Extracorporeal Shockwave Therapy Improves Outcome after Primary Anterior Cruciate Ligament Reconstruction with Hamstring Tendons.

PURPOSE: The decision regarding the timepoint of a return to sports after anterior cruciate ligament (ACL) reconstruction is complex and depends on many factors, including objectively tested physical and psychological readiness as well as biological healing. The aim of this study was to investigate the influence of repetitive extracorporeal shockwave therapy (ESWT) on return-to-sports duration, clinical results and MRI results after ACL reconstruction with hamstring tendons (HT). MATERIAL AND METHODS: In this prospective controlled study, all patients with acute ACL ruptures were treated by ACL reconstruction with HT. Patients were randomized into two groups (Group A: ESWT group; Group B: control group). Patients in the ESWT group received focused shockwave therapy 4, 5 and 6 weeks after ACL surgery. Follow-up investigations including IKDC score, Lysholm score, VAS and evaluation regarding return-to-sports timepoints that were conducted 3-, 6-, 9- and 12-months post-operation. An MRI investigation was performed 12-months post-operation and graft maturation (signal intensity ratio (SIR)) as well as femoral and tibial tunnel characteristics (bone marrow oedema, tunnel fluid effusion) were assessed. RESULTS: In total, 65 patients (27.65 ± 7.07 years; 35 male/30 female) were included in this study. The mean timepoint for "return-to-pivoting-sports" was 27.92 weeks (±2.99) in the ESWT group as well as 42.64 weeks (±5.18) in the control group (p < 0.001). In the ESWT group 31 patients (vs. CONTROL GROUP: n = 6) attained the "pre-injury activity level", whereas 6 patients (vs. CONTROL GROUP: n = 22) did not reach this level within 12 months post-operation. The IKDC score, Lysholm score, and VAS showed significant improvement in the ESWT group compared with the control group for all time-points (p < 0.001). The mean SIR in the ESWT group revealed 1.81 (±0.88), whereas the control group showed a mean SIR of 2.68 (±1.04) (p < 0.01). DISCUSSION: In conclusion, this is the first study investigating the effect of repetitive ESWT on ACL reconstruction with clinical outcome measurements, including the duration of return-to-sports activity and an MRI follow-up examination. Return-to-sports parameters, clinical scores and graft maturation were significantly improved in the ESWT group. This study may support an earlier return-to-sports timepoint by ESWT and is of high clinical relevance as ESWT is a cost-effective treatment option with no relevant side effects.

Combined press-fit and extracortical fixation in patellar tendon anterior cruciate ligament reconstruction results in reliable graft fixation and early bone block incorporation.

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction with bone-patellar-tendon-bone (BPTB) autograft has the potential biological advantage of direct bone-to-bone healing over soft tissue grafts. The primary aim of this study was to investigate possible graft slippage and therefore fixation strength in a modified BPTB autograft technique with suspensory fixation on both sides for primary ACL reconstruction until bony integration takes place. METHODS: Twenty-one patients undergoing primary ACL reconstruction with a modified BPTB autograft (bone-on-bone (BOB) technique) between August 2017 and August 2019 were included in this prospective study. A computed tomography (CT) scan of the affected knee was performed directly postoperatively, as well as 3 months postoperatively. Examiner-blinded parameters for graft slippage, early tunnel widening, bony incorporation, as well as remodeling of the autologous refilled patellar harvest site were investigated. RESULTS: A series of 21 patients treated with a BPTB autograft with this technique underwent two CT investigations. Comparison of CT scans showed no bone block displacement and therefore no graft slippage in the patient cohort. Only one patient showed signs of early tunnel enlargement. Radiological bone block incorporation took place showing bony bridging of the graft to the tunnel wall in 90% of all patients. Furthermore, 90% showed less than 1 mm bone resorption of the refilled harvest site at the patella. CONCLUSIONS: Our findings suggest graft fixation stability and reliability of anatomic BPTB ACL reconstruction with a combined press-fit and suspensory fixation technique by absence of graft slippage within the first 3 months postoperatively.

Anterior Cruciate Ligament Reconstruction Using a Fascia Lata Graft With FiberTape Augmentation.

