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. 2014 Dec 23:2:14043.
doi: 10.1038/boneres.2014.43. eCollection 2014.

New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide

Sakae Tanaka  1 , Taiji Adachi  2 , Tatsuhiko Kuroda  3 , Toshitaka Nakamura  4 , Masataka Shiraki  5 , Toshitsugu Sugimoto  6 , Yasuhiro Takeuchi  7 , Mitsuru Saito  8 , John P Bilezikian  9
Affiliations

New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide

Sakae Tanaka et al. Bone Res. .

Abstract

Daily 20-μg and once-weekly 56.5-μg teriparatide (parathyroid hormone 1-34) treatment regimens increase bone mineral density (BMD) and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.

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Conflict of interest statement

ST is on the advisory board of Merck Sharp & and receives lecture fees from Daiichi Sankyo, Eisai, Chugai Pharmaceutical, Asahi Kasei Pharma and Ono Pharmaceutical. TA has no financial interests or conflicts of interest to disclose. TK is an employee of Asahi Kasei Pharma Corporation. TNreceived research grants and/or consulting fees from Chugai Pharmaceutical, Teijin Pharma, Asahi Kasei Pharma and Daiichi Sankyo. MS received consulting fees from Chugai, Daiichi Sankyo, Asahi Kasei Pharma, Teijin Pharma and MSD. TS received consulting fees from Asahi Kasei Pharma and research grants from Eli Lilly Japan, Chugai Pharmaceutical Co, Eisai and MSD. YT received research grants and/or consulting fees from Eli Lily Japan, Chugai Pharmaceutical, Teijin Pharma, AsahiKasei Pharma and Daiichi Sankyo.MiS received consulting fees from Daiichi Sankyo, Asahi Kasei Pharma and Eli Lilly. JPB is a consultant for Amgen, Eli Lilly, Radius, NPS Pharmaceuticals, Merck and GSK and receives research support from NPS Pharmaceuticals and Amgen.

Figures

Figure 1
Figure 1
Percent change in bone turnover markers and bone mineral density in the TOWER trial (mean±95% CI). S-P1NP, serum procollagen type I N-terminal propeptide; U-NTX, urinary crosslinked N-telopeptide of type I collagen.
Figure 2
Figure 2
Sketch of the bone cycle. First, bone resorption occurs, and subsequently bone formation occurs on old bone. In the next step, the bone cycle occurs on the remaining old bone.
Figure 3
Figure 3
Preliminary simulation curves of bone formation, resorption and bone volume. (a) Changes of bone formation and resorption; (b) change of bone volume.
Figure 4
Figure 4
Comparison of the simulation and actual changes of bone turnover markers and bone mineral density. (a) Bone formation marker (P1NP); (b) bone resorption marker (NTX); (c) lumbar bone mineral density.
See this image and copyright information in PMC

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