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Life
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Novel Therapeutics for Musculoskeletal Disorders
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Novel Therapeutics for Musculoskeletal Disorders

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (26 March 2026) | Viewed by 8357

Special Issue Editors

Dr. Dalila Scaturro

E-Mail Website
Guest Editor
Precision Medicine in the Medical, Surgical and Critical Care Areas, University of Palermo, Palermo, Italy
Interests: osteoarthritis; osteoporosis; bone; arthropathy; joint; pain; low back pain
Prof. Dr. Giulia Letizia Mauro

E-Mail Website
Guest Editor
Precision Medicine in the Medical, Surgical and Critical Care Areas, University of Palermo, Palermo, Italy
Interests: osteoarthritis; osteoporosis; bone; arthropathy; joint; pain; low back pain

Special Issue Information

Dear Colleagues,

Musculoskeletal disorders represent a leading cause of disability globally, significantly affecting people's quality of life and productivity. Despite progress in understanding the pathophysiological basis of these conditions, many conventional therapies prove insufficient in ensuring complete and sustainable recovery.

This Special Issue of Life is dedicated to exploring the latest therapeutic innovations for musculoskeletal disorders, with a focus on multimodal approaches, emerging technologies and personalized strategies. The collected articles offer an overview of new frontiers in treatment, including regenerative medicine, gene therapy, tissue engineering, neuromodulation techniques and the integration of artificial intelligence in diagnosis and rehabilitation.

The goal of this Special Issue is to promote multidisciplinary dialogue between researchers, clinicians and medical technology developers, providing an updated reference point to guide clinical practice and stimulate new research directions.

We thank all the authors and reviewers for their valuable contribution, and we hope that this volume will inspire further progress in the increasingly patient-centered and evidence-based treatment of musculoskeletal disorders.

Dr. Dalila Scaturro
Prof. Dr. Giulia Letizia Mauro
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • osteoarthritis
  • osteoporosis
  • bone
  • arthropathy
  • joint
  • pain
  • lower back pain

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Published Papers (7 papers)

