Tibial Bone Area Research Articles

Technical and Biological Reliability of pQCT Measured Bone and Muscle Tissue Quality Across the Age-Span

Introduction: Reliable peripheral quantitative computed tomography (pQCT) assessment is essential to the accurate longitudinal reporting of bone and muscle quality. However, the between-day reliability of pQCT and the influence of age on outcome reliability is currently unknown.Objective: To quantify the same- and between-day reliability of morphological pQCT at proximal and distal segments of the forearm, shank, and thigh, and explore the influence of participant body size, age, and sex on outcome reliability.Methods: Men and women (49 % female, 18-85 years, n=72-86) completed two consecutive-day pQCT testing sessions, where repeat measurements were conducted on day-one for technical error, and between-day for biological error quantification. Testing was undertaken following best practice body composition testing guidance, including standardized presentation and consistent time-of-day.Results: All measurements of bone were classified as having ‘good’ to ‘excellent’ reliability [intraclass correlation coefficient (r=0.786- 0.999], as were measurements of muscle area (ICC r=0.991-0.999) and total fat (r=0.996-0.999). However, between- and same-day muscle density measurements at the thigh and forearm were classified as ‘poor’ (r=0.476) and ‘moderate’ (r=0.622), respectively. Likewise, intramuscular fat area at the thigh was classified as ‘moderate’ (r=0.737) for between-day measurement. Biological error was inflated compared to technical error by an average of 0.4 % for most measurements. Error values tended to increase proportionally with the amount of tissue quantified and males had significantly greater biological error for measurement of distal tibial bone (p<0.002) and trabecular area (p<0.002). Biological error was inflated among older adults for measurement of forearm muscle density (p<0.002).Conclusions: Most pQCT outcomes can be implemented with confidence, especially outcomes that assess bone area and density at any of the radial, tibial, and femoral sites investigated herein. However, it is important to account for the influence of biological measurement error in further studies, especially for muscle and intramuscular fat outcomes derived by pQCT.

Subchondral bone expansion in advanced knee osteoarthritis: Relation with radiographic severity and role in surgical decision-making

BackgroundJoint space width (JSW) is a traditional imaging marker for knee osteoarthritis (OA) severity, but it lacks sensitivity in advanced cases. We propose tibial subchondral bone area (TSBA), a new CT imaging marker to explore its relationship with OA radiographic severity, and to test its performance for classifying surgical decisions between unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) compared to JSW. MethodsWe collected clinical, radiograph, and CT data from 182 patients who underwent primary knee arthroplasty (73 UKA, 109 TKA). The radiographic severity was scored using Kellgren-Lawrence (KL) grading system. TSBA and JSW were extracted from 3D CT-reconstruction model. We used independent t-test to investigate the relationship between TSBA and KL grade, and binary logistic regression to identify factors associated with TKA risk. The accuracy of TSBA, JSW and established classification model in differentiating between UKA and TKA was assessed using AUC. ResultsAll parameters exhibited inter- and intra-class coefficients greater than 0.966. Patients with KL grade 4 had significantly larger TSBA than those with KL grade 3. TSBA (0.708 of AUC) was superior to minimal/average JSW (0.547/0.554 of AUC) associated with the risk of receiving TKA. Medial TSBA, together with gender and Knee Society Knee Score, emerged as independent classification factors in multivariate analysis. The overall AUC of composite model for surgical decision-making was 0.822. ConclusionTibial subchondral bone area is an independent imaging marker for radiographic severity, and is superior to JSW for surgical decision-making between UKA and TKA in advanced OA patients.

