Search Results (104)

Severe musculoskeletal disease characterized by marked joint laxity was the cause of euthanasia in two wild juvenile American black bears (Ursus americanus) admitted to a rehabilitation facility in eastern Tennessee in 2023. Previously, almost all reported musculoskeletal diseases in this population were of traumatic etiology, even in malnourished yearlings. Case 1 was an orphaned 11-month-old male cub exhibiting disproportionate dwarfism, progressive immobility, and joint laxity. Necropsy findings suggested either chondrodysplasia or rickets, and imaging findings supported a skeletal dysplasia. Case 2 was a 14-month-old emaciated male yearling exhibiting joint laxity and immobility. Necropsy findings showed osteoporosis and serous atrophy of fat, and imaging findings were inconsistent with a skeletal dysplasia. Both cases were clinically inconsistent with rickets based on normal calcium, phosphorous, and parathyroid hormone concentrations; however, Case 1 had hypovitaminosis D (9 nmol/L) compared to healthy juvenile black bears. We hypothesize that Case 1 had a genetic chondrodysplasia while the osteoporosis of Case 2 was due to chronic malnutrition. The goal of this case report is to inform wildlife agencies and facilities to monitor for similar, non-trauma-related debilitating musculoskeletal disease in free-ranging bears and evaluate cases that allow us to further understand the disease processes involved. Full article

Vitamin D₃ deficiency and insufficiency are becoming a common global issue for us, especially in the most industrially developed countries. The only acknowledged activity of vitamin D₃ in vertebrates is to promote the absorption of calcium and, therefore, allow for the mineralization of bones. Accordingly, its deficiency is associated with diseases such as rickets. Other numerous vital functions associated with vitamin D₃ are yet to be considered, and the function of vitamin D₂ in plants is unknown. Thus, 100 years after its discovery, the importance of vitamin D still seems to be unacknowledged (except for rickets), with little attention given to its decrease throughout the world. In this review, I suggest that vitamin D deficiency and insufficiency may be linked to the westernized lifestyle in more developed countries. Furthermore, I suggest that, rather than the calcemic activity, the main function of vitamin D is, in general, that of strengthening living organisms. I conclude with the hypothesis that vitamin D deficiency may represent a marker for a greater risk of chronic inflammatory diseases and a shorter life expectancy. Full article

Fat-soluble vitamins, including vitamins A, D, E, and K, are energy-free molecules that are essential to the body’s functioning and life. Their intake is almost exclusively exogenous, i.e., dietary. As a result, fat-soluble vitamin deficiencies are rarer in industrialized countries than in countries with limited resources. Certain groups of people are particularly affected, such as newborns or growing children, pregnant or breastfeeding women, and elderly or isolated individuals. Deficiencies in vitamins A, D, E, and K are also relatively frequent in subjects with digestive tract disorders, liver diseases, chronic pathologies, or in intensive care patients. Deficiencies or excesses of fat-soluble vitamins are responsible for a variety of more or less specific clinical pictures. Certain syndromes are typical of fat-soluble vitamin deficiency, such as the combination of ophthalmological and immunity impairments in the case of vitamin A deficiency or hemorrhagic syndrome and osteopenia in the case of vitamin E deficiency. This is also the case for osteomalacia, muscular weakness, even falls, and rickets in the case of vitamin D deficiency. Diagnosis of a deficiency in one of the fat-soluble vitamins relies on blood tests, which are not always essential for routine use. In this context, a therapeutic test may be proposed. Treatment of deficiencies requires vitamin supplementation, a well-balanced diet, and treatment of the cause. Full article

