The sequential antifracturative treatment: a meta-analysis of randomized clinical trials.

Background: Subjects with a fragility fracture have an increased risk of a new fracture and should receive effective strategies to prevent new events. The medium-term to long-term strategy should be scheduled by considering the mechanisms of action in therapy and the estimated fracture risk. Objective: A systematic review was conducted to evaluate the sequential strategy in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines. Design: Systematic review and meta-analysis. Data sources and methods: PubMed, Embase, and the Cochrane Library were investigated up to February 2021 to update the search of a recent systematic review. Randomized clinical trials (RCTs) that analyzed the sequential therapy of antiresorptive, anabolic treatment, or placebo in patients with or at risk of a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using fixed-effects models. The primary outcome was the risk of refracture, while the secondary outcome was the bone mineral density (BMD) change. Results: In all, 17 RCTs, ranging from low to high quality, met our inclusion criteria. A significantly reduced risk of fracture was detected at (i) 12 or 24 months after the switch from romosozumab to denosumab versus placebo to denosumab; (ii) 30 months from teriparatide to bisphosphonates versus placebo to bisphosphonates; and (iii) 12 months from romosozumab to alendronate versus the only alendronate therapy (specifically for vertebral fractures). In general, at 2 years after the switch from anabolic to antiresorptive drugs, a weighted BMD was increased at the lumbar spine, total hip, and femoral neck site. Conclusion: The Task Force formulated recommendations on sequential therapy, which is the first treatment with anabolic drugs or 'bone builders' in patients with very high or imminent risk of fracture.

A systematic review to evaluate the sequential therapy of antiresorptive (denosumab and bisphosphonate, such as alendronate, minodronate, risedronate, and etidronate), anabolic treatment (such as romosozumab, teriparatide), or placebo in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines Subjects with previous fragility fractures should promptly receive effective strategies to prevent the risk of subsequent events. Indeed, patients with a fragility fracture have a doubled risk of a new fracture. For this reason, it is essential to provide adequate sequential therapy based on the mechanisms and the rapidity of action. A systematic review was performed to identify the sequential strategy in patients at high- or imminent-risk of (re)fracture and to support the Panel of the Italian Fragility Fracture Guideline in formulating recommendations. Our systematic review included seventeen studies mostly focused on women and enabled us to strongly recommend the anabolic drugs as first-line treatment. Specifically, for the sequential therapy from anabolic to antiresorptive treatment, there was a significant reduction in the risk of different types of fractures after the switch from romosozumab to denosumab versus placebo to denosumab. These findings were confirmed at 24 months after the switch. Considering the sequential treatment from antiresorptive to anabolic medications, there was a decreased risk of fracture 12 months after the switch from placebo to teriparatide versus bisphosphonate or antiresorptive to teriparatide. Moreover, a greater bone mineral density increase after the switch from anabolic to antiresorptive medications was shown in the lumbar spine, total hip, and femoral neck. The results of this systematic review and meta-analysis confirm that initial treatment with anabolic drugs produces substantial bone mineral density improvements, and the transition to antiresorptive drugs can preserve or even amplify the acquired benefit. These findings support the choice to treat very high-risk individuals with anabolic drugs first, followed by antiresorptive drugs.

Bone involvement in the early stages of Parkinson's disease: a case-control study.

OBJECTIVE: To evaluate the qualitative and quantitative alterations of bone tissue in patients with early-stage Parkinson's disease (PD) and to measure the associations between bone mineral density (BMD), trabecular bone score (TBS) and physical performance. METHODS: This case-control study enrolled patients with early-stage PD and age-matched controls. BMDs for the left femoral neck (L-FN) and lumbar spine (LS) were measured. Bone microarchitecture for the LS was determined using TBS. Muscle performance was assessed using the short physical performance battery (SPPB). Patients and controls were stratified in two groups based on the SPPB score: a poor performance group (SPPB score ≤8) and high performance group (SPPB > 8). RESULTS: This study included 26 patients: 13 in the PD group and 13 age-matched controls. The mean ± SD BMD results in the PD group were: L1-L4 BMD = 0.935 ± 0.183 g/cm2; L-FN BMD = 0.825 ± 0.037 g/cm2; with bone microarchitecture degraded in four patients and partially degraded in three patients. TBS was significantly different in the patients with PD stratified according to SPPB. Among the controls, there was a significant difference in body mass index between the two SPPB groups. CONCLUSION: TBS might identify bone involvement earlier than BMD in the initial stages of PD.

