Gastrointestinal side effects in postmenopausal women using osteoporosis therapy: 1-year findings in the POSSIBLE US study.

OBJECTIVE: To characterize gastrointestinal side effects (GI SEs) and its associations with medication discontinuation, health-related quality of life (HRQoL), and treatment) satisfaction in postmenopausal women prescribed osteoporosis (OP) therapies. METHODS: Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US*) participants enrolled October 27, 2004 - January 25, 2007 and complete questionnaires for up to 3 years. GI SEs for women new to or stable on therapy at entry were characterized at 6 and 12 months. Adjusted odds of experiencing GI SEs; mean HRQoL and treatment satisfaction scores; and risk of discontinuing therapy for bisphosphonate (BP) versus non-BP users were compared with logistic and generalized linear models. RESULTS: About 20% of women reported >or=1 GI SE at entry. GI SEs at month 6 were more common in BP than non-BP users (new: OR = 1.5, 95% CI: 1.2-2.0; stable: OR = 1.7, 95% CI: 1.3-2.1). Women new to OP therapy with GI SEs at month 6 had lower LS Mean HRQoL (OPAQ-SV Emotional Status: 72.3 vs. 78.2, p = 0.005) and treatment satisfaction scores (SEs: 71.4 vs. 82.9; EFFICACY: 58.6 vs. 65.6; Global: 55.0 vs. 64.4; all p

Estimating long-term effects of treatment from placebo-controlled trials with an extension period, using virtual twins.

The best information about the benefits of long-term treatment is obtained from a long-term placebo-controlled trial. However, once efficacy has been demonstrated in relatively brief trials, it may not be possible to conduct long-term placebo-controlled trials, for ethical or practical reasons. This paper presents a method for estimating long-term effects of a treatment from a placebo-controlled trial in which some participants originally randomized to active-treatment volunteer to continue on treatment during an extension study, but follow-up of participants originally assigned to placebo ends with the trial, or they are crossed over to active treatment during the extension. We propose using data from the trial to project the outcomes for a 'virtual twin' for each active-treatment volunteer under the counterfactual placebo condition, and using bootstrap methods for inference. The proposed method is validated using simulation, and applied to data from the Fracture Intervention Trial and its extension, FLEX.

Single-point assessment of warfarin use and risk of osteoporosis in elderly men.

OBJECTIVES: To determine whether warfarin use, assessed at a single point in time, is associated with bone mineral density (BMD), rates of bone loss, and fracture risk in older men. DESIGN: Secondary analysis of data from a prospective cohort study. SETTING: Six U.S. clinical centers. PARTICIPANTS: Five thousand five hundred thirty-three community-dwelling, ambulatory men aged 65 and older with baseline warfarin use data. MEASUREMENTS: Warfarin use was assessed as current use of warfarin at baseline using an electronic medication coding dictionary. BMD was measured at the hip and spine at baseline, and hip BMD was repeated at a follow-up visit 3.4 years later. Self-reported nonspine fractures were centrally adjudicated. RESULTS: At baseline, the average age of the participants was 73.6 +/- 5.9, and 321 (5.8%) were taking warfarin. Warfarin users had similar baseline BMD as nonusers (n=5,212) at the hip and spine (total hip 0.966 +/- 0.008 vs 0.959 +/- 0.002 g/cm(2), P=.37; total spine 1.079 +/- 0.010 vs 1.074 +/- 0.003 g/cm(2), P=.64). Of subjects with BMD at both visits, warfarin users (n=150) also had similar annualized bone loss at the total hip as nonusers (n=2,683) (-0.509 +/- 0.082 vs -0.421 +/- 0.019%/year, P=.29). During a mean follow-up of 5.1 years, the risk of nonspine fracture was similar in warfarin users and nonusers (adjusted hazard ratio=1.06, 95% confidence interval=0.68-1.65). CONCLUSION: In this cohort of elderly men, current warfarin use was not associated with lower BMD, accelerated bone loss, or higher nonspine fracture risk.