Publications by authors named "Amling M"

Myeloproliferative neoplasm-associated myelofibrosis is a clonal stem cell process characterized by pronounced bone marrow fibrosis associated with extramedullary hematopoiesis and splenomegaly. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment leading to bone marrow fibrosis regression. Here we provide an in-depth skeletal characterization of myelofibrosis patients before and after allo-HSCT utilizing clinical high-resolution imaging, laboratory analyses, and bone biopsy studies.

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  • Iron deficiency anemia is typically treated with iron infusions, but evidence suggests these can lead to low phosphate levels and osteomalacia due to high levels of iFGF23.
  • A study on 13 patients receiving ferric carboxymaltose infusions showed that stopping these infusions along with phosphate and vitamin D supplementation normalized phosphate levels, reduced pain, and improved bone density.
  • One patient continued to receive iron infusions but benefitted from burosumab treatment, underscoring the need to monitor phosphate levels in patients undergoing such therapies.
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  • This study explores the connection between bone health and vascular health, particularly focusing on lower leg arterial calcifications in patients with low bone mineral density.
  • Using high-resolution imaging, researchers examined data from 774 HR-pQCT scans, narrowing it down to 132 patients after accounting for variables like age and BMI.
  • Results indicated that while calcium metabolism was similar between patients with and without arterial calcifications, sex-specific differences emerged: females had a higher cortical perimeter with calcifications, and males showed a relationship between plaque volume and bone structure.
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Bone is a dynamic tissue that is constantly remodeled throughout adult life. Recently, it has been shown that bone turnover decreases shortly after food consumption. This process has been linked to the fermentation of non-digestible food ingredients such as inulin by gut microbes, which results in the production of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate.

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Spermine synthase, encoded by the SMS gene, is involved in polyamine metabolism, as it is required for the synthesis of spermine from its precursor molecule spermidine. Pathogenic variants of SMS are known to cause Snyder-Robinson syndrome (SRS), an X-linked recessive disorder causing various symptoms, including intellectual disability, muscular hypotonia, infertility, but also skeletal abnormalities, such as facial dysmorphisms and osteoporosis. Since the impact of a murine SMS deficiency has so far only been analyzed in Gy mice, where a large genomic deletion also includes the neighboring Phex gene, there is only limited knowledge about the potential role of SMS in bone cell regulation.

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MTX is an effective and widely used immunomodulatory drug for rheumatoid diseases. MTX osteopathy is a very rare and specific side effect, characterized by stress fractures at multiple locations in the lower extremity, hampering the patient's mobility by pain and loss of function. In clinical practice, osteoporosis and MTX osteopathy are repeatedly confused and a comparative workup is needed to clarity it's specifics.

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  • Sacral insufficiency fractures primarily affect older women with low bone mineral density, and this study investigates the bone quality in these patients through core biopsies from the sacral region.
  • The research compared biopsy samples from patients with bilateral sacral insufficiency fractures to control samples from age- and sex-matched healthy donors, revealing significant loss of trabecular microstructure and signs of chronic microfractures in the fracture cohort.
  • Key findings included lower mineral content and higher levels of bone remodeling markers in the fractured samples, suggesting reduced fracture resistance and a unique phenotype in this population compared to healthy individuals.
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  • * By testing ten pairs of human cadaveric feet, researchers found that while both arches affect the collapse of the longitudinal arch and forefoot abduction, the MLA has a stronger influence compared to the TTA.
  • * The results highlight that although weakness in the TTA significantly impacts certain aspects of PCFD, it doesn't surpass the influence of the MLA, which may inform better treatment approaches for flatfoot conditions.
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Aim: The aim of this study was to investigate the role of pyridoxal-5-phosphate (PLP) level on the oral health status as a predictive marker in patients with hypophosphatasia (HPP).

Materials And Methods: Throughout a systematic retrospective assessment both bone metabolism and oral health status were analyzed. The oral health status was assessed by the decayed/missing/filled teeth index (DMFT), clinical attachment level (CAL), probing pocket depth (PPD), and the periodontal screening index (PSI).

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  • The study aims to compare the effectiveness of cone beam computed tomography (CBCT) and 3 T magnetic resonance imaging (MRI) in diagnosing subchondral insufficiency fractures in the knee.
  • Out of 30 patients, there were significant discrepancies in grading bone lesions between CBCT and MRI, with CBCT often providing more accurate and lower estimates of lesion size.
  • The reliability of lesion assessment was high for both imaging methods, but CBCT outperformed MRI in terms of accurately measuring bony defects.
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Skeletal growth, modeling, and remodeling are regulated by various molecules, one of them being the recently identified osteoanabolic factor WNT1. We have previously reported that WNT1 transcriptionally activates the expression of Omd, encoding Osteomodulin (OMD), in a murine mesenchymal cell line, which potentially explained the skeletal fragility of mice with mutational WNT1 inactivation, since OMD has been shown to regulate type I collagen fibril formation in vitro. In this study we confirmed the strong induction of Omd expression in a genome-wide expression analysis of transfected cells, and we obtained further evidence for Omd being a direct target gene of WNT1.