Vitamin D hydroxylation in the liver/kidney results in conversion to its physiologically active form of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃]. 1,25(OH)₂D₃ controls gene expression through the nuclear vitamin D receptor (VDR) mainly expressed in intestinal epithelial cells. Cytochrome P450 (CYP) 24A1 is a catabolic enzyme expressed in the kidneys. Interestingly, a recently identified mutation in another CYP enzyme, CYP3A4 (gain-of-function), caused type III vitamin D-dependent rickets. CYP3A are also expressed in the intestine, but their hydroxylation activities towards vitamin D substrates are unknown. We evaluated CYP3A or CYP24A1 activities on vitamin D action in cultured cells. In addition, we examined the expression level and regulation of CYP enzymes in intestines from mice. The expression of CYP3A or CYP24A1 significantly reduced 1,25(OH)₂D₃-VDRE activity. Moreover, in mice, Cyp24a1 mRNA was significantly induced by 1,25(OH)₂D₃ in the intestine, but a mature form (approximately 55 kDa protein) was also expressed in mitochondria and induced by 1,25(OH)₂D₃, and this mitochondrial enzyme appears to hydroxylate 25OHD₃ to 24,25(OH)₂D₃. Thus, CYP3A or CYP24A1 could locally attenuate 25OHD₃ or 1,25(OH)₂D₃ action, and we suggest the small intestine is both a vitamin D target tissue, as well as a newly recognized vitamin D-metabolizing tissue. Full article

The scientific literature supports that practicing positive coparenting leads to the healthy development of children. Consequently, professional interest in parenting and coparenting has experienced significant growth, and evaluating coparenting is crucial in family psychology for establishing action protocols in clinical practice. An instrument highly regarded within the scientific community for evaluating coparenting dynamics is The Coparenting Relationship Scale (CRS). This research aims to achieve two objectives: first, to adapt the CRS for the Spanish population of both engaged and separated/divorced parents and to ascertain its reliability, validity, and factorial invariance psychometric properties; second, to assess the effectiveness of the total coparenting measure in categorizing sample participants. A cross-sectional non-experimental investigation was conducted to address these objectives. The first objective was answered by conducting an instrumental study, and the second by an exploratory study using classification techniques and a causal-comparative study using multivariate inferential methods. It was concluded that the model comprising 20 items across two factors, Positive Coparenting and Negative Perception of Coparenting, is the simplest and best fit for the Spanish parent sample; it is invariant regarding gender and marital status, and the measures derived from each factor demonstrate reliability and convergent and discriminant validity. The resulting questionnaire for Spanish parents is named CRS-S_Eg-S&D. The Coparental Vitality measure calculated using the total weighted measure of CRS-S_Eg-S&D allows the sample of participants to be divided into three differentiated clusters called Coparental Robustness, Moderate Coparenting, and Coparenting Rickets. Full article

This case report sheds light on the management of skeletal deformity in a young child with X-linked hypophosphatemia (XLH), emphasizing the significance of a timely orthotic intervention alongside pharmacological treatment, which is a strategy not frequently highlighted in the XLH literature. The patient, a 2-year-and-7-month-old female, presented with classic XLH symptoms, including short stature, pronounced genu varum, and hypophosphatemia, with deformities observed in both the coronal and sagittal planes of the femur and tibia. Despite initial reliance on pharmacotherapy, which proved insufficient for skeletal realignment, the integration of orthotic treatment at age 3 marked a pivotal turn in the management strategy. By the age of 5 years and 9 months, this combined approach yielded significant improvements: the deformities in the femur and tibia were notably corrected, tibial torsion was addressed, and enhanced limb alignment was achieved, as corroborated by radiographic evidence. This case underscores the effectiveness of orthotic intervention as a critical and underemphasized adjunct to pharmacological therapy in managing XLH in early childhood. It advocates for the early inclusion of orthotic measures to optimize treatment outcomes and expand the range of management strategies for limb deformities. Full article

