Use of Drugs Against Osteoporosis in the Baltic Countries During 2010

Home , Clodronic acid, Risedronic acid, Strontium ranelate

m e d i c i n a 5 2 ( 2 0 1 6 ) 3 1 5 – 3 2 0

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Original Research Article

Use of drugs against osteoporosis in the Baltic countries

during 2010–2014

a,b,* a,c d a,c

Ott Laius , Katre Maasalu , Sulev Kõks , Aare Märtson

Department of Traumatology and Orthopedics, University of Tartu, Tartu, Estonia

Estonian State Agency of Medicines, Tartu, Estonia

Clinic of Traumatology and Orthopedics, Tartu University Hospital, Tartu, Estonia

Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia

a r t i c l e i n f o a b s t r a c t

Article history: Background and objective: Osteoporosis is a major health threat nowadays. Aging of the

Received 17 November 2015 population and changes in peoples' lifestyle result in a constant increase in the number

Received in revised form of fractures all over the world. Our study aimed at describing the drug utilization pattern and

20 September 2016 choice of active substances of antiosteoporotic medicines in the Baltic countries.

Accepted 2 October 2016 Materials and methods: Sales data of the antiosteoporotic medicines was obtained from the

Available online 13 October 2016 internet. These are available on the website of medicines regulatory agencies. The World

Health Organization (WHO) methodology of Anatomical Therapeutic Chemical (ATC) clas-

ﬁ ﬁ

Keywords: si cation and de ned daily dose (DDD) was used to compare the data among countries.

Osteoporosis Results: During the study period the consumption of antiosteoporotic medicines was rather

Bisphosphonates stable in all the countries. The overall choice of active substances used to treat osteoporosis

is similar in all the Baltic countries but the market shares of substances were different.

Deﬁned daily dose

Estonia stands out with high use of combination product of alendronic acid and colecalci-

Baltic countries

ferol. In Latvia the highest consumption was of risedronic acid. In Lithuania the most used

Drug utilization

active substance in 2014 was ibandronic acid and second was denosumab with 0.8 daily

doses per 1000 inhabitants per day (DID) and 25% of the total share.

Conclusions: The differences in consumption of drugs against osteoporosis in the Baltic

countries are not very big. The consumption of antiosteoporotic drugs is not to be regarded

as sufﬁcient though. The generally low consumption of osteoporotic medicines in the Baltic

countries can be attributed to the overall less than EU average wealth of the countries and

less than optimal expenditure on healthcare out of the GDP.

# 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier

Sp. z o.o. This is an open access article under the CC BY-NC-ND license (http://creative-

commons.org/licenses/by-nc-nd/4.0/).

* Corresponding author at: Estonian State Agency of Medicines, Nooruse 1, Tartu, Estonia.

E-mail address: [email protected] (O. Laius).

Peer review under the responsibility of the Lithuanian University of Health Sciences.

http://dx.doi.org/10.1016/j.medici.2016.10.001

1010-660X/# 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Sp. z o.o. This is an open access

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

316 m e d i c i n a 5 2 ( 2 0 1 6 ) 3 1 5 – 3 2 0

are mainly included in the group M05B, which is further divided

1. Introduction

into groups of plain bisphosphonates, bisphosphonate combi-

nations and other drugs affecting bone structure and minerali-

Osteoporosis is a major health threat nowadays [1–3]. It alters zation (e.g., strontium ranelate and denosumab).

bone architecture leaving them more fragile and more The DDD is the assumed average maintenance dose per day

susceptible to fractures [4]. The number of osteoporosis for a drug used for its main indication in adults. It is described

induced fractures is estimated to be 3.5 million annually in as a unit of measurement and not always reﬂecting the

the European Union [5]. The main negative health outcome of recommended dose or the actual prescribed daily dose. In case

fractures is loss of quality of life due to pain and disability of drugs against osteoporosis this is not the case as the doses

caused by them [6,7]. Loss of bone mass itself is asymptomatic used do not differ much and the DDD applied by the WHO

until a fracture occurs [8] and osteoporosis has clinical and depict very well the actual doses used. This allows us to

public health relevance only cause of the fractures [9]. Aging of evaluate the number of patients receiving the treatment in a

population and changes in people's lifestyle result in a period of time rather accurately.

constant increase in the number of fractures all over the The number of DDDs is reported as per 1000 inhabitants per

world [9,10]. day (DDD/1000 inhabitants/day or DID). This enables to

Effective pharmacological treatment options are available compare the consumption of medicines in different countries

(e.g., bisphosphonate and combination with the latter, and in different years.

