Search

Lysosomes are single membrane bounded group of acidic organelles that can be involved in a process called lysosomal exocytosis which leads to the extracellular release of their content. Lysosomal exocytosis is required for plasma membrane repair or remodeling events such as bone resorption, antigen presentation or mitosis, and for protection against toxic agents such as heavy metals. Recently, it has been showed that to fulfill this protective role, lysosomal exocytosis needs some autophagic proteins, in an autophagy-independent manner. In addition to these crucial physiological roles, lysosomal exocytosis plays a major protumoral role in various cancers. This effect is exerted through tumor microenvironment modifications, including extracellular matrix remodeling, acidosis, oncogenic and profibrogenic signals. This review provides a comprehensive overview of the different elements released in the microenvironment during lysosomal exocytosis, i.e. proteases, exosomes, and protons, and their effects in the context of tumor development and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We report here a rare case of an acute peripheral nerve compression by pseudotumoral calcinosis (PCT) at the right elbow in a patient with severe tertiary hyperaparathyroidism. This complication required urgent multidisciplinary management. Surgical decompression by PCT resection enabled rapid motor and sensory recovery., Competing Interests: There are none., (© 2024 Published by Elsevier Inc.)

Background: Osteoporosis (OP) is a pathology characterized by bone fragility affecting 30% of postmenopausal women, mainly due to estrogen deprivation and increased oxidative stress. An autophagy involvement is suspected in OP pathogenesis but a definitive proof in humans remains to be obtained., Methods: Postmenopausal women hospitalized for femoral neck fracture (OP group) or total hip replacement (Control group) were enrolled using very strict exclusion criteria. Western blot was used to analyze autophagy level., Results: The protein expression level of the autophagosome marker LC3-II was significantly decreased in bone of OP patients relative to the control group. In addition, the protein expression of the hormonally upregulated neu-associated kinase (HUNK), which is upregulated by female hormones and promotes autophagy, was also significantly reduced in bone of the OP group., Conclusions: These results demonstrate for the first time that postmenopausal OP patients have a deficit in bone autophagy level and suggest that HUNK could be the factor linking estrogen loss and autophagy decline., Clinical Trial Registration Number: ClinicalTrials.gov Identifier: NCT03175874, 2/6/2017., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition of RANKL reduced tumor volume. A beneficial effect of denosumab on pain in patients refractory to bisphosphonates has been reported, but without systematic quantification of pain improvement. This work describes the clinical experience of our group on the efficacy on pain of denosumab treatment, along with safety, in FD/MAS patients refractory to bisphosphonates., Materials and Methods: We have conducted a retrospective multicenter study in 6 academic rheumatology centers in France. We have collected patients and FD/MAS characteristics, duration of prior exposure to bisphosphonates, denosumab treatment modalities (dosage - administration regimen - number of courses); evolution of pain evaluated by Visual Analogic Scale (VAS)., Results: 13 patients were included (10 women and 3 men) 45 years on average, 5 MAS, 4 monostotic and 4 polyostotic forms. The average duration post-diagnosis of FD/MAS was 25 years and the mean duration of prior exposure to bisphosphonates was 4.7 years. Pain could be analyzed in 7 patients, showing a significant improvement from a mean VAS of 7.8 to 2.9 (-4.9 points, p = 0.003). In one patient with fronto-orbital FD/MAS, a 30 % decrease in lesional volume, assessed by MRI, was observed within 6 months of treatment, that was sustained over the following 12 months. Treatment regimens were heterogeneous. No hypercalcemia was observed after treatment cessation and the clinical tolerance was good., Discussion: This study suggests that denosumab reduces pain in patients with DF/MAS refractory to bisphosphonates, and quantifies this improvement for the first time in a multicenter study. In our cohort, no patients who discontinued denosumab developed hypercalcemia and clinical tolerance was overall good. This study also provides encouraging data regarding lesion volume control. Further controlled studies are required to determine the place and modalities of the denosumab treatment of FD/MAS., Conclusion: Denosumab significantly decreased pain in FD/MAS refractory to bisphosphonate. This study paves the way for a randomized clinical trial to validate and standardize the prescription of denosumab in FD/MAS., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Knee osteoarthritis-related pain limits physical function and leads to functional disability. Physical activity is one of the central recommendations for the management of knee osteoarthritis. Although concentric muscle activities are often preferred to eccentric ones, the corresponding rationale remains controversial., Objective: To explore the effect of a 6-week exercise program on function, pain, and performance in patients with symptomatic knee osteoarthritis., Methods: Patients with symptomatic knee osteoarthritis were included in the prospective EX-ART project (Walking performance in osteoARThritic subjects: effect of an ECCentric muscle strengthening program) and randomized in a 6-week rehabilitation program including either eccentric or concentric activities. Metrics of interest chosen as end points measured before and after the rehabilitation were WOMAC score, pain, and muscular performance (quadriceps power P MAX and contraction strength M MAX ). MRI was also used to assess muscle volume and fat infiltration changes., Results: 30 patients were included in each group; mean age was 74 (±7.6); 69% were women. At week 6, both groups showed a significant improvement in the WOMAC without difference between the two groups ( p  = 0.7). No difference between the two