Subchondral Bone Mineral Density Research Articles

Nasal septum-derived chondroprogenitor cells control mandibular condylar resorption consequent to orthognathic surgery: a clinical trial.

Condylar resorption is an aggressive and disability form of temporomandibular joint (TMJ) degenerative disease, usually non-respondent to conservative or minimally invasive therapies and often leading to surgical intervention and prostheses implantation. This condition is also one of the most dreaded postoperative complications of orthognathic surgery, with severe cartilage erosion and loss of subchondral bone volume and mineral density, associated with a painful or not inflammatory processes. Because regenerative medicine has emerged as an alternative for orthopedic cases with advanced degenerative joint disease, we conducted a phase I/IIa clinical trial (U1111-1194-6997) to evaluate the safety and efficacy of autologous nasal septal chondroprogenitor cells. Ten participants underwent biopsy of the nasal septum cartilage during their orthognathic surgery. The harvested cells were cultured in vitro and analyzed for viability, presence of phenotype markers for mesenchymal stem and/or chondroprogenitor cells, and the potential to differentiate into chondrocytes, adipocytes, and osteoblasts. After the intra-articular injection of the cell therapy, clinical follow-up was performed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and computed tomography (CT) images. No serious adverse events related to the cell therapy injection were observed during the 12-month follow-up period. It was found that autologous chondroprogenitors reduced arthralgia, promoted stabilization of mandibular function and condylar volume, and regeneration of condylar tissues. This study demonstrates that chondroprogenitor cells from the nasal septum may be a promise strategy for the treatment of temporomandibular degenerative joint disease that do not respond to other conservative therapies.

Long-Term Effects of Reproduction and Lactation on the Rat Supraspinatus Tendon and Proximal Humerus.

During pregnancy and breastfeeding, women undergo hormonal fluctuations required for fetal development, parturition, and infant growth. These changes have secondary consequences on the maternal musculoskeletal system, increasing the risk for joint pain and osteoporosis. Though hormone levels return to prepregnancy levels postpartum, women may experience lasting musculoskeletal pain. Sex disparities exist in the prevalence of musculoskeletal disorders, but it remains unclear how reproductive history may impact sex differences. Specifically, the effects of both reproductive history and sex on the rotator cuff have not been studied. Pregnancy and lactation affect bone microstructure, suggesting possible impairments at the enthesis of rotator cuff tendons, where tears commonly occur. Therefore, our objective was to evaluate how reproductive history affects sex differences of the supraspinatus tendon and proximal humerus using male, virgin female, and female rats with a history of reproduction (referred to as reproductive females). We hypothesized tendon mechanical properties and humeral bone microstructure would be inferior in reproductive females compared to virgin females. Results showed sex differences independent of reproductive history, including greater tendon midsubstance modulus but lower subchondral bone mineral density (BMD) in females. When considering reproductive history, reproductive rats exhibited reduced tendon insertion site modulus and trabecular bone micro-architecture compared to virgin females with no differences from males. Overall, our study identified long-term changes in supraspinatus tendon mechanical and humeral trabecular bone properties that result following pregnancy and lactation, highlighting the importance of considering reproductive history in investigations of sex differences in the physiology and pathology of rotator cuff injuries.

Mapping Subchondral Bone Density Distribution in the Canine C6-C7 Vertebral Endplates: A CT-OAM Study.

Intervertebral cage subsidence is a common complication in treating disc-associated cervical spondylomyelopathy in dogs. The mechanical stability of the vertebral endplate in contact with the cage is crucial to preventing subsidence. This study aims to assess subchondral bone mineral density (sBMD) in the canine vertebral endplate (specifically, the C6-C7 vertebral motion unit) as a measure of its mechanical stability. The sBMD distribution was mapped for the C6 caudal and C7 cranial vertebral endplates in 15 middle- to large-breed dogs using computed tomography osteoabsorptiometry. The sBMD distribution in the canine C6 and C7 vertebral endplates exhibited a heterogeneous pattern, with lower density observed in the central and dorsal contact areas of the nucleus pulposus, where common subsidence occurs. Our results suggest a potential need to redesign intervertebral cages to ensure that contact areas align with regions of higher bone density. A broad-based design extending toward the lateral and dorsal aspects of the annulus fibrosus contact area may enhance stability.

