Large osteocyte lacunae in iliac crest infantile bone are not associated with impaired mineral distribution or signs of osteocytic osteolysis

Jandl, Nico Maximilian<sup>1,2</sup>; von Kroge, Simon<sup>2</sup>; Stürznickel, Julian<sup>2</sup>; Baranowsky, Anke<sup>2</sup>; Stockhausen, Kilian Elia<sup>2</sup>; Mushumba, Herbert<sup>3</sup>; Beil, Frank Timo<sup>1</sup>; Püschel, Klaus<sup>3</sup>; Amling, Michael<sup>1</sup>; Rolvien, Tim<sup>1,2</sup>

Affiliations

¹Department of Orthopedics, University Medical Center Hamburg‐Eppendorf, Martinistr. 52, 20246 Hamburg, Germany

²Department of Osteology and Biomechanics, University Medical Center Hamburg‐Eppendorf, Lottestr. 59, 22529 Hamburg, Germany

³Department of Legal Medicine, University Medical Center Hamburg‐Eppendorf, Butenfeld 34, 22529 Hamburg, Germany

Abstract and keywords

The enlargement of osteocyte lacunae via osteocytic osteolysis was previously detected in situations of increased calcium demand (e.g., lactation, vitamin D deficiency). However, it is unclear whether similar processes occur also in the growing infantile skeleton and how this is linked to the mineral distribution within the bone matrix. Human iliac crest biopsies of 30 subjects (0–6 months, n = 14; 2–8 years, n = 6 and 18–25 years, n = 10) were acquired. Bone microarchitecture was assessed by micro-CT, while cellular bone histomorphometry was performed on undecalcified histological sections. Quantitative backscattered electron imaging (qBEI) was conducted to determine the bone mineral density distribution (BMDD) as well as osteocyte lacunar size and density. We additionally evaluated cathepsin K positive osteocytes using immunohistochemistry. Infantile bone was characterized by various signs of ongoing bone development such as higher bone (re)modeling, lower cortical and trabecular thickness compared to young adults. Importantly, a significantly higher osteocyte lacunar density and increased lacunar area were detected. Large osteocyte lacunae were associated with a more heterogeneous bone mineral density distribution of the trabecular bone matrix due to the presence of hypermineralized cartilage remnants, whereas the mean mineralization (i.e., CaMean) was not different in infantile bone. Absence of cathepsin K expression in osteocyte lacunae indicated nonexistent osteocytic osteolysis. Taken together, we demonstrated that the overall mineralization distribution in infantile bone is not altered compared to young adults besides high trabecular mineralization heterogeneity. Our study also provides important reference values for bone microstructure, BMDD and osteocyte characteristics in infants, children and young adults. Infantile bone displays large osteocyte lacunae indicating a developmental phenomenon rather than osteocytic osteolysis. Larger osteocytes may have superior mechanosensory abilities to enable bone adaption during growth.

Keywords: Infantile bone; Osteocyte; Osteocytic osteolysis; qBEI; Cathepsin K; Mineralization

Links

DOI: 10.1016/j.bone.2020.115324

PubMed: 32198110

WoS: 000530069000015

History

Received: 2019-12-22

Revised: 2020-2-29

Accepted: 2020-3-16

Online: 2020-03-19

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2022	Hedjazi G, Guterman-Ram G, Blouin S, Schemenz V, Wagermaier W, Fratzl P, Hartmann MA, Zwerina J, Fratzl-Zelman N, Marini JC. Alterations of bone material properties in growing Ifitm5/BRIL p.s42 knock-in mice, a new model for atypical type vi osteogenesis imperfecta. Bone. September 2022;162:116451.
2023	Misof BM, Roschger P, Mähr M, Fratzl-Zelman N, Glorieux FH, Hartmann MA, Rauch F, Blouin S. Accelerated mineralization kinetics in children with osteogenesis imperfecta type 1. Bone. January 2023;166:116580.
2020	Yorgan TA, Rolvien T, Stürznickel J, Vollersen N, Lange F, Zhao W, Baranowsky A, Rosenthal L, Hermans‐Borgmeyer I, Sharaf A, Karsak M, David J, Oheim R, Amling M, Schinke T. Mice carrying a ubiquitous R235W mutation of Wnt1 display a bone‐specific phenotype. J Bone Miner Res. September 2020;35(9):1726-1737.
2021	Stürznickel J, Jähn-Rickert K, Zustin J, Hennig F, Delsmann MM, Schoner K, Rehder H, Kreczy A, Schinke T, Amling M, Kornak U, Oheim R. Compound heterozygous frameshift mutations in MESD cause a lethal syndrome suggestive of osteogenesis imperfecta type XX. J Bone Miner Res. June 2021;36(6):1077-1087.
2022	Costantini A, Mäkitie RE, Hartmann MA, Fratzl-Zelman N, Zillikens MC, Kornak U, Søe K, Mäkitie O. Early-onset osteoporosis: rare monogenic forms elucidate the complexity of disease pathogenesis beyond type I collagen. J Bone Miner Res. September 2022;37(9):1623-1641.