groups was identified for the pain reduction ( p  = 0.7). A significant improvement in the change in P MAX and M MAX at high velocity ( p  = 0.001 and p  = 0.002) was observed in the eccentric group only. A vastus medialis hypertrophy was quantified in the eccentric group only ( p  = 0.002), whereas fat infiltration in the quadriceps muscles was unchanged., Conclusion: Physical activity, whether eccentric or concentric, has a benefit on function and pain in patients with symptomatic knee osteoarthritis. A few differences have been identified between the two types of rehabilitation. More particularly, a gain in muscle performance and vastus medialis volume was found with eccentric rehabilitation only., Registration: www.ClinicalTrials.gov, registration number NCT03167502., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Autophagy is a ubiquitous cellular process, allowing the removal and recycling of damaged proteins and organelles. At the basal level, this process plays a role in quality control, thus participating in cellular homeostasis. Autophagy can also be induced by various stresses, such as nutrient deprivation or hypoxia, to allow the cell to survive until conditions improve. In recent years, the role of this process has been widely studied in many pathologies such as neurodegenerative diseases or cancers. In bone tissue, various studies have shown that autophagy is involved in the survival, differentiation and activity of osteoblasts, osteocytes and osteoclasts. The evolution of this knowledge has led to the identification of new molecular pathophysiological mechanisms in bone pathologies. This review reports the current state of knowledge on the role of autophagy in 4 bone diseases: osteoporosis, which seems to be associated with a decrease in autophagy, osteopetrosis and Paget's disease where the course of the autophagic process is disturbed, and finally osteosarcoma where autophagy seems to play a protumoral role. A better understanding of the involvement of autophagy in these pathologies should eventually lead to the identification of new potential therapeutic targets., (Copyright © 2021 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Despite its potential biomechanical advantages, reverse shoulder arthroplasty (RSA) is still considered to be particularly high risk in rheumatoid patients who are osteoporotic and immunodeficient. Our purpose was to report prosthesis survival, complications, and outcomes of RSA in patients with rheumatoid arthritis (RA) at minimum 5-year follow-up., Methods: We conducted a retrospective multicenter study including 65 consecutive primary RSAs performed in 59 patients with RA between 1991 and 2010. We excluded rheumatoid patients with previous failed anatomic shoulder arthroplasty. Age at surgery averaged 69 years (range, 46-86 years). A structural bone grafting was performed in 18 cases (45%), using the humeral head in 15 cases (BIO-RSA technique), the iliac crest in 2 cases (Norris technique), and an allograft in 1 case. The mean follow-up was 92 months (range, 60-147 months) or until revision surgery., Results: Revision-free survivorship, using Kaplan-Meier curves, was 96% at 7 years. Two patients had revision surgeries for infections, with associated glenoid loosening in 1 case. No humeral loosening was recorded. The mean adjusted Constant score improved from 36% ± 23% preoperatively to 90% ± 26% postoperatively, and mean Subjective Shoulder Value improved from 21% ± 13% to 85% ± 12%, respectively (P < .001). Active anterior elevation increased from 65° ± 43° to 132° ± 27°, active external rotation increased from 10° ± 26° to 22° ± 27°, and internal rotation improved from buttocks to waist (P < .001). Stable fixation of the baseplate was achieved in all cases (including the 6 patients with end-stage RA), and we did not observe bone graft nonunion or resorption. Preoperative radiologic pattern (centered, ascending, or destructive), presence of acromial fractures or tilt (4 cases, 10%), and scapular notching (55%) on final radiographs were not found to influence outcomes or complication rate. Patients with absent/atrophied teres minor had lower functional results. Overall, 95% of the patients were satisfied with the procedure., Conclusion: RSA is a safe and effective procedure for the treatment of RA patients, with a low risk of complications and low rate of revision, regardless of the radiologic presentation and stage of the disease. Rheumatoid patients undergoing primary RSA, with or without glenoid bone grafting, can expect a revision-free survival rate of 96% at 7-year follow-up. RSA offers the benefit of solving 2 key problems encountered in rheumatoid shoulders: glenoid bone destruction and rotator cuff deficiency., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent data demonstrate the anabolic effect of oxytocin on bone. Bone cells express oxytocin receptors. Oxytocin promotes osteoblasts differentiation and function, leading to an increased bone formation with no effect on bone resorption and an improvement of bone microarchitecture. Oxytocin is synthetized by osteoblasts, and this synthesis is stimulated by estrogen. Animal studies demonstrate a direct action of oxytocin on bone, as the systemic administration of oxytocin prevents and reverses the bone loss induced by estrogen deficiency. Although oxytocin is involved in bone formation in both sexes during development, oxytocin treatment has no effect on male osteoporosis, underlining the importance of estrogen that amplifies its local autocrine and paracrine secretion. There are few human data showing a decrease in the oxytocin serum level in anorexia nervosa independently of estrogen and in amenorrheic women associated with impaired bone microarchitecture; in post-menopausal women a higher oxytocin serum level is associated with higher bone density, but not in osteoporotic men. Oxytocin displays many effects that may be beneficial in the management of osteoporosis, cardiovascular diseases, cognitive disorders, breast cancer, diabetes and body fat gain, all age-related diseases affecting elderly women, opening exciting therapeutic perspectives, although the issue is to find a single route, dosage and schedule able to reach all these targets.

