General and Specific Considerations as to why Osteoporosis-Related Care Is Often Suboptimal

As shown by the studies cited above, antiresorptive treatment rates both in primary and secondary fracture prevention increased until 5 to 10 years ago. The clinical situation was bolstered by policy and risk assessment advances, including the use of FRAX® and other risk calculators [22, 23] and guidance on intervention [15], combined with the availability of cheaper, generic bisphosphonates. In spite of this, outwardly prospering field treatment rates have declined in recent years, both in those at high risk of fracture and in those who have suffered a fracture, despite the huge expansion of the at-risk population [24].

Many factors appear to contribute to this phenomenon. One such reason is that strategies at a national and international level have not been implemented sufficiently to impact primary and secondary preventions. For patients and clinicians alike, the idea of managing a future “risk” makes primary fracture prevention more difficult, rather than treating a disease event which has already impacted upon the patient. Musculoskeletal diseases in general are viewed by policymakers and patients alike as a of lesser importance than outcomes such as cancers and heart disease [1], despite the fact that the musculoskeletal disease has been shown to be a leading course of disability worldwide by the Global Burden of Disease initiative [25].

In the case of osteoporosis, there is a stark mismatch between the perceived and actual severity of the condition. Many do not recognise that, for example, a hip fracture is associated with a 20% associated reduced survival compared with non-fracture peers and as such is a devastating life event [26]. Contrast this with a parallel event such as an acute myocardial infarction; it would be impossible to imagine that it would be acceptable in the developed world for less than 50% of such cardiac patients to receive risk-reducing therapies such as aspirin and other antiplatelet agents, antihypertensives and statins [27]. The large international women’s cohort, GLOW, clearly documents this risk misperception, in which many underestimated their own fracture risk in comparison with their peers [28]. Perhaps, in a world where many populations are ageing and physicians and patients are dealing with multimorbidity, osteoporosis treatment falls to the bottom of the priority list.

Physicians’ perceptions of osteoporosis and efficacy of treatments have been further confused by harmful and inaccurate conclusions about the treatment of osteoporosis in high impact journals including the British Medical Journal and Journal of Internal Medicine [29, 30]. These articles, claiming, for example that “the dominant approach to hip fracture prevention is neither viable as a public health strategy nor cost effective” and that “the main ways to prevent these fractures have not changed in nearly 25 years: stop smoking, be active and eat well” are frankly incorrect, unbalanced and refuted by overwhelming evidence (as stated by international and national societies such as the International Osteoporosis Foundation and the American Society for Bone and Mineral Research); nonetheless, such “fake news” presented in high impact journals has traction, and clear damage has been done [31].

There are abundant data showing that alarming reports about osteoporosis medication in the media have been followed by a reduction in use of these medications, despite evidence that the benefits of treatment clearly outweigh the risks for the vast majority of users [32]. In order to better understand patients’ concerns regarding medication safety, Jha et al. used data from the Medical Expenditure Panel Survey and National Inpatient Sample in the USA to examine relationships between medication use, internet searches for alendronate between 2006 and 2010, and safety concerns reported in the media [21]. Clear spikes of internet search activity were observed to correspond to events such as a 2006 lawsuit filed against Merck (for Fosamax allegedly causing osteonecrosis of the jaw (ONJ)), an ABC World News feature in 2010 on the associations between Fosamax and atypical femoral fractures (AFFs), and various other reports in the media of serious but rare side effects, set in parallel with the regression in bisphosphonate use by more than 50% between 2008 and 2012. The Australian Longitudinal Study on Women’s Health findings was in keeping with the findings from the USA; antiosteoporosis medication use grew over the period 2000 to 2007 but then shrank from 2007 to 2010. In Australia, interventions to remedy this, including the relaxation of the indications for bone density testing and a subsidy for antiosteoporosis medications, had little effect, the most marked declines in prescriptions coincided with negative press for antiresorptive therapy such as a 2007 major report on ONJ [33].

In absolute terms, the serious long-term adverse side effects of bisphosphonates are very rare (with incidences in ranging from 1/100,000 to 1/10,000 per year) [34]. However, the approach to risk/benefit communication has largely been on the side of declaring risk, amongst the media (as demonstrated above), physicians and policymakers. The substantial impact of the underlying condition on morbidity and increased mortality, with fracture risk markedly decreased by antiosteoporosis medications, appears often forgotten in these discussions. For example, UK National Institute for Health and Care Excellence (NICE) recently issued guidance on multi-morbidity [35] and targeted bisphosphonates for review after 3-year treatment despite the evidence for their longer-term efficacy and safety being of greater reliability than the other treatments considered for 3-year review.

