Prevalence of FRAX risk factors and the osteoporosis treatment gap among women ≥ 70 years of age in routine primary care across 8 countries in Europe

Osteoporosis (OP) is a systemic disease characterized by low bone mass and deterioration of bone tissue, which results in bone fragility and an increased risk of fracture [1]. Bone loss accelerates in the year just before menopause and remains high as long as 4–8 years after menopause, with women losing on average 10% of their bone mineral density (BMD) during the menopausal transition [2]. In 2015, the prevalence of BMD-defined OP in women aged 50 or more across the EU5 (France, Germany, Italy, Spain, and UK) and Sweden ranged from 21.8% in the UK to 23.1% in Italy [3]. The related fractures were found to impose a substantial economic burden in these countries, with direct costs in 2017 ranging from € 1199 million in Sweden to € 8176 million in Germany [3].

Dual-energy X-ray absorptiometry (DXA) is the most widely used technique for measuring BMD, upon which the diagnosis of OP is generally based. Tools such as the FRAX fracture risk assessment tool developed at the University of Sheffield, which integrates clinical risk factors and BMD, are being commonly used to calculate the risk of fracture [4]. Increasingly, FRAX values are used to set national or international thresholds for assessment and/or treatment to identify patients to be targeted for pharmacotherapy [5‐8]. Despite this, only a minority of women eligible for treatment receive appropriate treatment [9]. In 2010, the estimated treatment gap in Europe varied from 26% in Ireland to 78% in Poland [10, 11]. More recent studies have indicated that the treatment gap persists; e.g., > 75% of respondents (representative of the general French population) 50 years or older who reported a fracture had not been diagnosed with OP, or received appropriate care [12], and the treatment gap in women in the EU5 and Sweden was estimated as 73% for 2017 [3]. The primary analysis from our recent study of 8 European countries confirmed this large treatment gap (74.6%) in women aged ≥ 70 years at increased risk of FF in routine primary care across Europe [13]. The gap appeared to be related to a low rate of OP diagnosis. In this analysis, we wished to examine the relationship between fracture risk factors and the treatment gap across the 8 countries. In addition, the study provided an opportunity to compare the prevalence of fracture risk factors over the same countries.

Detailed methods for this cross-sectional, multicenter, observational study have been published previously [13].

A total of 3798 patients were enrolled; approximately 500 per country (except for Switzerland, n= 205), across 153 sites.

Our study found a large treatment gap for women aged ≥ 70 years at increased risk of FF who were in routine primary care across 8 countries in Europe. While the treatment gap varied (53.1% in Ireland to 90.8% in Germany), it was above 50% in all 8 countries. Across countries, the treatment gap was lower in patients with an OP diagnosis, with the difference between patients with and without a diagnosis ranging from 36.5% in Germany to 79.4% in Belgium.

Studies in other regions of the world have also identified a large OP treatment gap among older or postmenopausal women (in these studies, the treatment gap was usually defined as the proportion who did not receive OP medication in a defined period after a primary fracture or an OP diagnosis). In the USA, the treatment gap was reported as 72.1% (data from the Women’s Health Initiative study [15]) and 81. 4% [16]; in Asia, treatment gap varied from 64.5% in a multi-country study in China and South-East Asia [17] to as high as 98.6% in a cross-sectional study in China [18].

