The impact of preventive measures on the burden of femoral fractures – a modelling approach to estimating the impact of fall prevention exercises and oral bisphosphonate treatment for the years 2014 and 2025

With increasing age, the risk of fragility fractures such as femoral or vertebral fractures increases exponentially. Femoral fractures are the most common, costly, and resource consuming type of fragility fractures [1]. The secular trend in rates of femoral fractures remains unclear. While some countries report a lowering of femoral fracture rates over the last decade, other countries such as Germany report unchanged rates [2, 3]. Due to the growing number of old and very old persons in industrialised countries, the absolute number of fractures is expected to rise substantially over the coming decades; a trend that could only be reversed if prevention receives more attention [1, 4]. Therefore, it is of interest to explore what impact wider implementation of existing preventive measures could have on (i) the situation today and (ii) the projected increase in fractures over the coming years.

The two main underlying mechanisms of fragility fracture are osteoporosis and falls [5]. For both, there are evidence-based preventive interventions available. Several pharmaceutical agents offer effective treatment options to improve low bone mineral density (BMD) in osteoporosis. Best evidence exists for bisphosphonates, which are regarded as first line medication [6, 7]. Clearly, this treatment addresses only persons with decreased BMD. For the prevention of falls, various strategies have been shown to be effective [8]. A variety of exercise-based programmes have been developed for the general older population, e.g. persons across the spectrum of risk of falls. Most of these programmes are based on balance and strength training, delivered either in groups or individually [9].

The aim of this paper was to estimate the potential impact of these two interventions, (a) treating osteoporosis with oral bisphosphonates, and (b) preventing falls by Fall Prevention Exercise (FPE), on the expected burden of femoral fractures in community-dwelling persons 65 years and older at present and in 2025. We excluded nursing home residents as their fracture risk differs from that of community-dwelling persons [10].

The population structure of Bavaria, Germany was used for our modelling approach to provide a model for central Europe. This population was chosen because of the availability of age- and gender-stratified fracture rates [10], and official population data, both current and projected to 2025. Bavaria is one federal state of Germany with around 12.7 million inhabitants, with an estimated 2.42 million persons aged 65 years or older at the end of 2014 [11]. By 2025, this number is expected to increase to 2.83 million persons. We were interested in the impact of two different prevention strategies to lower the number of femoral fractures in 2014 and to lower the expected increase of femoral fractures between 2014 and 2025: fall prevention by exercise and osteoporosis treatment by bisphosphonate medication. The analyses were based on the following assumptions (see Appendix 1):

The modelling approach was employed in the German federal state of Bavaria. In 2014, about 2.42 million persons aged 65 years and older are estimated to live in Bavaria, of whom 4.5 % live in nursing homes. Due to the changing age structure of the Bavarian population, 4.9 % of this population are estimated to live in nursing homes in 2025. These persons were not considered in the analyses. Based on demographic information and using age- and gender-stratified fracture rates, 17,119 femoral fractures are estimated to occur in the year 2014 and 21,263 femoral fractures in the year 2025. Of all femoral fractures in 2014 and 2025, 64.6 and 65.6 % of fractures were estimated to occur in persons with osteoporosis, respectively (Table 1 Estimate for the year 2014).

In 2014, a moderate reduction of all femoral fractures by 10 % required 20.9 % of all community-dwelling persons aged 70–89 older to participate in FPE (Table 2). A substantial reduction by 25 % required a participation rate of 52.2 %. In order to lower the number of femoral fractures by 10 %, 36.9 % of persons with osteoporosis (N_osteoporosis) needed to receive bisphosphonates. A reduction of all femoral fractures by 25 % required a treatment rate of 92.2 % (Table 2).

In our model, between 2014 and 2025 the number of femoral fractures will increase by 24.2 % due simply to demographic changes - assuming that age- and sex-specific fracture rates are stable in this time period. Such projections have alerted policy makers in many countries and there is a growing need as well as interest in preventive measures to limit the upcoming burden for the health care systems. The objective of our model calculation was to estimate to theoretical impact of current available preventive measures on the burden of femoral fractures now and in the future.

Pillars of fracture prevention are fall-prevention strategies such as exercise programmes and the treatment of osteoporosis with anti-resorptive medications. About one third of all people aged 65 years and older have at least one fall each year and a past fall is a moderate predictor for future falls [23]. Therefore, falls are of relevance for most of the older people. Thus, fall prevention measures are justified in a broad range of the older population. Bisphosphonate treatment, however, is limited to patients with osteoporosis.

In our modelling approach, in order to achieve relevant changes in the absolute number of femoral fractures in 2014, a high participation rate in FPE of persons aged 70–89 years would be needed: 41.8 % of all persons in this age-group would need to participate in order to decrease the number of femoral fractures by 20 %. To lower the expected increase between 2014 and 2025, again high participation rates in FPE would be needed: an increase by 5 % in fractures instead of 24.2 % would require as many as 33.9 % of all community-dwelling older persons to participate in fall-prevention exercise. Translated to Bavaria’s largest city, Munich, to reduce the number of femoral fractures in Munich by 20 % in 2014 this translates to 80.000 persons training. Assuming that half of these persons would train at home and half in groups of 15 persons each, 2667 groups were required.

Although bisphosphonate treatment may be very effective only about 65 % of femoral fractures of persons 65 years and older are attributable to osteoporosis in our model. As a consequence, most persons with osteoporosis would need to receive bisphosphonates in order to reduce the number of femoral fractures: 79.4 % in 2014 and 56.2 % in 2025 to attain above mentioned reductions.

