Rev. Saúde Pública vol.47 número2

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Rev Saúde Pública 2013;47(2) Public Health Practice Original Articles

DOI: 10.1590/S0034-8910.2013047004163

Cristina Mariano Ruas BrandãoI

Felipe FerréII

Gustavo Pinto da Matta MachadoIII

Augusto Afonso Guerra JúniorI

Eli Iola Gurgel AndradeIV

Mariângela Leal CherchigliaIV

Francisco de Assis AcurcioI,IV

I_{Departamento de Farmácia Social.}

Faculdade de Farmácia. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil

II_{Programa de Pós-Graduação em}

Bioinformática. Instituto de Ciências Biológicas. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil

III_{Departamento de Clínica Médica.}

Faculdade de Medicina.Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil

IV_{Departamento de Medicina Social e}

Preventiva. Faculdade de Medicina. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil

Correspondence:

Cristina Mariano Ruas Brandão Departamento de Farmácia Social Faculdade de Farmácia da Universidade Federal de Minas Gerais

Av. Antônio Carlos, 6627 Campus Pampulha 31270-901 Belo Horizonte, MG, Brasil E-mail: crisruas@ufmg.br

Received: 1/24/2012 Approved: 10/3/2012

Article available from: www.scielo.br/rsp

Public spending on drugs for

the treatment of osteoporosis in

postmenopause

ABSTRACT

OBJECTIVE: To analyze expenditure on treatment for postmenopausal osteoporosis and associated factors on mean per capita expenditure.

METHODS: A probabilistic-deterministic linkage between the database of Authorizations for Highly Complex Procedures and the mortality information system was constructed, resulting in a historical cohort of patients using high-cost medications for the treatment of postmenopausal osteoporosis, between 2000 and 2006.Mean monthly spending on medicines was stratiﬁ ed by age group and described according to demographic and clinical characteristics and the type of drug used.A linear regression model was used to assess the impact of demographic and clinical characteristics on per capita mean monthly expenditure on medicines.

RESULTS: We identifi ed 72,265 women who received drugs for the treatment of postmenopausal osteoporosis.The average monthly expenditure per capita in the fi rst year of treatment was $ 54.02 (sd $ 86.72).The population was predominantly composed of women aged 60-69 years old, who had started treatment in 2000, resident in the Southeast of Brazil, who had previously suffered osteoporotic fractures, and Alendronate sodium was the drug most commonly used at baseline.For most of the patients, the same active ingredient remained in use throughout the treatment period.During the program, 6,429 deaths were identi_fi ed among participants.More than a third of women remained in treatment for up to 12 months.Raloxifen and calcitonin were the therapeutic alternatives with the greatest impact on the average monthly expenditure on medicine using alendronate sodium as a reference standard.

CONCLUSIONS: Due to the high impact of the type of drug used on

expenditure on medication, it is recommended that criteria for prescribing and dispensing be established by prioritizing those with lower costs and greater effectiveness in order to optimize the process of pharmaceutical care and provide the population with a greater number of pharmaceutical units.

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2 Spending on medications for osteoporosis Brandão CMR et al

Osteoporosis is characterized by low bone mineral density and the degeneration of the bone microar-chitecture, which increases fragility and the risk of fracture. It is recognized clinically by the occurrence of non-traumatic fracture, especially in the lumbar spine (vertebral fracture), and by fractures to the forearm and hip following falls. It is typical in the elderly and mainly affects females.26

This disease is a signiﬁ cant public health problem in developed and developing countries.26_{It is} asympto-matic and highly prevalent among the elderly due to this population’s greater risk of fracture, and incurs high medical and surgical treatment costs. With an ageing population, a growing number of people are affected each year.

A study carried out in Sao Paulo between 2000 and 2001 found prevalence rates for osteoporosis of 14.7% in the lumbar spine and 3.8% in the femur in post-menopausal women.12_{Another study, with a representative sample} of the Brazilian population, found a prevalence rate of 15.1% for fragility fractures in women < 40.18_The incidence of hip fractures was 27.7/10 thousand women and increased with age in the Northeast of Brazil.21

Medication for treating osteoporosis was initially provided by State Health Departments through the Ministry of Health Exceptional Drug Program (PME/ MS).a_{Subsequently, this program was restructured} and named Specialized Program for Pharmaceutical Assistance.Alendronate sodium became available through the Primary Health Care Program.b

In the WHO International Classi_ﬁ cation of Diseases (ICD-10), osteoporosis comes under the category of musculoskeletal diseases.In spite of not having the highest PME/MS costs, it is among the most prevalent in the program.8_{The disease affects a large part of the} population and therefore Alendronate is distributed through primary health care.11_{In addition to outpatient} treatment (medication) for osteoporosis, the Brazilian Uniﬁ ed Health System (SUS), provides hospitalizations for patients with osteoporotic fractures.Estimations of hospital costs for treating femur fractures in patients with osteoporosis in two Sao Paulo hospitals with SUS agreements (Hospital Universitário and Santa Casa de Misericórdia), found average costs of $4,961.14 and $1,170.12 respectively.7_{These hospitals used different} methods for evaluating the hospital costs of treating femur fractures. The Hospital Universitário used their own method based on evaluating the mean cost per patient in the various departments which provided care

INTRODUCTION

(nursing and intensive care), whereas Santa Casa based their estimates on SUS tables of costs. The costs do not correspond to the reality and may be underestimated due to the sources and to differences in methods of evaluating them.7_{In the (private) health insurance} system, the estimated cost for treating each fracture was $14,404.03.4

