Short-term increases in bone turnover markers predict parathyroid hormone-induced spinal bone mineral density gains in postmenopausal women with glucocorticoid-induced osteoporosis

The purpose of this study was to test the ability of early changes in marke rs of bone turnover to predict subsequent changes in bone mineral density ( BMD) induced by parathyroid hormone fragment, PTH (1-34), in postmenopausal osteoporotic women treated with estrogen and glucocorticoids. Forty-nine p ostmenopausal women with chronic, inflammatory diseases and BMD T-scores le ss than or equal to-2.5 at the lumbar spine or femoral neck who were concur rently treated with estrogen greater than or equal to 1 year and prednisone 5-20 mg/day for greater than or equal to 1 year participated. Subjects wer e randomized to treatment with human PTH (1-34) 400 IU/day or to a control group for 1 year and followed for an additional year. Serum and urine were collected at baseline and 1, 3, 6, 9, 12, 18 and 24 months for measurement of bone alkaline phosphatase (BAP), osteocalcin (OC) and deoxypyridinoline (DPD). We constructed an Uncoupling Index (UI) from all three markers (UI = [Z(BAP) + Z(OC)]/2 -Z(DPD), where the Z-score for each marker in each subj ect was calculated from the mean and standard deviation of the study popula tion at baseline). BMD of the lumbar spine and hip was measured at baseline and every 6 months thereafter by dual-energy X-ray absorptiometry (DXA) an d annually by quantitative computed tomography (QCT; spine only). BMD of th e spine, but not hip (total, femoral neck or trochanter), and levels of all three markers increased significantly as a result of PTH treatment (p<0.01 compared with controls). The resorption response lagged behind that of for mation as evidenced by a significant increase (p<0.05) in the UI for the fi rst 9 months of treatment. The UI values and changes from baseline to 1, 3 and 6 months in BAP, OC and DPD were correlated with the 22- and 24-month c hanges in spine BMD measured both with QCT and with DXA (Spearman's rank co efficients less than or equal to 0.76; p<0.05). Most PTH-treated subjects c ould be identified as biochemical responders by least significant change an alysis. Following 1 month of therapy, BAP and OC identified 65% and 81% as responders, respectively. The responder rates were 79%, 79% and 75% for BAP , OC and DPD, respectively by 6 months. Responders exhibited a high level o f diagnostic accuracy for predicting a gain in BMD (areas under the receive r operating characteristic curves exceeding 0.79 for QCT and 0.70 for DXA), but not the magnitude of the gain. These data suggest that serial bone mar ker measurements may be useful in identifying skeletal responders to an ana bolic therapy, such as PTH, in estrogen-replete postmenopausal women with g lucocorticoid-induced osteoporosis.