Improving the quantitative classification of Erlenmeyer flask deformities

Adusumilli, Gautam; Kaggie, Joshua D.; D’Amore, Simona; Cox, Timothy M.; Deegan, Patrick; Mackay, James; McDonald, Scott D.

doi:10.1007/s00256-020-03561-2

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…This deformity, resulting from defective bone modeling at the meta-diaphyseal region, leads to straight uncarved di-metaphyseal borders and cortical thinning ( 33 ). The cellular aspects of abnormal bone remodeling that lead to EM flask deformity are not fully understood; however, several studies discuss that osteoclast impairment could be implicated in EM deformity ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease

et al. 2022

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Patients with Gaucher disease (GD) have progressive bone involvement that clinically presents with debilitating bone pain, structural bone changes, bone marrow infiltration (BMI), Erlenmeyer (EM) flask deformity, and osteoporosis. Pain is referred by the majority of GD patients and continues to persist despite the type of therapy. The pain in GD is described as chronic deep penetrating pain; however, sometimes, patients experience severe acute pain. The source of bone pain is mainly debated as nociceptive pain secondary to bone pathology or neuropathic or inflammatory origins. Osteocytes constitute a significant source of secreted molecules that coordinate bone remodeling. Osteocyte markers, sclerostin (SOST) and Dickkopf-1 (DKK-1), inactivate the canonical Wnt signaling pathway and lead to the inhibition of bone formation. Thus, circulated sclerostin and DKK-1 are potential biomarkers of skeletal abnormalities. This study aimed to assess the circulating levels of sclerostin and DKK-1 in patients with GD and their correlation with clinical bone pathology parameters: pain, bone mineral density (BMD), and EM deformity. Thirty-nine patients with GD were classified into cohorts based on the presence and severity of bone manifestations. The serum levels of sclerostin and DKK-1 were quantified by enzyme-linked immunosorbent assays. The highest level of sclerostin was measured in GD patients with pain, BMI, and EM deformity. The multiparameter analysis demonstrated that 95% of GD patients with pain, BMI, and EM deformity had increased levels of sclerostin. The majority of patients with elevated sclerostin also have osteopenia or osteoporosis. Moreover, circulating sclerostin level increase with age, and GD patients have elevated sclerostin levels when compared with healthy control from the same age group. Pearson’s linear correlation analysis showed a positive correlation between serum DKK-1 and sclerostin in healthy controls and GD patients with normal bone mineral density. However, the balance between sclerostin and DKK-1 waned in GD patients with osteopenia or osteoporosis. In conclusion, the osteocyte marker, sclerostin, when elevated, is associated with bone pain, BMI, and EM flask deformity in GD patients. The altered sclerostin/DKK-1 ratio correlates with the reduction of bone mineral density. These data confirm that the Wnt signaling pathway plays a role in GD-associated bone disease. Sclerostin and bone pain could be used as biomarkers to assess patients with a high risk of BMI and EM flask deformities.

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Section: Discussionmentioning

confidence: 99%

Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease

et al. 2022

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“…The Erlenmeyer flask deformity can also be found in several other conditions, including multiple exostoses disease, metaphyseal dysplasia, Gaucher’s, Niemann-Pick, and achondroplasia [ 21 , 22 ].…”

Section: Imaging Of Osteopetrosismentioning

confidence: 99%

Spectrum of Skeletal Imaging Features in Osteopetrosis: Inheritance Pattern and Radiological Associations