In the US, a revision of the clinical and hospital costs associated with osteoporotic fractures in the _ﬁ rst year following the occurrence of the fracture showed them to be between 50.0% and 67.0% of the total value of the cost of treating fractures. Costs were higher for hip fractures and lower for wrist and forearm fractures.10

Correct treatment is the main component in reducing both mortality in osteoporosis patients and the resources consumed by hospital treatment for fractures. The PME/MS provides a large amount of resources for the prevention and treatment of this disease. Studies have been undertaken to evaluate the ef_ﬁ cacy/effective-ness of this medication although there are few which assess the costs of these procedures from the point of view of the SUS, the focus of this study. This study aims to analyze spending on medication for treating post-menopausal osteoporosis and associated factors on mean per capita spending.

METHODS

A national non-concurrent cohort was drawn from the PME/MS database, using women who were recorded as receiving medication for the treatment of postme-nopausal osteoporosis from SUS between 2000 and 2006. These patients were monitored throughout the duration of the program, in which spending on medi-cation was observed.

A national database of patients taking exceptional drugs was created based on existing records from the SUS Outpatient Information System (SIA), subsystem of complex procedures, database and from the Mortality Information System (SIM), using deterministic-proba-bilistic record linkage.The methodological procedures used to carry out the linkage and the main results are described in Brandão et al8_{(2011) and Acurcio et al}1 (2009). Patients selected were those who had been diagnosed with postmenopausal osteoporosis, with or without previous fractures.

Criteria for inclusion in the study were: (i) patients on their _ﬁ rst recorded use of medication for treating oste-oporosis; (ii) patients diagnosed with post-menopausal

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Rev Saúde Pública 2013;47(2)

osteoporosis (ICD-10 M80.0 and M81.0) and (iii) patients whose records include at least two uses of medication in the _ﬁ rst six months of treatment.

Exclusion criteria were the following: (i) individuals taking anti-osteoporotic drugs to treat other diseases than postmenopausal osteoporosis, such as osteo-malacia, Paget’s disease, multiple myeloma, renal or hepatic disease, malabsorptive diseases, primary hyperparathyroidism and uncontrolled hypo-or hyper-thyroidism; (ii) patients whose date of birth was not recorded; (iii) men and (iv) patients at the extremes of the age range, such as < 36 and > 93 years old. A box plot distribution of age was created and these values were excluded as extreme. Lower values indicated mistakes in completing the date of birth, as the study dealt with postmenopausal women, a population with particular characteristics, and extreme values may inﬂ uence the ﬁ nal result.

The variables studied were:

Dependent variables:

- per capita mean monthly spending on medication for treating postmenopausal osteoporosis. The values were obtained by summing the spending on medication for each individual during the _ﬁ rst year of treatment and dividing it by the number of months the patients received treatment per capita.

Independent variables:

- demographic: age (age group), region in which resi-dent (North; Northeast; South; Southeast; Midwest) and year in which the patient entered the program (2000 to 2006);

- clinical: diagnosis (with fracture – M80.0; no fracture – M80.1) and medication used for osteoporosis at the start of the treatment program (alendronate, raloxifene, calcitonin, calcitriol, alfacalcidol, risedronate), death (yes; no), alterations to medication during the treatment (yes; no) and length of treatment (months).

Distributions of the frequency and mean per capita monthly spending were carried out for the variables: year in which treatment started, region in which resi-dent, clinical diagnosis, followed treatment, length of treatment and death for the different age groups (49 and under, 50 to 59, 60 to 69, 70 to 79 and 80 and over). The ﬁ gures for spending were updated for December 2010 according to the Brazilian Institute of Geography and Statistics (IBGE) national index of consumer prices (IPCA). Comparisons of means between categories was carried out using the Bonferroni test and comparisons of proportions using the t test, with p < 0.05.

Univariate (p ≤ 0.25) and multivariate (p ≤ 0.05) analysis was carried out using a linear regression

model to assess the impact of demographic and clinical characteristics on per capita mean spending on medi-cation. The dependent variables was transformed into a base-10 logarithm in order to obtain the best _ﬁ t for the model. The data were interpreted using the follo-wing formula: 100(10β-1).25_{The statistical analysis} was carried out using R version 2.8.0 and SPSS 17.0 software. Dummy variables were created for various categories, establishing the category with the lowest per capita monthly spend as a standard of comparison.

The research adhered to the standards required by the Declaration of Helsinki and the names of the patients were hidden after the linking. This research was approved by the Research and Ethics Committee of the Universidade Federal de Minas Gerais (nº 0101/06) as part of the “Pharmaco-economic and epidemiological evaluation of the SUS Exceptional Drug −Avaliação farmacoeconômica e epidemiológica do Programa de Medicamentos Excepcionais do SUS, Brazil 2000-2005” program.

RESULTS

Between 2000 and 2006, 72,265 women taking medi-cation from the PME/MS to treat postmenopausal oste-oporosis were identiﬁ ed. The mean per capita monthly expenditure varied between $0.04 and $4,567.55, with a mean of $41.27 (standard deviation – sd $81.35 and median 29.82). The most frequent mean per capita expenditure was $1.31. The mean per capita monthly expenditure in the ﬁ rst year of treatment was $44.35 (sd $144,486.729, median $33.60) with a variation of $0.04 to $5,579.69.

