Marc K. Drezner

Bio: Marc K. Drezner is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Hypophosphatemia & Osteomalacia. The author has an hindex of 55, co-authored 162 publications receiving 21176 citations. Previous affiliations of Marc K. Drezner include National Institutes of Health & Veterans Health Administration.

Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee

Abstract: RACTITIONERS OF BONE HISTOMORPHOMETRY communicate P with each other in a variety of arcane languages, which in general are unintelligible to those outside the field. Many in the bone and mineral scientific community would like to keep abreast of the contributions of histology to their subject, but are dismayed by the semantic barriers they must overcome. The need for standardization has been recognized for many years,(') during which there has been much talk but no action. To meet the needs of ASBMR members, Dr. B.L. Riggs (President, 19851986) asked the senior author to convene a committee of the Society to develop a unified system of termnology, suitable for adoption by the Journal of Bone and Mineral Research as part of its Instructions to Authors. The committee includes members from Europe and Canada as well as the U.S., and represents most existing systems of nomenclature. A circular letter seeking suggestions and information on current usage was sent to several hundred persons, with names drawn from the Society membership roster and lists of attendees at various recent conferences, to which approximately 40 replies were obtained. These confirmed the magnitude of the semantic problem (for some measurements as many as nine different terms were in use) and suggested a range of solutions likely to be generally acceptable. In formulating the new system. the committee kept in mind certain agreed general principles. First, the primary reason for change was to help other scientists understand bone histomorphometry, not to help bone histomorphometrists undcntand each other. Second. names should be self-explanatory and dcscriptive, without implicit assumptions. Third. symbols should consist mainly of abbreviations that included the first letter of each word in the same order as in the name. without subscripts or superscripts. Fourth. each symbol component should have one and only one meaning, and so eliminate ambiguity. Fifth, primary measurements should be clearly distinguished from derived indices. Finally, the chosen system should be sufficiently flexible to apply to all surfaces and all types of bone, and to accommodate any new primary measurement or derived index. The recommended system shares common elements with. but also differs substantially from. all those in current usc. was tested in practice for several months before the final forniat was chosen, and is as complex and conceptually difficult ;I\\ the field with which it deals. For those within the field we hope that increased readership of their papers will be adequate conipensation for the inconvcnicncc of learning a new systcm. For those outside the field, mastering the new system will be hard work, but if we are able to secure its acceptance by all journals with an interest in bone and mineral metabolism, the effort will only have to be expended once rather than. as at present. rcpeated many times. To this end we give the reasons for our decisions in the areas of controversy and, as well as definitions, provide methods for calculation of derived indices and

Standardized nomenclature, symbols, and units for bone histomorphometry: A 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee

Abstract: Before publication of the original version of this report in 1987, practitioners of bone histomorphometry communicated with each other in a variety of arcane languages, which in general were unintelligible to those outside the field. The need for standardization of nomenclature had been recognized for many years,(1) during which there had been much talk but no action. To satisfy this need, B Lawrence Riggs (ASBMR President, 1985 to 1986) asked A Michael Parfitt to convene an ASBMR committee to develop a new and unified system of terminology, suitable for adoption by the Journal of Bone and Mineral Research (JBMR) as part of its Instructions to Authors. The resulting recommendations were published in 1987(2) and were quickly adopted not only by JBMR but also by all respected journals in the bone field. The recommendations improved markedly the ability of histomorphometrists to communicate with each other and with nonhistomorphometrists, leading to a broader understanding and appreciation of histomorphometric data. In 2012, 25 years after the development of the standardized nomenclature system, Thomas L Clemens (Editor in Chief of JBMR) felt that it was time to revise and update the recommendations. The original committee was reconvened by David W Dempster, who appointed one new member, Juliet E Compston. The original document was circulated to the committee members and was extensively revised according to their current recommendations. The key revisions include omission of terminology used before 1987, recommendations regarding the parameters and technical information that should be included in all histomorphometry articles, recommendations on how to handle dynamic parameters of bone formation in settings of low bone turnover, and updating of references.

Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism

Abstract: The osteocyte, a terminally differentiated cell comprising 90%-95% of all bone cells, may have multiple functions, including acting as a mechanosensor in bone (re)modeling. Dentin matrix protein 1 (encoded by DMP1) is highly expressed in osteocytes and, when deleted in mice, results in a hypomineralized bone phenotype. We investigated the potential for this gene not only to direct skeletal mineralization but also to regulate phosphate (P(i)) homeostasis. Both Dmp1-null mice and individuals with a newly identified disorder, autosomal recessive hypophosphatemic rickets, manifest rickets and osteomalacia with isolated renal phosphate-wasting associated with elevated fibroblast growth factor 23 (FGF23) levels and normocalciuria. Mutational analyses showed that autosomal recessive hypophosphatemic rickets family carried a mutation affecting the DMP1 start codon, and a second family carried a 7-bp deletion disrupting the highly conserved DMP1 C terminus. Mechanistic studies using Dmp1-null mice demonstrated that absence of DMP1 results in defective osteocyte maturation and increased FGF23 expression, leading to pathological changes in bone mineralization. Our findings suggest a bone-renal axis that is central to guiding proper mineral metabolism.

A gene (PEX) with homologies to endopeptidases is mutated in patients with X–linked hypophosphatemic rickets

Abstract: X–linked hypophosphatemic rickets (HYP) is a dominant disorder characterised by impaired phosphate uptake in the kidney, which is likely to be caused by abnormal regulation of sodium phosphate cotransport in the proximal tubules. By positional cloning, we have isolated a candidate gene from the HYP region in Xp22.1. This gene exhibits homology to a family of endopeptidase genes, members of which are involved in the degradation or activation of a variety of peptide hormones. This gene (which we have called PEX) is composed of multiple exons which span at least five cosmids. Intragenic non–overlapping deletions from four different families and three mutations (two splice sites and one frameshift) have been detected in HYP patients, which suggest that the PEX gene is involved in the HYP disorder.

Guidelines for assessment of bone microstructure in rodents using micro–computed tomography

Abstract: Use of high-resolution micro-computed tomography (microCT) imaging to assess trabecular and cortical bone morphology has grown immensely. There are several commercially available microCT systems, each with different approaches to image acquisition, evaluation, and reporting of outcomes. This lack of consistency makes it difficult to interpret reported results and to compare findings across different studies. This article addresses this critical need for standardized terminology and consistent reporting of parameters related to image acquisition and analysis, and key outcome assessments, particularly with respect to ex vivo analysis of rodent specimens. Thus the guidelines herein provide recommendations regarding (1) standardized terminology and units, (2) information to be included in describing the methods for a given experiment, and (3) a minimal set of outcome variables that should be reported. Whereas the specific research objective will determine the experimental design, these guidelines are intended to ensure accurate and consistent reporting of microCT-derived bone morphometry and density measurements. In particular, the methods section for papers that present microCT-based outcomes must include details of the following scan aspects: (1) image acquisition, including the scanning medium, X-ray tube potential, and voxel size, as well as clear descriptions of the size and location of the volume of interest and the method used to delineate trabecular and cortical bone regions, and (2) image processing, including the algorithms used for image filtration and the approach used for image segmentation. Morphometric analyses should be based on 3D algorithms that do not rely on assumptions about the underlying structure whenever possible. When reporting microCT results, the minimal set of variables that should be used to describe trabecular bone morphometry includes bone volume fraction and trabecular number, thickness, and separation. The minimal set of variables that should be used to describe cortical bone morphometry includes total cross-sectional area, cortical bone area, cortical bone area fraction, and cortical thickness. Other variables also may be appropriate depending on the research question and technical quality of the scan. Standard nomenclature, outlined in this article, should be followed for reporting of results.

Clinician’s Guide to Prevention and Treatment of Osteoporosis

Abstract: The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF. Readers are urged to consult current prescribing information on any drug, device, or procedure discussed in this publication.

Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis

Abstract: Background A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period. Methods In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes. Results Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the ...