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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 -
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 -
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 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Aug 2022Management of unstable tibial fractures (UTF) can be challenging due to widening of the proximal and distal metaphyseal zone, soft tissue problems, and poor vascularity....
BACKGROUND
Management of unstable tibial fractures (UTF) can be challenging due to widening of the proximal and distal metaphyseal zone, soft tissue problems, and poor vascularity. We aimed to compare the effect of novel tibial orthopedic reduction support (TORS) frame constructed by re-used tubular external fixator systems and manual traction with regard to the quality of re-duction, and fracture healing.
METHODS
A total of 65 patients who were admitted with UTF and underwent intramedullary nailing were assessed; 43 patients un-derwent manual traction technique, and 22 patients underwent TORS technique. The sagittal and coronal plane angulations were eval-uated in initial postoperative radiographs, and radiologic union scores for tibial fractures (RUST) were compared at follow-up X-rays.
RESULTS
The mean age of patients was 43.49±19.09 years in the manual-traction group and 43.41±16.8 years in the TORS group. The mean coronal plane angulation was 1.84±3.16 in the manual traction group and 1.86±4.21 in the TORS group. The mean sagittal plane angulation was 1.19±1.93 in manual traction group and 0.32±0.65 in the TORS group. The number of coronal and sagittal plane angulations >5° was higher in manual traction group than TORS group. The mean RUST was significantly higher in the TORS group than in the manual traction group at 6th, 9th, and 12th-month controls. The union rates were also higher in the TORS group at 9th and 12th-month controls.
CONCLUSION
TORS frame is a simple and cheap technique and should be considered as reduction support in the management of UTF by intramedullary nailing.
Topics: Adult; Bone Nails; Fracture Fixation, Intramedullary; Fracture Healing; Humans; Middle Aged; Retrospective Studies; Tibial Fractures; Treatment Outcome; Young Adult
PubMed: 35920423
DOI: 10.14744/tjtes.2021.47225 -
Journal of Veterinary Diagnostic... Sep 2021Rickets is a metabolic bone disease associated with failure of endochondral ossification and impaired osteoid mineralization in growing animals. As a consequence,... (Review)
Review
Rickets is a metabolic bone disease associated with failure of endochondral ossification and impaired osteoid mineralization in growing animals. As a consequence, affected individuals can develop gross and microscopic bone malformations. The most common causes of rickets in domestic species include vitamin D and phosphorus deficiency. Rickets has been described in multiple species; however, comprehensive postmortem characterizations with confirmatory histopathology in equids have not been published. A 6-mo-old, Thoroughbred-cross foal was diagnosed with rickets based on gross autopsy findings and microscopic examination of the ribs and long bones. Grossly, all costochondral junctions of the ribs were enlarged with a "rachitic rosary" appearance, and there were multiple fracture calluses in the rib bodies. Epiphyses and metaphyses of the long bones appeared widened on sagittal section, and their physes were irregularly thickened. Histologically, there were poorly organized columns of hypertrophic chondrocytes within the physes of affected bones, islands of chondrocytes embedded within the primary and secondary spongiosa, and faintly eosinophilic seams of poorly mineralized osteoid within the bone trabeculae. Areas of focally increased osteoclastic activity were observed in some of the sections, perhaps pointing to a more complex metabolic bone disease in a growing animal. Low serum concentrations of calcium and 25-hydroxyvitamin D were detected in an antemortem sample. The pathogenesis of these imbalances was not definitively established, but lack of sunlight exposure, low concentration of vitamin D precursors in the diet (perhaps secondary to malnutrition), or both, were suspected; a genetic basis cannot be ruled out.
