Capacitive biophysical stimulation improves the healing of vertebral fragility fractures: a prospective multicentre randomized controlled trial.

BACKGROUND: Capacitively coupling electric fields (CCEF) is a method of non-invasive biophysical stimulation that enhances fracture repair and spinal fusion. This multicentre randomized controlled trial aimed to further examine the roles of CCEF in (1) the resolution of vertebral bone marrow oedema (VBME) using a follow-up MRI study and (2) pain relief, analgesic drug consumption and quality of life improvement in stimulated patients who were referred with acute vertebral fragility fractures (VFFs) compared to non-stimulated patients. METHODS: Between September 2016 and December 2019, patients who were referred to the spine centres that participated in this multicentre randomized clinical study with acute VFFs of type OF1 or OF2 were included in the present study. All the VFFs were conservatively managed according to Good Clinical Practice. Moreover, the patients were randomized into two groups: the CCEF group received, as an adjunct to the clinical study protocol, biophysical stimulation with a CCEF device (Osteospine, IGEA) for 8 h per day for 60 days, whereas the control group was treated according to the clinical study protocol. At baseline (T0), the 30-day follow-up (T1), the 60-day follow-up (T2), and the 6-month follow-up (T3), each patient underwent clinical evaluation using the Visual Analogue Scale (VAS) for Pain and the Oswestry Disability Index (ODI). Analgesic therapy with paracetamol 1000 mg tablets for 7 days-or longer, depending on the pain intensity-was performed; patients were required to report their paracetamol consumption on a specific sheet between study day 8 to 180 days of follow-up. MRI studies of the thoracolumbar spine were performed at 0 (T0), 30 (T1) and 60 days of follow-up (T2) using a 1.5-T MRI system in all of the centres that took part in the study. For each VBME area examined via MRI, the vertebral body geometry (i.e. anterior wall height/posterior wall height and vertebral kyphosis) were assessed. RESULTS: A total of 66 patients (male: 9, 13.63%; mean age: 73.15 years old) with 69 VFFs were included in the present study and randomized as follows: 33 patients were included in the control group and the remaining 33 patients were randomized into the CCEF group. In the CCEF group, good compliance with CCEF therapy was observed (adherence = 94%), and no adverse effects were recorded. In the stimulated patients, faster VBME resolution and significantly less vertebral body collapse during follow-up were observed compared to the control patients. Moreover, in the active group, faster pain reduction and improvement in the ODI mean score were observed. Stimulated patients also reported a significantly lower paracetamol consumption rate from the third follow-up after treatment until the 6-month follow-up. In terms of sex-related differences, in the CCEF group, VBME showed a faster resolution in male patients compared with females. CONCLUSION: Biophysical stimulation with CCEF, as an adjunct to traditional conservative treatment, is a useful tool to hasten the VBME resolution process and prevent vertebral body deformation. These MRI findings also correlate with faster back pain resolution and quality of life improvement. From the third follow-up after treatment until the 6-month follow-up, stimulated patients reported a significantly lower paracetamol consumption than control patients, even though back pain and quality of life showed no significant differences between the two groups. LEVEL OF EVIDENCE: II. Trial Registration Register: ClinicalTrials.gov, number: NCT05803681.

Orthogeriatric co-management for the care of older subjects with hip fracture: recommendations from an Italian intersociety consensus.