Intra-articular delivery of micronized dehydrated human amnion/chorion membrane reduces degenerative changes after onset of post-traumatic osteoarthritis.

Background: Micronized dehydrated human amnion/chorion membrane (mdHACM) has reduced short term post-traumatic osteoarthritis (PTOA) progression in rats when delivered 24h after medial meniscal transection (MMT) and is being investigated for clinical use as a disease modifying therapy. Much remains to be assessed, including its potential for longer-term therapeutic benefit and treatment effects after onset of joint degeneration. Objectives: Characterize longer-term effects of acute treatment with mdHACM and determine whether treatment administered to joints with established PTOA could slow or reverse degeneration. Hypotheses: Acute treatment effects will be sustained for 6weeks, and delivery of mdHACM after onset of joint degeneration will attenuate structural osteoarthritic changes. Methods: Rats underwent MMT or sham surgery (left leg). mdHACM was delivered intra-articularly 24h or 3weeks post-surgery (n = 5-7 per group). Six weeks post-surgery, animals were euthanized and left tibiae scanned using equilibrium partitioning of an ionic contrast agent microcomputed tomography (EPIC-µCT) to structurally quantify joint degeneration. Histology was performed to examine tibial plateau cartilage. Results: Quantitative 3D µCT showed that cartilage structural metrics (thickness, X-ray attenuation, surface roughness, exposed bone area) for delayed mdHACM treatment limbs were significantly improved over saline treatment and not significantly different from shams. Subchondral bone mineral density and thickness for the delayed treatment group were significantly improved over acute treated, and subchondral bone thickness was not significantly different from sham. Marginal osteophyte degenerative changes were decreased with delayed mdHACM treatment compared to saline. Acute treatment (24h post-surgery) did not reduce longer-term joint tissue degeneration compared to saline. Histology supported µCT findings and further revealed that while delayed treatment reduced cartilage damage, chondrocytes displayed qualitatively different morphologies and density compared to sham. Conclusion: This study provides insight into effects of intra-articular delivery timing relative to PTOA progression and the duration of therapeutic benefit of mdHACM. Results suggest that mdHACM injection into already osteoarthritic joints can improve joint health, but a single, acute mdHACM injection post-injury does not prevent long term osteoarthritis associated with meniscal instability. Further work is needed to fully characterize the durability of therapeutic benefit in stable osteoarthritic joints and the effects of repeated injections.

Subchondral bone in knee osteoarthritis: bystander or treatment target?

The subchondral bone is an important structural component of the knee joint relevant for osteoarthritis (OA) incidence and progression once disease is established. Experimental studies have demonstrated that subchondral bone changes are not simply the result of altered biomechanics, i.e., pathologic loading. In fact, subchondral bone alterations have an impact on joint homeostasis leading to articular cartilage loss already early in the disease process. This narrative review aims to summarize the available and emerging imaging techniques used to evaluate knee OA-related subchondral bone changes and their potential role in clinical trials of disease-modifying OA drugs (DMOADs). Radiographic fractal signature analysis has been used to quantify OA-associated changes in subchondral texture and integrity. Cross-sectional modalities such as cone-beam computed tomography (CT), contrast-enhanced cone beam CT, and micro-CT can also provide high-resolution imaging of the subchondral trabecular morphometry. Magnetic resonance imaging (MRI) has been the most commonly used advanced imaging modality to evaluate OA-related subchondral bone changes such as bone marrow lesions and altered trabecular bone texture. Dual-energy X-ray absorptiometry can provide insight into OA-related changes in periarticular subchondral bone mineral density. Positron emission tomography, using physiological biomarkers of subchondral bone regeneration, has provided additional insight into OA pathogenesis. Finally, artificial intelligence algorithms have been developed to automate some of the above subchondral bone measurements. This paper will particularly focus on semiquantitative methods for assessing bone marrow lesions and their utility in identifying subjects at risk of symptomatic and structural OA progression, and evaluating treatment responses in DMOAD clinical trials.

Effects of Leptin and Body Weight on Inflammation and Knee Osteoarthritis Phenotypes in Female Rats.

