Small interfering RNAs in the management of human osteoporosis.

BACKGROUND: Osteoporosis results in reduced bone mass and consequent bone fragility. Small interfering RNAs (siRNAs) can be used for therapeutic purposes, as molecular targets or as useful markers to test new therapies. SOURCES OF DATA: A systematic search of different databases to May 2023 was performed to define the role of siRNAs in osteoporosis therapy. Fourteen suitable studies were identified. AREAS OF AGREEMENT: SiRNAs may be useful in studying metabolic processes in osteoporosis and identify possible therapeutic targets for novel drug therapies. AREAS OF CONTROVERSY: The metabolic processes of osteoporosis are regulated by many genes and cytokines that can be targeted by siRNAs. However, it is not easy to predict whether the in vitro responses of the studied siRNAs and drugs are applicable in vivo. GROWING POINTS: Metabolic processes can be affected by the effect of gene dysregulation mediated by siRNAs on various growth factors. AREAS TIMELY FOR DEVELOPING RESEARCH: Despite the predictability of pharmacological response of siRNA in vitro, similar responses cannot be expected in vivo.

Synthetic graft for medial patellofemoral ligament reconstruction: a systematic review.

BACKGROUND: This systematic review investigates the role of synthetic graft for primary medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent patellofemoral instability, focusing on clinical scores and the rate of complications. METHODS: This systematic review was conducted according to the PRISMA statement. The main online databases were accessed in January 2022 without time constraints. All clinical studies investigating the use of synthetic grafts for MPFL reconstruction were accessed. Revision settings were not considered. Only articles reporting data on patients with recurrent patellofemoral instability were eligible. Studies regarding congenital or acute patellofemoral dislocation were excluded. Only studies performing a follow-up longer than 24 months were considered. RESULTS: Data on 199 patients [mean age 22.3 (range 19.0-28.0) years] were collected. The mean follow-up was 60.5 (39.0-142.8) months. All the scores of interest improved at last follow-up: Kujala (+ 24.8; P = 0.0002), Lysholm (+ 42.0; P = 0.02), Tegner (+ 1.2; P = 0.03), IKDC (+ 20.9; P = 0.02). Post-operatively, a positive apprehension test was detected in 6.1% (7/115) of patients, and a sensation of instability was reported by 1.5% (3/199) of patients. The rate of re-dislocations was 2.5% (5 of 199 patients), and revision procedures were performed in less than 1% (1 of 199) of patients. CONCLUSION: Synthetic graft may be reliable and feasible for primary MPFL reconstruction in patients with recurrent patellofemoral instability.

Fragility Fractures: Risk Factors and Management in the Elderly.

Given the progressive ageing of Western populations, the fragility fractures market has a growing socioeconomic impact. Fragility fractures are common in the elderly, negatively impacting their quality of life, limiting autonomy, increasing disability, and decreasing life expectancy. Different causes contribute to the development of a fractures in frail individuals. Among all, targeting fragile patients before the development of a fracture may represent the greatest challenge, and current diagnostic tools suffer from limitations. This study summarizes the current evidence on the management of fragility fractures, discussing risk factors, prevention, diagnosis, and actual limitations of the clinical therapeutic options, putting forward new ideas for further scientific investigation.

Arthroscopy versus mini-arthrotomy approach for matrix-induced autologous chondrocyte implantation in the knee: a systematic review.

BACKGROUND: Matrix-induced autologous chondrocyte implantation (mACI) can be performed in a full arthroscopic or mini-open fashion. A systematic review was conducted to investigate whether arthroscopy provides better surgical outcomes compared with the mini-open approach for mACI in the knee at midterm follow-up. METHODS: This systematic review was conducted following the PRISMA guidelines. The literature search was performed in May 2021. All the prospective studies reporting outcomes after mACI chondral defects of the knee were accessed. Only studies that clearly stated the surgical approach (arthroscopic or mini-open) were included. Only studies reporting a follow-up longer than 12 months were eligible. Studies reporting data from combined surgeries were not eligible, nor were those combining mACI with less committed cells (e.g., mesenchymal stem cells). RESULTS: Sixteen studies were included, and 770 patients were retrieved: 421 in the arthroscopy group, 349 in the mini-open. The mean follow-up was 44.3 (12-60) months. No difference between the two groups was found in terms of mean duration of symptoms, age, body mass index (BMI), gender, defect size (P > 0.1). No difference was found in terms of Tegner Score (P = 0.3), Lysholm Score (P = 0.2), and International Knee Documentation Committee (IKDC) Score (P = 0.1). No difference was found in the rate of failures (P = 0.2) and revisions (P = 0.06). CONCLUSION: Arthroscopy and mini-arthrotomy approaches for mACI in knee achieve similar outcomes at midterm follow-up. LEVEL OF EVIDENCE: II, systematic review of prospective studies.

