(C-230) Evaluating the Risk of Stroke among Female Patients using Osteoporosis Treatments

Background: Information on cardiovascular safety of osteoporosis treatments is important to help patients and clinicians choose between osteoporosis treatment options. Studies have reported increased risks of fatal stroke among users of selective estrogen receptor modulators (SERMs), an osteoporosis treatment option, but information is limited.

Objectives: To describe the risks of stroke, including fatal stroke, among female users of various osteoporosis treatments.

Methods: We conducted a cohort study of female users of osteoporosis treatments, age 40–89, in the Clinical Practice Research Datalink Aurum (2000–2020). Exposed patients were those with a first prescription for a SERM (raloxifene), a bisphosphonate (alendronate, ibandronate, risedronate, zoledronic acid, etidronate), denosumab, teriparatide or calcitonin in 2000 or later. The common reference group comprised patients with an osteoporosis-related code and vitamin D (Vit D) prescriptions in 2000 or later. Patients with a history of cardiovascular disease (CVD) were excluded. Person-time was accumulated by study drug from first prescription through censor date (event, other CVD diagnosis, major comorbidity, age 90, death, end of record, or 31 Dec 2020). A patient was considered currently exposed from prescription date through prescription duration + 30 days. We calculated incidence rates (IRs) per 10,000 patient-years (PY) of stroke and fatal stroke for each osteoporosis treatment and adjusted incidence rate ratios (adjIRRs) with 95% confidence intervals (CI) for each exposure, controlling for age, calendar year, osteoporotic disease type and smoking, compared with Vit D-only group.

Results: Among 306,457 patients (median age 68 years [interquartile range, IQR, 59–77], median follow-up 6 years [IQR 3–11]), there were 7312 stroke and 739 fatal stroke cases. Most exposure was to alendronate (77%) or risedronate (12%). Zoledronic acid, teriparatide, and calcitonin use was too low to estimate stable IRs. Across all exposures, IRs per 10,000 PY for stroke and fatal stroke were 43.2 and 4.4, respectively. The incidence of stroke was highest for etidronate (140 cases; IR = 59.9 per 10,000 PY [95% CI 50.4–70.6]) and lowest for current users of raloxifene (71 cases; IR = 36.4 per 10,000 PY [28.4–45.9]). No difference in stroke risk among users of any study drug was observed after adjusting for covariates. Among study drugs with more than 5 exposed cases, there was no increased risk of fatal stroke for any study drug.

Conclusions: There was no significant difference in stroke or fatal stroke risk between osteoporosis treatments. However, the number of fatal stroke cases was too small to make robust comparisons between treatments for most study drugs, including raloxifene.