Reconstruction of the anterior cruciate ligament (ACL) is one of the most popular orthopedic surgical procedures. To date, numerous studies are available focusing on different reconstruction techniques using established autografts, such as hamstrings, bone patellar-tendon bone (BPTB), quadriceps tendon, or allograft tendons. In the present article, we describe a minimally invasive ACL reconstruction technique using a fascia lata autograft in combination with FiberTape (Arthrex, Naples, FL) augmentation using the TightRope II (Arthrex). The minimally invasive harvesting procedure is performed by using the new QuadPro Tendon Harvester (Arthrex). This technique is recommended for acute and chronic complete ACL ruptures or bundle ruptures in athletes or patients with high physical activity. The technique might allow early full weight bearing due to less donor site morbidity, early free range of motion, and early active rehabilitation due to the use of FiberTape as a augmentation device to reinforce the autograft. Clinical studies are necessary to prove the principle.

Arthroscopy with Lipoaspirate and Plasma Infiltration Using Adipose-Derived Stem Cells Plus Platelet-Rich Plasma: Harvesting and Injection for Arthroscopic Treatment of Cartilage Defects of the Knee.

Osteoarthritis, predominantly of the knee, is a highly prevalent disease leading to pain, reduced quality of life, and significantly reduced ability to work. With autologous orthobiologic options, new regenerative treatment methods have emerged, offering an alternative to early surgical intervention. Supercharged Liparthroplasty combines arthroscopy with lipoaspirate and plasma infiltration of the joint. Lipoaspirate contains high levels of adipose-derived stem cells, which show chondroprotective and anti-inflammatory qualities. Intra-articular injection, combined with platelet-rich plasma administration for accelerated cartilage metabolism, thus provides an optional approach in osteoarthritis treatment. This article aims to provide in detail our regimen for Supercharged Liparthroplasty, including tissue harvesting and preparation of the injectables, therefore enabling physicians to adopt this point-of-care technique.

Muscle-Specific Micro-Ribonucleic Acids miR-1-3p, miR-133a-3p, and miR-133b Reflect Muscle Regeneration After Single-Dose Zoledronic Acid Following Rotator Cuff Repair in a Rodent Chronic Defect Model.

BACKGROUND: Zoledronic acid improves bone microarchitecture and biomechanical properties after chronic rotator cuff repair (RCR) in rats. Besides the positive effects of zoledronic acid on bone mineral density and bone microarchitecture, bisphosphonates have positive effects on skeletal muscle function. PURPOSES/HYPOTHESIS: The purposes of this study were to (1) longitudinally evaluate circulating bone- and muscle-specific serum micro-ribonucleic acids (miRNAs) and (2) investigate supraspinatus muscle tissue after tenotomy and delayed RCR in a rat model. It was hypothesized that zoledronic acid would improve muscle regeneration after chronic RCR in rats. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 34 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy (time point 1) with delayed transosseous RCR after 3 weeks (time point 2). All rats were sacrificed 8 weeks after RCR (time point 3). Animals were randomly assigned to 2 groups. One day after RCR, the control group was given 1 mL of subcutaneous saline solution, and the intervention group was treated with a subcutaneous single-dose of 100 µg/kg body weight of zoledronic acid. All 34 study animals underwent miRNA analysis at all 3 time points. In 4 animals of each group, histological analyses as well as gene expression analyses were conducted. RESULTS: Circulating miRNAs showed significantly different expressions between both study groups. In the control group, a significant downregulation was observed for muscle-specific miR-1-3p (P = .004), miR-133a-3p (P < .001), and miR-133b (P < .001). Histological analyses showed significantly higher rates of regenerating myofibers on the operated side (left) of both study groups compared with the nonoperated side (right; P = .002). On the nonoperated side, significantly higher rates of regenerating myofibers were observed in the intervention group compared with the control group (P = .031). The myofiber cross-sectional area revealed significantly smaller myofibers on both sides within the intervention group compared with both sides of the control group (P < .001). Within the intervention group, significantly higher expression levels of muscle development/regeneration marker genes embryonal Myosin heavy chain (P = .017) and neonatal Myosin heavy chain (P = .016) were observed on the nonoperated side compared with the operated side. CONCLUSION: An adjuvant single-dose of zoledronic acid after RCR in a chronic defect model in rats led to significant differences in bone- and muscle-specific miRNA levels. Therefore, miR-1-3p, miR-133a-3p, and miR-133b might be used as biomarkers for muscle regeneration after RCR. CLINICAL RELEVANCE: Adjuvant treatment with zoledronic acid may improve muscle regeneration after chronic RCR in humans, thus counteracting fatty muscle infiltration and atrophy.