Characterization of an Italian population with neurological disorders in a rehabilitation setting using ClinFIT.

OBJECTIVE: To examine the functioning profile of people with neurological disorders who access rehabilitation services through ClinFIT Generic-30. METHODS: The functioning profile of people with neurological disorders accessing rehabilitation services was examined using the ClinFIT Generic-30, and the results compared with existing core set (neurological health conditions acute and post-acute,stroke, Multiple Sclerosis, Traumatic Brain Injury,Spinal Cord Injury). RESULTS: Data for 364 people were analysed. The 10 most commonly impaired ICF categories included 3 for Body Functions (exercise tolerance functions (b455), mobility of joint functions (b710), and muscle power functions (b730)) and 7 for Activities and Participation (carrying out daily routine (d230), handling stress and other psychological demands (d240), changing basic body position (d410), maintaining a body position (d415), transferring oneself (d420), walking (d450), and moving around (d455)), while the ICF categories that were severely impaired (ICF qualifiers 3 and 4) in more than 30% of the study cohort were: muscle power functions (b730), carrying out daily routine (d230), walking (d450), moving around (d455), doing housework (d640), and assisting others (d660). DISCUSSION: The current study data suggests that  ClinFIT Generic-30 appears to effectively identify impairments and/or restrictions, as perceived by individuals affected by selected health conditions. CONCLUSION: ClinFIT Generic-30 is a tool that can be used to characterize functioning profile in people with different neurological disorders and to collect important information not addressed by the disease-specific core sets (neurological health conditions acute and post-acute,stroke, Multiple Sclerosis, Traumatic Brain Injury,Spinal Cord Injury).

Anti-sclerostin antibodies: a new frontier in fragility fractures treatment.

Bone fragility is the determinant of the increased risk of minimal trauma fracture and must be treated with a multimodal approach that includes pharmacological therapy, physical exercise, and adequate nutrition. Pharmacological therapy, to date based on the administration of antiresorptive drugs, such as bisphosphonates and denosumab, or osteoanabolic drugs, such as teriparatide and abaloparatide, has shown to be effective in reducing the risk of fracture in osteoporotic patients. In the context of the cellular and molecular mechanisms that regulate bone metabolism, the discovery of the Wnt signaling pathway and its role in bone tissue homeostasis has allowed the identification of sclerostin as an inhibitor of osteoblastic activity and simultaneously as a stimulator of osteoclastic activity. Therefore, the use of a monoclonal antibody, romosozumab, against this protein has been tested as a potential drug with a dual action, stimulating bone neo-apposition and inhibiting bone resorption. The efficacy of romosozumab has been demonstrated in numerous clinical trials against both placebo and other drugs commonly used in the treatment of patients affected by osteoporosis. The advantages of this drug lie above all in its rapid action which makes it particularly suitable in clinical situations where it is necessary to improve bone strength very quickly due to the imminent risk of fragility fracture. Clinical studies and guidelines suggest romosozumab as an initial drug in an ideal sequential approach from osteoanabolic to antiresorptive drugs. Some aspects of cardiovascular safety remain to be fully investigated, therefore its use in osteoporotic patients at high cardiovascular risk should be avoided until further data become available.

Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on 'Diagnosis, risk stratification, and continuity of care of fragility fractures' based on a systematic literature review.

