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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 -
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 -
Seminars in Musculoskeletal Radiology Dec 2002Rickets is a metabolic bone disorder characterized by osteopenic changes resulting from the failure of calcification of the osteoid matrix and absent mineralization of... (Review)
Review
Rickets is a metabolic bone disorder characterized by osteopenic changes resulting from the failure of calcification of the osteoid matrix and absent mineralization of hypertrophic cartilage cells at the epiphyseal growth plates in growing primates, herbivores, swine, carnivores, and birds. The causes of rickets include inadequate dietary provision of calcium, phosphorus, and vitamin D. Osteomalacia in reptiles, simian bone disease in nonhuman primates, and osteodystrophia fibrosa (secondary hyperparathyroidism) or "bran disease" in herbivores are caused by a diet that has a much higher content of phosphorus than calcium, combined with inadequate exposure to direct sunlight. Medullary bone consists of interconnected spicules of bone resembling embryonic bone and is established in relation to the shell formation cycle of laying birds. Hypertrophic osteodystrophy develops in large-breed growing dogs, chickens, and guinea pigs and is possibly caused by vitamin C deficiency. Tibial dyschondroplasia is a defect in endochondral ossification characterized by a widened proximal tibial physis that is not penetrated by metaphyseal vascular sprouts, commonly found in growing broiler chickens, turkeys, and exotic birds.
Topics: Animals; Bone Diseases, Metabolic; Hyperparathyroidism; Radiography; Rickets
PubMed: 12541191
DOI: 10.1055/s-2002-36733 -
Child's Nervous System : ChNS :... Jul 2016Metaphyseal dysplasia (Pyle disease) is a rare autosomal recessive disease with impressive and characteristic radiological findings but relatively mild clinical...
INTRODUCTION
Metaphyseal dysplasia (Pyle disease) is a rare autosomal recessive disease with impressive and characteristic radiological findings but relatively mild clinical features. It is usually incidentally diagnosed, despite the impressive radiological findings of gross metaphyseal widening and thinning of cortical bone.
CASE REPORT
Herein, we report an exceptionally unusual case of metaphyseal dysplasia in association with chronic facial nerve palsy.
DISCUSSION
Chronic facial nerve palsy due to compression of the facial nerve in a patient with Pyle disease represents an unusual novelty. Furthermore, this case delineates the clinical spectrum and phenotype of such a rare clinical entity. To the best of our knowledge, this is the first time that such an association is being described.
Topics: Bone Diseases, Developmental; Child; Chronic Disease; Facial Nerve; Facial Paralysis; Female; Humans; Osteochondrodysplasias
PubMed: 26847543
DOI: 10.1007/s00381-016-3021-6 -
Radiologic Clinics of North America Jul 2001Growth disturbance of the long bones in children is frequently post-traumatic but also occurs because of physeal, epiphyseal, or metaphyseal ischemia. The imaging... (Review)
Review
Growth disturbance of the long bones in children is frequently post-traumatic but also occurs because of physeal, epiphyseal, or metaphyseal ischemia. The imaging features of growth arrest depend more on the anatomic site involved than on the cause. The physes of the distal tibia and femur and proximal tibia are disproportionately at risk because of their complex geometry. The central undulation in the distal femur and the bump in the anteromedial physis (Kump's bump) in the distal tibia are the sites of initial physiologic closure and the most frequent areas of premature fusion. The MR imaging features of growth disturbance are characteristic. T1-weighted images show low signal intensity GRL and variable signal intensity bony bridges. On GRE sequences, a bridge appears as low signal intensity interruption in the otherwise high signal intensity physeal cartilage. Physeal widening on GRE and T2-weighted images implies physeal dysfunction without bridge formation. Proton density and T2-weighted images best reveal associated metaphyseal and soft tissue changes. Regardless of the cause, MR imaging exquisitely depicts cartilaginous pathology at the physis. MR evaluation should be considered in patients at high risk for growth disturbance including young children with extensive residual growth potential; those with involvement of particularly vulnerable growth plates; and those with severe, complex fractures.
Topics: Child; Child, Preschool; Epiphyses; Female; Femur; Growth Disorders; Humans; Humerus; Infant; Infant, Newborn; Male; Radiography; Radius; Tibia
PubMed: 11549173
DOI: 10.1016/s0033-8389(05)70313-4 -
FASEB Journal : Official Publication of... Sep 2011Jansen metaphyseal chondrodysplasia (JMC) is caused by a constitutively activating mutation of the parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor (PTHR1)...
Jansen metaphyseal chondrodysplasia (JMC) is caused by a constitutively activating mutation of the parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor (PTHR1) and is characterized by widening of the metaphyses, reduction of long bone length, and short stature. A transgenic mouse expressing this mutation under the collagen α1(II) promoter has been generated to investigate the mechanisms responsible for this chondrodysplasia. We recently identified zinc finger protein 521 (Zfp521) as a downstream target gene of PTHrP signaling. Interestingly, loss of Zfp521 from chondrocytes leads to reduced cell proliferation and increased differentiation in the growth plate. Thus, we hypothesized that specifically ablating Zfp521 from Jansen chondrocytes could sufficiently rescue the chondrodysplasia phenotype. Our results show that Zfp521 expression is up-regulated in Jansen mouse growth plate chondrocytes and that PTHR1 is required for Zfp521 expression. Its ablation from Jansen chondrocytes restored normal cell differentiation, thus initiating chondrocyte apoptosis at the chondro-osseous junction, leading to partial rescue of endochondral bone formation shown by proper bone length. This study provides the first genetic evidence that Zfp521 is required downstream of PTHR1 signaling to act on chondrocyte proliferation, differentiation, and cell death.