Background: Vitamin D deficiency is the most frequent cause of impaired skeletal growth, and can lead to the development of nutritional rickets. The aim of this study was to evaluate the vitamin D status in a large group of children aged 0–18 years. Methods: We collected laboratory data on vitamin D levels from children who underwent blood sampling between 2014 and 2021. Results: We included 14,887 samples. In this group, 17.7% were vitamin D severely deficient (<12 ng/mL), 25.2% were insufficient (12–20 ng/mL), and another large proportion (28.3%) was borderline (20–30 ng/mL). Sufficient levels (>30 ng/mL) were met in 28.8% of children. We observed no association between gender and vitamin D status (p = 0.132). Adolescents aged 13–18 years (n = 3342) had the highest prevalence of severe vitamin D deficiency (24.9%). Vitamin D levels were higher in summer/autumn compared to winter/spring. Conclusions: Vitamin D deficiency/insufficiency has a high prevalence in children, mostly in children above 7 years of age. Many of these children (over 80%) do not meet the 30 ng/mL sufficiency threshold. It is essential that Belgian Health Authorities are aware of this high prevalence, as the current Belgian recommendation suggests ceasing vitamin D supplementation at the age of six. Additional research is required to investigate the consequences of our findings, and what specific approach is needed to achieve normal vitamin D levels in children aged 0 to 18 years. Full article

Bone differentiation is crucial for skeletal development and maintenance. Its dysfunction can cause various pathological conditions such as rickets, osteoporosis, osteogenesis imperfecta, or Paget’s disease. Although traditional two-dimensional cell culture systems have contributed significantly to our understanding of bone biology, they fail to replicate the intricate biotic environment of bone tissue. Three-dimensional (3D) spheroid cell cultures have gained widespread popularity for addressing bone defects. This review highlights the advantages of employing 3D culture systems to investigate bone differentiation. It highlights their capacity to mimic the complex in vivo environment and crucial cellular interactions pivotal to bone homeostasis. The exploration of 3D culture models in bone research offers enhanced physiological relevance, improved predictive capabilities, and reduced reliance on animal models, which have contributed to the advancement of safer and more effective strategies for drug development. Studies have highlighted the transformative potential of 3D culture systems for expanding our understanding of bone biology and developing targeted therapeutic interventions for bone-related disorders. This review explores how 3D culture systems have demonstrated promise in unraveling the intricate mechanisms governing bone homeostasis and responses to pharmacological agents. Full article

The definition of “Vitamin D” encompasses a group of fat-soluble steroid compounds of different origins with similar chemical structures and the same biological effects. Vitamin D deficiency and/or a defect in the process of its synthesis or transport predispose individuals to several types of rickets. In addition to cholecalciferol, ergocalciferol, and vitamins D3 and D2, there are also active metabolites for the treatment of this condition which are commercially available. Calcitriol and aphacalcidiol are active metabolites that do not require the renal activation step, which is required with calcifediol, or hepatic activation. The purpose of this review is to summarize current approaches to the treatment of rickets for generalist physicians, focusing on the best vitamin D form to be used in each type, or, in the case of X-linked hypophosphatemic rickets (XLH), on both conventional and innovative monoclonal antibody treatments. Full article

X-linked hypophosphatemia is a rare, hereditary disorder that significant influences teeth and alveolar bone. The first clinical sign leading to the diagnosis of X-linked hypophosphatemia is often dental impairment with dental abscesses and dentin mineralization defects. Genetic analysis helped find the responsible gene and therefore opened up new ways of therapeutically managing X-linked hypophosphatemia. The human monoclonal antibody Burosumab represents a milestone in the targeted therapy of this hereditary disease by directly addressing its pathophysiology. Targeted therapy has been shown to improve skeletal impairment, pain, and phosphate metabolism. However, the influence of this new therapy on dental impairment has only been addressed in a few recent studies with varying results. Therefore, in this review, we aim to summarize the dental phenotype and analyze the different treatment modalities with a focus on dental impairment. Full article

