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

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 59–80 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 placebo 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 lasofoxifene treatment for women with postmenopausal osteoporosis early in the course of treatment.

► Treatment of postmenopausal osteoporosis with two dosages of lasofoxifene resulted in similar decreases in 4 bone turnover markers in serum.
► Mean levels of bone turnover markers in subjects after 12 months were close to the mean values for premenopausal women.
► Using a definition of ‘responder’ based on least significant change, approximately 40% of patients ‘responded’ to therapy after 12 months.
► For each bone turnover marker, the key characteristic of responders was a high level of bone turnover marker before treatment.
► Inverse correlations between change in bone turnover markers and change in bone mineral density were weak but statistically significant.