BACKGROUND: Health outcomes of older subjects with hip fracture (HF) may be negatively influenced by multiple comorbidities and frailty. An integrated multidisciplinary approach (i.e. the orthogeriatric model) is, therefore, highly recommended, but its implementation in clinical practice suffers from the lack of shared management protocols and poor awareness of the problem. The present consensus document has been implemented to address these issues. AIM: To develop evidence-based recommendations for the orthogeriatric co-management of older subjects with HF. METHODS: A 20-member Expert Task Force of geriatricians, orthopaedics, anaesthesiologists, physiatrists, physiotherapists and general practitioners was established to develop evidence-based recommendations for the pre-, peri-, intra- and postoperative care of older in-patients (≥ 65 years) with HF. A modified Delphi approach was used to achieve consensus, and the U.S. Preventive Services Task Force system was used to rate the strength of recommendations and the quality of evidence. RESULTS: A total of 120 recommendations were proposed, covering 32 clinical topics and concerning preoperative evaluation (11 topics), perioperative (8 topics) and intraoperative (3 topics) management, and postoperative care (10 topics). CONCLUSION: These recommendations should ease and promote the multidisciplinary management of older subjects with HF by integrating the expertise of different specialists. By providing a convenient list of topics of interest, they might assist in identifying unmet needs and research priorities.

Hand-Wrist Disorders in Chainsaw Operators: A Follow-Up Study in a Group of Italian Loggers.

Despite the mechanization process implemented in arboriculture, logging tasks are still manually performed by chainsaw operators, which therefore are exposed to the risk of developing hand-wrist musculoskeletal disorders. Our research aimed to: (a) define whether the slight changes observed in 2017 showed an evolution to overt diseases; (b) study some risk determinants for these diseases such as age, working experience, and performing a secondary job. We recruited in a two-year follow-up study, 38 male forestry workers performing logging tasks employed in the Sicilian Forestry Department located in Enna. All the subjects underwent: (1) personal data collection; (2) administration of questionnaire addressed at upper limbs symptoms with a hand chart; (3) physical examination of the upper limbs, including Tinel's and Phalen's maneuvers; (4) ultrasound investigation of the hand-wrist area. In the two-year follow-up study we registered an overall increasing in wrist disorders, thus we can assume that forestry workers may be a target population for wrist diseases and deserve a particular attention in workers' health surveillance programs. Interestingly, the prevalence of wrist-hand disorders resulted to be higher in younger workers.

The Many Faces of Covid-19 at a Glance: A University Hospital Multidisciplinary Account From Milan, Italy.

In March 2020, northern Italy became the second country worldwide most affected by Covid-19 and the death toll overtook that in China. Hospital staff soon realized that Covid-19 was far more severe than expected from the few data available at that time. The Covid-19 pandemic forced hospitals to adjust to rapidly changing circumstances. We report our experience in a general teaching hospital in Milan, the capital of Lombardy, the most affected area in Italy. First, we briefly describe Lombardy's regional Covid-19-related health organizational changes as well as general hospital reorganization. We also provide a multidisciplinary report of the main clinical, radiological and pathological Covid-19 findings we observed in our patients.

Biophysical stimulation of bone and cartilage: state of the art and future perspectives.

INTRODUCTION: Biophysical stimulation is a non-invasive therapy used in orthopaedic practice to increase and enhance reparative and anabolic activities of tissue. METHODS: A sistematic web-based search for papers was conducted using the following titles: (1) pulsed electromagnetic field (PEMF), capacitively coupled electrical field (CCEF), low intensity pulsed ultrasound system (LIPUS) and biophysical stimulation; (2) bone cells, bone tissue, fracture, non-union, prosthesis and vertebral fracture; and (3) chondrocyte, synoviocytes, joint chondroprotection, arthroscopy and knee arthroplasty. RESULTS: Pre-clinical studies have shown that the site of interaction of biophysical stimuli is the cell membrane. Its effect on bone tissue is to increase proliferation, synthesis and release of growth factors. On articular cells, it creates a strong A2A and A3 adenosine-agonist effect inducing an anti-inflammatory and chondroprotective result. In treated animals, it has been shown that the mineralisation rate of newly formed bone is almost doubled, the progression of the osteoarthritic cartilage degeneration is inhibited and quality of cartilage is preserved. Biophysical stimulation has been used in the clinical setting to promote the healing of fractures and non-unions. It has been successfully used on joint pathologies for its beneficial effect on improving function in early OA and after knee surgery to limit the inflammation of periarticular tissues. DISCUSSION: The pooled result of the studies in this review revealed the efficacy of biophysical stimulation for bone healing and joint chondroprotection based on proven methodological quality. CONCLUSION: The orthopaedic community has played a central role in the development and understanding of the importance of the physical stimuli. Biophysical stimulation requires care and precision in use if it is to ensure the success expected of it by physicians and patients.

