Introduction: Metabolic syndrome (MS) is associated with increased carbonyl stress, accumulation of advanced glycation end products (AGE), and induction of arterial calcifications (AC) through the osteoblastic transdifferentiation of vascular smooth muscle cells (VSMC). Metformin (MET) inhibits this transdifferentiation in vitro. We evaluated whether oral MET can prevent AC in an experimental model of MS. Materials and Methods: Young adult male Wistar rats were divided into two groups: one received water as the drinking source (C) and the other a 20% fructose solution (F). After two weeks, and for an additional four weeks, each group was subdivided, and MET (100 mg/kg/day) was added to the drinking water of one half (thus, M and FM). Metabolic and body parameters were measured. The aorta was dissected for histomorphometric and immunohistochemical analyses. Aortic VSMC were isolated to assess alkaline phosphatase (ALP) activity, collagen production, extracellular matrix mineralization, and gene expression of Runx2 and the receptor for AGE (RAGE). Results: Group F developed features consistent with MS, including increased adiposity, non-fasting hyperglycemia, dyslipidemia, and elevated serum fructosamine. Aortas from F animals showed a reduced elastic-to-muscular ratio, increased collagen content, AGE accumulation, and RAGE overexpression. VSMC from F rats displayed higher ALP activity, increased collagen production and mineralization, and elevated expression of Runx2 and RAGE. Cotreatment with MET prevented all these MS-induced alterations. In vitro, MET blocked AGE-induced RAGE upregulation by VSMC, an effect abolished by an AMP-activated protein kinase (AMPK) inhibitor. Conclusion: These findings indicate that oral MET treatment attenuates extracellular glycation, AGE/RAGE activation, and vascular remodeling associated with experimental MS.
Introduction: bone mass undergoes dynamic changes throughout growth. The objective was to evaluate variations in bone remodeling markers, trabecular microarchitecture, and densitometric and biomechanical properties of the femur in female Wistar rats. Materials and methods: six age groups were studied (newborn, 21, 45, 90, 105, and 180 days; n=6/group). Serum levels of calcium (Ca), phosphorus (Pi), osteocalcin (OCN), and C-terminal telopeptide of type I collagen (CTX) were determined. Bone structure was evaluated by histomorphometry (BV/TV), density (BMDft), and femoral bone mineral content (BMOft) by densitometry (DXA), and biomechanics (CSMI, stiffness, fracture strength, Young's modulus) by three-point bending test. Results: the results showed that Ca was highest at 21 and 180 days, and the lowest Pi value was observed at 90 days (p<0.05). OCN decreased and CTX increased from 21 to 180 days of age. BV/TV increased significantly from birth to 45 days. DMOft and CMOft increased up to 180 days. Biomechanical properties reached their maximum values in early adulthood. Discussion: taken together, these findings describe the physiological sequence of bone maturation, where bone turnover initially predominates, followed by a phase of structural gain and, finally, mechanical consolidation of the bone. Conclusions: these data may serve as a reference for experimental studies evaluating interventions on bone health during growth.
Introduction: Angular deformities around the knee, i.e., genu varum and genu valgum, are common in children and can arise from various underlying conditions. Surgical treatment options include temporary hemiepiphysiodesis (guided growth), which is less invasive and carries fewer risks compared to traditional osteotomies. While effective for coronal deformities, the impact of this technique on persistent torsional deformities remains underexplored. Objectives: This study aims to assess the persistent torsional deformity following complete correction of varus coronal deformity in pediatric patients treated with 8-plate hemiepiphysiodesis. Methods: A retrospective case series study was conducted in a tertiary center from March 2023 to January 2025. The study included skeletally immature patients aged 2.5 to 12 years with genu varum deformity who underwent 8-plate hemi-epiphysiodesis for varus deformity correction. Clinical and radiological assessments-including foot progression angle, thigh-foot angle and heel bisector line-were used to evaluate rotational deformities after varus correction. Results: A total of 26 limbs of 14 patients with mean age 4.54 years were analyzed. The mean duration of epiphysiodesis was 10.46 months. Despite successful correction of coronal deformities, 61.5% of patients exhibited persistent intoeing. The persistent torsion was of tibial source which was manifested in the foot progression angle and the thigh-foot angle. Conclusion: While 8-plate is effective for coronal deformity correction in pediatric genu varum, a significant proportion of patients retain persistent torsional deformities.
