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      Treatment of adynamic bone disease in a haemodialysis patient with teriparatide

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          Abstract

          Prevalence of adynamic bone disease (ABD), characterized by low bone turnover and absence or a reduced number of osteoblasts and osteoclasts, is increasing steadily over the last years. We present a dialysis patient, with recurrent bone fractures and biopsy-proven ABD, who was treated with teriparatide. Nine months after initiation of treatment, iPTH plasma levels increased to 520 pg/mL and a second bone biopsy revealed high bone turnover, normal mineralization and normal bone volume. Two years later, iPTH was 250–350 pg/dL and bone metabolism parameters within normal range. The probable utility of teriparatide in the treatment of ABD in dialysis patients is discussed.

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          Treatment of Hemodialysis-Associated Adynamic Bone Disease with Teriparatide (PTH 1–34 ): A Pilot Study

          Background: Adynamic bone disease (ABD) is caused by a relative or absolute parathyroid hormone (PTH) deficiency. Teriparatide (PTH 1–34 ) is an osteoanabolic agent in clinical use. Here, it was hypothesized that treatment with teriparatide improves bone mineral density (BMD) of ABD patients. Patients and Methods: Seven hemodialysis patients with ABD and a median iPTH level of 22 pg/ml were evaluated in this open-label, prospective, 6-month observational pilot-study. All patients received 20 µg teriparatide/day subcutaneously. Serologic bone markers, BMD and coronary artery calcification (CAC) were measured at baseline and after 6 months. Results: Teriparatide therapy led to a significant increase in lumbar spine (0.885 ± 0.08 vs. 0.914 ± 0.09 g/cm 2 , p 2 , p = 0.18) BMD. Compared to pretreatment values, calculated monthly changes in BMD improved significantly in both the lumbar spine and femoral neck (p < 0.02). Changes in serologic markers of bone turnover and CAC scores were not statistically significant. Conclusion: Teriparatide therapy might improve low BMD in hemodialysis patients with ABD. Further clinical studies are needed to establish teriparatide as a therapeutic option for dialysis patients with ABD.
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            Therapy for patients with CKD and low bone mineral density.

            Susan Ott (2013)
            Patients with chronic kidney disease (CKD) have a high risk of bone fracture owing to their low bone mineral density, which resembles that of postmenopausal osteoporosis. However, the mineral and bone disorder associated with CKD (CKD-MBD) is more complex than osteoporosis and the same treatments might not be appropriate. In particular, vascular calcifications are strongly associated with CKD-MBD, and must be taken into consideration. Post hoc analyses of data from pivotal osteoporosis studies suggest that in patients with mild stage 3 CKD and normal parathyroid hormone (PTH), calcium and phosphate measurements, conventional medications for osteoporosis (such as raloxifene, bisphosphonates, teriparatide and denosumab) are effective at reducing fracture rates. However, for patients with stage 4-5 CKD, or those with abnormal PTH and mineral values, the available data are insufficient to determine whether these commonly used medications are effective against fractures. Moreover, all medications used to treat osteoporosis have known or potential adverse effects in patients with CKD. Medicines that increase bone formation by upregulating Wnt signalling have shown promise in patients with osteoporosis and might be used to treat CKD-MBD in the future, but off-target effects could limit their use in in this setting.
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              Improvement of bone and mineral parameters related to adynamic bone disease by diminishing dialysate calcium.

              The existence of adynamic bone disease (ABD) as most prevalent form of renal osteodystrophy in recent years and its reduced ability to handle an exogenous calcium load has implied a higher risk for vascular and soft-tissue calcifications. The effect of low dialysate calcium (LCD) on parathyroid hormone (PTH) secretion in ABD patients has not yet sufficiently been clarified. This randomized, prospective study aimed to compare the effects of LCD and high calcium dialysate (HCD) on the evolution of bone and mineral parameters related to ABD in dialysis patients. 52 out of 60 patients with predialysis intact PTH<100 pg/ml completed this study and were equally distributed over LCD (1.25 mmol/l) or HCD (1.75 mmol/l) treatment. The duration of the study was 6 months and the only peroral phosphate binder administered was calcium carbonate. Total and ionised calcium were measured monthly in serum before and after dialysis while serum parameters relevant to bone were measured at the enrollment and at 3-month intervals. There were no differences in predialysis mean phosphate or calcium x phosphorus product (Ca x P). The most common side effects of both treatments were comparable. Hypotension occurred in 16% and 17% and cramps in 6% and 8% of the dialysis sessions, in the HCD and LCD group, respectively. The groups did not differ in the mean tCa before dialysis, but this parameter was significantly higher in the HCD group vs. LCD at the end of dialysis (2.59+/-0.18 vs. 2.44+/-0.19 mmol/l; p<0.01). The patients of the HCD group also had a significantly higher mean iCa both before (1.08+/-0.05 vs. 1.04+/-0.06 mmol/l; p=0.02) and at the end of dialysis (1.18+/-0.04 vs. 1.48+/-0.04 mmol/l; p<0.01). There were no differences within the LCD group between baseline and end of dialysis treatment values of tCa and iCa. However, the mean tCa and iCa were markedly increased at the end of dialysis in the HDC group [2.40+/-0.21 vs. 2.59+/-0.18 mmol/l (p<0.01); 1.08+/-0.05 vs. 1.18+/-0.04 mmol/l (p<0.01)]. Mean serum levels of iPTH and total alkaline phosphatase in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels [(38.6+/-22.9 vs. 63.3+/-46.0 vs. 78.6+/-44.7 pg/ml); (59.5+/-18.7 vs. 75.9+/-26.7 vs. 84.0+/-35.4 U/l)], respectively, and bone alkaline phosphatase increased also only after 6 months of treatment (23.4+/-7.3 U/l vs. 35.6+/-22.3). The bone markers in the HCD group did not change. At the end of the study all bone parameters in the LCD group were significantly higher than in the HCD group. There was an evolution towards parameters reflecting higher bone turnover in patients treated with dialysate calcium of 1.25 mmol/l, probably by prevention of a positive calcium balance and enabling sustained stimulation of PTH secretion. Hence, LCD might be considered a valuable therapeutic option for ABD patients.
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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                ndtplus
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                April 2015
                10 February 2015
                10 February 2015
                : 8
                : 2
                : 188-190
                Affiliations
                Department of Nephrology, Aristotle University of Thessaloniki, Hippokration General Hospital , Thessaloniki, Greece
                Author notes
                Correspondence to: Aikaterini Papagianni; E-mail: aikpapag@ 123456otenet.gr
                Article
                sfv005
                10.1093/ckj/sfv005
                4370305
                93fe28fe-6beb-440c-a0ed-77815da9b34c
                © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 2 September 2014
                : 15 January 2015
                Categories
                Contents
                CKD-Mbd

                Nephrology
                adynamic bone disease,haemodialysis,teriparatide
                Nephrology
                adynamic bone disease, haemodialysis, teriparatide

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