Leptin is a proinflammatory adipokine that contributes to obesity-associated osteoarthritis (OA), especially in women. However, the extent to which leptin causes knee OA separate from the effect of increased body weight is not clear. We hypothesized that leptin is necessary to induce knee OA in obese female rats but not sufficient to induce knee OA in lean rats lacking systemic metabolic inflammation. The effect of obesity without leptin signaling was modeled by comparing female lean Zucker rats to pair fed obese Zucker rats, which possess mutant fa alleles of the leptin receptor gene. The effect of leptin without obesity was modeled in female F344BN F1 hybrid rats by systemically administering recombinant rat leptin versus saline for 23 weeks via osmotic pumps. Primary OA outcomes included cartilage histopathology and subchondral bone micro-computed tomography. Secondary outcomes included targeted cartilage proteomics, serum inflammation, and synovial fluid inflammation following an acute intra-articular challenge with interleukin-1β (IL-1β). Compared to lean Zucker rats, obese Zucker rats developed more severe tibial osteophytes and focal cartilage lesions in the medial tibial plateau, with modest changes in proximal tibial epiphysis trabecular bone structure. In contrast, exogenous leptin treatment, which increased plasma leptin sixfold without altering body weight, caused mild generalized cartilage fibrillation and reduced Safranin O staining compared to vehicle-treated animals. Leptin also significantly increased subchondral and trabecular bone volume and bone mineral density in the proximal tibia. Cartilage metabolic and antioxidant enzyme protein levels were substantially elevated with leptin deficiency and minimally suppressed with leptin treatment. In contrast, leptin treatment induced greater changes in systemic and local inflammatory mediators compared to leptin receptor deficiency, including reduced serum IL-6 and increased synovial fluid IL-1β. In conclusion, rat models that separately elevate leptin or body weight develop distinct OA-associated phenotypes, revealing how obesity increases OA pathology through both leptin-dependent and independent pathways. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

CARTILAGE THICKNESS, SUBCHONDRAL BONE MINERAL DENSITY, AND AMBULATORY LOADING ARE CORRELATED IN NON-OSTEOARTHRITIC FEMORAL CONDYLES

A few studies have reported correlations between structural and functional parameters in healthy knees, and sometimes alterations of these correlations with OA. These observations suggested a new concept where knee OA could be related to a maladaptation between joint features. However, studies analyzing multiple features from different domains simultaneously are missing, which makes it difficult to fully understand the importance of relationships in maintaining joint homeostasis and their role in the development of OA. To assess the correlations among cartilage thickness (CTh), subchondral bone mineral density (sBMD), and ambulatory loading in non-OA femoral condyles. As commonly done, ambulatory loading was quantified using the peak knee adduction moment during walking (pKAM), which is a proxy for the distribution of load between medial and lateral compartments. To analyze comparable data, CTh and sBMD were expressed as medial-to-lateral (M/L) ratios. Therefore, this study tested the hypothesis that CTh M/L ratios, sBMD M/L ratios, and pKAM are positively correlated in non-OA femoral condyles. This study analyzed a subgroup of 48 young (25.7 ± 4.8 years; 22 males) asymptomatic volunteers with healthy knees enrolled in the HIPPA-compliant IRB-approved Lausanne Knee Study. This study aims at characterizing the structure and function of the knee, with a particular emphasis on the relationships among knee features The study protocol included clinical evaluation, radiographic imaging (weight-bearing Schuss and lateral radiographs of both knees), CT imaging (calibrated by a solid calcium hydroxyapatite-based bone mineral reference phantom) and 3T MRI of one randomly selected knee. 3D gait recordings were performed using a 16-camera motion capture system and force plates. CTh was obtained by manually segmenting the cartilage and bone on the DESS images, building 3D mesh models of bone and cartilage, and calculating the distance between the models. sBMD was obtained by registering the bone models from the DESS segmentation to the CT images and calculating the average CT intensity in the 3 mm of bone adjacent to cartilage. Mean CTh and sBMD were then calculated for six common regions of interest (ROIs) in the medial and lateral condyles and expressed as M/L ratios. pKAM was obtained following a standard inverse dynamics procedure applied to the marker-based motion capture and force plate recordings. Data processing was done using in-house software and algorithms previously validated. The relationship among CTh M/L ratios, sBMD M/L ratios and pKAM were assessed using Pearson correlation, with an α-level set a priori at 5%. All statistically significant correlations were positive, indicating larger CTh M/L ratios in knees with larger sBMD M/L ratios and larger pKAM, and vice versa. Specifically, CTh and sBMD M/L ratios were correlated in 5 of the 6 ROIs (0.31 ≤ r ≤ 0.53; 0.001 ≤ p ≤ 0.035), CTh M/L ratios in 4 ROIs were correlated with pKAM (0.29 ≤ r ≤ 0.33; 0.021 ≤ p ≤ 0.047), and sBMD M/L ratio in one ROI was correlated with pKAM (r = 0.31; p = 0.032). The hypothesis was supported, confirming the idea that structural and mechanical features of the knee are positively correlated, or adapted, in non-OA knees. This first study to show correlations among bone, cartilage, and mechanical loading provided insight into the functioning of the joint and underlined the potential of evaluating knee health based on relationships among features rather than on individual features in isolation. The analyses in this study will be extended to OA knees in future studies in order to determine the alterations of the relationships between knee features with OA.

