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Pediatric Nephrology (Berlin, Germany) Sep 2022Rickets is a disease of the growing child arising from alterations in calcium and phosphate homeostasis resulting in impaired apoptosis of hypertrophic chondrocytes in... (Review)
Review
Rickets is a disease of the growing child arising from alterations in calcium and phosphate homeostasis resulting in impaired apoptosis of hypertrophic chondrocytes in the growth plate. Its symptoms depend on the patients' age, duration of disease, and underlying disorder. Common features include thickened wrists and ankles due to widened metaphyses, growth failure, bone pain, muscle weakness, waddling gait, and leg bowing. Affected infants often show delayed closure of the fontanelles, frontal bossing, and craniotabes. The diagnosis of rickets is based on the presence of these typical clinical symptoms and radiological findings on X-rays of the wrist or knee, showing metaphyseal fraying and widening of growth plates, in conjunction with elevated serum levels of alkaline phosphatase. Nutritional rickets due to vitamin D deficiency and/or dietary calcium deficiency is the most common cause of rickets. Currently, more than 20 acquired or hereditary causes of rickets are known. The latter are due to mutations in genes involved in vitamin D metabolism or action, renal phosphate reabsorption, or synthesis, or degradation of the phosphaturic hormone fibroblast growth factor 23 (FGF23). There is a substantial overlap in the clinical features between the various entities, requiring a thorough workup using biochemical analyses and, if necessary, genetic tests. Part I of this review focuses on the etiology, pathophysiology and clinical findings of rickets followed by the presentation of a diagnostic approach for correct diagnosis. Part II focuses on the management of rickets, including new therapeutic approaches based on recent clinical practice guidelines.
Topics: Alkaline Phosphatase; Child; Fibroblast Growth Factors; Humans; Infant; Phosphates; Rickets; Vitamin D Deficiency
PubMed: 34910242
DOI: 10.1007/s00467-021-05328-w -
Bone Feb 2023Dysosteosclerosis (DSS) refers to skeletal dysplasias that radiographically feature focal appendicular osteosclerosis with variable platyspondyly. Genetic heterogeneity...
Dysosteosclerosis (DSS) refers to skeletal dysplasias that radiographically feature focal appendicular osteosclerosis with variable platyspondyly. Genetic heterogeneity is increasingly reported for the DSS phenotype and now involves mutations of SLC29A3, TNFRSF11A, TCIRG1, LRRK1, and CSF1R. Typical radiological findings are widened radiolucent long bones with thin cortices yet dense irregular metaphyses, flattened vertebral bodies, dense ribs, and multiple fractures. However, the radiographic features of DSS evolve, and the metaphyseal and/or appendicular osteosclerosis variably fades with increasing patient age, likely due to some residual osteoclast function. Fractures are the principal presentation of DSS, and may even occur in infancy with SLC29A3-associated DSS. Cranial base sclerosis can lead to cranial nerve palsies such as optic atrophy, and may be the initial presentation, though not observed with SLC29A3-associated DSS. Gene-specific extra-skeletal features can be the main complication in some forms of DSS such as CSF1R- associated DSS. Further genetic heterogeneity is likely, especially for X-linked recessive DSS and cases currently with an unknown genetic defect. Distinguishing DSS can be challenging due to variable clinical and radiological features and an evolving phenotype. However, defining the DSS phenotype is important for predicting complications, prognosis, and instituting appropriate health surveillance and treatment.
