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      Bisphophonates in CKD Patients with Low Bone Mineral Density

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          Abstract

          Patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) have a high risk of bone fracture because of low bone mineral density and poor bone quality. Osteoporosis also features low bone mass, disarranged microarchitecture, and skeletal fragility, and differentiating between osteoporosis and CKD-MBD in low bone mineral density is a challenge and usually achieved by bone biopsy. Bisphosphonates can be safe and beneficial for patients with a glomerular filtration rate of 30 mL/min or higher, but prescribing bisphosphonates in advanced CKD requires caution because of the increased possibility of low bone turnover disorders such as osteomalacia, mixed uremic osteodystrophy, and adynamic bone, even aggravating hyperparathyroidism. Therefore, bone biopsy in advanced CKD is an important consideration before prescribing bisphosphonates. Treatment also may induce hypocalcemia in CKD patients with secondary hyperparathyroidism, but vitamin D supplementation may ameliorate this effect. Bisphosphonate treatment can improve both bone mineral density and vascular calcification, but the latter becomes more unlikely in patients with stage 3-4 CKD with vascular calcification but no decreased bone mineral density. Using bisphosphonates requires considerable caution in advanced CKD, and the lack of adequate clinical investigation necessitates more studies regarding its effects on these patients.

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          Most cited references98

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          Osteoporosis prevention, diagnosis, and therapy.

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          To clarify the factors associated with prevention, diagnosis, and treatment of osteoporosis, and to present the most recent information available in these areas. From March 27-29, 2000, a nonfederal, nonadvocate, 13-member panel was convened, representing the fields of internal medicine, family and community medicine, endocrinology, epidemiology, orthopedic surgery, gerontology, rheumatology, obstetrics and gynecology, preventive medicine, and cell biology. Thirty-two experts from these fields presented data to the panel and an audience of 699. Primary sponsors were the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institutes of Health Office of Medical Applications of Research. MEDLINE was searched for January 1995 through December 1999, and a bibliography of 2449 references provided to the panel. Experts prepared abstracts for presentations with relevant literature citations. Scientific evidence was given precedence over anecdotal experience. The panel, answering predefined questions, developed conclusions based on evidence presented in open forum and the literature. The panel composed a draft statement, which was read and circulated to the experts and the audience for public discussion. The panel resolved conflicts and released a revised statement at the end of the conference. The draft statement was posted on the Web on March 30, 2000, and updated with the panel's final revisions within a few weeks. Though prevalent in white postmenopausal women, osteoporosis occurs in all populations and at all ages and has significant physical, psychosocial, and financial consequences. Risks for osteoporosis (reflected by low bone mineral density [BMD]) and for fracture overlap but are not identical. More attention should be paid to skeletal health in persons with conditions associated with secondary osteoporosis. Clinical risk factors have an important but poorly validated role in determining who should have BMD measurement, in assessing fracture risk, and in determining who should be treated. Adequate calcium and vitamin D intake is crucial to develop optimal peak bone mass and to preserve bone mass throughout life. Supplementation with these 2 nutrients may be necessary in persons not achieving recommended dietary intake. Gonadal steroids are important determinants of peak and lifetime bone mass in men, women, and children. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and may reduce risk of falls in older persons. Assessment of bone mass, identification of fracture risk, and determination of who should be treated are the optimal goals when evaluating patients for osteoporosis. Fracture prevention is the primary treatment goal for patients with osteoporosis. Several treatments have been shown to reduce the risk of osteoporotic fractures, including those that enhance bone mass and reduce the risk or consequences of falls. Adults with vertebral, rib, hip, or distal forearm fractures should be evaluated for osteoporosis and given appropriate therapy.
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            Normal bone anatomy and physiology.