Spinnato

Pedrini

Petrera

et al. 2022

Genes

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Osteopetrosis (from the Greek “osteo”: bone; “petrosis”: stone) is a clinically and genetically heterogeneous group of rare diseases of the skeleton, sharing the same main characteristic of an abnormally increased bone density. Dense bones in radiological studies are considered the hallmark of these diseases, and the reason for the common term used: “Marble bone disease”. Interestingly, a radiologist, Dr. Albers-Schonberg, described this disease for the first time in Germany in 1904. Indeed, radiology has a key role in the clinical diagnosis of osteopetrosis and is fundamental in assessing the disease severity and complications, as well as in follow-up controls and the evaluation of the response to treatment. Osteopetrosis includes a broad spectrum of genetic mutations with very different clinical symptoms, age onset, and prognosis (from mild to severe). This diversity translates into different imaging patterns related to specific mutations, and different disease severity. The main recognized types of osteopetrosis are the infantile malignant forms with autosomal recessive transmission (ARO—including the rarer X-linked recessive form); the intermediate autosomal recessive form (IAO); and the autosomal dominant ones ADO, type I, and type II, the latter being called ‘Albers-Schonberg’ disease. Imaging features may change among those distinct types with different patterns, severities, skeletal segment involvement, and speeds of progression. There are several classical and well-recognized radiological features related to osteopetrosis: increased bone density (all types with different degrees of severity assuming a ‘Marble Bone Appearance’ especially in the ARO type), different metaphyseal alterations/enlargement including the so-called ‘Erlenmeyer flask deformity’ (particularly of femoral bones, more frequent in ADO type 2, and less frequent in ARO and IAO), ‘bone in bone’ appearance (more frequent in ADO type 2, less frequent in ARO and IAO), and ‘rugger-jersey spine’ appearance (typical of ADO type 2). After conducting an overview of the epidemiological and clinical characteristic of the disease, this review article aims at summarizing the main radiological features found in different forms of osteopetrosis together with their inheritance pattern.

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“…Fabry disease (FD) is an X-linked lysosomal disorder wherein pathogenic variants of the GLA gene result in the deficiency of the enzyme α-galactosidase A (α–Gal A) (EC entry 3.2.1.22). The presentation of FD is quite heterogeneous and includes signs and symptoms related to cardiovascular disease, renal failure, and cerebrovascular complications, including ischemic or hemorrhagic strokes, all of which are associated with reduced quality of life and early mortality [ 1 , 2 ]. While FD occurs in a spectrum, there is a subgroup of patients with predominant cardiac involvement with a higher residual α–Gal A activity, a phenotype occasionally referred to as the “cardiac variant” of FD.…”

Section: Introductionmentioning

confidence: 99%

Circulated TGF-β1 and VEGF-A as Biomarkers for Fabry Disease-Associated Cardiomyopathy

Ivanova,

Dao,

Slayeh

et al. 2023

Cells

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Fabry disease (FD) is a lysosomal disorder caused by α-galactosidase A deficiency, resulting in the accumulation of globotriaosylceramide (Gb-3) and its metabolite globotriaosylsphingosine (Lyso-Gb-3). Cardiovascular complications and hypertrophic cardiomyopathy (HCM) are the most frequent manifestations of FD. While an echocardiogram and cardiac MRI are clinical tools to assess cardiac involvement, hypertrophic pattern variations and fibrosis make it crucial to identify biomarkers to predict early cardiac outcomes. This study aims to investigate potential biomarkers associated with HCM in FD: transforming growth factor-β1 (TGF-β1), TGF-β active form (a-TGF-β), vascular endothelial growth factor (VEGF-A), and fibroblast growth factor (FGF2) in 45 patients with FD, categorized into cohorts based on the HCM severity. TGF-β1, a-TGF-β, FGF2, and VEGF-A were elevated in FD. While the association of TGF-β1 with HCM was not gender-related, VEGF was elevated in males with FD and HCM. Female patients with abnormal electrocardiograms but without overt HCM also have elevated TGF-β1. Lyso-Gb3 is correlated with TGF-β1, VEGF-A, and a-TGF-β1. Elevation of TGF-β1 provides evidence of the chronic inflammatory state as a cause of myocardial fibrosis in FD patients; thus, it is a potential marker of early cardiac fibrosis detected even prior to hypertrophy. TGF-β1 and VEGF biomarkers may be prognostic indicators of adverse cardiovascular events in FD.

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Improving the quantitative classification of Erlenmeyer flask deformities

Cited by 3 publications

References 16 publications

Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease

Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease

Spectrum of Skeletal Imaging Features in Osteopetrosis: Inheritance Pattern and Radiological Associations

Circulated TGF-β1 and VEGF-A as Biomarkers for Fabry Disease-Associated Cardiomyopathy

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