Background: Noncommunicable, chronic diseases need pharmacological interventions for long periods or even throughout life. The temporary or permanent cessation of medication for a specific period, known as a 'medication holiday,' should be planned by healthcare professionals. Objectives: We evaluated the association between continuity (adherence or persistence) of treatment and several outcomes in patients with fragility fractures in the context of the development of the Italian Guidelines. Design: Systematic review. Data Sources and Methods: We systematically searched PubMed, Embase, and the Cochrane Library up to November 2020 for randomized clinical trials (RCTs) and observational studies that analyzed medication holidays in patients with fragility fracture. Three authors independently extracted data and appraised the risk of bias of the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random effects models. Primary outcomes were refracture and quality of life; secondary outcomes were mortality and treatment-related adverse events. Results: Six RCTs and nine observational studies met our inclusion criteria, ranging from very low to moderate quality. The adherence to antiosteoporotic drugs was associated with a lower risk of nonvertebral fracture [relative risk (RR) 0.42, 95% confidence interval (CI) 0.20-0.87; three studies] than nonadherence, whereas no difference was detected in the health-related quality of life. A reduction in refracture risk was observed when continuous treatment was compared to discontinuous therapy (RR 0.49, 95% CI 0.25-0.98; three studies). A lower mortality rate was detected for the adherence and persistence measures, while no significant differences were noted in gastrointestinal side effects in individuals undergoing continuous versus discontinuous treatment. Conclusion: Our findings suggest that clinicians should promote adherence and persistence to antiosteoporotic treatment in patients with fragility fractures unless serious adverse effects occur.

Executive summary: Italian guidelines for diagnosis, risk stratification, and care continuity of fragility fractures 2021.

Background: Fragility fractures are a major public health concern owing to their worrying and growing burden and their onerous burden upon health systems. There is now a substantial body of evidence that individuals who have already suffered a fragility fracture are at a greater risk for further fractures, thus suggesting the potential for secondary prevention in this field. Purpose: This guideline aims to provide evidence-based recommendations for recognizing, stratifying the risk, treating, and managing patients with fragility fracture. This is a summary version of the full Italian guideline. Methods: The Italian Fragility Fracture Team appointed by the Italian National Health Institute was employed from January 2020 to February 2021 to (i) identify previously published systematic reviews and guidelines on the field, (ii) formulate relevant clinical questions, (iii) systematically review literature and summarize evidence, (iv) draft the Evidence to Decision Framework, and (v) formulate recommendations. Results: Overall, 351 original papers were included in our systematic review to answer six clinical questions. Recommendations were categorized into issues concerning (i) frailty recognition as the cause of bone fracture, (ii) (re)fracture risk assessment, for prioritizing interventions, and (iii) treatment and management of patients experiencing fragility fractures. Six recommendations were overall developed, of which one, four, and one were of high, moderate, and low quality, respectively. Conclusions: The current guidelines provide guidance to support individualized management of patients experiencing non-traumatic bone fracture to benefit from secondary prevention of (re)fracture. Although our recommendations are based on the best available evidence, questionable quality evidence is still available for some relevant clinical questions, so future research has the potential to reduce uncertainty about the effects of intervention and the reasons for doing so at a reasonable cost.

Pain and Motor Function in Myotonic Dystrophy Type 1: A Cross-Sectional Study.

Pain is an underestimated finding in myotonic dystrophy type 1 (DM1). We provide a characterization of pain in terms of functional implications through a multidimensional assessment in patients with DM1, focusing on gender differences. We assessed pain through the Brief Pain Inventory (BPI) and its indexes (the Severity Index (SI) and the Interference Index (II)), balance/gait (the Tinetti Performance-Oriented Mobility Assessment (POMA)), functional abilities (the Functional Independence Measure (FIM)), and fatigue (the Fatigue Severity Scale (FSS)). We divided our sample into a mild (<4) and a moderate-severe group (≥4) based on BPI indexes. A between-group analysis was performed. We recruited 23 males and 22 females with DM1. A statistically significant difference was found for the FSS and the BPI-SI ≥ 4, and for all outcomes in the BPI-II ≥ 4 (p ≤ 0.003). In the female group, all outcomes except for the FIM were statistically significantly worse (p ≤ 0.004). Dividing our sample into four groups based on gender and the BPI, a statistically significant difference was found for FSS between the two groups with BPI-II ≥ 4 (with worsen score in the female one) (p < 0.002). Pain in DM1 patients is highly reported and gender related, with increased fatigue and poor balance/gait in the female group.

