocking plate, with the Hansson Pin System (2 hook pins) for the treatment of femoral neck fractures. DESIGN: One hundred fourteen patients with displaced femoral neck fractures and 325 patients with nondisplaced fractures from 9 orthopaedic centers were randomized to either Hansson Pinloc system or Hansson Pin System and followed for 2 years or until death. Age at inclusion was 50 years or older. MAIN OUTCOME MEASUREMENTS: The primary outcome was failure (defined as early displacement, nonunion, symptomatic avascular necrosis, or deep infection). Secondary outcomes included revision surgery, Timed Up and Go (TUG) test and patient-reported outcome measures (PROMs: EQ-5D and WOMAC). RESULTS: For nondisplaced fractures, the incidence of failure was 14% (23/169) in the Pinloc group and 16% (25/156) in the Hansson group. For displaced fractures, the analysis was stratified by age. Patients aged 50-69 years with displaced fractures showed a 2-year failure rate of 44% (17/39) in the Pinloc group versus 44% (16/36) in the Hansson group. For patients 70 years or older with displaced fractures, 33% (7/21) in the Pinloc group versus 22% (4/18) in the Hansson group failed. At 3 and 12 months, no clinically significant differences between treatment groups were found for EQ-5D-3L, WOMAC, or for the TUG in any fracture type or age group. CONCLUSIONS: There were no advantages for Pinloc in any of the studies aspects. LEVEL OF EVIDENCE: 1.

Background and purpose - Data on incidence and on trends in treatment of hamstring injuries, including proximal hamstring tendon avulsions (PHA), is limited. We aimed to investigate the incidence, trends in operative treatment, age, and sex distribution of hamstring injuries in Sweden between 2001 and 2020. Patients and methods - We obtained data recorded in the National Patient Register between 2001 and 2020 on patients between 18 and 90 years of age, with the ICD-10 code S76.3, to calculate the incidence of patients treated operatively for hamstring injuries in Sweden. Patients with the NOMESCO classification NFL49 were considered as having been treated operatively. Data on quadriceps and Achilles tendon injuries were obtained for comparison. To calculate incidences, adult population data for every year were obtained from the Statistics Sweden website. Results - The incidence of patients diagnosed with hamstring injuries increased from 2.2 to 7.3 per 100,000 person-years. There was a rising trend of surgical treatment per diagnosed case from 3.0% to 14.2%. Patients diagnosed in units with the highest experience of surgical treatment of hamstring injuries tended to be operated on more often (22.2%) than patients diagnosed in units with limited experi-ence (5.1%), although the fraction of operated patients was increasing in both groups. Conclusion - Between 2001 and 2020 there was an increase in the proportion of operatively treated hamstring injuries.

Introduction: Leg immobilisation in a cast or an orthosis after lower limb injuries is associated with a high risk of complications of venous thromboembolism (VTE) and hampered healing. Current pharmacoprophylaxes of VTE are inefficient and associated with adverse events. Intermittent pneumatic compression (IPC) could represent a novel, efficient and safe VTE-prophylactic alternative that may enhance injury healing. The aim of STOP leg clots is to assess the efficacy of adjuvant IPC-therapy on reduction of VTE incidence and improvement of healing in lower leg immobilised outpatients. Methods and analys: STOP leg clots is a multicentre randomised controlled superiority trial. Eligible patients (700 patients/arm) with either an acute ankle fracture or Achilles tendon rupture will be randomised to either addition of IPC during lower-leg immobilisation or to treatment-as-usual. The primary outcome will be the total VTE incidence, that is, symptomatic and asymptomatic deep venous thrombosis (DVT) or symptomatic pulmonary embolism (PE), during the leg immobilisation period, approximately 6-8 weeks. DVT incidence will be assessed by screening whole leg compression duplex ultrasound at removal of leg immobilisation and/or clinically diagnosed within the time of immobilisation. Symptomatic PE will be verified by CT.Secondary outcomes will include patient-reported outcome using validated questionnaires, healing evaluated by measurements of tendon callus production and changes in VTE-prophylactic mechanisms assessed by blood flow and fibrinolysis. Data analyses will be blinded and based on the intention-to-treat.

