Low Bone Mineral Density is Associated with Bone Microdamage Accumulation in Postmenopausal Women with Osteoporosis

Marked suppression of bone turnover by bisphosphonates is associated with increased bone microdamage accumulation in animal models. The purpose of this study was to test the hypothesis that long-term treatment with alendronate (ALN) results in accumulation of microdamage in bone in women after menopause. Sixty-six postmenopausal women with osteoporosis (mean age of 68.0 years and mean BMD T-score of -1.7 at total hip and -2.8 at lumbar spine; 62% with prevalent fractures) were evaluated in this cross-sectional analysis. Thirty-eight had been treated previously with ALN (10 mg/day or 70 mg/week for a mean duration of 63.6 months) while twenty-eight were treatment naive (TN). Without adjustments, crack surface density (Cr.S.Dn) and crack density (Cr.Dn) were not different between ALN and TN patients. After adjustment for potential confounders (age, prevalent fractures, femoral neck BMD, activation frequency and center), Cr.Dn was elevated in ALN patients (P=0.028 and P=0.069 for Cr.S.Dn). In ALN patients only, lower femoral neck BMD (Cr.S.Dn, r=-0.58, P=0.003; Cr.Dn, r=-0.54, P=0.005) and increased age (Cr.S.Dn, r=0.43, P=0.03; Cr.Dn, r=0.43, P=0.03) were associated with microdamage accumulation. Among potential confounders, femoral neck BMD was the only independent predictor for these correlations (P=0.04 for Cr.Dn and P=0.03 for Cr.S.Dn). We conclude that increased microdamage accumulation may occur in low BMD patients treated with alendronate.