Effects of whole body vibration on bone properties in growing rats

ABSTRACT This study aimed to examine the continuous effects of whole body vibration (WBV) on bone properties, in growing rats. Fifty 5-week-old male rats were divided into control and experimental groups. Each experimental group underwent WBV at 50 Hz (0.5 g, 15 min/day, 5 days/week) for 5 or 10 weeks. Bone size, muscle weight and bone mechanical strength of the right tibia were measured. Trabecular bone microstructure, cortical bone geometry and bone mass of the left tibia were analyzed by micro-CT. Serum levels of bone formation/resorption markers were also measured. In rats that underwent 5-week WBV, tibial cortical bone mineral content and cortical bone area significantly increased (p < 0.05), and tibial cortical bone volume, thickness, maximum load, break point and stiffness tended to be increased (p = 0.05–0.09), compared with control rats. In rats that underwent 10-week WBV, stiffness tended to be increased (p = 0.07), and the serum level of osteocalcin decreased, compared with control rats. These findings suggest that 5-week WBV had beneficial effects on bone properties, and that increased bone mineral content and cortical bone geometry may lead to higher bone mechanical strength. Further studies will be needed to determine the optimal conditions of WBV for improving bone properties in the growth stage.

Modelling Changes in Bone and Body Composition Over a Season in Elite Male Footballers.

This study investigated the change in bone and body composition characteristics of elite football players and recreationally active control participants across the course of a season. Fortysix participants (20 footballers and 26 recreationally active controls) were assessed by dual-energy x-ray absorptiometry and peripheral Quantitative Computed Tomography for a range of bone and body composition characteristics at four points over the course of a competitive season. Multilevel modelling was used to examine changes. Footballers had higher characteristics than controls for 24 out of 29 dual-energy x-ray absorptiometry and peripheral Quantitative Computed Tomography variables (all p<0.05). However, there was also significant random inter-individual variation in baseline values for all variables, for both footballers and controls (p < 0.05). Wholebody bone mineral density, leg and whole-body bone mineral content, tibial bone mass and area (38%) increased across the season in footballers (p < 0.05), and there was significant random inter-individual variation in the rate of increase of leg and whole-body bone mineral content (p<0.05). Whole-body bone mineral density, leg and whole-body bone mineral content, tibial bone mass and area (38%) increased over the course of the season in elite football players. The modelling information on expected changes in bone characteristics provides practitioners with a method of identifying those with abnormal bone response to football training and match-play.

Female Runners With Multiple Bone Stress Injuries Have Smaller Bone Area Compared To Healthy Runners

Bone stress injury (BSI) is an overuse injury reported in up to 20% of female runners. Many runners sustain recurrent BSI. However, the role of impaired bone properties and other risk factors in those with recurrent BSI remain to be characterized. PURPOSE: To identify bone features that distinguish women with a history of multiple BSI. METHODS: We enrolled 41 female runners, ages 18-30, with a history of 1 lower extremity BSI (1 BSI; n=15), ≥ 3 lower extremity BSI (multi BSI; n=12), or no BSI (n=14), for this cross-sectional study. We collected high-resolution peripheral quantitative CT (HR-pQCT) scans of the distal tibia, areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry, bone material strength index (BMSi) using microindentation (Osteoprobe), and questionnaires. RESULTS: There were no differences between groups in age, BMI, age of menarche, or aBMD. Multi BSI had higher Eating Disorder Examination Questionnaire (EDE-Q) scores and prevalence of amenorrhea than no BSI (p<0.05). Adjusting for height and weight, multi BSI had smaller total tibial bone area (p=0.049, Fig.), and a trend for greater total and trabecular volumetric BMD (vBMD; p=0.07, p=0.09, respectively) compared to no BSI. 1 BSI had higher BMSi compared to no BSI and multi BSI (p=0.04), and lower cortical porosity compared to no BSI (p=0.048). Among the cohort, BMSi was significantly associated with cortical porosity (p=0.04), but not with cortical vBMD, cortical tissue mineral density, or aBMD. EDE-Q score was inversely associated with total bone area (p=0.02). CONCLUSIONS: Our findings suggest runners with multi BSI have smaller bones and higher EDE-Q scores than no BSI. Total and trabecular vBMD appear to be higher in multi BSI compared to no BSI, though due to the small sample size, differences were not significant. Collectively, our findings suggest several bone properties and eating behaviors distinguish women with multi BSI and 1 BSI from no BSI.

Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects.