Improved biomechanics in experimental chronic rotator cuff repair after shockwaves is not reflected by bone microarchitecture.

PURPOSE: The aim of this study was to investigate the effect of extracorporeal shockwave therapy (ESWT) on bone microstructure as well as the bone-tendon-interface and the musculo-tendinous transition zone to explain the previously shown improved biomechanics in a degenerative rotator cuff tear animal model. This study hypothesized that biomechanical improvements related to ESWT are a result of improved bone microstructure and muscle tendon properties. METHODS: In this controlled laboratory study unilateral supraspinatus (SSP) tendon detachment was performed in 48 male Sprague-Dawley rats. After a degeneration period of three weeks, SSP tendon was reconstructed transosseously. Rats were randomly assigned into three groups (n = 16 per group): control (noSW); intraoperative shockwave treatment (IntraSW); intra- and postoperative shockwave treatment (IntraPostSW). Eight weeks after SSP repair, all rats were sacrificed and underwent bone microstructure analysis as well as histological and immunohistochemical analyses. RESULTS: With exception of cortical porosity at the tendon area, bone microstructure analyses revealed no significant differences between the three study groups regarding cortical and trabecular bone parameters. Cortical Porosity at the Tendon Area was lowest in the IntraPostSW (p≤0.05) group. Histological analyses showed well-regenerated muscle and tendon structures in all groups. Immunohistochemistry detected augmented angiogenesis at the musculo-tendinous transition zone in both shockwave groups indicated by CD31 positive stained blood vessels. CONCLUSION: In conclusion, bone microarchitecture changes are not responsible for previously described improved biomechanical results after shockwave treatment in rotator cuff repair in rodents. Immunohistochemical analysis showed neovascularization at the musculo-tendinous transition zone within ESWT-treated animals. Further studies focusing on neovascularization at the musculo-tendinous transition zone are necessary to explain the enhanced biomechanical and functional properties observed previously. CLINICAL RELEVANCE: In patients treated with a double-row SSP tendon repair, an improvement in healing through ESWT, especially in this area, could prevent a failure of the medial row, which is considered a constantly observed tear pattern.

High-energy extracorporeal shockwave therapy in humeral delayed and non-unions.

INTRODUCTION: Within the last few decades, focused high-energy extracorporeal shockwave therapy (ESWT) has proven to be an effective alternative to standard of care revision surgery in delayed healing fractures or manifest non-unions in various anatomical regions. MATERIALS AND METHODS: A retrospective multi-variant analysis of an open prospective, single-armed clinical study was conducted. Patients receiving focused high-energy ESWT for a delayed healing or an apparent non-union of a humeral fracture between January 1999 and December 2015 at a single trauma center were included in the study. Bony healing was defined as cortical continuity in three of four cortices and pain-free force loading and evaluated using CT scans and clinical examination at three- and six-month follow-ups after ESWT. RESULTS: A total of 236 patients were included. N = 93 (43.8%) showed bony consolidation three months after ESWT and n = 105 (52.5%) after six months. Sub-group analysis showed significantly better healing for the proximal metaphyseal humerus (66.7% after six months, n = 42) compared to the diaphyseal region (48.1%, n = 133) and distal metaphyseal humerus (48.1%, n = 25). Regression analysis indicated significantly increased healing rates for patients of younger ages (p = 0.001) and a fracture diastasis of less than 5 mm (p = 0.002). CONCLUSION: The findings of this study indicate that ESWT can be considered as a treatment option for a well-selected patient population despite the lower healing rates compared to other anatomical regions.

Lugol's solution but not formaldehyde affects bone microstructure and bone mineral density parameters at the insertion site of the rotator cuff in rats.