Can Clinical and Surgical Parameters Be Combined to Predict How Long It Will Take a Tibia Fracture to Heal? A Prospective Multicentre Observational Study: The FRACTING Study.

BACKGROUND: Healing of tibia fractures occurs over a wide time range of months, with a number of risk factors contributing to prolonged healing. In this prospective, multicentre, observational study, we investigated the capability of FRACTING (tibia FRACTure prediction healING days) score, calculated soon after tibia fracture treatment, to predict healing time. METHODS: The study included 363 patients. Information on patient health, fracture morphology, and surgical treatment adopted were combined to calculate the FRACTING score. Fractures were considered healed when the patient was able to fully weight-bear without pain. RESULTS: 319 fractures (88%) healed within 12 months from treatment. Forty-four fractures healed after 12 months or underwent a second surgery. FRACTING score positively correlated with days to healing: r = 0.63 (p < 0.0001). Average score value was 7.3 ± 2.5; ROC analysis showed strong reliability of the score in separating patients healing before versus after 6 months: AUC = 0.823. CONCLUSIONS: This study shows that the FRACTING score can be employed both to predict months needed for fracture healing and to identify immediately after treatment patients at risk of prolonged healing. In patients with high score values, new pharmacological and nonpharmacological treatments to enhance osteogenesis could be tested selectively, which may finally result in reduced disability time and health cost savings.

Vertebroplasty and kyphoplasty for the treatment of thoracic fractures in osteoporotic patients: a finite element comparative analysis.

BACKGROUND: Vertebral compression fractures occur in the thoracolumbar junction, causing the collapse of the vertebral body. For their treatment, vertebroplasty and kyphoplasty are used, but it is still unknown which technique is to be preferred. METHODS: Finite element models of the thoracic spine were developed to evaluate the outcomes of vertebroplasty and kyphoplasty. A mild and severe collapse of T10 treated with vertebroplasty or kyphoplasty was studied. Stresses on the endplates and intradiscal pressures were extrapolated to determine the stress distribution in the adjacent structures. RESULTS: The validation ensured a correct stiffness and a proper kinematic of each functional spinal unit. The results demonstrated that a consolidation following vertebroplasty caused slight variations of intradiscal pressures and stresses. If a kyphoplasty was performed after a mild collapse of the vertebral body, a 25% stress reduction on endplates was found. In cases of severe collapse, when a partial height restoration was achieved, a 15% stress reduction was obtained, while with a full recovery of the anterior wall of the collapsed vertebra, there was a further reduction of 40%. CONCLUSIONS: To reduce the stresses on the adjacent endplates and the risk of fracture, the results suggest a kyphoplasty is to be preferred, trying to restore the initial vertebral body height.

Functional characterisation of a novel mutation affecting the catalytic domain of MMP2 in siblings with multicentric osteolysis, nodulosis and arthropathy.

Multicentric osteolysis, nodulosis and arthropathy (MONA) is a rare autosomal recessive disorder. To date, 13 mutations of the matrix metalloproteinase 2 (MMP2) gene have been detected in 26 patients with MONA and other osteolytic syndromes. Here, we describe the molecular and functional analysis of a novel MMP2 mutation in two adult Italian siblings with MONA. Both siblings displayed palmar-plantar subcutaneous nodules, tendon retractions, limb arthropathies, osteolysis in the toes and pigmented fibrous skin lesions. Molecular analysis identified a homozygous MMP2 missense mutation in exon 8 c.1228G>C (p.G410R), not detected in 260 controls and predicted by several bioinformatic tools to be pathogenic. By protein modelling, the mutant residue was predicted to affect the main chain conformation of the catalytic domain. Gelatin zymography, the gold standard test for MMP2 function, of serum-free conditioned medium from G410R-MMP2-expressing human embryonic kidney (HEK) cells, showed a complete loss of gelatinolytic activity. The novel mutation is located in the catalytic domain, as are 3 (p.E404K, p.V400del and p.G406D) of the other 13 MMP2 mutations described to date; however, p.G410R underlies a phenotype that is only partially overlapping that of other MMP2 exon 8 mutation carriers. Our results further delineate the complexity of genotype-phenotype correlations in MONA, broaden the repertoire of reported MMP2 mutation and enhance the comprehension of the protein motifs crucial for MMP2 catalytic activity.

