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.
Bibliographical noteFunding Information:
Dr Cummings received grant support from Amgen; honoraria from Novartis and Eli Lilly; served as an expert witness for Pfizer; and received consulting fees from Amgen, Eli Lilly, and Pfizer Inc. Dr Cummings helped to design the trial, planned the analyses, critically reviewed drafts, and approved the final manuscript.
Dr Eastell received consulting or advisory board fees from Amgen, Novartis, Procter & Gamble, Servier, Ono Pharmaceutical, and GlaxoSmithKline; lecture fees from Eli Lilly; and grant support from AstraZeneca, Procter & Gamble, and Novartis. Dr Eastell drafted and reviewed the manuscript.
Dr Ensrud received travel support from Pfizer Inc and Merck. Dr Ensrud served on the PEARL Scientific Advisory Committee, provided input into the analysis plan, and reviewed and edited the manuscript.
Dr LaCroix received grant support from Pfizer and served on Scientific Advisory Boards for Pfizer Inc, the Alliance for Better Health, and Amgen. Dr LaCroix reviewed and commented on the manuscript.
Dr Reid received consulting or advisory board fees from Amgen, Novartis, and Servier, lecture fees from Roche, and grant support from Wyeth. He is a steering committee member for Pfizer Inc. and critically reviewed and commented on the manuscript.
This study was sponsored by Pfizer Inc. Editorial support was provided by Elizabeth Melby Wells and Nick Rusbridge of PAREXEL and was funded by Pfizer Inc. Pfizer provided support to Drs. Cummings, Ensrud, Eastell, LaCroix, Reid, and Vukicevic as paid consultants for the PEARL study. Dr Eastell is supported by the National Institute of Health Research as a Senior Investigator.
- Bone turnover marker
- Clinical trial