Bone fragility during the COVID-19 pandemic: the role of macro- and micronutrients.

Bone fragility is the susceptibility to fracture due to poor bone strength. This condition is usually associated with aging, comorbidities, disability, poor quality of life, and increased mortality. International guidelines for the management of patients with bone fragility include a nutritional approach, mainly aiming at optimal protein, calcium, and vitamin D intakes. Several biomechanical features of the skeleton, such as bone mineral density (BMD), trabecular and cortical microarchitecture, seem to be positively influenced by micro- and macronutrient intake. Patients with major fragility fractures are usually poor consumers of dairy products, fruit, and vegetables as well as of nutrients modulating gut microbiota. The COVID-19 pandemic has further aggravated the health status of patients with skeletal fragility, also in terms of unhealthy dietary patterns that might adversely affect bone health. In this narrative review, we discuss the role of macro- and micronutrients in patients with bone fragility during the COVID-19 pandemic.

Bone fragility: conceptual framework, therapeutic implications, and COVID-19-related issues.

Bone fragility is the susceptibility to fracture even for common loads because of structural, architectural, or material alterations of bone tissue that result in poor bone strength. In osteoporosis, quantitative and qualitative changes in density, geometry, and micro-architecture modify the internal stress state predisposing to fragility fractures. Bone fragility substantially depends on the structural behavior related to the size and shape of the bone characterized by different responses in the load-deformation curve and on the material behavior that reflects the intrinsic material properties of the bone itself, such as yield and fatigue. From a clinical perspective, the measurement of bone density by DXA remains the gold standard for defining the risk of fragility fracture in all population groups. However, non-quantitative parameters, such as macro-architecture, geometry, tissue material properties, and microcracks accumulation can modify the bone's mechanical strength. This review provides an overview of the role of different contributors to bone fragility and how these factors might be influenced by the use of anti-osteoporotic drugs and by the COVID-19 pandemic.

Osteosarcopenia and type 2 diabetes mellitus in post-menopausal women: a case-control study.

Background: Osteosarcopenia has been defined as the concomitance of low bone density (osteopenia/osteoporosis) and sarcopenia. Osteoporosis is characterized by alterations in bone microarchitecture and decrease of bone mineral density (BMD), whereas sarcopenia is the progressive decrease of both muscle mass and function that increase the risk of falls. Type 2 diabetes mellitus (T2DM) is associated with poor bone strength and muscle wasting. Objective: The aim of this study is to analyze the association between osteosarcopenia and T2DM in post-menopausal women (PMW). Methods: We performed an age matched case-control study (1:2 ratio), considering as cases PMW affected by T2DM, and PMW without T2DM as control group. For all patients a DXA evaluation to investigate bone density and body composition measures were performed. Moreover, we carried out muscle strength and performance assessments. Outcome measures were femoral neck and lumbar spine BMD T-scores, appendicular lean mass (ALM), handgrip strength and the Short Physical Performance Battery (SPPB). Data from both groups were analyzed and compared. Results: Thirty-six PMW (12 T2DM vs 24 non-T2DM) were recruited. The frequency of osteosarcopenia was significantly higher in the T2DM group compared to controls (50% vs 17%; OR 5.0, 95% CI 1.05 to 23.79, p = 0.043). Handgrip strength was significantly lower in the T2DM group (10.09 ± 4.02 kg vs 18.40 ± 6.83 kg; p = 0.001). Conclusions: Post-menopausal women with T2DM have a 5 times higher risk to have osteosarcopenia compared to non-diabetic ones. Further studies on larger cohorts are required to confirm these findings.