Topics: Humans; Osteopetrosis; Osteosclerosis; Osteochondrodysplasias; Mutation; Vacuolar Proton-Translocating ATPases; Nucleoside Transport Proteins
PubMed: 36402365
DOI: 10.1016/j.bone.2022.116615 -
Academic Forensic Pathology Jun 2017Rickets was a common metabolic disease of bone a century ago in Europe, North America, and East Asia (mainly due to vitamin D deficiency) but was largely eradicated in... (Review)
Review
Rickets was a common metabolic disease of bone a century ago in Europe, North America, and East Asia (mainly due to vitamin D deficiency) but was largely eradicated in growing children by use of cod liver oil and the introduction of vitamin D fortification of milk in the 1930s in the United States. Vitamin D deficiency (VDD) remains the most common form of metabolic bone disease that is entirely preventable and treatable. Historically, rickets has appeared in sporadic epidemics and, despite the introduction of numerous preventive strategies, VDD has remained a global health problem amongst children. Moreover, developed countries such as Canada, Australia, the United Kingdom, and the United States have not been exempt from this. The radiological and histological features of rickets are both distinctive and characteristic and they reflect the underlying pathophysiological issue of decreased mineralization of bone as a result of VDD. The radiological features include 1) metaphyseal cupping and fraying, 2) poor mineralization of epiphyseal centers, 3) irregular and widened epiphyseal plates, 4) increased distance between the end of shaft and epiphyseal center, 5) cortical spurs at right angles to the metaphysis, 6) coarse trabeculation, and 7) periosteal reactions. Fractures may also be evident. The histological features of rickets reflect the failure of cartilage to mineralize and undergo resorption. This results in 1) disordered proliferation of chondrocytes in the hypertrophic zone secondary to a lack of apoptosis, 2) loss of the columnar arrangement of chondrocytes that results in thickening and disorganization of the hypertrophic zone, 3) tongue-like projections of cartilage that extend into the spongiosa, 4) irregularity of the limit between the proliferative and hypertrophic zones, and 5) penetration of blood vessels into the hypertrophic zone. The case of a premature 3-month-old female infant, born in the winter months in the arctic region of Canada who died from a lobar pneumonia with an incidental finding of radiological and pathological evidence of rickets, is presented. The case is used to review the entity of rickets from historical, pathophysiological, radiological, and histological perspectives.
PubMed: 31239976
DOI: 10.23907/2017.024 -
Radiographics : a Review Publication of... Oct 2016Metabolic bone diseases are a diverse group of diseases that result in abnormalities of (a) bone mass, (b) structure mineral homeostasis, (c) bone turnover, or (d)... (Review)
Review
Metabolic bone diseases are a diverse group of diseases that result in abnormalities of (a) bone mass, (b) structure mineral homeostasis, (c) bone turnover, or (d) growth. Osteoporosis, the most common metabolic bone disease, results in generalized loss of bone mass and deterioration in the bone microarchitecture. Impaired chondrocyte development and failure to mineralize growth plate cartilage in rickets lead to widened growth plates and frayed metaphyses at sites of greatest growth. Osteomalacia is the result of impaired mineralization of newly formed osteoid, which leads to characteristic Looser zones. Hypophosphatasia is a congenital condition of impaired bone mineralization with wide phenotypic variability. Findings of hyperparathyroidism are the result of bone resorption, most often manifesting as subperiosteal resorption in the hand. Renal osteodystrophy is the collection of skeletal findings observed in patients with chronic renal failure and associated secondary hyperparathyroidism and can include osteopenia, osteosclerosis, and "rugger jersey spine." Hypoparathyroidism is most commonly due to iatrogenic injury, and radiographic findings of hypoparathyroidism reflect an overall increase in bone mass. Thyroid hormone regulates endochondral bone formation; and congenital hypothyroidism, when untreated, leads to delayed bone age and absent, irregular, or fragmented distal femoral and proximal tibial epiphyses. Soft-tissue proliferation of thyroid acropachy is most often observed in the hands and feet. The findings of acromegaly are due to excess growth hormone secretion and therefore proliferation of the bones and soft tissues. Vitamin C deficiency, or scurvy, impairs posttranslational collagen modification, leading to subperiosteal hemorrhage and fractures. RSNA, 2016.
Topics: Bone Diseases, Metabolic; Bone and Bones; Diagnosis, Differential; Diagnostic Errors; Evidence-Based Medicine; Humans; Image Enhancement; Patient Positioning; Tomography, X-Ray Computed
PubMed: 27726750
DOI: 10.1148/rg.2016160004 -
Journal of Children's Orthopaedics Aug 2019In 1959, Maroteaux and Lamy initially designated pseudoachondroplasia as a distinct dysplasia different from achondroplasia the most common form of skeletal dysplasia....
PURPOSE
In 1959, Maroteaux and Lamy initially designated pseudoachondroplasia as a distinct dysplasia different from achondroplasia the most common form of skeletal dysplasia. Pseudoachondroplasia is caused by a mutation in the collagen oligomeric matrix protein gene (COMP) gene on chromosome 19p13.1-p12 encoding the COMP. The COMP gene mutations result in rendering the articular and growth plate cartilages incapable of withstanding routine biomechanical loads with resultant deformity of the joints. The purpose of the study was to characterize the typical orthopaedic findings in pseudoachondroplasia.