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).Design: Randomized double-blind placebo-controlled pilot trial.Methods: Twenty-three obese men (BMI≥35 kg/m2), 35–65 years old, were randomized to weight loss (diet and exercise) plus either anastrozole (AI+WL, n = 12) at 1 mg daily or placebo (PBO+WL, n = 11) for 6 months. Inclusion criteria: total testosterone <300 ng/mL (average of 2 measurements), estradiol≥10.9 pg/ml, LH <9 IU/l. Symptoms of hypogonadism by questionnaires; muscle strength by Biodex dynamometer; body composition and bone mineral density by dual-energy X-ray absorptiometry; bone microarchitecture and finite element analysis by high resolution peripheral quantitative-computed tomography.Results: After 6 months of therapy, AI+WL group had higher testosterone (p = 0.003) and lower estradiol (p = 0.001) compared to PBO+WL. Changes in symptoms and muscle strength did not differ between groups. AI+WL resulted in higher fat mass loss than PBO+WL (p = 0.04) without differences in changes in lean mass. Total and LDL cholesterol reduced more in the PBO+WL group compared to AI+WL (p = 0.03 for both), who experienced a minimal increase with unlikely meaningful clinical impact. Tibial trabecular bone area decreased more in PBO+WL than AI+WL group for which it remained stable (p = 0.03).Conclusions:Although AI+WL is effective in reversing the hormonal profile of HHG in severely obese men without causing major side effects, it does not lead to greater improvements in muscle strength and symptoms of hypogonadism compared to WL alone.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02959853.

MON-094 Aromatase Inhibitors and Weight Loss in Severely Obese Male Veterans with Hypogonadism: A Randomized Clinical Trial

Introduction: The prevalence of hypogonadism among males is influenced by aging and obesity. The increased expression of the aromatase enzyme in the adipose tissue of obese men leads to a high conversion of androgens to estrogen, exerting a negative feedback on the hypothalamus-pituitary-gonadal axis contributing to hypogonadotropic hypogonadism. Our objective is to determine if anastrozole, an aromatase inhibitor (AI), in combination with weight loss could have a positive effect on symptoms of hypogonadism and muscle strength, and to evaluate the impact on bone mineral density (BMD) and bone quality. Methods: Twenty-three obese men (BMI≥35kg/m2) aged 35-65 years old with hypogonadotropic hypogonadism were randomized in a 6-month double-blind placebo-controlled trial of weight loss (with diet and exercise) plus either anastrozole (n=12) or placebo (PBO) (n=11). The inclusion criteria were morning testosterone <300 ng/mL (mean of 2 measurements), estradiol >10.9 pg/mL, and LH <9 IU/L. The hypogonadal symptoms were evaluated by 4 questionnaires: IPSS, qADAM, IWQOL, and IIEF-5, and the muscle strength was measured by Biodex machine. The body composition and BMD were determined by DXA, and the bone microarchitecture by HR-pQCT. The hormonal levels, hypogonadal symptoms, muscle strength, and body composition were assessed at baseline, 3 months, and 6 months; whereas the BMD and bone microarchitecture were evaluated at baseline and 6 months. Results: Average weight loss at 6 months was -7.0±6.9% in the AI group vs -2.4±2.9% in the PBO group (p=0.12). At 6 months, testosterone levels increased by +95.2±66.3% in the AI group vs +0.8±29.4% in the PBO group (p<0.01), and estradiol levels decreased by -60.9±21.8% in the AI group vs +5.2±18.6% in the PBO group (p<0.01). LH levels increased by +66.6±89.3% in patients treated with AI and decreased by -4.8±24.2% in those who received PBO (p=0.06). There was no improvement of symptoms in the AI group (+18.9±48.7%) vs placebo (+7.8±34.1%) based on IIEF-5 questionnaire (p=NS) and no significant difference in muscle strength between groups. Lean mass was better preserved in the AI compared to the PBO group (-0.73±2.5% vs -3.60±2.70%, respectively; p=0.05). There was no change in spine BMD in the AI compared to the PBO group (-0.71±3.32% vs +3.22±4.90%, respectively; p=0.08), and no change in tibial trabecular bone area in the AI compared to the decrease in the PBO group (+0.12±0.68% vs -2.09±2.20%, respectively; p<0.05). Conclusion: AI plus weight loss improves the hormonal profile of severely obese men with hypogonadism and prevents weight loss-induced loss of lean mass without causing major side effect on BMD within 6 months of therapy. However, in this short-term study with limited sample size, we found no significant improvement in symptoms of hypogonadism. Further large and long-term trials are needed to confirm these results.

