4.7 Article

Severe Abdominal Aortic Calcification in Older Men Is Negatively Associated With DKK1 Serum Levels: The STRAMBO Study

Journal

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 99, Issue 2, Pages 617-624

Publisher

ENDOCRINE SOC
DOI: 10.1210/jc.2013-3201

Keywords

-

Funding

  1. Roche (Basel, Switzerland)
  2. Agence Nationale de la Recherche, Abondement Agence Nationale de Valorisation de la Recherche, and Hospices Civils de Lyon
  3. Deutsche Forschungsgemeinschaft [Transregio-67]
  4. SKELMET Forschergruppe [1586]

Ask authors/readers for more resources

Context: Experimental data show that dickkopf-1 (DKK1) may be involved in the regulation of arterial calcification. However, clinical data on the association between serum DKK1 levels and severity of abdominal aortic calcification (AAC) are scarce. Objective: Our aim was to determine the association between serum DKK1 concentration and AAC severity in men. Design: This is a cross-sectional analysis in the STRAMBO cohort. Setting: The cohort was recruited from the general population. Participants: We examined 1139 male volunteers aged 20 to 87 years. No specific exclusion criteria were used. Interventions: We collected blood samples and assessed AAC severity on the lateral spine scans obtained by a Discovery A Hologic device using the semiquantitative Kauppila score. Main Outcome Measures: We tested the hypothesis that low DKK1 levels are associated with AAC severity in men. Results: In men aged 20 to 60 years, serum DKK1 levels were not associated with other variables. In men aged 60 years and older, lower DKK1 levels were associated with higher odds of severe AAC (AAC score >5). After adjustment for confounders, odds of severe AAC increased with decreasing DKK1 levels (odds ratio = 1.42, 95% confidence interval = 1.13-1.79, P < .005) and was higher below vs above the median DKK1 level (odds ratio = 2.19, 95% confidence interval = 1.37-3.49, P < .005). Heavy smoking, hypertension, ischemic heart disease, and elevated levels of fibroblast growth factor 23 were associated with severe AAC significantly, independently of DKK1 and additively with low DKK1 levels. Conclusion: In older men, lower serum DKK1 levels are associated with severe AAC regardless of age and other potential confounders.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Endocrinology & Metabolism

Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial

Aliya A. Khan, Mishaela R. Rubin, Peter Schwarz, Tamara Vokes, Dolores M. Shoback, Claudia Gagnon, Andrea Palermo, Claudio Marcocci, Bart L. Clarke, Lisa G. Abbott, Lorenz C. Hofbauer, Lynn Kohlmeier, Susanne Pihl, Xuebei An, Walter Frank Eng, Alden R. Smith, Jenny Ukena, Christopher T. Sibley, Aimee D. Shu, Lars Rejnmark

Summary: TransCon PTH demonstrated efficacy in maintaining normocalcemia and allowing independence from conventional therapy in individuals with hypoparathyroidism. The treatment also showed significant improvements in health-related quality of life and hypoparathyroidism-related symptoms.

JOURNAL OF BONE AND MINERAL RESEARCH (2023)

Review Geriatrics & Gerontology

Abdominal Aortic Calcification, Bone Mineral Density, and Fractures: A Systematic Review and Meta-analysis of Observational Studies

Abadi K. Gebre, Joshua R. Lewis, Kevin Leow, Pawel Szulc, David Scott, Peter R. Ebeling, Marc Sim, Germaine Wong, Wai H. Lim, John T. Schousboe, Douglas P. Kiel, Richard L. Prince, Alexander J. Rodriguez

Summary: Abdominal aortic calcification (AAC) is associated with lower bone mineral density (BMD) and increased fracture risk. Detecting AAC during BMD testing may provide guidance for diagnosing bone health and predicting fracture risk.

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES (2023)

Article Endocrinology & Metabolism

Reduced Bone Mass and Increased Osteocyte Tartrate-Resistant Acid Phosphatase (TRAP) Activity, But Not Low Mineralized Matrix Around Osteocyte Lacunae, Are Restored After Recovery From Exogenous Hyperthyroidism in Male Mice

Eva Maria Woelfel, Franziska Lademann, Haniyeh Hemmatian, Stephane Blouin, Phaedra Messmer, Lorenz C. Hofbauer, Bjoern Busse, Martina Rauner, Katharina Jaehn-Rickert, Elena Tsourdi

Summary: Hyperthyroidism causes secondary osteoporosis by promoting bone resorption. Osteocytic osteolysis and elevated tartrate-resistant acid phosphatase (TRAP) activity were observed in hyperthyroid mice. The bone microarchitecture and turnover recovered after treatment, but the osteocytic osteolysis effects were not reversed.

