Runx2 and Polycystins in Bone Mechanotransduction: Challenges for Therapeutic Opportunities.

Bone mechanotransduction is a critical process during skeletal development in embryogenesis and organogenesis. At the same time, the type and level of mechanical loading regulates bone remodeling throughout the adult life. The aberrant mechanosensing of bone cells has been implicated in the development and progression of bone loss disorders, but also in the bone-specific aspect of other clinical entities, such as the tumorigenesis of solid organs. Novel treatment options have come into sight that exploit the mechanosensitivity of osteoblasts, osteocytes, and chondrocytes to achieve efficient bone regeneration. In this regard, runt-related transcription factor 2 (Runx2) has emerged as a chief skeletal-specific molecule of differentiation, which is prominent to induction by mechanical stimuli. Polycystins represent a family of mechanosensitive proteins that interact with Runx2 in mechano-induced signaling cascades and foster the regulation of alternative effectors of mechanotransuction. In the present narrative review, we employed a PubMed search to extract the literature concerning Runx2, polycystins, and their association from 2000 to March 2024. The keywords stated below were used for the article search. We discuss recent advances regarding the implication of Runx2 and polycystins in bone remodeling and regeneration and elaborate on the targeting strategies that may potentially be applied for the treatment of patients with bone loss diseases.

Prosthetic Reconstruction of the Shoulder After Resection of Proximal Humerus Bone Tumor.

Prosthetic reconstruction after wide resection of tumors of the proximal humerus presents a unique challenge. The shoulder is a complex articulation, and patients have high expectations for postoperative function. The goal of this study is to compare functional outcomes, oncologic outcomes, and complication rates for 2 reconstructive methods. Forty patients with proximal humeral tumors were reviewed retrospectively. Proximal humeral endoprosthesis (PHE) was used for 21 patients, and reverse shoulder arthroplasty (RSA) was used for 19 patients. Clinical results, oncologic outcomes, and complication rates were assessed. The functional outcomes of the patients were assessed with the Musculoskeletal Tumor Society scoring system (MSTS), the shortened version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, and shoulder range of motion. The mean follow-up was 62±15 months. Shoulder dislocations occurred among 8 patients with PHE and 1 patient with RSA (P=.021). The other complication rates were similar for the 2 groups (P<.05). At the latest follow-up, the mean MSTS score was 68±10.3 for those with PHE and 76±7.7 for the patients with RSA (P=.72). However, the QuickDASH score was significantly better (P=.031) for those with RSA (mean, 19±6.3) compared with patients with PHE (mean, 30±4.8). Additionally, shoulder active abduction and forward flexion were significantly greater for the RSA group (P=.04 and P=.03, respectively). Five patients had local recurrence. Prosthetic reconstruction after oncologic re-section of the proximal humerus is associated with significant limitation of shoulder range of motion and a high rate of revision surgery. However, in this study, RSA was associated with fewer dislocations, improved Quick-DASH score, and greater abduction and forward flexion compared with PHE. [Orthopedics. 2022;45(6):e335-e341.].

Epithelioid Hemangioma of Bone: A Rare Vascular Neoplasm. A Case Report and Literature Review.

Epithelioid hemangioma (EH) of bone is a rare benign, albeit locally aggressive vascular neoplasm. It is usually solitary and involves the metaphysis or diaphysis of long tubular bones, especially in the lower extremities. Rarely it may present as multifocal lesions. The differential diagnosis includes malignant vascular bone tumors such as epithelioid hemangioendothelioma and epithelioid angiosarcoma. Clinical presentation and radiographic and histological findings are not specific and diagnosis is based mostly on immunohistochemical and molecular studies. There is no consensus regarding the optimal treatment. Curettage and bone grafting or en bloc resection are the current treatment options, however local recurrence have been reported. We present a case of multifocal EH of the distal tibia, distal fibula and hindfoot in a 38 year-old male managed with curettage, radiofrequency ablation and cement osteoplasty. The imaging features, histological findings and treatment options of this rare vascular tumor are discussed.

