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      Serum bone alkaline phosphatase is a useful marker to evaluate lumbar bone mineral density in Japanese postmenopausal osteoporotic women during denosumab treatment

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          Abstract

          A worldwide health concern, osteoporosis (OP), increases the risk of bone fracture and results in morbidity. This study examined whether the representative bone absorption marker serum tartrate-resistant acid phosphatase 5b (TRACP-5b) or bone formation marker bone alkaline phosphatase (BAP) could estimate primary OP status and denosumab efficacy in a real-world setting. We retrospectively enrolled 114 female postmenopausal primary OP patients in Japan. Values and percent changes in TRACP-5b, BAP, lumbar 1–4 bone mineral density (L-BMD), and total hip BMD (H-BMD) were assessed before treatment and at 4, 8, and 12 months of therapy to identify the correlations between the percent changes in bone metabolic markers and BMD. We also established two sets of subgroups based on the upper limits of reference values in Japan for serum: TRACP-5b (<420 mU/dL) and (≥420 mU/dL) and BAP (<14.5 µg/L) and (≥14.5 µg/L). Negative correlations were observed for the percent changes of TRACP-5b and H-BMD at 4 months ( r=−0.3476) and 8 months ( r=−0.3880), for the percent changes of BAP and H-BMD at 8 months ( r=−0.3354), and for the percent changes of BAP and L-BMD at 12 months ( r=−0.3186). We observed a significant difference between the subgroups for the percent changes of L-BMD at 8 months ( p=0.013) and 12 months ( p=0.004) in BAP values. These results suggest that TRACP-5b and BAP had negative correlations with BMD, and that BAP represented a useful serum marker to evaluate L-BMD during denosumab therapy for OP.

          Most cited references17

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          Japanese 2011 guidelines for prevention and treatment of osteoporosis—executive summary

          Introduction In 1998, the first Japanese practice guidelines on osteoporosis was published. It has been updated several times, with the most recent being the full-scale 2011 edition and its abridged edition. The present guidelines provide information for the managements of primary osteoporosis in postmenopausal women and men over 50 years old, a summary of the evidence for the treatment of secondary osteoporosis, and a summary of the evidence for the prevention of osteoporosis in younger people. Method The present Executive Summary is primarily based on the content of the 2011 Japanese abridged edition. One of the key changes is revision of the criteria for initiation of pharmacological treatment, along with an introduction of the fracture risk factors used in FRAX®. Key figures and tables were selected from the Japanese abridged edition and a reference list was added. Result and conclusions The essential points of the Japanese practice guidelines on osteoporosis were translated into English for the first time. It is hoped that the content of the guidelines becomes known throughout the world.
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            Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption.

            Human serum contains two forms of tartrate-resistant acid phosphatase (TRAP), 5a and 5b. Of these, 5a contains sialic acid and 5b does not. We show here that antigenic properties and pH optimum of TRAP purified from human osteoclasts are identical to those of serum TRAP 5b and completely different from those of serum TRAP 5a, suggesting that 5b would be derived from osteoclasts and 5a from some other source. We developed a novel immunoassay specific for 5b using a monoclonal antibody O1A as capture antibody. O1A did not bind acid phosphatase derived from platelets and erythrocytes. Western analysis showed that O1A was specific for TRAP in both human bone and serum. We measured bound TRAP activity at pH 6.1, where 5b is highly active and 5a almost completely inactive. The immunoassay detected more than 90% of the initial TRAP 5b activity after 8-h incubation of serum samples at 25 degrees C and after 3 days incubation at 4 degrees C. Serum TRAP 5b activity decreased significantly after 6 months of hormone replacement therapy (HRT) of postmenopausal women compared with the change observed in postmenopausal women receiving placebo (p < 0.0001). Instead, no significant differences were observed between the changes in the placebo and HRT groups in total serum TRAP amount. These results show that serum TRAP 5b is a specific and sensitive marker for monitoring antiresorptive treatment. Instead, total serum TRAP cannot be used for that purpose. These findings may turn out to be a significant improvement in using serum TRAP as a resorption marker.
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              Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates

              Context: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. Objective: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. Design and Setting: This was an international, multicenter, randomized, double-blind trial. Participants: A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study. Interventions: Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. Main Outcome Measures: Changes in BMD and bone turnover markers were measured. Results: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs −0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). Conclusions: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2017
                09 October 2017
                : 13
                : 1343-1348
                Affiliations
                [1 ]Department of Orthopedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan
                [2 ]Department of Orthopedic Surgery, Showa-Inan General Hospital, Komagane, Japan
                Author notes
                Correspondence: Yukio Nakamura, Department of Orthopedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan, Tel +81 263 372 659, Fax +81 263 358 844, Email yxn14@ 123456aol.jp
                Article
                tcrm-13-1343
                10.2147/TCRM.S142828
                5640396
                2ef3cf82-be47-4597-91f6-2fa05025ba95
                © 2017 Nakamura et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

                Medicine
                bone mineral density,bone alkaline phosphatase,tartrate-resistant acid phosphatase 5b,denosumab,osteoporosis

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