THE SPATIAL CORRELATION BETWEEN CARTILAGE THICKNESS AND SUBCHONDRAL BONE MINERAL DENSITY INVERSES WITH INCREASING OA SEVERITY

While several properties of bone and cartilage have been extensively studied with respect to knee osteoarthritis (OA), little is known about the relationship between these tissues. To assess the spatial correlation between cartilage thickness (CTh) and subchondral bone mineral density (sBMD) in OA femoral condyles of varying disease severities. CT arthrograms of 60 knees (from 27 men, 33 females, 64.3 ± 9.1 years old) with various severities of medial compartment OA were analyzed in this IRB-approved study (26 K/L2, 25 K/L3, and 9 K/L4). CT images were manually segmented to reconstruct 3D mesh models of the femoral bone and cartilage. 3D CTh maps were calculated based on the distance between bone and cartilage models, and 3D sBMD maps were obtained by averaging the CT intensity in the 3mm of subchondral bone adjacent to cartilage. The spatial correlation between CTh and sBMD maps was quantified for the medial and lateral condyles of each knee using a statistical index ranging between –1.0 (CTh is thinner where sBMD is denser) and 1.0 (CTh is thicker where sBMD is denser). For comparison with standard methods described in the literature, the average CTh and sBMD were calculated for the load-bearing region of the medial and lateral condyles. Wilcoxon rank-sum tests were used to compare the spatial correlations and the average CTh and sBMD between the three OA severity groups. The level of significance was set at 5%, with Bonferroni correction for multiple comparisons. In the medial compartment, the spatial relationship between CTh and sBMD progressively shifted from being positively correlated in K/L2 knees to negatively correlated in K/L4 knees, with statistically significant differences among the three groups (Table 1). The average CTh and sBMD showed irregular patterns, with differences among groups rarely reaching statistical significance. No statistically significant difference was observed in the lateral compartment. The spatial correlation supported the concept of bone and cartilage working as a functional unit and the alteration of this functional unit with OA. The positive correlation in early disease suggests a link with mechanical loading, where cartilage is thicker and bone denser in areas of larger mechanical stimulation. Interestingly, evaluating the CTh-sBMD relationship instead of CTh or sBMD individually showed more consistent patterns across the stages of the disease.

280 mT static magnetic field promotes the growth of postpartum condylar cartilage

ABSTRACT Purpose Functional appliances made of permanent magnets have been used in jaw orthopedic treatment. However, whether the static magnetic field (SMF) generated by permanent magnets promotes the developmental sequence of condylar cartilage and thus promotes the growth of the mandible remains to be studied. The aim of this study was to investigate the effects of 280 mT SMF on postnatal condylar chondrogenesis and endochondral ossification and the roles of FLRT3, FGF2 and BMP2 signaling in this chondrodevelopmental sequences. Methods Forty-eight rats were assigned to two groups (control and SMF). The condyles were collected at the specified time points. The histomorphological changes in the condyle were observed by histological staining. The expression of proteins related to the proliferation and differentiation of the condylar cartilage and the changes in subchondral bone microstructure were analyzed by immunohistochemical staining and micro-CT scanning. FLRT3, FGF2, and BMP2 expression was detected by immunofluorescence staining. Results Under SMF stimulation, the cartilage of young rats grew longitudinally and laterally, and the thickness of the cartilage became thinner as it grew. The SMF promoted the proliferation and differentiation of condylar chondrocytes and endochondral ossification and increased subchondral bone mineral density, and BMP2 signaling was involved. Moreover, under SMF loading, the increased expression of FGF2 and FLRT3 were involved in regulating cartilage morphogenesis and growth. In late development, the decreased expression of FGF2/FLRT3 and the increased expression of BMP2 promoted endochondral ossification. The SMF accelerated this opposite expression trend. Conclusion FGF2/FLRT3 and BMP2 signals are involved in the regulatory effect of SMF exposure on chondrogenesis and endochondral ossification, which provides a theoretical basis for the clinical use of magnetic appliances to promote condylar growth.