Intensive terrestrial or marine locomotor strategies are associated with inter- and intra-limb bone functional adaptation in living female athletes.

ObjectivesTo systematically characterize intra‐limb patterns of skeletal plasticity to loading among living women, in order to better understand regional complexity in structural adaptation within the lower limb and more accurately infer behavior in the past.Materials and methodsWe used peripheral quantitative computed tomography imaging of the femur, tibia, first and second metatarsals to quantify bone morphology among female controls and athletes representative of either terrestrial or marine mobility, grouped by loading category (odd‐impact, repetitive low‐impact, and high‐magnitude). Parameters included midshaft bone density, areas, rigidity, and shape, epiphyseal bone densities and areas. We assessed between‐group differences and the influence of training history on significant variation among the loading groups.ResultsTerrestrial mobility strategies were best distinguished by significant midshaft periosteal hypertrophy across the lower limb/foot relative to controls, and by particularly high midshaft femoral and tibial cortical bone areas relative to rowers. Enhanced midshaft bone area was typically paired with decreased bone density among athlete groups. Sport‐specific variation in training duration/timing was significantly correlated with multiple midshaft parameters.DiscussionResults demonstrate characteristic patterns of intra‐limb adaptation to terrestrial and marine mobility strategies among active women relative to controls, and highlight components of these patterns that may be shaped in part by differences in loading duration/timing. Additionally, our findings support constraints on skeletal variation in the distal tibia and foot relative to more proximal locations about the knee among living women. For example, metatarsal variation was constrained, but where present reflected sport‐specific variation in force distribution in the foot.

Patellar tendon enthesis abnormalities and their association with knee pain and structural abnormalities in older adults

Purpose: The patellar tendon works together with the quadriceps tendon to enable knee flexion. Its attachment site (enthesis) is at risk of micro damage and degeneration. Recent studies suggest that enthesis abnormalities are associated with development of osteoarthritis through the synovio-entheseal complex. However, no studies have assessed the presence of patellar enthesis abnormalities in older adults and its association with osteoarthritis outcomes. Therefore, we aimed to describe associations between presence of patellar tendon enthesis (PTE) abnormalities visible on magnetic resonance (MR) images at baseline and knee pain, physical function limitations, and osteoarthritic structural abnormalities both cross-sectionally and longitudinally over 10.7 years. Methods: Patellar tendon enthesis abnormalities, defined as presence of abnormal bone signal and/or bone erosion were measured on T2-weighted fat suppressed fast spin echo MR images at baseline in 961 community-dwelling older adults. Knee pain and physical function limitation score were assessed using WOMAC at baseline and 10.7 years. Tibial, femoral, and patella bone marrow lesions (BMLs), cartilage volume and cartilage defects were assessed at baseline and 10.7 years, tibial bone area at baseline and 2.7 years, and infrapatellar fat pad area at baseline using validated methods. Associations were assessed using hurdle, log binomial, linear, and mixed models, after adjusting for confounders. Results: 20% of participants had bone signal and/or erosion at PTE. Cross-sectionally, presence of PTE abnormalities were associated with greater intensity of pain while going up and down stairs (β = 0.22 (95% CI; 0.03, 0.41)), greater risk of having a femoral (RR = 1.46 (1.22, 1.90)) BML, greater lateral tibial bone area (β = 25.95 (1.00, 50.91)), smaller infrapatellar fat pad area (β = −0.26 (−0.46, −0.05)), and a worse tibial cartilage defect score (RR = 1.70 (1.16, 2.47), after adjustment for age, sex, BMI, and structural confounders. Longitudinally, presence of PTE abnormalities at baseline predicted an increased risk of deleterious changes in tibial BML size (RR = 1.52 (1.12, 2.05)) only over 10.7 years but not pain or other structural changes. Conclusions: Patellar tendon enthesis abnormalities are common in the elderly. The presence of cross-sectional but not longitudinal associations suggests they commonly co-exist with other knee structural abnormalities. This suggests they may not be a major player in symptom development or structural changes with the exception of tibial BMLs.