The mean age of the participants was 64.8 (sd 9.8 years, median 64.7), with a variation of 36 and 93 years old. Of the patients, 6.0% were aged 49 and below; 26.4% between 50 and 59; 36.8% from 60 to 69; 24.3% between 70 and 79; and 6.5% were aged ≥ 80.

Mean per capita monthly spending in the ﬁ rst year of treatment increased progressively with age from 50 onwards: $38.61, sd $73.68 for women aged 50 to 59, $44.83, sd $86.59 for those aged 60 to 69, $48.07 sd $79.23 for those between 70 and 79, and $52.72, $102.41 for those aged ≥ 80 (p < 0.05). Patients aged < 49 years old had a mean per capita monthly expenditure of $42.55, sd $135.44.

Of the women, 17.4% began treatment in 2000, 9.5% in 2001, 12.8% in 2002, 16.7% in 2003, 23.0% in 2004, 12.95 in 2005 and 7.8% in 2006.Mean per capita expenditure for women who started treatment in 2000 ($93.35; sd $130.10) and 2001 ($51.85; sd $86.93) (p < 0.01) (Table 1).

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Table 1. Mean monthly expenditure and frequency of the year in which treatment started for women with postmenopausal osteoporosis treated by the Ministry of Health Exceptional Drug

Programaa_{, stratifi ed by age group, 2000 to 2006.}

Age group (years)

Year in which patient entered the Exception Drug Program

2000 2001 2002 2003 2004 2005 2006 Total

< 49 n (%) 536 (4.3) 370 (5.4) 586 (6.3) 817 (6.8) 1,032 (6.2) 639 (6.9) 362 (6.40) 4,342 (6.0)

$; SD 94.93; 205.55 56.84; 123.89 30.28; 46.32 26.53; 52.62 38.65; 190.19 33.24;92.16 33.90; 94.08 42.55; 135.44

50 to 59 n (%) 2,392 (19.0) 1,525 (22.2) 2,305 (24.9) 3,495 (29.0) 4,999 (30.1) 2,776 (29.9) 1,552 (27.6) 19,044 (26.4)

$; SD 87.86; 121.81 46.41; 54.09 28.78; 65.89 30.37; 82.99 31.49; 57.38 27.51; 36.67 30.99; 37.31 38.61; 73.68

60 to 69 n (%) 4,866 (38.7) 2,544 (37.1) 3,357 (36.3) 4,350 (36.1) 6,120 (36.9) 3,339(35.9) 2,041 (36.2) 26,617 (36.8)

$; SD 93.91; 138.37 48.28; 55.68 30.48; 59.17 30.64; 6.60 35.41; 73.73 30.04; 72.73 29.78; 32.79 44.83; 86.59

70 to 79 n (%) 3,755 (29.8) 1,945 (28.4) 2,341 (25.3) 2,681 (22.2) 3,509 (21.1) 1,996 (21.5) 1,317 (23.4) 17,544 (24.3)

$; SD 94.46; 110.84 54.24; 74.30 35.30; 67.32 30.06; 49.47 35.02; 76.38 28.69; 38.41 30.22; 34.27 48.07; 79.23

80 + n (%) 1,037 (8.2) 473 (6.9) 656 (7.1) 709 (5.9) 940 (5.7) 543 (5.8) 360 (6.4) 4,718 (6.5)

$; SD 98.55; 122.53 74.82; 219.45 41.61; 66.47 31.60; 36.37 35.71; 51.76 28.85; 66.42 32.46; 35.91 52.51; 102.41

Total n (%) 12,586 (100.0) 6,857(100.0) 9,245 (100.0) 12,052 (100.0) 16,600 (100.0) 9,293 (100.0) 5,632 (100.0) 72,265 (100.0)

$; SD 93.35; 130.12 51.85; 86.90 32.05; 62.95 30.21; 65.96 34.37;81.44 29.20; 57.44 30.65; 41.21 44.36; 86.72

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and in the Midwest (14.6%), and a small proportion in the North (4.6%) and South (4.5%). The highest proportion of patients were aged between 60 and 69 and the lowest proportion were < 49 (Midwest, North, Southeast and South) or ≥ 80 (Northeast). Higher mean per capita monthly expenditure was observed for women living in the Southeast ($50.25; sd $82.81) and North ($44.84; sd $78.34). Per capita mean monthly spending was $34.85; sd $163.97, $36.75; sd $79.61 and $41.61; sd $80.08 for women living in the South, Midwest and Northeast, respectively. The same tendency was observed when strati_ﬁ ed by age (Table 2).

Around 55.8% of patients entered the program after suffering an osteoporotic fracture, the majority aged between 60 and 69 (36.2%). Higher proportions of fractures occurred in the groups aged 70 to 79 (26.3% versus 21.8%) and 80 and over (7.4% versus 5.4%) (p < 0.03). Higher per capita mean monthly spending was observed in women who had been previously diagnosed with fractures ($55.77; sd $101.76), when compared with those who just had osteoporosis ($26.96; sd $59.78). The same tendency was observed when stratiﬁ ed by age group (p < 0.05).

The medication most commonly used at the beginning of treatment was sodium alendronate (57.0%), followed by synthetic salmon calcitonin (24.6%) and raloxifene (15.6%). Risedronate and alfacalcidol calcitriol were less frequently used (0.4%, 2.2% and 0.1%, respecti-vely). Higher proportions of individuals used sodium alendronate and raloxifene in the < 49 and 50 to 59 age groups; for women aged > 60, this was alendronate and calcitonin (Table 3).

