Determinants of Oral Bisphosphonate Use Beyond 5 Years

Abstract

BACKGROUND: Few studies have examined factors that determine bisphosphonate (BP) continuation beyond 5 years in clinical practice. OBJECTIVE: To investigate factors associated with BP continuation among women who completed 5 years of BP therapy. METHODS: Women who received 5 consecutive years of oral BP treatment entered the cohort during 2002-2014 and were followed up to 5 additional years. Multivariable logistic regression was used to evaluate the association of demographic and clinical factors with adherent treatment continuation. RESULTS: The cohort included 19,091 women with a median age of 72 years. Baseline and time-varying factors associated with increased odds of BP continuation after 5 years were (a) most recent bone mineral density (BMD) T-score-2 to-2.4 (OR = 1.31, 95% CI = 1.25-1.38), T-score-2.5 to-2.9 (OR = 1.48, 95% CI = 1.39-1.57), and T-score ≤-3.0 (OR = 1.57, 95% CI = 1.47-1.68) versus T-scores above-2.0; (b) index date before 2008 (OR =1.35, 95% CI = 1.29-1.41); and (c) diabetes mellitus (OR = 1.08, 95% CI = 1.01-1.16). In contrast, factors associated with decreased odds of BP continuation were (a) recent hip (OR = 0.61, 95% CI = 0.52-0.71) or humerus (OR = 0.79, 95% CI = 0.66-0.94) fracture or fracture other than hip, wrist, spine, or humerus (OR = 0.90, 95% CI = 0.84-0.97); (b) Charlson Comorbidity Index score > 2 (OR = 0.91, 95% CI = 0.84-0.98); (c) history of rheumatoid arthritis (OR = 0.89, 95% CI = 0.80-0.99); (d) Hispanic (OR = 0.89, 95% CI=0.85-0.94) or Asian (OR = 0.90, 95% CI = 0.85-0.94) race/ethnicity; and (e) use of proton pump inhibitors (OR = 0.65, 95% CI = 0.59-0.71). Patient age and fracture before BP initiation were not associated with treatment continuation. CONCLUSIONS: Clinical factors predicting continued BP treatment beyond 5 years include low BMD T-score, absence of recent fracture, and earlier era of treatment. Use of proton pump inhibitors was associated with lower likelihood of BP continuation. Other clinical and demographic factors were also noted to have variable effects on BP treatment continuation.

Bisphosphonate Treatment Beyond 5 Years and Hip Fracture Risk in Older Women

“…Following the index date and for each successive 90-day interval (quarter) of follow-up, women were categorized as receiving bisphosphonate if at least 60% of the time period was covered by days’ supply of drug in health plan pharmacy records (proportion of days covered [PDC], ≥0.60). 17 , 18 Women were considered not receiving bisphosphonate if they received drug for less than the specified PDC. Stockpiling was allowed for bisphosphonate prescriptions that overlapped by 30 days or less.…”

“…We considered an extensive set of baseline and time-dependent covariates that may be associated with treatment 17 or the risk of hip fracture. Baseline measures included age (in 5-year increments) and self-reported race/ethnicity (classified as non-Hispanic White, Hispanic/Latina, Black, Asian or Pacific Islander, and other or unknown).…”

“… 17 Body mass index (calculated as weight in kilograms divided by height in meters squared and categorized as normal/underweight [<25], overweight [25 to <30], or obesity [≥30]), self-reported smoking status, evidence of vitamin D deficiency (25-hydroxyvitamin D level [25-OHD] <20 ng/mL [to convert to picomoles per liter, multiply by 2.496]), and an indicator of 25-OHD assessment were obtained within 5 years of the index date. We additionally considered indicators of hip, humerus, vertebral, wrist, or other fracture 17 prior to bisphosphonate initiation. An indicator of whether a woman experienced a hip fracture in the 5 years between bisphosphonate initiation and the index date was included in analyses.…”

“…We used US Census data to estimate surrogate markers of socioeconomic status, including low educational attainment (residence in a census block where >25% of individuals aged >25 years had less than a 12th grade education) and low income (residence in a census block with a median annual household income <$35 000). 17 17 prior to bisphosphonate initiation. An indicator of whether a woman experienced a hip fracture in the 5 years between bisphosphonate initiation and the index date was included in analyses.…”

“…eGFR], 45-59 mL/min/1.7 m 2 and 30-44 mL/min/1.7 m 2 , respectively); indicators of spine, humerus, wrist, or other clinical fracture17 within the prior 5 years for baseline and the prior 12 months during follow-up; most recent bone mineral density (BMD) T score (described in next paragraph); and treatment with proton-pump inhibitors, aromatase inhibitors, or systemic oral glucocorticoids (cumulative prednisone dose equivalent Ն1825 mg received in the prior year, averaging 5 mg/d). For participants with missing eGFR at baseline (7742 [26%]) the mean baseline value (74 mL/min/1.7 m 2 )…”