In a recent review of the benefits versus risks for BP therapy [36], the benefits for fracture reduction for short-term therapy for 3 to 5 years was shown to far outweigh any risks of AFFs. Using the set of assumptions about AFF risk with best evidence (relative risk of 1.7 for any BP use [37]), the study states that treating 10,000 osteoporotic women for 3 years would lead to the prevention of 1000 fractures (including 110 hip fractures) whilst causing only 0.08 AFFs. Put another way, for one AFF associated with 3 years of BP treatment, 1200 fractures (including about 130 hip and 850 vertebral fractures) would be prevented [38•].

In longer-term users, the concerns regarding the rare side effects of AFFs and ONJ are compounded by studies suggesting that longer therapy duration increases these risks. This has led to the widely held opinion that all patients on long-term treatment with bisphosphonates or denosumab should be offered a treatment holiday; however, the existing evidence does not entirely support this. For example, following denosumab discontinuation, rapid bone loss has been described, with around a 5% incidence of vertebral fractures [39], indicating that treatment holidays on denosumab should not be offered without replacing with another anti-osteoporosis therapy. In terms of long-term bisphosphonate use, reassuringly, a Danish study has demonstrated that users of alendronate, even after 10 years of use, have a lasting reduction in fracture risk compared with matched controls, and that the number of hip fractures prevented is still substantially greater than the number of subtrochanteric femoral fractures occurring [40]. A new systematic review led by the International Osteoporosis Foundation has concluded that drug holidays should only be considered in patients at low fracture risk [41••]. Thus, it is evident that the osteoporosis field needs to vastly improve its approach to communicating the balance of treatment risks and benefits and to work towards countering poorly evidenced stories in the media as and when they occur.

Osteoporosis, when compared with other non-communicable diseases, has rarely attracted justifiable levels of attention from governments, policy makers and healthcare providers. National policies on access to and reimbursement of measurement of bone density with dual-energy x-ray absorptiometry (DXA) will have a great impact on the assessment and treatment of this disease. Various regional audits have been published by the International Osteoporosis Foundation (IOF) (https://​www.​iofbonehealth.​org/​regional-audits) covering Latin America, the European Union, Eastern Europe the Middle East, Africa, Central Asia and Asia Pacific. These have demonstrated large variations in terms of the epidemiology, financial and societal costs, and burden of osteoporosis e.g. in the Asia Pacific region, whilst Hong Kong, Japan, Republic of Korea, Singapore, Australia and New Zealand had 12–24 DXA machines per million of population, India, Pakistan, China, Indonesia, Philippines, Sri Lanka and Vietnam were severely under-resourced, having less than 1 DXA machine per million of population. The audits demonstrated that insurance or healthcare policies in many countries did not reimburse BMD testing and osteoporosis treatment which served as a barrier to osteoporosis care access. Similar inequalities were seen in Europe, where it was calculated that 11 DXA machines per million of population were needed for adequate osteoporosis care provision. Only 16 European countries fell into this category of “adequate” provision, and 9 countries were considered to have “very inadequate” provision with fewer than 8.4 DXA units per million (the UK, Luxembourg, Czech Republic, Hungary, Bulgaria, Latvia, Lithuania, Poland, Romania and), as shown in Table 1 [42]. In addition, reimbursement for DXA scanning was extremely variable between EU member states, with reimbursement for DXA only offered if the BMD turned out to show osteoporosis in certain countries (Bulgaria and Switzerland), only if BMD was measured after a fracture (Germany), or only if the patient was referred by a specialist (Poland).

Whilst no official IOF audit is available for North America, treatment reimbursement also varies greatly, depending on each patient’s health insurance. The evolution of healthcare reform in the USA from a “fee for service” system to a system which supports improved disease prevention and care coordination, with financial incentives to encourage healthcare professionals or systems to improve patient outcomes, ought to improve osteoporosis detection and treatment. However, the number of DXA providers has fallen following a major drop in reimbursement in this area, resulting in over 1 million fewer DXA scans performed per year in women aged 50–64 in recent years [43], a change which coincides with a plateau in the secular decline (up until 2012) in age- and sex-adjusted hip fracture rates [44].

As described by the evidence detailed above, fragility fractures represent a huge burden on societies worldwide. Patient perception of fracture risk is often underestimated as osteoporosis is a silent condition until a fracture happens [45, 46], so primary prevention initiation is usually reliant on health care practitioners who need to have the time and incentive to assess fracture risk and explain the purpose of treatment to their patients. Secondary prevention, in which patients are identified for treatment on the basis of a previous low trauma fracture, is therefore the approach usually taken.