BACKGROUND: This study aimed to investigate whether rodent shoulder specimens fixed in formaldehyde for histological and histomorphometric investigations and specimens stained using Lugol's solution for soft tissue visualization by micro-computed tomography (microCT) are still eligible to be used for bone architecture analysis by microCT. METHODS: In this controlled laboratory study, 11 male Sprague-Dawley rats were used. After sacrifice and exarticulation both shoulders of healthy rats were assigned into three groups: (A) control group (n = 2); (B) formaldehyde group (n = 4); (C) Lugol group (n = 5). Half of the specimens of groups B and C were placed in a 4% buffered formaldehyde or Lugol's solution for 24 h, whereas the contralateral sides and all specimens of group A were stored without any additives. MicroCT of both sides performed in all specimens focused on bone mineral density (BMD) and bone microstructure parameters. RESULTS: BMD measurements revealed higher values in specimens after placement in Lugol's solution (p < 0.05). Bone microstructure analyses showed increased BV/TV and Tb.Th values in group C (p < 0.05). Specimens of group C resulted in clearly decreased Tb.Sp values (p < 0.05) in comparison to the control group. Formaldehyde fixation showed minimally altered BMD and bone microstructure measurements without reaching any significance. CONCLUSIONS: MicroCT scans of bone structures are recommended to be conducted natively and immediately after euthanizing rats. MicroCT scans of formaldehyde-fixed specimens must be performed with caution due to a possible slight shift of absolute values of BMD and bone microstructure. Bone analysis of specimens stained by Lugol's solution cannot be recommended.

The role of shockwaves in the enhancement of bone repair - from basic principles to clinical application.

Extracorporeal shockwave therapy is a treatment modality, originally introduced into the clinic as lithotripsie, which has also been successfully used in the last two decades in the non-invasive treatment of delayed or non-healing fractures. Initially, the mechanism of action was attributed to microfracture-induced repair, but intensive basic research has now shown that the shockwave generates its effect in tissue via mechanotransduction. Numerous signal transduction pathways have already been demonstrated, which in their entirety trigger an endogenous regeneration process via cell proliferation, migration and differentiation. Clinically, these shockwave-conveyed biological signals support healing of acute, delayed and non-union fractures. The attainable outcome is comparable to surgery but avoiding an open approach with associated potential complications. These advantageous properties with a clearly positive cost-benefit ratio make shockwave therapy a first line treatment in delayed and non-union fractures.

Longitudinal Changes of Circulating miRNAs During Bisphosphonate and Teriparatide Treatment in an Animal Model of Postmenopausal Osteoporosis.

MicroRNAs regulate bone homeostasis, and circulating microRNAs have been proposed as novel bone biomarkers. The effect of anti-osteoporotic treatment on circulating microRNAs has not been described in detail. Therefore, we performed a comprehensive analysis of microRNA serum levels in ovariectomized (OVX) and sham-operated (SHAM) rats over 12 weeks of antiresorptive or osteoanabolic treatment. Forty-two Sprague Dawley rats underwent SHAM surgery (n = 10) or ovariectomy (n = 32). After 8 weeks, OVX rats were randomized to antiresorptive treatment with zoledronate (n = 11), osteoanabolic treatment with teriparatide (n = 11), or vehicle treatment (n = 10). Serum samples were collected at weeks 8, 12, 16, and 20 after surgery. A total of 91 microRNAs were analyzed by RT-qPCR in serum samples collected at week 20. Based on the results, 29 microRNAs were selected for longitudinal analysis at all four study time points. Changes in bone mineral density and microstructure were followed up by in vivo micro-CT and ex vivo nano-CT. Ovariectomy resulted in the loss of trabecular bone, which was reversed by osteoanabolic and antiresorptive treatment. Differential expression analysis identified 11 circulating miRNAs that were significantly regulated after treatment. For example, miR-107 and miR-31-5p increased in vehicle-treated OVX animals, whereas they decreased during teriparatide treatment. Additional miRNAs were identified that showed significant correlations to bone microstructure or bone miRNA expression, including miR-203a-3p, which exhibited a significant negative correlation to vertebral and tibial trabecular bone volume fraction (%). Longitudinal analysis confirmed eight microRNAs with significant changes in serum over time that were prevented by teriparatide and zoledronate treatment (miR-34a-5p, miR-31-5p, miR-30d-3p, miR-378a-5p) or teriparatide treatment only (miR-375-3p, miR-183-5p, miR-203a-3p, miR-203b-3p). Gene target network analysis identified WNT and Notch signaling as the main signaling pathways controlled by these miRNAs. Thus, ovariectomy results in time-dependent deregulation of circulating miRNAs compared with SHAM animals. Anti-osteoporotic treatments can rescue this effect, showing that bone-related miRNAs might act as novel biomarkers for treatment monitoring. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Surgery improves the clinical and radiological outcome in Rockwood type IV dislocations, whereas Rockwood type III dislocations benefit from conservative treatment.

