Low-level laser therapy (LLLT) is a treatment that is increasingly used in orthopedics practices. In vivo and in vitro studies have shown that low-level laser therapy (LLLT) promotes angiogenesis, fracture healing and osteogenic differentiation of stem cells. However, the underlying mechanisms during bone formation remain largely unknown. Factors such as wavelength, energy density, irradiation and frequency of LLLT can influence the cellular mechanisms. Moreover, the effects of LLLT are different according to cell types treated. This review aims to summarize the current knowledge of the molecular pathways activated by LLLT and its effects on the bone healing process. A better understanding of the cellular mechanisms activated by LLLT can improve its clinical application.

The proof of principle of the therapeutic potential of heat shock protein 47 (HSP47) for diseases characterized by defects in collagen I synthesis is here demonstrated in osteogenesis imperfecta (OI), a prototype of collagen disorders. Most of the OI mutations delay collagen I chain folding, increasing their exposure to posttranslational modifications that affect collagen secretion and impact extracellular matrix fibril assembly. As a model, we used primary fibroblasts from OI individuals with a defect in the collagen prolyl 3-hydroxylation complex, since they are characterized by the synthesis of homogeneously overmodified collagen molecules. We demonstrated that exogenous recombinant HSP47 (rHSP47) is taken up by the cells and localizes at the ER exit sites and ER-Golgi intermediate compartment. rHSP47 treatment increased collagen secretion, reduced collagen posttranslational modifications and intracellular collagen retention, and ameliorated general ER proteostasis, leading to improved cellular homeostasis and vitality. These positive changes were also mirrored by an increased collagen content in the OI matrix. A mutation-dependent effect was found in fibroblasts from 3 probands with collagen I mutations, for which rHSP47 was effective only in cells with the most N-terminal defect. A beneficial effect on bone mineralization was demonstrated in vivo in the zebrafish p3h1 ^–/– OI model.

Background: Ehlers–Danlos syndrome (EDS) is a phenotypically and genetically heterogeneous group of connective tissue disorders. Currently, diagnosis of EDS is based on a series of clinical and genetic tools. On the other hand, the hypermobile form has not yet been characterized from a genetic point of view: it is considered a part of a continuous spectrum of phenotypes, ranging from isolated non syndromic joint hypermobility, through to the recently defined hypermobility spectrum disorders (HSD). The aim of this study is to characterize the pain symptom that is not considered among the diagnostic criteria but is relevant to what concerns the quality of life of patients with EDS. (2) Methods: A review of the literature was performed on two medical electronic databases (PubMed and Embase) on 20 December 2022. Study selection and data extraction were achieved independently by two authors and the following inclusion criteria were determined a priori: published in the English language and published between 2000 and 2022. (3) Results: There were fifty eligible studies obtained at the end of the search and screen process. Pain is one of the most common symptoms found in Ehlers–Danlos (ED) patients. Different causes seem to be recognized in different phases of the syndrome. (4) Conclusions: Pain is a nonspecific symptom and cannot be considered among the diagnostic criteria, but it is a negative predictive factor in the quality of life of patients with EDS. Therefore, proper evaluation and treatment is mandatory.

Factor VIII (FVIII) is involved in several molecular pathways and biological processes; indeed, it has a role in the coagulative cascade, cardiovascular disease, hypertension, brain and renal function, cancer incidence and spread, macrophage polarization, and angiogenesis. Hemophilic patients usually present an increase in fracture risk, bone resorption, and an excess of osteoporosis as compared to healthy individuals. Several studies have tried to clarify their etiology but unfortunately it is still unclear. This review focuses on the role of FVIII in bone biology by summarizing all the knowledge present in the literature. We carried out a systematic review of the available literature following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Several studies demonstrated that FVIII is involved in different molecular pathways interfering with bone physiology; it exerts interesting effects on OPG/RANK/RANKL pathways and thrombin/PAR1 pathways. These data confirm a relationship between FVIII and bone metabolism; however, there are still many aspects to be clarified. This review highlights the role of the coagulation factor FVIII in bone metabolism, suggesting new hypotheses for future studies both in vitro and in vivo to better understand the important pleiotropic role of FVIII and hopefully to develop new therapeutic agents for skeletal diseases.

