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. 2023 Nov 1;18(11):1456-1465.
doi: 10.2215/CJN.0000000000000254. Epub 2023 Aug 14.

Changes in Bone Quality after Treatment with Etelcalcetide

Pascale Khairallah  1 , Jenna Cherasard  2 , Joshua Sung  3 , Sanchita Agarwal  3 , Maria Alejandra Aponte  3 , Mariana Bucovsky  3 , Maria Fusaro  4 , Jeffrey Silberzweig  5 , Gail N Frumkin  5 , Karim El Hachem  5 , Linda Schulman  5 , Donald McMahon  3 , Matthew R Allen  6 , Corinne E Metzger  6 , Rachel K Surowiec  6 , Joseph Wallace  6 , Thomas L Nickolas  3
Affiliations

Changes in Bone Quality after Treatment with Etelcalcetide

Pascale Khairallah et al. Clin J Am Soc Nephrol. .

Abstract

Introduction: Secondary hyperparathyroidism is associated with osteoporosis and fractures. Etelcalcetide is an intravenous calcimimetic for the 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 or older, on hemodialysis ≥1 year, without calcimimetic exposure within 12 weeks of enrollment. We measured pretreatment 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 peripheral quantitative computed tomography. Bone-tissue quality was assessed using 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, and 15% White). Five underwent bone biopsy (mean±SD age 52±16 years and 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), respectively. Bone biopsy demonstrated a decreased bone formation rate (mean difference -25±4 µ m 3 / µ m 2 per 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.

Clinical trial registry name and registration number: The Effect of Etelcalcetide on CKD-MBD (Parsabiv-MBD), NCT03960437.

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Conflict of interest statement

S. Agarwal, M.A. Aponte, and M. Bucovsky report the employment with Columbia University. M.R. Allen reports employment with Roudebush Veterans Administration; research funding from MBX Biosciences; and role on the Editorial Boards for Bone, Calcified Tissue International, and Osteoporosis International. M. Fusaro reports consultancy for Vifor-Pharma and honoraria from Abiogen and Amgen. P. Khairallah reports role on the Editorial Board of American Journal of Kidney Diseases. D. McMahon provides statistical consulting services to Hospital for Special Surgery and New York University, both located in New York City. T.L. Nickolas reports employment with Columbia University; consultancy for Alnylam and Pharmacosmos; research funding from Amgen; honoraria from Alnylam and Pharmacosmos; and advisory or leadership roles for Amgen and Pharmacosmos. Columbia University has licensed patents on NGAL to Abbott Diagnostics and Alere. J. Silberzweig reports consultancy work for Honeywell, Kaneka, and St. Gobain; stock in A&T, American Express, IBM, and Wells Fargo; research funding as the national principal investigator for two clinical trials sponsored by Kaneka: one is using their Lixelle device for treatment of Beta-2-microglobulin amyloidosis in patients with ESKD and the other is using lipid apheresis for the treatment of focal glomerulosclerosis; and advisory or leadership roles for American Society of Nephrology: Nephrologists Transforming Dialysis Safety COVID-19 and Other Current and Emerging Threats workgroup, COVID-19 Response team, and Emergency Partnership Initiative. J. Silberzweig's wife is an employee of Anthem and holds stock in the company. J. Sung reports ownership interest in Alphabet, Amazon, Bank of America, Citigroup, Intel, and Meta. J. Wallace reports employment with Boardable and roles on the Editorial Boards for Advances in Computed Tomography, Bone, Bone Reports, Current Osteoporosis Reports, Journal of Biomechanical Engineering, PLOS One, and Scientific Reports. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Consort diagram. COVID-19, coronavirus disease 2019. Figure 1 can be viewed in color online at www.cjasn.org.
Figure 2
Figure 2
Dynamic measures of histomorphometry from quadruple-label bone biopsy after 36 weeks of etelcalcetide treatment. Data presented as individual values for each of the five patients. *P < 0.05; **P < 0.01; ***P < 0.001. Reference ranges (mean+SD, on the basis of postmenopausal women aged 45–74 years) are as follows: MAR (0.53+0.08), MS/BS (7.0+4.1), and BFR/BS (8+6). BFR/BS, bone formation rate/bone surface; MAR, mineral apposition rate; MS/BS, mineralizing surface/bone surface.
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