Total Talectomy and Reconstruction Using a 3-dimensional Printed Talus Prosthesis for Ewing's Sarcoma: A 3.5-Year Follow-up.

Ewing's sarcoma is extremely rare in the foot. Below the knee amputation is indicated for most primary malignant bone tumors of the hindfoot, with few cases of successful limb salvage surgery having been reported. The use of 3-dimensional printed implants may successfully address reconstruction challenges after tumor resection. The authors present a case of a 30-year-old woman with a Ewing's sarcoma of the talus who underwent total talectomy and replacement of the entire talus with a custom-made 3-dimensional printed talar prosthesis. [Orthopedics. 2019; 42(4):e405-e409.].

Total Calcaneus Resection and Reconstruction Using a 3-dimensional Printed Implant.

Considering the specific anatomic features of the foot, below-knee amputation is the treatment of choice for foot malignancies. However, advances in imaging modalities, adjuvant therapies, and improved surgical techniques have made foot salvage surgery increasingly possible. The calcaneus is an unusual location for malignant tumors, and there is limited information about foot salvage. Currently, 3-dimensional printed implants may successfully address reconstruction challenges after tumor resection. The authors present 2 patients with Ewing's sarcoma of the calcaneus who underwent total calcaneus resection and reconstruction using a custom-made 3-dimensional printed implant. [Orthopedics. 2019; 42(2):e282-e287.].

Similar 2-point discrimination and stereognosia but better locognosia at long term with an independent home-based sensory reeducation program vs no reeducation after low-median nerve transection and repair.

STUDY DESIGN: Prospective controlled study. INTRODUCTION: Previous studies evaluated the effectiveness of sensory reeducation (SR) after peripheral nerve injury and repair. However, evidence for long-term clinical usefulness of SR is inconclusive. PURPOSE OF THE STUDY: The purpose of this study is to compare the sensory results of patients with low-median nerve complete transection and microsurgical repair, with and without SR at long term. METHODS: We prospectively studied 52 consecutive patients (mean age, 36 years; range, 20-47 years) with low-median nerve complete transection and microsurgical repair. When reinnervation was considered complete with perception of vibration with a 256-cycles per second tuning fork (mean, 3.5 months after nerve injury and repair), the patients were sequentially allocated (into 2 groups [group SR, 26 patients, SR; group R, 26 patients, reassured on recovery without SR). SR was conducted in a standardized fashion, in 2 stages, as an independent home-based program: the first stage was initiated when reinnervation was considered complete, and included instruction in home exercises to identify familiar objects and papers of different roughness, and localization of light touch (eyes open and closed); the second stage was initiated when the patients experienced normal static and moving 2-point discrimination (2PD) at the index fingertip of injured hand, and included instruction in home exercises for stereognosia, supplementary exercises for localization of light touch, and identification of small objects (eyes open and closed). Exercises were prescribed for 5-10 minutes, 4 times per day. At 1.5, 3, and 6 years after nerve injury and repair, we evaluated the static and moving 2PD, stereognosia with the Moberg's pick-up test, and locognosia with the modified Marsh test. Comparison between groups and time points was done with the nonparametric analysis of variance (Kruskal-Wallis analysis of variance). RESULTS: Static and moving 2PD and stereognosia were not significantly different between groups at any study period. Locognosia was significantly better at 1.5 and 3 years in group SR; locognosia was excellent in 17 patients of group SR vs 5 patients of group R at 1.5-year follow-up and in 14 patients of group SR vs 5 patients of group R at 3-year follow-up. Locognosia was not different between the study groups at 6-year follow-up. CONCLUSION: A 2-stage home program of SR improved locognosia at 1.5 and 3 years after low-median nerve complete transection and repair without significant differences in other modalities or the 6-year follow-up of a small subsample.

Similar function and complications for patients with short versus long hip nailing for unstable pertrochanteric fractures.

