Patient Characteristics

From 2,255,224 patients in the BIG-PAC® database, a total of 22,142 women met the study eligibility criteria: 3190 with an index event of a first FF (cohort 1) and 18,952 with an index event of PMO diagnosis (cohort 2). The attrition table is presented in Fig. 2.

Fig. 2

Attrition table. If a patient’s activity in BIG-PAC® stopped during the follow-up, it is then considered as a loss of follow-up. FF fragility fracture, PMO postmenopausal osteoporosis, OP osteoporosis

Patient characteristics for both cohorts are presented in Table 1 and Supplementary Table S7. Women in cohort 1 were older than those in cohort 2 (mean [SD] age, 75.4 [10.2] vs 71.8 [10.8] years) and had a higher comorbidity burden (mean [SD] CCI score 1 [1.3] vs 0.6 [1.1]) (Table 1). Across both cohorts, other inflammatory arthropathies (than rheumatoid arthritis and osteoarthritis) and hypertension were the most common comorbidities (Supplementary Table S7).

Table 1 Patient characteristics at the index event of a first FF (cohort 1) or PMO diagnosis (cohort 2)

In cohort 1 (index event of a first FF), the most common index FF was vertebral, followed by hip/femur and forearm/wrist/radius fractures (30.8%, 21.2%, and 16.1%, respectively) (Table 1). Over half (59.2%) of the women in cohort 1 were subsequently diagnosed with PMO. Diagnosis frequencies increased with age (from 37.4% in women aged 50‒59 years to 74.4% in women aged ≥ 80 years) (Fig. 3i). They were highest among women with vertebral fractures (83.9%), followed by those with hip/femur and forearm/wrist/radius fractures (78.1% and 62.4%, respectively) (Fig. 3ii). The percentage of fractures was similar across age groups (Fig. 3iii). Traumatologists, followed by general practitioners, diagnosed FF most frequently (Fig. 3iv).

Fig. 3

Percentage of fractures in cohort 1. i Fractures by age group (the proportion of the fractures within each group for which there was a PMO diagnosis in parallel to the FF is shown in light blue). ii Fractures by fracture site (the proportion of the fractures within each group for which there was a PMO diagnosis in parallel to the FF is shown in light blue). iii Fracture sites within each age group. iv Fractures diagnosed by particular specialists. PMO postmenopausal osteoporosis, FF fragility fracture

OP Treatment Following First FF or PMO Diagnosis (Index Date)Treatment Gap

OP treatment frequencies following the index event (first FF or PMO diagnosis) are summarised in Fig. 4. Over 40% (1325/3190 [41.5%]) of women in cohort 1 (first FF) and approximately one-quarter (4477/18,952 [23.6%]) of women in cohort 2 (PMO diagnosis) were not prescribed OP treatment (but could be receiving calcium) in the 6 months after the index event (Fig. 4i) (treatment gap). Excluding calcium, 61.1% (1950/3190) and 40.8% (7735/18,952) of women were not prescribed treatment, respectively.

Fig. 4

i OP treatment prescription in the 6 months following a first FF (cohort 1) or PMO diagnosis (cohort 2). Non-treated patients include those who were taking calcium only or in combination with vitamin D or analogues. ii Percentage of non-treated and treated patients within each fracture site (cohort 1, n = 3190; 6 months after the index event). iii Presence or absence of a previous OP treatment in women starting OP treatment in the 6 months after the index event. iv OP treatment prescription by the site of first FF (cohort 1, n = 3190; 6 months after the index event); the asterisk is used to reflect that iii comes from the population squared in i. FF fragility fractures, OP osteoporosis, PMO postmenopausal osteoporosis

In cohort 1, the treatment gap varied by fracture site, being largest in women with clavicle/rib/phalangeal (55.4%), humerus (50.5%), and forearm/wrist (50.9%) fractures (Fig. 4ii). Among women prescribed OP treatment, and compared with cohort 2 (PMO diagnosis), those in cohort 1 (first FF) were more likely to have a history of prior (to their index date) OP treatment (30.7% vs 4.5%) (Fig. 4iii). In cohort 1, the most treated fracture site was the vertebral/cervical/spine region (Fig. 4iv).

Osteoporosis Treatment

Patients in cohort 2 were prescribed a higher number of OP treatments in the 2 years after the index event (mean [SD], 1.4 [0.8] vs 1.1 [0.8]) and were more likely to be prescribed bisphosphonates and other drugs affecting bone structure and mineralisation (48.0% vs 30.1% and 36.5% vs 18.5%, respectively) (Table 2).

Table 2 OP treatment in the 2-year observation period (overall and by cohort)Time from Index Date to Osteoporosis Treatment

The mean (SD) time from index date to OP treatment initiation was 41 (114.12) days in cohort 1 and 52 (273.9) in cohort 2; the median time to treatment was 10 days in both cohorts (Table 2). The median (IQR) treatment duration was higher in cohort 1 vs cohort 2 (609 days [272–730] vs 496 days [142–730]) (Table 2).

Concomitant Medications

The most common concomitant medications were proton pump inhibitors, followed by benzodiazepines (Supplementary Fig. S2i). Women in cohort 1 were more likely to take five or more medications (polymedicated) than those in cohort 2 (4.8% vs 3.7%) (Supplementary Fig. S2ii).