Higher per capita mean monthly spending was observed in women who started their treatment in the program using calcitriol ($66.86, sd $73.50), synthetic salmon calcitonin ($91.78, sd $134.87) and raloxifene ($69.17, sd $64.96). The same tendency could be seen in all age groups, with statistically signiﬁ cant diffe-rences between the drugs (Table 3).

For most patients, the active ingredient with which they were treated did not change during their treatment (89.8%). Higher proportions of those who remained on the same treatment were aged between 60 and 79 years old, compared with the group of patients whose medication was changed during the period.Patients whose medication was changed during the _ﬁ rst year had higher per capita mean monthly costs ($75.16; sd $159.34) than those who remained on the same medication ($40.84; $73.21). This was similar when stratiﬁ ed by age group.

There were 6,429 deaths which occurred during the program (8.9%), 6.4% were women < 49, 28.0% in the 50 to 59 age group, 37.9% were women aged between

60 and 69, 22.7% occurred in patients in the 70 to 79 age group and 4.9% were in patients aged ≥ 80. Those women who died had higher per capita mean expendi-ture ($57.05; sd $95.51) that women who lived ($43.12; sd $85.71) (p < 0.01).

More than one third remained in the program and under treatment for up to 12 months; 20.6% for between 12 and 23 months; 19.3%, from 24 to 35 months; 11.4%, for between 36 and 47 months; 7.1%, from 49 to 60 months; 4.7%, for between 61 and 72 months; and 5.7%, for 73 to 88 months. The average expenditure on medication was greatest for women who were part of the program for between 61 and 72 months ($87.74; sd $62.39) and between 73 and 88 months ($96.40; sd $126.24) (Table 4).

Around 76.3% (R2_{adjusted) of variability of}_per capita mean monthly spending on medication was explained by the medication used, the year in which treatment began, the length of treatment, alterations in medication, region in which the patient resided, age group, death during the course of treatment and diagnosis of fractures.The model ﬁ t to the data was signiﬁ cant (p < 0.01) (Table 5).

Medication was the variable which had the most impact on per capita mean monthly expenditure. Starting the course of treatment using raloxifene increased mean expenditure by 951.1% compared with those patients who started treatment using sodium; taking synthetic salmon calcitonin meant an increase of 428.1%; calcitriol an increase of 281.5%; alfacalcidol an increase of 124.7% and risedronate a decrease of 63.7%, when the other variables were considered to be constant.

The increase in per capita mean monthly spending was inversely proportional to the duration of treatment. Starting treatment in 2001 decreased the per capita mean monthly cost by 21.6%; starting in 2002 meant a decrease of 58.5%; in 2003, 70.4%; in 2004, 70.2%; in 2005, 72.7%; and in 2006 the reduction was 83.9% (p < 0.01), taking 2000 as the reference year and holding all other variables constant.

Changing the medication during the period in question, compared to those patients whose medication was not changed, meant a mean increase of 96.4% in the per capita mean monthly spending, when the other varia-bles remained constant.

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Table 2. Region of residence of female patients with postmenopausal osteoporosis, treated by the Ministry of Health Exceptional Drug Programa_{, stratifi ed by age group, 2000 to 2006.}

Age group (age)

Region of residence

North Northeast Southeast South Midwest Total

< 49 n (%) 458 (4.3) 1,840 (7.4) 185 (5.6) 1,262 (4.2) 145 (4.5) 4,342 (6.0)

$; SD 40.43; 106.96 36.41; 111.04 50.92; 108.62 65.17; 450.83 37.35; 56.57 42.55; 135.44

50 to 59 n (%) 2,644 (25.1) 7,528 (30.2) 892 (26.8) 6,413 (21.2) 740 (22.9) 19,044 (26.4)

$; SD 36.75; 56.46 34.48; 70.11 46.17; 71.43 30.98; 139.45 34.43; 65.46 38.61; 73.68

60 to 69 n (%) 4,310 (40.9) 8,728 (35.0) 1,241 (37.3) 11,129 (36.9) 1,264 (39.1) 26,617 (36.8)

$; SD 47.77; 101.26 44.30; 80.19 49.48; 84.19 32.18; 158.69 36.63; 67.66 44.83; 86.59

70 to 79 n (%) 2,464 (23.4) 5,353 (21.4) 781 (23.5) 8,757 (29.0) 894 (27.6) 17,544 (24.3)

$; SD 48.36; 49.84 48.17; 80.20 52.30; 79.92 36.05; 83.45 37.16; 79.25 48.07; 79.23

80 + n (%) 662 (6.3) 1,518 (6.1) 231(6.9) 2,634 (8.7) 192 (5.9) 4,718 (6.5)

$; SD 55.40; 47.43 48.25; 73.41 57.83; 96.93 36.60; 54.83 746.37; 178.54 52.51; 102.41

Total n (%) 10,538 (100.0) 24,967 (100.0) 3,330 (100.0) 30,195 (100.0) 3,235 (100.0) 72,265 (100.0)

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Table 3. Frequency and per capita mean monthly cost, according to medication taken and age group, for female patients with postmenopausal osteoporosis, treated by the Ministry of Health

Exceptional Drug Programa_{, 2000 to 2006.}

Age group (years)

Medication

Alendronate Alfacalcidol Calcitriol Calcitonin Raloxifene Risedronate Total

49 and under n (%) 2,814 (6.8) 4 (10.0) 111 (6.9) 673 (3.8) 727 (6.4) 13 (4.0) 4,342 (6.0)