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14 pages, 590 KB  
Article
Reliability and Validity of Plantar Pressures and the Modified ICPBL Test vs. Telemetry for Diagnosing Anatomical Discrepancies: A Pilot Study
by Arian Marcelino Argemi, Dan Iulian Alexe, Ismael Ortuño Soriano, Ignacio Zaragoza García, Alvaro Saura Sempere, Rebeca Bueno Fermoso, Álvaro Gómez Carrión and Rubén Sánchez-Gómez
Life 2026, 16(4), 612; https://doi.org/10.3390/life16040612 - 7 Apr 2026
Viewed by 395
Abstract
Background/Objectives: Several methods have been proposed to assess lower limb-length discrepancies; however, none have demonstrated sufficient reliability and validity for diagnosing anatomical discrepancies (DA). Objectives: This study primarily aims to evaluate the accuracy of two traditional tests—the Modified Iliac Crests Palpation and Pelvimeter [...] Read more.
Background/Objectives: Several methods have been proposed to assess lower limb-length discrepancies; however, none have demonstrated sufficient reliability and validity for diagnosing anatomical discrepancies (DA). Objectives: This study primarily aims to evaluate the accuracy of two traditional tests—the Modified Iliac Crests Palpation and Pelvimeter with Blocks test (ICPBL) and plantar pressure analysis—by comparing them with the gold standard telemetry (TE) method for diagnosing DA. The secondary objective is to assess the intra-rater reliability of these two tests and determine their potential applicability in clinical settings. Methods: Thirty subjects between the ages of 20 and 80 were enrolled in the present prospective, cross-sectional diagnostic accuracy pilot study; thirteen with a positive TE for DA of more than 3 mm were classified into the group with the condition DA, and 17 were classified into the group without the condition DA. Pelvic tilting and plantar pressures were evaluated. Results: The TE revealed a difference of 8.09 ± 3.24 mm between the short and long limbs, while subjects without DA had only a 0.41 mm difference (p < 0.001). Similarly, the Modified ICPBL test showed a 4.38 ± 2.10 mm difference in subjects with DA, compared to 0.51 ± 0.53 mm in those without DA (p < 0.001). Additionally, plantar pressure measurements supported these findings, with a difference of 5.17 ± 3.28 kg/cm2 between the short and long limbs in subjects with DA, versus 2.28 ± 1.77 kg/cm2 in subjects without DA (p < 0.05). The area under the receiver operating characteristic (ROC) curve was 0.783 (95% CI: 0.456–0.877) for plantar pressures and 1.000 (95% CI: 0.742–0.942) for the Modified ICPBL test. Conclusions: The Modified ICPBL and plantar pressure tests demonstrated high diagnostic accuracy within the sample studied, suggesting they are useful tools for supporting the diagnosis of DA. In this pilot study, the Modified ICPBL showed very high discriminative ability, while plantar pressure testing demonstrated moderate sensitivity. Both methods may serve as preliminary practical alternatives to telemetry TE, potentially reducing X-ray exposure; however, these results should be interpreted with caution due to the limited sample size and the specific clinical setting of this study. Full article
(This article belongs to the Special Issue Novel Therapeutics for Musculoskeletal Disorders)
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21 pages, 1883 KB  
Article
Mineral Metabolism Assays, Central DXA, and Fracture Risk Probabilities in Menopausal Patients with Non-Functional Adrenal Tumors with/Without Mild Autonomous Cortisol Secretion: Does the Presence of Unilateral Versus Bilateral Tumors Matter?
by Alexandra-Ioana Trandafir, Mara Carsote, Mihai Costachescu, Oana-Claudia Sima and Alexandru-Florin Florescu
Life 2025, 15(10), 1639; https://doi.org/10.3390/life15101639 - 21 Oct 2025
Viewed by 1051
Abstract
Introduction/Background: Most adrenal incidentalomas (AIs) are non-functioning adrenal tumors (NFATs) without clinically overt hormonal hypersecretion; one-third show subtle endocrine over-activity and mild autonomous cortisol secretion (MACS). One out of ten NFATs involves not a unilateral (UTs), but bilateral tumors (BTs). Bone health, as [...] Read more.
Introduction/Background: Most adrenal incidentalomas (AIs) are non-functioning adrenal tumors (NFATs) without clinically overt hormonal hypersecretion; one-third show subtle endocrine over-activity and mild autonomous cortisol secretion (MACS). One out of ten NFATs involves not a unilateral (UTs), but bilateral tumors (BTs). Bone health, as opposed to cardio-metabolic complications, is less studied in NFAs/MACS, particularly in BTs. Hence, we aimed to analyze (blood) mineral metabolism assays (MMAs), including bone turnover markers (BTMs), central Dual-Energy X-ray Absorptiometry (DXA), and 10-year fracture risk estimation (FRAX/FRAXplus) in menopausal patients with UTs vs. BTs. Methods: This was a retrospective, single-center study. The inclusion criteria were women aged ≥50 y and CT-based AI detection. The exclusion criteria were medication against osteoporosis, malignancies, bone metabolic disorders, and cs-1mg-DST >5 