Introduction
Osteoporosis is a disease characterized by low bone mineral density and structural decay, which increases the risk of fracture [
1]. Fractures result in great patient suffering, negative effects on quality of life and increased mortality, especially after hip fracture, and high financial costs [
2,
3]. In 2010, three and a half million osteoporosis-related fractures occurred in the EU at an annual cost of 37 billion euros [
4]. The number of fractures is expected to rise and by 2025, the estimated number is four and a half million fractures to a cost of 46.8 billion euros annually [
4]. Fracture rates increase markedly with age and the incidence of hip fracture in Swedish women is among the highest in the world [
5]. Although effective pharmacological treatment is available [
6], treatment rates in Sweden remain low even for older patients with prevalent fracture [
7,
8]. Only limited data are available regarding treatment rates in relation to a thoroughly evaluated fracture risk in a population-based setting in older women [
9].
Eligibility for treatment varies in different countries. Relevant criteria include the presence of osteoporosis at one or more densitometric site, prior fracture (particularly spine, hip, or multiple fractures), and high fracture probabilities. Irrespective of the criteria used, the uptake of bone-specific treatment is low [
10,
11]. A large Danish register study found that only a small fraction of the expected number of women with osteoporosis were diagnosed and that very few women with fractures received osteoporosis medication after age 50 years [
10,
11]. Studies from Germany and the US have shown that only 21.7% and 28.6% of patients with diagnosed osteoporosis received an osteoporosis medication, respectively [
10,
11].
Common barriers for not being treated are fear of potential side effects, such as gastro-intestinal events [
12], and rare side effects, such as atypical femur fractures and osteonecrosis of the jaw [
13], as well as costs of osteoporosis evaluations and medications [
14].
Factors associated with receiving osteoporosis medication are partly driven by characteristics such as a diagnosis of osteoporosis and osteopenia as well as hip, spine, and multiple fractures [
15,
16].
The fracture risk calculation tool FRAX® is recommended in many clinical guidelines to calculate the absolute 10-year probability of major osteoporosis and hip fracture [
17], based on clinical risk factors and bone mineral density (BMD) [
18]. FRAX has been incorporated in the guidelines issued by the American National Osteoporosis Foundation (NOF), the National Osteoporosis Guideline Group (NOGG), and the Swedish Osteoporosis society (SvOS). The incorporation of FRAX into treatment guidelines emphasizes a substantial need for osteoporosis medication in the elderly, in whom a very small minority currently receives treatment in the United States (US) [
19,
20].
The aim of this study was to investigate the proportion of older Swedish women eligible for treatment according to the SvOS guidelines, and to determine whether factors could be identified that predicted prescription of osteoporosis medication. As a sensitivity analysis, we also aimed to determine the treatment gap if the NOF and NOGG guidelines were to be applied to this Swedish population of older women.
Discussion
In this study, we report the existence of a large treatment gap among well characterized elderly Swedish women with a high fracture risk. As many as 1107 (37%) women were found to be eligible for treatment according to SvOS guidelines, but only 21.8% of these women had current or recent osteoporosis medication. Interestingly, as many as 74 women, not eligible for treatment according to SvOS guidelines, were treated despite being in the low-risk group. Factors associated with osteoporosis treatment were predominantly prior fracture and oral treatment with glucocorticoids but also high blood pressure, obesity, and body mass index.
The present study was designed to investigate different lifestyle factors (e.g., smoking, medications, and physical activity) and bone phenotypes’ association with incident fractures, therefore the ability to investigate osteoporosis prevalence might be limited. With a rather low inclusion rate (47.4%), which probably has resulted in inclusion of a healthier part of the population with a lower fracture risk, these findings might not be applicable to the general population of older women. To investigate the potential generalization of our findings, other clinical markers were used (e.g., blood pressure). Within this cohort (SUPERB), 1783 women (59.8%) were hypertensive defined as either having a systolic pressure above or equal to 140 mmHg or a diastolic pressure above or equal to 90 mmHg. The prevalence of hypertension found in SUPERB corresponds well to earlier presented data from a large population based study in Sweden, in which in total 60% of both men and women (age 45–73 years) and 54% for only women, were diagnosed with hypertension [
30]. This finding indicates that the SUPERB population is representative of the general population.