$; SD 16.90; 51.43 38.16; 25.57 86.40; 186.30 116.05; 303.09 67.84; 24.86 1.22; 0.00 42.55; 135.44

50 to 59 n (%) 11,786 (28.6) 6 (15.0) 312 (19.3) 3,291 (18.5) 3,586 (31.7) 63 (19.6) 19,044 (26.4)

$; SD 14.94; 36.78 37.44; 22.09 56.20; 45.57 89.09; 118.89 69.19;77.93 1.55; 2.54 38.61; 73.68

60 to 69 n (%) 15,133 (36.7) 13 (32.5) 590 (36.4) 6,376 (35.8) 4,382 (38.8) 123 (38.3) 26,617 (36.8)

$; SD 17.21; 54.65 45.58; 30.26 70.00; 66.16 91.57; 125.36 70.06; 72.02 1.22; 0.13 44.83; 86.59

70 to 79 n (%) 9,232 (22.4) 10 (25.0) 476 (29.4) 5,566 (31.3) 2,160 (19.1) 100 (31.2) 17,544 (24.3)

$; SD 17.19; 37.02 49.47; 42.80 65.50; 45.29 90.72; 115.06 68.47;34.89 1.79; 8.83 48.07; 79.23

80 + n (%) 2,220 (5.4) 7 (17.5) 130 (8.0) 1,897 (10.7) 442 (3.9) 22 (6.9) 4,718 (6.5)

$; SD 16.63; 26.31 31.05; 22.79 66.43; 70.41 91.65; 147.53 65.82; 14.54 1.25; 0.11 52.51; 102.41

Total n (%) 41,185 (100.0) 40 (100.0) 1,619 (100.0) 17,803 (100.0) 11,297 (100.0) 321 (100.0) 72,265 (100.0)

$; SD 16.50; 44.84 42.05; 30.69 66.86; 73.50 91.78; 134.87 69.17; 64.96 1.47; 3.44 44.36; 86.72

a_{Ministério da Saúde. Portaria GM nº 2.577 de 27 de outubro de 2006. Aprova o componente de medicamentos de dispensação excepcional. Diario Ofi cial Uniao. 30 out 2006}

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Table 4. Frequency and per capita mean monthly cost according to length of treatment for female patients with postmenopausal osteoporosis, treated by the Ministry of Health Exceptional Drug

Programa_{, 2000 to 2006.}

Age (years)

Length of treatment (months)

< 12 13 to 24 25 to 36 37 to 48 49 to 60 61 to 72 73 to 88 Total

49 and under n (%) 1,487 (6.6) 960 (6.4) 827 (5.9) 490 (5.9) 292 (5.7) 151 (4.4) 135 (3.3) 4,342 (6.0)

$; SD 40.03; 96.17 39.80; 141.28 46.78; 214.85 34.21; 63.53 39.14; 126.57 63.61; 93.26 78.02; 52.71 42.55; 135.44

50 to 59 n (%) 5,860 (26.1) 4,035 (27.1) 3,954 (28.3) 2,269 (27.4) 1,267 (24.6) 787(23.0) 872 (21.3) 19,044 (26.4)

$; SD 36.40; 68.62 35.34; 80.31 35.05; 81.81 34.10; 64.72 34.88; 41.65 54.89; 63.83 87.26; 82.75 38.61; 73.68

60 to 69 n (%) 7,837 (34.9) 5,323 (35.7) 5,229 (37.4) 3,146 (38.0) 1,964 (38.1) 1,391(40.7) 1,727 (42.2) 26,617 (36.8)

$; SD 41.75; 76.10 39.69; 95.92 39.68; 82.98 38.51; 51.50 40.12; 64.59 56.19±62.23 97.97; 155.50 44.83; 86.59

70 to 79 n (%) 5,452 (24.3) 3,570 (24.0) 3,152 (22.6) 1,950 (23.6) 1,329 (25.8) 926 (27.1) 1,165 (28.5) 17,544 (24.3)

$; SD 42.43; 76.20 43.39; 88.34 41.62; 65.58 44.72; 63.61 48.01; 83.78 61.55; 51.51 101.25; 104.55 48.07; 79.23

80 + n (%) 1,823 (8.1) 1,018 (6.8) 809 (5.8) 414 (5.0) 298 (5.8) 165 (4.8) 191 (4.7) 4,718 (6.5)

$; SD 47.41; 120.51 52.41; 100.53 48.13; 69.03 47.01; 55.51 57.47; 77.13 78.32; 72.76 107.46; 148.66 52.51; 102.41

Total n (%) 22,459 (100.0) 14,906 (100.0) 13,971 (100.0) 8,269 (100.0) 5,150 (100.0) 3,420 (100.0) 4,090 (100.0) 72,265 (100.0)

$; SD 40.87; 80.59 40.27; 94.30 39.72; 91.98 38.93; 59.36 41.81; 71.50 58.74; 62.39 96.40; 126.24 44.36; 86.72

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Women aged between 50 and 59 had mean monthly expenditure 3.9% lower than women aged < 49. The difference between women aged 60 to 69 was 2.7% lower than those aged < 49 (p ≤ 0.01).

Those women who died during the period of the program had per capita mean monthly expenditure 2.2% higher than those who did not (p = 0.02).

