New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide.
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.
Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo , Tokyo, Japan.
Sakae
S
Tanaka
Department of Biomechanics, Institute for Frontier Medical Sciences, Kyoto University , Kyoto, Japan.
Taiji
T
Adachi
Medical Affairs Department , Asahi Kasei Pharma Corporation, Tokyo, Japan.
Tatsuhiko
T
Kuroda
National Center for Global Health and Medicine , Tokyo, Japan.
Toshitaka
T
Nakamura
Research Institute and Practice for Involutional Diseases , Nagano, Japan.
Masataka
M
Shiraki
Internal Medicine 1, Shimane University Faculty of Medicine , Izumo, Japan.
Toshitsugu
T
Sugimoto
Toranomon Hospital Endocrine Center , Tokyo, Japan.
Yasuhiro
Y
Takeuchi
Department of Orthopaedic Surgery, Jikei University School of Medicine , Tokyo, Japan.
Mitsuru
M
Saito
Metabolic Bone Diseases Program, Division of Endocrinology, Department of Medicine, College of Physicians and Surgeons, Columbia University , New York, USA.
John P
JP
Bilezikian