Transitory Activation and Improved Transition from Erosion to Formation within Intracortical Bone Remodeling in Hypoparathyroid Patients Treated with rhPTH(1–84)

Pernille van Dijk Christiansen, Tanja Sikjær, Christina Møller Andreasen, Jesper Skovhus Thomsen, Annemarie Brüel, Ellen Margrethe Hauge, Jean Marie Delaisse, Lars Rejnmark, Thomas Levin Andersen*

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

9 Downloads (Pure)

Abstract

In hypoparathyroidism, lack of parathyroid hormone (PTH) leads to low calcium levels and decreased bone remodeling. Treatment with recombinant human PTH (rhPTH) may normalize bone turnover. This study aimed to investigate whether rhPTH(1–84) continued to activate intracortical bone remodeling after 30 months and promoted the transition from erosion to formation and whether this effect was transitory when rhPTH(1–84) was discontinued. Cortical histomorphometry was performed on 60 bone biopsies from patients (aged 31 to 78 years) with chronic hypoparathyroidism randomized to either 100 μg rhPTH(1–84) a day (n = 21) (PTH) or similar placebo (n = 21) (PLB) for 6 months as add-on to conventional therapy. This was followed by an open-label extension, where patients extended their rhPTH(1–84) (PTH) (n = 5), continued conventional treatment (CON) (n = 5), or withdrew from rhPTH(1–84) and resumed conventional therapy (PTHw) for an additional 24 months (n = 8). Bone biopsies were collected at months 6 (n = 42) and 30 (n = 18). After 6 and 30 months, the overall cortical microarchitecture (cortical porosity, thickness, pore density, and mean pore diameter) in the PTH group did not differ from that of the PLB/CON and PTHw groups. Still, the PTH group had a significantly and persistently higher percentage of pores undergoing remodeling than the PLB/CON groups. A significantly higher percentage of these pores was undergoing bone formation in the PTH compared with the PLB/CON groups, whereas the percentage of pores with erosion only was not different. This resulted in a shift in the ratio between formative and eroded pores, reflecting a faster transition from erosion to formation in the PTH-treated patients. In the rhPTH(1–84) withdrawal group PTHw, the latter effects of PTH were completely reversed in comparison to those of the PLB/CON groups. In conclusion, rhPTH(1–84) replacement therapy in hypoparathyroidism patients promotes intracortical remodeling and its transition from erosion to formation without affecting the overall cortical microstructure. The effect persists for at least 30 months and is reversible when treatment is withdrawn.

OriginalsprogEngelsk
Artikelnummere10829
TidsskriftJBMR Plus
Vol/bind7
Udgave nummer12
Antal sider14
ISSN2473-4039
DOI
StatusUdgivet - dec. 2023

Bibliografisk note

Funding Information:
The VELUX Foundation (VELUX25723), a Danish Southern Region Research Grant (18/17871), Aase and Ejnar Danielsen Foundation (10‐001584), Nycomed (for free study drugs (rhPTH[1–84] and similar placebo), Danish Council for Independent Research in Medical Science, The Novo Nordic Foundation, and the Central Denmark Region Foundation.

Funding Information:
Tanja Sikjær received an unrestricted research Grant from Shire (Takeda) to finance an unrelated study and received speaker's fees from Takeda and UCB. Lars Rejnmark received a research grant and is a research investigator and/or advisory board member of Takeda, Amolyt, Kyowa Kirin, Ascendis Pharma, and Calcilytix Therapeutics. Annemarie Brüel and Jesper Skovhus Thomsen received a research grant from Keros Therapeutics for an unrelated study. Thomas Levin Andersen received reagents for free and collaborated with ACD Bioscience, 10X Genomics, NanoString, ROWIAK LaserLabSolutions, Amgen, Merck, and Shire on unrelated studies.

Publisher Copyright:
© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Fingeraftryk

Dyk ned i forskningsemnerne om 'Transitory Activation and Improved Transition from Erosion to Formation within Intracortical Bone Remodeling in Hypoparathyroid Patients Treated with rhPTH(1–84)'. Sammen danner de et unikt fingeraftryk.

Citationsformater