Using a duration of 12 months of treatment as the stan-dard of reference for comparison, women who remained under treatment for between 13 and 24 months had costs 2% lower, those between 25 and 36 months 2.85%

lower; between 37 and 48 months, 3.4% lower; and 2.3% lower for those who were under treatment for 49 to 60 months; for 61 to 72 months, costs were 1.1% higher for those whose treatment lasted between 61 and 72 months; and 6.15% higher for those who were under treatment for more than 73 months (p ≤ 0.05).

DISCUSSION

The majority of the population with postmenopausal osteoporosis dealt with by the PME/MS were aged between 60 and 69, which is in agreement with Table 5. Multivariate analysis Results, 2000 to 2006.

Independent variable Beta Coeffi cient Standard error t Pr (>|t|) Intercept 1.5649 0.0081 192.597 < 0.01 Region of residence

Midwest/South 0.0070 0.0058 1.196 0.23

Northeast/South 0.0126 0.0054 2.317 0.02 Southeast/South -0.0128 0.0054 -2.354 0.02 North/South 0.0574 0.0072 8.014 < 0.01

Deceased 0.0091 0.0040 2.293 0.02

Polytherapy/monotherapy 0.2932 0.0036 80.384 < 0.01 Diagnosis of osteoporosis

Fracture/no fracture 0.0036 0.0026 1.380 0.17 Medication

Alfacalcidol/alendronate 0.3516 0.0456 7.707 < 0.01 Calcitriol/alendronate 0.5815 0.0075 77.200 < 0.01 Calcitonin/alendronate 0.7227 0.0031 232.820 < 0.01 Raloxifene/alendronate 1.0216 0.0032 319.461 < 0.01 Risedronate/alendronate -0.4406 0.0166 -26.484 < 0.01 Length of treatment (months)

13 to 24 -0.0087 0.0034 -2.570 0.01

25 to 36 -0.0125 0.0036 -3.503 < 0.01

37 to 48 0.0147 0.0043 3.428 < 0.01

49 to 60 -0.0101 0.0052 -1.951 0.05

61 to 72 0.0049 0.0062 0.790 0.43

73 + 0.0259 0.0059 4.420 < 0.01

Year treatment started

2001/2000 -0.1057 0.0051 -20.927 < 0.01 2002/2000 -0.3824 0.0048 -79.303 < 0.01 2003/2000 -0.5295 0.0047 -111.891 < 0.01 2004/2000 -0.5261 0.0047 -111.216 < 0.01 2005/2000 -0.5639 0.0052 -108.305 < 0.01 2006/2000 -0.7925 0.0060 -132.230 < 0.01 Age group at start of treatment (years)

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the literature. Similar results were found in the Framingham Osteoporosis Study (1987-2001), which found that the 65 to 75 age group was that in which postmenopausal osteoporosis was most prevalent,6 and with national studies.5,13

Costs of medication were lower for the more elderly patients.These values may be higher if the cost of hospitalization due to fractures was included, as found in a revision of North American studies.10

A large proportion of the patients were treated in 2000, possibly due to the recent computerization of the APAC system and structuring of the program as an integrated whole, occasioning an increase in the number of records of women treated that year. Increasing use of medica-tion was noted between 2001 and 2004. Greater use of these health care services may be related to better management, increased divulgation of the program and to public policies regarding exceptional drugs. Despite the growing use of these medications which has observed, the mean spending on medication actually slightly decreased over the period in question, possible due to alterations in the values set by the Ministry of Health. With the exception of 100 IU vials of calcitonin and 1 mcg vials of calcitriol, the reimbursement prices for medication to treat osteoporosis were reduced over the years 1999 to 2006.a,c,d,e,f

A large number of the patients live in the South and Northeast. Various determinants of health care service use are described and may contribute to understanding the differences between regions, such as factors related to: (a) the need for health care – morbidity, seriousness and urgency of the disease (e.g., fractures); (b) the users – demographic (age), socio-economic (income, educa-tion), cultural (religion) and psychological characte-ristics; (c) the service providers – when they qualiﬁ ed, specialty, psychological characteristics, professional experience, type of practice; and (d) the organization – available resources, supply characteristics (availability of doctors, hospitals, outpatient clinics), method of remuneration, geographical and social access.23_The difference between spending per region can, in part, be explained by the difference in the type of prescrip-tion. In the case of osteoporosis, this depends on the agreements in place in each State and at the discretion of the prescribing physician.g

The majority of the patients treated began taking medi-cation after an osteoporotic fracture. This is especially important as there are safe and effective treatments available which increase the mineral density of the bone and reduce the risk of fractures.19_{Osteoporosis is often} only detected after a fractures, which could increase the risk of this recurring and of death.24

One of the hypotheses for the high number of patients with fractures is difﬁ culty of access. In order for osteo-porosis to be diagnosed, a pre-requisite for exceptional drugs to be prescribed, it is necessary for patients to see a specialist and undergo bone densitometry. Difﬁ culties in access to this service may become a barrier to the use of these medications.

Although there is no data on income and whether or not patients have health insurance, it is possible that SUS users have dif_ﬁ culty in arranging diagnostic tests. Brazilian authors have reported inequality in the supply of specialist services.2,20_{Higher numbers of} hospitaliza-tions indicate probable inequalities in access to appoint-ments and show that the capacity of the elderly to make use of the public health care network may be limited to emergencies, that chronic illness is not being monitored and that families are less able to manage serious condi-tions.17_{This information is relevant when evaluating} equality of access to treatments for osteoporosis.

