Review
Chemistry, Analytical
Umile Giuseppe Longo, Vincenzo Candela, Alessandra Berton, Sergio De Salvatore, Sara Fioravanti, Lucia Giannone, Anna Marchetti, Maria Grazia De Marinis, Vincenzo Denaro
Summary: This systematic review evaluates the advantages of biosensors in the early diagnosis of osteoarthritis, showing that biosensors can detect biomarkers with high accuracy and low costs. However, due to a lack of data and low levels of evidence, significant results could not be found, indicating the need for further high-quality studies to confirm the findings.
Article
Cell & Tissue Engineering
C. C. Stewart, N. N. O'Hara, S. Bzovsky, C. S. Bahney, S. Sprague, G. P. Slobogean
Summary: This study aims to investigate whether BTMs can be used as early markers of delayed fracture healing and to examine the effect of vitamin D on BTM response after fracture.
BONE & JOINT RESEARCH
(2022)
Article
Endocrinology & Metabolism
S. E. Bonlokke, M. S. Rand, B. Haddock, S. Arup, C. D. Smith, J. E. B. Jensen, P. Schwarz, P. Hovind, P. S. Oturai, L. T. Jensen, S. Moller, P. Eiken, K. H. Rubin, M. F. Hitz, B. Abrahamsen, N. R. Jorgensen
Summary: Anti-resorptive osteoporosis treatment may be more effective in patients with high bone turnover, as indicated by biochemical markers. Pre-treatment levels of bone turnover markers can predict patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP may benefit more from antiresorptive treatment with larger increases in BMD.
OSTEOPOROSIS INTERNATIONAL
(2022)
Review
Medicine, General & Internal
Mohammad Hassan Sohouli, Sicong Wang, Faisal Almuqayyid, Mariana Papini Gabiatti, Fateme Mozaffari, Zahra Mohamadian, Nazanin Koushki, Kamar Allayl Alras, Abdullah M. AlHossan, Saud K. Albatati, Aya Alfardous Alazm, Saeed Baradwan, Mihnea-Alexandru Gaman, Sicheng Wang, Ahmed Abu-Zaid
Summary: This meta-analysis examined the effects of vitamin D supplementation on bone turnover markers (BTMs) in adults. The results showed that vitamin D administration can decrease the levels of specific BTMs, but no significant effect was observed on other BTMs.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Endocrinology & Metabolism
Aurelie Ladang, Frank Rauch, Edgard Delvin, Etienne Cavalier
Summary: Bone turnover markers (BTMs) in children and adolescents show age- and gender-dependent variations under pathological conditions. However, due to the specificities of pediatric patients, the clinical use of BTMs is still limited in practice.
CALCIFIED TISSUE INTERNATIONAL
(2023)
Article
Endocrinology & Metabolism
Weiwei He, Tine Vrist Dam, Rebekka Thogersen, Mette Hansen, Hanne Christine Bertram
Summary: This study found that the menstrual cycle and use of oral contraceptives can affect levels of metabolites and bone turnover markers in women. During the menstrual cycle, plasma levels of certain amino acids vary significantly and are correlated with fluctuations in progesterone and estrogen levels. Additionally, users of oral contraceptives have lower levels of metabolites and bone turnover markers compared to nonusers.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Medical Laboratory Technology
Yiduo Zhang, Xiaocui Huang, Chao Li, Jing Zhang, Xingnan Yu, Ye Li, Wenjie Zhou, Fan Yu
Summary: Bone turnover markers are crucial in pediatric medicine, as they can aid in the diagnosis and prognosis of bone metabolic disorders.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Hematology
Srila Gopal, Richard F. W. Barnes, Esther J. Cooke, Jenny Y. Zhou, Ilana Levin, Pamela Emery, Tudor H. Hughes, Morten A. Karsdal, Tina Manon-Jensen, Annette von Drygalski
Summary: This study found that basement membrane turnover markers, closely associated with synovial vascular remodeling, may serve as systemic biomarkers of acute hemarthrosis. Vascular instability during neovascularization may play a role in the dynamics of hemarthrosis.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Endocrinology & Metabolism
Rawan Hikmet, Torben Harslof, Bente Lomholt Langdahl
Summary: This study aimed to compare the effectiveness of buffered and effervescent alendronate (ALN-EFF) with conventional alendronate (ALN) in suppressing bone turnover markers (BTM). The results showed no significant difference in BTM suppression between the two groups, but the non-inferiority of ALN-EFF could not be established.