            This review describes normal bone anatomy and physiology as an introduction to the subsequent articles in this section that discuss clinical applications of iliac crest bone biopsy. The normal anatomy and functions of the skeleton are reviewed first, followed by a general description of the processes of bone modeling and remodeling. The bone remodeling process regulates the gain and loss of bone mineral density in the adult skeleton and directly influences bone strength. Thorough understanding of the bone remodeling process is critical to appreciation of the value of and interpretation of the results of iliac crest bone histomorphometry. Osteoclast recruitment, activation, and bone resorption is discussed in some detail, followed by a review of osteoblast recruitment and the process of new bone formation. Next, the collagenous and noncollagenous protein components and function of bone extracellular matrix are summarized, followed by a description of the process of mineralization of newly formed bone matrix. The actions of biomechanical forces on bone are sensed by the osteocyte syncytium within bone via the canalicular network and intercellular gap junctions. Finally, concepts regarding bone remodeling, osteoclast and osteoblast function, extracellular matrix, matrix mineralization, and osteocyte function are synthesized in a summary of the currently understood functional determinants of bone strength. This information lays the groundwork for understanding the utility and clinical applications of iliac crest bone biopsy.
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              Bone mineralization density distribution in health and disease.

              Human cortical and trabecular bones are formed by individual osteons and bone packets, respectively, which are produced at different time points during the (re)modeling cycle by the coupled activity of bone cells. This leads to a heterogeneously mineralized bone material with a characteristic bone mineralization density distribution (BMDD) reflecting bone turnover, mineralization kinetics and average bone matrix age. In contrast to BMD, which is an estimate of the total amount of mineral in a scanned area of whole bone, BMDD describes the local mineral content of the bone matrix throughout the sample. Moreover, the mineral content of the bone matrix is playing a pivotal role in tuning its stiffness, strength and toughness. BMDD of healthy individuals shows a remarkably small biological variance suggesting the existence of an evolutionary optimum with respect to its biomechanical performance. Hence, any deviations from normal BMDD due to either disease and/or treatment might be of significant biological and clinical relevance. The development of appropriate methods to sensitively measure the BMDD in bone biopsies led to numerous applications of BMDD in the evaluation of diagnosis and treatment of bone diseases, while advancing the understanding of the bone material, concomitantly. For example, transiliacal bone biopsies of postmenopausal osteoporotic women were found to have mostly lower mineralization densities than normal, which were partly associated by an increase of bone turnover, but also caused by calcium and Vit-D deficiency. Antiresorptive therapy causes an increase of degree and homogeneity of mineralization within three years of treatment, while normal mineralization levels are not exceeded. In contrast, anabolic therapy like PTH decreases the degree and homogeneity of matrix mineralization, at least transiently. Osteogenesis imperfecta is generally associated with increased matrix mineralization contributing to the brittleness of bone in this disease, though bone turnover is usually increased suggesting an alteration in the mineralization kinetics. Furthermore, BMDD measurements combined with other scanning techniques like nanoindentation, Fourier transform infrared spectroscopy and small angle X-ray scattering can provide important insights into the structure-function relation of the bone matrix, and ultimately a better prediction of fracture risk in diseases, and after treatment.
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                Author and article information

                Journal
                ScientificWorldJournal
                ScientificWorldJournal
                TSWJ
                The Scientific World Journal
                Hindawi Publishing Corporation
                1537-744X
                2013
                31 December 2013
                : 2013
                : 837573
                Affiliations
                1Department of Internal Medicine, Department of Health, Ministry of Health and Welfare, Chia-Yi Hospital, Chia-Yi, Taiwan
                2Department of Internal Medicine, Cardinal Tien Hospital, Yong He Branch, New Taipei, Taiwan
                3Division of Nephrology, Department of Medicine, Cathay General Hospital, Taipei, Taiwan
                4Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, 362 Chung-Cheng Road, Hsin-Tien, New Taipei 231, Taiwan
                Author notes

                Academic Editors: D. Geetha and F. Thaiss

                Author information
                http://orcid.org/0000-0002-3212-9218
                http://orcid.org/0000-0003-0412-3596
                Article
                10.1155/2013/837573
                3899701
                2562a2a1-9ec1-4337-8172-f85f93901eb5
                Copyright © 2013 Wen-Chih Liu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 November 2013
                : 27 November 2013
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