A novel method for assessing proximal tibiofibular joint on magnetic resonance images in patients with knee osteoarthritis

Purpose: Knee osteoarthritis (OA) is well accepted as a whole organ disease that involves abnormalities of various structures. Proximal tibiofibular joint (ProxTibFibJ) is a synovial sliding joint that has been estimated to transmit one-sixth of the leg’s static load. Despite extensive studies on tibiofemoral and patellofemoral compartments, little attention has been paid to the ProxTibFibJ in OA research. One study has reported that proximal fibular osteotomy could significantly improve the clinical outcomes in patients with medial compartment OA. However, no study has delineated the measurement of ProxTibFibJ morphological parameters (ProxTibFibJ contacting area, load-bearing area, lateral stress-bolstering area and posterior stress-bolstering area) on magnetic resonance imaging (MRI) and investigated their correlations with knee OA structural abnormalities. This study, therefore, is to describe and validate a pragmatic method of measuring the ProxTibFibJ morphological parameters, and to investigate the longitudinal associations with joint abnormal structural changes in patients with knee OA. Methods: A total of 408 participants with knee OA were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) Study, which was a multi-center, randomized and double-blind clinical trial. ProxTibFibJ morphological parameters were measured on coronal and sagittal MRI. The contacting area of ProxTibFibJ (S), its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ) and coronal plane (posterior stress-bolstering area, Sυ) were assessed, respectively. MRI knee structural abnormalities, including cartilage defects, bone marrow lesions (BMLs) and cartilage volume, were evaluated at baseline and 2 years later. Ordinal logistic regression analyses were used to assess the cross-sectional associations between ProxTibFibJ morphological parameters and cartilage defects, BMLs, osteophytes, and JSN. Log binominal regression and linear regression models were used to assess the longitudinal associations between ProxTibFibJ morphological parameters and osteoarthritic structural changes. The reliabilities were examined by calculating the intra- and inter-observer correlation coefficients. Results: The average ProxTibFibJ fibular contacting area was 2.4 ± 0.7 cm2. The intra- and inter-observer correlation coefficients for all measures were excellent (all ≥0.90). In cross-sectional analyses, the ProxTibFibJ morphological parameters (S, Sτ, Sυ and Sφ) were significantly associated with radiographic medial JSN (OR 1.72 for S; 2.20 for Sτ; 1.65 for Sυ), radiographic medial osteophyte (OR 0.51 for Sφ) and MRI-assessed knee joint structural abnormalities including cartilage volume (β −0.07 for S; −0.09 for Sτ), cartilage defects (OR 1.63 for S; 1.95 for Sτ) and BMLs (OR 1.54 for S; 1.74 for Sτ) at medial tibiofemoral compartment. In longitudinal analyses, S (RR, 1.45) and Sτ (RR, 1.55) of ProxTibFibJ were significantly and positively associated with an increase in medial tibial cartilage defects over 2 years, after adjustment for age, gender, height, weight, ROA, tibial plateau bone area and intervention. Sτ (β, −0.07), Sυ (β, −0.07) and S (β, −0.06) of ProxTibFibJ were significantly and negatively associated with change in medial tibial cartilage volume, after adjusted for above covariates. Sτ (RR, 1.55) of ProxTibFibJ was positively associated with an increase in medial tibial BML, and Sφ (RR, 0.35) was negatively associated with an increase in medial femoral BMLs. No significant associations were found between ProxTibFibJ morphological parameters and osteoarthritic changes in lateral tibiofemoral compartment. Conclusions: This novel method to assess the morphological parameters of ProxTibFibJ using MRI is reproducible, and has clinical construct validity. The longitudinal associations with osteoarthritic changes suggest that higher load-bearing area of ProxTibFibJ is a potential risk factor for medial compartment OA. This may contribute to a theoretical basis of proximal fibular osteotomy in the treatment of medial tibiofemoral OA.

