Analysis of Bone Mineral Density and Bone Quality of Cortical Bone in the Human Hyoid Body and Histological Observation of the Entheses.

The hyoid is the only bone in the human body that is completely independent, not forming a joint with any other bone; its position is maintained by the suprahyoid and infrahyoid muscles, as well as several ligaments. The purpose of this study was to ascertain the effect of the functional pressure arising from these muscles and ligaments on the hyoid body structure from its bone mineral density, bone quality, and histological observations. The area between the mesial-most part of each lesser horn and the center of the hyoid body was divided equally into four measurement regions. We conducted histological investigations at each measurement region and observed the entheses. To analyze bone mass and bone quality, we also measured bone mineral density (BMD) and analyzed biological apatite (BAp) crystallite orientation in the same regions. Histological observations identified periosteal insertions and fibrocartilaginous entheses. There was no significant difference in BMD between any of the measurement regions, but the preferential orientation of BAp crystallites was stronger in the infrahyoid muscles and ligaments, where fibrocartilaginous entheses are found, than in other places. This suggests that the functional pressure at these sites might exert a major effect not only on the morphological characteristics of the entheses but also on bone quality.

Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: a post hoc analysis of SELECT-PsA 1 and 2.

OBJECTIVES: To characterize the effect of upadacitinib 15 mg once daily (UPA15) on enthesitis in patients with psoriatic arthritis from the SELECT-PsA Phase 3 trials. METHODS: Patients with an inadequate response/intolerance to ≥ 1 non-biologic DMARD (SELECT-PsA 1) or ≥ 1 biologic DMARD (SELECT-PsA 2) received UPA15, adalimumab 40 mg every other week or placebo (weeks 0-24) switched to UPA15 (week 24 onward). The Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index were used to assess improvement in enthesitis, enthesitis resolution, maintenance of enthesitis resolution, and protection from enthesitis development through week 56. RESULTS: Data from 639 patients receiving UPA15 and 635 patients receiving placebo (including 317 patients who switched from placebo to UPA15) were analysed. UPA15 led to higher rates of enthesitis resolution vs placebo at week 24 (LEI: 59.8% vs 38.0%; SPARCC index: 50.6% vs 31.5%, respectively) and greater improvements in the LEI (-1.7 vs -1.0) and SPARCC index (-3.4 vs -1.9); improvements were maintained through week 56. Improvements were observed after 12 weeks of UPA15 treatment. Over 90% of patients without enthesitis (LEI = 0) at baseline receiving UPA15 were enthesitis-free at week 56, and UPA15 prevented recurrence of enthesitis at week 56 in > 80% of patients with enthesitis at baseline who achieved resolution (LEI = 0) at week 24. CONCLUSIONS: UPA15 is associated with a comprehensive improvement in enthesitis, with improvements observed after 12 weeks of treatment. Additionally, treatment with UPA15 was associated with maintaining an enthesitis-free state after resolution and protection against new-onset enthesitis. CLINICALTRIALS.GOV IDENTIFIERS: NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2).

2D shear wave elastography for the assessment of quadriceps entheses-a methodological study.

OBJECTIVE: To establish the scanning protocol for 2-dimensional shear wave elastography (SWE) on normal entheses by investigating the possible confounding factors that may increase the variability of measured elasticity. MATERIAL AND METHODS: 30 normal quadriceps entheses were scanned using SWE to compare the stiffness and coefficient variation by changing the ultrasonic coupling gel thickness, knee position, region of interest size, and scanning plane. RESULTS: No significant difference in median shear wave velocity (SWV) was observed in different coupling gel thicknesses. The median SWV was higher in the knee flexion position than in the extended position (p < 0.001). Increased knee flexion led to stiffer quadriceps enthesis and higher SWV (ρ = 0.8, p < 0.001). The median SWV was higher when the diameter region of interest was 4.0 mm than 2.0 mm (p = 0.001). The median SWV was higher in the transverse plane than in the longitudinal plane (p < 0.001). Strong correlation was found between SWV and the degree of the shear wave to muscle fiber direction (ρ = 0.8, p < 0.001). The coefficient variation was lower in a gel thickness of 2.5 cm, with an extended knee, a region of interest of 2.0 mm, and a longitudinal plane (p > 0.05). For interobserver reliability for the proposed protocol, the intraclass correlation coefficients was 0.763. CONCLUSION: In this study, we determined supine position with the knee extended; using 2.0 mm diameter region of interest and image acquisition at the longitudinal plane with thicker layer coupling gel seems most appropriate to reliably image healthy quadriceps entheses with SWE.