Introduction: Fragility fractures in older adults often coexist with comorbidities, affecting their location and severity. Objective: To analyze whether the number of comorbidities acts as a mediator in the association between hypertension and fragility fracture type in older adults. Materials and methods: A cross-sectional study based on secondary data from 719 adults aged >= 50 years with non-vertebral fragility fractures. Hayes' PROCESS model 4 was used to assess whether the total number of comorbidities mediated the association between hypertension and fracture type (upper vs. lower limb). Linear and logistic regressions were adjusted for age, sex, diabetes, dyslipidemia, smoking, and calcium/vitamin D supplementation. Bootstrap resampling with 5000 iterations was applied. Results were illustrated in a mediation model diagram to represent the theoretical analytical framework. Results: Hypertension (B=1.35; p<0.001), diabetes mellitus (B=1.09; p<0.001), dyslipidemia (B=1.36; p<0.001), and vitamin D use (B=0.73; p<0.001) were associated with a higher number of comorbidities. In the logistic regression, a direct positive association between hypertension and upperlimb fractures was observed (B=0.43; p=0.042), along with a significant indirect association mediated by comorbidities (B=-0.48; 95% CI: -0.73 to-0.28). A higher number of comorbidities was associated with lower limb fractures (B=-0.36; p<0.001). Sex (B=-0.50; p=0.012), dyslipidemia (B=0.82; p<0.001), smoking (B=0.42; p=0.033), and low calcium intake (B=-0.71; p=0.008) were also significant. Conclusions: Hypertension was associated with upper limb fractures; however, this association was attenuated or reversed in the presence of multiple comorbidities, favoring lower limb fractures.
Introduction: medical history increases the risk of fragility fractures, predisposing to more vulnerable areas according to the type of history. Objective: to determine the most vulnerable areas of fragility fractures according to clinical history. Materials and method: analytical and crosssectional study of a secondary database of 719 adults. The variables were the presence of shoulder, wrist, hip and ankle fractures, age, sex, diabetes mellitus, hypertension, obesity, smoking, reduced mobility, dyslipidemia, osteoporosis, age, arthritis, renal, cardiovascular and thyroid disease, cancer and number of comorbidities. The automatic detection tree of chi-square interactions and Cramer's V were used. Results: the decision tree identified key variables of fragility fracture areas, age group, diabetes and comorbidities. Ankle fractures were associated primarily with individuals aged 50 to 65 years with diabetes (V=0.181; p<0.001). Hip fractures with individuals aged 84 years or older (V=0.332; p<0.001). Shoulder and wrist fractures with individuals aged 66 to 83 years with two or fewer comorbidities (V=0.216; p<0.001). Conclusions: fragility fractures are significantly associated with age and the presence of comorbidities, especially diabetes. People older than 84 years have a greater propensity for hip fractures, those between 50 and 65 years with diabetes are more prone to ankle fractures. Shoulder and wrist fractures are more common in individuals aged 66 to 83 years with few comorbidities.
Introduction: A rare disease (RD) is defined as one whose prevalence in the population is equal to or less than 1 in 2,000 individuals. This term not only relates to the few reported cases but also to the lack of understanding of their pathophysiology or the absence of therapeutic options to treat them. They are also referred to as "orphan diseases" or "rare diseases." It is estimated that currently, there are more than 8,000 different rare diseases. Methodology: A retrospective study was conducted from January 2013 to December 2024. Medical records of patients diagnosed and followed for rare bone diseases, where the initial consultation was due to bone involvement (defined as persistent bone pain or nontraumatic fractures), were analyzed. Both male and female patients of all ages were included. Patients with rare diseases not involving bone, as well as those diagnosed with rare diseases of rheumatologic, endocrinologic, infectious, neoplastic causes, or those presenting with osteoporosis or osteoporotic fractures, were excluded. Results: A registry of 133 cases of rare bone diseases from a center in the city of Rosario over the past 12 years is presented. The diagnosed cases included the following: Complex Regional Pain Syndrome (CRPS), X-linked Hypophosphatemia (XLH), Paget's disease, fibrous dysplasia, osteogenesis imperfecta, osteopetrosis, Gorham's disease, pseudohypoparathyroidism, pseudomiogenetic hemangioendothelioma, Ollier's disease, calcinosis (CREST), brown tumors due primary hyperparathyroidism, tumor-induced osteomalacia, high bone mass disease due LRP6 mutation, MEN1, extensive heterotopic ossification secondary to COVID, Mazabraud's syndrome, Gaucher disease, sarcoidosis, uremic tumoral calcinosis, systemic mastocytosis, Rosai-Dorfman disease, congenital central core myopathy, hypoparathyroidism. Discussion: 80% of rare diseases have an identified genetic origin, affecting one or more genes. Most of these conditions begin in childhood, but many are diagnosed in adulthood, especially when the forms are nonlife-threatening. Most do not have specific treatments. Interdisciplinary management is crucial in handling these cases, as is genetic study to advance research and treatment of these conditions.