Background: The goal of treatment for a proximal hamstring avulsion (PHA) is an objectively restored muscle and a subjectively satisfied, pain-free patient at follow-up. Different self-reported and performance-based outcome measures have been used to evaluate recovery, but their validity is poorly investigated. Purpose: To investigate (1) the correlation between the commonly used self-reported outcome measurements, the Perth Hamstring Assessment Tool (PHAT) and the Lower Extremity Functional Scale (LEFS); (2) to what extent these scores can be explained by physical dysfunction as measured by performance-based tests; (3) whether performance-based tests can discriminate between the injured and uninjured extremity; and (4) which activity limitations are perceived by patients several years after the injury. Study design: Cohort study (Diagnosis); Level of evidence, 3. Methods: We included a consecutive series of patients treated for or diagnosed with PHA in our department between 2007 and 2016 having at least 2 tendons avulsed from the ischial tuberosity. Participants attended 2 study visits, answered questionnaires (PHAT, LEFS, and Patient-Specific Functional Scale [PSFS]), and performed physical performance-based tests (single-leg hop tests, single-step down test, and isometric and isokinetic strength tests). Results: A total of 50 patients were included (26 men [52%], 24 women [48%]; mean age, 50.9 years [SD, 9.8 years]). The mean follow-up time was 5.5 years (SD, 2.7 years), and 74% had been surgically treated. The correlation between PHAT and LEFS was strong (r = 0.832) and statistically significant (P < .001). Seven of the performance-based tests exhibited a statistically significant but weak correlation with LEFS (0.340-0.488) and 3 of the tests to PHAT (-0.304 to 0.406). However, only peak torque could significantly discriminate between the extremities. The activity limitation most commonly mentioned in PSFS was running (16 patients [32%]). Conclusion: Althou

Background and purpose - There are few reports on the efficiency of the Hansson Pinloc System (Pinloc) for fixation of femoral neck fractures. We compare Pinloc with the commonly used Hansson Pin System in a randomized clinical trial. The primary outcome measure is non-union or avascular necrosis within 2 years. We now report fracture failures and reoperations within the first year. Patients and methods - Between May 2014 and February 2017, 439 patients were included in the study. They were above 50 years of age and treated for a femoral neck fracture at 9 orthopedic departments in Sweden. They were randomized to either Pinloc or Hansson pins. The fractures were grouped as (a) non-displaced regardless of age, (b) displaced in patients < 70 years, or (c) >= 70 years old, but deemed unfit to undergo arthroplasty. Follow-up with radiographs and outpatient visits were at 3 and 12 months. Failure was defined as early displacement/non-union, symptomatic segmental collapse, or deep infection. Results - 1-year mortality was 11%. Of the 325 undisplaced fractures, 12% (21/169) Pinloc and 13% (20/156) Hansson pin patients had a failure during the first year. The reoperation frequencies were 10% (16/169) and 8% (13/156) respectively. For the 75 patients 50-69 years old with displaced fractures, 11/39 failures occurred in the Pinloc group and 11/36 in the Hansson group, and 8/39 versus 9/36 patients were reoperated. Among those 39 patients >= 70 years old, 7/21 failures occurred in the Pinloc group and 4/18 in the Hansson group. Reoperation frequencies were 4/21 for Pinloc and 3/18 for the Hansson pin patients. No statistically significant differences were found in any of the outcomes between the Pinloc and Hansson groups. Interpretation - We found no advantages with Pinloc regarding failure or reoperation frequencies in this 1-year follow-up.

Background Urinary tract infection (UTI) is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries (lat. Vaccinium macrocarpon Ait.) are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters. Aim To investigate whether cranberry capsules given pre- and postoperatively are useful in preventing hospital-acquired UTIs in female patients with hip fracture and urinary catheter. Design Randomised, placebo-controlled double-blind trial. Method Female patients, age 60 years and older, with hip fracture were recruited (n=227). The patients were randomised to receive cranberry (n=113) or placebo (n=114) capsules daily, from admission to the ward, until five days postoperatively. Urine cultures were obtained at admission and at five and 14 days postoperatively. In addition, EQ-5D assessments were performed and patients were screened for UTI symptoms. Result There was no difference between the groups in the proportion of patients with postoperative positive urine cultures. When excluding patients with positive cultures at admission, patients with antibiotic treatment during follow-up, and patients that did not adhere to the protocol, there was a trend towards a protective effect of cranberry treatment against hospital-acquired UTIs ; e.g. 36% (n=33) in the control group vs. 22% (n=41) in cranberry group (p=0.17) at 5 days postoperatively. Conclusion Cranberry concentrate does not seem to have an effect in preventing UTI in female patients with hip fracture and indwelling urinary catheter., The manuscript version of this article is part of the thesis "Patients with Hip Fracture: Various aspects of patient safety" http://uu.diva-portal.org/smash/record.jsf?pid=diva2:751476

