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Analysis of Utilization of Bisphosphonates, Strontium Ranelate and Denosumabe in Serbia, Finland, Norway and Denmark in the Period 2013 – 2016

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Analysis of Utilization of Bisphosphonates, Strontium Ranelate and Denosumabe in Serbia, Finland, Norway and Denmark in the Period 2013 – 2016 ISSN 2334-9492 (Online) Hospital Pharmacology. 2019; 6(3):857-867 UDC: 616.71-007.234-085(497.11)”2013/2016” doi:10.5937/hpimj1903857C Analysis of Utilization of Bisphosphonates, Strontium Original Study Ranelate and Denosumabe in Serbia, Finland, Norway and Denmark in the Period 2013 – 2016 A Đurđa M. Cvjetković, Sara M. Cvjetković-Nedeljković, Nikola B. Martić, Ana J. Sabo, Zdenko S. Tomić, Boris Ž. Milijašević A Department of Pharmacology, Toxicology and Clinical Pharmacology‚ Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Vojvodina, Serbia SUMMARY Introduction: Osteoporosis is the most common metabolic bone disease. Aim: This study aimed to measure the utilization of drugs aff ecting bone structure and mineralization in Serbia from 2013 to 2016, and to compare this data with that from countries with well-developed pharmacotherapeutic practice, such as Finland, Norway, and Denmark. Methods: The utilization of drugs is estimated using the Anatomical Therapeutic Chemical/Defi ned Daily Dose (DDD) methodology. The amount of total drugs con- sumed has been expressed in the number of Defi ned Daily Dose on 1000 inhabitants per day (DDD/1000 inhabitants/day). Results: In 2016, a total of 2.91 DDD/1000 inh/day of all drugs was used in Serbia of which 75.26% belonged to bisphosphonates, whereas they made 37.15% in Finland, 81.56% in Norway and 77.84% in Denmark of the total utilization of M05 drugs sub- class. The most frequently used bisphosphonate in Serbia in 2013 was alendronic acid, while in 2016 it was ibandronic acid. In three compared countries the rate of utiliza- tion among bisphosphonates was the highest for alendronic acid. The level of other bisphosphonates’ utilization in Serbia, as well as the utilization of strontium ranelate, is constantly low compared to other drugs. In comparison to other countries, the utili- zation of denosumab in Serbia is multiple folds lower, however with an upward trend. Conclusions: The utilization of drugs aff ecting bone structure and mineralization in the examined period in Serbia compared to Finland, Norway and Denmark is three to six fold lower. Furthermore, there is a diff erence between the structure of prescribed and consumed drugs. Keywords: osteoporosis, bisphosphonates, denosumab, utilization of drugs, pharmacoepidemiology Corresponding author: Associate Professor Boris Milijasevic MD, PhD Specialist in Clinical Pharmacology © The Serbian Medical Society 2014 Department of Pharmacology, Toxicology and Clinical Pharmacology, Medical Faculty of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia E-mail: [email protected] 857 Hospital Pharmacology. 2019; 6(3):857-867 INTRODUCTION Osteoporosis is the commonest metabolic porosis-related fracture or in patients with a bone disease. It is believed that almost every T-score between −1.0 and −2.5 between −1.0 second woman and every fi ft h man above 50 and −2.5 combined with or high fracture prob- years of age will suff er a fracture caused by ability. Prior to initiating treatment, patients osteoporosis [1]. All fractures are associated should be evaluated for secondary causes of os- with greater morbidity, whereas hip fractures teoporosis [5]. Pharmacological interventions are associated with greater mortality. Every can be classifi ed into antiresorptive agents that fi ft h woman above 50 years of age that has suf- prevent bone resorption and anabolic agents fered hip fracture dies within one year aft er the that help in the new bone formation. Anti- fracture. Th erefore early detection, prevention, resorptive agents include bisphosphonates, and rational treatment are of great importance hormone replacement therapy (HRT), selec- not only for an individual but for the entire tive estrogen receptor modulators (SERM), population – it should be one of the national and denosumab [6]. Anabolic agents include health priorities at the primary health-care teriparatide, bone growth factors, growth hor- level [2]. mone. Th ere are also medications both with According to the defi nition of the the antiresorptive and anabolic mechanism Consensus Development Conference from of action (strontium ranelate) [2,7]. Th e most 1993, “osteoporosis is a progressive, systemic, commonly used agents in Europe are bisphos- skeletal disease characterized by low bone phonates (alendronic, ibandronic, risedronic density and microarchitectural deteriora- and zoledronic acid), denosumab, teripara- tion in the bone that predisposes patients to tide, strontium ranelate, raloxifene. Hormone increased bone fragility and fracture”. By the replacement therapy (HRT) is used