Ankle fractures can cause significant functional impairment in the short and long term. In recent years, gait analysis using inertial sensors has gained special relevance as a reliable measurement system. This study aimed to evaluate the differences in spatiotemporal gait parameters and clinical–functional measurements in patients with bimalleolar ankle fracture and healthy subjects, to study the correlation between the different variables, and to analyze the test–retest reliability of a single inertial sensor in our study population. Twenty-two subjects with bimalleolar ankle fracture six months after surgery and eleven healthy subjects were included in the study. Spatiotemporal parameters were analyzed with the G-WALK sensor. Functional scales and clinical measures were collected beforehand. In the ankle fracture group, the main differences were obtained in bilateral parameters (effect size: 0.61 ≤ d ≤ 0.80). Between-group differences were found in cadence, speed, stride length, and stride time (effect size: 1.61 ≤ d ≤ 1.82). Correlation was moderate (0.436 < r < 0.554) between spatiotemporal parameters and clinical–functional measures, explaining up to 46% of gait performance. Test–retest reliability scores were high to excellent (0.84 ≤ ICC ≤ 0.98), with the worst results in the gait phases. Our study population presents evident clinical–functional impairments 6 months after surgery. The G-WALK can be considered a reliable tool for clinical use in this population.

To analyze how balance and other physical capacities evolved after surgery in patients with a bimalleolar fracture and how these capacities and clinical variables (immobilization or unloading time) contribute to restoring patients’ functionality, 22 patients and 10 healthy people (HC) were assessed for static and dynamic balance (Y-Balance test, YBT), dorsiflexion ankle mobility (ADF_ROM) and hip strength at 6 and 12 months after surgery. Patients’ functional status was assessed through the Olerud Molander Ankle Score (OMAS) and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Twenty-one patients with ankle fractures who completed the study showed a worse static and dynamic balance at 6 months. The YBT in the anterior direction (YBT_A) revealed balance deficits in the operated limb at 12 months compared to the non-operated limb (−5.6%) and the HC (−6.7%). They also showed a decreased ADF_ROM compared to the non-operated limb (−7.4°) and the HC (−11°). In addition, medium-term (6 months) deficits in abductor strength hip but no hip strength deficits were found at 12 months after surgery. Relative weight analyses showed that ADF_ROM and hip strength explained 35–63% of the YBT_A variance and AOFAS/OMAS scores. Balance, hip strength and ADF_ROM seem to be reliable indexes for assessing the functional status of these patients. These results could help to understand the relationship between these physical capacities and the patients’ perceived functional status.

Mesenchymal stem cell (MSC) transplantation has emerged as a promising approach for bone regeneration. Importantly, the beneficial effects of MSCs can be improved by modulating the expression levels of specific genes to stimulate MSC osteogenic differentiation. We have previously shown that Smurf1 silencing by using Locked Nucleic Acid-Antisense Oligonucleotides, in combination with a scaffold that sustainably releases low doses of BMP-2, was able to increase the osteogenic potential of MSCs in the presence of BMP-2 doses significantly smaller than those currently used in the clinic. This would potentially allow an important reduction in this protein in MSs-based treatments, and thus of the side effects linked to its administration. We have further improved this system by specifically targeting the Wnt pathway modulator Sfrp1. This approach not only increases MSC bone regeneration efficiency, but is also able to induce osteogenic differentiation in osteoporotic human MSCs, bypassing the need for BMP-2 induction, underscoring the regenerative potential of this system. Achieving successful osteogenesis with the sole use of LNA-ASOs, without the need of administering pro-osteogenic factors such as BMP-2, would not only reduce the cost of treatments, but would also open the possibility of targeting these LNA-ASOs specifically to MSCs in the bone marrow, allowing us to treat systemic bone loss such as that associated with osteoporosis.

The purpose of this study was to analyze the regenerative capacity of mesenchymal stem cells (MSCs) in the treatment of fractures. MSCs extracted from patients with osteoporotic hip fractures or hip osteoarthritis undergoing hip replacement surgeries were cultured and injected into mice with femoral fracture. Two experimental models were established, one for the systemic administration of MSCs (n = 29) and another one for local administration (n = 30). Fracture consolidation was assessed by micro-CT and histology. The degree of radiological consolidation and corticalization was better with MSCs from osteoporosis than from osteoarthritis, being significant after systemic administration (p = 0.0302 consolidation; p = 0.0243 corticalization). The histological degree of consolidation was also better with MSCs from osteoporosis than from osteoarthritis. Differences in histological scores after systemic infusion were as follows: Allen, p = 0.0278; Huo, p = 0.3471; and Bone Bridge, p = 0.0935. After local administration at the fracture site, differences in histological scores were as follows: Allen, p = 0.0764; Huo, p = 0.0256; and Bone Bridge, p = 0.0012. As osteoporosis and control groups were similar, those differences depended on an inhibitory influence by MSCs from patients with osteoarthritis. In conclusion, we found an unexpected impairment of consolidation induced by MSCs from patients with osteoarthritis. However, MSCs from patients with osteoporosis compared favorably with cells from patients with osteoarthritis. In other words, based on this study and previous studies, MSCs from patients with osteoporosis do not appear to have worse bone-regenerating capabilities than MSCs from non-osteoporotic individuals of similar age.

The possible association of common polymorphic variants related to thrombophilia (the rs6025(A) allele encoding the Leiden mutation, rs1799963(A), i.e., the G20210A mutation of the prothrombin F2 gene, the rs1801133(T) variant of the methylenetetrahydrofolate reductase (MTHFR) gene that encodes an enzyme involved in folate metabolism, and rs5918(C), i.e., the ‘A2’ allele of the platelet-specific alloantigen system that increases platelet aggregation induced by agonists), with the risk of Legg–Calvé–Perthes disease (LCPD) and the degree of hip involvement (Catterall stages I to IV) was analyzed in a cohort study, including 41 children of ages 2 to 10.9 (mean 5.4, SD 2.2), on the basis of clinical and radiological criteria of LCPD. In 10 of the cases, hip involvement was bilateral; thus, a total of 51 hips were followed-up for a mean of 75.5 months. The distribution of genotypes among patients and 118 controls showed no significant differences, with a slightly increased risk for LCPD in rs6025(A) carriers (OR: 2.9, CI: 0.2–47.8). Regarding the severity of LCPD based on Catterall classification, the rs1801133(T) variant of the MTHFR gene and the rs5918(C) variant of the platelet glycoprotein IIb/IIIa were associated with more severe forms of Perthes disease (Catterall III–IV) (p < 0.05). The four children homozygous for mutated MTHFR had a severe form of the disease (Stage IV of Catterall) and a higher risk of non-favorable outcome (Stulberg IV–V).