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BACKGROUND: Lipocalin-2 (LCN-2) is an osteokine that suppresses appetite, stimulates insulin secretion, regulates bone remodeling, and is induced by proinflammatory cytokines. The aim of this work was to investigate the participation of LCN-2 in periodontitis associated with type 2 diabetes (T2D) by evaluating alveolar bone loss, glycemic control, inflammation, and femur fragility. METHODS: A murine model of periodontitis with T2D and elevated LCN-2 concentration was used. Functional LCN-2 inhibition was achieved using an anti-LCN-2 polyclonal antibody, and isotype immunoglobulin G was used as a control. The alveolar bone and femur were evaluated by micro-CT. Glucose metabolism was determined. Tumor necrosis factor (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) levels in alveolar bone lysates were quantified using ELISA, and serum cytokines were quantified using flow cytometry. A three-point bending test was performed in the femur, and RANKL levels were measured in femur lysates using ELISA. RESULTS: Functional inhibition of LCN-2 in T2D-periodontitis mice decreased alveolar bone loss in buccal and palatal surfaces and preserved the microarchitecture of the remaining bone, decreased TNF-α and RANKL in alveolar bone, reduced hyperglycemia, glucose intolerance, and insulin resistance, and increased insulin production through improving the functionality of pancreatic ß cells. Furthermore, this inhibition increased serum free-glycerol levels, decreased serum interleukin (IL)-6, increased serum IL-4, and reduced femur fragility and RANKL expression in the femur. CONCLUSIONS: LCN-2 participates in periodontitis associated with T2D. Inhibiting its function in mice with T2D and periodontitis improves pancreatic ß-cell function, and glucose metabolism and decreases inflammatory cytokines and bone-RANKL levels, which results in the preservation of femoral and alveolar bone microarchitecture. PLAIN LANGUAGE SUMMARY: In this study, we explored the role of a bone protein known as lipocalin-2 (LCN-2) in the connection between periodontitis and type 2 diabetes (T2D). Periodontitis is a destructive gum and alveolar bone disease. LCN-2 levels are increased in both T2D and periodontitis. Using a mouse model of T2D with periodontitis, we examined how blocking LCN-2 function affected various aspects of these two diseases. We found that this inhibition led to significant improvements. First, it reduced alveolar bone loss and preserved bone structure by decreasing local inflammation and bone resorption. Second, it improved glucose and lipid metabolism, leading to better blood-sugar control and decreased insulin resistance. Blocking the functions of LCN-2 also decreased systemic inflammation throughout the body and strengthened bone integrity. Overall, our results suggest that LCN-2 plays a crucial role in the periodontitis associated with T2D. By inhibiting LCN-2 function, we were able to improve pancreatic function, improve glucose metabolism, reduce inflammation, and enhance bone health. Targeting LCN-2 could be a promising strategy for the harmful effects of T2D and periodontitis.

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Bone marrow stromal cells (BMSCs) play a significant role in bone metabolism as they can differentiate into osteoblasts, bone marrow adipocytes (BMAds), and chondrocytes. BMSCs chronically exposed to nutrient overload undergo adipogenic programming, resulting in bone marrow adipose tissue (BMAT) formation. BMAT is a fat depot transcriptionally, metabolically, and morphologically distinct from peripheral adipose depots. Reactive oxygen species (ROS) are elevated in obesity and serve as important signals directing BMSC fate. ROS produced by the NADPH oxidase (NOX) family of enzymes, such as NOX4, may be responsible for driving BMSC adipogenesis at the expense of osteogenic differentiation. The dual nature of ROS as both cellular signaling mediators and contributors to oxidative stress complicates their effects on bone metabolism. This review discusses the complex interplay between ROS and BMSC differentiation in the context of metabolic bone diseases.Special attention is paid to the role of NOX4-ROS in regulating cellular processes within the bone marrow microenvironment and potential target in metabolic bone diseases.

