Time-dependent changes in skeletal response to teriparatide: escalating vs. constant dose teriparatide (PTH 1-34) in osteoporotic women

Abstract

Once-daily injections of teriparatide initially increase biochemical markers of bone formation and resorption, but markers peak after 6-12 months and then decline despite continued treatment. We sought to determine whether increasing teriparatide doses in a stepwise fashion could prolong skeletal responsiveness. We randomized 52 postmenopausal women with low spine and/or hip bone mineral density (BMD) to either a constant or an escalating subcutaneous teriparatide dose (30 μg daily for 18months or 20 μg daily for 6 months, then 30 μg daily for 6 months, and then 40 μg daily for 6 months). Serum procollagen I N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type I collagen were assessed frequently. BMD of the spine, hip, radius, and total body was measured every 6 months. Acute changes in urinary cyclic AMP in response to teriparatide were examined in a subset of women in the constant dose group. All bone markers differed significantly between the two treatment groups. During the final six months, bone markers declined in the constant dose group but remained stable or increased in the escalating dose group (all markers, p<0.017). Nonetheless, mean area under the curve did not differ between treatments for any bone marker, and BMD increases were equivalent in both treatment groups. Acute renal response to teriparatide, as assessed by urinary cyclic AMP, did not change over 18 months of teriparatide administration. In conclusion, stepwise increases in teriparatide prevented the decline in bone turnover markers that is observed with chronic administration without altering BMD increases. The time-dependent waning of the response to teriparatide appears to be bone-specific.

Conflict of interest statement

Conflict of interest: Robert Neer has consulted for Eli Lilly, and Joel Finkelstein has consulted for Merck. All other authors have no conflicts of interest.

Copyright © 2010 Elsevier Inc. All rights reserved.

Figures

Figure 1

Recruitment and progression through the study protocol.

Figure 2

In the left column, mean (± SE) serum PINP, OC, and CTX levels in the escalating dose (solid line) and constant dose (dashed line) teriparatide groups over the 18-month study. In the right column, mean % change per 6 month time period (± SE) in serum P1NP, OC, and CTX levels in the escalating dose (black bar) and constant dose (open bar) teriparatide groups. In the first 6 months, there was a greater increase in P1NP and OC in the constant dose group than in the escalating dose group. In the last 6 months, bone markers declined with a negative rate of change in the constant dose group, and remained steady or increased in the escalating dose group. (* indicates p

Figure 3

Mean (± SE) percent change in bone mineral density by DXA of the posterior-anterior spine, lateral spine, total hip, femoral neck, distal radius and total body and by QCT of the trabecular lumbar spine in the escalating dose (solid bar) and constant dose (open bar) teriparatide groups. Note that the scale for QCT BMD is different and is marked on the rightward y-axis. There were no significant differences between the two treatment groups at any skeletal site.