Background/Purpose: We recently reported prescription opioid use in nearly one-third of systemic lupus erythematosus (SLE) patients in our population-based cohort. Data suggest that opioids may be associated with falls and decreased bone mineral density (postulated via impaired osteoblast activity and indirectly via hypothalamic-pituitary-adrenal axis dysfunction and hypogonadism), both of which increase fracture risk. Osteoporosis rates are elevated in SLE due to factors including use of glucocorticoids and gonadotoxic therapies (that can result in primary ovarian insufficiency). This analysis examines the association between opioid use and osteoporotic fractures in SLE.

Methods: The study included SLE patients from the population-based MILES Cohort. Sociodemographic, clinical and prescription data were obtained by structured interviews. Osteoporotic fracture history was ascertained from the validated Lupus Damage Index Questionnaire (LDIQ). Locally weighted scatterplot smoothing (Lowess) curve was fit to visualize the relationship between opioid duration and osteoporotic fracture, and determine the appropriate functional form for modelling. Multivariable logistic regression was then used to model the relationship between opioid usage and osteoporotic fracture, controlling for other variables specified a priori as relevant: age, sex, race, ethnicity, smoking history (daily cigarette smoking for ≥6 months), body mass index, SLE duration, high steroid exposure history (≥10 mg oral steroids for ≥1 month) and for females, cessation of menses prior to age 40 years, not due to surgery (indicator of primary ovarian insufficiency).

Results: Among the 458 SLE participants in this study, average age was 53.4 years (SD 12.3), 427 (93.2%) were female, and race was primarily self-reported as black (205; 44.8%) or white (233; 50.9%). Current prescription opioid use was reported by 141 participants (30.8%). History of osteoporotic fracture was reported in 16/141 participants with current prescription opioid use (11.4%) vs 17/317 not using opioids (5.4%); p=0.022. From multivariable regression, current opioid use (binary variable) was not associated with fractures; however, duration of opioid use was significantly associated. Lowess curve indicated a piecewise linear relationship with an inflection at 15 years: for those with opioid use ≤15 years (n=120), odds of fracture were 16% more likely per year increase [OR 1.16 (95% CI 1.06, 1.26), p< 0.001], after adjusting for the covariates. Results were similar when restricting to females. Data were sparse beyond 15 years of opioid use (n=11) thus statistically unstable.

Conclusion: Duration of opioid use was associated with osteoporotic fracture in SLE patients. The odds of fracture increased by 16% for each year of use within 15 years of opioid initiation. Although a temporal association cannot be established from this study, and mitigating factors such as inactivity secondary to pain may be involved, our data suggest that chronic opioid therapy is an indicator for osteoporosis screening in the SLE. The potential for adverse effects on bone health further provides impetus for alternative pain management strategies.

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/prescription-opioid-use-and-osteoporotic-fractures-in-systemic-lupus-erythematosus-the-michigan-lupus-epidemiology-surveillance-miles-cohort/