Anna-Karin Gunnarsson,1 Lena Gunningberg,2 Sune Larsson,1 Kenneth B Jonsson1 1Institution of Surgical Sciences, Uppsala University, Uppsala, Sweden; 2Institution of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden Background: Urinary tract infection (UTI) is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters. Aim: The aim of this study is to investigate whether intake of cranberry juice concentrate preoperatively decreases the incidence of postoperative UTIs in hip fracture patients that received a urinary catheter. Design: This study employed a randomized, placebo-controlled double-blind trial. Method: Female patients, aged 60 years and older, with hip fracture (n=227) were randomized to receive cranberry or placebo capsules daily, from admission, until 5 days postoperatively. Urine cultures were obtained at admission, 5 and 14 days postoperatively. In addition, Euro Qual five Dimensions assessments were performed and patients were screened for UTI symptoms. Result: In the intention-to-treat analysis, there was no difference between the groups in the proportion of patients with hospital-acquired postoperative positive urine cultures at any time point. When limiting the analysis to patients that ingested at least 80% of the prescribed capsules, 13 of 33 (39%) in the placebo group and 13 of 47 (28%) in the cranberry group (P=0.270) had a positive urine culture at 5 days postoperatively. However, this difference was not statistically significant (P=0.270). Conclusion: Cranberry concentrate does not seem to effectively prevent UTIs in female patients with hip fracture and indwelling urinary

Here we addressed the potential impact of chymase, a mast-cell restricted protease, on mouse bone phenotype. We show that female mice lacking the chymase Mcpt4 acquired a persistent expansion of diaphyseal bone in comparison with wild type controls, reaching a 15% larger diaphyseal cross sectional area at 12 months of age. Mcpt4(-/-) mice also showed increased levels of a bone anabolic serum marker and higher periosteal bone formation rate. However, they were not protected from experimental osteoporosis, suggesting that chymase regulates normal bone homeostasis rather than the course of osteoporosis. Further, the absence of Mcpt4(-/-) resulted in age-dependent upregulation of numerous genes important for bone formation but no effects on osteoclast activity. In spite of the latter, Mcpt4(-/-) bones had increased cortical porosity and reduced endocortical mineralization. Mast cells were found periosteally and, notably, bone-proximal mast cells in Mcpt4(-/-) mice were degranulated to a larger extent than in wild type mice. Hence, chymase regulates degranulation of bone mast cells, which could affect the release of mast cell-derived factors influencing bone remodelling. Together, these findings reveal a functional impact of mast cell chymase on bone. Further studies exploring the possibility of using chymase inhibitors as a strategy to increase bone volume may be warranted.

Introduction: Comorbidities and polypharmacy complicate the treatment of geriatric patients with acute orthopedic injuries. A correct medication history and an updated medication list are a prerequisite for safe treatment of these debilitated patients. Published evidence suggests favorable outcomes with comanaged care. The aim of this study was to assess the accuracy of the inpatient medication lists generated at admission and investigate the efficacy of a dedicated ward-based pharmacist to find and correct mistakes in these lists. Methods: A total of 254 patients were enrolled. The ward-based pharmacist performed the assessment regarding the accuracy of the medication list generated at admission by the method of medication reconciliation. Number of discrepancies and types of discrepancy were noted. Results: The 254 patients (176 women) had a mean age of 85 years (standard deviation 7.4 years, range 42-100 years). The most common reason for orthopedic admission was hip fracture. The mean number of discrepancies was 2.1 for all patients (range 0-13). Omission of a prescribed drug was the most common mistake. Fifty-six (22%) of the 254 assessed patients had a correct medication list. Discussion: The many discrepancies in our study may have several explanations but highlight the difficulties in taking a correct medication history of patients in a stressful environment with an extremely high workload. Moreover, electronic medication lists create challenges. Implementing new electronic tools for health care requires feedback, redesign, and adaptation to meet various needs of the users. Conclusion: In conclusion, orthogeriatric patients have an unsatisfactory high number of discrepancies in their medication lists. Clinical pharmacists can accurately identify many of these mistakes.