Introduction: chronic kidney disease (CKD) can cause disturbances in mineral and bone metabolism, manifesting as abnormalities in serum levels of calcium, phosphorus, PTH, or vitamin D, and may lead to vascular and soft tissue calcification. Calciphylaxis, a life-threatening complication associated with CKD, results from calcium deposition in the dermal and adipose microvasculature. Uremic tumoral calcinosis (UTC) is another common complication in patients undergoing hemodialysis. Clinical Case: a 27-year-old female patient was referred for a large mass in her right shoulder, characterized by 4 months of pain. Her medical history includes hemolytic uremic syndrome at 8 months of age, requiring hemodialysis. At 16 years old, she underwent a kidney transplant until the age of 21, after which she continued with hemodialysis due to transplant rejection. A CT scan and MRI of the right shoulder revealed a lesion compatible with UTC. Biochemical evaluation showed elevated phosphate levels with an increased calcium-phosphate product. Due to the functional impairment it caused, marginal surgical resection was decided. The specimen was sent for delayed pathological examination, confirming the diagnosis. Conclusion: the management of UTC focuses on improving phosphorus, calcium, and parathyroid hormone levels through various strategies. Vascular evaluation is crucial due to the high cardiovascular risk in these patients, which is one of the leading causes of mortality in CKD.
Despite significant advances in understanding the etiology of many rare diseases (RDs), these scientific breakthroughs have not always translated into direct benefits for patients. Rare diseases (also known as orphan diseases) are officially defined in the U.S. as those affecting fewer than 200,000 people in the country. It is estimated that there are approximately 7,000 rare diseases; however, only between 250 and 300 have FDA-approved treatments. One of the greatest challenges in the development of drugs for rare diseases is the difficulty of conducting clinical trials in small populations. Translational science, which serves as the foundation for the rational development of treatments, has progressed at a slower pace compared to basic scientific innovation. This has created a gap between laboratory discoveries and their application in clinical practice, limiting the availability of effective therapies. To achieve a real impact on patients' lives, it is crucial to strengthen research on rare diseases through translational science, which transforms basic knowledge into practical, multidisciplinary applications. In this context, designing innovative clinical trial strategies, optimizing biomarker identification, and fostering collaboration among various scientific and medical sectors becomes essential. Only through these efforts it will be possible to overcome existing barriers and accelerate the development of effective treatments for these rare conditions.
Rare diseases or EPF (Rare Conditions) are conditions that affect a small percentage of the population but represent a significant public health challenge, impacting approximately 6-8% of the global population. It is estimated that there are between 6,000 and 8,000 rare diseases, though the number varies due to inconsistent definitions and differences in diagnostic technologies across countries. In some places, such as the United States, a disease is considered rare if it affects fewer than 200,000 people, while in Europe and Japan, the definitions differ. In Argentina, rare diseases affect 1 or less in 2,000 people, and the National Law 26.689 of 2011 ensures rights for diagnosis, treatment, and comprehensive care for patients. This lack of consensus complicates both diagnosis and treatment. Despite advances in research and the creation of orphan drugs, many disorders still lack approved treatments. It is estimated that around 80% of rare diseases have a genetic cause, although this data has not been confirmed through thorough analysis. Additionally, certain diseases are more prevalent in specific regions due to particular genetic mutations. The exact number of rare diseases remains uncertain, and although the range is cited as 6,000 to 8,000, databases list more than 21,000 diseases, suggesting the number could be significantly higher. This highlights the need for greater harmonization in the definition and research of these conditions.