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Osteoporosis is a metabolic and systemic disease characterized by alterations at the level of bone tissue with loss of bone mineral density, changes in microarchitecture, mineralization and remodeling that determine greater bone fragility and risk of fracture.Falls in the elderly are a risk factor closely related to fragility fractures and numerous studies demonstrate this relationship.Vertebral fractures are a major cause of morbidity and mortality. The epidemiology differs from osteoporotic fractures at other skeletal sites, as only one-third are clinically recognized. In the elderly, the approach to osteoporotic vertebral fracture involves comprehensive evaluation of the patient since it is both a cause and a consequence of multiple geriatric syndromes. This fracture, in its acute phase and subsequently, can lead to destabilization of other organs and systems of the elderly, medical complications at different levels, functional deterioration, dependence, and even the need for institutionalization.Therefore, multiple assessment of patients with vertebral fractures is necessary, addressing not only the history and risk factors of osteoporosis, but also those factors that lead to falls, as well as a comprehensive geriatric assessment and the complications closely associated with it.In this chapter we address each of these aspects that are necessary in the individual and multidimensional approach to the elderly patient with vertebral fracture due to bone fragility.

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OBJECTIVES: Increasing ratio of bone fragility, and susceptibility to fractures constitutes a major health problem worldwide. Therefore, we aimed to identify new compounds with a potential to increase proliferation and differentiation of osteoblasts. METHODS: Cellular and molecular assays, such as ALP activity, alizarin staining, and flow cytometry were employed to check the effect of TMF on osteogenesis. Moreover, gene expression analysis of certain important genes and transcriptional factors was also performed. RESULTS: Our findings report for the first time that 7,3',4'-trimethoxyflavone is capable of enhancing proliferation, and differentiation in osteoblast cells. Results from flow cytometry analysis also indicated that TMF increases the number of cells in S-phase. Furthermore, treatment with TMF altered the expression of osteogenic genes, OCN and Axin-2 indicating possible activation of Wnt signaling pathway. CONCLUSION: Taken together, this study identified that 7,3',4'-trimethoxyflavone has the potential to enhance osteoblast proliferation and differentiation, possibly due to the activation of Wnt/ß-catenin pathway. Thus, demonstrating TMF as naturally occurring agent to promote osteogenesis and prevention of bone fragility, and related disorders.

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Background: Improved bone health during adolescence can have lifelong implications, reducing the risk of bone fragility. Objective: This study aims to evaluate the effectiveness of an e-book in increasing knowledge about and promoting healthy practices related to bone health among Malay adolescents in Kuala Lumpur, Malaysia. Methods: A total of 72 adolescents (female: n=51, 71%; age: mean 15, SD 0.74 y) were recruited from selected secondary schools. The participants answered a pretest web-based questionnaire on sociodemographic data, knowledge about osteoporosis, and physical activity. A video call was conducted to assess dietary calcium intake. Participants were provided with a link to an e-book on bone health and instructed to read it within 2 weeks. Postintervention assessments included those for knowledge, physical activity, dietary calcium intake, and acceptance of the e-book. Results: There was a significant increase in the median knowledge score, which was 40.6% (IQR 31.3%-46.9%) during the pretest and 71.9% (IQR 53.9%-81.3%) during the posttest (P<.001). However, no changes were observed in dietary calcium intake or physical activity levels. Most participants did not meet the recommended calcium requirements (61/62, 98%) and exhibited sedentary behavior (pretest: 51/62, 82%; posttest: 48/62, 77%). The e-book, however, was well accepted, with the majority reporting that they understood the contents (70/72, 97%), liked the graphics (71/72, 99%), and approved of the layout (60/72, 83%) and font size (66/72, 92%) used. Conclusions: The developed e-book effectively increases knowledge levels related to bone health and is well accepted among participants. However, this educational material did not improve bone health practices. Additional strategies are necessary to bridge the gap between knowledge and behavior change.