Life history traits such as fecundity are important to evolution because they make up components of lifetime fitness. Due to their polygenic architectures, such traits are difficult to investigate with genetic mapping. Therefore, little is known about their molecular basis. One possible way toward finding the underlying genes is to map intermediary molecular phenotypes, such as gene expression traits. We set out to map candidate quantitative trait genes for egg fecundity in the chicken by combining quantitative trait locus mapping in an advanced intercross of wild by domestic chickens with expression quantitative trait locus mapping in the same birds. We measured individual egg fecundity in 232 intercross chickens in two consecutive trials, the second one aimed at measuring brooding. We found 12 loci for different aspects of egg fecundity. We then combined the genomic confidence intervals of these loci with expression quantitative trait loci from bone and hypothalamus in the same intercross. Overlaps between egg loci and expression loci, and trait-gene expression correlations identify 29 candidates from bone and five from hypothalamus. The candidate quantitative trait genes include fibroblast growth factor 1, and mitochondrial ribosomal proteins L42 and L32. In summary, we found putative quantitative trait genes for egg traits in the chicken that may have been affected by regulatory variants under chicken domestication. These represent, to the best of our knowledge, some of the first candidate genes identified by genome-wide mapping for life history traits in an avian species.

The development of biomaterial for bone regeneration requires animal models that are reliable and designed to mimic clinically relevant situations. We have previously investigated hydrogels comprised of modified hyaluronic acid and polyvinyl alcohol in models of ectopic bone formation. This hydrogel induces bone regeneration when loaded with bone morphogenetic proteins (BMPs). To allow further optimization of hydrogels, we developed a new, femoral, non-critical-sized cortical defect model. In the rat femur, we drilled standardized, elongated unilateral cortical defects that did not require stabilization and that could be created bilaterally to allow paired comparisons of biomaterials. After optimizing the defect size, subsequent stress fractures occurred in only 8% and the defect healed partially over the 40 day study period. In a time-course experiment, we treated bone defects with the previously studied hyaluronan hydrogel loaded with 10 µg hydroxyapatite and 6 µg BMP-2. The shape of the defect allowed controlled containment of the material within the defect. The defect in the right leg was left untreated, while the left defect was filled with 40 µl of the BMP hydrogel. As determined by pQCT analysis, the treated defects had a higher bone mineral content, bone area and bone density than control defects. The relative difference was greatest between the groups at 10 and 20 days and diminished as the defect healed in the untreated legs. We conclude that this animal model allows facile and rapid screening of biomaterials for bone regeneration in cortical femoral defects without requiring external fixation.

Birds have a unique bone physiology, due to the demands placed on them through egg production. In particular their medullary bone serves as a source of calcium for eggshell production during lay and undergoes continuous and rapid remodelling. We take advantage of the fact that bone traits have diverged massively during chicken domestication to map the genetic basis of bone metabolism in the chicken. We performed a quantitative trait locus (QTL) and expression QTL (eQTL) mapping study in an advanced intercross based on Red Junglefowl (the wild progenitor of the modern domestic chicken) and White Leghorn chickens. We measured femoral bone traits in 456 chickens by peripheral computerised tomography and femoral gene expression in a subset of 125 females from the cross with microarrays. This resulted in 25 loci for female bone traits, 26 loci for male bone traits and 6318 local eQTL loci. We then overlapped bone and gene expression loci, before checking for an association between gene expression and trait values to identify candidate quantitative trait genes for bone traits. A handful of our candidates have been previously associated with bone traits in mice, but our results also implicate unexpected and largely unknown genes in bone metabolism. In summary, by utilising the unique bone metabolism of an avian species, we have identified a number of candidate genes affecting bone allocation and metabolism. These findings can have ramifications not only for the understanding of bone metabolism genetics in general, but could also be used as a potential model for osteoporosis as well as revealing new aspects of vertebrate bone regulation or features that distinguish avian and mammalian bone.

Sexual selection and the ornaments that inform such choices have been extensively studied, particularly from a phenotypic perspective. Although more is being revealed about the genetic architecture of sexual ornaments, much still remains to be discovered. The comb of the chicken is one of the most widely recognized sexual ornaments, which has been shown to be correlated with both fecundity and bone allocation. In this study, we use a combination of multiple intercrosses between White Leghorn populations and wild-derived Red Junglefowl to, first, map quantitative trait loci (QTL) for bone allocation and, second, to identify expression QTL that correlate and colocalize with comb mass. These candidate quantitative genes were then assessed for potential pleiotropic effects on bone tissue and fecundity traits. We identify genes that correlate with both relative comb mass and bone traits suggesting a combination of both pleiotropy and linkage mediates gene regulatory variation in these traits.