Introduction: The emergence of the SARS-CoV-2 pandemic presented numerous challenges, including identifying disease predictors and developing effective therapeutic options. Numerous studies have reported the potential protective effect of vitamin D (VD) against respiratory infections. However, the literature remains inconclusive regarding the benefits of VD on COVID-19 progression. Objectives: This study aimed to assess the prevalence of VD deficiency (VDD) and its association with COVID-19 severity in hospitalized patients. Methods: prospective cohort study. We enrolled 250 adults (>= 50 years) of both sexes with COVID-19 admitted between 2020-09-01 and 2021-06-31. VD levels, comorbidities, inflammatory markers, oxygen or mechanical ventilation needs, ICU admission, and mortality were analyzed. VDD was defined as <20 ng/mL. The association between VD value and death was evaluated with a logistic regression model. Results: Mean age was 73.4 +/- 11 years, and 49% males. Median VD level was 20.2 ng/mL. The prevalence of VDD was 49.2% (n 123; CI95 43-55.4%). Hypovitaminosis D (<30 ng/mL) was observed in 77.2%. Patients with VDD had a higher Charlson index (p=0.02). VD levels did not correlate with oxygen saturation, inflammatory markers, or severity events (mechanical ventilation, ICU admission and death). In a mortality analysis, VD level was not a prognostic factor (OR 0.98 CI 0.95-1; p 0.1). Conclusion: The prevalence of VDD in our cohort was 49.2%. We found no association between VD levels and COVID-19 severity, similar to several published studies.
In recent years, it has been discovered that mutations in CYP24A1 (24 alpha-hydroxylase) promote an excess of calcidiol and calcitriol due to a failure in catabolic activity, which manifests as hypercalcemia, renal lithiasis, and nephrocalcinosis. This condition is known as Idiopathic Infantile Hypercalcemia (IIH). Biallelic alterations are severe expressions of the disease and are diagnosed in childhood. Little is known about heterozygous forms. This report presents an adult patient illustrating this alteration. A 27-year-old male was referred for evaluation due to repeated low PTH levels. The patient has had bilateral renal lithiasis associated with hypercalciuria since the age of 8, without response to conventional treatment. Persistent lithiasis, chronic kidney disease, and intermittent hypercalcemia were observed. His mother presented with hypercalciuria. The physical examination was normal. Highlights of the studies include hypercalcemia, inhibited PTH, high-normal levels of 25OH vitamin D and 1,25(OH)2D3, increased creatinine, normal phosphatemia and alkaline phosphatase. The 1,25(OH)2D3/PTH ratio was elevated (> 40 pmolL/pmol/L). Granulomatous and oncological diseases were ruled out by specific studies. The possible mutation of the CYP24A1 gene was considered. Molecular study of CYP24A1 showed mutations described in IIH: exon 2 variant c.428-430delAAG / alteration p. Glu143del, heterozygous, pathogenic, and exon 8 variant c.999_1006delCAGTCTAA / p. Ser334Valfs*9, heterozygous, likely pathogenic. It was assumed that the patient presents a monoallelic form of IIH. It is important to consider the mutations of the enzyme CYP24A1, which catabolizes the metabolites of vitamin D, calcidiol and calcitriol, in the differential diagnosis of non-PTH-dependent hypercalcemia and hypercalciuria.
Dengue is a viral disease transmitted by Aedes aegypti mosquitoes that has recently experienced a significant increase in incidence. This report presents an unusual case of osteonecrosis affecting both the upper and lower jaw in a young patient without a history of pathological or medication exposure before contracting dengue virus infection. Similar to other viral diseases associated with maxillary osteonecrosis, Dengue induces endothelial inflammation that triggers a series of events leading to thrombosis and necrosis of bone tissue. Considering that the increase in dengue cases is linked to climate change, it is plausible to speculate that dengue will become more frequent in the future, as well as its association with osteonecrosis.