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BACKGROUND: Both bone fragility and poor cognitive functions are known to contribute to fracture occurrence, but it remains unclear whether their contribution is independent of each other and which cognitive dysfunctions are most involved. This study aimed to clarify the involvement of various cognitive abilities in fall-related fractures among community-dwelling fallers aged 55 and over, and to determine whether poor cognitive abilities is a risk factor independent of bone fragility. METHODS: In a cross-sectional study, we collected sociodemographic and medical data, including bone mineral density (BMD), and performed cognitive and mobility assessments in 189 individuals with a history of fall in the previous year. RESULTS: Fallers with a fracture had poorer cognitive and mobility performance than non-injured fallers. Multivariate regressions revealed that cognition, BMD and other risk factors were independently associated with fracture among all participants (OR = 1.04, 95% CI = 1.01-1.08, p = 0.034 for completion time on part A of the Trail Making Test [TMT-A], and OR = 0.53, 95% CI = 0.33-0.84, p < 0.001 for BMD), particularly in women (OR = 0.77, 95% CI = 0.60-0.98, p = 0.039 for backward digit span score, and OR = 0.43, 95% CI = 0.25-0.75, p = 0.001 for BMD). CONCLUSION: Thus, poor cognition, especially poor processing speed and working memory, is associated with an increased risk of fracture in fallers, particularly in women, regardless of BMD or other fracture risk factors. Hence, an in-depth cognitive evaluation should enhance the detection of fallers at risk of fracture, particularly in the absence of signs of osteoporosis, and thus ensure the best possible prevention.

Asunto(s)

Accidentes por Caídas , Cognición , Fracturas Óseas , Humanos , Accidentes por Caídas/estadística & datos numéricos , Femenino , Estudios Transversales , Masculino , Anciano , Persona de Mediana Edad , Cognición/fisiología , Factores de Riesgo , Fracturas Óseas/epidemiología , Densidad Ósea , Anciano de 80 o más Años , Disfunción Cognitiva/epidemiología

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This study investigates the biomechanics of type 2 diabetic bone fragility through a multiscale experimental strategy that considers structural, mechanical, and compositional components of ex vivo human trabecular and cortical bone. Human tissue samples were obtained from the femoral heads of patients undergoing total hip replacement. Mechanical testing was carried out on isolated trabecular cores using monotonic and cyclic compression loading and nanoindentation experiments, with bone microdamage analysed using micro-computed tomography (CT) imaging. Bone composition was evaluated using Raman spectroscopy, high-performance liquid chromatography, and fluorometric spectroscopy. It was found that human type 2 diabetic bone had altered mechanical, compositional, and morphological properties compared to non-type 2 diabetic bone. High-resolution micro-CT imaging showed that cores taken from the central trabecular region of the femoral head had higher bone mineral density (BMD), bone volume, trabecular thickness, and reduced trabecular separation. Type 2 diabetic bone also had enhanced macro-mechanical compressive properties under mechanical loading compared to non-diabetic controls, with significantly higher apparent modulus, yield stress, and pre-yield toughness evident, even when properties were normalised against the bone volume. Using nanoindentation, there were no significant differences in the tissue-level mechanical properties of cortical or trabecular bone in type 2 diabetic samples compared to controls. Through compositional analysis, higher levels of furosine were found in type 2 diabetic trabecular bone, and an increase in both furosine and carboxymethyl-lysine (an advanced glycation end-product) was found in cortical bone. Raman spectroscopy showed that type 2 diabetic bone had a higher mineral-to-matrix ratio, carbonate substitution, and reduced crystallinity compared to the controls. Together, this study shows that type 2 diabetes leads to distinct changes in both organic and mineral phases of the bone tissue matrix, but these changes did not coincide with any reduction in the micro- or macro-mechanical properties of the tissue under monotonic or cyclic loading.

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Diabetes Mellitus Tipo 2 , Microtomografía por Rayos X , Humanos , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Fenómenos Biomecánicos , Anciano , Femenino , Huesos/patología , Huesos/fisiopatología , Huesos/diagnóstico por imagen , Masculino , Espectrometría Raman , Densidad Ósea/fisiología , Hueso Esponjoso/patología , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/fisiopatología , Persona de Mediana Edad , Estrés Mecánico

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Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic diseases in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search for differences in clinical characteristics. Methods: This is a single-center retrospective, case-controlled study. A total of 589 patients attending CTO Bone Unit between 2 January 2010 and 31 May 2023, due to osteoporosis and fragility fractures, were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 12.7%. Compared to patients without DM, the median age at the time of first fracture was similar: 72 years ± 13.5 interquartile range (IQR) vs. 71 years ± 12 IQR; prevalence of combination of vertebral and hip fractures was higher (p = 0.008), as well as prevalence of males (p = 0.016). Bone mineral density (BMD) at all sites was higher in DM group; trabecular bone score (TBS), instead, was significantly lower (p < 0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and, therefore, might be used as a diagnostic tool in clinical practice.