CALCIFIED TISSUE INTERNATIONAL
(2023)
Article
Medical Laboratory Technology
Jacques P. Brown, Andrew Don-Wauchope, Pierre Douville, Caroline Albert, Samuel D. Vasikaran
Summary: Bone turnover markers provide a dynamic assessment of bone remodeling, but are not useful in diagnosing osteoporosis or predicting bone loss and fractures. However, they have proven to be valuable in elucidating the pharmacodynamics and effectiveness of osteoporosis medications in clinical trials.
CLINICAL BIOCHEMISTRY
(2022)
Article
Medical Laboratory Technology
Harjit P. Bhattoa, Etienne Cavalier, Richard Eastell, Annemieke C. Heijboer, Niklas R. Jorgensen, Konstantinos Makris, Candice Z. Ulmer, John A. Kanis, Cyrus Cooper, Stuart L. Silverman, Samuel D. Vasikaran
Summary: The International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine have designated PINP and beta-CTX as reference bone turnover markers. Efforts are being made to harmonize and standardize these markers, with the development of common calibrators and reference measurement procedures, in order to establish universally acceptable practice guidelines for the management of osteoporosis.
CLINICA CHIMICA ACTA
(2021)
Article
Endocrinology & Metabolism
Hui Guo, Chunhua Sui, Shaohong Ge, Jian Cai, Dongping Lin, Yuyu Guo, Ningjian Wang, Ying Zhou, Rong Ying, Kexi Zha, Tao Gu, Yan Zhao, Yingli Lu, Zengmei An
Summary: Glucagon has a positive effect on bone metabolism in type 2 diabetes patients. It is associated with increased bone turnover markers (BTMs), indicating that it may accelerate skeletal remodeling, osteogenesis, and promote the formation of mature bone tissue. This finding suggests the possibility of developing a preparation to reduce osteoporosis in diabetic patients.
DIABETES-METABOLISM RESEARCH AND REVIEWS
(2022)
Article
Oncology
Troels D. Christensen, Christina Jensen, Ole Larsen, Bonna Leerhoy, Carsten P. Hansen, Kasper Madsen, Dan Hogdall, Morten A. Karsdal, Inna M. Chen, Dorte Nielsen, Julia S. Johansen, Nicholas Willumsen
Summary: Collagen remodeling is increased in patients with biliary tract cancer (BTC) and is associated with survival. The pro-peptides of collagen (PRO-C3 and PRO-C6) could be used as novel biomarkers for these patients.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Endocrinology & Metabolism
Jing Zhang, Rui Gao, Yongmei Jiang, Yiduo Zhang, Chuanjiao Liu, Fan Yu, Wenjie Zhou
Summary: The study found that serum levels of P1NP, beta-CTX, Vit D, and E2 may be effective indicators for the auxiliary diagnosis of idiopathic central precocious puberty. Three serum biomarker models composed of P1NP and beta-CTX, P1NP, beta-CTX, and Vit D, and P1NP, beta-CTX, Vit D, and E2 respectively, showed varying sensitivity and specificity for ICPP diagnosis.
Article
Public, Environmental & Occupational Health
Jarika Vatrasresth, Ammarin Suwan, Krasean Panyakhamlerd
Summary: Compared with a natural process, surgically induced menopausal women have a higher bone loss rate. Early treatment with estradiol valerate can significantly suppress the high bone remodeling in surgically induced menopausal women, indicating its potential benefits in preserving bone health in this population. Women who did not receive hormone treatment after surgery showed significantly elevated levels of bone turnover markers, highlighting the importance of early intervention in preventing bone loss in postmenopausal women.
Article
Rheumatology
Lotte A. van de Stadt, Feline P. B. Kroon, Christian F. Thudium, Anne C. Bay-Jensen, Margreet Kloppenburg
Summary: This study found that higher levels of C1M and hsCRP were associated with erosive hand OA, but these biomarkers were not influenced by treatment with prednisolone. The current biomarkers were not able to predict the response to prednisolone in hand OA.
