The osteoporosis treatment gap in patients at risk of fracture in European primary care: a multi-country cross-sectional observational study

Over 8.9 million osteoporotic or fragility fractures occur every year across the globe, more than a third of which occur in Europe [1, 2]. In 2010, 3.5 million new fragility fractures (FFs) in 22 million women aged over 50 were estimated to have occurred across the EU; and FFs are predicted to increase due to changing demographics [3]. It has been suggested that approximately 51% of the hip fractures that occur globally are potentially preventable [4]. Hence, disease awareness, early diagnosis, prevention, and appropriate treatment of fractures are critical in osteoporosis (OP) management. However, the diagnosis of OP frequently occurs only after a fracture, and even then treatment rates can be low [4].

General practitioners (GPs) play a critical role in OP management. To begin with, they are well positioned to assess risk factors in the general population [5]. For example, in a cross-sectional survey on women 45 years or older in the French general population, the diagnosis of OP was most commonly made by a GP (approximately 45% of diagnoses [6]); and in a single OP clinic in the UK, 94% of the referrals for bone mineral density (BMD) scans over the course of 1 year had been made by GPs [7]. For patients who experience OP-related fractures, a cost burden is also placed on primary care. A study of UK databases reported that primary care costs increased significantly in the first 2 years after hip fracture [8]. Coordinator-based fracture liaison services for secondary prevention also usually require the GP’s involvement as part of a multi-disciplinary team for treating patients and monitoring their progress [9, 10].

Diagnostic methods and fracture risk assessment have improved in recent years. However, despite new interventions to reduce fracture risk and new clinical practice guidelines, only a small fraction of eligible women receive treatment for OP, implying a high treatment gap [11]. It was estimated that 10.6 out of the 18.4 million women in the EU who exceeded the threshold risk for FF were not treated, representing a treatment gap of 57% [3]. This is likely to be an underestimate, as the analysis assumed that all OP drug usage was targeted appropriately at individuals at high risk. In the absence of recent real-world data, we designed this study to specifically focus on assessing the treatment gap in a large sample of women ≥ 70 years in Europe who were routinely visiting their GPs.

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. Overall, just over half were found to be at increased risk of FF, of whom three-quarters were not receiving any OP medication. Even among patients with prior spine or hip fractures, the treatment gap was high, with 42% and 64%, respectively, not receiving OP treatment. While the treatment gap varied, it was above 50% in all 8 countries. The treatment gap in patients with prior hip fracture was lowest in Ireland (43%), Belgium (46%), and the UK (55%), and highest in Switzerland (88%) and Germany (94%). We observed that a diagnosis of OP has a substantial impact; the treatment gap was much smaller in those with an OP diagnosis (30.9% vs. 74.6% in the overall population) and much larger in those without an OP diagnosis (94.1%). The treatment gap therefore appears to be largely related to a gap in diagnosis or awareness.

The large treatment gap reported here is consistent with previous studies. For example, treatment gaps of 55–68% have been reported for Europe using different methodologies [1, 3, 13]. Even in the presence of a prior fracture, treatment rates have been reported to be low for secondary prevention [2] and have also been shown to be declining over time [3]. Across the EU, less than 20% of patients with FFs were reported to receive treatment within the year following fracture [1]. This treatment gap has also been reported in the elderly, for whom the consequences of untreated OP are more severe. Treatment gap was between 48 and 68% in Swedish women aged over 70, with as few as 10% of elderly women with FFs receiving any OP therapy [11]. Wide intercountry variability in treatment uptake in women with higher risk of osteoporotic fractures has also been reported in other studies [1, 3], and could be due to different availability and reimbursement of medications and differences in fracture risk. Fracture registries may play an important role in improving access to treatment: Ireland and the UK have national hip fracture registries and had a relatively low treatment gap compared with other countries. In all of these countries, treatment guidelines suggest a case-finding approach for patient identification, but there is variation in terms of which risk factors are acknowledged, how fracture risk should be assessed, how BMD measurements should be used, and the thresholds for treatment initiation. Notwithstanding the wide availability of national guidelines, it is clear that their recommendations are not always followed.