Entheseal changes and activity patterns in southern African hunter-gatherer/herders from the Holocene.

OBJECTIVES: Activity patterns and lifeways in southern African hunter-gatherer/herders (sAHGH) during the Holocene were dynamic, with subsistence activities and mobility varying through space and time. In this study, spatial and temporal variations in entheseal changes (ECs) are assessed as physical activity markers in sAHGH from the Holocene. METHODS: The Coimbra method was used to assess fibrocartilaginous ECs in the upper and lower limbs of 118 sAHGH from the Holocene. Descriptive statistics and generalized estimating equations were used to explore the association between ECs, sex, age, ecological biomes, and temporality. RESULTS: A total of 118 individuals were sampled, comprising 67 males, and 42 females, mostly from the fynbos (59/118), forest (30/118) and succulent karoo biomes (16/118). ECs were identified in 94% of the sample. Interobserver scoring suggests our findings are likely to underrepresent the extent of EC score differences in sAHGH. Findings indicate a complex pattern of physical activity in sAHGH with differences attributable to regional ecology rather than age or sex. More prominent ECs were identified in individuals from the forest biome, relative to the fynbos and succulent karoo biomes. These were consistent with resource search and processing costs, and terrain differences in these ecozones. ECs were only detected temporally relative to the infiltration of pastoralism (at 2000 BP) when the data were stratified by ecological biome. DISCUSSION: This study provides evidence that regional ecology plays a central role in driving activity patterns regardless of social or cultural organization. Ecological biomes provide a gradient along which the temporal impact of resource limitations on human biology, activity patterns and sociocultural behaviors can be studied.

Architecture of head and neck soft tissues and associated entheses: An exploration of sexual dimorphism in, and population differences between, New Zealand and Thai individuals.

Understanding the musculoskeletal anatomy of soft tissues of the head and neck is important for surgical applications, biomechanical modelling and management of injuries, such as whiplash. Additionally, analysing sex and population differences in cervical anatomy can inform how biological sex and population variation may impact these anatomical applications. Although some muscles of the head and neck are well-studied, there is limited architectural information that also analyses sex and population variation, for many small cervical soft tissues (muscles and ligaments) and associated entheses (soft tissue attachment sites). Therefore, the aim of this study was to present architectural data (e.g., proximal and distal attachment sites, muscle physiological cross-sectional area, ligament mass, enthesis area) and analyse sex and population differences in soft tissues and entheses associated with sexually dimorphic landmarks on the cranium (nuchal crest and mastoid process) and clavicle (rhomboid fossa). Through the dissection and three-dimensional analysis of 20 donated cadavers from New Zealand (five males, five females; mean age 83 ± 8 years; range 67-93 years) and Thailand (five males, five females; 69 ± 13 years; range 44-87 years), the following soft tissues and their associated entheses were analysed: upper trapezius, semispinalis capitis and the nuchal ligament (nuchal crest); sternocleidomastoid, splenius capitis and longissimus capitis (mastoid process); the clavicular head of pectoralis major, subclavius, sternohyoid and the costoclavicular (rhomboid) ligament (rhomboid fossa). Findings indicate that although muscle, ligament and enthesis sizes were generally similar to previously published data, muscle size was smaller for six of the eight muscles in this study, with only the upper trapezius and subclavius demonstrating similar values to previous studies. Proximal and distal attachment sites were largely consistent with the current research. However, some individuals (six of 20) had proximal upper trapezius attachments on the cranium, with most attaching solely to the nuchal ligament, contrasting with existing literature, which often describes attachment to the occipital bone. With respect to sexual dimorphism, the Thai sample exhibited more sex differences in muscle size than the New Zealand sample, but for enthesis size (area), both samples had the same amount of statistically significant sex differences (5 of 10). Additionally, some significant population differences were found when comparing muscle and enthesis size data between the New Zealand and Thai samples. Despite these findings, no sex or population differences were found for ligament size (mass) in either group. This paper presents new architectural data for several understudied areas of the head and neck, as well as providing analyses on sex and population differences, two areas that have limited representation in anatomy.

