Search Results (69)

Noonan syndrome (NS) is a genetic disorder characterized by distinctive craniofacial and skeletal features, short stature, mild to moderate developmental impairment, and multisystem involvement, notably affecting the cardiovascular, musculoskeletal, and endocrine systems. Although abnormalities of the bone matrix, as well as osteopenia and osteoporosis, are well recognized in individuals with NS and other RASopathies, the specific impact of RAS/MAPK pathway dysregulation on bone health remains poorly understood. Objectives: The aim of this study was to evaluate bone turnover and bone remodeling markers in a cohort of children with NS, to gain further insights into the bone status of these patients. Methods: In this cross-sectional, case-control study, we analyzed 28 children (20 males) with a molecular diagnosis of NS and 35 healthy subjects (21 males), matched by age and sex. We assessed markers of bone metabolism and bone turnover (calcium, phosphate, PTH, 25(OH)-vitamin D, osteocalcin, procollagen I N-propeptide-P1NP, bone alkaline phosphatase-BALP, C-telopeptides of type I collagen-CTX) and bone remodeling (RANKL, OPG, and sclerostin). Bone mineralization was measured at the lumbar spine (L2–L4) using dual-energy X-ray absorptiometry (DEXA). Results: Serum CTX levels were significantly higher in NS patients compared to controls (1.8 ± 0.7 vs. 1.3 ± 0.5 ng/mL, p = 0.0004). RANKL levels were higher in NS patients, although the difference did not reach statistical significance. No significant differences were found for OPG, sclerostin, or other markers of bone metabolism between patients and controls. Conclusions: Children with NS exhibit increased bone resorption, as indicated by elevated CTX levels, suggesting a potential imbalance in bone remodeling processes. Further studies are warranted to better define the impact of RAS/MAPK pathway dysregulation on bone health in this population. Full article

Osteoporosis is the most common metabolic bone disorder, characterized by reduced bone mass and abnormal bone microarchitecture, resulting in increased bone fragility and a heightened risk of low-energy fractures. Pediatric osteoporosis may be either primary, due to genetic factors, or secondary, arising from chronic diseases and/or their treatment. Oral health and proper occlusion are integral components of overall health, influencing functionality, nutrition, facial aesthetics, and psychosocial development during childhood. Severe malocclusion can adversely affect speech, mastication, appearance, psychological well-being, and social interactions. The aim of this narrative review is to examine the existing literature on orthodontic anomalies and management strategies in pediatric patients with osteoporosis while highlighting clinical challenges, treatment limitations, and areas necessitating further research. A comprehensive literature search was conducted in the PubMed database, focusing on studies involving human subjects aged 3 to 18 years, published in English between 2002 and 2024. The findings indicate that children with osteoporosis present with more severe dental and occlusal complications compared to their healthy peers, often facing increased orthodontic complexity due to skeletal fragility and systemic comorbidities. These challenges necessitate careful, individualized treatment planning and close multidisciplinary collaboration. Although research in this field remains limited due to the rarity of pediatric osteoporosis, recognizing and addressing the specific needs of this population is critical to improving clinical outcomes and guiding future therapeutic approaches. Full article

Primary osteoporosis in children and young adults often suggests a monogenic disease affecting bone microarchitecture and bone mineral density. While Osteogenesis Imperfecta (OI) is the most recognized genetic cause of recurrent fractures, many other genes involved in bone metabolism may contribute to osteoporosis. Among them, FGFR2 plays a critical role in bone growth and development by regulating osteoblast differentiation and proliferation, as well as chondrogenesis. Germline pathogenic FGFR2 variants are typically associated with syndromic craniosynostosis, conditions not characterized by bone fragility or osteoporosis. A report recently identified FGFR2 as a potential cause of dominant early-onset osteoporosis and bone fractures in a family. We report the case of a child affected by severe osteoporosis with multiple fractures. We performed clinical exome sequencing in trio to investigate potential genetic causes of the observed phenotype and identified a likely mosaic pathogenic FGFR2 variant, absent in both parental samples. Our findings provide further evidence that FGFR2 pathogenic variants can lead to a novel non-syndromic bone mineralization disorder, reinforcing the role of FGFR2 in the pathogenesis of early-onset osteoporosis. Full article

