Hetereogeneity in skeletal response to full-length parathyroid hormone in the treatment of osteoporosis

Summary: In the PaTH trial, among the 119 women randomized to parathyroid hormone PTH(1-84) and 60 to alendronate, we found much greater variation in BMD and markers in response to PTH(1-84) compared to alendronate. No baseline participant characteristic consistently predicted increased bone density response to PTH(1-84), although women with larger changes in 1,25 dihydroxyvitamin D during therapy had larger increases in BMD. Introduction: We examined variability in BMD and markers of bone turnover in response to treatment with PTH(1-84) or alendronate in the PaTH trial. Methods: Differences in SD were examined using Levine's test for homogeneity of variance. Change in BMD across quartiles of participant characteristics was examined using ANOVA. Results: We found much greater variation in response to PTH(1-84) compared to alendronate. The SD for change in cancellous spine BMD (by QCT) was 32% on PTH(1-84) compared to 13% on alendronate (p<0.0001). The higher variability in the PTH(1-84) group was due to substantial numbers of women with large increases in BMD on PTH(1-84). Similarly, the SD of changes in markers of formation and resorption were significantly higher on PTH(1-84) than on ALN. No baseline participant characteristics predicted increased bone density response to PTH(1-84) therapy. However, change in 1,25-OH₂D explained 16% of the variance in BMD response to PTH(1-84). Conclusion: There is significant variability in the skeletal response to PTH(1-84), which exceeds that observed with alendronate. Changes in 1,25-OH₂D were related to larger gains in BMD. This finding may have implications for elucidating either the pathway by which PTH affects the skeleton or traits that result in particular responsiveness to PTH therapy.