The present study reports on long-term persistence of treatment with AOM in patients with hip fracture in the context of FLS. Our comparison of FLS with standard management clearly shows the differences in persistence of treatment after hip fracture (72% vs 14% at 12 months and 59% vs 12% at 3 years). In addition, our data support the effectiveness of the FLS model for hip fracture, and indicate that recommendations on treatment should be made at admission, since the persistence to treatment is higher and the number of patients included might be potentially higher, and that the approach could prove more cost-effective, given the lower number of outpatient visits and tests such as DXA.
Only a fifth of patients who sustain a fragility fracture receive AOM (5). Analysis of the studies included in a systematic review showed lower mortality after hip fracture associated with AOM, mostly bisphosphonates (6). Kim et al reported the use of AOM in 3 cohorts of patients after hip fracture (United States, Korea, and Spain). In the year before the index fracture, 16-18% were taking AOM, with an increase to 11-39% at 3 months. For those who received ≥1 prescription for AOM, the mean proportion of days covered in the year after the fracture was 43-70% (1). Another study of hip fracture found that 48% of patients started AOM after discharge, but that only 34% of those prescribed treatment reported still taking their medication 1 year later (7). In other words, only 16.3% of the original total were on treatment 12 months after discharge. A multicenter, prospective cohort of 5,456 hip fracture patients in England and Wales found that 52% were prescribed AOM at discharge and, of these, 33% reported still taking their medication 120 days later (8), that is, 17% of the original total were taking AOM 4 months after discharge. These results are in line with our data on standard care: persistence in patients not cared for by the FLS in our hospital was 14% at 12 months.
In its 2019 summary (13,181 patients), the Spanish registry of hip fracture reported the prescription of AOM in 5.9% of patients before the fracture and 42.8% at 30 days after discharge. These data were similar to those reported in the 2017 and 2018 summaries (9). In the analysis of UK primary care prescriptions of any AOM after hip fracture, 5% of patients were prescribed AOM in 1999, increasing to 51% in 2011 before decreasing to 39% in 2013 (10). Neither the Spanish registry nor the UK registry (9, 10) has reported 1-year adherence, which, as previously described, is usually reduced by approximately half in standard care.
In summary, initiation of AOM after hip fracture in standard care seems to have improved in recent years in some countries, although adherence at 12 months remains low (around 20%).
The FLS model is associated with more frequent initiation of treatment. One systematic review found that, compared with standard management, FLS-based care increased initiation of treatment by 20 percentage points (2). However, adherence rates vary depending on the study. For example, a US study found that of the 1,840 patients from an FLS who were initially prescribed medication, 77% initiated AOM and 62% remained adherent to treatment (11). Chandran et al. (12) reported a 2-year adherence of 75% in 938 patients from Singapore, while a study of patients discharged from an FLS ≥12 months in Australia showed that 74% self-reported adherence to bisphosphonates (13). In an FLS in Lille, France, parenteral drugs were prescribed to most patients, with a primary adherence of 75% (14). However, results from other FLS experiences were less optimistic. The FLS Database of the Royal College of Physicians reported a mean adherence at 12 months of 23% (range, 7-73% between FLS) (15), and a French FLS found that less than half of patients adhered to the 1-year follow-up course and that this was strongly associated with adherence to treatment (16). In the same way, a Spanish FLS reported adherence of 35% to oral bisphosphonates at 12 months in patients with hip fracture (17). On the other hand, the FLS from Seville reported treatment adherence in the first year after of 96% in both sexes (18).
The FLS model is effective compared with standard care, although not all patients with hip fracture are candidates for treatment, since they may have serious comorbidities or a very short life expectancy. In addition, the patient or the patient’s family or primary care physician may reject initiation of AOM. Taking all these aspects into account, the most favorable expectation 1 year after hip fracture is that up to 60% of patients who survive remain in treatment. In other words, when analyzing adherence, we must consider whether the patients included comprise all discharged hip fractures or only those for whom treatment with AOM has been recommended.
Regarding the reasons for the high compliance rates related to the FLS model, a study found that patients with fragility fractures resulting from osteoporosis had greater adherence to medication. Thus, the study highlighted the key roles of FLS staff in helping patients recognize fragility fractures as a sign of underlying bone disease and encouraging adherence to care recommendations (19). In addition, a single education session on bone health at baseline was shown to be associated with increased adherence (13). Follow-up was associated with better adherence in the same study: at the time of telephone contact, one-third of patients required further advice to optimize their bone health (13).