Osteoporosis in Childhood Cancer Survivors: Physiopathology, Prevention, Therapy and Future Perspectives.

The improvement of chemotherapy, radiotherapy, and surgical interventions, together with hematopoietic stem cell transplantation, increased childhood cancer survival rate in the last decades, reaching 80% in Europe. Nevertheless, anti-cancer treatments are mainly responsible for the onset of long-term side effects in childhood cancer survivors (CCS), including alterations of the endocrine system function and activity. In particular, the most frequent dysfunction in CCS is a metabolic bone disorder characterized by low bone mineral density (BMD) with increased skeletal fragility. BMD loss is also a consequence of a sedentary lifestyle, malnutrition, and cancer itself could affect BMD, thus inducing osteopenia and osteoporosis. In this paper, we provide an overview of possible causes of bone impairment in CCS in order to propose management strategies for early identification and treatment of skeletal fragility in this population.

Functioning issues in inpatients affected by COVID-19-related moderate pulmonary impairment: a real-practice observational study.

OBJECTIVE: To investigate the correlations between clinical, functional, and radiological outcomes in inpatients with coronavirus disease 2019 (COVID-19). METHODS: In this observational study, we recruited inpatients affected by moderate COVID-19 disease. The clinical evaluation comprised the Cumulative Illness Rating Scale (CIRS), numerical rating scale (NRS), modified Rankin scale (mRS), and the modified Borg dyspnea scale (mBDS). Respiratory involvement was assessed with computed tomography (CT) and graded with a CT-severity score (CT-SS). We retrospectively assessed functioning using the International Classification of Functioning, Disability and Health (ICF) codes of the Clinical Functioning Information Tool (ClinFIT) COVID-19 in the acute phase. Correlation analysis was performed 1) between clinical, instrumental, and functional parameters and 2) between ICF categories. RESULTS: The data showed statistically significant moderate correlations between CT-SS and the following categories: b152 "emotional functions" and b440 "respiratory functions". CONCLUSION: This is the first study to use the ICF framework in people with a moderate form of COVID-19 in the acute phase. Considering the correlations between some ICF categories and radiological findings, our results support the use of the ClinFIT COVID-19 for a comprehensive assessment of COVID-19 patients.

Impact of extracorporeal shockwave therapy for erectile dysfunction and Peyronie's disease on reproductive and hormonal testicular function.

INTRODUCTION: Extracorporeal shock wave therapy is an established treatment for erectile dysfunction and Peyronie's disease. Concerns regarding the safety of extracorporeal shock wave therapy for andrological purposes on testicular function were raised by animal studies. AIM: To evaluate the impact of extracorporeal shock wave therapy for erectile dysfunction or Peyronie's disease on reproductive and hormonal testicular function. METHODS: We designed a prospective controlled study in which consecutive patients were enrolled. Males aged between 18 and 40 years with mild vasculogenic erectile dysfunction or acute inflammatory Peyronie's disease and normozoospermia were included. All enrolled patients were offered extracorporeal shock wave therapy, and subjects who refused extracorporeal shock wave therapy for any reason were considered as the Control group. All patients in the Intervention group were treated with DUOLITH SD1 T-TOP by a single expert urologist. Semen analysis and serum total testosterone dosage were performed before the start (T0) and 3 months after the end of extracorporeal shock wave therapy (T1) in Intervention group. The same parameters were evaluated after the extracorporeal shock wave therapy refusal (T0) and at the end of the following 3 months (T1) in Control group. Normozoospermia was chosen as the primary outcome, serum total testosterone concentration was selected as the secondary outcome. RESULTS: A total of 94 patients were enrolled in the study (48 Group A, 46 Group B). At T0, all patients were normozoospermic in both groups (p = 0.563), and no significant difference in mean ± SD total testosterone levels was recorded between the groups (582.5 ± 107.2 vs. 634.6 ± 108.4 ng/dl; p = 0.221). At T1, no significant deterioration (p > 0.05) in semen parameters was recorded in both groups. Only a statistically significant reduction in seminal pH was found after extracorporeal shock wave therapy compared to baseline (7.9 ± 0.3 vs. 7.5 ± 0.2; p < 0.001) and untreated patients (7.8 ± 0.2 vs. 7.5 ± 0.2; p < 0.001). No significant difference in total testosterone levels was recorded in Intervention group after extracorporeal shock wave therapy compared to baseline (p = 0.584). CONCLUSION: Extracorporeal shock wave therapy in erectile dysfunction and Peyronie's disease patients does not seem to affect reproductive and hormonal testicular function.