Even after a fracture, the diagnosis is not always correctly made, as a recent study shows. After a signiﬁ -cant event such as a hip fracture, 13.9% of patients were diagnosed with osteoporosis and 11.6% were started on some kind of treatment upo discharge from hospital.14

There is controversy in the literature regarding the use of medication to prevent fractures which could occur 20 or 30 years after starting treatment.3,15_However, bisphosphonates are still the most widely used drugs for treating postmenopausal osteoporosis and have shown good efficacy in increasing bone mineral density and reducing the incidence of fractures.9,22_In the cohort analyzed here, the most widely used medi-cation was alendronate sodium, which is consistent with the guidelines.

It was observed that those patients who did not die had lower costs than those who did, which may be explained by the fact that patients whose cases are more serious need more clinical care and/or are using

c_{Ministério da Saúde. Portaria SAS nº 125 de 19 de abril de 2001. Altera a Tabela Descritiva do SIA/SUS estabelecida pela Portaria GM/MS nº}

1.230, de 14 de outubro de 1999 no que diz respeito ao Grupo 36. Diario Ofi cial Uniao. 20 abr 2001.

d_{Ministério da Saúde. Portaria SAS nº 341 de 22 de agosto de 2001. Defi ne, para o Grupo 36 da Tabela Descritiva do SIA/SUS, a forma e a}

redação estabelecidas no Anexo desta Portaria. Diario Ofi cial Uniao. 23 ago 2001.

e_{Ministério da Saúde. Portaria nº 346, de 14 de maio de 2002. Defi ne, para o Grupo 36 da Tabela Descritiva do SIA/SUS, a forma e a redação}

estabelecidas no Anexo desta Portaria. Diario Ofi cial Uniao. 15 maio 2002.

f_{Ministério da Saúde. Portaria GM nº 1.318, de 23 de julho de 2002. Defi ne, para o Grupo 36 da Tabela Descritiva do SIA/SUS, a forma e a}

redação estabelecidas no Anexo desta Portaria. Diario Ofi cial Uniao. 24 jul 2002.

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more than one medication belonging to the high cost program. There was a high level of mortality, possibly because the program treated very seriously ill patients, with comorbidities and because of the conditions of the disease itself. The study found that the most frequent causes of mortality among the elderly were falls and events of an indeterminate nature,16_{falls are, very often,} a consequence of osteoporosis.

The medication used at the start of treatment, changes in medication, region in which resident, age group, death during the course of treatment and diagnosis were responsible for 76.3% of linear variation in spending. Raloxifene and calcitonin were the alternatives which had the greatest impact on spending compared to alen-dronate sodium.

One of the limitations of this study was the use of the administrative database which had gaps in clinical information and input errors. Nevertheless, the great

potential of administrative data in following service users throughout the course of their health care service use stands out, as this is fundamental to support decision making and organizing services, through planning campaigns and monitoring and evaluating the proposed objectives.

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1. Acurcio FA, Brandão CMR, Almeida AM, Guerra Jr AA, Cherchiglia ML, Andrade EIG et al. Perfi l demográfi co e epidemiológico dos usuários de medicamentos de alto custo no Sistema Único de Saúde. Rev Bras Estud Popul. 2009;26(2):263-82. DOI:

http://dx.doi.org/10.1590/S0102-30982009000200007

2. Almeida WS, Szwarcwald CL. Mortalidade infantil e acesso geográfi co ao parto nos municípios brasileiros.

Rev Saude Publica. 2012;46(1):68-76. DOI: http:// dx.doi.org/10.1590/S0034-89102012005000003 3. Alonso-Coello P, García-Franco AL, Guyatt G,

Moynihan R. Drugs for pre-osteoporosis: prevention or disease mongering? BMJ. 2008;336(7636):126-9. DOI: http://dx.doi.org/10.1136/bmj.39435.656250.AD 4. Araújo DV, Oliveira JHA, Bracco OL. Custo da fratura

osteoporótica de fêmur no sistema suplementar de saúde brasileiro. Arq Bras Endocrinol Metab.

2005;49(6):897-901. DOI: http://dx.doi.org/10.1590/ S0004-27302005000600007

5. Bandeira F, Carvalho EF. Prevalência de osteoporose e fraturas vertebrais em mulheres na pós-menopausa atendidas em serviços de referência. Rev Bra Epidemiol. 2007;10(1):86-9. DOI: http://dx.doi. org/10.1590/S1415-790X2007000100010 6. Berry SD, Kiel DP, Donaldson MG, Cummings

SR, Kanis JA, Johansson H, et al. Application of the National Osteoporosis Foundation Guidelines to postmenopausal women and men: the Framingham Osteoporosis Study. Osteoporos Int.

2010;21(1):53-60. DOI: http://dx.doi.org/10.1007/ s00198-009-1127-3

7. Bracco OL, Fortes EM, Raffaelli MP, Araújo DV, Santili C, Castro ML. Custo hospitalar para tratamento da fratura aguda do fêmur por osteoporose em dois hospitais-escola conveniados ao Sistema Único de Saúde. JBES. 2009;1(1):3-10.

8. Brandão CMR, Guerra Jr AA, Cherchiglia ML, Andrade EIG, Almeida AM, Silva GD, et al. Gastos do Ministério da Saúde do Brasil com Medicamentos de Alto Custo: uma análise centrada no paciente. Value Health. 2011;14(5 Supll 1).S71-7. DOI: http://dx.doi. org/10.1016/j.jval.2011.05.028

9. Brandão CMR, Lima MG, Silva AL, Silva GD, Guerra Jr AA, Acurcio FA. Treatment of postmenopausal osteoporosis in women: a systematic review. Cad Saude Publica. 2008;24(Supll4):592-606. DOI: http:// dx.doi.org/10.1590/S0102-311X2008001600011 10. Budhia S, Mikyas Y, Tang M, Badamgarav E.