PURPOSE: Despite the available classifications, diagnostics and treatment of acute acromioclavicular joint (ACJ) injuries are still vague and challenging for trauma and shoulder surgeons. This study aimed to evaluate the dynamic radiographic as well as clinical outcome of operatively and conservatively treated Rockwood (RW) type III and IV ACJ dislocations. MATERIALS AND METHODS: All patients with RW type III and IV ACJ dislocations between 2009 and 2016 (n = 226) were included in this retrospective data analysis with a prospective follow-up examination. According to their injury classification, patients were subdivided in an operative and conservative treatment group. Examiner blinded clinical evaluation including the constant score (CS), American shoulder and elbow surgery (ASES) score, the acromioclavicular joint instability (ACJI) score, visual analog scale (VAS), bilateral force measurements, and posttraumatic/postsurgical sequelae were assessed. Fluoroscopic evaluations including dynamic stability assessment with functional axillary views were performed for every patient. RESULTS: For follow-up examination (mean 4.8 years ± 0.3 SEM) 56 patients (29 RW type III, 27 RW type IV) were available. In patients with RW type III ACJ dislocations [operative (n = 10); conservative (n = 19)] prolonged duration of treatment was seen in operatively treated patients (p < 0.05). Clear improvement could be shown for the ACJI score (p < 0.05) and coracoclavicular (CC) and acromioclavicular (AC) distance (p < 0.05) in the operative group. In patients with RW type IV ACJ dislocations [operative (n = 18); conservative (n = 9)] superior clinical results were found in operated patients with highly significant differences for the ACJI score (p < 0.001). Radiographic dynamic horizontal analysis showed nearly normalized anteroposterior translation in operated patients (p < 0.05). No differences were found regarding arthroscopic or open procedures. CONCLUSION: Accurate diagnostics including sufficient dynamic stability assessment with functional axillary views are strongly advised for patients with ACJ dislocations. Conservative treatment should be recommended for patients with RW type III ACJ dislocations, due to shorter duration of treatment with good clinical results but lacking operative risks. In patients with RW type IV ACJ dislocations, surgical treatment is recommended because of superior clinical and radiological results. LEVEL OF EVIDENCE: Level III.

Zoledronic Acid Substantially Improves Bone Microarchitecture and Biomechanical Properties After Rotator Cuff Repair in a Rodent Chronic Defect Model.

BACKGROUND: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. HYPOTHESIS: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro-computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted. RESULTS: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head (P = .005) and the medial humeral head (P = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head (P = .004) and the medial humeral head (P = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group (P < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group (r = 0.69; P = .026). Histological assessment revealed increased bone formation in the intervention group. CONCLUSION: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats. CLINICAL RELEVANCE: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations.

Bone-on-Bone Anatomic Patellar Tendon Graft Anterior Cruciate Ligament Reconstruction: A Reproducible Technique Combining Press-Fit and Extracortical Fixation.

Scientific interest in optimizing outcomes after anterior cruciate ligament (ACL) reconstruction is ongoing, and some recent developments have focused on graft shape as one of the most important factors of anatomic graft placement. The double-bundle or fanlike structure of the native ACL seems to more closely restore normal function and control of rotational stability of the knee with implant-free or press-fit techniques, creating a favorable situation in terms of direct graft-tunnel healing. The ACL reconstruction technique presented in this article enables safe, reproducible, and anatomic fixation of the patellar tendon autograft, providing the biological and biomechanical benefits of direct bony integration of the ribbonlike bone-patellar tendon-bone graft. Because press-fit fixation represents a technically challenging surgical procedure, the goal of the described technique is to enable direct bone-to-bone healing by using secondary extracortical femoral and tibial fixation without the need for a true press-fit situation. Safe and anatomic femoral tunnel drilling is achieved with an outside-in technique (retrograde drilling), hence providing advantages in the routine clinical setting in terms of applicability and time effort. To reduce donor-site morbidity caused by bone block harvesting, refilling of the harvest sites with autologous material is performed.

Correction to: Serum levels of sclerostin reflect altered bone microarchitecture in patients with hepatic cirrhosis.