Hemophilic arthropathy (HA) is a complication of hemophilia, which is a genetic disorder characterized by a deficiency in blood clotting factors. HA is characterized by joint damage with inflammatory responses, pain, and movement limitations due to recurrent bleeding in the joints. The inflammatory reactions contribute to the activation of coagulation factors, which can exacerbate bleeding and further damage the affected joints. Therefore, the interaction between inflammation and coagulation plays a crucial role in the progression and complications of HA. Management strategies often focus both on inflammation and coagulation to alleviate symptoms and preserve joint function. Temperature can influence the inflammatory response and coagulation. The aim of this work was to understand how temperature management can positively or negatively influence the HA. We have carried out a narrative review of the available literature. This review explores the impacts of temperature on biological processes, and it discusses the possible clinical implications for the HA treatment. Our research shows that cold exposure has anti-inflammatory and analgesic effects, while heat is linked to pro-inflammatory cytokine release. Both hot and cold treatments are ill-advised for hemophilia patients. Heat stimulates neo-angiogenesis, and cold hampers coagulation, posing risks for increased bleeding in individuals with hemophilia.

The first objective of this paper is to report the clinical and functional results of a cohort of patients who underwent total knee arthroplasty revision at mid–long-term follow-up. The second objective is to investigate possible differences in postoperative functional and clinical outcomes between preoperative-cause-of-revision groups. Methods: we collected data from 105 surgeries performed between January 2008 and December 2014. Eighty-five of these patients were divided into subpopulations according to the causes of revision in order to study differences regarding their outcome. All the patients underwent a standard follow-up protocol with clinical and radiological exams at 1, 3, 6, 12, 24, and 36 months and at last follow-up. During the last follow-up, patient-reported outcome measures (PROMs) were used. We implemented the functional outcomes obtained with clinical data determined by the Oxford knee score (OKS), EQ-VAS, EQ-5D-5L, Knee Society Score (KKS), and range of motion (ROM). Statistically significant differences among the medians of the groups of OKS, EQ-VAS, EQ-5D-5L, KKS, and ROM (p < 0.05) were noticed. The Dunn’s test was used to perform post hoc comparisons, and it determined where the differences lie. Results: the median follow-up was 99 months (interquartile range (IQR) 80–115). The median age was 71.5 IQR 65.1–74.8)) with no relevant differences between the groups. More patients presented a preoperative diagnosis of aseptic loosening (29%), malpositioning (28%), and infection (24%), while a preoperative diagnosis of instability (11%) and periprosthetic fracture was observed in fewer cases. For OKS, the highest median value was in the periprosthetic fracture group (43.25, IQR 32.7–45.3) and the lowest median value was in the infection group (24.8, IQR 17.4–34.8). For EQ-VAS, the highest median value was in the periprosthetic fracture group (73.0, IQR 67.0–78.0) and the lowest median value was in the instability group (39.0, IQR 36.0–48.0). For EQ-5D-5L, the highest median value was in the aseptic loosening group (0.81, IQR 0.74-0.85) and the lowest median value was in the infection group (0.44, IQR 0.32–0.60). For KKS, the highest median value was in the aseptic loosening group (84.0, IQR 81.0–88.0) and the lowest median value was in the malpositioning group (56.5, IQR 49.4–66.0). For ROM, the highest median value was in the periprosthetic fracture group (105.0°, IQR 96.0–111.0°) and the lowest median value was in the infection group (88.5°, IQR 77.5–98.0°). Conclusion: Constrained condylar knee (CCK) prostheses can also be considered a good option to manage difficult cases of total knee arthroplasty revision, with satisfactory results being maintained over time; a preoperative diagnosis of infection is associated with a worse clinical and functional outcome.