Efficacy and Effectiveness of Extracorporeal Shockwave Therapy in Patients with Myofascial Pain or Fibromyalgia: A Scoping Review.

Myofascial pain syndrome (MPS) and fibromyalgia (FM) are underestimated painful musculoskeletal conditions that could impact function and quality of life. A consensus about the most appropriate therapeutic approach is still not reached. Considering the long course of the diseases, prolonged assumption of drugs, such as NSAIDs and pain killers, could increase the risk of adverse events, often leading affected patients and physicians to prefer non-pharmacological approaches. Among these, radial and focused extracorporeal shock waves therapies (ESWT) are widely used in the management of painful musculoskeletal conditions, despite the fact that the mechanisms of action in the context of pain modulation should be further clarified. We performed a scoping review on PubMed using Mesh terms for analyzing the current evidence about the efficacy and effectiveness of ESWT for patients with MPS or FM. We included 19 clinical studies (randomized controlled trials and observational studies); 12 used radial ESWT, and 7 used focused ESWT for MPS. Qualitative analysis suggests a beneficial role of ESWT for improving clinical and functional outcomes in people with MPS, whereas no evidence was found for FM. Considering this research gap, we finally suggested a therapeutic protocol for this latter condition according to the most recent diagnostic criteria.

Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review.

The aim of the present systematic review was to provide a clear overview of the clinical current research progress in the use of adipose-derived mesenchymal stem cells (ASCs) as an effective therapeutic option for the management of tendinopathies, pathologies clinically characterized by persistent mechanical pain and structural alteration of the tendons. The review was carried out using three databases (Scopus, ISI Web of Science and PubMed) and analyzed records from 2013 to 2021. Only English-language papers describing the isolation and manipulation of adipose tissue as source of ASCs and presenting ASCs as treatment for clinical tendinopathies were included. Overall, seven clinical studies met the inclusion criteria and met the minimum quality inclusion threshold. Data extraction and quality assessment were performed by groups of three reviewers. The available evidence showed the efficacy and safety of ASCs treatment for tendinopathies, although it lacked a clear description of the biomolecular mechanisms underlying the beneficial properties of ASCs.

Characterization of neuropathic component of back pain in patients with osteoporotic vertebral fractures.

BACKGROUND: Osteoporotic vertebral fractures (OVFs) are often followed by chronic back pain which may have a nociceptive, neuropathic, or mixed component. However, literature on this topic is lacking. OBJECTIVE: The objective of this cross-sectional study is to characterize the neuropathic component of chronic back pain in patients with OVFs. METHODS: Spine fractures were detected by morphometric examination. Pain severity and its impact on activities of daily living (ADL) were evaluated through the Brief Pain Inventory (BPI). Neuropathic pain was investigated through the Italian versions of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS) and the painDETECT questionnaire (PD-Q). RESULTS: We included 72 patients, mainly women (88.8%), with mean age of 69.2 years. The 70.8% of patients had multiple OVFs, of which 47% located at the thoracic spine, 43.1% at the thoracic and at lumbar spine, and 9.8% at the lumbar spine. The BPI showed moderate back pain in 23.6% of cases and severe in 8.3% of cases, with high interference with ADL in 38.9% of patients. The PD-Q revealed the presence of neuropathic pain in 5.5% of cases, while the LANSS in 23.6% of cases. CONCLUSIONS: In our study, the prevalence of neuropathic component of chronic back pain ranged from 5.5% to 23.6%, according to PD-Q and LANSS respectively, in patients with OVFs. Further studies should investigate if the characterization of chronic back pain might contribute to appropriateness of interventions for this population.