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Osteoid osteoma (OO) is a common, benign bone tumor. However, there are no case reports of OO associated with osteogenesis imperfecta (OI), or pathological fractures in OO. A 3-year-old girl with OI sustained a complete right tibial diaphyseal fracture. Bony fusion was completed after 4 months of conservative therapy; nevertheless, 18 months later spontaneous pain appeared at the fracture site, without any cause. Plain radiographs showed a newly apparent, rounded area of translucency 1 cm in diameter, just overlapping the previous fracture. Images obtained using three-dimensional time-resolved contrast-enhanced magnetic resonance angiography showed strong central enhancement in the early phase, with an apparent nidus, suggesting the diagnosis of OO. Nineteen months after the first fracture, while skipping, the patient refractured her tibial diaphysis at the site of the previous fracture. This is a very rare case of OO, apparently co-existing with OI and leading to a bony fracture. In our case, the combination of bone fragility in OI and a recent fracture at the site of the OO may have caused the re-fracture.

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Musculoskeletal alterations in hepatocellular carcinoma (HCC) are less common than liver-related complications. However, they can significantly impact the quality of life and overall prognosis of patients with HCC. The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asymptomatic and unapparent during routine clinical evaluations. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to the changes in the musculoskeletal system in patients with HCC, focusing on its clinical implications and underlying etiopathogenetic mechanisms. Osteolytic bone metastases are the most common skeletal alterations associated with HCC, which could be associated with an increased risk of low-trauma bone fracture. Moreover, previous studies reported that osteopenia, sarcopenia, and myosteatosis are associated with poor clinical outcomes in patients with HCC. Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients, these complications are frequently overlooked in the clinical management of patients with HCC. Taken together, contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis. Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.

Asunto(s)

Carcinoma Hepatocelular , Neoplasias Hepáticas , Sarcopenia , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Pronóstico , Sarcopenia/etiología , Sarcopenia/diagnóstico , Sarcopenia/terapia , Trasplante de Hígado , Calidad de Vida , Neoplasias Óseas/terapia , Neoplasias Óseas/complicaciones , Neoplasias Óseas/secundario , Neoplasias Óseas/patología , Neoplasias Óseas/mortalidad , Factores de Riesgo , Densidad Ósea , Enfermedades Musculoesqueléticas/terapia , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/etiología , Enfermedades Musculoesqueléticas/fisiopatología , Sistema Musculoesquelético/fisiopatología , Sistema Musculoesquelético/patología

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Osteoporosis is a metabolic and systemic disease characterized by alterations at the level of bone tissue with loss of bone mineral density, changes in microarchitecture, mineralization and remodeling that determine greater bone fragility and risk of fracture. Falls in the elderly are a risk factor closely related to fragility fractures and numerous studies demonstrate this relationship. Vertebral fractures are a major cause of morbidity and mortality. The epidemiology differs from osteoporotic fractures at other skeletal sites, as only one-third are clinically recognized. In the elderly, the approach to osteoporotic vertebral fracture involves comprehensive evaluation of the patient, since it is both a cause and a consequence of multiple geriatric syndromes. This fracture, in its acute phase and subsequently, can lead to destabilization of other organs and systems of the elderly, medical complications at different levels, functional deterioration, dependence, and even the need for institutionalization. Therefore, it is important to carry out a multiple assessment of patients with vertebral fractures, addressing not only the history and risk factors of osteoporosis, but also those factors that lead to falls, as well as a comprehensive geriatric assessment and the complications closely associated with it. In this chapter we address each of these aspects that are necessary in the individual and multidimensional approach to the elderly patient with vertebral fracture due to bone fragility.