Imaging Characteristics of Diffuse Idiopathic Skeletal Hyperostosis: More Than Just Spinal Bony Bridges.

Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic condition characterized by new bone formation and enthesopathies of the axial and peripheral skeleton. The pathogenesis of DISH is not well understood, and it is currently considered a non-inflammatory condition with an underlying metabolic derangement. Currently, DISH diagnosis relies on the Resnick and Niwayama criteria, which encompass end-stage disease with an already ankylotic spine. Imaging characterization of the axial and peripheral skeleton in DISH subjects may potentially help identify earlier diagnostic criteria and provide further data for deciphering the general pathogenesis of DISH and new bone formation. In the current review, we aim to summarize and characterize axial and peripheral imaging findings of the skeleton related to DISH, along with their clinical and pathogenetic relevance.

Back-to-back: The co-occurrence of DISH and ankylosing spondylitis from early modern Poland.

OBJECTIVE: This case study evaluates an individual with skeletal changes consistent with DISH and ankylosing spondylitis. We present here an evaluation of the individual's pathological skeletal changes and a review of the potential diagnoses. Finally, we offer a differential diagnosis of co-morbidity infrequently found in the paleopathological record. MATERIALS: The skeletal remains of a male, aged 50 + years from the early modern Polish (17th-18th century CE) site of Drawsko 1. METHODS: Skeletal remains were examined for the presence of spondyloarthropathies. RESULTS: The individual presented with anterolateral fusion of the vertebral bodies of T6-T10 with a "dripping candle wax" appearance, fusion of the right costovertebral joint at rib 8, fusion of the left apophyseal joints of T8-T10, and the calcification of the supraspinous ligament at T3-T4. The left sacroiliac joint shows intra-articular and para-articular fusion; the right has bony changes consistent with ongoing fusion. Entheseal reactions were noted on the left clavicle, scapulae, first metacarpals, ulnae, and humerii. Diffuse idiopathic skeletal hyperostosis (DISH), ankylosing spondylitis (AS), reactive arthritis (RA), psoriatic arthritis (PA), and enteropathic arthritis (EA) are considered as differential diagnoses. CONCLUSIONS: Based on the skeletal pattern of involvement, the individual suffered from both DISH and AS, which has previously been reported once in the paleopathological literature since 1950. The clinical literature indicates that co-occurrence of these two conditions is possible, with approximately 40 individuals affected. SIGNIFICANCE: This case study is significant for demonstrating the co-occurrence of DISH and AS in the paleopathological record. Additionally, this case contributes to the understanding of heterogenous frailty and syndemics. LIMITATIONS: No radiographs were taken to confirm the differential diagnosis. No aDNA analysis was conducted. SUGGESTIONS FOR FURTHER RESEARCH: The remains have been reburied; no further analysis is possible.

Entheseal Involvement in Spondyloarthritis (SpA) and Gout: An Ultrasound Comparative Study.

