Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis

CONTEXT: Treatment of osteoporotic women with PTH increases biochemical markers of bone turnover, increases axial bone mineral density (BMD), and reduces fracture risk. OBJECTIVE: Our objective was to determine the relationship between levels of baseline turnover before PTH therapy and short-term changes in turnover during PTH therapy and subsequent changes in areal and volumetric BMD. DESIGN AND SETTING: We conducted a randomized, placebo-controlled trial at four academic centers. PATIENTS: Patients included 238 postmenopausal women with low hip or spine BMD. INTERVENTION: Subjects were randomized to sc PTH (1-84), 100 mug/d (119 women), for 1 yr. MAIN OUTCOME MEASURE: Bone turnover markers were measured in fasting blood samples collected before therapy and after 1 and 3 months. Areal and volumetric BMD at the spine and hip were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography (QCT) after 1 yr of therapy. RESULTS: Among women treated with PTH alone, the relationships between baseline turnover and 1-yr changes in dual-energy x-ray absorptiometry and QCT BMD were inconsistent. Greater 1- and 3-month increases in turnover, particularly the formation marker N-propeptide of type I collagen, were associated with greater increases in areal BMD. When volumetric hip and spine BMD were assessed by QCT, greater short-term increases in turnover were even more positively associated with 1-yr increases in BMD. Each sd increase in the 3-month change of N-propeptide of type I collagen was associated with an a 21% greater increase in QCT spine trabecular BMD. CONCLUSIONS: Greater short-term changes in turnover with PTH therapy are associated with greater 1-yr increases in spine and hip BMD among postmenopausal osteoporotic women.