Systemic iron reduction via an iron deficient diet decreases the severity of knee cartilage lesions in the Dunkin-Hartley guinea pig model of osteoarthritis

Iron accumulation is emerging as a player in aging-related disorders due to its propensity for generating reactive oxygen species (ROS). Studies investigating the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. We designed a proof-of-principle study to determine the effect of systemic iron deficiency, via an iron deficient diet, on knee OA in an animal model. Twelve-week-old male Hartley guinea pigs received the standard diet (n=6) or a diet devoid of iron (n=6) for 19-weeks. Iron levels were determined in the serum, liver, and articular cartilage. Knees were collected to assess structural changes related to OA (microcomputed tomography, histopathology). Immunohistochemistry was performed to evaluate the presence and distribution of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ROS-driven 4-hydroxynonenal (4-HNE)-induced protein adducts. Transcript expression was also assessed. Relative to control animals, an iron deficient diet reduced the concentration of this mineral in serum, liver, and articular cartilage. Iron deficient animals had lower histologic OA scores; decreased subchondral bone mineral density was also noted. This reduction in knee joint pathology was accompanied by a decrease in: ADAMTS4 in synovium; and 4-HNE protein adducts from lipid peroxidation in both the menisci and articular cartilage of iron deficient animals. Expression of iron-related genes in these tissues was also altered in treated animals. Results from this study suggest that systemic iron levels may play a role in knee OA pathogenesis, with a short-term deficit in dietary iron reducing the severity of knee cartilage lesions.

Psoralen downregulates osteoarthritis chondrocyte inflammation via an estrogen-like effect and attenuates osteoarthritis

Estrogen and its receptor play a positive role in the development of osteoarthritis (OA). Psoralen is a plant-derived estrogen analog. This study aimed to verify whether psoralen inhibits OA through an estrogen-like effect. First, human primary chondrocytes in the late stage of OA were extracted to complete collagen type II immunofluorescence staining and cell proliferation experiments. Subsequently, estrogen, psoralen and estrogen receptor antagonists were co-cultured with OA chondrocytes, and RT-PCR was performed to detect the gene expression. A rabbit OA model was subsequently made by anterior cruciate ligament transection (ACLT). They were set as Sham group, OA group and Psoralen group, respectively. The articular cartilage samples were taken after 5 weeks of treatment, and the effect was observed by gross observation, histological staining, micro-CT scanning of subchondral bone. The results of cellular experiments displayed that the cultured cells were positive for collagen II fluorescence staining and 12 μg/mL psoralen was selected as the optimal concentration. In addition, psoralen had effects similar to estrogen, promoting the expression of estrogen tar-get genes CTSD, PGR and TFF1 and decreasing the expression of the inflammation-related gene TNF- α, IL-1β and IL-6. The effect of psoralen was blocked after the use of an estrogen receptor antagonist. Further animal experiments indicated that the psoralen group showed less destruction of cartilage tissue and decreased OASRI scores compared with the OA group. A subchondral bone CT scan demonstrated that psoralen significantly increased subchondral bone mineral density (BMD), trabecular thickness and trabecular number and decreased trabecular separation. In summary, psoralen inhibits the inflammatory production of chondrocytes, which is related to estrogen-like effect, and can be used to attenuate the progression of OA.

Physiological levels of estradiol limit murine osteoarthritis progression.