Achilles tendinopathy.

BACKGROUND: Achilles Tendinopathy (AT) is essentially a failed healing response with haphazard proliferation of tenocytes, abnormalities in tenocytes with disruption of collagen fibers, and subsequent increase in non-collagenous matrix. METHODS: The diagnosis of Achilles tendinopathy is clinical, and MRI and utrasound imaging can be useful in differential diagnosis. Conservative manegement, open surgery or minimally invasive techniques are available. Injections and physical therapy are also vauable options. RESULTS: Eccentric exercises are useful tools to manage the pathology. If the condition does not ameliorate, shock wave therapy, or nitric oxide patches might be considered. Peritendinous injections or injections at the interface between the Achilles tendon and Kager's triangle could be considered if physical therapy should fail. Surgery is indicated after 6 months of non-operative management. CONCLUSIONS: The clinical diagnosis and management of AT are not straightforward. Hence, patients should understand that symptoms may recur with either conservative or surgical approaches.

Isokinetic functional outcomes of open versus percutaneous repair following Achilles tendon tears.

BACKGROUND: Rupture of the Achilles tendon (AT) is frequent in young recreational athletes. Conservative management, open surgery and percutaneous/minimally invasive approaches are all advocated, and conflicting data are available. This study compared functional and anthropometric outcomes of patients who underwent open or percutaneous repair. METHODS: A retrospective comparative study, in which 38 patients underwent open and percutaneous techniques to manage AT ruptures. For functional assessment, the calf circumference of both injured and uninjured legs was evaluated. Isokinetic testing included total plantar flexion work, peak plantar flexion torque, total dorsiflexion work peak and dorsiflexion torque. The Achilles Tendon Rupture Score (ATRS) and the American Orthopedic Foot and Ankle Score (AOFAS) were evaluated at a final minimum follow-up of 12months. RESULTS: No major complications were observed. The average time to return to sport was 9months. AOFAS and ATRS values did not differ statistically between groups. Isokinetic variables and circumference were similar in the operated and non-operated limb in both groups, and did not differ either when comparing open and percutaneous repair. CONCLUSIONS: Open and percutaneous repair of a torn Achilles tendon produced similar functional outcomes.

Surgical approach on combined chronic patellar tendon and bicruciate knee ligament injury.

A combined injury of the patellar tendon and both the anterior and posterior cruciate ligaments is disabling. It directly affects knee kinematics and biomechanics, presenting a considerable surgical challenge. In this complex and uncommon injury, decision-making should take into account the surgeon's experience and consider one- or two-stage surgery, tendon graft, graft fixation, and rehabilitation protocol. This manuscript discusses the surgical approach based on a comprehensive understanding of the patellar tendon and bicruciate biomechanics to guide which structures should be reconstructed first, especially when a two-stage procedure is chosen.

Diagnosis and management of Achilles tendon ailments: the Scottish mist.

The diagnosis and management of Achilles tendon ailments continue to be widely discussed by the scientific community. Also, the nomenclature used to describe the tendinopathic lesion in patients changed over the last decades together with the evolution in the knowledge of the physiopathology of Achilles tendinopathy, and unfortunately, through ignorance and possibly laziness, confusion still abounds. To emerge from these foggy paths, some clarifications are still necessary. The present Editorial tries to clarify some of these issues.

Changes in daily physical activity before and after total hip arthroplasty. A pilot study using accelerometry.

The present single-centre prospective follow-up study assessed the objective changes in physical activity undertaken before and after total hip arthroplasty (THA) using accelerometry. We enrolled 12 female patients who underwent home-based accelerometry assessment one month before and six months after the THA procedure. We assessed the daily amount of physical activity and energy expenditure related to physical activities. We also recorded the intensity of the physical activity, and pre- and post-operative clinical evaluation with the Harris Hip Score (HHS). At 6 months after surgery, we found a statistically significant increase of the total energy cost of physical activity (DA) (P=0.02), without significant increase of activity time (P>0.05). The energy cost of moderate/vigorous activity was statistically significant increased after surgery (P=0.008). Finally, HHS improved form 53.9±15.3 pre-operatively to 78.1±12.2 post-operatively (P=0.03). In our patients, the improvement was significant only for the total energy cost of daily activity. Thus, although patients did not exhibit a more active lifestyle, as shown by the slight increase of the activity time, they significantly increased the amount of moderate or vigorous activities performed after surgery.

Z-shortening of healed, elongated Achilles tendon rupture.