Osteoporotic Fractures: A Systematic Review of US Healthcare Costs and Resource Utilization.

Pharmacoeconomics. 2012;30(2):83-170. DOI: http:// dx.doi.org/10.2165/11596880-000000000-00000 11. Carias CM, Vieira FS, Giordano CV, Zucchi P.

Medicamentos de dispensação excepcional: histórico e gastos do Ministério da Saúde do Brasil. Rev Saude Publica. 2011;45(2)233-40. DOI: http://dx.doi. org/10.1590/S0034-89102011000200001 12. Costa-Paiva L, Horovitz AP, Santos AO,

Fonsechi-osteoporose em mulheres na pós-menopausa e associação com fatores clínicos e reprodutivos. Rev Bras Ginecol Obstet. 2003;25(7):507-12. DOI: http:// dx.doi.org/10.1590/S0100-72032003000700007 13. Faisal-Cury A, Zacchello KP. Osteoporose:

prevalência e fatores de risco em mulheres de clínica privada maiores de 49 anos de idade. Acta Ortop Bras. 2007;15(3):146-50. DOI: http://dx.doi. org/10.1590/S1413-78522007000300005 14. Fortes E, Raffaelli MP, Bracco OL, Takata ETT, Reis

FB, Santili C, et al. Elevada morbimortalidade e reduzida taxa de diagnóstico de osteoporose em idosos com fratura de fêmur proximal na cidade de São Paulo. Arq Bras Endocrinol Metab.

15. Fundació Institut Catalã de Farmacologia. Bifosfonatos: uma relación benéfi co-riesgo dudosa.

ButlletI Groc. 2009;22(3):9-12.

16. Lima-Costa MF, Peixoto SV, Giatti L. Tendências da mortalidade entre idosos brasileiros (1980 - 2000). Epidemiol Serv Saude. 2004;13(4):217-28. DOI:

http://dx.doi.org/10.5123/S1679-49742004000400004

17. Louvison MCP, Lebrão ML, Duarte YAO, Santos JLF, Malik AM, Almeida EA. Desigualdades no uso e acesso aos serviços de saúde entre idosos do município de São Paulo. Rev Saude Publica.

18. Pinheiro MM, Ciconelli RM, Martini LA, Ferraz MB. Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS). Osteoporos Int.

2009;20(3):399-408.DOI: http://dx.doi.org/10.1007/ s00198-008-0680-5

19. Pinheiro MM. Mortalidade após fratura por osteoporose. Arq Bras Endocrinol Metab.

20. Scatena LM, Villa TCS, Ruffi no Netto A, Kritski AL, Figueiredo TMRM, Vendramini SHF, et al. Difi culdades de acesso a serviços de saúde para diagnóstico de tuberculose em municípios do Brasil.

Rev Saude Publica. 2009;43(3):389-97. DOI: http:// dx.doi.org/10.1590/S0034-89102009005000022 21. Silveira VAL, Medeiros MMC, Coelho-Filho JM, Mota

RS, Noleto JCS, Costa FC, et al. Incidência de fratura do quadril em área urbana do Nordeste brasileiro.

Cad Saude Publica. 2005;21(3):907-12. DOI: http:// dx.doi.org/10.1590/S0102-311X2005000300025 22. Stevenson M, Jones ML, De Nigris E, Brewer N,

Davis S, Oakley J. A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis. Health Technol Assess. 2005;9(22):1-160.

23. Travassos C, Martins M. Uma revisão sobre os conceitos de acesso e utilização de serviços de

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The authors declare that there are no confl icts of interests. DOI:

http://dx.doi.org/10.1590/S0102-311X2004000800014

24. Vestergaard P, Rejnmark L, Mosekilde L. Increased mortality in patients with a hip fracture-effect of pre-morbid conditions and post-fracture

complications. Osteoporos Int. 2007;18(12):1583-93. DOI: http://dx.doi.org/10.1007/s00198-007-0403-3

25. Vittinghoff E, Glidden DV, Shiboski SC, McCulloch CE. Regression Methods in Biostatistics: linear, logistic, survival and repeated measures models.New York: Springer; 2004.

26. World Health Organization. Scientifi c Group on the Prevention and Management of Osteoporosis: Prevention and Management of Osteoporosis.Geneva; 2003 (Technical Report Series, 921).

Between 2000 and 2006, 72, 265 postmenopausal women received medication to treat osteoporosis through the Ministry of Health exceptional medicines program.

Mean monthly spending was R$ 68.76, with a median value of R$ 49.68. Mean monthly cost became progressively greater as these women aged, going from R$ 64.33 in women aged from 50 to 59 to R$ 170.63 in the group aged 80 and over. The mean cost was higher in women who had suffered fractures beforehand.

The factor which had the greatest impact on mean cost was the medication prescribed. Using alendronate sodium as the reference medication, costs were nine times higher when raloxifene was prescribed, four times higher for calcitonin and three times higher for calcitriol. Prescribing risedronate reduced the cost.

The data from the study may guide Mi nistry of Health updates of clinical protocols and treatment directives, as well as supporting the effective allocation of resources for treating osteoporosis.

Profa. Rita de Cássia Barradas Barata Scienti_ﬁ c Editor