Topics: Animals; Bone and Bones; Calcium; Horse Diseases; Horses; Rickets
PubMed: 34160312
DOI: 10.1177/10406387211025232 -
Journal of Bone and Mineral Research :... Nov 2010Dysosteosclerosis (DSS), an extremely rare dense bone disease, features short stature and fractures and sometimes optic atrophy, cranial nerve palsy, developmental... (Review)
Review
Dysosteosclerosis (DSS), an extremely rare dense bone disease, features short stature and fractures and sometimes optic atrophy, cranial nerve palsy, developmental delay, and failure of tooth eruption in infancy or early childhood consistent with osteopetrosis (OPT). Bone histology during childhood shows unresorbed primary spongiosa from deficient osteoclast action. Additionally, there is remarkable progressive flattening of all vertebrae and, by adolescence, paradoxical metaphyseal osteopenia with thin cortical bone. Reports of consanguinity indicate autosomal recessive inheritance, yet more affected males than females suggest X-linked recessive inheritance. We investigated a nonconsanguineous girl with DSS. Osteosclerosis was discovered at age 7 months. Our studies, spanning ages 11 to 44 months, showed weight at approximately 50th percentile, and length diminishing from approximately 30th percentile to -2.3 SD. Head circumference was +4 SD. The patient had frontal bossing, blue sclera, normal teeth, genu valgum, and unremarkable joints. Radiographs showed orbital and facial sclerosis, basilar thickening, bone-in-bone appearance of the pelvis, sclerotic long bone ends, and fractures of ribs and extremities. Progressive metaphyseal widening occurred as vertebrae changed from ovoid to flattened and became beaked anteriorly. A hemogram was normal. Consistent with OPT, serum parathyroid hormone (PTH) concentrations reflected dietary calcium levels. Serum bone alkaline phosphatase, osteocalcin, and TRACP-5b were subnormal. The iliac crest contained excessive primary spongiosa and no osteoclasts. No mutations were identified in the splice sites or exons for the genes encoding chloride channel 7, T-cell immune regulator 1, OPT-associated transmembrane protein 1, and monocyte colony-stimulating factor (M-CSF) and its receptor C-FMS, ANKH, OPG, RANK, and RANKL. Genomic copy-number microarray was unrevealing. Hence, DSS is a distinctive OPT of unknown etiology featuring osteoclast deficiency during early childhood. How osteopenia follows is an enigma of human skeletal pathobiology.
Topics: Adult; Bone and Bones; Child, Preschool; DNA Mutational Analysis; Diagnosis, Differential; Family; Female; Humans; Infant; Infant, Newborn; Osteoclasts; Osteopetrosis; Osteosclerosis; Pregnancy; Radiography, Thoracic; Tomography, X-Ray Computed
PubMed: 20499338
DOI: 10.1002/jbmr.131 -
Acta Ortopedica Brasileira 2022Many experimental models exist to better understand the necrosis of the femoral head etiology, both in terms of the species variety in which necrosis is induced and in...
UNLABELLED
Many experimental models exist to better understand the necrosis of the femoral head etiology, both in terms of the species variety in which necrosis is induced and in the operative techniques used for treatment.
OBJECTIVE
This study has two main objectives, the first is to review the literature concerning experimental models of avascular necrosis of the growing femoral head, the second, to demonstrate the experimental pig model's reproducibility using a pilot study.
METHODS
This was a bibliographic review to describe the attempts over time to find the best species and technique for induction that would reproduce ischemic necrosis of the growing femoral head in humans. Simultaneously, a pilot study was performed to verify the replication of induction in pigs, the species that has more similarities with the human hip. The pilot's methodological analysis consists of conventional radiology and verification of possible anatomical, pathological changes.
RESULTS
In imaging exams; lateral sub-dislocation of the femur head and triangular appearance of the head were observed, characterizing its flattening; in macroscopic examination, the femoral head flattening with femoral neck widening and shortening was identified; in histology, the proliferation of articular cartilage with the presence of vascular granulation regenerative tissue, with osteoclasts and fibrocartilaginous tissue in the metaphyseal femoral neck region was identified.
CONCLUSION
The experimental pig model can be used as a valuable tool for the reproducibility of anatomical, pathological changes in ischemic necrosis of the growing femoral head. The model is reproducible and feasible and can be beneficial for future studies on the anatomical pathology of necrosis of the growing femoral head. .
PubMed: 35719181
DOI: 10.1590/1413-785220223002247996