Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women

Abstract

Context: Treatment of osteoporosis with an anabolic agent, teriparatide [human PTH 1-34 (TPTD)], is effective in reducing incident fractures, but patient resistance to daily sc injections has limited its use. A novel transdermal patch, providing a rapid, pulse delivery of TPTD, may provide a desirable alternative.

Objective: The aim of the study was to determine the safety and efficacy of a novel transdermal TPTD patch compared to placebo patch and sc TPTD 20-microg injection in postmenopausal women with osteoporosis.

Design: Our study consisted of 6-month, randomized, placebo-controlled, positive control, multidose daily administration.

Patients: We enrolled 165 postmenopausal women (mean age, 64 yr) with osteoporosis.

Interventions: A TPTD patch with a 20-, 30-, or 40-microg dose or a placebo patch was self-administered daily for 30-min wear time, or 20 microg of TPTD was injected daily.

Outcomes: The primary efficacy measure was mean percentage change in lumbar spine bone mineral density (BMD) from baseline at 6 months.

Results: TPTD delivered by transdermal patch significantly increased lumbar spine BMD vs. placebo patch in a dose-dependent manner at 6 months (P < 0.001). TPTD 40-microg patch increased total hip BMD compared to both placebo patch and TPTD injection (P < 0.05). Bone turnover markers (procollagen type I N-terminal propeptide and C-terminal cross-linked telopeptide of type I collagen) increased from baseline in a dose-dependent manner in all treatment groups and were all significantly different from placebo patch (P < 0.001). All treatments were well tolerated, and no prolonged hypercalcemia was observed.

Conclusion: Transdermal patch delivery of TPTD in postmenopausal women with osteoporosis for 6 months is safe and effective in increasing lumbar spine and total hip BMD.

Trial registration: ClinicalTrials.gov NCT00489918.

Figures

Figure 1

Consort diagram of study recruitment and retention.

Figure 2

Comparison of TPTD pharmacokinetic profile administered by transdermal microprojection patch and sc injection. The symbols (○, TPTD-I 20-μg; ▪, TPTD-P 20-μg; •, TPTD-P 30-μg; and ▴, TPTD 40-μg) correspond to the mean observed TPTD plasma concentration at different time points after administration. The corresponding continuous lines are averaged data from four previous phase 1 pharmacokinetic studies including 106 women and is based on a one-compartment model. The mean observed TPTD-I PTH values are slightly lower than the predicted model value but are not significant.

Figure 3

A, LS BMD mean percentage change from baseline (±se). After 24 wk of daily administration, all active treatment groups produced increases in LS BMD (P < 0.001) with no significant change in the Pbo-P group. B, Total hip BMD mean percentage change from baseline (±se). *, After 24 wk of daily treatment, the TPTD-P 40-μg group increased hip BMD (P < 0.05) compared with Pbo-P. C, Femoral neck and distal forearm BMD mean percentage changes from baseline (±se). There were no statistically significant BMD changes in any of the treatment groups from baseline value.

Figure 4

A, P1NP mean percentage change from baseline (±se). After 4 wk of daily treatment, all active treatments showed an increase in P1NP. At 6 months, the P1NP level for the TPTD-I group was 314% vs. 116% for the 40-μg patch. B, CTX mean percentage change from baseline (±se). At 3 and 6 months, CTX levels were highest for the TPTD-I group at 76% and 105%, respectively, compared with the TPTD-P 40-μg group at 30% for 3 months and 47% for 6 months.