RESUMEN

The high occurrence of distal fibula fractures among older women suggests a potential link to impaired bone health. Here we used a multiscale imaging approach to investigate the microarchitecture, mineralization, and biomechanics of the human distal fibula in relation to age and sex. Micro-computed tomography was performed to analyze the local volumetric bone mineral density and various microarchitectural parameters of the trabecular and the cortical compartment. Bone mineral density distribution and osteocyte lacunar parameters were quantified using quantitative backscattered electron imaging in periosteal, endocortical, and trabecular regions. Additionally, cortical hardness and Young's modulus were assessed by nanoindentation. While cortical porosity strongly increased with age independent of sex, trabecular microarchitecture remained stable. Notably, nearly half of the specimens showed non-bony hypermineralized tissue located at the periosteum, similar to that previously detected in the femoral neck, with no consistent association with advanced age. Independent of this finding, cortical and trabecular mineralization, i.e., mean calcium content, as well as endocortical tissue hardness increased with age in males but not females. Importantly, we also observed mineralized osteocyte lacunae that increased with age specifically in females. In conclusion, our results indicate that skeletal aging of the distal fibula is signified not only by pronounced cortical porosity but also by an increase in mineralized osteocyte lacunae in females. These findings may provide an explanation for the increased occurrence of ankle fractures in older women.

Asunto(s)

Calcinosis , Fracturas Óseas , Masculino , Humanos , Femenino , Anciano , Microtomografía por Rayos X , Peroné/diagnóstico por imagen , Porosidad , Osteocitos , Densidad Ósea , Envejecimiento

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INTRODUCTION: Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder characterized by reduced bone density and increased proneness to fractures. It manifests across a varied clinical spectrum of expressions in children and young adults. It is crucial for children with OI to have a multidisciplinary follow-up, including orthopedics, pediatrics, and physical medicine and rehabilitation. Although exercise may have no effect on the disease itself, it might improve the autonomy, self-esteem, and fitness of these children.  Methods: Retrospective cohort analysis of children and young adults aged three or more years old followed-up in a Level III Pediatric Hospital between 1995 and 2020. Demographic and clinical data were obtained from the hospital records and from the caregivers via phone calls. To our knowledge, this is the first national case series published assessing exercise habits in children with this condition. RESULTS: Among the 21 patients studied, the median age was 14 years, with no gender predominance. Eighteen (86%) practiced regular physical activity, while the remaining three (14%), all of whom were type III OI, were totally dependent. Of the aforementioned 18 children, 12 (67%) considered practicing the same level of physical activity compared to their healthy peers, although most of them needed adaptations. The most reported extracurricular activity was swimming, in 50% of the cases. About 39% engaged in physical activity two times or less per week, and 89% practiced for one hour or less per session. DISCUSSION: Over the years, it has become clear that physical activity is an important part of OI management. While awareness of the importance of exercise already exists, proper planning, follow-up, and monitoring are essential.

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Pediatric osteoporosis (PO) is a condition that is currently gaining recognition. Due to the lack of official definitions over the past few decades, the exact incidence of PO is unknown. The research does not provide a specific prevalence of PO in different world regions. However, this is expected to change with the latest 2019 guidelines proposed by the International Society of Clinical Densitometry. Although adult osteoporosis (AO) has been postulated a pediatric disease because its manifestation in adulthood is a result of the bone mass acquired during childhood, differences between PO and AO should be acknowledged. AO is defined as low bone density; however, PO is diagnosed based on existing evidence of bone fragility (vertebral fractures, pathological fractures). This is particularly relevant because unlike in adults, evidence is lacking regarding the association between low bone density and fracture risk in children. The enhanced capacity of pediatric bone for reshaping and remodeling after fracture is another difference between the two entities. This contrast has therapeutic implications because medication-free bone reconstitution is possible under certain conditions; thus, background therapy is not always recommended. In this narrative review, differences between PO and AO in definition, assessment, and medical approach were investigated.