Introduction: the use of grip strength measurement in research studies and clinical practice has gained relevance due to its close relationship with health events. The European Working Group on Sarcopenia (EWGSOP) introduced the measurement of muscle function (muscle strength and physical performance) as an essential criterion for the diagnosis of sarcopenia. For this reason, the primary objective of our study was to evaluate three different methods for determining handgrip strength measurements. Methods: a quasi-experimental study was conducted in three bone health centers in Argentina. Healthy male and female volunteers, aged between 18 and 40 years were included. We assessed the impact of limb dominance, posture (sitting vs standing), time of day (morning vs afternoon), and verbal encouragement (yes/no) on handgrip strength measurements. Results: a total of 117 participants were analyzed with males comprising 41% of the sample. The mean age of men was 27.7 years and mean age of women was 28.7 years. Men exhibited greater handgrip strength compared women (46.5 +/- 11.7 kg vs. 27.0 +/- 6.8, p<0.001). Handgrip strength was consistently greater in the dominant limb across all tests (p<0.05). No variations were observed in handgrip strength with respect to posture or time of day (p>0.05). However, a significant difference was noted before and after verbal encouragement (29.81 +/- 12.14 kg vs. 33.50 +/- 11.40 p<0.001). Conclusions: according to our results, handgrip strength should be measured using the dominant limb and evaluators should use verbal encouragement to obtain maximum grip strength. Ethics approval information: National University of Rosario (resolution N degrees 5596/2023)
Purpose: Toassessthefrequencyofdysmobility syndrome (DS) in a group of postmenopausal women, to determine the frequency of fragility fractures in these patients, and to compare the frequency of fragility fractures and other clinical, biochemical, densitometric, and muscle health characteristics between patients with and without DS. Methods: Postmenopausal women aged >= 60 years were invited to participate in a muscle health study program in our bone clinic. The diagnosis of DS was considered when at least three of the following factors were present: osteoporosis, >= 1 fall in the preceding year, low muscle mass, slow gait speed, low grip strength, and high-fat mass. The cohort was divided into patients with DS and without DS. Results: The mean age in the study cohort (n = 250) was 70.36 +/- 7.72 years. DS was diagnosed in 77 patients (30.8 %). A history of falls in the preceding year and the prevalence of fragility fractures were more frequent in patients with DS in comparison with the control group (60% vs. 19%, p <0.001 and 42% vs 17%, p <0.001, respectively). Furthermore, the history of fragility fractures was significantly associated with the presence of DS (OR 4.92, 95% CI 2.3-10.4, p <0.001). Discussion: A significant association was found between DS and a history of fragility fractures. Although this new concept needs further investigation, it seems that the identification of various compartments affected by the aging process results in an opportunity to better predict major adverse events in the elderly.
Tissue engineering is an interdisciplinary science that is constantly searching for materials that can help repair damaged tissue, in our case, bone and cartilage. In this work, we obtained a biomaterial using sodium alginate (natural polymer) and synthetic cationic polyelectrolyte (PEC) produced in our laboratories. The union of both polymers, given by ionic forces, was increased thanks to the application of ultrasound. When we evaluated the in vitro toxicity of the biomaterials using RAW 264.7 macrophage cells, we found that the application of ultrasound produced a non-toxic material compared to when this technology is not applied, in addition to a greater capacity to promote the proliferation of MC3T3-E1 preosteoblastic cells , chondrocytic cells grown on them. Although additional experiments are needed, our Alginate-PEC biomaterial with ultrasound is a promising approach that can be used to generate scaffolds for bone , cartilage tissue engineering.