Objective: To compare the assessment of entheses in subjects with spondyloarthritis (SpA) with patients with gout by the Madrid Sonographic Enthesis Index (MASEI). Method: This cross-sectional study includes videos of entheses evaluated by ultrasound (US) of 30 patients with SpA diagnosed according to the ASAS criteria and 30 patients with gout established by the presence of monosodium urate crystals. Entheses were evaluated for MASEI in 2 Institutes located in two different countries. Demographic and clinical data were registered. Total MASEI score, MASEI-inflammatory, and MASEI-chronic damage were analyzed. Comparisons between groups were obtained by chi-square test and Student's t-test. An inter-reading US reliability was realized. Results: Patients with gout were older and had significantly more comorbidities than those with SpA. The total MASEI score was not significantly different among diseases (p = 0.07). MASEI-inflammatory was significantly more prevalent at the Achilles tendon in SpA, while the proximal patellar tendon was in gout. Power Doppler was higher in SpA compared to gout (p = 0.005). MASEI-chronic damage related to calcification/enthesophytes predominated in gout (p = 0.043), while calcaneal erosions did in SpA (p = 0.008). The inter-reader concordance was excellent (0.93, CI 95% 0.87-0.96, p = 0.001). Conclusions: SpA and gout similarly involve entheses according to MASE, however, some inflammatory and chronic lesions differ significantly depending on the underlying disease and tendon scanned.

Evaluating bony predictors of bite force across the order Carnivora.

In carnivorans, bite force is a critical and ecologically informative variable that has been correlated with multiple morphological, behavioral, and environmental attributes. Whereas in vivo measures of biting performance are difficult to obtain in many taxa-and impossible in extinct species-numerous osteological proxies exist for estimating masticatory muscle size and force. These proxies include both volumetric approximations of muscle dimensions and direct measurements of muscular attachment sites. In this study, we compare three cranial osteological techniques for estimating muscle size (including 2D-photographic and 3D-surface data approaches) against dissection-derived muscle weights and physiological cross-sectional area (PCSA) within the jaw adductor musculature of 40 carnivoran taxa spanning eight families, four orders of magnitude in body size, and the full dietary spectrum of the order. Our results indicate that 3D-approaches provide more accurate estimates of muscle size than do surfaces measured from 2D-lateral photographs. However, estimates of a muscle's maximum cross-sectional area are more closely correlated with muscle mass and PCSA than any estimates derived from muscle attachment areas. These findings highlight the importance of accounting for muscle thickness in osteological estimations of the masticatory musculature; as muscles become volumetrically larger, their larger cross-sectional area does not appear to be associated with a proportional increase in the attachment site area. Though volumetric approaches approximate muscle dimensions well across the order as a whole, caution should be exercised when applying any single method as a predictor across diverse phylogenies.

Resolution of enthesitis by guselkumab and relationships to disease burden: 1-year results of two phase 3 psoriatic arthritis studies.

OBJECTIVE: To further characterize the effect of guselkumab, a selective IL-23p19-subunit inhibitor approved for PsA, on enthesitis and assess relationships between enthesitis resolution and patient status/outcomes. METHODS: Adults with active PsA despite standard therapies in the phase 3 DISCOVER-1 and DISCOVER-2 studies were randomized 1:1:1 to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, Q8W; or placebo through week 20 followed by guselkumab 100 mg Q4W. Independent assessors evaluated enthesitis using the Leeds Enthesitis Index (LEI; total score 0-6). Enthesitis findings through week 24 were pre-specified to be pooled across studies; post hoc and week 52 analyses also employed pooled data. RESULTS: Among 1118 randomized, treated patients in DISCOVER-1 and 2 who had ≥1 LEI site evaluated, 65% had enthesitis at baseline. These patients exhibited numerically more swollen and tender joints, systemic inflammation and impaired physical function than patients without enthesitis. Guselkumab Q4W and Q8W were superior to placebo in resolving pre-existing enthesitis at week 24 (45 and 50% vs 29%; both adjusted P = 0.0301). Enthesitis resolution rates continued to rise; 58% of guselkumab-randomized patients achieved resolution at week 52, including patients with mild (LEI = 1; 70-75%), moderate (LEI = 2; 69-73%) or severe (LEI = 3-6; 42-44%) enthesitis at baseline. Among guselkumab-randomized patients with resolved enthesitis at week 24, 42% achieved minimal disease activity at week 52, vs 17% of patients with unresolved enthesitis. CONCLUSION: Guselkumab resulted in higher proportions of PsA patients with resolved enthesitis by week 24, with maintenance of resolution rates through 1 year. As enthesitis confers greater disease burden, sustained resolution could portend better patient outcomes. CLINICAL TRIAL REGISTRATION: DISCOVER 1 (NCT03162796) and DISCOVER 2 (NCT03158285).