Among patients with knee osteoarthritis (OA), postmenopausal women are over-represented. The purpose of this study was to determine whether deficiency of female sex steroids affects OA progression and to evaluate the protective effect of treatment with a physiological dose of 17β-estradiol (E2) on OA progression using a murine model. Ovariectomy (OVX) of female mice was used to mimic a postmenopausal state. OVX or sham-operated mice underwent surgery for destabilization of the medial meniscus (DMM) to induce OA. E2 was administered in a pulsed manner for 2 and 8 weeks. OVX of OA mice did not influence the cartilage phenotype or synovial thickness, while both cortical and trabecular subchondral bone mineral density (BMD) decreased after OVX compared with sham-operated mice at 8 weeks post-DMM surgery. Additionally, OVX mice displayed decreased motor activity, reduced threshold of pain sensitivity, and increased number of T cells in the inguinal lymph nodes compared to sham-operated mice 2 weeks after OA induction. Eight weeks of treatment with E2 prevented cartilage damage and thickening of the synovium in OVX OA mice. The motor activity was improved after E2 replacement at the 2 weeks time point, which was also associated with lower pain sensitivity in the OA paw. E2 treatment protected against OVX-induced loss of subchondral trabecular bone. The number of T cells in the inguinal lymph nodes was reduced by E2 treatment after 8 weeks. This study demonstrates that treatment with a physiological dose of E2 exerts a protective role by reducing OA symptoms.

Cervical and First Thoracic Spine Hounsfield Units Assessment and Relationship to Clinical Outcomes and Cervical Sagittal Parameters in Patients Undergoing Anterior Cervical Spine Surgery

This study had 3 objectives: to compare bone mineral density (BMD) from 3 axial slices, subchondral trabecular bone 2 mm inferior to the cranial endplate, middle of the vertebral body, and subchondral trabecular bone 2 mm superior to the caudal endplate; assess BMD variations and correlations of C1-T1 vertebrae; and correlate BMD with clinical outcomes and cervical sagittal parameters in patients undergoing anterior cervical discectomy and fusion. The study enrolled 71 patients who underwent anterior cervical discectomy and fusion between March 2017 and January 2020. Patient demographics, clinical outcomes, cervical sagittal parameters, and Hounsfield units (HUs) of C1-T1 vertebrae were recorded. Analysis of variance was performed to compare HUs from the axial slices. Pearson correlation coefficient was performed to calculate the relationship between mean HUs of C1-T1 and to assess correlations of mean HUs with clinical outcomes and cervical sagittal parameters. There were no significant differences between HUs of 3 axial levels. Mean HUs were highest in the mid-cervical spine (C4). Significant correlations in mean HUs among all measured spinal levels were observed. Age, sex, and body mass index were not related to mean HUs. Visual analog scale, Neck Disability Index, and Patient Health Questionnaire-9 scores were not related to HUs before and after surgery. There were significant correlations among mean HUs of C2-T1 vertebrae, C2-C7 sagittal vertical axis, and cranial tilt. Mean HUs of C4 had the strongest correlation with C2-C7 sagittal vertical axis. To our knowledge, this is the first study of cranial and caudal subchondral trabecular BMD using HUs and comparing them with the middle of the vertebral body and study of correlations between mean HUs of C1-T1 vertebrae and clinical outcomes and cervical sagittal parameters. Correcting C2-C7 sagittal vertical axis and cranial tilt would improve BMD of C1-T1 vertebrae.

The Utility of Quantitative Computed Tomography to Detect Differences in Subchondral Bone Mineral Density Between Healthy People and People With Pain Following Wrist Trauma.

The mechanisms underlying chronic pain development following musculoskeletal trauma are complex and multifactorial. In their search, some researchers are turning to the subchondral bone as a potential contributor to pain due to its vascularity, using a depth-specific imaging technique. However, this technique has been mainly used in the knee. We propose the use of a quantitative computed tomography (QCT) depth-specific analysis to measure subchondral bone following wrist trauma. Ten participants (n = 5 post-trauma; n = 5 healthy) underwent bilateral computed tomography scans of their wrist accompanied by a calibration phantom with known densities. Average subchondral volumetric bone mineral density (vBMD) was studied at three depths from the subchondral surface (0-2.5, 2.5-5, 5-7.5 mm) according to radial articular surface contact in both wrists of each participant. Percentage differences and Cohen's d effect sizes were calculated to analyze bilateral vBMD and vBMD differences between groups. This image-based tool demonstrated subject-specific, depth-specific, and joint-specific measures of vBMD within the wrist. This methodology highlighted the differences between depth-specific vBMD in healthy people and people who have experienced wrist trauma. Overall, the healthy cohort demonstrated higher vBMD across all three depths and both articular surfaces. This imaging technique further distinguished between subchondral cortical and trabecular bones, wherein clinical implications can be drawn from these distinctions in future work. Our study therefore supports the utility of a QCT imaging technique in detecting differences in depth-specific vBMD in the wrist.