PURPOSE: A rupture of the Achilles tendon may heal in continuity, resulting in a lengthened Achilles tendon. The elongated structure must be shortened to restore effective push off. We report the results of a longitudinal study using Z-shortening of ruptured Achilles tendons that healed in continuity but were elongated. METHODS: Nine patients underwent surgery for elongation of a healed Achilles tendon rupture. All participants were prospectively followed up for two to five years, and final review was performed at 32 ± 14 months from operation. Clinical and functional assessment (anthropometric measurements, isometric strength, postoperative total rupture score) was performed. RESULTS: All patients were able to walk on tiptoes, and no patient used a heel lift or walked with a visible limp. No patient developed clinically evident deep-vein thrombosis or sustained a rerupture. Two patients were managed conservatively following a superficial surgical wound infection. At final review, maximum calf circumference remained significantly decreased in the operated leg. The operated limb was significantly weaker than the nonoperated one. CONCLUSIONS: Managing a healed Achilles tendon rupture using Z-shortening is safe and effective, providing good recovery and early weight bearing and active ankle mobilisation. Such patients should be warned that they are at risk for postoperative complications and that their ankle-plantar flexion strength is likely to be permanently reduced.

Light microscopic histology of quadriceps tendon ruptures.

PURPOSE: To assess histological changes and possible differences in the quadriceps of patients undergoing open repair of the tendon after spontaneous rupture, and subjects with no history of tendon pathology. MATERIALS: Biopsies were harvested from the quadriceps tendon of 46 patients (34 men, 12 women) who had reported unilateral atraumatic quadriceps tendon rupture and had undergone surgical repair of the tendon. Samples were also harvested from both the tendons in 11 (N = 11 × 2) patients, nine males and two females, dying from cardiovascular disorders. For each tendon, three slides were randomly selected and examined under light microscopy, and assessed using a semiquantitative grading scale (range 0-21) which considers fibre structure, fibre arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, and hyalinisation. RESULTS: The pathological sum-score averaged 19.2 ± 3.7 in ruptured tendons and 5.6 ± 2.0 in controls, and all variables considered were significantly different between the two groups, showing an association between tendon abnormalities and rupture (0.05 < P < 0.001). CONCLUSION: This study confirms that the presence of histological degenerative changes in torn quadriceps tendons increases the risk of rupture.

Intensive Physical Activity Increases the Risk of Knee and Hip Arthroplasty: A Systematic Review.

PURPOSE: The present study investigated the type of sport and activity level of athletes before they underwent knee and/or hip arthroplasty for osteoarthritis (OA), and compared them with a control group of subjects who did not undergo knee and hip arthroplasty. We hypothesed athletes exposed to high physical loads during sports had the highest risk of developing OA requiring arthroplasty. MATERIALS AND METHODS: This systematic review was conducted according to the PRISMA guidelines. All the comparative clinical trials to August 2021 investigating the sport activity level between subjects who underwent arthroplasty versus those who did not undergo arthroplasty for OA were considered. RESULTS: Data from 5 studies and 3638 patients were collected. The mean age for both groups was 47.61±15.5 years, and the mean body mass index was 24.6±2.1 kg/m2 17.6% were women. The Newcastle-Ottawa scale attested good quality of the methodology of the investigations included in the present study. CONCLUSION: Intense physical exercise, implying a high cumulative number of hours of exercise which can lead to excessive joint overload, in both sexes is associated with greater likelihood of early knee and hip OA which may lead to prosthetic surgery. Moderate and recreational exposure to sport has minor degenerative effects, and is not associated with early onset OA requiring arthroplasty.

Single versus double bundle in posterior cruciate ligament (PCL) reconstruction: a meta-analysis.

Posterior cruciate ligament (PCL) reconstruction can be performed using single bundle (SB) and double bundle (DB) techniques. The present study investigated whether DB PCL reconstruction is superior to SB reconstruction in terms of patient reported outcome measures (PROMs) and joint stability. In December 2021 Embase, Google Scholar, Pubmed, Scopus databases were accessed. All clinical trials comparing SB versus DB reconstruction to address PCL insufficiency in skeletally mature patients were considered. Data from 483 procedures were retrieved. The mean follow-up was 31.0 (28.0 to 107.6) months, and the mean timespan between injury and surgery was 11.3 (6 to 37) months. The mean age of the patients was 29.3 ± 3.8 years. 85 of 483 patients (18%) were women. At a mean of 31.0 months post reconstruction, ROM (P = 0.03) was slightly greater in the SB group, while the Tegner score (P = 0.03) and the Telos stress (P = 0.04) were more favorable in the DB cohort. Similarity was found in instrumental laxity (P = 0.4) and Lysholm score (P = 0.3). The current evidence does not support the use of DB techniques for PCL reconstruction. Both methods could restore knee stability and motion with satisfactory short term patient reported outcome measures. Further high quality clinical trials are required to validate these results on a larger scale.