Biomechanics of the human thumb and the evolution of dexterity.

Systematic tool production and use is one of humanity's defining characteristics, possibly originating as early as >3 million years ago.1-3 Although heightened manual dexterity is considered to be intrinsically intertwined with tool use and manufacture, and critical for human evolution, its role in the emergence of early culture remains unclear. Most previous research on this question exclusively relied on direct morphological comparisons between early hominin and modern human skeletal elements, assuming that the degree of a species' dexterity depends on its similarity with the modern human form. Here, we develop a new approach to investigate the efficiency of thumb opposition, a fundamental component of manual dexterity, in several species of fossil hominins. Our work for the first time takes into account soft tissue as well as bone anatomy, integrating virtual modeling of musculus opponens pollicis and its interaction with three-dimensional bone shape form. Results indicate that a fundamental aspect of efficient thumb opposition appeared approximately 2 million years ago, possibly associated with our own genus Homo, and did not characterize Australopithecus, the earliest proposed stone tool maker. This was true also of the late Australopithecus species, Australopithecus sediba, previously found to exhibit human-like thumb proportions. In contrast, later Homo species, including the small-brained Homo naledi, show high levels of thumb opposition dexterity, highlighting the increasing importance of cultural processes and manual dexterity in later human evolution.

Biocultural evidence of precise manual activities in an Early Holocene individual of the high-altitude Peruvian Andes.

OBJECTIVES: Cuncaicha, a rockshelter site in the southern Peruvian Andes, has yielded archaeological evidence for human occupation at high elevation (4,480 masl) during the Terminal Pleistocene (12,500-11,200 cal BP), Early Holocene (9,500-9,000 cal BP), and later periods. One of the excavated human burials (Feature 15-06), corresponding to a middle-aged female dated to ~8,500 cal BP, exhibits skeletal osteoarthritic lesions previously proposed to reflect habitual loading and specialized crafting labor. Three small tools found in association with this burial are hypothesized to be associated with precise manual dexterity. MATERIALS AND METHODS: Here, we tested this functional hypothesis through the application of a novel multivariate methodology for the three-dimensional analysis of muscle attachment surfaces (entheses). This original approach has been recently validated on both lifelong-documented anthropological samples as well as experimental studies in nonhuman laboratory samples. Additionally, we analyzed the three-dimensional entheseal shape and resulting moment arms for muscle opponens pollicis. RESULTS: Results show that Cuncaicha individual 15-06 shows a distinctive entheseal pattern associated with habitual precision grasping via thumb-index finger coordination, which is shared exclusively with documented long-term precision workers from recent historical collections. The separate geometric morphometric analysis revealed that the individual's opponens pollicis enthesis presents a highly projecting morphology, which was found to strongly correlate with long joint moment arms (a fundamental component of force-producing capacity), closely resembling the form of Paleolithic hunter-gatherers from diverse geo-chronological contexts of Eurasia and North Africa. DISCUSSION: Overall, our findings provide the first biocultural evidence to confirm that the lifestyle of some of the earliest Andean inhabitants relied on habitual and forceful precision grasping tasks.

Imaging in the diagnosis and management of axial spondyloarthritis in children.

Imaging is often used at the time of diagnosis to exclude conditions other than arthritis, to confirm the physical examination if equivocal, and to assess the degree of inflammation and baseline damage. Plain radiography is helpful in the evaluation of damage from chronic inflammation, while ultrasound and magnetic resonance imaging (MRI) are helpful in the assessment of early disease and active inflammation. Multiple studies have shown that tenderness on physical examination of the sacroiliac joint is often discordant with imaging results, so MRI is increasingly relied upon to assess for objective evidence of inflammation. There are no widely accepted, validated tools for the pediatric population using ultrasound or MRI assessment of the peripheral joints. Validated tools exist for objective assessment of pediatric hip disease on radiographs and axial disease on MRI, but not on other imaging modalities. The utility of these scoring systems in clinical care and clinical trials remains untested.