µg/dL. Results: The cohort [N = 129; mean age: 62.39 ± 7.9 y; and y since menopause (YSM): 13.7 ± 8] included UT (62.22%) and BT (31.78%) groups with a similar age, YSM, type 2 diabetes rate (35.23% vs. 36.59%), arterial hypertension (73.6% vs. 75.5%), BMI, fasting glycemia, and glycated hemoglobin A1c (p > 0.5 for each). The borderline significance for morning cortisol was higher in UTs vs. BTs [median (interquartile interval): 13.9 (11.16, 15.00) vs. 10.10 (8.88, 12.95) µg/dL; p = 0.05] and the MACS-positive rate (24.45% vs. 36.59%; p = 0.051). The largest tumor diameter was similar (2.26 ± 0.97 vs. 2.51 ± 0.87 cm; p = 0.175), as was cs-1mg-DST [1.27 (1.01, 1.95) vs. 1.52 (0.92, 2.78) µg/dL; p = 0.357]. MMAs, BTMs, and DXA-BMD/T scores were similar in the UT vs. BT groups. The most prevalent DXA categories were osteopenia (50.82%) and normal (41.38%). The rate of DXA bone impairment (osteoporosis + osteopenia) was 72.13% vs. 58.62%. A generally low prevalence of fragility fractures was found (3.88%; N = 5, 3/2 between the groups). Out of the 25.58% (N = 33) females who were found to be MACS-positive, 54.55% were in the UT group and 45.45% were in the BT group. Age, YSM, the rate of analyzed comorbidities, BMI, biochemical parameters, DXA/BMDs, and FRAX/FRAXplus (lumbar BMD adjustment)-based probabilities were similar between the UT and BT groups, regarding MACS-positive vs. MACS-negative groups. Diabetic patients were all MACS-positive. A higher PTH level in the MACS-positive UT vs. MACS-positive BT groups (36.32 ± 9.21 vs. 51.65 ± 9.58 pg/mL; p = 0.01) was found, with the mean 25-hydroxyvitamin D showing mild deficiency (24.21 ± 12.73 vs. 26.16 ± 9.89 ng/mL; p = 0.694). In UTs, the largest tumor diameter statistically significantly correlated with baseline ACTH (r = −0.391; p < 0.001) and cs-1mg-DST (r = 0.306; p < 0.001), while in BTs, the largest diameter of the two tumors showed a positive correlation with cs-1mg-DST (r = 0.309; p = 0.012). Conclusions: The findings from this real-life setting (similar age, YSM, and diabetes and MACS-positive rates) could help us to better understand the bone features in UTs vs. BTs, noting that ACTH/cs-1mg-DST measurements showed no difference. The study population was associated with a generally low fracture prevalence and 10-year fracture risk probabilities, which might act as a bias in this distinct clinical exploration. Whether a multifactorial algorithm is needed to provide a 360-degree perspective of the bone health assessment in these patients remains an open matter. So far, starting from the current guidelines, a patient-centered approach is mandatory. To our best knowledge, this study adds to the limited number of prior studies regarding bone impairment in bilateral tumors. Full article
(This article belongs to the Special Issue Novel Therapeutics for Musculoskeletal Disorders)
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14 pages, 600 KB  
Article
A Retrospective Study on Wilson Osteotomy with Intramedullary Locking Plate for Failed Hallux Valgus Correction: Insights from a Single-Surgeon Experience
by Yi Ping Wei, Meng Chen Kuo and Yi Jiun Chou
Life 2025, 15(10), 1592; https://doi.org/10.3390/life15101592 - 12 Oct 2025
Viewed by 1201
Abstract
Background/Objective: The recurrence of hallux valgus (HV) after primary surgical correction remains a clinical challenge, often requiring combined approaches to address both bony realignment and soft tissue imbalance. While locking plates have shown some biomechanical advantages in HV correction, evidence regarding their [...] Read more.
Background/Objective: The recurrence of hallux valgus (HV) after primary surgical correction remains a clinical challenge, often requiring combined approaches to address both bony realignment and soft tissue imbalance. While locking plates have shown some biomechanical advantages in HV correction, evidence regarding their application in revision procedures is limited. This study presents a retrospective single-surgeon experience with a small cohort, aiming to describe radiographic and functional outcomes and to share practical insights rather than provide definitive conclusions. Methods: In this retrospective case series, patients undergoing revision surgery for failed HV correction over the past ten years at a single tertiary institution were analyzed. Radiographic parameters—hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), and sesamoid position—were assessed. Functional outcomes included the American Orthopaedic Foot and Ankle Society (AOFAS) score and the Visual Analog Scale for pain. Surgical strategies were tailored according to recurrence mechanisms, and some cases involved Wilson osteotomy with intramedullary plate fixation. The Mann–Whitney U test and the Wilcoxon signed-rank test were applied to assess efficacy. Results: A total of 11 feet treated by one surgeon were included. Both soft tissue procedures and combined osteotomy with intramedullary plate fixation led to statistically significant but preliminary improvements in HVA, IMA, DMAA, and sesamoid alignment. Functional scores improved, and the complication rate was within the range reported in the previous literature. Conclusions: This retrospective single-surgeon study with a limited sample size suggests that Wilson osteotomy combined with intramedullary plate fixation may represent a joint-preserving and biomechanically supportive option for recurrent HV, particularly in cases with large DMAAs and severe sesamoid displacement. However, the findings should be interpreted cautiously given the small cohort, retrospective design, and absence of multi-angle radiographic visualization. The results highlight a potential approach in specific clinical settings rather than a definitive solution. Larger, prospective, multi-center studies are required to confirm long-term utility. Full article
