Osteoarthritis (OA) is one of the most prevalent conditions in the world, particularly in the developed world with a significant increase in cases and their predicted impact as we move through the twenty-first century and this will be exacerbated by the covid pandemic. The degeneration of cartilage and bone as part of this condition is becoming better understood but there are still significant challenges in painting a complete picture to recognise all aspects of the condition and what treatment(s) are most appropriate in individual causes. OA encompasses many different types and this causes some of the challenges in fully understanding the condition. There have been examples through history where much has been learnt about common disease(s) from the study of rare or extreme phenotypes, particularly where Mendelian disorders are involved. The often early onset of symptoms combined with the rapid and aggressive pathogenesis of these diseases and their predictable outcomes give an often-under-explored resource. It is these “rarer forms of disease” that William Harvey referred to that offer novel insights into more common conditions through their more extreme presentations. In the case of OA, GWAS analyses demonstrate the multiple genes that are implicated in OA in the general population. In some of these rarer forms, single defective genes are responsible. The extreme phenotypes seen in conditions such as Camptodactyly Arthropathy-Coxa Vara-pericarditis Syndrome, Chondrodysplasias and Alkaptonuria all present potential opportunities for greater understanding of disease pathogenesis, novel therapeutic interventions and diagnostic imaging. This review examines some of the rarer presenting forms of OA and linked conditions, some of the novel discoveries made whilst studying them, and findings on imaging and treatment strategies.

There are three types of adipocytes in the human body, classified as white, brown and beige. Bone marrow adipose tissue (BMAT) is often described as having a heterogeneous appearance and has been suggested to be a distinct class of ‘yellow’ adipocytes. However, recent studies have also identified beige‐like adipocytes present in the bone marrow cavity, and they appear to have a relationship with the formation of bone like structures found in patients with osteoarthropathies, termed trabecular excrescences. The BMAT in osteoarthritic (OA) patients has an increased number of adipocytes compared to healthy and osteoporotic bone marrow. The objective of this study was to identify changes in BMAT composition between non‐osteoarthritic and osteoarthritic (OA) bone samples. Human joint samples from 28 patients (14 non‐OA, 14 OA) were obtained with informed consent from patients undergoing joint surgery at University Hospitals of Morecambe Bay NHS Trust (Lancaster, UK). North of Scotland NHS Research Ethics Committee (UK) approved this research. Samples were prepared for routine histological analysis and flow cytometry. Flow cytometric analysis gated for adipocytes by size and lipid content. Markers for adiponectin (Acrp30), uncoupling protein 1 (UCP1) and myogenic factor 5 (Myf5), were used to distinguish between white, beige and brown adipocytes. To corroborate the results, sections of joint tissues underwent immunohistochemical analysis. The anatomical location of the adipocytes within the bone marrow cavity was also studied. The data analysis showed an approximate 9:1 ratio of white to beige adipocytes found within BMAT, with only trace amounts of brown adipocytes identified. Statistical analysis to account for disease, age and biological sex demonstrated no significant difference in the adipocytes present between control and OA samples. However, male sex and ageing were shown to be factors for an increase in beige adipocytes. The histological study confirmed the presence of beige adipocytes and showed that, when present the beige adipocytes were found closer to the bone surface than the centre of the bone marrow adipose tissue. Previous studies have argued that BMAT is a distinct class of adipocyte. This study has demonstrated the presence of beige adipocytes within the BMAT of patients with and without OA. The methods used give a quantitative method of identifying different types of bone marrow adipocytes. Understanding changes in the anatomical composition of BMAT and the role of adipocytes in skeletal health may prove important in understanding the progression of age associated bone disorders. Support or Funding Information This work was funded by the Anatomical Society and sponsored by the American Association for Anatomy.