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BACKGROUND: Osteoporosis in males is largely under-diagnosed and under-treated, with most of the diagnosis confirmed only after an osteoporotic fracture. Therefore, there is an urgent need for highly accurate and precise technologies capable of identifying osteoporosis earlier, thereby avoiding complications from fragility fractures. AIMS: This study aimed to evaluate the diagnostic accuracy and precision of the non-ionizing technology Radiofrequency Echographic Multi Spectrometry (REMS) for the diagnosis of osteoporosis in a male population in comparison with conventional Dual-energy X-ray Absorptiometry (DXA). METHODS: A cohort of 603 Caucasian males aged between 30 and 90 years were involved in the study. All the enrolled patients underwent lumbar and femoral scans with both DXA and REMS. The diagnostic agreement between REMS and DXA-measured BMD was expressed by Pearson correlation coefficient and Bland-Altman method. The accuracy of the diagnostic classification was evaluated by the assessment of sensitivity and specificity considering DXA as reference. RESULTS: A significant correlation between REMS- and DXA-measured T-score values (r = 0.91, p < 0.0001) for lumbar spine and for femoral neck (r = 0.90, p < 0.0001) documented the substantial equivalence of the two measurement techniques. Bland-Altman outcomes showed that the average difference in T-score measurement is very close to zero (-0.06 ± 0.60 g/cm2 for lumbar spine and - 0.07 ± 0.44 g/cm2 for femoral neck) confirming the agreement between the two techniques. Furthermore, REMS resulted an effective technique to discriminate osteoporotic patients from the non-osteoporotic ones on both lumbar spine (sensitivity = 90.1%, specificity = 93.6%) and femoral neck (sensitivity = 90.9%, specificity = 94.6%). Precision yielded RMS-CV = 0.40% for spine and RMS-CV = 0.34% for femur. CONCLUSION: REMS, is a reliable technology for the diagnosis of osteoporosis also in men. This evidence corroborates its high diagnostic performance already observed in previous studies involving female populations.

Asunto(s)

Osteoporosis , Fracturas Osteoporóticas , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Densidad Ósea , Osteoporosis/diagnóstico por imagen , Cuello Femoral , Análisis Espectral

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Background: The usefulness and problems with lateral lumbar interbody fusion (LLIF) with a percutaneous pedicle screw (PPS) for dialysis-related spondyloarthropathy are not clear. Therefore, we investigated the usefulness and problems with LLIF with PPS in dialysis-related spondyloarthropathy. Methods: In total, 77 patients who underwent LLIF with PPS were divided into two groups: the dialysis-related spondyloarthropathy group ("Group D") consisted of 15 patients (10 males and 5 females) with a mean age of 70.4 years and a mean duration of hemodialysis of 10.8 years; and the lumbar degenerative disease group ("Group L") included 62 patients (31 males and 31 females) with a mean age of 71.0 years. The mean follow-up period was 4 years in Group D and 3 years 9 months in Group L. We compared surgical invasiveness (operative time, blood loss), perioperative complications, clinical outcomes (Improvement ratio of the JOA score), bone fusion rate, reoperation, sagittal alignment, and coronal imbalance between the two groups. Results: There were no significant differences in operative time, blood loss, or the improvement ratio of the JOA score, but dialysis-related spondyloarthropathy was observed in one patient with superficial infection, three patients with endplate failure, and one patient with restenosis due to cage subsidence. Conclusions: We consider LLIF with PPS for dialysis-related spondyloarthropathy to be an effective treatment option because its surgical invasiveness and clinical outcomes were comparable to those for cases of lumbar degenerative disease. However, as endplate failure due to bone fragility and a reduced bone fusion rate were observed in dialysis spondylolisthesis cases, we advise a careful selection of indications for indirect decompression as well as the application of suitable pre- and postoperative adjuvant therapies.