Background/Objectives: This scoping review explores the relationship between ultra-processed food (UPF), bone health, and joint diseases, focusing on its potential impact on bone mineral density (BMD), osteoporosis, osteoarthritis, and inflammatory arthritis, including rheumatoid arthritis (RA), gout, and spondyloarthritis. Methods: A search strategy was developed using key terms such as “ultra-processed food” and related terms like “fast food,” alongside various definitions of bone health impairment, chronic degenerative joint diseases, and inflammatory arthritis. Results: A total of 19 studies were included: 12 on bone health, 3 on osteoarthritis, and 4 on inflammatory arthritis. Preclinical studies showed that UPF consumption negatively affects bone structure and strength. In studies on children and adults, four investigations (2013–2017) found no association between fast food intake and BMD. However, more recent large-scale cross-sectional studies linked higher UPF consumption to lower BMD, increased osteoporosis risk, and greater prevalence of osteopenia, particularly in postmenopausal women. UPF intake was associated with knee osteoarthritis risk, with evidence suggesting an interaction with cartilage thickness, though no association was found for hip osteoarthritis. In inflammatory arthritis, UK Biobank data indicated a higher risk of RA and gout in UPF consumers, while a Brazilian study reported worse metabolic profiles in RA patients. No significant differences in UPF intake were found in spondyloarthritis. Conclusions: This review highlights relevant considerations about the deleterious role of UPF on bone health and joint diseases, providing additional evidence to suggest healthier dietary patterns to patients and to the general population. Full article

Background/Objective: With increasing cases of osteoporosis in children and adolescents, the need for timely diagnosis, management, and follow-up has become important. This study aimed to determine whether bone turnover markers (BTMs), particularly serum bone-specific alkaline phosphatase (BsALP) and serum C-telopeptide of collagen type 1 (CTx), accurately reflect BMD. Methods: In this retrospective study, 280 post-puberty males and females who were previously diagnosed with hemato-oncologic, rheumatic, gastrointestinal, and endocrinologic diseases at a single tertiary care center were reviewed. The association between the lumbar spine bone mineral density (LSBMD) Z-scores and BTMs, such as BsALP and CTx, were assessed. The LSBMD was measured in the anterior–posterior direction using DXA, and BTMs were determined using the blood samples obtained. Results: Of the 280 patients, 95 were male (33.9%), and the mean age was 15.4 $\pm$ 2.07 years. With multivariate regression analysis, LSBMD Z-scores and BsALP showed a negative correlation with p < 0.007, while CTx was not statistically significant. The logistic regression models showed that after adjusting for underlying diseases and sex, as BsALP increased, the probability of LSBMD Z-score being ≤−2 increased with an odds ratio of 1.043 (p = 0.048). When comparing BTMs with vertebral fracture while adjusting for underlying diseases and sex, as BsALP increased, the probability of vertebral fracture increased with an odds ratio of 1.035 (p = 0.005). Conclusions: The positive correlation between BsALP and LSBMD Z-scores being ≤−2, as well as with vertebral fracture after adjusting for underlying diseases and sex, suggests the possible application of BsALP as a predictor of bone health in patients. Full article

Background/Objectives: This study aimed to determine the frequency of osteoporosis in children and adolescents with thalassemia major (TM) and to identify risk factors for the early development of osteoporosis. Methods: This retrospective study included 27 patients under 18 years of age receiving regular blood transfusions and chelation therapy for TM at our hospital. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry, and a lumbar spine Z-score <−2 was considered osteoporotic. Patients with osteoporosis were classified as Group 1 and those without osteoporosis as Group 2. Results: Osteoporosis was detected in 22.2% of the study population. The mean age was 13.83 ± 2.85 years in Group 1 and 7.95 ± 5.05 years in Group 2 (p = 0.012). Body weight and height were significantly lower in Group 1 (p = 0.012 and p = 0.004). Ferritin levels were 5306 ± 1506 ng/mL in Group 1 and 2020 ± 1205 ng/mL in Group 2, and the difference was significant (p = 0.001). Group 1 had significantly lower Ca and P levels (p < 0.001, p = 0.038). BMD was negatively correlated with ferritin (r = −0.791, p < 0.001) and positively correlated with calcium (r = 0.499, p = 0.008). Conclusions: Osteoporosis is a common condition in TM patients. Patients with risk factors should be followed more closely. These patients should be identified before BMD decreases. To prevent osteoporosis, regular BMD scans should be performed, calcium and vitamin D supplementation should be provided, and physical activity should be encouraged. Full article

Background: Bisphosphonates used for the treatment of osteoporosis, hypercalcemia, or heterotopic calcifications can cause serious adverse dental events such as osteonecrosis of the maxillary and mandibular bones. However, the effects in childhood remain scarcely explored. Case Presentations: We encountered two children who had started bisphosphonate therapy before completion of the primary dentition. No systemic disease causing congenital delayed tooth eruption was diagnosed. Although the children’s height and weight increased with age, their tooth eruption was significantly delayed compared with the mean. The primary teeth gradually erupted in the follow-up period; however, some teeth did not completely erupt and needed to be extracted to allow for permanent tooth eruption. Conclusions: We report a case of children with early use of bisphosphonates and eruption disturbance, highlighting the need for further investigation into the relationship between these factors. Full article