Symptomatic disc herniation and serum lipid levels.

Insufficient blood supply to the intervertebral disc (IVD) has been proposed to play a role as causative factor in IVD degeneration. There is an association between IVD diseases and increased risk of dying of ischaemic heart disease. Obesity and tobacco are potential risk factors for degenerative IVD disease. High blood cholesterol and triglycerides serum levels are risk factors for atherosclerosis, and could be responsible for a decreased in the blood supply to the already poor vascularized IVD. We performed a frequency-matched case-control study to determine the serum levels of patients with symptomatic herniated lumbar disc. We examined the fasting serum lipid levels in 384 subjects who were operated at our institution. Group 1 included 169 consecutive patients (115 men and 54 women; mean age: 59.1 years, range 29-85) who underwent surgery for symptomatic disc herniation. Group 2 (control group) included 169 patients (115 men and 54 women; mean age: 61 years, range 26-86) who underwent arthroscopic meniscectomy for a meniscal tear in the same period. These patients were frequency-matched by age (within 3 years) and gender with patients of Group 1. Sera were extracted from blood samples and the concentrations of total cholesterol (TC) and triglycerides (TG) were determined. When comparing the two groups, patients with symptomatic herniated lumbar disc showed statistically significant higher triglyceride concentration (P = 0.02) and total cholesterol concentration (P = 0.01). Serum lipid levels may be a risk factor for IVD pathology. An enhanced understanding of these factors holds the promise of new approaches to the prevention and management of IVD pathology.

Sonographic measurement of iliotibial band thickness: an observational study in healthy adult volunteers.

PURPOSE: Iliotibial tract friction syndrome (ITBFS) might be caused by repetitive friction and abrasion of the iliotibial (ITB) tract across the lateral femoral epicondyle. Thickening in the ITB adjacent to the lateral femoral epicondyle has been reported. The values of ITB thickness at the lateral femoral epicondyle in healthy adult volunteers were determined, and the association between the thickness of the ITB and the subjects' age, weight, height, dominant limb and the volume of training or sporting activity was assessed. METHODS: An Ultrasound Scan (high resolution 3-2 MHz transducer Voluson-i G E Medical Systems, UK) was used to measure the thickness of the ITB in 38 healthy volunteers (30 men and 8 women, mean age 22.5 ± 1.5 years, range 18-25 years). One measurement from each of the subjects' knees at the level of lateral femoral epicondyle was taken. Reliability was established by measuring 11 of the subjects on three separate occasions at least I week apart. RESULTS: The thickness of the ITB on the right and left knees was 1.1 ± 0.2 mm. There was no evidence of a significant association between the thickness of the ITB and the subjects' age, weight, height, dominant limb and the volume of training or sporting activity. CONCLUSIONS: There is no evidence of significant correlation between the thickness of the ITB and subjects' age, weight, height, dominant limb and volume of training or sporting activity.

The low-profile Roman bridge technique for knotless double-row repair of the rotator cuff.

With advances in arthroscopic surgery, many techniques have been developed to increase the tendon-bone contact area, reconstituting a more anatomic configuration of the rotator cuff footprint and providing a better environment for tendon healing. We present a low-profile arthroscopic rotator cuff repair technique which uses suture bridges to optimize rotator cuff tendon-footprint contact area and mean pressure. A 5.5 mm Bio-Corkscrew suture anchor (Arthrex, Naples, FL, USA), double-loaded with No. 2 FiberWire sutures (Arthrex, Naples, FL, USA), is placed in the anteromedial aspect of the footprint. Two suture limbs from a single suture are both passed through a single anterior point in the rotator cuff. One suture limb is retrieved from the cannula. The second suture limb is passed through a single posterior point in the rotator cuff producing two points of fixation in the tendon, with a tendon bridge between them. The same suture limb is retrieved through the lateral portal, and then inserted into the bone by means of a Pushlock (Arthrex, Naples, FL, USA), placed approximately 1.5-2 cm posterior to the first anchor. This second suture is passed again in the posterior aspect of the cuff. The limbs of the first suture are pulled to compress the tendon in the medial aspect of the footprint. The two free suture limbs are used to produce suture bridges over the tendon by means of a Pushlock (Arthrex, Naples, FL, USA), placed 1 cm distal to the lateral edge of the footprint relative to the medially placed suture anchors anterior to posterior. This technique allows us to perform a low-profile (single pulley-suture bridges) repair for knotless double-row repair of the rotator cuff.