Correction to: Wien Klin Wochenschr 2019 https://doi.org/10.1007/s00508-019-01595-8 The original version of this article unfortunately contained a mistake. The last sentence should read: Patients with ALD had significantly lower sclerostin levels, compared to controls. The authors apologize for the ….

Serum levels of sclerostin reflect altered bone microarchitecture in patients with hepatic cirrhosis.

BACKGROUND: Patients with hepatic cirrhosis are at increased risk of bone loss. Recent work on areal bone mineral density has reported contradictory findings. As the assessment of bone microarchitecture is complex, a search was made for correlations with new serum markers of bone turnover. Current data on serum sclerostin levels in patients with increased fracture risk are divergent and to date only one study has examined patients with hepatic cirrhosis. Therefore, the aim of this study was to evaluate serum sclerostin levels and to test for correlations with microarchitecture. METHODS: This study was performed in 32 patients with recently diagnosed hepatic cirrhosis and 32 controls. The parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. Sclerostin was detected via a new ELISA that detects the active receptor interaction site at loop 2 of the sclerostin core region. RESULTS: Sclerostin levels were slightly, but not significantly lower in the patient group, compared to controls. In contrast, patients with alcoholic liver cirrhosis had significantly lower levels than the controls. A significant correlation with areal bone mineral density (BMD) and trabecular microarchitecture was observed in the patient group. However, there was hardly any correlation between sclerostin and bone microarchitecture in the controls. CONCLUSION: In hepatic cirrhosis, sclerostin is related to altered bone microarchitecture and lower areal BMD. In alcoholic liver disease, low sclerostin concentrations were seen.

Fracture patterns in patients with multiple fractures: the probability of multiple fractures and the most frequently associated regions.

INTRODUCTION: Multiple fractures are of high clinical relevance, as a significant increase in mortality rate has been described. The purpose of this study was to evaluate differences in age and gender distribution in multiple fractures dependent on severity of trauma. Furthermore, affected anatomic regions and frequently associated fracture regions were investigated. METHODS: Patients who had sustained multiple fractures between 2000 and 2012 were included in this study. At hospital admission, patients were divided according to trauma severity (high- vs low-traumatic), gender, and age for demographic analysis. Fractures were grouped in anatomical regions, and multiple fracture event probabilities as well as frequently associated regions were calculated. RESULTS: In total, 25,043 patients at an age range of 0-100 years (5.8% of all fracture patients; 14,769 male and 10,274 female patients) who sustained 57,862 multiple fractures were included. The lumbar/thoracic spine, cervical spine, femoral shaft, skull, and pelvis showed a probability of more than 40% of the presence of further fractures in each high-traumatic fracture event. In high-traumatic fracture events, male patients were more affected (p < 0.001). Considering low-traumatic fractures, female patients had a significantly higher proportion (p < 0.001) of multiple fractures among all fractures than male patients. CONCLUSIONS: As a novelty, gender as well as age distributions in multiple fracture patients and a probability statement with the most affected anatomic regions, the risk of presence of further fractures for every region, and the frequently associated fracture regions including the percentage of occurrence are provided. These aspects yield new opportunities for clinical work and may reduce the high rate of overlooked fractures stated in the literature.

Bone Stress Injuries Are Associated With Differences in Bone Microarchitecture in Male Professional Soldiers.

Bone stress injuries are commonly due to repetitive loading, as often described in competitive athletes or military recruits. The underlying pathophysiology of bone stress injuries is multifactorial. The present cross-sectional study investigated (i) cortical and trabecular bone microstructure as well as volumetric bone mineral density in subjects with bone stress injuries at the tibial diaphysis, measured at the distal tibia and the distal radius by means of high-resolution peripheral quantitative computed tomography (CT), (ii) areal bone mineral density using dual-energy X-ray absorptiometry as well as calcaneal dual X-ray absorptiometry and laser, and (iii) the influence on bone turnover markers of formation and resorption at the early phase after injury. A total of 26 Caucasian male professional soldiers with post-training bone stress injury at the tibial diaphysis were included (case group). A total of 50 male, Caucasian professional soldiers from the same military institution served as controls (control group). High-resolution peripheral quantitative CT revealed a higher total area at the radius within the case group. Cortical bone mineral density was reduced at the radius and tibia within the case group. The trabecular number and trabecular thickness were reduced at the tibia in the case group. The trabecular network was more inhomogeneous at the radius and tibia within the case group. Calcaneal dual X-ray absorptiometry and laser was significantly reduced in the case group. This study quantified differences in bone microstructure among otherwise healthy individuals. Differences in bone microarchitecture may impair the biomechanical properties by increasing the susceptibility to sustain bone stress injuries. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2516-2523, 2019.