METHODS
The charts and radiographs of 141 patients with pseudoachondroplasia were analyzed. This cohort, to our knowledge, represents the largest group of patients describing the typical orthopaedic manifestations of pseudoachondroplasia.
RESULTS
Patients with pseudoachondroplasia have normal craniofacial appearance with normal intelligence. Short stature is not present at birth and generally appears by two to four years of age. The condition is a form of spondyloepiphyseal dysplasia and the long bones are characterized by dysplastic changes in the epiphysis, metaphysis and vertebral bodies. Radiographically the long bones have altered the appearance and structure of the epiphyses with small irregularly formed or fragmented epiphyses or flattening. The metaphyseal regions of the long bones show flaring, widening or 'trumpeting'. The cervical (89%) and thoracic and lumbar vertebrae show either platyspondyly, ovoid, 'cod-fish' deformity or anterior 'beaking'. Kyphosis (28%), scoliosis (58%) and lumbar lordosis (100%) are commonly seen. The femoral head and acetabulum are severely dysplastic (100%). The knees show either genu valgum (22%), genu varum (56%) or 'windswept' deformity (22%).
CONCLUSION
Most commonly these distortions of the appendicular and the axial skeleton lead to premature arthritis particularly of the hips and often the knees not uncommonly in the 20- to 30-year-old age group.
LEVEL OF EVIDENCE
III.
PubMed: 31489048
DOI: 10.1302/1863-2548.13.190066 -
Orthopaedic Surgery Aug 2018There are several types of metaphyseal chondrodysplasia and various clinical types have been differentiated. The Schmid type of metaphyseal chondrodysplasia is the most...
OBJECTIVES
There are several types of metaphyseal chondrodysplasia and various clinical types have been differentiated. The Schmid type of metaphyseal chondrodysplasia is the most common. Diffuse metaphyseal flaring, irregularity, and growth plate widening, which are most severe in the knees, are the most striking radiological features of this disease. The Schmid type of metaphyseal dysostosis is characterized by failure of normal mineralization of the zone of provisional calcification, leading to widened physes and enlarged knobby metaphyses, effectively causing shortening of the tubular bones, splaying of the metaphyses, coxa vara, and bow legs. Orthopaedic interventions were primarily performed on the lower extremities.
METHODS
Twelve children (seven girls and five boys) aged 7-10 years were enrolled in this study. Moderate short stature was a uniform feature associated with predominant involvement of the proximal femora and bow legs resulted in the development of angular deformities. A waddling gait was a consequence of coxa vara in eight children. Valgus osteotomy of the proximal femur was planned after physeal closure for the group of children with coxa vara. Hemiepiphysiodesis was performed to re-align the genu varum in three children.
RESULTS
Other forms of metaphyseal dysostosis were ruled based on full clinical and radiographic phenotypes, with confirmation through molecular pathology. Mutations in the COL10A1 gene located on chromosome 6q21-q22.3 were confirmed. Re-alignment was accomplished in our group of patients.
CONCLUSION
The most striking clinical features of Schmid metaphyseal chondrodysplasia which appear within the first 2-3 years of life are: moderate short limbs and short stature, a waddling gait, and increasing shortness of stature with age. The Schmid type of metaphyseal chondrodysplasia is a disorder that arises from defective type X collagen, which is typically found in the hypertrophic zone of the physes. Moderate short stature and a waddling gait associated with pain are the most common clinical presentations. Osteotomies to correct bow legs are sometimes combined with lengthening procedures. Recurrence of the deformities with growth is not uncommon; therefore, hemiepiphysiodesis or stapling might be indicated in some cases.
Topics: Child; Child, Preschool; Collagen Type X; Female; Femur; Genu Varum; Humans; Male; Mutation; Osteochondrodysplasias; Osteotomy; Phenotype; Radiography
PubMed: 30027601
DOI: 10.1111/os.12382 -
Radiographics : a Review Publication of... Oct 2017The growth plates, or physes, are visible on virtually all images obtained in skeletally immature children. The proper function of these growth plates depends on an...