Teriparatide in the treatment of non-unions: scientific and clinical evidences.

INTRODUCTION: Each fracture has a failing risk which can lead to a non-union. Among the non-invasive strategies proposed to improve bone healing, also in non-union, the use of teriparatide, a drug for the treatment of the osteoporosis, has increasing supporting data. EXPERIMENTAL DATA: Many studies mainly on rats, but also on primates, demonstrate the positive effect on fracture healing of teriparatide, both in physiological and pathological conditions, with a more rapid evolution of the reparative callus. CLINICAL DATA: A double blinded randomized controlled study on wrist fractures demonstrated a positive effect, in term of healing speed, of teriparatide at the dose of 20 µg/day, but not at the higher dose of 40 µg/day. A prospectic randomized study on pelvic fractures showed a faster healing in teriparatide treated patients. The use of teriparatide in non-unions is reported as effective in numerous case report. The effect of teriparatide seems very useful in the non-unions consequent to an atypical femoral fracture after long-term administration of bisphosphonates. CONCLUSIONS: A conceivable positive effect of teriparatide on fracture healing is well-documented on animals, and very likely on humans, however further studies are needed to confirm these hopeful hypotheses.

Conservative treatment of a femoral neck fracture following nail removal.

With increased longevity, the management of fragility fractures in the elderly is becoming more frequent. In particular, hip fractures have considerable importance due to the significant morbidity and mortality. A 67-year-old woman underwent intramedullary nail (IMN) removal inserted for a pertrochanteric fracture that had occurred 20 months earlier. This was indicated due to continuous discomfort related to the protruding apex of the implant over the great trochanter. Due to pain persistence two days after surgery, a computed tomography (CT) scan was performed, documenting a minimally displaced impacted subcapital femoral neck fracture. Conservative management with close radiographic follow-up was conducted. After six months, the patient had returned to previous daily activities and a satisfactory range of motion was achieved without pain on walking. The purpose of our paper is to discuss the decision of removing hardware in the elderly osteoporotic patient and to analyze the possibility to conservatively treat an impacted minimally displaced subcapital fracture occurring after the removal of an IMN inserted previously for the treatment of a trochanteric fracture. In the elderly population with decreased bone quality, the removal of intramedullary implants of the proximal femur should be carefully evaluated, and osteoporotic patients undergoing reduction and fixation of femoral fractures should be encouraged to start antiosteoporotic therapy (bisphosphonate, teriparatide) to reduce the risk of further bone loss. Conservative treatment should be considered for the management of lesser symptomatic minimally displaced impacted fractures, where the inherent stability of the fracture allows rapid healing without further surgical attempts.

Recognition of morphometric vertebral fractures by artificial neural networks: analysis from GISMO Lombardia Database.