Substantial Biomechanical Improvement by Extracorporeal Shockwave Therapy After Surgical Repair of Rodent Chronic Rotator Cuff Tears.

BACKGROUND: Characteristics of chronic rotator cuff tears include continuous loss of tendon structure as well as tendon elasticity, followed by a high failure rate after surgical reconstruction. Several studies have already shown the beneficial effect of extracorporeal shockwave therapy (ESWT) on tissue regeneration in tendon pathologies. HYPOTHESIS: ESWT improves biomechanical tendon properties as well as functional shoulder outcomes in chronic rotator cuff reconstruction in rodents. STUDY DESIGN: Controlled laboratory study. METHODS: After tendon detachment and 3 weeks of degeneration, a subsequent transosseous reattachment of the supraspinatus tendon was performed in 48 adult male Sprague-Dawley rats (n = 16 per group). Rodents were randomly assigned to 3 study groups: no ESWT/control group, intraoperative ESWT (IntraESWT), and intra- and postoperative ESWT (IntraPostESWT). Shoulder joint function, as determined by gait analysis, was assessed repeatedly during the observation period. Eight weeks after tendon reconstruction, the rats were euthanized, and biomechanical and gene expression analyses were performed. RESULTS: Macroscopically, all repairs were intact at the time of euthanasia, with no ruptures detectable. Biomechanical analyses showed significantly improved load-to-failure testing results in both ESWT groups in comparison with the control group (control, 0.629; IntraESWT, 1.102; IntraPostESWT, 0.924; IntraESWT vs control, P≤ .001; IntraPostESWT vs control, P≤ .05). Furthermore, functional gait analyses showed a significant enhancement in intensity measurements for the IntraPostESWT group in comparison with the control group (P≤ .05). Gene expression analysis revealed no significant differences among the 3 groups. CONCLUSION: Clearly improved biomechanical results were shown in the single-application and repetitive ESWT groups. Furthermore, functional evaluation showed significantly improved intensity measurements for the repetitive ESWT group. CLINICAL RELEVANCE: This study underpins a new additional treatment possibility to prevent healing failure. Improved biomechanical stability and functionality may enable faster remobilization as well as an accelerated return to work and sports activities. Furthermore, as shockwave therapy is a noninvasive, easy-to-perform, cost-effective treatment tool with no undesired side effects, this study is of high clinical relevance in orthopaedic surgery. Based on these study results, a clinical study has already been initiated to clinically confirm the improved functionality by ESWT.

Bone-related Circulating MicroRNAs miR-29b-3p, miR-550a-3p, and miR-324-3p and their Association to Bone Microstructure and Histomorphometry.

The assessment of bone quality and the prediction of fracture risk in idiopathic osteoporosis (IOP) are complex prospects as bone mineral density (BMD) and bone turnover markers (BTM) do not indicate fracture-risk. MicroRNAs (miRNAs) are promising new biomarkers for bone diseases, but the current understanding of the biological information contained in the variability of miRNAs is limited. Here, we investigated the association between serum-levels of 19 miRNA biomarkers of idiopathic osteoporosis to bone microstructure and bone histomorphometry based upon bone biopsies and µCT (9.3 µm) scans from 36 patients. Four miRNAs were found to be correlated to bone microarchitecture and seven miRNAs to dynamic histomorphometry (p < 0.05). Three miRNAs, namely, miR-29b-3p, miR-324-3p, and miR-550a-3p showed significant correlations to histomorphometric parameters of bone formation as well as microstructure parameters. miR-29b-3p and miR-324-p were found to be reduced in patients undergoing anti-resorptive therapy. This is the first study to report that serum levels of bone-related miRNAs might be surrogates of dynamic histomorphometry and potentially reveal changes in bone microstructure. Although these findings enhance the potential value of circulating miRNAs as bone biomarkers, further experimental studies are required to qualify the clinical utility of miRNAs to reflect dynamic changes in bone formation and microstructure.