Bisphosphonates intake and its association with changes of periarticular bone area and three-dimensional shape: data from the Osteoarthritis Initiative (OAI)

To determine the association between bisphosphonate treatment with the change of periarticular bone area and three-dimensional (3D) shape in participants of the Osteoarthritis Initiative (OAI) study. Using propensity score (PS) matching method in females, 48 bisphosphonate users and 105 non-users, who were matched for osteoarthritis (OA) and osteoporosis (OP) related factors were included. Baseline and 24-month magnetic resonance imaging (MRI)-based periarticular bone area and 3D shape measurements were used. The association between bisphosphonate intake and 24-month interval changes of the periarticular bone area and 3D shape were evaluated using paired Wilcoxon signed rank test. We used conditional logistic regression models for determining the association between bisphosphonate intake and periarticular bone change, defined using the standard deviation of difference (SDD) and reliable change index (RCI) methods. P-values have been adjusted for multiple comparisons using Benjamini & Hochberg procedure and false discovery rate (FDR)-adjusted P-values were reported. The 24-month interval increases in the periarticular bone area in medial side of tibia were significantly greater in non-users than users (FDR-adjusted P-value: 0.002). There was an approaching significance trend for lower medial tibial periarticular bone area expansion in bisphosphonate users in comparison with non-users (For 1SDD change, odds ratio 95% confidence interval (OR (95% CI)): 0.514 (0.271-0.975), FDR-adjusted P-value: 0.085) (For 1.96RCI change, OR (95% CI): 0.552 (0.309-0.986), FDR-adjusted P-value: 0.085). Bisphosphonate intake was associated with a reduction in the odds (approaching but not achieving significance) of expansion periarticular bone area, specifically in the medial tibial sub-region.

The effect of oral dabigatran etexilate on bone density, strength, and microstructure in healthy mice

Thrombin is a key component in the coagulation cascade where it converts factor V, VIII, XI, and fibrinogen. In addition to the abundant production of thrombin in the liver, osteoclasts synthesize and secrete thrombin as well. Osteoblasts express thrombin receptors, and it has been reported that thrombin stimulates the expression of RANKL relatively to OPG, resulting in greater osteoclast activation and bone degradation. Pradaxa (dabigatran etexilate, DE) is a new anticoagulant, which has recently been approved for clinical use. DE is a direct thrombin inhibitor with potential to modulate the RANKL/OPG ratio and thereby limit osteoclast activation and bone degradation. The purpose of the study was to investigate whether DE can increase bone density, bone strength, and bone microstructure in healthy male and female mice and to investigate whether the effect of DE is sex-dependent. Twenty-eight 14-week-old male C57BL/6 mice were stratified by weight into 4 groups: 1. Control 3weeks; 2. DE 3weeks; 3. Control 6weeks; 4. DE 6weeks. An identical study design was applied to twenty-four 14-week-old female C57BL/6 mice. Chow mixed with DE was offered ad libitum, resulting in a dose of 1.70mgDE/g body weight and 1.52mgDE/g body weight, to female and male mice, respectively. The animals were euthanized after 3 or 6weeks. Bone mineral density (aBMD) and bone mineral content (BMC) were evaluated with DEXA, 3D microstructural properties were determined with μCT, bone strength was determined with mechanical testing, and bone formation and resorption was evaluated with bone histomorphometry. In female mice, DE resulted in significant higher tibial aBMD values after 6weeks of intervention. Furthermore, DE significantly increased tibial diaphyseal cortical bone area and tissue area, which was accompanied by significantly increased strength of the tibial shaft. DE had no effect on femoral cortical bone or on femoral and vertebral trabecular 3D microstructure. Finally, bone histomorphometry showed that DE had no effect on MS/BS or Oc.S/BS. In male mice, no bone positive effects of DE were found in any of the parameters investigated. In conclusion, intervention with DE may result in a weak positive site specific effect at tibial cortical bone in female mice, and importantly, no major deleterious effects of DE on bone tissue were seen in either female or male mice despite the relatively high dose of DE used.

Skeletal and dental effects on rats following in utero/lactational exposure to the non-dioxin-like polychlorinated biphenyl PCB 180.

