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Khairallah P, Cherasard J, Sung J, Agarwal S, Aponte MA, Bucovsky M, Fusaro M, Silberzweig J, Frumkin GN, El Hachem K, Schulman L, McMahon D, Allen MR, Metzger CE, Surowiec RK, Wallace J, Nickolas TL.

2023

Introduction: Secondary hyperparathyroidism is associated with osteoporosis and fractures. Etelcalcetide is an intravenous calcimimetic for control of hyperparathyroidism in patients on hemodialysis. Effects of etelcalcetide on the skeleton are unknown.

Methods: In a single-arm, open-label, 36-week prospective trial we hypothesized that etelcalcetide improves bone quality and strength without damaging bone-tissue quality. Participants were ≥18 years, on hemodialysis ≥1 year, without calcimimetic exposure within 12-weeks of enrollment. We measured pre- and post-treatment areal bone mineral density by dual energy X-ray absorptiometry, central skeleton trabecular microarchitecture by trabecular bone score, and peripheral skeleton volumetric bone density, geometry, microarchitecture and estimated strength by high resolution pQCT. Bone-tissue quality was assessed by quadruple-label bone biopsy in a subset of patients. Paired T-Tests were used in our analysis.

Results: Twenty-two participants were enrolled; 13 completed follow-up (mean±SD age 51±14 years; 53% male; 15% white). Five underwent bone biopsy (mean±SD age 52±16 years; 80% female). Over 36-weeks, parathyroid hormone levels declined 67%±9% (p<0.001), areal bone mineral density at the spine, femoral neck and total hip increased 3±1%, 7±2% and 3±1% respectively (p<0.05), spine trabecular bone score increased 10±2% (p<0.001) and radius stiffness and failure load trended to a 7±4% (p=0.05) and 6±4% increase (p=0.06). Bone biopsy demonstrated decreased bone formation rate (mean difference -25±4 µm3/µm2/year; p<0.01). Conclusions: Treatment with etelcalcetide for 36-weeks was associated with improvements in central skeleton areal bone mineral density and trabecular quality and lowered bone turnover without affecting bone material properties.