AUTHOR=Chavassieux Pascale , Chapurlat Roland TITLE=Interest of Bone Histomorphometry in Bone Pathophysiology Investigation: Foundation, Present, and Future JOURNAL=Frontiers in Endocrinology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.907914 DOI=10.3389/fendo.2022.907914 ISSN=1664-2392 ABSTRACT=Despite the development of non-invasive methods, bone histomorphometry remains the only method to analyse bone at the tissue and cell levels. Quantitative analysis of transiliac bone sections requires strict methodologic conditions but since its foundation more 60 years ago, this methodology has progressed. Our purpose was to review the evolution of bone histomorphometry over the years and its contribution in the knowledge in bone tissue metabolism under normal and pathological conditions and the understanding of the mechanisms of action of therapeutic drugs in humans. The two main applications of bone histomorphometry are the diagnosis of bone diseases and research. It is warranted for the diagnosis of mineralization defects as in osteomalacia, of other causes of osteoporosis as bone mastocytosis or the classification of renal osteodystrophy. Bone biopsies are required in clinical trials to evaluate the safety and mechanism of action of new therapeutic agents and were applied to anti-osteoporotic agents as bisphosphonates and denosumab, an anti-RANKL, which induce a marked reduction of the bone turnover with a consequent elongation of the mineralization period. In contrast, an increased bone turnover with an extension of the formation site is observed with teriparatide. Romosozumab, an anti-sclerostin, has a dual effect with an early increased formation and reduced resorption. Bone histomorphometric studies allows to understand the mechanism of coupling between formation and resorption and to evaluate the respective role of bone modeling and remodeling. The adaptation of new image analysis techniques will help bone biopsy analysis in the future.