for both age of 35 or 40 bone density naturally begins prevention and treatment of postmenopausal to weaken. Th e rate of mineral loss is 0,3-0,5% osteoporosis. However, it is not the fi rst-choice per year. Besides postmenopausal estrogen treatment. Considering the progressive devel- defi ciency, major risk factors for osteoporosis opment of pharmacotherapy, new eff ective include early natural or surgical menopause osteoporosis treatment options are anticipated (before the age of 45), hysterectomy with at [8]. least one ovary retained before the age of 45, positive family history for osteoporosis and AIM fractures (especially mother’s hip fracture his- tory), white race, gracile body type, long-term Th e aim of this study was to measure the uti- immobilization, long-term drug utilization lization of drugs aff ecting bone structure and (prednisone or equivalent 5mg/day for at least mineralization in Serbia from 2013 to 2016 three months), low calcium and vitamin D and to compare with countries with well-de- intake, sedentary lifestyle, physical inactivity, veloped pharmacotherapeutic practice, such smoking, alcohol utilization [1-3]. as the Norway, Finland, and Denmark. Th e most common osteoporotic frac- tures are those of the distal forearm, spine, and METHODS hip. Risk factors for fractures are low bone mineral density (BMD), advanced age, female We conducted a descriptive retrospective gender, previous falls, weak muscles, poor bal- pharmacoepidemiological study based on ance, conditions and medications aff ecting data already placed in the public domain by cognitive function, gait and balance [1,4]. Th e the regulatory authorities, therefore no Ethical gold standard for diagnosing osteoporosis, Committee or Agency approval for conduct- fracture risk prediction and for monitoring of ing the study was obligatory. treatment response is the evaluation of bone Drug utilization and price data in mineral density – BMD that is primarily de- the Republic of Serbia in the period 2013 – termined by bone mineral content [1-3, 5]. 2016 were collected from the offi cial website Along with nonpharmacological of Medicines and Medical Devices Agency of measures, pharmacologic therapy is indicated Serbia and offi cial website of National Health in patients with a T-score equal to or worse Insurance Fund of Serbia [9-12]. than -2.5, in patients who have had an osteo- Drug utilization and price data in the 858 Volume 6 • Number 3 • December 2019 • HOPH Cvjetković ĐM et al: Analysis of Utilization of Bisphosphonates, Strontium Ranelate and Denosumabe in Serbia, Finland, Norway and Denmark in the Period 2013 – 2016 Kingdom of Norway in the period 2013 – 2016 Kingdom of Norway, the Republic of Finland were collected from the offi cial website of the and the Kingdom of Denmark are presented in Norwegian Institute for Public Health [13]. a tabular form. Drug utilization and price data in Th e Anatomical Th erapeutic Chemi- the Republic of Finland in the period 2013 – cal (ATC) Classifi cation System is based on a 2016 were collected from the offi cial website of combination of seven alphanumeric charac- Finnish Medicines Agency – Fimea [14-17]. ters that represent the International Nonpro- Drug utilization and price data in prietary Name (INN) – an offi cial generic and the Kingdom of Denmark in the period 2013 non-proprietary name given to a pharmaceu- – 2016 were collected from offi cial website of tical drug or an active ingredient [20]. Th e Danish Health Data Authority – Sund- Th is type of study includes data al- hedsdatastyrelsen [18]. ready placed in the public domain by the regu- Th e utilization of drugs is estimated latory authorities, so no patient consent or using the Anatomical Th erapeutic Chemical/ agency approval for data protection is needed. Defi ned Daily Dose (DDD) methodology. De- Apart from descriptive statistics, for- fi ned Daily Dose (DDD) is a statistical measure mal statistical analyses were not used. Data are that represents an assumed average mainte- presented in tables. nance dose per day for a drug used for its main indication in adults. Th e amount of total drug RESULTS utilization has been expressed in the number of Defi ned Daily Dose on 1000 inhabitants per In Serbia, the utilization of bisphosphonates day (DDD/1000 inhabitants/day). Th e param- predominates and their utilization increased eter DDD per 1000 inhabitants per day gives from 2.25 DDD/1000 inhabitants/day or an insight into the number of inhabitants that 69.23% of the utilization of all drugs aff ecting used a certain drug and were exposed to its ef- bone structure and mineralization (M05B) in fect during one day [19]. Th e results regarding 2013 to 2.89 DDD/1000 inhabitants/day or drug utilization in the Republic of Serbia, the 82.57% in 2015 (Table 1). However, in 2016 Table 1. Utilization of drugs Country Serbia aff ecting bone structure and Year 2013 2014 2015 2016 mineralization in Serbia
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