Reporting Guidelines, Review of Methodological Standards, and Challenges Toward Harmonization in Bone Marrow Adiposity Research. Report of the Methodologies Working Group of the International Bone Marrow Adiposity Society
Josefine Tratwal, Laboratory of Regenerative Hematopoiesis, Institute of Bioengineering and Swiss Institute for Experimental Cancer Research, Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Rossella Labella, Tissue and Tumour Microenvironments Lab, The Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
Nathalie Bravenboer, Department of Clinical Chemistry, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam Movement Sciences, Amsterdam, Netherlands.
Greet Kerckhofs, Biomechanics Lab, Institute of Mechanics, Materials and Civil Engineering, UCLouvain, Louvain-la-Neuve, Belgium.
Eleni Douni, Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, Athens, Greece.
Erica L. Scheller, Division of Bone and Mineral Diseases, Department of Medicine, Washington University, St. Louis, MO, United States.
Sammy Badr, Univ. Lille, EA 4490 - PMOI - Physiopathologie des Maladies Osseuses Inflammatoires, Lille, France.
Dimitrios C. Karampinos, Department of Diagnostic and Interventional Radiology, Technical University of Munich, Munich, Germany.
Sarah Beck-Cormier, Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, France.
Biagio Palmisano, Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, United States.
Antonella Poloni, Hematology, Department of Clinic and Molecular Science, Università Politecnica Marche-AOU Ospedali Riuniti, Ancona, Italy.
Maria J. Moreno-Aliaga, Centre for Nutrition Research and Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain.
Jackie Fretz, Department of Orthopaedics and Rehabilitation, Cellular and Developmental Biology, Yale University School of Medicine, New Haven, CT, United States.
Matthew S. Rodeheffer, Department of Comparative Medicine and Molecular, Cellular and Developmental Biology, Yale University School of Medicine, New Haven, CT, United States.
Parastoo Boroumand, Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
Clifford J. Rosen, Maine Medical Center Research Institute, Center for Clinical and Translational Research, Scarborough, ME, United States.
Mark C. Horowitz, Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, United States.
Bram C. van der Eerden, Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
Annegreet G. Veldhuis-Vlug, Section of Endocrinology, Department of Internal Medicine, Center for Bone Quality, Leiden University Medical Center, Leiden, Netherlands.
Olaia Naveiras, Laboratory of Regenerative Hematopoiesis, Institute of Bioengineering and Swiss Institute for Experimental Cancer Research, Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
The interest in bone marrow adiposity (BMA) has increased over the last decade due to its association with, and potential role, in a range of diseases (osteoporosis, diabetes, anorexia, cancer) as well as treatments (corticosteroid, radiation, chemotherapy, thiazolidinediones). However, to advance the field of BMA research, standardization of methods is desirable to increase comparability of study outcomes and foster collaboration. Therefore, at the 2017 annual BMA meeting, the International Bone Marrow Adiposity Society (BMAS) founded a working group to evaluate methodologies in BMA research. All BMAS members could volunteer to participate. The working group members, who are all active preclinical or clinical BMA researchers, searched the literature for articles investigating BMA and discussed the results during personal and telephone conferences. According to the consensus opinion, both based on the review of the literature and on expert opinion, we describe existing methodologies and discuss the challenges and future directions for (1) histomorphometry of bone marrow adipocytes, (2) BMA imaging, (3) BMA imaging, (4) cell isolation, culture, differentiation and modulation of primary bone marrow adipocytes and bone marrow stromal cell precursors, (5) lineage tracing and BMA modulation, and (6) BMA biobanking. We identify as accepted standards in BMA research: manual histomorphometry and osmium tetroxide 3D contrast-enhanced μCT for quantification, specific MRI sequences (WFI and H-MRS) for studies, and RT-qPCR with a minimal four gene panel or lipid-based assays for quantification of bone marrow adipogenesis. Emerging techniques are described which may soon come to complement or substitute these gold standards. Known confounding factors and minimal reporting standards are presented, and their use is encouraged to facilitate comparison across studies. In conclusion, specific BMA methodologies have been developed. However, important challenges remain. In particular, we advocate for the harmonization of methodologies, the precise reporting of known confounding factors, and the identification of methods to modulate BMA independently from other tissues. Wider use of existing animal models with impaired BMA production (e.g., , Kit) and development of specific BMA deletion models would be highly desirable for this purpose.