The calculations are based on meta-analyses pooling data from studies with various inclusion criteria. Effect size of FPE was taken from a meta-analysis that included participants with different fall risks at baseline. While some studies included participants only on the basis of age, other studies required the presence of specific risk factors [12]. However, fall risk at baseline does not seem to modify the effect size of FPE and was not considered in our analyses.

FPE studies conducted to date do not have sufficient power to use fractures as primary outcome variable. For our calculations a meta-analysis was used which demonstrated a reduction of all fractures combined, but did not report femoral fractures separately. However, femoral fractures represent the most frequent type of fragility fractures in older age and are nearly always the result of a fall. Therefore, it seems reasonable to assume a linear correlation between fracture incidence and femoral fracture incidence [1].

The effect size of bisphosphonate treatment on fracture reduction was taken from a meta-analysis including studies of four different oral bisphosphonates [13]. Inclusion criteria of these studies varied: some studies required a prior fracture, others recruited based on BMD with different T-score thresholds. In our analyses, we focused on persons aged 65 years and older with osteoporosis and did not consider persons with osteopenia. The incremental benefit of bisphosphonate treatment for persons with osteopenia is lower than for persons with osteoporosis. Including persons with osteopenia, the number of potentially preventable fractures would increase. At the same time, the proportion of persons that need to receive bisphosphonate treatment in order to prevent the targeted number of fractures would increase as well.

The estimated treatment and participation rates are far from the current situation. While some countries such as Australia and the UK may offer population-wide FPE classes, other countries such as Germany are only at the beginning of a wider implementation [24, 25]. Currently, FPE classes are sparse in Germany and there is no registry to estimate the number of classes or participants. The best acceptance of FPE has been observed in settings where FPE is an integral part of a population-based strategy to prevent falls [26]. However, even in countries with established structures such as Australia, a modelling calculation on the impact of population-wide implementation of Tai Chi found little impact on the absolute number of femoral fractures due to low uptake [27]. Uptake by older persons is hampered by numerous beliefs and attitudes [28]. Risk appraisal is particularly low in the “young old” while mobility problems often account for difficulties to reach the “oldest old” [29]. For these reasons we excluded these two age groups from our calculation of FPE participation.

Treatment of osteoporosis faces challenges as well. There is an on-going debate about the best screen-and-treat strategy [30, 31]. Still, osteoporosis is regarded as an under-diagnosed and under-treated condition and even amongst those at high risk of fractures, less than half receive specific medication [32‐34].

Our modelling approach is optimistic in its conception for several reasons. First, we did not consider exclusion criteria for either FPE or bisphosphonate treatment. Furthermore, we did not assume any FPE or bisphosphonate treatment until beginning of the intervention in 2014. As for bisphosphonate treatment, it is estimated that about 10 % of persons with osteoporosis already receive bisphosphonate treatment in Germany [32]. In a sensitivity analysis we assumed identical age- and gender-specific treatment rates. As a result, the proportion of untreated persons with osteoporosis that need to receive bisphosphonate treatment would be slightly higher (e.g. 39.1 % instead of 36.9 % for a fracture reduction of 10 and 97.9 % instead of 92.2 % for a fracture reduction of 25 %). Since these assumptions are based on only vague data we did not include them in the final model. Structured FPE has not been implemented and reimbursed within the health care system until recently. There is no estimate on participation available due to the scarce availability of exercise classes and heterogeneity of providers. Local experts would estimate participation rates to be less than 1 %. As a consequence, we assumed that there was no relevant participation prior to 2014. In a sensitivity analysis we assumed again 10 % participation rates prior to 2014. Applying such an assumption, even more persons aged 70 to 89 years would need to practice FPE in 2014 in order to attain defined reductions in the number of femoral fractures (e.g. 29.6 % instead of 20.9 % for a fracture reduction of 10 % and 59.0 % instead of 52.2 % for a fracture reduction of 25 %).

Furthermore, we did not exclude those with contraindication to bisphosphonate treatment. Chronic kidney disease is the most relevant contraindication. Excluding persons with contra-indications for bisphosphonate treatment, again even higher treatment rates are needed in those eligible to achieve the defined reductions. Second, we assumed effect sizes as reported from trials. However, effect sizes in routine care may be lower than under study conditions due to a lower adherence or persistence to the prescribed treatment and interventions. As for bisphosphonate medication, there are analyses based on drug registries indicating poor persistence and adherence to bisphosphonate treatment that decrease effectiveness of bisphosphonate treatment [35, 36]. Whether new regimes such as once-yearly infusions will help to overcome the issue of adherence and persistence remains uncertain [37].

Furthermore, we assumed that age- and gender-specific fracture rates over time are influenced only by FPE or bisphosphonate treatment. Secular trends could decrease fracture rates in 2025 and could reduce the required participation and treatment rates. Interpreting the results with respect to FPE, one has to bear in mind that fall prevention offers benefits beyond fracture prevention like prevention of other fall-related injuries, reduction of fear of falling or social benefits.

The prevalence of osteoporosis was based on the Rotterdam study which provided age- and gender-specific rates of osteopenia and osteoporosis in a European population [20]. These rates, however, may not apply to populations from other regions of the world. Furthermore, the analyses included only community-living people. In Germany, about 20 % of all femoral fractures occur in institutionalised people [10]. To decrease the absolute number of femoral fractures across all populations, preventive efforts need to be extended to this relevant population.

The burden of femoral fractures will increase considerably within the next years. Both bisphosphonates and FPE are effective measures to prevent femoral fractures. However, unrealistic high treatment and participation rates of these two interventions are needed to achieve substantial effects on the expected burden of femoral fractures in the total population of persons 65 years and older at present and in the future.