Background: Inflammatory bowel disease (IBD) is associated with multiple factors that influence bone metabolism. This study aimed to compare the clinical manifestations and diagnostic parameters of patients with Crohn’s disease (CD) and ulcerative colitis (UC) at the time of diagnosis, as well as to assess their relationship with subsequent bone disorders. Methods: Blood tests (including calcium–phosphate metabolism) and fecal tests (including calprotectin) were performed in eighty children recently diagnosed with IBD. Additionally, the bone densitometry results were evaluated in 25 of them. Results: Diarrhea (p = 0.02) and bloody stools (p < 0.001) were more frequent in patients with UC, whereas fever was more common in patients with CD (p = 0.003). Laboratory tests revealed anemia in 62.5% (50/80) and thrombocytosis in 36.3% (29/80). Higher calprotectin levels in the feces were found in girls at the time of diagnosis (p = 0.02). Osteopenia was detected in almost half of the examined patients (12/25), and 20% (5/25) met the criteria for osteoporosis. Low calcium levels at diagnosis were correlated with subsequent bone disorders (p = 0.005). Insufficient levels of vitamin D were detected in 77.8% (56/80). Conclusions: Early disease detection and the appropriate monitoring of children with IBD may decrease the risk of serious consequences, including osteoporosis. Full article

The incidence of osteoporosis in children is increasing because of the increased survival rate of children with chronic diseases and the increased use of bone-damaging drugs. As childhood bone fragility has several etiologies, its management requires a thorough evaluation of all potentially contributing pathogenetic mechanisms. This review focuses on the main causes of primary and secondary osteoporosis and on the benefits and limits of the different radiological methods currently used in clinical practice for the study of bone quality. The therapeutic and preventive strategies currently available and the most novel diagnostic and treatment strategies are also presented. Optimal management of underlying systemic conditions is key for the treatment of bone fragility in childhood. DXA still represents the gold standard for the radiologic evaluation of bone health in children, although other imaging techniques such as computed tomography and ultrasound evaluations, as well as REMS, are increasingly studied and used. Bisphosphonate therapy is the gold standard for pharmacological treatment in both primary and secondary pediatric osteoporosis. Evidence and experience are building up relative to the use of monoclonal antibodies such as denosumab in cases of poor response to bisphosphonates in specific conditions such as osteogenesis imperfecta, juvenile Paget’s disease and in some cases of secondary osteoporosis. Lifestyle interventions including adequate nutrition with adequate calcium and vitamin D intake, as well as physical activity, are recommended for prevention. Full article

There is robust evidence linking diet and physical activity to major public health concerns such as cardiovascular diseases, type 2 diabetes, and osteoporosis. Dietary habits of children and adolescents are frequently discussed in health policy debates due to their modifiability, making them viable targets for prevention and health promotion initiatives. This study aimed to assess the dietary habits of 14–15-year-old Faroese adolescents using an online 24 h recall tool, examining their intake relative to public recommendations and exploring associations with health behaviour and wellbeing. A total of 78 participants (45 girls, 33 boys), with a mean age of 14.3 years, recorded their food intake and completed a questionnaire. Results indicated a higher intake of saturated fats and sugar and a lower intake of dietary fibre, n-3 fatty acids, fruits, and vegetables compared to recommendations. Healthier food intake was associated with better health behaviour and wellbeing. This very first study of Faroese adolescents’ overall diet underscores the need for health-promoting interventions, and suggests the feasibility of using an online 24 h recall tool for dietary assessment in this age group, albeit with necessary adjustments for Faroese language and traditional foods. Full article

Low serum vitamin D levels have been associated with a variety of health conditions which has led the medical community but also the general population to evaluate vitamin D status quite liberally. Nevertheless, there remain questions about the efficacy and cost-effectiveness of such a broad and untargeted approach. This review therefore aims to summarize the current evidence and recommendations on when and how to evaluate vitamin D status in human health and disease. For the general population, most guidelines do not recommend universal screening but suggest a targeted approach in populations at risk. Also, some guidelines do not even recommend evaluating vitamin D status when vitamin D substitution is indicated anyway, such as in children or patients receiving anti-osteoporosis drugs. In those guidelines that recommend the screening of vitamin D status, serum 25(OH)D levels are universally proposed as the preferred screening tool. However, little attention is given to analytical considerations and almost no guidelines discuss the timing and frequency of screening. Finally, there is the known variability in diagnostic thresholds for defining vitamin D insufficiency and deficiency. Overall, the existing guidelines on the evaluation of vitamin D status differ broadly in screening strategy and screening implementation, and none of these guidelines discusses alternative screening modes, for instance, the vitamin metabolic ratio. Efforts to harmonize these different guidelines are needed to enhance their efficacy and cost-effectiveness. Full article