Patients who do not withdraw their medication from the pharmacy after the recommendation of the FLS represent an unresolved issue. In our previous report (20), the reasons for the lack of initiation of treatment in the first 12 months were as follows: patient refusal to take treatment, 30%; unknown reasons, 29%; AOM not started by the primary care physician, 21%; gastrointestinal complaints, 9%; polypharmacy, 6%; and other diseases, 2%. After analyzing these results in our FLS and taking into account our efforts to achieve greater adherence to treatment after baseline visit, we began to fill the electronic prescription of the first treatment one week after the baseline visit (both inpatient and outpatient). This procedure is monitored by the medical coordinator after reviewing and signing the report. The patient is then contacted by telephone notifying of the prescription and reinforcing the message provided by the nurse a week before.
Poor adherence to bisphosphonates for treatment of osteoporosis increases the risk of fracture. A meta-analysis of 5 articles (234,737 patients) reported a mean PDC of 67% (3). The authors observed a 46% higher risk of fracture (higher for clinical vertebral fractures) in non-adherent patients than in adherent patients.
We previously reported results on medium- and long-term persistence of treatment in the FLS (20, 21). The analysis presented here on hip fractures followed for at least 3 years revealed better persistence of AOM than those observed in standard clinical practice (persistence of alendronate and denosumab at 12 and 24 months in standard practice of 47-65% and 28-45%, respectively) (22).
In a Canadian study on adherence in the context of FLS, PDC at 1 year was >80% in 66.4% of patients who started treatment in the first 3 months (23). Our results at 1 year were similar to those of the Canadian study, with a PDC >80% of 68.3% (50.9% across the whole sample) for the entire follow-up. Other reports from the USA and France showed a PDC >80% of around 60-70% (11, 14).
We found that around 60% of patients for whom treatment was indicated were adherent for at least 3 years. Considering that clinical trials with drugs for osteoporosis generally last ≥3 years, the percentage of patients who adhere to treatment for at least 3 years seems a relevant indicator of the effectiveness of an FLS.
There are few studies on adherence to osteoporosis treatment over 2 years, and none report on the FLS model. An observational study with a large sample showed that 25% of incident users of bisphosphonates continued taking treatment for up to 3 years and 14% for up to 5 years (24). In the randomized SOS study, adherence at 3 years was 46% (25), while in the SCOOP trial, adherence at 5 years was 26% (26). Persistence in our FLS after a mean 5 years of follow-up was approximately 47%, i.e., almost twice that observed in non-FLS studies.
In the present report, we found a non-significant PDC >80% in patients seen by the rheumatologist compared with a first prescription made in primary care (63% vs 54%). A Danish study found a similar persistence of AOM at up to 5 years in patients with osteoporosis, irrespective of whether they were treated by a specialist or primary care physician (27).
An analysis of UK primary care prescriptions revealed the independent predictors of initiation of treatment to be female sex, not being obese, and living in the northeastern region of the country (10). Another study from Spain showed that patients treated within 3 months of hip fracture discharge were more likely to be female, to have had previous osteoporosis treatment, to have a diagnosis of osteoporosis and rheumatoid arthritis and to use oral corticosteroids (29). Female sex is thought to be linked to greater persistence (20), since both physicians and patients are less likely to associate osteoporosis with male sex. In our study, previous treatment with AOM was associated with prescription and persistence to treatment. In our opinion, the association of persistence with previous bisphosphonate treatment is equally obvious, i.e., for patients who have already received these agents, FLS messaging reinforces the benefits of maintaining treatment. We found a higher rate of persistence to denosumab than for oral bisphosphonates, as reported in studies outside the FLS setting (7, 29).
We also report the first finding of an association between PDC and inpatient identification of fracture. This association is interesting, because it has consequences for patient management, reinforces the role of the nurse, and may increase the effectiveness of the FLS model. Organization of the FLS based on a nurse and a coordinator, as well as a strong liaison with primary care, is probably the best option for secondary prevention after hip fracture. In this context, a UK analysis showed that, compared with standard care, it is cost-effective to introduce an ortho-geriatrician- or a nurse-led FLS secondary care service for patients with hip fracture, mainly because of the effects on mortality as opposed to refracture. (30)
FLS reduces the frequency of refractures and mortality (1). In a Dutch study, patients who were fully assessed after fracture at an FLS and were recommended bisphosphonates had substantially lower risks for both subsequent fragility fractures and mortality (31, 32). Although we observed a lower incidence of hip refracture in patients with a prescription of AOM, the sample of patients was too small to draw conclusions on mortality and refracture.
The main limitation of our study is its partially retrospective observational design. However, the number of patients analyzed was high, and the quality of the electronic prescription data from a public healthcare system was good. The results of our study cannot be generalized to all FLS models, since the baseline visit was managed mainly by nurses and because many of the prescriptions were made by primary care physicians.
In conclusion, long-term persistence of AOM after hip fracture in an FLS unit was around 60%. Eight out of 10 patients who started treatment adhered to their regimen for at least 3 years, and this adherence was higher when the baseline visit was in the inpatient setting.