The presence of novel bone structures, termed trabecular excrescences, have previously been found in surgical waste tissue samples from patients with osteoarthritis, alkaptonuria and from aged bone samples. A form of trabecular excrescence is found associated with the presence of bone marrow adipocytes and the absence of bone lining cells. We hypothesize that the adipocytes are contributing to the formation of bone like structures. This is inconsistent with the current paradigm of osteoclast‐osteoblast coupled remodelling. This study aimed to determine the topographical distribution of trabecular excrescences throughout the trabecular bone in human joint samples and to further characterise their internal structure. Joint samples were obtained as surgical waste, with informed patient consent, from 20 patients with OA (mean age = 75.3) and 20 control patients without OA (mean age = 78.5). North of Scotland NHS Research Ethics Committee (UK) approved this research. Joint samples obtained included femoral heads, humeral heads, ankles, knees and shaft of femur. Each joint sample was sliced into sagittal sections. The sections were decalcified and processed for histology. Unstained sections were viewed under fluorescence microscopy. Sections were stained with haematoxylin and eosin and with immunohistochemical staining for collagen I, collagen VI and osteocalcin. Excrescences were found in both control and osteoarthritic samples. When found, the excrescences were often clustered, with several protrusions shown along a region of trabeculae. These results demonstrate that trabecular excrescences are globally distributed throughout the femoral head, and not specific to areas of osteoarthritic change. This suggests the formation of these structures may be linked to the ageing process rather than disease progression. Immunohistochemical staining demonstrated the presence of collagen VI within the extracellular matrix of the newly formed excrescences. However, we also noted the presence of osteocalcin in ‘smoothed over’ versions of excrescences. This study has shown that trabecular excrescences are initially formed by the deposition of collagen VI by adipocytes. However, the presence of osteocalcin suggested that excrescences have the potential to be remodelled through typical osteoblast‐osteoclast remodelling. Future treatments for skeletal disorders could look to exploit the scaffold like properties of structures formed by adipocytes. Support or Funding Information Anatomical Society PhD Studentship

A mammoth tusk contains an inner mineralized protein matrix of dentine and an outer layer of cementum. Enamel is only present on the tips of the tusks of young mammoths, and is worn away in older mammoths. Dentine is a mineralized connective tissue containing the inorganic component of dahlite [Ca10(PO4)6(CO3)H2O]. To determine the species from which ivory originated, often destructive methods are used. Raman spectroscopy is a non‐invasive laser‐based technique that has proven applications in the chemistry of mineralized tissue. Ivory and bone have similar biochemical properties. The aim of this study is to test the hypothesis that mammoth ivory is identifiable using Raman spectroscopy. Mammoth tusks were kindly loaned from the Natural History Museum, London, UK. All tusks were from the species Mammuthus primigenius discovered either in Lyakhov Islands or next to the Yenisei river, Krasnoyarsk (Siberia, Russia) and span the Pleistocene epoch, Cenerzoic era. The ivory was scanned with an inVia Raman micro spectrometer (Renishaw Ltd) equipped with a x50 objective lens and a 785nm laser. Spectra were acquired using line maps on cross sections of two samples, and individual spectral points were acquired independently at random or at points of interest on all samples. Data was analysed with principal component analysis (PCA) using an in‐house Matlab script. To date, the results of this study establishes that well preserved mammoth ivory can be characterized through the comparison of peak intensity ratios between organic v(CH) collagen peaks and inorganic v(PO) hydroxyapatite peaks. Differences were observed in the hydroxyapatite peak from spectra acquired near the medulla of the tusk compared to the cortex. This suggests that the tusk is more mineralized towards the cortex compared to dentine found closer to the medulla. A comparison of the average data from each mammoth tusk demonstrated that the mammoth spectral ‘fingerprint’ remains similar for all samples, though there was some inter‐variation in the mineralization of the tusks from mammoths of the same species. Further work in this study aims to compare the Raman spectra between mammoth and elephant ivory. This will have direct applications in archaeology, as the species from which an ivory sample is found could be identified without the need for more traditional, destructive techniques of valuable artefacts. Additionally, international trade regulations require proof of the species from which ivory is obtained. The information obtained in this study will be valuable in developing quick and non‐destructive methods for the identification of ivory from an unknown origin.