Gendered division of labor in a Celtic community? A comparison of sex differences in entheseal changes and long bone shape and robusticity in the pre-Roman population of Verona (Italy, third-first century BC).

OBJECTIVES: The presence of a gendered subdivision of labor has been bioarchaeologically investigated in various prehistoric and historical contexts. Little is known, however, about the type of differences in daily activities characterizing men and women among the Celtic communities of Italy. The focus of the present study is the analysis of differences in patterns of entheseal changes (ECs) and long bone shape and robusticity between sexes among the Cenomani Gauls of Seminario Vescovile (SV-Verona, Italy, third-first century BC). MATERIALS AND METHODS: The sample includes 56 adult individuals (22 females and 34 males). Presence of ECs on nine bilateral postcranial attachment sites, and values of humeral and femoral shape and robusticity indices based on external measurements were compared between sexes by means of generalized linear models and Mann-Whitney tests. RESULTS: Results show a lack of difference between sexes in long bone shape and robusticity, and a higher incidence of upper and, especially, lower limb ECs in males. DISCUSSION: These results suggest the presence of sex-specific activities at SV mostly related to farming and differently influencing the considered variables. Also, this study suggests the relevance of a series of nonbiomechanical factors (developmental, hormonal, genetic, and methodological) when attempting biocultural reconstructions from osteoarchaeological samples.

Micro- and nano-bone analyses of the human mandible coronoid process and tendon-bone entheses.

The coronoid process provides attachment to temporalis and masseter muscles, and thus plays an important role in mastication. Tendons connect muscles and bones, mediating the transmission of functional loads to bones. Thus, tendon-bone entheses govern mechanical stress in bones. The preferential orientation of biological apatite (BAp) crystallites, the main mineral component in bones, is an important index for bone quality and function, and is largely influenced by locally applied stress. In this study, we analyzed BAp orientation, Young's modulus, and bone mineral density (BMD) at different sites in the human coronoid process. No differences in BMD were found among the analyzed sites, but BAp crystal orientation was observed to differ. BAp crystallites showed a uni-directional orientation in the mesiodistal direction at the coronoid process apex, but were oriented in the direction vertical to the occlusal plane at other sites. Young's modulus tended to vary according to the BAp orientation. At the apex, a tendon form with characteristics different from those at other sites, including the presence of a fibrocartilaginous layer that may act as a stretching brake to control stress concentration, was observed. These findings suggest that the functional pressure of the temporalis muscle affects bone quality and strength.

Ultrasound verified enthesophytes are associated with radiographic progression at entheses in psoriatic arthritis.

OBJECTIVES: The aim of this prospective study was to examine whether ultrasound or clinical abnormalities at enthesal sites predict radiographic progression at entheses in psoriatic arthritis (PsA). METHODS: Consecutive PsA patients were included and subjected to clinical and ultrasound assessments at 14 entheses at baseline, 6 and 12 months. Radiographs were performed at 0 and 12 months. By US, we investigated structural (erosions, osteophytes) and inflammatory changes [grey scale (0-32) and power Doppler (0-14, range global ultrasound score 0-140)], and radiographs were evaluated for enthesophytes and erosions (score range 0-56). Multivariate regression models were conducted to identify the possible association of clinical and ultrasound findings with radiographic progression. RESULTS: We examined 83 patients at baseline, of whom 43 (51.8%) had complete clinical, ultrasound and X-ray data. Twenty-four of 43 patients (55.8%) developed radiographic progression of entheses. These patients were younger (49.6 vs 59.3, P =0.005), had shorter disease duration (9.7 vs 17.9 years, P=0.015) and lower clinical disease activity at 6-months [disease activity in psoriatic arthritis (DAPSA) 6.7 vs 17.0, P=0.018] as compared with patients without progression. Non-progressors had higher ultrasound enthesophyte scores at baseline than progressors (20 vs 15, P<0.05). The multivariate regression analysis revealed that 48.6% of the variance of the X-ray score at 12-months follow-up (RegcoeffB = 0.827, P=0.000) could be explained by the baseline US enthesophyte score. CONCLUSION: Our data indicate that radiographic progression at entheses is linked with age, disease duration and ultrasound verified enthesophytes at baseline. No other ultrasound parameter predicted radiographic progression at entheses.

