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

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.

Osteoporosis: Remodeling bone

Simulating bone turnover marker changes seen during weekly parathyroid hormone treatment reveals bone remodeling during treatment. A human parathyroid hormone fragment called teriparatide is an approved treatment for osteoporosis, decreasing fracture risk and increasing bone density. Weekly treatment with teriparatide leads to a temporary increase in markers of bone formation and a decrease in markers of bone breakdown in the blood. Sakae Tanaka at the University of Tokyo generated a simulation model which matched the changes in bone turnover markers and bone mineral density over time. This suggests that teriparatide affects both the formation of new bone and the loss of old bone, a process called bone remodeling. The findings explain how treatment with teriparatide has beneficial effects on bone density and osteoporosis.

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