An earlier study [10], which used a different methodology and was not limited to primary care, reported lower treatment gaps for the countries in our study; however, that study also identified Ireland as having the lowest treatment gap (26%). The treatment gap in our study was substantially lower in patients diagnosed with OP; however, the gap in these patients also varied across countries, from 9.9% in Ireland to 61.7% in Germany. This suggests there are substantial differences across Europe in how well women eligible for OP treatment are identified, as well as differences in treatment uptake in those who are diagnosed with OP. In some countries, such as Germany, most OP patients may be treated by orthopedic physicians instead of general practitioners (GPs), which could contribute to a low rate of DXA measurements and a high treatment gap. The involvement of GPs is an important aspect of OP prevention and management. Two studies in France revealed that physician’s attitudes and lack of awareness of OP can be a significant barrier to identifying and treating patients at risk for fracture [19, 20]. Physicians’ attitudes also influence those of the OP patients themselves, which can have an impact on treatment adherence [19]. A qualitative study in Sweden [21] found that primary care physicians perceive OP as a silent disease that is overshadowed by other conditions and seen as a low priority. The recently published SCOPE scorecard provides a detailed comparison of OP epidemiology and care across Europe, including estimate of the treatment gap in those aged 50 or more [22]. The treatment gap in Europe was estimated to be 71% overall, and as for our study was lowest in Ireland (32%). Gaps in knowledge, diverse opinions on who should be responsible for management, and uncertainty about treatment protocol could affect the management of OP. Furthermore, FRAX use may be limited by absence of linkage to electronic medical records.

The FRAX uptake reported in SCOPE was substantially lower in those countries where we found a higher treatment gap in our study (Germany, France, Poland, and Slovakia) [22]. In our study, the three countries with the lowest rates of DXA scans (Poland [8.3%], France [11.4%], and Germany [12.3%]) also had the highest treatment gap overall (88.0%, 82.2%, and 90.8%, respectively); conversely, Ireland, with the highest rate of scans (44.6%), had the lowest treatment gap (53.1%). Availability of DXA is similar across all countries except Poland and the UK, and scans are fully or partially reimbursed in all the countries [22]; therefore, differences observed in rates of DXA between countries may reflect differences in awareness of OP and fracture risk, which in turn drives the treatment gap.

Among OP medications, oral BPs were used at high rates in most countries in our study (32.1 to 96.1% of those using any OP medication), reflecting their use as a standard first-line treatment. Denosumab was used at relatively high rates in Belgium, Germany, Ireland, and Switzerland (39.9 to 55.4%), and at low rates in other countries (1.0 to 26.1%), which may be due to differences in access or reimbursement. In general, the other medications assessed (parenteral BP, PTH, SERM, and strontium) were used at low rates. Treatment patterns reported in the literature are consistent with these findings. BPs were reported as by far the dominant treatment in UK primary care for the period 2010 to 2015 [23]. An analysis of German pharmacy prescription data showed that most first-time prescriptions between 2010 and 2014 were for oral BPs, but denosumab treatment was more common than found in the UK study [24].

This study has some important strengths as well as limitations. GPs willing and able to participate in observational studies could represent a specialized subgroup; therefore, as noted earlier [13], steps were taken to reduce bias during recruitment. The prevalence of risk factors and comorbidities agreed with that reported earlier [25‐30], indicating that the study population is typical for this demographic. However, since the patients were women ≥ 70 years visiting their GP, they may not be representative of the general population. The study was not also designed to establish causality between the prevalence of risk factors and treatment gap. All analyses were descriptive; no statistical comparisons were made across countries. The sample sizes were small in relation to the total number of women with OP in the countries in the study, and therefore the results may not be representative. This is especially true for Switzerland, which had the smallest number of subjects (205, across 6 sites).

In conclusion, our study highlights differences across countries in Europe with respect to clinical risk factors for fracture, DXA scanning, and the rates of OP diagnosis. The OP treatment gap differed but still fewer than 50% of women at increased risk of FF were treated in any country. Our findings suggest that there is variable success across Europe in identifying and treating women at risk for fracture. More emphasis needs to be placed on BMD measurements as a tool for screening elderly women, and on the use of FRAX or other risk assessment tools. It is also important that patients and physicians across Europe be educated about the importance of screening and prevention measures for OP. Finally, further studies are needed to understand the reasons for large treatment gaps in primary care, to identify potential solutions and appropriate steps to improve the treatment of OP and lower the occurrence of fracture in elderly women.