Efficacy and safety of twice-weekly teriparatide in hemodialysis patients with osteoporosis: protocol for a randomized controlled trial (START-HOP trial)

Abstract Background Patients with chronic kidney disease (CKD), particularly those undergoing hemodialysis (HD), are at increased risk of bone fractures due to multifactorial skeletal fragility associated with CKD–mineral and bone disorder (CKD–MBD), secondary osteoporosis, and metabolic and nutritional abnormalities. Although secondary hyperparathyroidism (SHPT) can be managed using vitamin D analogs and calcimimetics, fracture risk often remains elevated despite appropriate CKD–MBD management, highlighting the need for therapies directly targeting skeletal fragility. Teriparatide, a synthetic human parathyroid hormone (PTH 1–34), has shown potential to improve bone mineral density (BMD) in patients with low PTH levels, although the evidence remains limited, particularly in dialysis populations. Notably, previous studies have employed once-weekly formulations, which have been associated with transient hypotension and a high rate of treatment discontinuation, thereby limiting the accumulation of robust evidence in this population. In contrast, the twice-weekly teriparatide autoinjector formulation may cause fewer adverse effects and would enhance treatment adherence. This improved tolerability could lead to better outcome of bone density maintenance over time. This trial aims to address the lack of evidence regarding teriparatide use in HD patients with adequately controlled SHPT. Methods The START-HOP trial is a multicenter, prospective, randomized, open-label, controlled trial designed to evaluate the efficacy and safety of twice-weekly teriparatide (28.2 μg) in HD patients with osteoporosis. A total of 50 participants will be enrolled and randomized (1:1) to either immediate initiation of teriparatide or a delayed-start group beginning treatment at week 48. The primary analysis will compare the percentage change in lumbar spine BMD at week 48 between groups in a randomized controlled trial (RCT) framework. In addition, within-group analyses will be conducted to assess changes before and after teriparatide administration in all participants over a 48-week treatment. Secondary endpoints include changes in femoral BMD, incidence of fractures, bone turnover markers, cardiovascular biomarkers, echocardiographic parameters, and adverse events. Between-group comparisons will be performed using unpaired t -tests, and within-group comparisons using paired t -tests. Conclusions The START-HOP trial will investigate the efficacy and safety of twice-weekly teriparatide in osteoporosis patients who undergo hemodialysis. Trial registration The study was registered with the Japan Registry of Clinical Trials (jRCTs011230047-2) on 13 November 2023.