Development of an algorithm for using PINP to monitor treatment of patients with teriparatide.

Introduction: Teriparatide effects are mediated via the preferential stimulation of osteoblastic activity over osteoclastic activity. Amino-terminal propeptide of type I procollagen (PINP) is an indicator of osteoblastic activity.

Objective: Develop an algorithm using PINP as an aid in the management of patients with postmenopausal osteoporosis treated with teriparatide.

Research Design And Methods: For inclusion in this post-hoc analysis, trials had to be investigations of teriparatide 20 microg/day in postmenopausal women with osteoporosis having measurements of PINP at 3 months and bone mineral density (BMD) at 12 months. Signal-to-noise ratio was calculated for a series of markers of bone turnover in the Fracture Prevention Trial. An algorithm was developed to monitor patients treated with teriparatide using PINP.

Results: Three trials met inclusion criteria and included the Fracture Prevention, Forteo-Alendronate Comparator and Anabolic After Antiresorptive trials. PINP had the highest signal-to-noise ratio of all bone-turnover markers. Positive PINP responses defined as increases > 10 microg/L were observed in 77-79% of teriparatide- and in 6% of placebo-treated patients after 3 months of study drug. Mean lumbar spine BMD increases after 12 months of teriparatide in patients having PINP changes > 10 microg/L ranged from 8.3% to 9.5% and in patients with PINP changes < or = 10 microg/L ranged from 5.9% to 7.6%. In the algorithm, PINP is measured at baseline and after 1-3 months of therapy. Patients with PINP increases > 10 microg/L are given a positive message. Patients with PINP increases < or = 10 microg/L are assessed for adherence, teriparatide administration and storage techniques, and for the presence of medical conditions that might limit their therapeutic response, and these issues are addressed as appropriate. Patients without these issues and with PINP increases < or = 10 microg/L should be given a neutral message because BMD may significantly increase with continued therapy.

Conclusions: The PINP algorithm provides information regarding the anabolic response to teriparatide therapy and has the potential to identify patients requiring help with issues of adherence, injection technique, teriparatide storage, and medical problems limiting therapeutic responsiveness to teriparatide treatment. Data assessing the relationship of changes in PINP to fracture risk reduction are not available. We recommend physicians audit the use of the algorithm in practice so that improvements can be made.