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PURPOSE: Prevention of fractures is an unmet need in glucocorticoid (GC)-treated Duchenne muscular dystrophy. This study explored factors associated with incident vertebral fractures (VFs) to inform future fracture prevention efforts. METHODS: VFs were evaluated prospectively at study baseline and 12 months on lateral spine radiographs in participants aged 4 to 25 years with Duchenne muscular dystrophy. Clinical factors were analyzed for their association with the change in Spinal Deformity Index (sum of the Genant-defined VF grades from T4 to L4) between baseline and 12 months. RESULTS: Thirty-eight males were evaluated (mean ± SD age at baseline 11.0 ± 3.6 years; mean ± SD GC duration at baseline 4.1 ± 3.1 years; 74% ambulatory). Nine of 38 participants (24%) had 17 incident VFs, of which 3/17 VFs (18%) were moderate/severe. Participants with 12-month incident VF had lower mean ± SD baseline lumbar spine areal bone mineral density Z-scores (-2.9 ± 1.0 vs -1.9 ± 1.1; P = .049) and lower total body less head areal bone mineral density Z-scores (-3.1 ± 1.2 vs -1.6 ± 1.7; P = .036). Multivariable linear regression showed that at least 1 VF at baseline (P < .001), a higher number of antecedent non-VF (P < .001), and greater bone age delay at baseline (P = .027) were significant predictors of an increase in the Spinal Deformity Index from baseline to 12 months. CONCLUSION: The observation that ≥ 1 prevalent VF and/or non-VF were the strongest predictors of incident VFs at 12 months supports the need for prevention of first fractures in this high-risk setting. Bone age delay, a marker of GC exposure, may assist in the prioritization of patients in efforts to prevent first fractures.

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Fracturas Óseas , Distrofia Muscular de Duchenne , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Masculino , Humanos , Densidad Ósea , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/epidemiología , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología , Fracturas Óseas/etiología , Fracturas Óseas/inducido químicamente , Factores de Riesgo , Glucocorticoides/efectos adversos , Vértebras Lumbares/diagnóstico por imagen , Esteroides , Fracturas Osteoporóticas/etiología

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Glucocorticoid use in Duchenne and Becker muscular dystrophy prolongs ambulation but cause significant skeletal toxicity. Our analysis has immediate clinical implications, suggesting that growth hormone and testosterone have a stronger effect prior to first and subsequent vertebral fracture, respectively, relative to bisphosphonates alone in children with dystrophinopathies on chronic glucocorticoids. PURPOSE: Glucocorticoids prolong ambulation in boys with Duchenne muscular dystrophy; however, they have significant endocrine side effects. We assessed the impact of growth hormone (GH), testosterone, and/or zoledronic acid (ZA) on vertebral fracture (VF) incidence in patients with dystrophinopathies on chronic glucocorticoids. METHODS: We conducted a longitudinal retrospective review of 27 males with muscular dystrophy. Accelerated failure time (AFT) models were used to estimate the relative time to VF while on GH, testosterone, and/or ZA compared to ZA alone. Results are reported as failure time ratio, where >1 indicates prolonged time versus <1 indicates shorter time to next VF. RESULTS: The prevalence of growth impairment was 96% (52% utilized GH), pubertal delay was 86% (72% utilized testosterone), and low trauma fractures were 87% (72% utilized ZA). Multivariable analysis of the AFT models showed that participants on either GH or testosterone treatment relative to ZA alone experienced prolonged time to next VF (1.253, P<0.001), with GH being the significant contributor when analyzed independently from testosterone (1.229, P<0.001). Use of ZA with GH or testosterone relative to ZA alone resulted in prolonged time to next VF (1.171, P<0.001), with testosterone being a significant contributor (1.130, P=0.033). CONCLUSION: GH and testosterone each decreased VF risk in patients independent of or in combination with ZA, respectively.