(This article belongs to the Special Issue Novel Therapeutics for Musculoskeletal Disorders)
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13 pages, 369 KB  
Article
Movement-Evoked Pain and Temporal Summation in Individuals with Symptomatic Rotator Cuff Tears: A Cross-Sectional Study
by Anupama Prabhu B, Arun G. Maiya, Vivek Pandey, Kiran K. V. Acharya, Vennila Jaganathan, James M. Elliott and Mira Meeus
Life 2025, 15(9), 1394; https://doi.org/10.3390/life15091394 - 3 Sep 2025
Viewed by 1653
Abstract
Musculoskeletal shoulder pain due to rotator cuff (RC) tears is a prevalent condition that significantly impacts function and quality of life. Understanding the underlying pain mechanisms, including movement-evoked pain (MEP) and pain facilitation phenomena such as temporal summation (TS), is essential for improving [...] Read more.
Musculoskeletal shoulder pain due to rotator cuff (RC) tears is a prevalent condition that significantly impacts function and quality of life. Understanding the underlying pain mechanisms, including movement-evoked pain (MEP) and pain facilitation phenomena such as temporal summation (TS), is essential for improving targeted interventions. This cross-sectional study examined relationships among TS, pain at rest, and MEP in 85 individuals with symptomatic RC tears. Mechanical TS was assessed on the contralateral forearm using standardized mechanical stimuli, while pain at rest and MEP during active arm elevation were measured via numerical rating scales. Spearman’s correlations were performed for the overall cohort and stratified by pain duration (<3 months, acute; ≥3 months, chronic). Weak but statistically significant correlations were found between TS and MEP (r = 0.23, p = 0.02) and between pain at rest and MEP (r = 0.30, p = 0.005), whereas no correlation existed between TS and pain at rest. The logistic regression model showed limited predictive ability. These exploratory findings suggest partially overlapping but distinct pain mechanisms in RC tear patients and should be interpreted as hypothesis-generating, warranting validation in larger, prospective cohorts. Full article
(This article belongs to the Special Issue Novel Therapeutics for Musculoskeletal Disorders)
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12 pages, 548 KB  
Article
The Role of Postural Assessment, Therapeutic Exercise and Foot Orthoses in Haemophilic Arthropathy: A Pilot Study
by Dalila Scaturro, Sofia Tomasello, Vincenzo Caruso, Isabella Picone, Antonio Ammendolia, Alessandro de Sire and Giulia Letizia Mauro
Life 2025, 15(8), 1217; https://doi.org/10.3390/life15081217 - 1 Aug 2025
Viewed by 1183
Abstract
Haemophilic arthropathy is caused by repeated joint bleeding episodes, primarily affecting knees, ankles and elbows. Conservative options should be considered prior to surgery, as well as postural evaluation, since any functional overload promotes the development of new bleeding. The aim of this study [...] Read more.
Haemophilic arthropathy is caused by repeated joint bleeding episodes, primarily affecting knees, ankles and elbows. Conservative options should be considered prior to surgery, as well as postural evaluation, since any functional overload promotes the development of new bleeding. The aim of this study is to verify the use of foot orthoses in combination with postural rehabilitation, assessing the incidence of spontaneous haemarthroses and haematomas. In total, 15 patients were enrolled and randomly divided into two groups: 8 in group A, composed of patients who were prescribed foot orthoses and a 20-session rehabilitation program, and 7 in group B, composed of patients who were instructed to use foot orthoses only. All patients were evaluated at baseline (T0), at 3 months (T1—end of the rehabilitation program), and at 12 months (T2), using the following scales: Functional Independence Score in Haemophilia (FISH), Haemophilia Joint Health Score (HJHS) and Numerical Rating Scale (NRS). During the 12 months between the first and the last assessment, no patient in group A developed hemarthroses or hematomas, while one case of hemarthrosis was recorded in group B. The HJHS improved significantly (≤0.05) in group A at both T1 and T2, while in group B it improved significantly only in T2. As for FISH, it showed significant improvements in both groups at T1 and T2. NRS showed a significant reduction only at T2 in both groups (p-value T0–T1 0.3 in group A e 0.8 in group B). No patient reported any adverse effects from the use of orthotic insoles. The combination of postural rehabilitation, the use of foot orthoses and pharmacological prophylaxis could improve functioning and joint status in patients affected by haemophilic arthopathy, delaying or preventing new hemarthroses by improving the distribution of joint loads and the modification of musculoskeletal system’s characteristics. Full article