Several methods have been explored to enable fracture risk assessment and initiation of appropriate treatment—some based upon staff, others on IT and others upon a combination of the two. The multi-disciplinary Fracture Liaison Service (FLS) is one of the most successful of these systems [47, 48], incorporating rheumatologists, orthogeriatricians, other physicians, clinical nurse specialists and allied health professionals. Members of the FLS multidisciplinary team, coordinated by a lead clinician, work together to optimise the medical management of patients admitted with fracture, both in hospital and for long-term fracture prevention. [49•]. “Capture the Fracture®”, an initiative instituted by the International Osteoporosis Foundation (http://​www.​capturethefractu​re.​org/​), is “a global campaign to facilitate the implementation of coordinated, multi-disciplinary models of care for secondary fracture prevention.” Capture the Fracture has provided secondary fracture prevention guidance, and also a global map of secondary fracture prevention services, with a quality grading scheme, graded by assessed application and description of the service [50, 51]. This scheme has helped to document the huge variation in the quality, scope and availability of secondary prevention facilities, not only within but also between countries. The Capture the Fracture initiative aims to raise the quality and coverage of these services and has been shown to be both clinically valuable and cost-effective [52].

Vertebral fracture case finding is an additive approach to secondary fracture prevention as many such events go undetected—it has been shown that around 12% of postmenopausal women with osteoporosis have one or more vertebral deformities, but fewer than one in three of these individuals come to clinical attention [53]. Primary care-based screening strategies [54] and history taking methods distinguishing “vertebral fracture-type back pain” from other types of back pain may assist their detection [55]. Different methods for radiological assessment of vertebral fractures exist, including radiographs, CT scans and vertebral fracture software in DXA. The automated detection of prevalent vertebral fracture on CT scans using artificial intelligence technologies will be another avenue for secondary fracture prevention [56, 57].

In osteoporosis, there is an ongoing debate regarding the benefits of a widespread systematic screening approach, leading to higher treatment rates (with its associated cost and side effect risk), and a case finding approach focused on those at highest individual risk (with its associated issue of under-treatment). Whilst DXA-based osteoporosis screening is officially a standard policy in the USA (at age 65 years in women, age 70 in men, and in individuals over 50 years who have suffered a fracture as an adult) [58], in the majority of countries, population screening is not judged to be cost-effective. Primary prevention is therefore generally focused on case finding strategies, reliant on the physician identifying clinical risk factors [15‐17, 59].

In the UK, a randomised controlled trial across seven centres was recently undertaken (the UK SCOOP study), examining both the clinical and cost-effectiveness of screening older women in primary care for primary fracture prevention. Around 12,500 older women were randomised to either screening and subsequent treatment (stratified using FRAX hip fracture probability) or usual care. The screening intervention was shown to lead to reduction in hip fracture risk by 28% (Fig. 3) [60, 61••]. Those at highest baseline fracture risk appeared to benefit most from screening (as would be expected, since these were the individuals targeted for treatment) [62], and importantly, were shown to be cost-effective (the cost per quality adjusted life year (QALY) gained was £2772 compared with the control arm) [63]. The finding that women who were identified by FRAX as moderate or high risk of fracture benefited most from a screening programme was supported by the Danish risk-stratified osteoporosis strategy evaluation (ROSE) study, though this study found no overall effect on fracture incidence of a screening strategy [64]. A recent evidence report and systematic review for the US Preventive Services Task Force concluded that screening to prevent osteoporosis in women may reduce hip fractures [65].

Once a patient has been identified as requiring fracture risk assessment, the threshold at which treatment should be given will vary according to factors such as healthcare provision, willingness to pay and cost of medications [5]. The majority of guidelines internationally use FRAX as the arbiter of fracture risk, but 38 of the 120 guidelines identified in a recent systematic review gave no direction on translating FRAX probabilities into a treatment decision [23]. Threshold setting is as much a philosophical as scientific process, which decisions around whether a level should be fixed, or age dependent, and calibrated to the specific country. Given the marked variation in fracture rates between countries, this latter consideration seems mandatory, and the benefits and caveats associated with fixed or age-dependent thresholds are presented in detail in [23]. In the UK, FRAX is linked to the age-dependent (up to the age of 70 years) thresholds of the National Osteoporosis Guideline Group (NOGG) [17], with the threshold predicated on the probability of future fracture conferred by a prior fracture. This approach has been shown to be cost effective in the UK, and contrasts markedly with that of the UK National Institute of Health and Care Excellence (NICE). In the 2017 technology appraisal of bisphosphonates [66], a pure health economic approach, in the context of a very common disease and extremely inexpensive therapies, led to a 1% risk of major osteoporotic fracture over 10 years as the threshold above which these medications were considered cost-effective. Unfortunately this was often interpreted as payers as an intervention threshold, a situation which if permitted to continue would have resulted in many adults at low risk of fracture being inappropriately treated [67], but which was later resolved by referral to NOGG guidance for clinical, rather than health economic thresholds [68].