PURPOSE: To compare short with long intramedullary hip nailing for elderly patients with unstable pertrochanteric fractures. METHODS: We prospectively studied 50 patients (33 women, 17 men; mean age, 80 years; range, 74-93 years) with unstable pertrochanteric fractures admitted and treated with a short (group A) or a long (group B) intramedullary hip nail from January 2013 to 2017. The patients were randomly allocated into each group according to their order of admission. The mean follow-up was 2 years (range, 1-5 years). We evaluated operative time, function, fracture healing, varus/valgus loss of reduction, and distance between the distal line of the fracture and the distal locking screw of the nail. RESULTS: Operative time was significantly shorter in group A. Function, fracture healing and varus/valgus loss of reduction was similar between the two groups. The mean distance between the distal fracture line and distal locking screw was 7.2 cm (range, 3-10 cm) in patients of group A; in all patients of group B, an appropriate nail length was chosen so that the distal locking screw was inserted at least 3 times the diameter of the bone at the distal fracture line. Complications included periprosthetic fracture (one patient of group A), and z-effect phenomenon (one patient of group B); complications rate was similar between the two groups. CONCLUSION: Short intramedullary hip nailing is associated with similar function and complications, but shorter operative time compared to long intramedullary hip nails for patients with unstable pertrochanteric fractures.

Fall Risk Assessment Metrics for Elderly Patients With Hip Fractures.

The most common surgery performed by orthopedic surgeons likely involves that for hip fractures. The incidence of hip fractures is anticipated to rise in the coming decades. Hip fractures most commonly occur in elderly women with osteoporosis after a fall from standing position. In an effort to reduce the incidence, improve the postoperative care, and accelerate the rehabilitation of hip fractures, it is important to evaluate the fall risk of these patients, as it is an objective indication of their level of physical activity. Metrics currently available for the evaluation of fall risk in the elderly vary widely, with each having been designed to assess a specific patient population. However, their applicability has often proved to be much broader than expected. This review summarizes the metrics available for fall risk assessment of elderly patients with hip fractures, describes their individual features and efficacy, and highlights those that seem to be more reliable for the assessment of rehabilitation of these patients after hip fracture surgery. [Orthopedics. 2018; 41(3):142-156.].

Epineural Sleeve Reconstruction Technique for Median Nerve Complete Transection.

In microsurgical nerve repair, the epineural sleeve technique can be used to bridge short nerve defects and to cover the coaptation site with the epineurium of the nerve stump. The epineurium serves as a mechanical aid to reduce gap size, and increase repair strength, effectively assisting nerve regeneration. This article presents a 32-year-old patient who experienced complete transection of the median nerve at the distal forearm, which was treated with the epineural sleeve graft reconstruction technique. Nerve regeneration was followed-up for 18 months and evaluated with the Rosén and Lundborg scoring system. The final outcome was excellent; at the last follow-up, the patient experienced complete sensory and motor function of the median nerve. Level of evidence: V.

Dual head screw hip nailing for trochanteric fractures.

INTRODUCTION: There are limited information and inconclusive results for dual head screw intramedullary hip nails for trochanteric fractures. Therefore, we performed a prospective study to evaluate the healing of fractures, and survival, function, and complications of patients operated with this implant. METHODS: We prospectively studied 79 patients (61 women and 18 men; mean age: 84.7 years; range: 65-96 years) with a low-energy trochanteric fracture, treated with a dual head screw intramedullary hip nail from 2013 to 2016. The mean follow-up was 2.1 years (range: 1-3 years); seven patients were lost to follow up. This left 72 patients for further analysis. We evaluated the healing of fractures, and survival, function, and complications of patients. RESULTS: Fracture healing was evident in 70 patients (97.2%) at 2-3 months postoperatively. One patient experienced cut-out and z-effect phenomenon of the head screws. Another patient experienced a periprosthetic femoral diaphysis fracture at the distal tip of the nail. A third patient experienced an acute postoperative superficial skin infection that was treated successfully with wound dressing changes and a course of antibiotics. Sixteen patients (22.2%) deceased within 12 months postoperatively. In the remaining patients, the Harris Hip Score (HHS) at 12 months postoperatively was excellent in 16 (28.6%), good in 23 (41.1%), fair in 10 (17.8%), and poor in 7 patients (12.5%). The function declined after the patients' fracture. Fair and poor results were related to age > 85 years, poor pre-fracture level of function, and AO/OTA-31-A3 fracture types. CONCLUSION: The dual head screw intramedullary hip nail is associated with high healing and low complication rates for intertrochanteric fractures. The function of the patients is good or excellent in most cases; however, it declines, especially for those patients with age > 85 years, poor pre-fracture level of function, and AO/OTA-31-A3 fracture types.