denosumab, strontium ranelate) [11] that have all been shown We used the 2015 version of the ATC/DDD classiﬁcation in

to reduce the risk of vertebral fracture, some have also been the study.

shown to reduce the risk of non-vertebral fractures and Our study included consumption data from the years 2010

fracture risk at the hip [11,12]. With no single agent to 2014. Data included in the study was obtained from the

demonstrating superiority over another in preventing frac- internet, published by the authorities gathering medicines

tures [13]. consumption data. All the study countries collect the data

Osteoporosis pharmacotherapy needs to be used for a from wholesalers and it represents medicine sales to pharma-

longer period of time and patients need to adhere to treatment cies [23]. Sales data from all the countries cover 100% of

to be effective and cost-effective [14,15]. The number of consumption of antiosteoporotic medicines in the countries

patients who receive treatment within a year after a fragility [24–26].

fracture is less than 20% [16]. Half (50%) of the patients We used comparison of regression lines with STAT-

receiving the treatment adherence to it sufﬁciently and only GRAPHICS Centurion XVII Version 17.1.12 in order to establish

35% continue the treatment for at least a year [17,18]. The differences in trends of medication consumption between the

International Osteoporosis Foundation has declared an in- study countries.

creasing need for management strategies to be placed in an

appropriate health economic perspective for guideline devel-

3. Results

opment and for reimbursement [10,19]. Osteoporosis as a

growing chronic health state in the Western world is putting a

signiﬁcant load on both the individual and the society [20]. During the study period the consumption of antiosteoporotic

Our study aimed to describe the drug utilization pattern medicines was rather stable in all the countries (Fig. 1).

and choice of active substances of antiosteoporotic medicines In Lithuania there was a slight decrease in consumption

in the Baltic countries. Such studies have been carried out while in 2010 the consumption was 3.4 DID and in 2014 it was

before to describe consumption change of drugs against 3.3 DID. In Estonia, the consumption of antiosteoporotic

osteoporosis within country [21,22], but none has compared medicines was exactly on the same level in 2014 as it was in

consumption in the Baltic region. 2010, i.e., 4.6 DID. In 2013, the consumption increased to 5.0

DID but an 8% decrease in consumption the following year put

it back on 2010 level. In Latvia we can see the only increase in

2. Materials and methods

consumption of antiosteoporotic medicines in the Baltic

countries during the study period. In 2010 the consumption

Drug utilization data was analyzed using the Anatomical in Latvia was 4.2 DID and in 2014 it was 5.2 DID which is an

Therapeutic Chemical (ATC) classiﬁcation and deﬁned daily overall increase of almost 24%. The consumption was even

dose (DDD) methodology that is developed and maintained by higher in Latvia in 2012 when 5.6 DID of antiosteoporotic

the World Health Organization (WHO) (www.whocc.no). The medicines were used (33% more than in 2010). There was a

methodology is used in most of the European countries to drop in consumption in all the countries during the last year of

serve as the tool for drug utilization research. The national the study compared to the year before. The decrease was on

statistics of medicine consumption gathered by governmental average 6% with 4.7% in Latvia, 6.2% in Lithuania and 7.8% in

bodies is usually based on this to keep track of changes in drug Estonia. The annual average change of consumption was

utilization. +0.3% in Estonia, +5.9% in Latvia, and À0.8% in Lithuania. The

An ATC code classiﬁes active substances according to their trends were not statistically signiﬁcantly different with a P

main indication of use and chemical characteristics. The value of 0.41 between Estonia and Latvia; 0.46, between Estonia

classiﬁcation consists of 5 levels with therapeutic areas as and Lithuania; and 0.24, between Latvia and Lithuania.

the first level and specific active substances as the fifth level. The choice of active substances used within the country

Active substances that affect bone structure and mineralization changed little during the study period (Fig. 2), with the only

m e d i c i n a 5 2 ( 2 0 1 6 ) 3 1 5 – 3 2 0 317

6.0

5.0

4.0

Estonia 3.0 Latvia Lithuania 2.0

DDD/1000 inhabitants/day 1.0

0.0

2010 2011 2012 2013 2014

Fig. 1 – The consumption of drugs against osteoporosis (ATC group code M05B) in the Baltic countries from 2010 to 2014,

expressed as the amount of defined daily doses per 1000 inhabitants per day (DDD/1000 inhabitants/day).