Domestication is one of the strongest forms of short-term, directional selection. Although selection is typically only exerted on one or a few target traits, domestication can lead to numerous changes in many seemingly unrelated phenotypes. It is unknown whether such correlated responses are due to pleiotropy or linkage between separate genetic architectures. Using three separate intercrosses between wild and domestic chickens, a locus affecting comb mass (a sexual ornament in the chicken) and several fitness traits (primarily medullary bone allocation and fecundity) was identified. This locus contains two tightly-linked genes, BMP2 and HAO1, which together produce the range of pleiotropic effects seen. This study demonstrates the importance of pleiotropy (or extremely close linkage) in domestication. The nature of this pleiotropy also provides insights into how this sexual ornament could be maintained in wild populations.

Hyaluronic acid-based hydrogels are proven biocompatible materials and excellent carriers of bone morphogenetic protein-2 (BMP-2) that have been successfully tested for bone generation in vivo. Different formulations, with or without nanohydroxyapatite, have shown promise for craniofacial applications. In this study, 28 rats were used to investigate whether it is possible to achieve mandibular bone augmentation upon injection of novel hyaluronic acid-based hydrogels containing nanohydroxyapatite and different concentrations of BMP-2 (0, 5 and 150ÎŒg/ml). The biomaterials were injected subperiosteally through fine needles into the innate mandibular diastema, imitating a clinical procedure for resorbed mandibles. No incisions, flaps or sutures were necessary. After 8weeks the mandibles were evaluated by peripheral quantitative computed tomography (pQCT), micro-computed tomography (ÎŒCT), histology, immunohistochemistry and fluorochrome labelling. As a result, engineered bone was observed in all treated mandibles, with a statistically significant increase in mandibular bone volume correlated with the amount of BMP-2 loaded in the hydrogel formula. We therefore demonstrated that minimally invasive mandibular bone augmentation is possible upon injection in rats, when using the appropriate injectable scaffolds. This represents an attractive clinical alternative for oral implantology patients., Correspondence Address: Hilborn, J.; Polymer Chemistry, Department of Chemistry - Å…ngström Laboratory, Science for Life Laboratory email: hilborn@mkem.uu.se

Over the last decade, the regulation of phosphate (Pi) homeostasis has been under intense investigation. By utilizing modern biochemical and genetic tools, the pathophysiological mechanisms behind several known hereditary and acquired hypo- and hyperphosphatemic diseases have been clarified. The results of these efforts have opened new insights into the causes of Pi dysregulation and hereby also the physiological mechanisms determining Pi homeostasis. Although several potential Pi-regulating proteins have been discovered and investigated, current data strongly argues for fibroblast growth factor-23 (FGF23), a hormonal factor produced in bone, as a particularly important regulator of Pi homeostasis. In this article, we review the discovery of the FGF23 protein, as well as its biochemistry, localization of production, receptor specificity and mechanisms of action.

We evaluated the relation between serum FGF23 and bone mineral density (BMD) in a community-based cohort of elderly men. There was a weak correlation between FGF23 and BMD, which was primarily dependent on body weight. INTRODUCTION: FGF23 is a hormonal factor produced in bone and regulates serum levels of phosphate (Pi) and vitamin D. FGF23 over-expression is associated with skeletal abnormalities, including rickets/osteomalacia. The relation between FGF23 and Bone Mineral Density (BMD) in the community remains unexplored. METHODS: We employed a large, population-based cohort of 3014 Swedish men aged 69-80 years, without known renal disease. BMD was measured with dual X-ray absorptiometry (DXA) in the hip and lumbar spine. Serum intact FGF23 was analyzed with a two-site monoclonal ELISA. RESULTS: There was a weak but significant correlation between FGF23 and BMD in femoral neck (r = 0.04, p < 0.05), femoral trochanter (r = 0.05, p = 0.004), total hip (r = 0.06, p = 0.0015) and lumbar spine (r = 0.07, p = 0.0004). The correlations remained significant when adjusting for biochemical covariates (Pi, calcium, PTH, 25(OH)D and renal function). However, the association became insignificant in all regions when adjusting for established confounding variables including age, height, weight and smoking. Further analysis confirmed a significant correlation between FGF23 and body weight (r = 0.13, p < 0.0001). CONCLUSIONS: The weak correlation between FGF23 and BMD in elderly male subjects is mainly due to an association between FGF23 and body weight. Therefore, FGF23 may not play a significant role in the hormonal regulation of BMD.