Tumors of the hand.

Tumors of the hand comprise a vast array of lesions involving skin, soft tissue and bone. The majority of tumors in the hand are benign. Malignant tumors, although rare, do occur and frequently have unique characteristics in this specific anatomic location. Careful staging, histological diagnosis and treatment are essential to optimize clinical outcome. However, straightforward most of the time, hand tumor management does have pitfalls; caution is advised, as a missed or delayed diagnosis or an improperly executed biopsy may have devastating consequences. This article reviews the clinical spectrum of the most common benign and malignant bone and soft tissue tumors of the hand and discusses the clinicopathological findings, imaging features and current concepts in treatment for these tumors.

Osteoarticular Allograft Reconstruction for an Angiosarcoma of the Distal Radius.

Angiosarcoma of bone is a rare high-grade malignant vascular tumor accounting for <1% of malignant bone tumors. Tumor location in the distal radius is very rare. Complete surgical resection with limb salvage surgery or amputation is essential for the outcome of the patient. However, the literature is vague regarding the best surgical approach for resection of the distal radius and the optimal reconstruction option after a bone tumor resection. Several reconstruction techniques have been described, varying from arthrodesis to arthroplasties. In this article, we present a report of a patient with angiosarcoma of the distal radius treated with complete resection and reconstruction with a distal radius osteoarticular allograft. We discuss the advantages and the limitations of this surgical technique for the distal radius.

Complications After Hip Nailing for Fractures.

Pertrochanteric fractures in elderly patients represent a major health issue. The available surgical options are fixation with extramedullary devices, intramedullary nailing, and arthroplasty. Intramedullary nailing for hip fractures has become more popular in recent years. Advantages of intramedullary nailing for hip fracture fixation include a more efficient load transfer due to the proximity of the implant to the medial calcar, less implant strain and shorter lever arm because of its closer positioning to the mechanical axis of the femur, significantly less soft tissue disruption and periosteal stripping of the femoral cortex, shorter operative time and hospital stay, fewer blood transfusions, better postoperative walking ability, and lower rates of leg-length discrepancy. Compromise of the posteromedial cortex and/or the lateral cortex, a subtrochanteric extension of the fracture, and a reversed obliquity fracture pattern represent signs of fracture instability, warranting the use of intramedullary nailing. However, the use of intramedullary nailing, with its unique set of clinical implications, has introduced a new set of complications. The reported complications include malalignment, cutout, infection, false drilling, wrong lag screw length and drill bit breakage during the interlocking procedure, external or internal malrotation (≥20°) of the femoral diaphysis, elongation of the femur (2 cm), impaired bone healing, periprosthetic fracture distal to the tip of the nail, fracture collapse, implant failure, lag screw intrapelvic migration, neurovascular injury, secondary varus deviation, complications after implant removal, trochanteric pain, and refracture. Many of these complications are related to technical mistakes. This article reviews intramedullary nailing for the treatment of pertrochanteric femoral fractures, with an emphasis on complications.

When and how to operate on spondylodiscitis: a report of 13 patients.