Effect of periacetabular osteotomy on the distribution pattern of subchondral bone mineral density in patients with hip dysplasia.

Despite the availability of long-term follow-up data, the effect of pelvic osteotomy on the natural history of osteoarthritis is not yet fully understood, partly because there is untapped potential for radiographs to better describe osteoarthritis. Therefore, this study aimed to assess the distribution of subchondral bone mineral density (BMD) across the acetabulum in patients with hip dysplasia immediately (2 weeks) and 1 year after undergoing periacetabular osteotomy (PAO). To that end, we reviewed 40 hips from 33 patients with developmental dysplasia of the hip who underwent PAO between January 2016 and July 2019 at our institution. We measured subchondral BMD through the articular surface of the acetabulum using computed tomography osteoabsorptiometry, dividing the distribution map into nine segments. We then compared the subchondral BMD between 2 weeks and 1 year after PAO in each area. At 2 weeks after PAO, the high-density area tended to be localized particularly in the lateral part of the acetabulum, whereas 1 year after PAO, the high-density area moved to the central and lateral parts. The percentage ratios of the subchondral BMD for the central-posterior, lateral-central, and lateral-posterior areas relative to the central-central area were significantly decreased at 1 year after PAO, as compared to those at 2 weeks after PAO. These findings suggest that loading was altered by PAO to be more similar to physiological loading. A long follow-up observational study is warranted to confirm the association between early changes in subchondral BMD by PAO and joint degeneration.

Hemodynamic stress shapes subchondral bone in osteoarthritis: An emerging hypothesis.

Osteoarthritis (OA) is no longer regarded as a simple wear-and-tear problem of articular cartilage. Instead, OA is a whole joint disorder involving both cartilaginous and non-cartilaginous tissues such as subchondral bone and synovium. Among them, subchondral bone undergoes constant remodeling in response to the changes of mechanical environment. Current understanding of subchondral bone disturbance in OA is limited to its link with an altered local mechanical loading as a result of ligament or meniscus injury. Very recently, hypertension, the most common vascular morbidity, has been emerged as an independent risk factor of OA. It might suggest a plausible role of systemic hemodynamic mechanical stress in subchondral bone remodeling and the pathogenesis of OA. However, their relationship remains not fully understood. Based on our preliminary clinical observation on the association of hemodynamic parameters with subchondral bone mass and microstructure in late-stage knee OA patients, we formulate a vascular etiology hypothesis of OA from a mechanobiology perspective. Noteworthily, hemodynamic stress associated with subchondral bone mineral density; yet compressive mechanical loading does not. Furthermore, hemodynamic parameters positively correlated with subchondral plate-like trabecular bone volume but negatively associated with rod-like trabecular bone volume. In contrast, compressive mechanical loading tends to increase both plate-like and rod-like trabecular bone volume. Taken together, it warrants further investigations into the distinct role of hemodynamic or compressive stress in shaping subchondral bone in the pathophysiology of OA.The Translational potential of this articleThis work provides a new insight, from the angle of biomechanics, into the emerging role of vascular pathologies, such as hypertension, in the pathogenesis of OA. It might open up a new avenue for the development of a mechanism-based discovery of novel diagnostics and therapeutics.

Computed Tomography Osteoabsorptiometry Evaluation of Cervical Endplate Subchondral Bone Mineral Density.

Basic Science. Poor subchondral bone mineral density (sBMD) has been linked with subsidence of cervical interbody devices or grafts, which are traditionally placed centrally on the endplates. Considering that sBMD reflects long-term stress distributions, we hypothesize that the cervical uncovertebral joints are denser than the central endplate region. This study sought to investigate density distributions using computed tomography osteoabsorptiometry (CT-OAM). Twelve human cervical spines from C3-C7 (60 vertebrae, 120 endplates) were imaged with CT and segmented to create 3D reconstructions. The superior and inferior endplates were isolated, and the sBMD of the whole endplate, endplate center, and uncus was evaluated using CT-OAM. Density distributions were compared across the subaxial cervical spine. The uncinate region of the inferior and superior endplates was significantly denser than the central endplate across all vertebral levels (P < .01). When comparing sBMD of the whole inferior and superior endplates, the superior endplate was significantly denser than the inferior endplate (P < .0001). However, the inferior uncus was denser than the superior uncus (P = .035). When assessing sBMD by vertebral level, peak densities were observed at C4 and C5, while C7 was, on average, significantly less dense than all other vertebrae. The subchondral bone of the cervical uncovertebral joints is significantly denser than the central endplates. While the superior endplate in its entirety is denser than the inferior endplate, the inverse was true for the uncovertebral joints. This study serves as a basis for future investigations of new implant designs and their implications on subsidence.