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  • Tumor-induced osteomalacia (TIO) is difficult to diagnose, often requiring invasive iliac crest biopsies, which can extend the duration of disease and increase patient burden due to missed clinical suspicion.
  • A noninvasive method to assess the patient's condition is being sought, focusing on estimating osteoid volumes and addressing complications like hungry bone syndrome after tumor removal.
  • The study used advanced imaging and biopsy analysis techniques to confirm high osteoid volumes in TIO patients and developed a model that enables the noninvasive prediction of the osteoid volume to bone volume ratio, showing significant differences compared to osteoporosis patients and healthy controls.
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Physical activity-induced mechanical stimuli play a crucial role in preserving bone mass and structure by promoting bone formation. While the Wnt pathway is pivotal for mediating the osteoblast response to loading, the exact mechanisms are not fully understood. Here, we found that mechanical stimulation induces osteoblastic Wnt1 expression, resulting in an upregulation of key osteogenic marker genes, including Runx2 and Sp7, while Wnt1 knockdown using siRNA prevented these effects.

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Objective: The subchondral bone is an emerging regulator of osteoarthritis (OA). However, knowledge of how specific subchondral alterations relate to cartilage degeneration remains incomplete.

Method: Femoral heads were obtained from 44 patients with primary OA during total hip arthroplasty and from 30 non-OA controls during autopsy.

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Piezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for bone-anabolic processes, there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage. Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis (OA) development.

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The age-related maturation of the human midpalatal suture is challenging to predict, but critical for successful non-surgical rapid maxillary expansion (RME). While cone-beam computed tomography (CBCT) can be used to categorize the suture into stages, it remains unclear how well the stages predict the actual micromorphology of the palate. To address this clinically relevant question, we used CBCT together with three-dimensional micro-computed tomography (μCT) analysis on 24 human palate specimens from individuals aged 14-34 years.

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  • The study examines the advancements in high-resolution peripheral quantitative computed tomography (HR-pQCT), particularly comparing its first-generation (XCT1) and second-generation (XCT2) models in measuring bone microstructure.
  • XCT2 demonstrated significantly improved image quality with lower motion artifacts, showing that motion-corrupted scans decreased by more than half at the radius and improved image quality at the tibia.
  • The finders also highlight that factors such as age, gender, and body size influence motion artifacts, indicating that special care is needed for specific patient groups during scans.
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Cholesteatoma can lead to progressive destruction of the auditory ossicles along with conductive hearing loss but precise data on the microstructural, cellular, and compositional aspects of affected ossicles are not available. Here, we obtained incus specimens from patients who had cholesteatoma with conductive hearing loss. Incudes were evaluated by micro-computed tomography, histomorphometry on undecalcified sections, quantitative backscattered electron imaging, and nanoindentation.

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  • Pregnancy- and lactation-associated osteoporosis (PLO) is a rare condition leading to low bone density and severe pain, often resulting from bone marrow edema and fractures in pregnant or lactating women.
  • There is a noted connection between PLO and hereditary bone disorders that can complicate the condition and its severity.
  • A study of three women with PLO and genetic variants showed no additional fractures during subsequent pregnancies when proper treatment and monitoring were implemented, contributing valuable insights for managing this condition.
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Hypophosphatasia (HPP) is characterized by severe skeletal symptoms including mineralization defects, insufficiency fractures, and delayed facture healing or non-unions. HPP is caused by mutations of the tissue non-specific alkaline phosphatase (TNSALP). Zinc is a cofactor of TNSALP and vitamin D an important regulator of bone matrix mineralization.

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Background: Heterotopic ossification (HO) is a common complication after THA. Although current research primarily focuses on treatment and prevention, little is known about the local bone metabolism of HO and clinical contributing factors.

Questions/purposes: We aimed to assess bone remodeling processes in HO using histomorphometry, focusing on the effects of inflammation and prior NSAID treatment.

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Mechanosensory ion channels are proteins that are sensitive to mechanical forces. They are found in tissues throughout the body and play an important role in bone remodeling by sensing changes in mechanical stress and transmitting signals to bone-forming cells. Orthodontic tooth movement (OTM) is a prime example of mechanically induced bone remodeling.

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Hypophosphatasia (HPP) is an inborn disease that causes a rare form of osteomalacia, a mineralization disorder affecting mineralized tissues. Identification of patients at high risk for fractures or other skeletal manifestations (such as insufficiency fractures or excessive bone marrow edema) by bone densitometry and laboratory tests remains clinically challenging. Therefore, we examined two cohorts of patients with variants in the ALPL gene grouped by bone manifestations.

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