(This article belongs to the Special Issue Novel Therapeutics for Musculoskeletal Disorders)
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12 pages, 1687 KB  
Study Protocol
Myotonometric, Static Plantar Pressure, and Stabilometric Assessment in Children and Adolescents with Idiopathic Scoliosis: A Study Protocol
by Oana-Cristina Rădulescu, Alina-Daniela Totorean, Oana Suciu, Andreea Niță, Liliana Catan, Alessandro Iatarola, Iuliu Șerban and Elena-Constanta Amaricai
Life 2026, 16(1), 101; https://doi.org/10.3390/life16010101 - 11 Jan 2026
Viewed by 593
Abstract
Adolescent idiopathic scoliosis (AIS) is a 3D structural deformity of the spine that can cause decreased spinal movement, paraspinal muscle weakness, or chronic pain. Our study aims to evaluate biomechanical and viscoelastic properties of the paravertebral muscles in adolescents with idiopathic S-type scoliosis, [...] Read more.
Adolescent idiopathic scoliosis (AIS) is a 3D structural deformity of the spine that can cause decreased spinal movement, paraspinal muscle weakness, or chronic pain. Our study aims to evaluate biomechanical and viscoelastic properties of the paravertebral muscles in adolescents with idiopathic S-type scoliosis, static plantar pressure, and stabilometry at the beginning of a physical exercise program and after 3 months. The myotonometry performed by using MyotonPro will determine five parameters (frequency, stiffness, logarithmic decrement, stress relaxation time, and ratio of relaxation time to deformation time). Measurements will be taken at the level of the left/right middle trapezius, left/right lower trapezius, left/right latissimus dorsi, and left/right lumbar erector muscles. Static pressure assessment and stabilometry (length described by the center of pressure, confidence area, and speed described by the center of pressure) will be determined by a PoData device in different testing positions (eyes open, eyes closed, head rotated to the right/left, head tilted to the right/left, and head in hyperextension). We expect to record a difference between the muscles on the concave side and the convex side in terms of myotonometric parameters, as well as differences between the initial and 3-month assessment. We predict an improvement in stabilometric parameters after the 3-month physical exercise program. Full article
(This article belongs to the Special Issue Novel Therapeutics for Musculoskeletal Disorders)
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21 pages, 4769 KB  
Case Report
Is a Bacteriophage Approach for Musculoskeletal Infection Management an Alternative to Conventional Therapy?
by Jörg Eschweiler, Christian Fischer, Filippo Migliorini, Johannes Greven, Thomas Mendel, Philipp Kobbe and Steffen Langwald
Life 2025, 15(10), 1534; https://doi.org/10.3390/life15101534 - 29 Sep 2025
Cited by 2 | Viewed by 1537
Abstract
Antimicrobial resistance is a global threat to public health. The growing resistance of bacteria to commonly used antibiotics necessitates the search for and development of alternative treatments. Bacteriophage (or phage) therapy fits this trend perfectly. Phages that selectively infect and kill bacteria might [...] Read more.
Antimicrobial resistance is a global threat to public health. The growing resistance of bacteria to commonly used antibiotics necessitates the search for and development of alternative treatments. Bacteriophage (or phage) therapy fits this trend perfectly. Phages that selectively infect and kill bacteria might represent, in some cases, the last therapeutic option. This overview provides case examples and discusses the potential development of phage therapy, examining its ethical and legal considerations in the context of current clinical practices. Additionally, it explores the advantages of utilizing phage products in patients for whom existing therapeutic options are limited or unavailable. Further clinical studies are necessary to broaden the understanding of phages, their dosage, and a standardised delivery system. These efforts are essential to ensure that phage-based therapy is not viewed as experimentation but as a routine medical treatment. Bacterial viruses are unlikely to become a miracle cure or a panacea for infections, but they may find an important role in medicine. Full legalisation of this treatment could help solve the problem of multidrug-resistant infectious diseases on a global scale. Full article
(This article belongs to the Special Issue Novel Therapeutics for Musculoskeletal Disorders)
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