JOURNAL OF BONE AND MINERAL RESEARCH (2023)

Article Endocrinology & Metabolism

C-reactive protein predicts endocortical expansion but not fracture in older men: the prospective STRAMBO study

Dylan Girard, Philippe P. P. Wagner, Danielle E. E. Whittier, Steven K. K. Boyd, Roland Chapurlat, Pawel Szulc

Summary: In older men, higher hsCRP concentrations are associated with faster endocortical expansion and slightly higher cortical bone loss, but not with fracture risk. High hsCRP levels have limited impact on bone decline in older men.

OSTEOPOROSIS INTERNATIONAL (2023)

Article Engineering, Biomedical

Osteocyte apoptosis and cellular micropetrosis signify skeletal aging in type 1 diabetes

Sofie Dragoun Kolibova, Eva Maria Woelfel, Haniyeh Hemmatian, Petar Milovanovic, Herbert Mushumba, Birgit Wulff, Maximilian Neidhardt, Klaus Pueschel, Antonio Virgilio Failla, Annegreet Vlug, Alexander Schlaefer, Benjamin Ondruschka, Michael Amling, Lorenz C. Hofbauer, Martina Rauner, Bjoern Busse, Katharina Jaehn-Rickert

Summary: Type 1 diabetes mellitus (T1DM) is associated with increased bone fragility. Our study found accelerated osteocyte apoptosis and local mineralization in T1DM patients, suggesting that T1DM speeds up bone aging and impairs its biomechanical competence. Dysfunction of the osteocyte network hampers bone remodeling and repair, contributing to the increased fracture risk in T1DM individuals.

ACTA BIOMATERIALIA (2023)

Article Endocrinology & Metabolism

Activation of b-adrenergic receptor signaling prevents glucocorticoid-induced obesity and adipose tissue dysfunction in male mice

Manuel Gado, Annett Heinrich, Denise Wiedersich, Katrin Sameith, Andreas Dahl, Vasileia I. Alexaki, Michael M. Swarbrick, Ulrike Baschant, Ingo Grafe, Nikolaos Perakakis, Stefan R. Bornstein, Martina Rauner, Lorenz C. Hofbauer, Holger Henneicke

Summary: This study demonstrates that activation of the sympathetic nervous system through cold exposure or selective I33-adrenergic receptor agonist can alleviate the adverse metabolic effects caused by chronic glucocorticoid exposure. Cold exposure preserves the function of brown adipose tissue and reverses white adipose tissue lipid accumulation, correcting obesity, hyperinsulinemia, and hyperglycemia caused by glucocorticoids.

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM (2023)

Article Engineering, Biomedical

Rational engineering of glycosaminoglycan-based Dickkopf-1 scavengers to improve bone regeneration

Gloria Ruiz-Gomez, Juliane Salbach-Hirsch, Jan-Niklas Duerig, Linda Koehler, Kanagasabai Balamurugan, Sandra Rother, Sophie-Luise Heidig, Stephanie Moeller, Matthias Schnabelrauch, Giulia Furesi, Sophie Paehlig, Pedro M. Guillem-Gloria, Christine Hofbauer, Vera Hintze, M. Teresa Pisabarro, Joerg Rademann, Lorenz C. Hofbauer

Summary: The WNT signaling pathway is important for bone development and regeneration, and abnormalities in WNT ligands and inhibitors are associated with various bone diseases. This study focused on glycosaminoglycan (GAG) recognition by DKK1, a WNT inhibitor, and aimed to develop WNT signaling regulators. Through a multidisciplinary approach, researchers designed and synthesized GAG derivatives with improved neutralizing properties for DKK1. These derivatives showed increased WNT pathway activity and improved bone regeneration in experimental models. The findings suggest that rationally engineered GAG variants could be used as novel therapeutic approaches.

BIOMATERIALS (2023)

Article Endocrinology & Metabolism

Rapid Cortical Bone Loss at the Distal Radius Is Associated With Higher Risk of Fracture in Older Men - The STRAMBO Study

Elina Gunsing, Philippe P. P. Wagner, Danielle E. E. Whittier, Steven K. K. Boyd, Roland Chapurlat, Pawel Szulc

Summary: Rapid cortical bone loss at the distal radius is associated with a higher risk of fracture in older men. However, repeated HR-pQCT measurements did not improve the assessment of fracture risk.

JOURNAL OF BONE AND MINERAL RESEARCH (2023)

Article Endocrinology & Metabolism

A Fracture Risk Assessment Tool for High Resolution Peripheral Quantitative Computed Tomography

Danielle E. Whittier, Elizabeth J. Samelson, Marian T. Hannan, Lauren A. Burt, David A. Hanley, Emmanuel Biver, Pawel Szulc, Elisabeth Sornay-Rendu, Blandine Merle, Roland Chapurlat, Eric Lespessailles, Andy Kin On Wong, David Goltzman, Sundeep Khosla, Serge Ferrari, Mary L. Bouxsein, Douglas P. Kiel, Steven K. Boyd

Summary: This study developed a fracture risk assessment tool based on high-resolution peripheral quantitative compute tomography (HR-pQCT) to evaluate patient-specific fracture risk. The tool, called mu FRAC, outperformed the current Fracture Risk Assessment Tool (FRAX) and models based on bone mineral density (BMD). It provides an alternative approach by utilizing direct measures of bone density and structure.

