P0902DAILY TERIPARATIDE TREATMENT AND PHARMACOKINETICS IN HEMODIALYSIS PATIENTS WITH LOW BONE MASS

Abstract

Abstract Background and Aims Daily 20µg teriparatide (PTH1-34) is an osteoanabolic agent approved for use treating osteoporosis. However, there are few reports about concerning use of this agent in hemodialysis patients. Method We conducted an observational study, single centre study on 5 patients with low bone mineral density (BMD) and low iPTH levels defied as iPTH below 60 pg/mL, who were treated with recombinant human PTH1-34; teriparatide 20 µg 3 times per week between January 2012 and January 2015. All patients were 20 years of age or older, had undergone regular hemodialysis treatment and were without skeletal malignancies and bone metastasis. Low BMD in this study was defined either as BMD T-score -2.5 at the lumbar spine (LS) or /and femoral neck (FN) and distal one –third radius (RS) analyzed by dual-energy X-ray absorptiometry (DXA), or BMD T-score of -2.5 to -1.0 with history of fragility fractures. We analyzed the biochemical data including bone metabolic makers (intact amino-terminal propeptide of type I collagen (iP1NP), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) at baseline, and after 3, 6, and 12 months of teriparatide treatment. BMD at LS and FN were evaluated at 6months of treatment. Results Data from five patients (mean age: 69.2±7.4years; mean hemodialysis time: 23.2±6.2years) were reviewed. Laboratory data at baseline were iPTH: 34.2±24.2 pg/mL, BAP: 13.0±4.9 µg/L, iP1NP: 45.3±14.3 ng/mL, TRACP-5b: 350±201 mU/dL, corrected Ca (cCa): 9.7±0.3 mg/dL, and P:4.1±0.7 mg/dL. Baseline BMD T-score at LS and FN were -2.8±1.7 and -3.0±0.6, respectively. During a 12 month- teriparatide treatment, mean cCa levels significantly decreased from 9.7±0.3 to 9.1±0.2 mg/dL at 3 months (P < 0.05) and returned to 9.5±0.4 mg/dL at 12 months. As for bone metabolic markers, BAP and iP1NP significantly increased from baseline by 31.3±12.9 (P < 0.05) and 47.4±14.5% (P < 0.05) at 6 months of teriparatide treatment, while TRACP-5b significantly decreased by 10.5±2.5% at 3 months, which did not reach a statistical significance. BMD changes from baseline at LS and FN were 2.1±2.5% and 1.2±1.5% at 6 months of treatment with a significant change at LS. Pharmacokinetics of Teriparatide The time-course of changes in plasma teriparatide acetate concentration was evaluated in one patient who had undergone parathyroidectomy 20 years before enrollment in this study and her serum endogenous iPTH level was undetectable at baseline. After teriparatide injection, serum teriparatide acetate levels peaked at 30 minutes at 157.2 pg/mL, and then rapidly decreased to undetectable levels at 240 minutes. Conclusion We report that teriparatide improved LS and FN BMD in hemodialysis patients with low iPTH. Pharmacokinetics showed this agent might not accumulate in dialysis patients and can be used safely. Adequate Ca supplementation might be needed to adjust serum Ca levels.