CT Osteoabsorptiometry Assessment of Subchondral Bone Density Predicts Intervertebral Implant Subsidence in a Human ACDF Cadaver Model.

Cadaveric biomechanics study. Subchondral bone mineral density (sBMD) reflects the long-term mineralization and distribution of stress on joints. The use of 3-dimensional (3-D) methods to evaluate sBMD, including computed tomography osteoabsorptiometry (CT-OAM), enables the assessment of density distribution with emphasis on subchondral bone. This study sought to measure the sBMD of cervical endplates using CT-OAM and correlate it to mechanical implant subsidence in a cadaveric model. Fourteen fresh human cadaveric cervical spines were subjected to dynamic testing after single level discectomy and instrumentation using a PEEK interbody spacer. Specimens were imaged with CT 3 times: 1st) whole intact cervical spine, 2nd) after implantation, and 3 rd) after testing. These images were used to assess sBMD distributions using CT-OAM directly underneath the spacer. Subsidence was defined as the displacement of the device into the endplates. The observed "failure mode" was consistently recorded as subsidence, with a mean of 0.45 ± 0.36 mm and 0.40 ± 0.18 mm for the C4-5 and C6-7 levels, respectively. There were no differences by level. The experimental cyclic test showed that denser endplates experienced less deformation under the same load. This study achieved its stated aim of validating the use of CT-OAM as a method to analyze the sBMD of the cervical endplates. Studies such as this are providing new information on available technology such as CT-OAM, providing new tools for clinicians treating spinal conditions in need of augmentation and stabilization via interbody devices.

Does medial-to-lateral tibial bone mineral density ratio change following six weeks of twice weekly neuromuscular exercise in patients with knee osteoarthritis?

Purpose: Knee osteoarthritis (OA) is characterized by increased subchondral bone mineral density (BMD). At the knee joint, proximal tibial BMD is associated with dynamic joint loads, and thereby serves as a surrogate structural marker of altered joint loading patterns. Neuromuscular exercise is an effective means of altering knee joint biomechanics as well as improving pain and function in people with knee OA. However, the mechanisms underlying reductions in pain following exercise therapy are poorly understood.

Subchondral bone microarchitecture and mineral density in human osteoarthritis and osteoporosis: A regional and compartmental analysis.

Osteoarthritis (OA) and osteoporosis (OP) are historically considered to be inversely correlated but there may be an overlap between the pathophysiology of the two diseases. This study aimed to investigate the subchondral bone microarchitecture and matrix mineralization, and the association between them in OA and OP in relation to the degree of cartilage degeneration. Fifty-six osteochondral plugs were collected from 16 OA femoral heads. They were graded on a regional basis according to the stages of cartilage degeneration, as evaluated by a new macroscopic and a modified microscopic grading system. Twenty-one plugs were collected from seven femoral heads with OP. Plugs were scanned by microcomputed tomography and the microarchitectural and mineral properties were obtained for both subchondral plate and trabecular bone. Microarchitecture and material and apparent densities of subchondral bone in OP were similar to regions with early cartilage degeneration but different from regions with advanced cartilage degradation in OA femoral heads. Subchondral trabecular bone was more mineralized than subchondral plate in both OP and OA, and this compartmental difference varied by severity of cartilage degradation. Furthermore, the relationship among trabecular bone volume fraction, tissue mineral density, and apparent bone density was similar in OP and different stages of OA. Subchondral bone microarchitecture and mineral properties in OP are different from OA in a regionalized manner in relation to stages of cartilage degeneration. Both regional and compartmental differences at structural, material, and cellular levels need to be studied to understand the transition of OA subchondral bone from being osteoporotic to sclerotic.