Impact d'un service de liaison pour fractures sur des issues cliniques et d'adhésion au traitement, incluant une analyse économique des trajectoires de soins

Introduction. Osteoporosis is an asymptomatic chronic disease until the development of osteoporosis-related fractures. Furthermore, the occurrence of a previous fragility fracture strongly increases the risk of subsequent fractures. Given the current suboptimal management of fragility fractures in usual clinical practice, several secondary fracture prevention strategies have been studied. However, continuous access to care is typically not central to these interventions as they mostly involve only one visit to a specialized healthcare professional. Objectives. This thesis had four main objectives derived from research questions focusing on the implementation of a high-intensity Fracture Liaison Service (FLS) with a systematic follow-up of two years. The first objective was to measure the performance of the intervention using key indicators. The second objective was to report on the utilization patterns of osteoporosis drugs. The third objective was to identify trajectories of compliance to follow-up care. The last objective was to evaluate the economic impact of trajectory groups of compliance to follow-up care with respect to usual care. Methodology. An FLS intervention called the Lucky BoneTM Program was approved as a prospective cohort study and implemented in two hospital-based outpatient orthopedic clinics. The intervention encompassed four components: 1) the identification of fragility fractures in women and men aged 40 years or older, 2) the investigation for bone fragility, 3) the initiation of treatment, 4) the integration of patients to a two-year systematic follow-up. Both clinical and administrative data were collected prospectively and retrospectively to measure the impact of the intervention. The first component of this thesis reported on the performance of the FLS. A cohort study design allowed for the measuring of key performance indicators (KPIs) such as the rates of bone mineral density (BMD) investigation, treatment initiation, and follow-up participation over two years, as well as the incidence rate of subsequent fragility fractures. A secondary outcome was to longitudinally measure the change in bone biomarker levels and questionnaire scores using mixed-effect models. The second component of this work aimed to measure patterns of osteoporosis drug use with a cohort study design by reporting 1 and 2-year persistence rates and compliance levels (compliance being defined as a proportion of days covered (PDC) > 0.8). The third component of this thesis consisted in the identification of trajectory groups of compliance to follow-up care using group-based trajectory modelling (GBTM). The fourth and final component iv of this thesis was a cost-utility analysis using Markov decision analytic models to evaluate the economic impact of trajectory groups of compliance to follow-up care with respect to a usual care in a simulated cohort. Results. Of the 532 fragility fracture patients that provided informed consent, 85.7% were female and the mean age was 63±11 years. First component: The FLS intervention yielded the following KPIs: BMD results were collected in almost 86% upon ordinance in the FLS, a prescription for anti-osteoporosis therapy was handed to > 86% of participants, 83.6% of subjects attended at least one follow-up visit (22.2% attended all visits) over two years, and the subsequent fracture incidence rate was of 2.6 per 100 person-years. Biomarker levels significantly decreased after six months in the FLS, supporting the inhibition of bone resorption induced by therapy. Questionnaire scores showed significant improvement of functional capacity over time (14%-64%). Second component: The one and two-year persistence rates were 66.4% and 55.6%, respectively. The proportions of patients with a one and two-year PDC > 0.8 were 64.2% and 62.5%, respectively. Third component: Through GBTM, three follow-up compliance trajectory groups were identified and consisted of high followers (HF, 48.4%), intermediate followers (IF, 28.1%) and low followers (LF, 23.5%). Fourth component: The incremental cost-utility ratios of the HF, IF and LF trajectory groups relative to usual care were $3,600, $22,000 and $74,000 per quality-adjusted life year gained, respectively. Conclusions. A high-intensity FLS intervention with a systematic follow-up of fragility fracture patients allowed ongoing access to care over a two-year period. This resulted in high rates of investigation and treatment initiation, a low subsequent fracture rate, but follow-up participation could be improved over two years. More than half of the patients were persistent and compliant to therapy after two years. Almost half the cohort had a high compliance to follow-up care trajectory and this behaviour was found to be very cost-effective compared to usual care. The main limitation of this research program was the lack of a control group to assess effectiveness. A large pragmatic randomized controlled trial is needed to support these results. Further research should focus on understanding behaviours related to compliance to care using patient-centered outcomes, especially considering the high risk of fractures over time.

Keyphrases: Osteoporosis, fragility fracture, secondary prevention, fracture liaison service, indicators of performance, drug use, anti-osteoporosis therapies, trajectories of care, economic evaluation