Persistence with Osteoporosis Treatment

Across both cohorts, persistence with OP treatment decreased over time, from 82.7% and 72.0% at month 6 to 32.2% and 27.6% at 24 months in cohorts 1 and 2, respectively (Fig. 5i). Twenty-four-month persistence increased with age (Fig. 5ii) and was below 33% for all OP treatments in the overall population, except for denosumab and other drugs affecting bone structure and mineralisation (Fig. 5iii). In cohort 1 (FF), 24-month persistence was highest in women with vertebral fractures (35.2%), followed by clavicle/rib/phalangeal (21.4%), hip/femur (20.9%), and forearm/wrist/radius (14.5%) fractures (Fig. 5iv).

Fig. 5

Treatment persistence. i Treatment persistence at 6, 12, and 24 months. ii–iv Treatment persistence at 24 months summarised by ii age, iii OP treatment, and iv fracture site. Cohort 1 corresponded to patients with a first FF; cohort 2 to those with a PMO diagnosis. CI confidence interval, FF fragility fractures, OP osteoporosis, PMO postmenopausal osteoporosis

Discontinuation of Osteoporosis Treatment

The most common reasons for discontinuing OP treatment were medication switch/change and abandonment of treatment (67.1% and 32.3% of women in cohort 1; 53.5% and 46.2% of women in cohort 2) (Table 2).

Adherence to Osteoporosis Treatment

Adherence to OP medication at 12 months, evaluated as mean (95% CI) PDC, was 80.9% (79.4‒82.4%) and 72.8% (71.6‒74.0%) in cohorts 1 and 2, respectively, and 77.3% (76.2–78.4%) overall.

Fractures and Mortality in the 2 Years After the Index Event

Most (2821/3190 [88.4%]) women in cohort 1 experienced at least one subsequent FF in the 2 years after the index event, compared with only 6.5% (1238/18,952) of those in cohort 2. Fracture incidence increased with age in both cohorts (Supplementary Fig. S3i), with vertebral fractures being the most common fracture type (27.9%), followed by hip/femur fractures (24.6%) (Supplementary Fig. S3ii). All-cause mortality incidence was higher in cohort 1 vs cohort 2 (4.9% vs 2.3%) (Supplementary Table S8).

Fracture and mortality event rates for the 2-year observation period are shown in Fig. 6. Overall, fracture rates were higher in women not prescribed OP treatment in the 6 months after the index date and those who were non-persistent with and non-adherent to treatment at 24 and 12 months, respectively, vs women who were prescribed OP treatment in the 6 months post-index, and those who were persistent with and adherent to treatment. Mortality rates were higher in non-persistent vs persistent patients and were similar among treated and untreated and adherent and non-adherent patients. Annual fractures and mortality rates increased with age in both cohorts (Fig. 7). Overall, vertebral fractures had the highest rate; rates of forearm/wrist/radius fractures were higher in cohort 1 vs cohort 2, and rates of hip/femur fractures were higher in cohort 2 vs cohort 1 (Fig. 7).

Fig. 6

Event rates of fracture and mortality during the 2-year observation period following the index event (first FF or PMO diagnosis). Cohort 1 corresponded to patients with a first FF; cohort 2 to those with a PMO diagnosis. CI confidence interval, FF fragility fractures, PMO postmenopausal osteoporosis

Fig. 7

Incidence rates of fracture and mortality during the 2-year observation period following the index event (first FF or PMO diagnosis). Cohort 1 corresponded to patients with a first FF; cohort 2 to those with a PMO diagnosis. CI confidence interval, FF fragility fractures, PMO postmenopausal osteoporosis

Healthcare Resource Utilisation and Costs in the 2 Years Post-event

Table 3 summarises HCRU, sick leave, and associated direct and indirect costs during the 2-year observation period. HCRU was higher in cohort 1 (index event of a first FF) vs cohort 2 (index event of PMO diagnosis), with the largest difference observed for hospital admissions (57.7% of women in cohort 1 had at least one hospital admission vs 0.8% in cohort 2). The percentage of working-age patients taking at least 1 day of sick leave was also higher in cohort 1 (11.0%) vs cohort 2 (4.9%), with a mean (SD) of 6.8 (24.9) vs 2.3 (17.1) days off work, respectively. The mean (SD) total cost per patient was €10,601 (13,952) in cohort 1 and €1659 (2436) in cohort 2. After adjusting for age, gender, and CCI, the mean (95% CI) cost per patient was €10,446 (10,245–10,646) in cohort 1 and €1685 (1603–1766) in cohort 2.

Table 3 HCRU and costs in the 2-year observation period after the index event (overall and by cohort)

Costs increased with age and were higher in cohort 1 vs cohort 2 across all age groups. Hip fractures had the highest mean (SD) cost per patient (€15,833 [14,666]), followed by vertebral fractures (€10,593 [14,326]) (Supplementary Table S9). Across both cohorts, costs were higher for non-adherent and non-persistent patients and switchers vs adherent and persistent patients and those not switching treatment (Supplementary Table S9).