PURPOSE: Conflicting reports exist regarding the surgical indications, timing, approach, staged or not operation, and spinal instrumentation for patients with spondylodiscitis. Therefore, we performed this study to evaluate the outcome of a series of patients with spondylodiscitis aiming to answer when and how to operate on these patients. MATERIALS AND METHODS: We retrospectively studied the files of 153 patients with spondylodiscitis treated at our institution from 2002 to 2012. The approach included MR imaging of the infected spine, isolation of the pathogen with blood cultures and/or biopsy, and further conservative or surgical treatment. The mean follow-up was 6 years (range 1-13 years). We evaluated the indications, timing (when), and methods (how) for surgical treatment, and the clinical outcome of these patients. RESULTS: Orthopedic surgical treatment was necessary for 13 of the 153 patients (8.5 %). These were patients with low access to healthcare systems because of low socioeconomic status, third-country migrants, prisoners or intravenous drug use, patients in whom a bacterial isolate documentation was necessary, and patients with previous spinal operations. The most common pathogen was Mycobacterium tuberculosis. The surgical indications included deterioration of the neurological status (11 patients), need for bacterial isolate (10 patients), septicemia due to no response to antibiotics (five patients), and/or spinal instability (three patients). An anterior vertebral approach was more commonly used. Nine of the 13 patients had spinal instrumentation in the same setting. Improvement or recovery of the neurological status was observed postoperatively in all patients with preoperative neurological deficits. Postoperatively, two patients deceased from pulmonary infection and septicemia, and heart infarction. At the last follow-up, patients who were alive were asymptomatic; ten patients were neurologically intact, and one patient experienced paraparesis. Imaging showed spinal fusion, without evidence of recurrent spondylodiscitis. Complications related to the spinal instrumentation were not observed in the respective patients. CONCLUSIONS: Conservative treatment is the standard for spondylodiscitis. Physicians should be alert for Mycobacterium tuberculosis spondylitis because of the low access to healthcare systems of patients with low social and economic status. Surgical indications include obtaining tissue sample for diagnosis, occurrence or progression of neurological symptoms, failure of conservative treatment, large anterior abscesses, and very extensive disease. Thorough debridement of infected tissue and spinal stability is paramount. The anterior approach provides direct access and improved exposure to the most commonly affected part of the spine. Spinal instrumentation is generally recommended for optimum spinal stability and fusion, without any implant-related complications.

Modern Palliative Treatments for Metastatic Bone Disease: Awareness of Advantages, Disadvantages, and Guidance.

BACKGROUND: Metastatic disease is the most common malignancy of the bone. Prostate, breast, lung, kidney, and thyroid cancer account for 80% of skeletal metastases. Bone metastases are associated with significant skeletal morbidity including severe bone pain, pathologic fractures, spinal cord or nerve roots compression, and malignant hypercalcemia. These events compromise greatly the quality of life of the patients. The treatment of cancer patients with bone metastases is mostly aimed at palliation. OBJECTIVE: This article aims to present these palliative treatments for the patients with bone metastases, summarize the clinical applications, and review the techniques and results. METHODS: It gives an extensive overview of the possibilities of palliation in patients with metastatic cancer to the bone. RESULTS AND DISCUSSION: Currently, modern treatments are available for the palliative management of patients with metastatic bone disease. These include modern radiation therapy, chemotherapy, embolization, electrochemotherapy, radiofrequency ablation, and high-intensity focused ultrasound. As such it is of interest for all physicians with no experience with these developments to make palliative procedures safer and more reliable.

Rapid destructive arthritis of the hip revisited.

Rapid destructive arthritis of the hip is a rare entity with unknown pathogenesis and outcome. First described by Forestier in 1957, it is characterized by a rapidly progressive hip disease resulting in rapid destruction of both the femoral and acetabular aspects of the hip joint, with almost complete disappearance of the femoral head within a few months. Since the original description, case reports and small series have been reported, and many names have been proposed to describe the rapid destruction of the femoral head and occasionally the acetabulum. Initial presentation includes acute hip pain with the lack of radiographic evidence of joint destruction, rapidly progressing to complete vanishing of the proximal femur within a few months. This article summarizes the related literature aiming to present the current concepts for the diagnosis and treatment of rapid destructive arthritis of the hip.

State-of-the-art approach for bone sarcomas.

Bone sarcomas are a variety of non-epithelial, malignant neoplasms of bone. The most common bone sarcomas are osteosarcoma, Ewing's sarcoma, and chondrosarcoma. The approach to a patient with a suspected bone sarcoma from initial examination to the histological diagnosis and classification is staging. Staging is of critical importance, in order to classify different treatment options and point out which combination of them is more suitable depending on the severity of the tumor in every individual patient. Staging should include medical history, physical and imaging examination, and biopsy. This article presents the current approach for staging, principles of biopsy, tumor classification, treatment, and follow-up of patients with bone sarcomas.