Asunto(s)

Distrofia Muscular de Duchenne , Fracturas de la Columna Vertebral , Masculino , Niño , Humanos , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/tratamiento farmacológico , Glucocorticoides/efectos adversos , Testosterona/efectos adversos , Hormona del Crecimiento/efectos adversos , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/tratamiento farmacológico , Ácido Zoledrónico/uso terapéutico

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PURPOSE: Bone fragility in sickle cell disease (SCD) has been previously reported even in young patients, but the clinical consequences and specific management remain unclear. The objective of this study was to assess the prevalence of bone fragility in sickle cell patients and to evaluate the potential risk factors and associated complications. METHODS: We conducted a single-center cross-sectional study. Bone mineral densitometry (BMD) at the lumbar spine and the hip, Vertebral Fracture Assessment (VFA) and biological measurements were performed in patients aged between 20 and 40 years. RESULTS: One hundred and thirty-eight patients with sickle cell disease were included between June 2020 and December 2021. One hundred and one patients (73.2 %) were from Sub-Saharan Africa, 13 from North Africa (9.4 %), 11 from the Caribbean (7.9 %), 6 from the Indian Ocean. A Z-score < -2 was found in 43 patients (31.2 %) at the lumbar spine, in 4 patients (3 %) at the total hip, and in 5 patients (3.7 %) at the femoral neck. 59 patients (46.8 %) had vertebral deformities. Fragility fractures were recorded in 9 patients (10.8 %). Patients with low BMD had lower BMI (21.3 (19.0, 24.0) versus 24.0 (20.7, 26.1) Kg/m2, p = 0.003), lower osteonecrosis history (7 % versus 25.3 %, p = 0.011) and lower hemoglobin levels (9.0 (8.0, 10.0) versus 10.0 (9.0, 11.0) g/dL, p < 0.01). No association was found between history of fracture and low BMD. CONCLUSION: Young patients with SCD commonly have low BMD at the lumbar spine, but the prevalence of fragility fracture was low. Low BMD - specifically at the spine - may not be tantamount to bone fragility.

Asunto(s)

Anemia de Células Falciformes , Enfermedades Óseas Metabólicas , Fracturas Óseas , Fracturas de la Columna Vertebral , Humanos , Adulto Joven , Adulto , Densidad Ósea , Prevalencia , Estudios Transversales , Absorciometría de Fotón/efectos adversos , Fracturas Óseas/epidemiología , Fracturas Óseas/complicaciones , Fracturas de la Columna Vertebral/epidemiología , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/epidemiología , Vértebras Lumbares/diagnóstico por imagen , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología

RESUMEN

CONTEXT: The impairment of bone microarchitecture is a key determinant of skeletal fragility in patients with chronic kidney disease (CKD). Trabecular bone score (TBS) has been developed as a reliable non-invasive index of bone quality. However, its utility in this setting is still debated. OBJECTIVE: The aim of this systematic review and meta-analysis was to summarize the available evidence about TBS as a marker of skeletal fragility across the spectrum of CKD. METHODS: PubMed/Medline, EMBASE and Cochrane Library databases were systematically searched until July 2023 for studies reporting data about TBS in patients with CKD. Effect sizes were pooled through a random-effect model. RESULTS: Compared to controls, lower TBS values were observed in CKD patients not on dialysis (-0.057, 95%CI:[-0.090, -0.024], p < 0.01), in dialysis patients (-0.106, 95%CI:[-0.141, -0.070], p < 0.01) and in kidney transplant recipients (KTRs) (-0.058, 95%CI:[-0.103, -0.012], p = 0.01). With respect to fracture risk, TBS was able to predict incident fractures in non-dialysis patients at unadjusted analyses (hazard ratio (HR) per standard deviation decrease: 1.45, 95%CI:[1.05,2.00], p = 0.02), though only a non-significant trend was maintained when fully adjusting the model for FRAX® (HR = 1.26, 95%CI:[0.88,1.80], p = 0.21). Dialysis patients with prevalent fractures had lower TBS values compared to unfractured ones (-0.070, 95% CI:[-0.111, -0.028], p < 0.01). Some studies supported a correlation between TBS and fracture risk in KTRs, but results could not be pooled due to the lack of sufficient data. CONCLUSIONS: CKD patients are characterized by an impairment of bone microarchitecture, as demonstrated by lower TBS values, across the whole spectrum of kidney disease. TBS can also be helpful in the discrimination of fracture risk, with lower values being correlated with a higher risk of prevalent and incident fractures.