We observed that a diagnosis of OP has a substantial impact on the treatment gap; in women at high risk, the gap was much smaller in those with an OP diagnosis than in those without (30.9% vs. 94.1%, respectively). A similarly reduced treatment gap in those with a diagnosis of OP was reported in the GLOW study [13]. A diagnosis of OP was therefore found to be a key factor in the decision to treat patients at increased risk of fracture. It is unclear why approximately one-third of patients with a diagnosis still remain untreated: physicians may be managing multiple other competing conditions and may consider vitamin D/calcium supplements sufficient to reduce fracture risk, or patients may have declined treatment because of confusion about the future risk of fracture compared with the risk of adverse effects, or may have developed side effects to one treatment and not transitioned to another.

Our data demonstrate that oral bisphosphonates are still the most widely used agents, comprising 58% of first-line OP medication (58.3%) compared with 28% receiving denosumab, and only 8% accessing parenteral bisphosphonate therapy. The vast majority of patients on second-line therapy received non-oral treatment (denosumab, 76%; parenteral BP, 10%), a pattern that is consistent with recommendations in key European guidelines [9, 14‐16].

This study has a number of strengths as well as limitations. Care was taken during the study design and implementation to reduce bias and optimize the generalizability of the results within the participating countries. For example, site selection and assessment was conducted by a third party, to avoid inclusion of sites with an existing relationship with the sponsor and potentially having a particular interest in OP. The prevalence of risk factors and comorbidities is consistent with other studies [17‐19], indicating that the current study population is representative of the primary care population. Furthermore, the consistency of patient characteristics between those recruited early to the study and those recruited later indicates that the selection criteria were not altered to fulfill enrollment targets. Our findings are consistent with a recent study in older Swedish women that showed a treatment gap of 78% in those eligible for treatment according to national guidelines [20]. Although there appears to be a clear link between osteoporosis diagnosis and the treatment gap, the study was not designed to establish causality for factors associated with lack of treatment. We cannot exclude that a treatment decision by a GP may affect whether they enter an osteoporosis diagnosis into the medical record. Notably, the treatment gap was lowest in the subgroup of patients with a T-score ≤ − 2.5 (21%), a finding that suggests that treatment followed the diagnosis at least in this subset of patients.

Taken together, our study and earlier studies suggest no improvement in treatment rates over the last 10 years. The increase in the treatment gap could be attributed to several factors such as misconceptions about OP, lack of perceived benefits of therapy, concern about side effects and medication costs, lack of motivation, and lack of patient education [21]. Importantly, inadequate or incorrect information in the media related to OP and its treatment are also associated with a low awareness of the disease and, subsequently, low treatment rates [22]. It is likely that novel strategies will be needed to narrow the treatment gap, particularly in older women. Greater awareness and ease of access to fracture risk assessment and treatment are likely to play a part; for example, the establishment of fracture liaison services in primary or secondary care settings increases BMD uptake and treatment exposure and is associated with reductions in fracture risk [23]. The application of fracture risk assessment in primary care and community settings was the focus of three recent randomized controlled trials of screening using the FRAX tool [17, 24, 25]. A meta-analysis of the three studies [26] showed a statistically significant reduction of major osteoporotic fractures (hazard ratio [HR] = 0.91; 95% CI = 0.84–0.98) and hip fractures (HR = 0.80; 95% CI = 0.71–0.91). The number needed to be treated to prevent one fracture was 25–28 patients. Educational and information technology–based solutions that could further facilitate fracture risk assessment in primary care could therefore be a critical step; it is of interest that there is a negative correlation between frequency of FRAX usage in the 8 countries studied (derived from [27] and the observed treatment gap (r = − 0.74, data not shown)), though this is not evidence of causation.

In conclusion, our study provides insight into the treatment gap and treatment practices in women ≥ 70 years of age in the primary care setting in Europe. Improved identification and assessment of fracture risk by primary care physicians should be a priority for medical bodies and policymakers, to enable informed treatment decisions that target those at greatest risk of fracture, and who are most likely to benefit from OP medications.