The growth plates, or physes, are visible on virtually all images obtained in skeletally immature children. The proper function of these growth plates depends on an intricate balance between chondrocyte proliferation, which requires nourishment from the epiphyseal vessels, and chondrocyte death, which requires the integrity of the metaphyseal vessels. Therefore, injury to the growth plate (ie, direct insult) or vascular compromise on either side of the growth plate (ie, indirect insult) can cause growth plate dysfunction. Direct growth plate insults occur most commonly with Salter-Harris fractures, and injuries that allow the transphyseal communication of vessels are at a higher risk for subsequent transphyseal bone bridge formation. Indirect insults lead to different sequelae that are based on whether the epiphyseal blood supply or metaphyseal blood supply is compromised. Epiphyseal osteonecrosis can result in slowed longitudinal bone growth, with possible growth plate closure, and is often accompanied by an abnormal secondary ossification center. In contrast, the disruption of metaphyseal blood supply alters endochondral ossification and allows the persistence of chondrocytes within the metaphysis, which appear as focal or diffuse growth plate widening. Imaging remains critical for detecting acute injuries and identifying subsequent growth disturbances. Depending on the imaging findings and patient factors, these growth disturbances may be amenable to conservative or surgical treatment. Therefore, an understanding of the anatomy and physiologic features of the normal growth plate and the associated pathophysiologic conditions can increase diagnostic accuracy, enable radiologists to anticipate future growth disturbances, and ensure optimal imaging, with the ultimate goal of timely and appropriate intervention. RSNA, 2017.
Topics: Bone and Bones; Child; Diagnosis, Differential; Growth Plate; Humans
PubMed: 29019753
DOI: 10.1148/rg.2017170029 -
AJR. American Journal of Roentgenology Dec 2022Despite evidence supporting the specificity of classic metaphyseal lesions (CML) for the diagnosis of child abuse, some medicolegal practitioners claim that CML result...
Despite evidence supporting the specificity of classic metaphyseal lesions (CML) for the diagnosis of child abuse, some medicolegal practitioners claim that CML result from rickets rather than trauma. The purpose of this study was to evaluate radiologists' diagnostic performance in differentiating rickets and CML on radiographs. This retrospective seven-center study included children younger than 2 years who underwent knee radiography from January 2007 to December 2018 and who had either rickets (25-hydroxyvitamin D level < 20 ng/mL and abnormal knee radiographs) or knee CML and a diagnosis of child abuse from a child abuse pediatrician. Additional injuries were identified through medical record review. Radiographs were cropped and zoomed to present similar depictions of the knee. Eight radiologists independently interpreted radiographs for diagnoses of rickets or CML, rated confidence levels, and recorded associated radiographic signs. Seventy children (27 girls, 43 boys) had rickets; 77 children (37 girls, 40 boys) had CML. Children with CML were younger than those with rickets (mean, 3.7 vs 14.2 months, < .001; 89.6% vs 5.7% younger than 6 months; 3.9% vs 65.7% older than 1 year). All children with CML had injuries in addition to the knee CML identified at physical examination or other imaging examinations. Radiologists had almost perfect agreement for moderate- or high-confidence interpretations of rickets (κ = 0.92) and CML (κ = 0.89). Across radiologists, estimated sensitivity, specificity, and accuracy for CML for moderate- or high-confidence interpretations were 95.1%, 97.0%, and 96.0%. Accuracy was not significantly different between pediatric and nonpediatric radiologists ( = .20) or between less experienced and more experienced radiologists ( = .57). Loss of metaphyseal zone of provisional calcification, cupping, fraying, and physeal widening were more common in rickets than CML, being detected in less than 4% of children with CML. Corner fracture, bucket-handle fracture, subphyseal lucency, deformed corner, metaphyseal irregularity, and subperiosteal new bone formation were more common in CML than rickets, being detected in less than 4% of children with rickets. Radiologists had high interobserver agreement and high diagnostic performance for differentiating rickets and CML. Recognition that CML mostly occur in children younger than 6 months and are unusual in children older than 1 year may assist interpretation. Rickets and CML have distinct radiographic signs, and radiologists can reliably differentiate these two entities.
Topics: Male; Female; Humans; Child; Infant; Child, Preschool; Retrospective Studies; Rickets; Radiography; Bone and Bones; Child Abuse; Fractures, Bone; Radiologists
PubMed: 35792137
DOI: 10.2214/AJR.22.27729