Anti-osteoporosis drug prescribing after hip fracture in the UK: 2000–2010

The last decade has seen a striking change in prescribing practices for anti-osteoporosis drugs following a hip fracture. The probability of initiating anti-osteoporotic treatment has increased dramatically, particularly for patients over the age of 75 years. It was also apparent that the initiation of anti-osteoporosis drugs was paired with the initiation of calcium/vitamin D supplementation. However, this encouraging trend slowed down from 2006 onwards. Ultimately, the overall prescribing rate has remained inadequate with just over 50 % of hip fracture patients not receiving any anti-osteoporosis drug in 2010. The factors which were associated with reduced likelihood of receiving anti-osteoporosis drug therapy were male gender, being overweight, having dementia or exposed to certain psychotropic drugs (antipsychotics, sedatives/hypnotics) or opioid analgesics.

Our findings of a steady increase in the prescribing of anti-osteoporosis drugs up until 2005 are consistent with most studies performed in other countries [15‐19] and form an extension to the study performed on the former version of the CPRD (GPRD) for the period 1991–2005 by Watson et al. [20]. The pattern of anti-osteoporosis drug prescribing may be reflective of changes in bisphosphonate formulation, advice from various committees and changes to NHS guidelines. As from 2005, there was a pronounced difference in prescribing of anti-osteoporosis medications between patients under and over 75 years. This is most likely a consequence of the NICE Technology Appraisal 87 published in 2005 [28], which advocated the use of anti-osteoporosis therapies without the need for prior dual energy X-ray absorptiometry (DXA) scanning for women over the age of 75 years who had already suffered a hip fracture. This, however, does not explain why the prescribing rate plateaued for those <75 years. We have no clear explanation for this phenomenon, but it may be partly related to the actual proportion of hip fractures that was attributable to osteoporotic BMD. This proportion has been reported to a range between 28 and 64 %, depending on age and sex [29, 30]. Since DXA-derived diagnosis of osteoporosis has been the cornerstone for indicating anti-osteoporosis drug therapy, an increase in DXA referrals may not necessarily have resulted in a further increase in anti-osteoporosis drug prescribing as osteoporosis may subsequently not have been diagnosed for many younger hip fracture patients. Furthermore, the cost of anti-osteoporotic drugs has been reduced further since the release of generic forms of alendronic acid in August 2005. Subsequently, NICE guidance (TA161) endorsed alendronic acid as the first-line therapy. This resulted in the stabilisation in the prescribing of risedronic acid in 2005 whose use then went into decline [26]. The majority of anti-osteoporosis drug prescribing was paired with the prescribing of vitamin D/calcium supplements which is in line with clinical guidelines. Another UK study that was conducted in 2006 among nine general practitioner practices showed that 34 % of patients were co-prescribed calcium and/or vitamin D with anti-osteoporosis drugs [23]. This coincides well with our results with a cumulative incidence probability of 39 % in 2006. Unfortunately, there was a considerable number of patients who only received vitamin D/calcium supplementation.

Inline with the results by Wang et al. [31], we found a slowing down in the increasing prescribing trend from 2006 onwards, while an Australian study showed a decline between 2007 and 2010 [32]. Reasons for the stagnation or even decline in anti-osteoporosis drug prescribing may coincide with revised labelling of bisphosphonates for risk of osteonecrosis of the jaw in 2005 and reports for increased risk of atypical femoral fractures and atrial fibrillation, with increasing publicity in the years thereafter. A US study showed a decline in use of anti-osteoporosis drugs after hip fracture from 2002 onwards (40.2 % in 2002 to 20.5 % in 2011) [12]. Together with the possible influence of safety issue reports, this could have been attributed to a fragmented health care system with a lack of, or insufficient, communication between emergency/orthopaedic departments and outpatient care for follow-up osteoporosis assessment. A service model to bridge this gap, the Fracture Liaison Service (FLS), now exists for over a decade in the UK which has proven to reduce the care gap for secondary fracture prevention [33]. However, this care model has been developed in 27 % of UK NHS Hospital Trusts prior to 2006, which has barely increased to 29 % by 2009. This is in line with the flattening in prescribing rates for this period.