Biomechanical pathways of dentoalveolar fibrous joints in health and disease.

Spatial and temporal adaptations within periodontal tissues and their interfaces result from functional loads. Functional loads can be physiologic and/or pathologic in nature. The prolonged effect of these loads can alter the overall biomechanics of a dentoalveolar fibrous joint (dentoalveolar joint) by changing the form of the tooth root and its socket. This "sculpting" of the tooth root and alveolar bony socket is a consequence of several mechano-biological changes that occur within the periodontal complex of a load-bearing dentoalveolar joint. These include changes in biochemical expressions, structure, elemental composition, and mechanical properties of alveolar bone, the underlying tissues of the roots of teeth, and their interfaces. These physicochemical changes in tissues continue to prompt mechano-responsive biochemical activities at the attachment sites of periodontal ligament (soft) with bone (hard), and ligament with cementum (hard), which are the entheses of a load-bearing dentoalveolar joint. Forces at soft-hard tissue attachment sites between disparate materials with different stiffness values theoretically generate strain singularities or discontinuities. These discontinuities under prolonged functional loading increase the probability for failure to occur specifically at the enthesial zones. However, in a normal dentoalveolar joint, gradual stiffness gradients exist from ligament to bone, and from ligament to cementum. The gradual transitions in stiffness from softer ligament (lower stiffness) to harder bone or cementum (higher stiffness) or vice versa optimize tissue and interfacial strains. Optimization of tissue and ligament-enthesial physical and chemical properties facilitates transmission of cyclic forces of varying magnitudes and frequencies that collectively maintain the overall biomechanics of a dentoalveolar joint. The objectives of this review are 3-fold: (i) to illustrate physicochemical adaptations at the periodontal ligament entheses of a human periodontal complex affected by subgingival calculus; (ii) to demonstrate how to "program" the hallmarks of periodontitis in small-scale vertebrates in vivo to generate spatiotemporal maps of physicochemical adaptations in a diseased dentoalveolar joint; and (iii) to correlate dentoalveolar joint biomechanics in healthy and diseased states to spatiotemporal maps of physicochemical adaptations within respective periodontal tissues. This interdisciplinary approach demonstrates that physicochemical adaptations within periodontal tissues using the mechanics of materials (tissue mechanics), materials science (tissue composition), and mechano-biology (matrix molecules) can help explain the mechano-adaptation of dentoalveolar joints in normal and diseased functional states. Multiscale biomechanics and mechano-biology approaches can provide insights into the functional competence of a diseased relative to a normal dentoalveolar joint. Insights gathered from interdisciplinary and multiscale biomechanics approaches include the following: (i) physiologic loads related to chewing maintain a balance between mineral-forming and-resorbing biochemical cellular events, resulting in gradual stiffness gradients at the periodontal ligament entheses, and, in turn, sustain the overall biomechanics of a normal "healthy" dentoalveolar joint; (ii) pathologic loads resulting from tissue degradation and physical changes to the periodontal complex promote an abrupt stiffness gradient at the periodontal ligament entheses. The shift from gradual to an abrupt stiffness gradient could prompt a shift in the biochemical cascades, exacerbate mechano-responsive biochemical expressions at periodontal ligament entheses farther away from the site of insult, and culminate in joint degradation; (iii) sustained pathologic function on periodontally diseased joints exacerbates degradation of periodontal ligament entheses providing insights into "rescue therapy", such as the use of an adequate "mechanocal dose" to regain joint function; and (iv) spatiotemporal maps of changes in biochemical expressions, and physicochemical properties of strain-dominated affected sites, including the periodontal ligament entheses, can guide anatomy-specific therapeutics for tissue regeneration and/or disease control with the purpose of regaining dentoalveolar joint function. Modulation of occlusal loads could minimize disease progression and potentially assist in regaining functional attachment of ligament to bone and/or ligament to cementum of the dentoalveolar joint. Elucidating mechanisms that drive the breakdown of the functionally active periodontal complex burdened with microbes will provide the required critical insights into regenerative medicine and/or biomimetic approaches that would facilitate rescue/regain of dentoalveolar joint function.