JOURNAL OF BONE AND MINERAL RESEARCH (2023)

Article Biochemistry & Molecular Biology

Transferrin receptor 2 deficiency promotes macrophage polarization and inflammatory arthritis

Maria G. Ledesma-Colunga, Ulrike Baschant, Heike Weidner, Tiago C. Alves, Peter Mirtschink, Lorenz C. Hofbauer, Martina Rauner

Summary: In this study, the authors investigated the role of transferrin receptor 2 (Tfr2) in the pathogenesis of inflammatory arthritis. They found that Tfr2-deficient mice developed more severe joint inflammation and bone erosion compared to control mice. Further experiments suggested that Tfr2 deficiency promoted macrophage polarization towards a pro-inflammatory state, contributing to the progression of arthritis.

REDOX BIOLOGY (2023)

Article Endocrinology & Metabolism

Machine-Learning Assessed Abdominal Aortic Calcification is Associated with Long-Term Fall and Fracture Risk in Community-Dwelling Older Australian Women

Jack Dalla Via, Abadi K. Gebre, Cassandra Smith, Zulqarnain Gilani, David Suter, Naeha Sharif, Pawel Szulc, John T. Schousboe, Douglas P. Kiel, Kun Zhu, William D. Leslie, Richard L. Prince, Joshua R. Lewis, Marc Sim

Summary: Abdominal aortic calcification (AAC), a measure of vascular disease, is associated with increased cardiovascular risk and poorer prognosis. An automated machine-learning algorithm has been developed for assessing AAC, which is associated with long-term incident fractures and falls.

JOURNAL OF BONE AND MINERAL RESEARCH (2023)

Article Endocrinology & Metabolism

Dysregulation of MicroRNAs in Adult Osteogenesis Imperfecta: The miROI Study

Alexandre Mercier-Guery, Marjorie Millet, Blandine Merle, Corinne Collet, Flora Bagouet, Olivier Borel, Elisabeth Sornay-Rendu, Pawel Szulc, Emmanuelle Vignot, Deborah Gensburger, Elisabeth Fontanges, Martine Croset, Roland Chapurlat

Summary: miRNAs are potential prognostic markers in bone diseases, regulating gene expression as epigenetic factors. This study aims to identify circulating miRNAs associated with the severity of osteogenesis imperfecta (OI) and found a miRNA signature in OI patients. The study validates the expression of specific miRNAs in OI patients and explores the relationship between miRNA expression and clinical characteristics of OI. The findings suggest a potential role of miRNAs in regulating the physiopathology of OI.

JOURNAL OF BONE AND MINERAL RESEARCH (2023)

Article Endocrinology & Metabolism

Effects of adipocyte-specific Dkk1 deletion on bone homeostasis and obesity-induced bone loss in male mice

Souad Daamouch, Sylvia Thiele, Lorenz Hofbauer, Martina Rauner

Summary: The link between obesity and low bone strength is a significant medical concern. Previous research has shown that Dkk1, a Wnt inhibitor, is upregulated in bone tissue in obesity and drives obesity-induced bone loss. This study investigated the role of adipogenic Dkk1 in bone homeostasis and obesity-induced bone loss in mice. The results suggest that adipogenic Dkk1 plays a transient role in bone mass regulation during adolescence, but does not contribute to bone homeostasis or obesity-induced bone loss later in life.

ENDOCRINE CONNECTIONS (2023)

Article Medicine, Research & Experimental

Deconstructing cellular senescence in bone and beyond

Lorenz C. Hofbauer, Franziska Lademann, Martina Rauner

Summary: Osteocytes, senescent cells implicated in bone loss disorders, have been shown to be effectively cleared through systemic senolysis, preventing age-related bone loss and mitigating bone marrow adiposity. Cell-specific senolysis in osteocytes alone had only a partial effect. Surprisingly, transplantation of senescent fibroblasts into young mice led to osteocyte senescence and bone loss. These findings on osteocyte senescence and the effects of remote senolysis suggest potential strategies against multisystem aging.

JOURNAL OF CLINICAL INVESTIGATION (2023)

Article Endocrinology & Metabolism

Spondyloarthritis and Sarcopenia: Prevalence of Probable Sarcopenia and its Impact on Disease Burden: The Saspar Study

Blandine Merle, Marie Cottard, Elisabeth Sornay-Rendu, Pawel Szulc, Roland Chapurlat

Summary: The study evaluates the prevalence of sarcopenia in spondyloarthritis (SpA) patients and its association with inflammation, disease activity, muscle performance, and quality of life. The results show that probable sarcopenia is significantly higher in SpA patients compared to controls. Probable sarcopenic SpA patients had higher inflammation and disease activity, impaired muscle performance, and lower quality of life. These findings suggest that muscle strength is an important aspect of SpA.

CALCIFIED TISSUE INTERNATIONAL (2023)

No Data Available