Finding infant rib fractures was for many years an almost undisputed proof that physical child abuse took place. Yet, these rib fractures are virtually always occult and asymptomatic and are only identified when looked for, usually with X-rays, from physical child abuse accusations related to, e.g., suspicion of the shaken baby syndrome. In a recent systematic literature review (searched in Cochran, Embase, PubMed and Sociological Abstracts), Güvensel questioned the diagnostic accuracy of rib fractures to be caused by abuse, due to lack of sufficient scientific evidence. Further, there is currently a world-wide disagreement between physicians considering themselves child abuse specialized, and physicians that explore non-abuse-related symptoms that may mimic physical abuse, which, it is hoped, will significantly reduce current unjustified child abuse diagnoses. In an attempt to help resolving this disagreement, we hypothesize that the probability of physical child abuse-related infant rib fractures is significantly lower than the probability of all other possible non-abuse-related causes of occult asymptomatic infant rib fractures, e.g., from birth trauma, prematurity, osteogenesis imperfecta, hypermobile Ehlers-Danlos Syndrome, severe chronic placental pathology (e.g., massive perivillous fibrin depositions and severe chronic histiocytic intervillositis), and vitamin-D deficiency. As method, we attempted to assess the incidence of these various causes of infant rib fractures, in the Netherlands and the USA. The results are that the estimated Dutch and USA physical abuse-related infant rib fracture incidences are at least about 250 and 45 times lower than the sum of all the non-abuse-related estimates. Because these latter rib fractures are occult and asymptomatic, it is likely that (many) more could be out there. In conclusion, occult asymptomatic rib fractures develop perinatally, virtually always as birth trauma, in infants with sufficiently weak bones due to vitamin D deficiency, transmitted by their vitamin D deficient pregnant mothers. This group also includes cortical rib cracks due to deformation forces, with an estimated 186/100,000 incidence. And, despite obvious uncertainties in all estimated incidences, we provided strong evidence that our hypothesis has relevance, implying that the abundant occult asymptomatic rib fractures, when found in infants, should not be used to assess potential physical child abuse. Full article

Vitamin D has been known to exert a wide range of physiological effects, including calcemic, osteogenic, anticancer, and immune responses. We previously generated genetically modified (GM) rats and performed a comparative analysis of their physiological properties to elucidate the roles of vitamin D and vitamin D receptor (VDR). In this study, our primary goal was to investigate the manifestations of type II rickets in rats with the VDR(H301Q) mutation, analogous to the human VDR(H305Q). Additionally, we created a double-mutant rat with the VDR(R270L/H301Q) mutation, resulting in almost no affinity for 1,25-dihydroxy-vitamin D3 (1,25D3) or 25-hydroxy-vitamin D3 (25D3). Notably, the plasma calcium concentration in Vdr(R270L/H301Q) rats was significantly lower than in wild-type (WT) rats. Meanwhile, Vdr(H301Q) rats had calcium concentrations falling between those of Vdr(R270L/H301Q) and WT rats. GM rats exhibited markedly elevated plasma parathyroid hormone and 1,25D3 levels compared to those of WT rats. An analysis of bone mineral density in the cortical bone of the femur in both GM rats revealed significantly lower values than in WT rats. Conversely, the bone mineral density in the trabecular bone was notably higher, indicating abnormal bone formation. This abnormal bone formation was more pronounced in Vdr(R270L/H301Q) rats than in Vdr(H301Q) rats, highlighting the critical role of the VDR-dependent function of 1,25D3 in bone formation. In contrast, neither Vdr(H301Q) nor Vdr(R270L/H301Q) rats exhibited symptoms of alopecia or cyst formation in the skin, which were observed in the Vdr-KO rats. These findings strongly suggest that unliganded VDR is crucial for maintaining the hair cycle and normal skin. Our GM rats hold significant promise for comprehensive analyses of vitamin D and VDR functions in future research. Full article

Phosphorus is essential for all living organisms. It plays an important role in maintaining biological functions, such as energy metabolism, cell membrane formation, and bone mineralization. Various factors in the intestine, kidneys, and bones regulate the homeostasis of the inorganic phosphate (Pi) concentration in the body. X-linked hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets, is characterized by an impaired mineralization of the bone matrix, hypertrophic chondrocytes with hypophosphatemia, and active vitamin D resistance in childhood. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome was recognized as the responsible gene for XLH. XLH is classified as fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets. The enhanced FGF23 stimulates renal phosphate wasting by downregulating sodium-dependent Pi cotransporters, NaPi2a and NaPi2c proteins, in the proximal tubules. Recently, transmembrane protein (Tmem) 174 has been identified as a novel regulator of phosphate transporters. This review introduces the role of Tmem174 in the Pi homeostasis in the body. Full article