1.0 Denosuma b

0.9

Stron tium ranelate

0.8

0.7 Risedroni c acid, calcium and

colecalciferol

0.6 Risedroni c acid 0.5 Ibandronic acid

Percentage 0.4 Alend ronic

0.3 acid+Colecalciferol

0.2 Alend ronic acid

0.1

Clod ronic acid 0.0

201020112012201320142010201120122013201420102011201220132014

Fig. 2 – The consumption of drugs against osteoporosis (ATC group M05B) in the Baltic countries in 2010–2014 expressed as

the proportion of different active substances used out of the total.

exception of denosumab, the consumption of which and share The overall choice of active substances used to treat

of total consumption of the antiosteoporotic medicines osteoporosis is similar in all the Baltic countries but the market

increased in all the countries. Most noticeably in Lithuania shares of substances were a bit different amongst the study

where in 2010 denosumab was not used at all and in 2014 its countries (Fig. 3). Estonia stands out with high use of

consumption was 0.8 DID. In Estonia and Latvia, the increase combination product of alendronic acid and colecalciferol

was slower with 0.4 DID and 0.2 DID, respectively, during the 5 that formed almost 60% of the drug class's total consumption

year period but it still brought denosumab to a share of 5%–10% in 2014. Other more used active substances were ibandronic

of the total of medicines against osteoporosis. While con- acid and plain alendronic acid with 14% and 10% market share,

sumption of bisphosphonates was stable in all the countries respectively of the total consumption in 2014. In Latvia the

and the consumption of denosumab increased then the highest consumption was of risedronic acid – 2.1 DID (40% of

consumption of strontium ranelate decreased in Lithuania total). The combination of alendronic acid and colecalciferol

and in Estonia following the restriction of its use by the and ibandronic acid were also used more than 1 DID, 1.3 and

European Medicines Agency in April 2013, in Latvia the 1.1, respectively. Plain alendronic acid which is the oldest

consumption stayed on the same level. As its former share bisphosphonate was used less than 0.01 DID in Latvia in 2014.

was biggest in Lithuania, the decrease was also steepest – from In Lithuania the most used active substance in 2014 was

0.6 DID in 2013 to 0.2 DID in 2014. ibandronic acid with 0.9 DID (26% of the total share). Close

318 m e d i c i n a 5 2 ( 2 0 1 6 ) 3 1 5 – 3 2 0

Denosuma b

5 0.19 Stron tium ranelate 0.47

0.35 0.05 Risedronic acid, calcium

4 0.34 and colecalciferol

0.66 2.10 Risedroni c acid 3 0.82 Ibandronic acid 0.23

2 2.72 1.12 Alend ronic 0.57 acid+Colecalciferol

DDD/1000 inhabitants/day

1 0.86 Alend ronic acid

0.27

0.47 1.26 Clod ronic acid

0 0.00 0.29

Estonia Latvia Lithuania

Fig. 3 – The consumption of drugs against osteoporosis (ATC group M05B) in the Baltic countries in 2014 expressed as the

number of defined daily doses per 1000 inhabitants per day (DDD/1000 inhabitants/day) and dived by the active substances.

second was denosumab with 0.8 DID and 25% of the total consumption in Estonia. In Latvia the most used active

share. High consumption of denosumab differentiates Lithua- substance was plain risedronic acid with 40% of the total.

nia from the other Baltic countries where all the most used Lithuania stood out of the rest of the countries with high 25% of

antiosteoporotic preparations are plain or combinations of the total M05B consumption of denosumab. In the other

bisphosphonates. The consumption is more equally divided countries denosumab comprised 7.6% in Estonia and 3.7% in

between active substances in Lithuania as three most used Latvia of the total in 2014. While in Estonia and Latvia the top 3

active substances made up 68% of the total consumption most used active substances (or combination of substances)

compared to 84% in Estonia and 86% in Latvia. remained the same all through the study, in Lithuania

denosumab was not used at all at the beginning of the study

in 2010 and it rose to be the second most used active substance

4. Discussion

by the end of the study in 2014.

The most used active substance in 2014 in Estonia was the

Studies on osteoporosis medication consumption carried out in combination of alendronic acid and colecalciferol. The cheap-

Europe before have showed continues increase in consumption est out of oral products was ibandronic acid with 0.25s per

[21,27]. On the other hand, the trend in the United States seems DDD but its market share was still only 14% in 2014. The most

to be decreasing [22]. Our study shows a rather stable expensive in 2014 of oral bisphosphonates or combinations of

consumption in all the Baltic countries, although changes in the latter was the combination of alendronic acid and

peoples lifestyles and the aging of population would suggest an colecalciferol with 0.51s per DDD which is twice as much as

overall increase in the consumption of medicines [28]. The the cheapest plain bisphosphonate. This can be explained by

possible reason for the stability in consumption might be that the fact that for the patient the combination preparation is

our study period follows the economic recession and as one of reimbursed and the plain colecalciferol product is not. This

the key elements to inﬂuence drug use is affordability [29] makes the combination product still cheaper to use for the

downturn in peoples income probably inﬂuenced the con- patient and explains the high proportion of combination

sumption of osteoporosis medication. product use out of the total of the drugs against osteoporosis.