Human dermal allograft for massive rotator cuff tears.

Previously published studies reported variable results using various suture techniques and reconstruction options for massive rotator cuff tears. Therefore, the current authors retrospectively studied 21 consecutive patients/shoulders with massive rotator cuff tears treated from January 2005 to October 2011 with a human dermal allograft through a mini-open approach. Mean patient age was 58 years (range, 33-72 years). Mean follow-up was 29 months (range, 18-52 months). Ten patients underwent revision repair for a failed rotator cuff repair. The authors measured the tendon gap (mean, 1.7 cm) and acromiohumeral interval (mean, 6.5 mm). They evaluated pain, shoulder range of motion (ROM) and function, patient satisfaction with the operation and outcome, and complications. At last follow-up, all patients experienced significant pain relief (P=.001) and improved ROM (P=.001) and American Shoulder and Elbow Surgeons (ASES) score (P=.001). Eighteen patients reported that they were satisfied or very satisfied and 3 reported that they were not satisfied with the operation and outcome. Comparison of outcomes between patients who underwent primary repair and those who underwent revision repair and between patients who had muscle atrophy and fatty infiltration grades 0 to II and those who had grades III to IV showed no statistically significant differences. A statistically significant correlation was observed between the size of the tendon gap and postoperative pain, ROM (except external rotation), and ASES score (P<.050). No significant correlation was observed between postoperative pain, ROM, and ASES score and the acromiohumeral interval (P>.050). Complications related to the dermal human allograft were not observed.

Salvage of failed total hip arthroplasty with proximal femoral replacement.

EDUCATIONAL OBJECTIVES: As a result of reading this article, physicians should be able to: 1. Identify the available types of reconstruction for failed total hip arthroplasty. 2. Summarize the preoperative workup of patients with failed total hip arthroplasty and massive proximal femoral bone loss. 3. Assess the surgical technique of proximal femoral replacement for failed total hip arthroplasty. 4. Recognize treatment complications, patient outcomes, and survival of proximal femoral megaprostheses for revision of failed total hip arthroplasty. Despite recent advances in device manufacturing and surgical techniques, the management of proximal femoral bone loss in revision total hip arthroplasty remains challenging. Currently, failed total hip arthroplasty in elderly and less active patients, nonunion of the proximal femur with multiple failed attempts at osteosynthesis, resection arthroplasty, and massive proximal femoral bone loss can be salvaged with proximal femoral replacement using a megaprosthesis. The procedure is technically demanding and requires careful preoperative planning. Instability and aseptic loosening are the major complications, especially in younger and more active patients. The new generation of modular proximal femoral replacement megaprostheses and the increased experience obtained with these surgeries have reduced complication rates and improved outcomes.

PEEK rod systems for the spine.

Traditional materials for the spine such as titanium and stainless steel have produced satisfying long-term fusion rates, mainly due to their strength and stiffness. However, although fixation with titanium rods leads to high fusion rates, increased stiffness of titanium constructs may also contribute to stress shielding and adjacent segment degeneration. Dynamic and flexible materials such as the Dynesys system allow better stress distribution to all of the spinal columns, but increase the rate of complications including screw loosening, infection, back and leg pain, and endplate vertebral fracture. Semi-rigid instrumentation systems using rods made from synthetic polymers such as the polyetheretherketone (PEEK) have been recently introduced as an alternative biomaterial for the spine. PEEK is a fully biocompatible and inert semi-crystalline thermoplastic polymer with minimal toxicity; it has a modulus of elasticity between that of cortical and cancellous bone, and significantly lower than titanium. However, there are very few clinical studies with small sample size and short-term follow-up using PEEK rod-pedicle screw spinal instrumentation systems. Additionally, their results are conflicting. To enhance the literature, this review discusses the effect of this medical for the spine and summarizes the results of the most important related series.