Effects of 3 years of lasofoxifene treatment on bone turnover markers in women with postmenopausal osteoporosis

article i nfo The aims of this study were to describe the changes in bone turnover markers (BTMs) in response to lasofox- ifene 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 59-80 years with femoral neck or spine bone mineral density T-scores ≤−2.5 were randomized to lasofoxifene 0.25 mg/d, 0.5 mg/d, or pla- cebo for 5 years. 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 36 months. 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 24 months. The effect of lasofoxifene 0.5 mg/d was similar to that of lasofoxifene 0.25 mg/d. The decrease in bone ALP was less than the decreases in CTX, osteocalcin, and PINP. Lasofoxifene therapy 0.5 mg/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 36 months of lasofoxifene 0.5 mg/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 laso- foxifene treatment for women with postmenopausal osteoporosis early in the course of treatment.