Topics: Animals; Bone Development; Cells, Cultured; Chondrocytes; Disease Models, Animal; Gene Deletion; Gene Expression Regulation; Genotype; Growth Plate; Mice; Mice, Knockout; Osteochondrodysplasias; Phenotype; Transcription Factors; Up-Regulation
PubMed: 21642473
DOI: 10.1096/fj.11-183277 -
Journal of Dental Research Jun 2014Craniometaphyseal dysplasia (CMD) is a rare genetic disorder encompassing hyperostosis of craniofacial bones and metaphyseal widening of tubular bones. Dental...
Craniometaphyseal dysplasia (CMD) is a rare genetic disorder encompassing hyperostosis of craniofacial bones and metaphyseal widening of tubular bones. Dental abnormalities are features of CMD that have been little discussed in the literature. We performed dentofacial examination of patients with CMD and evaluated consequences of orthodontic movement in a mouse model carrying a CMD knock-in (KI) mutation (Phe377del) in the Ank gene. All patients have a history of delayed eruption of permanent teeth. Analysis of data obtained by cone-beam computed tomography showed significant bucco-lingual expansion of jawbones, more pronounced in mandibles than in maxillae. There was no measurable increase in bone density compared with that in unaffected individuals. Orthodontic cephalometric analysis showed that patients with CMD tend to have a short anterior cranial base, short upper facial height, and short maxillary length. Microcomputed tomography (micro-CT) analysis in homozygous Ank (KI/KI) mice, a model for CMD, showed that molars can be moved by orthodontic force without ankylosis, however, at a slower rate compared with those in wild-type Ank (+/+) mice (p < .05). Histological analysis of molars in Ank (KI/KI) mice revealed decreased numbers of TRAP(+) osteoclasts on the bone surface of pressure sides. Based on these findings, recommendations for the dental treatment of patients with CMD are provided.
Topics: Acid Phosphatase; Animals; Bone Density; Bone Diseases, Developmental; Cephalometry; Cone-Beam Computed Tomography; Craniofacial Abnormalities; Disease Models, Animal; Gene Knock-In Techniques; Humans; Hyperostosis; Hypertelorism; Isoenzymes; Mandible; Maxilla; Mice; Mutation; Osteoclasts; Phenylalanine; Phosphate Transport Proteins; Sequence Deletion; Skull Base; Tartrate-Resistant Acid Phosphatase; Tooth Abnormalities; Tooth Movement Techniques; Vertical Dimension; X-Ray Microtomography
PubMed: 24663682
DOI: 10.1177/0022034514529304 -
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 -
Ultrasound in Obstetrics & Gynecology :... Jul 2014It has recently been reported that fetuses with achondroplasia have a wider than expected femoral proximal diaphysis-metaphysis angle (femoral angle). The aim of this...
OBJECTIVES
It has recently been reported that fetuses with achondroplasia have a wider than expected femoral proximal diaphysis-metaphysis angle (femoral angle). The aim of this case-control study was to investigate this finding.
METHODS
Cases with confirmed achondroplasia (n = 6), small-for-gestational-age fetuses (n = 70) and a group of normal fetuses (n = 377) were included in this study. The ultrasound image of the femur was examined by two independent experienced observers blinded to the diagnosis, who measured the femoral angle. These values were converted into multiples of the expected median (MoM), after adjustment for gestational age and femur length. Prevalence of various prenatal ultrasound signs of achondroplasia was determined in affected fetuses. Intra- and interobserver agreement of measurement of femoral angle was assessed using 95% limits of agreement and kappa statistics.
RESULTS
The femoral angle can be measured accurately by ultrasound, and increases with both increasing gestational age and increasing femur length. The femoral angle-MoM was significantly higher in fetuses with achondroplasia than in the control group (1.36 vs 1.00 MoM, P < 0.001) and in the SGA group (1.36 vs 1.04 MoM, P < 0.001). It measured more than 130° in five of the six cases with achondroplasia (83.3%), which was the most consistent finding other than shortening of the long bones.
CONCLUSIONS
The femoral angle is wider in fetuses with achondroplasia. This new ultrasound sign appears promising as an additional discriminatory marker when clinicians are faced with a case of short long bones in the third trimester.
Topics: Achondroplasia; Adult; Case-Control Studies; Diaphyses; Female; Femur; Humans; Infant, Small for Gestational Age; Observer Variation; Pregnancy; Pregnancy Trimester, Third; ROC Curve; Regression Analysis; Single-Blind Method; Ultrasonography, Prenatal
PubMed: 24623391
DOI: 10.1002/uog.13339 -
European Journal of Human Genetics :... Oct 2023Acromesomelic dysplasia, PRKG2 type (AMDP, MIM 619636), is an extremely rare autosomal recessive skeletal dysplasia characterized by severe disproportionate short...
Acromesomelic dysplasia, PRKG2 type (AMDP, MIM 619636), is an extremely rare autosomal recessive skeletal dysplasia characterized by severe disproportionate short stature presenting with acromesomelia, mild metaphyseal widening of the long bones and mild spondylar dysplasia. To date, only four variants have been reported; one nonsense, one splice-site, and two frameshifts in five AMDP families. Here, we report the first missense variant and a second splice-site variant in PRKG2 in two patients with clinical and radiological features of acromesomelic dysplasia. Furthermore, functional studies of the novel missense variant, p.Val470Gly, revealed that it was unable to down-regulate FGF2-induced MAPK signaling and, thus, would be predicted to cause growth delay. Hence, this report expands the mutational spectrum in skeletal dysplasias associated with PRKG2 variants. In addition, we propose recognizable facial features with acromesomelic dysplasia, PRKG2 type.
PubMed: 37789084
DOI: 10.1038/s41431-023-01472-z