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      The secular trends in the use of medications for osteoporosis in South Korea using Intercontinental Medical Statistics Health Sales Audit 2006–2018

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          Abstract

          Objectives

          Osteoporosis medications are widely available in South Korea, and well reimbursed by the Government Health Insurance; however, some expensive drugs are not reimbursed. The prescription of anti-osteoporosis drugs (AODs) are increasing for the elderly and for postmenopausal women. We investigate the secular trends of AODs in South Korea.

          Methods

          We used the Intercontinental Medical Statistics Health Sales Audit between January 1, 2006 and December 31, 2018. We analyzed the total sales costs and market share of AODs including bisphosphonates, selective estrogen receptor modulators (SERMs), parathyroid hormone (PTH), calcitonins, and denosumab using the number of days of therapy (DOT). Changes of prescription patterns including original versus generic drugs, vitamin D combination, and types of medical institutions were also analyzed.

          Results

          Bisphosphonates were the most frequently used drug during the study period although its DOT declined from 92.5% in 2008 to 80.0% in 2018. SERMs were the second-most used medication, and has maintained around 13% since 2015. The proportion of calcitonins has decreased since 2011, mainly due to malignancy risk. In contrast, the DOT of PTH and denosumab increased to 0.8% and 4.7% in 2018, respectively. The use of generics, vitamin D combination, and intravenous bisphosphonates has been increasing throughout the study period.

          Conclusions

          Prescription patterns using DOT are changing probably due to the increase in older adult patients and severely osteoporotic patients. There are other issues including safety and the launching of new drugs.

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          Most cited references26

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          Prevention and treatment of postmenopausal osteoporosis.

          In the beginning, that is from the 1960's, when a link between menopause and osteoporosis was first identified; estrogen treatment was the standard for preventing bone loss, however there was no fracture data, even though it was thought to be effective. This continued until the Women's Health Initiative (WHI) study in 2001 that published data on 6 years of treatment with hormone therapy that showed an increase in heart attacks and breast cancer. Even though the risks were small, 1 per 1500 users annually, patients were worried and there was a large drop off in estrogen use. In later analyses the WHI study showed that estrogen reduced fractures and actually prevented heart attacks in the 50-60 year age group. Estrogen alone appeared to be safer to use than estrogen+the progestin medroxyprogesterone acetate and actually reduced breast cancer. At the same time other drugs were being developed for bone that belong to the bisphosphonate group and the first generation of compounds showed moderate potency on bone resorption. The second and third generation compounds were much more potent and in a series of large trials were shown to reduce fractures. For the last 15 years the treatment of osteoporosis belonged to the bisphosphonate compounds, most of which reduce fracture rates by 50 percent. With the exception of gastrointestinal irritation the drugs are well tolerated and highly effective. The sophistication of the delivery systems now allow treatment that can be given daily, weekly, monthly and annually either orally or intravenously. Bone remodeling is a dynamic process that repairs microfractures and replaces old bone with new bone. In the last 10 years there has been a remarkable understanding of bone biology so that new therapies can be specifically designed on a biological basis. The realization that RANKL was the final cytokine involved in the resorption process and that marrow cells produced a natural antagonist called Osteoprotegerin (OPG) quickly led to two lines of therapy. First OPG was used as a therapy to block RANKL was initially successful but later antibodies against OPG developed and this line of treatment had to be discontinued. The next step was to develop a monoclonal antibody against RANKL and this proved to be highly effective in blocking bone resorption. It led to development of a drug Denosumab that successfully reduces fractures and is now one of the therapeutic options for osteoporosis treatment. On the anabolic side bone biology research showed that osteocytes produces sclerostin an inhibitor of the anabolic WNT signaling pathway. Recent development of a monoclonal antibody against sclerostin has shown remarkable anabolic activity in bone showing large increases in bone density and fracture trials are now underway. The newer treatments for osteoporosis are likely to be based on our understanding of bone biology and the design of new highly specific compounds with fewer side effects. This review summarizes the diagnosis of postmenopausal osteoporosis and various available non-pharmacological and pharmacological therapies available for its management. This article is part of a Special Issue entitled 'Menopause'.
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            Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis.

            Systematic review of adherence to bisphosphonates for the treatment of osteoporosis finds suboptimal levels of persistence and compliance. Poor bisphosphonate compliance increases fracture risk. The objectives of the study were to measure the persistence and compliance with bisphosphonates for the treatment of osteoporotic patients, and to estimate the influence of compliance on fracture risk. A systematic review of bisphosphonate adherence in clinical practise provided new evidence to perform a meta-analysis of the means of bisphosphonate persistence and compliance, with a subsequent meta-analysis of fracture risk comparing poorly versus highly compliant patients. Fifteen articles, totalling 704,134 patients, met our inclusion criteria. Most of the patients were postmenopausal women treated with bisphosphonates. The 3.95% of the patients received hormone replacement therapy, but the rest received bisphosphonates. The meta-analysis of five articles totalling 236,540 patients, who were followed for 1 year, provided a pooled persistence mean of 184.09 days. The meta-analysis of five articles, totalling 234,737 patients, who were also followed for 1 year, provided a pooled medication possession ratio mean of 66.93%. The meta-analysis of six articles, totalling 171,063 patients, who were followed for varying periods of time between 1 and 2.5 years, provided a pooled 46% increased fracture risk in non-compliant patients versus compliant patients. The increased fracture risk was lower for non-vertebral (16%) and hip (28%) than for clinical vertebral fractures (43%). Persistence and compliance are suboptimal for postmenopausal women undergoing bisphosphonate therapy for osteoporosis. The clinical consequence of this low compliance is an increased risk of fracture, which is lower for non-vertebral than for clinical vertebral fractures.
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              Management of Hypoparathyroidism: Present and Future.

              Conventional management of hypoparathyroidism has focused upon maintaining the serum calcium with oral calcium and active vitamin D, often requiring high doses and giving rise to concerns about long-term consequences including renal and brain calcifications. Replacement therapy with PTH has recently become available. This paper summarizes the results of the findings and recommendations of the Working Group on Management of Hypoparathyroidism.
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                Author and article information

                Contributors
                Journal
                Osteoporos Sarcopenia
                Osteoporos Sarcopenia
                Osteoporosis and Sarcopenia
                Korean Society of Osteoporosis
                2405-5255
                2405-5263
                03 December 2020
                December 2020
                03 December 2020
                : 6
                : 4
                : 185-190
                Affiliations
                [1]Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea
                Author notes
                []Corresponding author. Department of Endocrinology and Metabolism, Ajou University School of Medicine, 164 Worldcup-ro Yeoungtong-gu, Suwon City, 16499, South Korea. yschung@ 123456ajou.ac.kr
                Article
                S2405-5255(20)30107-2
                10.1016/j.afos.2020.11.007
                7783074
                884f51b5-efbe-44a2-b9ca-c74e67425214
                © 2020 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 2 July 2020
                : 11 November 2020
                : 18 November 2020
                Categories
                Original Article

                bisphosphonate,calcitonin,denosumab,parathyroid hormone,selective estrogen receptor modulator

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