Osteoarthritis: A problematic disease in past human populations. A dependence between entheseal changes, body size, age, sex, and osteoarthritic changes development.

Osteoarthritis is a problematic trait in terms of etiology and interpretation in past human populations. The relationships between osteoarthritic changes (osteophytes, porosity, and eburnation) and entheseal changes, body mass, stature, bone massiveness, sex, and age on the basis of skeletal material from Lekno (Poland) are analyzed here. Entheses were the strongest contributor to the prediction of osteophyte expression and when all types of changes and all joints were taken together. Stature demonstrates a negative dependence on porosity. When each joint was analyzed separately, entheses were the strongest contributor to the prediction of arthritis expression in the wrist and hip. Age was the strongest contributor to the prediction of arthritis expression in the elbow. Body mass, stature, bone massiveness, and sex had no effect on osteoarthritic changes in any of the examined joints. The results of the present study suggest an important dependence between entheses and osteoarthritic changes. Other factors had little to no effect on differences in OA severity. These results do not dispel all doubts but enrich knowledge about the effect of etiological factors on osteoarthritic change formation. This knowledge is essential for proper, reliable interpretation of osteoarthritic changes in the context of past human biology, ecology, and behavior.

A three-dimensional digital microscopic investigation of entheseal changes as skeletal activity markers.

OBJECTIVES: The current article explores the effectiveness of entheseal changes (EC) as skeletal activity markers by testing the correlation between such changes and cross-sectional geometric (CSG) properties while controlling for the effect of age and body size. MATERIALS AND METHODS: The originality of the article lies in capturing EC in a continuous quantitative manner using three-dimensional microscopy. Roughness and bone resorption were recorded on Zones 1 and 2 of three humeral entheses (subscapularis, supraspinatus, and infraspinatus) in a documented sample of 29 male skeletons. RESULTS: Our analysis found that merely 5.91% of the partial correlations between EC and CSG properties were statistically significant. In addition, two unexpected patterns were identified, namely a higher number of significant correlations on the left side entheses compared to the right side ones, and a higher number of correlations between minimum roughness and CSG properties compared to mean and maximum roughness. DISCUSSION: These patterns are the inverse of what we would expect if activity had exerted an important effect on EC expression. Therefore, they support the lack of association between EC and habitual activity, even though various factors potentially affecting the above results are discussed.

The mechanical hypothesis of septal aperture formation tested in an early medieval population from Ostrów Lednicki (Poland).

The aetiology of septal aperture formation is still an open question. The influence of bone robusticity, osteoarthritis, osteoporosis, and the size and shape of ulnar processes has been discussed. Some researchers have shown that weaker muscles lead to greater joint hypermobility, the impingement of ulnar processes on the humeral lamina, and, consequently, septal aperture formation. Assuming this theory is correct, the question is whether flexion or extension or both play a role in septal lamina perforation. The aim of the study was to examine the mechanical hypothesis of septal aperture formation in samples of skeletal material derived from an early medieval cemetery in Ostrów Lednicki (Poland). A total of 136 pairs of bones (humeri and ulnae) were examined. Septal aperture was scored as present or absent. Entheseal changes in ulna were used as markers of activity patterns, especially involving elbow extension and flexion. Entheseal changes were assessed based on a three-point rating scale. A significant negative correlation between septal aperture and triceps muscles was noted in right bones in females (τ = -0.331) and in both sexes combined (τ = -0.322). The relationship between septal aperture and the brachialis muscle was positive but non-significant. This means that looser triceps lead to greater looseness of the elbow, greater protrusion of the olecranon process, and consequent septal aperture formation. Different results were obtained for the brachialis, which may suggest that forearm flexion does not significantly affect septal lamina perforation.