Cancer stem cells (CSCs) represent a minor population of cancer cells with stem cell-like properties which are able to fuel tumor growth and resist conventional treatments. Autophagy has been described to be upregulated in some CSCs and to play a crucial role by maintaining stem features and promoting resistance to both hostile microenvironments and treatments. Osteosarcoma (OS) is an aggressive bone cancer which mainly affects children and adolescents and autophagy in OS CSCs has been poorly studied. However, this is a very interesting case because autophagy is often deregulated in this cancer. In the present work, we used two OS cell lines showing different autophagy capacities to isolate CSC-enriched populations and to analyze the autophagy in basal and nutrient-deprived conditions. Our results indicate that autophagy is more efficient in CSCs populations compared to the parental cell lines, suggesting that autophagy is a critical process in OS CSCs. We also showed that the antipsychotic drug thioridazine is able to stimulate, and then impair autophagy in both CSC-enriched populations, leading to autosis, a cell death mediated by the Na+/K + ATPase pump and triggered by dysregulated accumulation of autophagosomes. Taken together, our results indicate that autophagy is very active in OS CSCs and that targeting this pathway to switch their fate from survival to death could provide a novel strategy to eradicate these cells in osteosarcoma.

Osteoporosis treatment. Osteoporosis treatment is a public health issue that requires a comprehensive approach combining drugs and lifestyle measures. Lifestyle measures (nutrition, prevention of falls, etc.) are essential. Pharmacological therapy are teriparatide, reimbursed in the presence of two vertebral fractures, raloxifene to be reserved for women under 70 years of age with a low risk of peripheral fracture, bisphosphonates (oral or IV) and denosumab, efficient to reduce all types of fractures and that require dental precautions. Zoledronic acid is the first choice recommended after femoral neck fracture. The patient must be informed of the benefits, risks, and duration of treatment and the consolidation treatment required after teriparatide or denosumab discontinuation. Adherence and tolerance to treatment must be monitored to ensure its efficiency., Competing Interests: M.-C. Trojani déclare n’avoir aucun lien d’intérêts.V. Breuil déclare des liens ponctuels (interventions et/ou prise en charge lors de congrès) avec MSD, Lilly, BMS, Astra Zeneca, Amgen, Roche, Pfizer, Expanscience, UCB et AbbVie.

Background: Staphylococcus saccharolyticus is a rarely encountered coagulase-negative, which grows slowly and its strictly anaerobic staphylococcus from the skin. It is usually considered a contaminant, but some rare reports have described deep-seated infections. Virulence factors remain poorly known, although, genomic analysis highlights pathogenic potential., Case Presentation: We report a case of Staphylococcus saccharolyticus spondylodiscitis that followed kyphoplasty, a procedure associated with a low rate but possible severe infectious complication (0.46%), and have reviewed the literature. This case specifically stresses the risk of healthcare-associated S. saccharolyticus infection in high-risk patients (those with a history of alcoholism and heavy smoking)., Conclusion: S. saccharolyticus infection is difficult to diagnose due to microbiological characteristics of this bacterium; it requires timely treatment, and improved infection control procedure should be encouraged for high-risk patients.