BACKGROUND: It is known that bone mineral density (BMD) predicts the fracture's risk only partially and the severity and number of vertebral fractures are predictive of subsequent osteoporotic fractures (OF). Spinal deformity index (SDI) integrates the severity and number of morphometric vertebral fractures. Nowadays, there is interest in developing algorithms that use traditional statistics for predicting OF. Some studies suggest their poor sensitivity. Artificial Neural Networks (ANNs) could represent an alternative. So far, no study investigated ANNs ability in predicting OF and SDI. The aim of the present study is to compare ANNs and Logistic Regression (LR) in recognising, on the basis of osteoporotic risk-factors and other clinical information, patients with SDI≥1 and SDI≥5 from those with SDI = 0. METHODOLOGY: We compared ANNs prognostic performance with that of LR in identifying SDI≥1/SDI≥5 in 372 women with postmenopausal-osteoporosis (SDI≥1, n = 176; SDI = 0, n = 196; SDI≥5, n = 51), using 45 variables (44 clinical parameters plus BMD). ANNs were allowed to choose relevant input data automatically (TWIST-system-Semeion). Among 45 variables, 17 and 25 were selected by TWIST-system-Semeion, in SDI≥1 vs SDI = 0 (first) and SDI≥5 vs SDI = 0 (second) analysis. In the first analysis sensitivity of LR and ANNs was 35.8% and 72.5%, specificity 76.5% and 78.5% and accuracy 56.2% and 75.5%, respectively. In the second analysis, sensitivity of LR and ANNs was 37.3% and 74.8%, specificity 90.3% and 87.8%, and accuracy 63.8% and 81.3%, respectively. CONCLUSIONS: ANNs showed a better performance in identifying both SDI≥1 and SDI≥5, with a higher sensitivity, suggesting its promising role in the development of algorithm for predicting OF.

Biological and pharmacological factors influencing the fracture healing.

Many experimental data are available about the positive effect of some molecules on fracture repair, but data on their efficacy in the clinical use in humans are still lacking. Bone Morphogenetic Proteins are currently used in the treatment of delayed unions, but it is necessary to insert them surgically in the fracture site. The only pharmacological factor with clinical data is teriparatide, but more data are needed to confirm its effect on fracture healing in humans, even if experimental data in animals are robust. Data are also available on the effect on bone healing of other molecules used in osteoporosis treatments. Bisphosphonates favour the formation of a bigger callus, mechanically competent, but with a slow rate of remodelling. Estrogens and strontium ranelate have some experimental evidence of stimulating healing process. Robust experimental data are also available on an anti-Sost antibody. Anti-inflammatory drugs have a negative effect on bone healing, interfering with the early phases of inflammation. In conclusion more data, experimental and mainly clinical, are advocated to define whether it is possible to enhance bone healing, even if promising molecules, as teriparatide, are already available.

Update on the efficacy, safety, and adherence to treatment of full length parathyroid hormone, PTH (1-84), in the treatment of postmenopausal osteoporosis.

Full length (1-84) parathyroid hormone (PTH) was introduced in Europe as a treatment for postmenopausal osteoporosis in 2006. The efficacy of PTH (1-84) in the prevention of vertebral fractures is very high, and is similar to that of teriparatide. Its action in the prevention of femoral fractures has yet to be fully demonstrated, but the incidence of such fractures in trials was very low, and a decrease in nonvertebral fractures was seen in high-risk patients. The effect on bone mineral density (BMD) was clearly demonstrated in the spine and also in the hip. The effects on BMD were evident and increased progressively with treatment until 36 months. After its discontinuation there was a clear decrease in BMD if no antiresorptive treatment was initiated. Increases in bone volumetric density and bone volume in trabecular sites were also reported. Moreover, a bone volume increase was detected in cortical sites. Hypercalcemia and hypercalciuria are frequent consequences of PTH treatment, but rarely have clinical effects and are usually well controlled by reducing calcium and vitamin D supplementation.

Isolated congenital absence of posterior cruciate ligament? A case report.

A rare case of a 28-year-old Asiatic male with the isolated absence of a posterior cruciate ligament is reported. Clinical features, diagnostic steps, therapeutic strategies and follow-up are described. A review of the literature is also presented.

Severe low turnover osteoporosis.

Severe osteoporosis, a situation with fractures, can worsen in the case of poor response to usual therapies, such as bisphosphonates associated with calcium and vitamin D, especially if bone turnover is strongly suppressed. One way of inverting the poor evolution of non-responders is to use Teriparatide. The case of a non-responder is reported, with considerations about the possibility of detecting these patients before a new fracture takes place.