EARLY CHANGES IN BIOCHEMICAL MARKERS OF BONE TURNOVER PREDICT THE LONG-TERM RESPONSE TO ALENDRONATE THERAPY IN REPRESENTATIVE ELDERLY WOMEN- A RANDOMIZED CLINICAL-TRIAL

Although the antiresorptive agent alendronate has been shown to increa se bone mineral density (BMD) at the hip and spine and decrease the in cidence of osteoporotic fractures in older women, few data are availab le regarding early prediction of long-term response to therapy, partic ularly with regard to increases in hip BMD. Examining short-term chang es in biochemical markers incorporates physiologic response with thera peutic compliance and should provide useful prognostic information for patients. The objective of this study was to examine whether early ch anges in biochemical markers of bone turnover predict long-term change s in hip BMD in elderly women. The study was a double-blind, placebo-c ontrolled, randomized clinical trial which took place in a community-b ased academic hospital. One hundred and twenty community-dwelling, amb ulatory women 65 years of age and older participated in the study. Int ervention consisted of alendronate versus placebo for 2.5 years. All p atients received appropriate calcium and vitamin D supplementation. Th e principal outcome measures included BMD of the hip (total hip, femor al neck, trochanter, and intertrochanter), spine (posteroanterior [PA] and lateral), total body, and radius. Biochemical markers of bone res orption included urinary N-telopeptide cross-linked collagen type I an d free deoxypyridinoline; markers of bone formation included serum ost eocalcin and bone-specific alkaline phosphatase. Long-term alendronate therapy was associated with increased BMD at the total hip (4.0%), fe moral neck (3.1%), trochanter (5.5%), intertrochanter (3.8%), PA spine (7.8%), lateral spine (10.6%), total body (2.2%), and one-third dista l radius (1.3%) in elderly women (all p < 0.01). In the placebo group, bone density increased 1.9-2.1% at the spine (p < 0.05) and remained stable at all other sites. At 6 months, there were significant decreas es in all markers of bone turnover (-10% to -53%, p < 0.01) in women o n alendronate. The changes in urinary cross-linked collagen at 6 month s correlated with long-term bone density changes at the hip (r = -0.35 , p < 0.01), trochanter (r = -0.36, p < 0.01), PA spine (r = -0.41, p < 0.01), and total body (r = -0.34,p < 0.05). At 6 months, patients wi th the greatest drop in urinary cross-linked collagen (65% or more) de monstrated the greatest gains in total hip, trochanteric, and vertebra l bone density (all p < 0.05). A 30% decrease in urinary cross-linked collagen at 6 months predicted a bone density increase of 2.8-4.1% for the hip regions and 5.8-6.9% for the spine views at the 2.5-year time point (p < 0.05). There were no substantive associations between chan ges in biochemical markers and bone density in the placebo group. Alen dronate therapy was associated with significant long-term gains in BMD at all clinically relevant sites, including the hip, in elderly women . Moreover, these improvements were associated with early decreases in biochemical markers of bone turnover. Early dynamic decreases in urin ary cross-linked collagen can be used to monitor and predict long-term response to bisphosphonate therapy in elderly women. Future studies a re needed to determine if early assessment improves long-term patient compliance or uncovers poor compliance, thereby aiding the physician i n maximizing the benefits of therapy.