Effectiveness of Neridronate in the Management of Bone Loss in Patients with Duchenne Muscular Dystrophy: Results from a Pilot Study.

INTRODUCTION: Bone loss is a major issue in patients affected by Duchenne muscular dystrophy (DMD), a rare musculoskeletal disorder, particularly in those treated with glucocorticoids (GCs). We aimed to assess the effectiveness of neridronate in terms of bone mineral density (BMD) changes in this population. METHODS: We retrospectively reviewed the records of patients affected by DMD receiving GCs referred to our outpatient from 2015 to 2020. All patients were treated with an intramuscular (IM) injection of neridronate (25 mg every month). Bone density was measured at the lumbar spine (LS; L1-L4 tract) using dual-energy x-ray absorptiometry (DXA) (GE Lunar), no more than 4 weeks before (T0) and after 1 year from neridronate treatment (T1). RESULTS: Eight boys with DMD were included with a mean age at diagnosis of 4.75 ± 2.81 years. Six of them were non-ambulant and two of them had previous low-trauma fractures (a distal femur fracture and a vertebral compression fracture, respectively). All patients were receiving deflazacort [median duration of therapy 11.5 years (interquartile range 2-25)]. At the DXA evaluation (T0), the mean L1-L4 BMD value was 0.716 ± 0.164 g/cm2. Six patients (75%) showed an L1-L4 Z-score height-adjusted of less than - 2. The mean age of neridronate initiation was 18.87 ± 6.81 years. All patients were supplemented with calcium carbonate and vitamin D at baseline. After 12 months of treatment (T1), the mean L1-L4 BMD value was 0.685 ± 0.190 g/cm2. Seven patients (87.5%) showed an L1-L4 Z-score of less than - 2. Changes in LS BMD and Z-score were not significant between T0 and T1 in our cohort (p = 0.674 and p = 0.208, respectively) as well as among non-ambulant patients with DMD without previous fragility fractures. CONCLUSIONS: In this study, we reported for the first time that neridronate may slow bone loss in GC-treated patients with DMD at 1-year follow-up.

Physical Agent Modalities in Early Osteoarthritis: A Scoping Review.

Early osteoarthritis (EOA) still represents a challenge for clinicians. Although there is no consensus on its definition and diagnosis, a prompt therapeutic intervention in the early stages can have a significant impact on function and quality of life. Exercise remains a core treatment for EOA; however, several physical modalities are commonly used in this population. The purpose of this paper is to investigate the role of physical agents in the treatment of EOA. A technical expert panel (TEP) of 8 medical specialists with expertise in physical agent modalities and musculoskeletal conditions performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP searched for evidence of the following physical modalities in the management of EOA: "Electric Stimulation Therapy", "Pulsed Electromagnetic field", "Low-Level Light Therapy", "Laser Therapy", "Magnetic Field Therapy", "Extracorporeal Shockwave Therapy", "Hyperthermia, Induced", "Cryotherapy", "Vibration therapy", "Whole Body Vibration", "Physical Therapy Modalities". We found preclinical and clinical data on transcutaneous electrical nerve stimulation (TENS), extracorporeal shockwave therapy (ESWT), low-intensity pulsed ultrasound (LIPUS), pulsed electromagnetic fields stimulation (PEMF), and whole-body vibration (WBV) for the treatment of knee EOA. We found two clinical studies about TENS and PEMF and six preclinical studies-three about ESWT, one about WBV, one about PEMF, and one about LIPUS. The preclinical studies demonstrated several biological effects on EOA of physical modalities, suggesting potential disease-modifying effects. However, this role should be better investigated in further clinical studies, considering the limited data on the use of these interventions for EOA patients.