UC San Diego

The aims of this study were to describe the changes in bone turnover markers (BTMs) in response to lasofoxifene therapy; to describe the changes in BTMs in the individual; and to examine the relationships between BTM levels on treatment and treatment outcomes. Women (n=1126) aged 59-80years with femoral neck or spine bone mineral density T-scores ≤-2.5 were randomized to lasofoxifene 0.25mg/d, 0.5mg/d, or placebo for 5years. We measured serum C-telopeptide of type I collagen (CTX) and serum procollagen I N-propeptide (PINP), osteocalcin, and bone alkaline phosphatase (ALP) at baseline and at 1, 3, 6, 12, 24, and 36months. Lasofoxifene therapy resulted in a decrease in the concentrations of bone resorption and bone formation markers compared with placebo; the decrease was maximal between 6 and 24months. The effect of lasofoxifene 0.5mg/d was similar to that of lasofoxifene 0.25mg/d. The decrease in bone ALP was less than the decreases in CTX, osteocalcin, and PINP. Lasofoxifene therapy 0.5mg/d resulted in BTM-defined response rates for CTX (decrease in concentration from baseline >60%), PINP (>50%), and bone ALP (>30%) of 35%, 45%, and 43% of women at month 12, respectively, compared with placebo responses of 4%, 4%, and 7%. In contrast, the increase in BMD took longer (50% responded after 36months of lasofoxifene 0.5mg/d) and was not as specific (15% of placebo group responded). Bone density change was weakly inversely correlated with change in the concentrations of BTMs. BTMs may prove useful in the monitoring of the response to lasofoxifene treatment for women with postmenopausal osteoporosis early in the course of treatment.