Indoxyl sulfate exacerbates low bone turnover induced by parathyroidectomy in young adult rats |
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| Affiliation: | 1. Safety Research Center, Kureha Corporation, Tokyo 169-8503, Japan;2. Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, Tokyo 184-8588, Japan;1. EA Martin Program, South Dakota State University, Brookings, SD 57007, USA;2. College of Nursing, South Dakota State University, Brookings, SD 57007, USA;1. Department of Medicine DIMED, Geriatrics Division; University of Padova, Italy;2. National Research Council, Neuroscience Institute, Padova, Italy;3. Department of Medicine DIMED, Clinica Medica I, University of Padova, Italy;4. Division of Health Care Planning and Evaluation of the Regione Veneto, Venice, Italy;5. Internal Medicine Division, Azienda Ospedaliera, Padova, Italy;6. Department of Cardiac, Thoracic and Vascular Sciences, Biostatistics, Epidemiology and Public Health Unit, University of Padova, Padova, Italy;1. St. Vincent Hospital, Medical Department II, Academic Teaching Hospital of the Medical University of Vienna, Austria;2. Institute of Lightweight Design and Structural Biomechanics, Vienna University of Technology, Vienna, Austria;3. Center for Medical Statistics, Informatics and Intelligent Systems, The Medical University of Vienna, Austria;4. Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria;5. Center of Bone Diseases, Lausanne University Hospital Switzerland;6. Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria;7. Department of Internal Medicine, Division of Endocrinology and Metabolism, The Medical University of Graz, Austria |
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| Abstract: | Low-turnover bone disease is one of the bone abnormalities observed in patients with chronic kidney disease (CKD) and is recognized to be associated with low serum parathyroid hormone (PTH) level and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood as renal dysfunction progresses in CKD patients. A recent in vitro study using an osteoblastic cell culture system suggests that IS has an important role in the pathogenesis of low bone turnover through induction of skeletal resistance to PTH. However, the effects of IS on the progression of low bone turnover have not been elucidated. In the present study, we produced rats with low bone turnover by performing parathyroidectomy (PTX) and fed these rats a diet containing indole, a precursor of IS, to elevate blood IS level from indole metabolism. Bone metabolism was evaluated by measuring histomorphometric parameters of secondary spongiosa of the femur. Histomorphometric analyses revealed significant decreases in both bone formation–related parameters and bone resorption–related parameters in PTX rats. In indole-treated PTX rats, further decreases in bone formation–related parameters were observed. In addition, serum alkaline phosphatase activity, a bone formation marker, and bone mineral density of the tibia tended to decrease in indole-treated PTX rats. These findings strongly suggest that IS exacerbates low bone turnover through inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH. |
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