Autologous Bone Grafting in Trauma and Orthopaedic Surgery: An Evidence-Based Narrative Review.

Autologous bone grafting is common in trauma and orthopaedic surgery. Both the Reamer Irrigator Aspirator (RIA) and Iliac Crest Bone Graft (ICBG) aim to obtain autologous bone graft. Although the process of harvesting a bone graft is considered simple, complications may occur. This study examined morbidity and pain at the donor site, blood loss, and iatrogenic fractures, comparing RIA and ICBG. The source of the autologous bone graft, the alternative graft sites, and the storage modalities of the harvested bone marrow were also evaluated. In May 2021, PubMed, Embase, Scopus, and Google Scholar were accessed, with no time constraints. RIA may produce greater blood loss, but with less morbidity and complications, making it a potential alternative source of bone grafting.

Potential of biomarkers during pharmacological therapy setting for postmenopausal osteoporosis: a systematic review.

BACKGROUND: Biochemical markers of bone turnover (BTMs), such as the bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are used to manage therapy monitoring in osteoporotic patients. This systematic review analyzed the potential of these BMTs in predicting the clinical outcomes in terms of BMD, t-score, rate of fractures, and adverse events during the therapy setting in postmenopausal osteoporosis. METHODS: All randomized clinical trials (RCTs) reporting data on biomarkers for postmenopausal osteoporosis were accessed. Only articles reporting quantitative data on the level of biomarkers at baseline and on the outcomes of interest at the last follow-up were eligible. RESULTS: A total of 36,706 patients were retrieved. Greater values of bALP were associated with a greater rate of vertebral (P = 0.001) and non-vertebral fractures (P = 0.0001). Greater values of NTx at baseline were associated with a greater rate of adverse events at the last follow-up (P = 0.02). Greater values of CTx at baseline were associated with a greater rate of adverse events leading to discontinuation (P = 0.04), gastrointestinal adverse events (P = 0.0001), musculoskeletal adverse events (P = 0.04), and mortality (P = 0.04). Greater values of PINP at baseline were associated with greater rates of gastrointestinal adverse events (P = 0.02) at the last follow-up. CONCLUSION: The present analysis supports the adoption of BMTs during pharmacological therapy setting of patients suffering from osteoporosis. LEVEL OF EVIDENCE: I, systematic review of RCTs.

Strategies for large bone defect reconstruction after trauma, infections or tumour excision: a comprehensive review of the literature.

Large bone defects resulting from musculoskeletal tumours, infections, or trauma are often unable to heal spontaneously. The challenge for surgeons is to avoid amputation, and provide the best functional outcomes. Allograft, vascularized fibular or iliac graft, hybrid graft, extracorporeal devitalized autograft, distraction osteogenesis, induced-membrane technique, and segmental prostheses are the most common surgical strategies to manage large bone defects. Given its optimal osteogenesis, osteoinduction, osteoconduction, and histocompatibility properties, along with the lower the risk of immunological rejection, autologous graft represents the most common used strategy for reconstruction of bone defects. However, the choice of the best surgical technique is still debated, and no consensus has been reached. The present study investigated the current reconstructive strategies for large bone defect after trauma, infections, or tumour excision, discussed advantages and disadvantages of each technique, debated available techniques and materials, and evaluated complications and new perspectives.

Association between HLA genotypes and COVID-19 susceptibility, severity and progression: a comprehensive review of the literature.

The COVID-19 pandemic has markedly impacted on cultural, political, and economic structures all over the world. Several aspects of its pathogenesis and related clinical consequences have not yet been elucidated. Infection rates, as well morbidity and mortality differed within countries. It is intriguing for scientists to understand how patient genetics may influence the outcome of the condition, to clarify which aspects could be related the clinical variability of SARS-CoV-2 disease. We reviewed the studies exploring the role of human leukocyte antigens (HLA) genotypes on individual responses to SARS-CoV-2 infection and/or progression, discussing also the contribution of the immunological patterns MHC-related. In March 2021, the main online databases were accessed. All the articles that investigated the possible association between the HLA genotypes and related polymorphisms with susceptibility, severity and progression of COVID-19 were considered. Although both genetic and environmental factors are certainly expected to influence the susceptibility to or protection of individuals, the HLA and related polymorphisms can influence susceptibility, progression and severity of SARS-CoV-2 infection. The crucial role played by HLA molecules in the immune response, especially through pathogen-derived peptide presentation, and the huge molecular variability of HLA alleles in the human populations could be responsible for the different rates of infection and the different patients following COVID-19 infection.