Few studies have examined which factors lead to the initiation of anti-osteoporosis drugs after hip fracture. Many of the factors which increase the risk of fracture were also significant determinants for initiation of anti-osteoporosis drug therapy. Hence, female gender, increasing age (except for very old age), a history of major osteoporotic fracture, rheumatoid arthritis, secondary osteoporosis and the use of corticosteroids all increased the likelihood of receiving osteoporosis treatment which is in line with previous studies [12, 34‐37]. Conversely, patients who were suffering from mental illness (i.e. using antipsychotics, sedatives and hypnotics or having dementia) or patients who were overweight or used opioid analgesics were less likely to receive osteoporosis therapy. Other factors which have been associated with the initiation of anti-osteoporosis drug treatment are patients’ self-perception of osteoporosis risk [34] and their appraisal for their treatment need [38], but these could not be identified in our data. The fact that an increasing number of prescriptions was not inversely associated with the instigation of osteoporosis therapy was unexpected given the findings of Duyvendak et al. [39] who found that poly-pharmacy was a barrier to osteoporosis treatment in long-term corticosteroid users. The study of Solomon et al. [12] even found an increased likelihood of being prescribed anti-osteoporosis drugs with increasing number of prescriptions which was also conducted among hip fracture patients. Consistent with other findings is the observation that male hip fracture patients were less likely to be prescribed anti-osteoporosis drugs than female patients [12, 16, 40]. The difference in prescribing patterns between men and women is likely partly due to osteoporosis primarily being considered a health problem of older women [41, 42], rather than of men; consequently, men often have poor knowledge of the condition and therefore do not consider themselves as susceptible [43, 44] and hence would not consider asking their GP for treatment. Furthermore, the number of clinical trials examining the effect of bisphosphonates on fracture reduction in men is limited, where the majority of trials used change in bone mineral density (BMD) as the primary end point [45, 46]. The few trials into the effects of bisphosphonate use on fracture reduction in men and lack of clinical guidance for anti-osteoporosis drug prescribing for men may explain why GPs do not habitually provide bisphosphonate treatment to men. However, seeing as the bisphosphonate has a similar effect on bone turnover and density in both men and women, the difference in prescribing habits is likely unjustified.

We studied a large community-dwelling population representative of the UK as a whole. However, there are several limitations that should be considered in the interpretation of our results. By studying hip fracture patients, we have assumed that all of our study population was eligible for anti-osteoporosis medication according to a confirmed diagnosis of osteoporosis, while this may not necessarily have been the case. BMD measurements are not routinely available in the CPRD which limits our interpretation as to the eligibility for treatment. Additionally, it is possible that some fractures were pathological or due to trauma. Furthermore, we have only considered initial prescription rates and did not include repeat prescriptions. Therefore, we cannot make any comments regarding adherence with treatment. It is well known that a large proportion of patients do not adhere to their treatment regimen, although the exact reasons for this phenomenon remain poorly understood [47]. Zoledronic acid as well as PTH analogues (teriparatide) and denosumab are not fully captured in CPRD records as this database only includes prescriptions issued by general practitioners and not specialists. This may have resulted in an underestimate of anti-osteoporosis therapy initiation. However, denosumab became available in the UK at the end of the study period (2010), and although we cannot directly estimate the magnitude of this limitation for PTH analogues and zoledronic acid, indirect evidence from other countries has shown that the utilisation of these drugs remained limited until the year 2010 [12, 32]. Furthermore, NICE guidance places teriparatide under restrictive conditions for the secondary prevention of fragility fractures. Similarly, data for non-prescription over-the-counter vitamin D or calcium were not available in our database, which may have resulted in an underestimate of use of these drugs. Finally, the generalisability of this study is limited to free-living individuals as it excluded those who were institutionalized. Just under 10 % of the patients transferred out of the database, most likely to nursing homes where prescribing practices could differ.

In conclusion, our study has shown that although the prescribing rate for anti-osteoporosis medications has increased substantially since 2000, the overall rate in 2010 was still markedly inadequate. This was particularly so in men, where the prescribing of anti-osteoporosis drugs was notably less than that observed in women at any given point in time. Other patient characteristics that were associated with decreased likelihood of receiving anti-osteoporosis drugs were being overweight, having dementia and exposed to antipsychotics, sedatives/hypnotics or opioid analgesics. Increase in the prescribing of anti-osteoporosis medications may be facilitated by recent major advances in risk assessment, such as the FRAX calculator [48], linked to treatment thresholds, as exemplified by the UK NOGG Guidelines [49]. There is much work to promote secondary fracture prevention services [50], notably by the current International Osteoporosis Foundation Capture the Fracture initiative [51]. With the absolute number of hip fractures expected to increase inexorably across the world over coming decades, our findings clearly demonstrate the acute need for such activity and for the generally increased awareness of osteoporosis and prevention of fragility fracture.