Hip fractures due to osteoporosis constitute a health problem and are associated with increased morbidity and mortality. Objective: To determine the rates, causes, and risk factors for mortality in patients with hip fractures over a 10-year follow-up period. Methodology: This retrospective cohort study included patients aged >= 50 years who were part of the health plan at the Italian Hospital of Buenos Aires and were hospitalized for hip fracture between July 1, 2005, and December 31, 2010. Sex, age, comorbidities, and pre- and post-fracture bisphosphonate treatment were evaluated. Statistical methods included chi-square tests, mean, median, standard deviation, Kaplan-Meier survival analysis, and Cox proportional hazards model. Results: A total of 965 patients were included. The mean age at the time of fracture was 81.6 years, and 80.7% were women. The overall mortality rate at one year was 14.9%, increasing to 73.2% at 10 years. Mortality was higher in men (HR: 1.31; 95% CI 1.10-1.58; p=0.003), older age (HR: 1.10; 95% CI 1.091.11; p<0.001), and Charlson comorbidity score (HR: 1.29; 95% CI 1.23-1.34; p<0.001) at ten years of follow-up. Risk factors for mortality during the study period, according to multivariate Cox analysis, included age, Charlson index, male sex, medial fracture, dementia, and congestive heart failure. Bisphosphonates improved survival (Cox analysis). The most common causes of death were infectious and cardiovascular. Patients that survived after ten years of followup were healthier, younger at baseline, and showed a higher proportion of treatment with bisphosphonates after hip fracture. Conclusions: This long-term observation highlights the importance of follow-up and osteoactive drug treatment after hip fracture, especially in older, male and patients with comorbidities
Vitamin D has anti-inflammatory actions, increasing the expression of antimicrobial peptides. Low levels of 25hydroxyvitamin D (25OHD) are associated with obesity. Secretory leukocyte protease inhibitor (SLPI) is a non-glycosylated serine protease peptide with antimicrobial and anti-inflammatory activity, which could be associated with obesity and inflammation. Objective: to evaluate the correlation between 25OHD and SLPI in women and its relationship with obesity. Thirty-two postmenopausal women (69 +/- 6 years), without conditions or medications that could affect their inflammatory status, were included. Body weight (BW) (kg) and height (m) were measured and body mass index (BMI) was calculated. SLPI (ng/mL) (ELISA) and 25OHD (ng/mL) (RIA) levels were determined. Fat mass (densitometry) (gr) was normalized by BW to obtain percent fat mass (PFM). Results (X +/- SD): BMI was 30.3 +/- 6.9 and PFM was 43.9 +/- 9.6. SLIP ranged from 1.9 to 29.7 (13.1 +/- 6.8) and 25OHD ranged from 8.2 to 48 ng/mL (22.1 +/- 13.7). PFM, but not BMI, negatively correlated with SLIP (r=-0.64, p=0.01) and 25HOD (r=-0.69, p=0.01). SLPI correlated with 25OHD (r=0.61, p=0.01). For obese women with 25OHD sufficiency, the correlation between both was highly significant (r=0.97; p<0.0001). Conclusions: In addition to favoring the release of antimicrobial peptides, our results showed that adequate 25OHD levels correlate positively with SLIP in obesity. Further studies in a larger population would be necessary to clarify whether this correlation is clinically relevant.
This paper presents two separate sections, dealing with I. a synthesis of the recent advances in the knowledge and understanding of the biomechanical-structural relationships involved in the muscle-bone interactions, and II. a practical application of these concepts to the analysis and interpretation of some tomographic data of bone and muscle indicators obtained from individuals chronically exposed to different intensities of physical activity. The first section recalls that in all vertebrates the skeletal development is normally influenced by both genetic and epigenetic factors. Among the latter, virtually only mechanical and endocrine-metabolic determinants are acknowledged. Mechanical modulators exert chiefly directional effects and constitute the input of bone mechanostat, a feedback system which regulates the only bone property subjected to a cybernetic control, namely, the structural stiffness of every bone. This control is carried out with a high degree of regional specificity. Endocrine-metabolic modulators exert only systemic (non-directional) effects, with a wide spectrum of actions on virtually every bone property, but with no role at all in any kind of feedback regulation within the skeletal system. A technical reference to pQCT technology is also provided, concerning its relevance to the non-invasive analysis of the musculoskeletal status in humans. The application section presents some recent tomographic (pQCT) studies performed in healthy adults of both sexes who either had sedentary habits or have been chronically trained in long-distance running. The analysis of the collected data shows some original evidence of 1. the relevance of the vectorial influence of the mechanical environment of the skeleton to the biological regulation of the efficiency of bone structure; 2. the role of those mechanical factors as determinants of the input of the mechanostat system; 3. the high dependence of all the above relationships upon the activity of the regional muscles, and 4. the systemic influence of endocrine-metabolic factors as determinants of significant, sex-related differences in the observed results.