Letter
Dermatology
Signe Holm Nielsen, Solveig Skovlund Groen, Yiqiu Yao, Astrid-Helene Ravn Jorgensen, Valdemar Wendelboe Nielsen, Morten Karsdal, Kristoffer Gehring, Anne-Christine Bay-Jensen, Simon Francis Thomsen
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Helena Port, Anne-Christine Bay-Jensen, Yi He, Morten A. A. Karsdal, Thorbjorn Gantzel, Christian S. S. Thudium, Signe Holm Nielsen
Summary: The development of a competitive chemiluminescence enzyme-linked immunosorbent assay, CALC2, targeting the type II collagen C-terminal pro-peptide as a marker of cartilage formation was evaluated. The CALC2 level was measured after in vitro cleavage of recombinant type II collagen and treatment of human osteoarthritis cartilage explant model with insulin-like growth factor-1. Serum CALC2 levels were found to be decreased in patients with rheumatoid arthritis and ankylosing spondylitis compared to controls. These results suggest that CALC2 may be a novel biomarker of type II collagen formation, but further studies are needed to confirm these findings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Stefania Kalogera, Mylene P. Jansen, Anne-Christine Bay-Jensen, Peder Frederiksen, Morten A. Karsdal, Christian S. Thudium, Simon C. Mastbergen
Summary: The association between structural changes and pain sensation in osteoarthritis (OA) is still not clear. This study found that some biomarkers were associated with structural outcomes, while most were associated with pain outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Thomas Levin Andersen, Pia Rosgaard Jensen, Tanja Tvistholm Sikjaer, Lars Rejnmark, Charlotte Ejersted, Jean-Marie Delaisse
Summary: Proper bone remodeling relies not only on the actions of osteoclasts and osteoblasts, but also on the delivery of osteoblast lineage cells to the remodeling site. A CD271-positive/PDGF beta-R-positive cell layer surrounding the bone marrow provides osteoblastogenic potential on all bone surfaces, including both quiescent and remodeling sites. This cell layer, known as the canopy, plays a critical role in initiating bone remodeling by activating early markers of osteoblastogenesis and supporting cell delivery to the bone surface.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Li Chen, Kaikai Shi, Nicholas Ditzel, Weimin Qiu, Florence Figeac, Louise Himmelstrup Dreyer Nielsen, Michaela Tencerova, Justyna Magdalena Kowal, Ming Ding, Christina Moller Andreasen, Thomas Levin Andersen, Moustapha Kassem
Summary: The levels of KIAA1199, a factor secreted by bone marrow stromal cells, are associated with the risk of osteoporotic fracture. KIAA1199 deficiency enhances bone formation, accelerates bone healing, and protects against ovariectomy-induced bone loss. Transplanted skeletal stem cells generate secreted factors that regulate bone regeneration, and KIAA1199 is identified as one of these factors. Patients with higher plasma levels of KIAA1199 have a higher risk of osteoporotic fracture, while lower expression levels of KIAA1199 in patient bone marrow stromal cells are associated with reduced osteogenic differentiation potential. In vitro and in vivo experiments show that KIAA1199-deficient bone marrow stromal cells exhibit enhanced osteoblast differentiation and ectopic bone formation. KIAA1199 knockout mice have increased bone mass, biomechanical strength, bone formation rate, and accelerated healing of surgically generated bone defects, and are protected from ovariectomy-induced bone loss. Mechanistically, KIAA1199 regulates osteogenesis by inhibiting the production of osteopontin by osteoblasts through integrin-mediated AKT and ERK-MAPK signaling pathways. Therefore, KIAA1199 is a regulator of osteoblast differentiation and bone regeneration, and could be a potential target for treating or managing low bone mass conditions.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Qihua Tan, Anais Marie Julie Moller, Chuan Qiu, Jonna Skov Madsen, Hui Shen, Troels Bechmann, Jean-Marie Delaisse, Bjarne Winther Kristensen, Hong-Wen Deng, David Karasik, Kent Soe
Summary: Clinical trials have shown that zoledronic acid is effective in preventing bone loss, but its potency varies among patients. Smoking has been reported as a contributing factor to the variation in sensitivity to zoledronic acid. In this study, DNA methylation profiling was performed on blood cells to investigate the molecular basis of smoking-mediated variation in treatment sensitivity. The results revealed significant associations between DNA methylation, smoking, and the half-maximal inhibitory concentration (IC50) of zoledronic acid. Genomic sites associated with bone and body size measures were also found to be enriched near the smoking-associated CpG sites. Furthermore, gene ontology analysis identified several significant functional terms related to ion channel activity and extracellular matrix strength. These findings suggest that smoking affects individual sensitivity to zoledronic acid treatment through epigenetic regulation, highlighting the potential for personalized treatment based on DNA methylation analysis.
CLINICAL EPIGENETICS
(2023)
Review
Medicine, General & Internal
Yunyun Luo, Martin Pehrsson, Lasse Langholm, Morten Karsdal, Anne-Christine Bay-Jensen, Shu Sun
Summary: Immunoassays have become increasingly important in clinical practice and biomedical research, but they are plagued by lot-to-lot variance, which negatively affects assay accuracy and precision. This article explores the reasons and locations of lot-to-lot variance, and proposes methods to mitigate its effects. The findings highlight the importance of considering lot-to-lot variance in assay development and application.