The differences in consumption of drugs against osteopo- After the increase of antiosteoporotic medicines consump-

rosis in the Baltic countries are not very big, though utilization tion of 25% in Latvia in 2011 compared to 2010 the differences

in Lithuania is somewhat smaller than in Estonia and Latvia. of total consumption has stayed relatively the same with

The trends in consumption are not statistically signiﬁcantly Latvia using around 0.6 DID more than Estonia and 1.9 DID

different, but if we had a longer study period the results would more than Lithuania. In 2010 Estonia lead the consumption

be more reliable. There are some differences in the choice of with 4.6 DID.

active substances used in the different countries. In all the In the Baltic countries the population at risk of osteoporosis

countries the consumption of antiosteoporotic drugs is similar with estimated prevalence of 5.3% in Lithuania and

remained rather stable during the 5 year study period, with 5.8% in Estonia and Latvia of total population [10]. The

only Latvia showing an increase in consumption. Utilization consumption of antiosteoporotic drugs is not to be regarded

decreased compared to the previous year in all the countries in as sufﬁcient though as the estimated number of women and

the last year of the study – 2014. men with osteoporosis is assessed to be around 80,000 in

In 2014 alendronic acid combined with colecalciferol Estonia, 130,000 in Latvia and 175,000 in Lithuania [19] and

constituted to 59% of total antiosteoporotic medicines according to our study daily treatment was received by

m e d i c i n a 5 2 ( 2 0 1 6 ) 3 1 5 – 3 2 0 319

approximately 6000 patients in Estonia, 11,000 in Latvia and highlights some differences in choices of active substances

10,000 in Lithuania in 2014. This is <10% of patients with used to treat osteoporosis in the Baltic countries as the most

osteoporosis risk. The same conclusions are stated also in EU used preparation in Estonia is the combination product of

osteoporosis report that use of pharmacological prevention of alendronic acid and colecalciferol, in Latvia risedronic acid and

osteoporosis is signiﬁcantly less than optimal in the Baltic in Lithuania ibandronic acid but closely followed by denosu-

countries, suggesting that a change in healthcare policy mab which consumption is more than 2-fold of that in Estonia

concerning the disease is warranted [19]. Though several and more than 4-fold of that in Latvia.

factors inﬂuence drug utilization the key drivers for not

sufﬁcient use seem to be availability and price of medicines.

Conﬂict of interest

The generally low consumption of osteoporotic medicines

in the Baltic countries can be attributed to the overall less than

EU average wealth of the countries and less than optimal The authors declare that they have no conﬂict of interest.

expenditure on healthcare out of the GDP. This results in

general as higher co-payment for patients in the Baltic

Authors' contributions

countries which the patients cannot afford.

The dynamics of consumption in the study countries is

peculiar as one would expect an increase in consumption O.L. and K.M. conceived the study, participated in its design

while bisphosphonates are getting cheaper and the number of and drafted the initial manuscript. OL collected the data. S.K.

people at risk of osteoporosis is rising. Instead for the ﬁve year and A.M. participated in the design of the study, coordinated

study we saw a 25% increase in Latvia during one year, stable data interpretation and helped to draft the manuscript.

consumption for 3 years with a drop in consumption in the last All authors read and approved the ﬁnal manuscript.

year and stable consumption throughout the study for Estonia

and Lithuania. It can be related to the fact that for instance in

Funding

Estonia reimbursement system for the drugs against osteopo-

rosis is not changed and there are still only limited group of

patients (fragility fracture + DXA T-score < À2.5SD) who get This work was supported by institutional research funding IUT

medications reimbursed at 75% or 90% (patients over 63) rate. 20-46 of the Estonian Ministry of Education and Research. The

The interpretation of results from our study is limited to the source had no involvement in conducting the research or

extent of overall consumption and preference of active preparation of the article.

substances in different countries and assessment of prescribing

quality or real treatment recommendations for patients cannot

r e f e r e n c e s

be monitored as the study is based on wholesale data. Also the

data derives from wholesales and there is a gap between

delivering the medication to the pharmacy and when a patient

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