Contents lists available at ScienceDirect Bone journal homepage: www.elsevier.com/locate/bone Full Length Article Age-related histological changes in calcifed cartilage and subchondral bone in femoral heads from healthy humans Andreas Wiggers Nielsen a, ⁎ , Rasmus Klose-Jensen a , Louise Brøndt Hartlev a , Lene Warner Thorup Boel b , Jesper Skovhus Thomsen c , Kresten Krarup Keller a , Ellen-Margrethe Hauge a,d a Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark b Institute of Forensic Medicine, Aarhus University, Aarhus, Denmark c Institute of Biomedicine – Anatomy, Aarhus University, Aarhus, Denmark d Department of Clinical Medicine, Aarhus University, Aarhus, Denmark ARTICLEINFO Keywords: Osteoarthritis Ageing Sex Calcifed cartilage Subchondral bone plate ABSTRACT Objective: Age is the most important risk factor for osteoarthritis (OA). It is suggested that changes in sub- chondral bone and calcifed cartilage may occur in early OA. Therefore, the aim was to investigate age-related changes in the femoral head composition. We hypothesise that the thickness of the subchondral bone plate decreases with age, while the thickness of the calcifed cartilage increases with age as seen in early-stage OA. Methods: Femoral heads from 29 women (20–74 years) and 32 men (23–78 years), who had died suddenly and unexpectedly, were obtained at autopsy. Individuals with bone or joint diseases or macroscopic abnormal car- tilagewereexcluded.Usingdesign-basedstereology,femoralheadvolumeaswellasthicknessandvolumeofthe calcifed cartilage and subchondral bone plate were estimated and correlated to sex and age. Results: The thickness and volume of the subchondral bone plate were not correlated with age. Calcifed car- tilage thickness and volume correlated positively with age in women, while the femoral head volume was correlated positively with age in men. Conclusion: In human femoral heads obtained from a cross-sectional population without macroscopic OA changes, the thickness of the subchondral bone plate did not change with age, which difers from the thinning seen in early OA. Surprisingly, the age-related changes of the volume and thickness of the calcifed cartilage and of the volume of the femoral head were diferent for women and men. This indicate that cartilage and bone metabolism is sex-specifc, which may infuence ageing of the hip joint. 1. Introduction Osteoarthritis (OA) is the most frequent joint disease in western countries with socioeconomic expenses exceeding billions of dollars every year [1]. Age is a signifcant risk factor for OA [2]. Wear and tear are considered as the major cause of OA, and treatment strategies have therefore focused on reinforcing and rebuilding the damaged cartilage [3-5]. However, age-related changes in the mineralised joint tissue may occur prior to cartilage damage [6]. Studies suggest that the subchondral bone may also be involved in the pathogenesis of OA as it increases in thickness [7,8] causing bone sclerosis in late-stage OA [7,9]. However, in early OA stages, thinning of the subchondral bone has been observed in human [10] and animal studies [11,12]. These early subchondral bone changes suggest that the juxta-articular bone turnover may also play an important role in the pathogenesis of OA [13]. The calcifed cartilage has been described to thicken in relation to local OA severity not only in animal studies [14,15], but also in human studies [16,17]. It has been hypothesised that alterations of the calci- fed cartilage may compromise its mechanical function as a connective andcushioningtissue,leadingtodegenerationoftheoverlyingarticular cartilage [18-20]. In aged humans, multiple tidemarks have been de- scribed [21], indicating advancement of the calcifed cartilage, but whether this is due to age or early OA transformations is currently unknown. The majority of human studies use μCT to investigate the bone https://doi.org/10.1016/j.bone.2019.115037 Received 5 April 2019; Received in revised form 18 July 2019; Accepted 15 August 2019 ⁎ Corresponding author at: Department of Rheumatology, Aarhus University Hospital, Nørrebrogade 44, Building 3, 8000 Aarhus C, Denmark. E-mail addresses: andreas.wiggers.nielsen@gmail.com (A.W. Nielsen), raujen@rm.dk (R. Klose-Jensen), louihart@rm.dk (L.B. Hartlev), lwb@forens.au.dk (L.W.T. Boel), jst@biomed.au.dk (J.S. Thomsen), kresten@au.dk (K.K. Keller), ellhau@rm.dk (E.-M. Hauge). Bone 129 (2019) 115037 Available online 16 August 2019 8756-3282/ © 2019 Elsevier Inc. All rights reserved. T