Alendronate (ALN) has been shown to increase BMD and reduce fracture risk in trials up to 5 years but optimal longer term use remains an important clinical question. FLEX was a 5-year randomized, placebo-controlled trial to test the hypothesis that in women previously on ALN for 3-6 years, continued ALN would preserve or increase total hip BMD vs placebo (PBO). BMD at other sites and bone turnover were secondary endpoints; fractures were exploratory.
Women on ALN in the Fracture Intervention Trial (FIT) with T-scores > -3.5 were eligible. 1099 participants with a mean of 5 (range 3-6) years previous ALN (5 mg/d in yrs 1-2 & 10 mg/d thereafter) in FIT were randomized to 5 years of PBO (n=437) or ALN 5 mg/d (n=329) or 10 mg/d (n=333).
The mean age at FLEX baseline was 73 yrs; mean total hip BMD T-score was -1.77. Women switched to PBO had significant loss of hip BMD (p<0.001) and significant increases in bone turnover (p<0.001) relative to FLEX baseline. In contrast, spine and total body BMD were preserved in the PBO group.
Total hip BMD decreased 1% among those receiving alendronate compared to 3.4% in the placebo group (2.4% difference, p<0.001 between groups). At the lumbar spine, women receiving alendronate had an increase in BMD of 5.3% compared to 1.5% in the placebo group (3.8% difference, p<0.001). Additionally, differences between alendronate and placebo were 1.9% for femoral neck BMD, 1.3% for total body BMD, -32% for urinary NTx, and -23% for serum BSAP, all p<0.001 between groups.
Compared to FIT baseline, women treated with ALN up to 11 years increased their spine BMD by 14.8%, total hip BMD by 2.4%, and total body by 3.6%. Women treated with PBO in the last 5 of 11 years had respective changes (vs. FIT baseline) of 11.0% (p<0.001 vs. continuous ALN), -0.2% (p<0.001), and 2.5% (p=0.005). During the 5 years of FLEX, clinical spine fracture risk was reduced in ALN vs PBO (RR=0.45, 95% CI (0.23,0.84)) but risks were similar for non-spine fractures (RR=1.0, 95% CI (0.76,1.32)) and morphometric spine fractures (0.87, 95% CI (0.61,1.25)). Adverse experiences were similar in both treatment groups.
We conclude that 4-6 years of ALN followed by continued treatment with ALN for up to 5 additional years increases spine BMD, maintains other BMD measures and preserves decreases in bone markers. Decreases in hip BMD and increases in bone turnover markers occurred among those who stopped ALN during FLEX; nevertheless, BMD levels were similar or higher and marker levels remained slightly lower than at FIT baseline 11 years earlier.
Disclosure Information:
Faculty Member's Name: A.V. Schwartz
I have no relationships to disclose.
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