Article
Endocrinology & Metabolism
Christina Moller Andreasen, Bilal Mohamad El-Masri, Birgit MacDonald, Kaja Sondergaard Laursen, Malene Hykkelbjerg Nielsen, Jesper Skovhus Thomsen, Jean-Marie Delaisse, Thomas Levin Andersen
Summary: This study reveals the association between bone resorption events and vascular development. Analysis of proximal femoral cortical bone showed that vessels were more prevalent in non-quiescent pores compared to quiescent pores. Remodeling of existing pores had a higher density of vessels compared to de novo created pores. Additionally, pores at the eroded-formative remodeling stage had the highest density of vessels. Through 3D reconstruction, it was found that osteoclasts in the cutting cone and preosteoclasts in the lumen expressed VEGFA, while VEGFA-receptors were mainly expressed in endothelial cells in the adjacent vasculature. Therefore, it is proposed that the progression of the vascular network in intracortical remodeling events is driven by osteoclasts expressing VEGFA, and the vasculature is continuously reconfigured according to the demands of the remodeling events at the surrounding bone surfaces.
Article
Endocrinology & Metabolism
Louise Alstrup Drejer, Bilal Mohamad El-Masri, Charlotte Ejersted, Christina Moller Andreasen, Lisbeth Koch Thomsen, Jesper Skovhus Thomsen, Thomas Levin Andersen, Stinus Hansen
Summary: This case report describes a patient with postmenopausal osteoporosis who experienced multiple vertebral fractures after discontinuing denosumab treatment. The study found that reinitiating denosumab treatment led to extensive bone resorption and delayed bone formation. This highlights the importance of developing optimal discontinuation strategies to prevent such complications.
Article
Rheumatology
Christian S. Thudium, Amalie Engstrom, Anne-Christine Bay-Jensen, Peder Frederiksen, Nuria Jansen, Arjan De Zwart, Marike van der Leeden, Joost Dekker, Willem Lems, Leo Roorda, Willem Evert van Spil, Martin van der Esch
Summary: This study investigated the turnover of cartilage tissue in patients with knee osteoarthritis after a supervised exercise-related joint loading training program followed by a period of unsupervised training. It was found that both high- and low-intensity training led to increased cartilage tissue turnover, with high-intensity training showing a greater impact on cartilage degradation.
ARTHRITIS RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Patryk J. Drobinski, Neel I. Nissen, Dovile Sinkeviciute, Nicholas Willumsen, Morten A. Karsdal, Anne C. Bay-Jensen
Summary: This study investigated the relationship between blood levels of MMP-degraded and citrullinated vimentin (VICM) and MMP-degraded and non-citrullinated vimentin (VIM), as well as the standard anti-CCP biomarker, in RA patients undergoing treatment. The results showed that VICM can serve as a marker to differentiate between RA and healthy donors, and it is also a pharmacodynamic marker.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Martin Johansen, Mette Boegh Levring, Kasper Stokbro, Marta Diaz-delCastillo, Abdul Ahad Khan, Line Adsboll Wickstroem, Michael Tveden Gundesen, Ida Bruun Kristensen, Charlotte Guldborg Nyvold, Mikkel osterheden Andersen, Thomas Levin Andersen, Niels Abildgaard, Thomas Lund, Efstathios Kastritis, Moshe Gatt
Summary: Multiple myeloma patients often have osteolytic bone disease, causing fractures and reduced quality of life. This paper reviews current and novel treatment modalities, including medication, surgery, and radiation, as well as improvements in managing therapy-related complications. Oral surgery has been successful in managing osteonecrosis of the jaw, while procedures like vertebroplasty and kyphoplasty can provide pain relief and improved mobility for patients with spinal involvement. The first oral proteasome inhibitor, Ixazomib, shows promising results in increasing bone formation activity. Other potential treatment strategies are also discussed.
Article
Endocrinology & Metabolism
Pernille van Dijk Christiansen, Tanja Sikjaer, Christina Moller Andreasen, Jesper Skovhus Thomsen, Annemarie Brueel, Ellen Margrethe Hauge, Jean-Marie Delaisse, Lars Rejnmark, Thomas Levin Andersen
Summary: The study found that the use of rhPTH(1-84) in patients with hypoparathyroidism can promote intracortical remodeling and the transition from erosion to formation. This effect lasts for 30 months and is reversible.
Article
Endocrinology & Metabolism
Pernille van Dijk Christiansen, Christina Moller Andreasen, Bilal Mohamad El-Masri, Kaja Sondergaard Laursen, Jean-Marie Delaisse, Thomas Levin Andersen
Summary: This study investigates the gradual recruitment, proliferation, and differentiation of osteoprogenitors into bone-forming osteoblasts during intracortical remodeling events in healthy adolescent humans. The initiation of bone formation requires a critical density of these osteoprogenitors, which is achieved through proliferation and recruitment of local osteoprogenitors.