Previously performed studies in Europe and in the US have been based on register data for prevalence of osteoporosis and osteoporosis medication [
10,
11,
31], and were therefore not able to fully take all relevant clinical risk factors into account. Being able to take most relevant clinical risk factors into account, we found in the present study that the treatment gap, according to NOF guidelines, in our older Swedish women was similar or somewhat lower than what was previously reported in older women in the US [
19,
20]. With the updated NOF guidelines [
19], Donaldson et al. found that 93%, of the women aged 75 or older included in the study of osteoporotic fractures, and Berry et al. found that 86%, of women in the same age category participating in the Framingham study, would be eligible for treatment with the incorporation of FRAX into the NOF guidelines [
19,
20]. However, there is a large variation in fracture risk between different regions of the world [
5]. An Israeli study was able to investigate treatment eligibility using also common clinical risk factors. The proportion eligible for treatment using NOF guidelines was only 30.5% compared to the 81% rate observed in the present study. Such difference might be explained by the much higher fracture risk in Swedish elderly women compared to Israeli patients, a group consisting both of men and women with a wide age span from 50 to 90 years of age [
32]. The much more treatment conservative SvOS guidelines identify women eligible for treatment at higher risk than the NOF and NOGG guidelines but result in a lower prevalence of women eligible for treatment. Thus, interventions in women according to SvOS vs. NOF or NOGG guidelines will likely result in larger absolute risk reductions in fractures, at the cost of failing to prevent fractures in women with intermediate risk according to SvOS guidelines. Based on the numbers of treatment eligible women and the FRAX hip fracture probabilities, the SvOS guidelines would only identify 193 hip fractures (17.4% FRAX hip fracture probability in 1107 women) while the NOGG guidelines would identify as many as 272 women with hip fractures (16.0% FRAX hip fracture probability in 1698 women).
The existing treatment gap has many potential explanations. To be able to increase the proportion of treated patients, we need a better understanding in which factors that are associated with increased probability of receiving osteoporosis medication. In a large population-based study, women were divided into high- and low-risk groups and different predictors of receiving treatment were investigated. For both groups, a self-reported diagnosis of osteoporosis followed by a self-reported diagnosis of osteopenia were the strongest predictors for treatment. In addition, the study looked at the proportion of treated women for each FRAX variable and compared to women without and found that women who had the most included FRAX risk factors were more likely to receive treatment [
16]. However, a higher treatment rate in women with a higher prevalence of FRAX-included risk factors is somewhat expected. Therefore, we investigated different characteristics predictive value of receiving osteoporosis medication when competing with the actual FRAX-score as well as looking at all characteristics individually in a high-risk population-based study. Our results demonstrate that important risk factors for women to receive osteoporosis medication include prior fracture, previous or current treatment with glucocorticoids, and FRAX-scores for major osteoporotic and hip fracture.
The FRAX-score for a major osteoporotic or hip fracture is country specific, resulting in men and women, in different parts of the world (e.g., Sweden and USA), obtaining different FRAX-scores, even if the same risk factors are present. To evaluate potential undertreatment of Swedish elderly women with an American or British treatment definition could be questioned. The obtained fracture risk for the Swedish elderly women in the present study would have been lower if they had been analyzed using the US or UK FRAX calculators. However, these findings emphasize that an even larger proportion of the included Swedish women would have been recommended osteoporosis medication, if the lower treatment thresholds applied by NOF or NOGG would have been used also in Sweden.
This study has some limitations. Treatment with osteoporosis medication was assessed by questionnaire, which is limited by the patient’s recollection of treatment. Preferably, treatment for osteoporosis should have been obtained from the prescription registry. The present study was only performed on elderly women. Therefore, treatment eligibility cannot be presented for younger postmenopausal women or men. The FRAX calculator is a widely used web-based tool for fracture prediction and has been validated in several large cohorts. However, FRAX has some limitations, which include the inability to account for, e.g., falls risk, recency and number of prevalent fractures, dose of glucocorticoid treatment, alcohol, and smoking.
This study also has strengths. It is a population-based study in which we had information not only about the participating women’s skeletal phenotypes but also all other commonly used risk factors for fracture. Such information enables a comprehensive evaluation of fracture risk allowing a well-founded decision regarding treatment eligibility. The cohort (SUPERB) has a rather narrow age span (75–80 years), which enables us to visualize the critical situation close to the dramatic exponential increase in hip fracture risk, the fracture type that results in most patient suffering and highest societal costs, commonly seen after the age of 80 [
33].
The present study is first to report of a substantial treatment gap in a well-characterized population of older Swedish women with high fracture risk. The probability to receive osteoporosis medication was higher in women with prior fracture or previous use of oral glucocorticoids.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.