Introduction: Hereditary multiple exostosis or hereditary multiple osteochondromas is a very rare clinical condition. Usually, these lesions tend to occur in the pediatric population, remaining silent until adulthood. Moreover, current studies show a small prevalence in the male population. The osteochondromas usually occur at sites with great bone activity and turnover, such as the diaphysis or metaphyseal plates (especially in children) of long bones. Their appearance in short bones (such as vertebrae) is very rare. Case presentation: We present a case of familial HME in a 53-year-old female patient with a very uncommon clinical description of the disease. The patient presented at our hospital with Frankel D-type paraparesis, with multiple osteochondromas (located at the right humerus, bilateral femurs, right tibia, and hip joints, besides the numerous ones over the spinal column) and urinary incontinence. She was suffering from bilateral coxarthrosis and gonarthrosis, which limited severely the range of her movements. An early menopause status was brought into consideration by the patient, being installed circa 15 years before, at 38 years old. She was currently in treatment with bisphosphonates for her concomitant osteoporosis. Conclusions: Despite the relatively rare nature of the disease, it may be an important concern for the patient’s quality of life. Intraspinal processes may trigger paraparesis or other neurological statuses, which may require a surgical treatment. The nature of the lesions is usually benign and do not require further radio- or chemotherapy. Full article

Background: Idiopathic juvenile osteoporosis (IJO) is a rare condition characterized by low bone mass that can increase the risk of fractures in children. Treatment options for these patients are limited as the molecular mechanisms of disease initiation and progression are incompletely understood. Sclerostin inhibits canonical Wnt signaling, which is important for the bone formation activity of osteoblasts, and elevated sclerostin has been implicated in adult osteoporosis. Objective: To evaluate the role of sclerostin in IJO, high-resolution confocal microscopy analyses were performed on bone biopsies collected from 13 pediatric patients. Methods: Bone biopsies were stained with sclerostin, and β-catenin antibodies showed elevated expression across osteocytes and increased sclerostin-positive osteocytes in 8 of the 13 total IJO patients (62%). Results: Skeletal sclerostin was associated with static and dynamic histomorphometric parameters. Further, colocalization analyses showed that bone sclerostin colocalized with phosphorylated β-catenin, a hallmark of Wnt signaling that indicates Wnt inhibition. In contrast, sclerostin-positive osteocytes were not colocalized with an “active” unphosphorylated form of β-catenin. Conclusions: These results support a model that altered levels of sclerostin and Wnt signaling activity occur in IJO patients. Full article

This systematic review aims to investigate the relationship between muscle mass and specific health outcomes in pediatric populations with neuromuscular disorders. A search was performed for any relevant studies published in English from 1996 to 2023 in five databases. To be included in this analysis, articles must have had participants with an average age ≤21, focus on children with neuromuscular disabilities, and primarily examine relationships between muscle mass and any functional or health outcomes measure. Studies including typically developing children were used to contrast and enhance findings. Thirty-two studies were included, with 10,129 unique individuals represented: seventeen studies focused on healthy/typically developing children; seven on children with cerebral palsy; three on children with Duchenne muscular dystrophy; two on children with sarcopenia; and one study each on children with osteoporosis, congenital muscular dystrophy, and other various neurologic disorders. Thirteen studies assessed functional outcomes, ten assessed bone outcomes, and nine assessed other cardiovascular/metabolic outcomes. All of the included studies demonstrated relationships between muscle mass and respective outcomes in varying measures. The results of this review demonstrate that there is a consistently recognized relationship between muscle mass and important health outcomes in children, supporting clinically targeting muscle mass as a means to optimize desired outcomes. Full article

For a wide range of chronic autoimmune and inflammatory diseases in both adults and children, synthetic glucocorticoids (GCs) are one of the most effective treatments. However, besides other adverse effects, GCs inhibit bone mass at multiple levels, and at different ages, especially in puberty. Although extensive studies have investigated the mechanism of GC-induced osteoporosis, their target cell populations still be obscure. Here, our data show that the osteoblast subpopulation among Gli1⁺ metaphyseal mesenchymal progenitors (MMPs) is responsive to GCs as indicated by lineage tracing and single-cell RNA sequencing experiments. Furthermore, the proliferation and differentiation of Gli1⁺ MMPs are both decreased, which may be because GCs impair the oxidative phosphorylation(OXPHOS) and aerobic glycolysis of Gli1⁺ MMPs. Teriparatide, as one of the potential treatments for GCs in bone mass, is sought to increase bone volume by increasing the proliferation and differentiation of Gli1⁺ MMPs in vivo. Notably, our data demonstrate teriparatide ameliorates GC-caused bone defects by targeting Gli1⁺ MMPs. Thus, Gli1⁺ MMPs will be the potential mesenchymal progenitors in response to diverse pharmaceutical administrations in regulating bone formation. Full article