Polychlorinated biphenyls (PCBs) are a large class of persistent organic pollutants that are potentially harmful to human and wildlife health. Although a small number of dioxin-like (DL) PCBs are well characterized, the majority of PCBs have non-dioxin-like (NDL) modes of action and biological effects that are less understood. We conducted a dose-response study of the skeletal and dental effects of in utero/lactational exposure to 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180), a NDL PCB congener that is abundantly present in the environment and foods, including mother’s milk. In a sample of 35- and 84-day-old male and female offspring from pregnant rats exposed to different doses of PCB 180 (0, 10, 30, 100, 300, and 1000 mg/kg bw), we measured the three-dimensional (3D) coordinates of 27 landmarks on the craniofacial skeleton with a Microscribe G2X system, the buccolingual width of all molars with digital sliding calipers, and a variety of tibial parameters with peripheral quantitative computed tomography (pQCT) and a biomechanical testing apparatus. The landmark coordinates were analyzed for variation in size, shape, and fluctuating asymmetry (FA) using MorphoJ software, showing no effects on cranial size, on FA in females only (i.e., decreased asymmetry), and on shape in both sexes (i.e., decreased facial length and shift in the palatal suture). In the maxillary teeth, females in the highest dose group showed a significant decrease of 0.1 mm (p = 0.033) of the second molar only, whereas males in most dose groups showed average increases of 0.1 mm (p = 0.006–0.044) in all three molars. In the mandibular teeth, the only significant response to PCB 180 exposure was the average increase of 0.1 mm (p = 0.001–0.025) in the third molars of males only. Males also shower greater sensitivity in postcranial effects of increased tibial length and decreased cortical bone mass density, although only females showed significant effects on tibial bone area and thickness. These results demonstrate marked sex differences in effects of PCB 180, which can be attributed to differences in their underlying biological mechanisms of toxicity. Furthermore, although tooth and bone development are targets of both DL and NDL compounds, this study shows that there are marked differences in their mechanisms and effects.

Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial

BackgroundFew clinical trials have investigated the safety and efficacy of mesenchymal stem cells for the management of post-traumatic osteoarthritis. The objectives of this pilot study were to determine the safety and tolerability and to explore the efficacy of a single intra-articular injection of allogeneic human mesenchymal precursor cells (MPCs) to improve clinical symptoms and retard joint structural deterioration over 24 months in patients following anterior cruciate ligament (ACL) reconstruction.MethodsIn this phase Ib/IIa, double-blind, active comparator clinical study, 17 patients aged 18–40 years with unilateral ACL reconstruction were randomized (2:1) to receive either a single intra-articular injection of 75 million allogeneic MPCs suspended in hyaluronan (HA) (MPC + HA group) (n = 11) or HA alone (n = 6). Patients were monitored for adverse events. Immunogenicity was evaluated by anti-HLA panel reactive antibodies (PRA) against class I and II HLAs determined by flow cytometry. Pain, function, and quality of life were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and SF-36v2 scores. Joint space width was measured from radiographs, and tibial cartilage volume and bone area assessed from magnetic resonance imaging (MRI).ResultsModerate arthralgia and swelling within 24 h following injection that subsided were observed in 4 out of 11 in the MPC + HA group and 0 out of 6 HA controls. No cell-related serious adverse effects were observed. Increases in class I PRA >10% were observed at week 4 in the MPC + HA group that decreased to baseline levels by week 104. Compared with the HA group, MPC + HA-treated patients showed greater improvements in KOOS pain, symptom, activities of daily living, and SF-36 bodily pain scores (p < 0.05). The MPC + HA group had reduced medial and lateral tibiofemoral joint space narrowing (p < 0.05), less tibial bone expansion (0.5% vs 4.0% over 26 weeks, p = 0.02), and a trend towards reduced tibial cartilage volume loss (0.7% vs –4.0% over 26 weeks, p = 0.10) than the HA controls.ConclusionsIntra-articular administration of a single allogeneic MPC injection following ACL reconstruction was safe, well tolerated, and may improve symptoms and structural outcomes. These findings suggest that MPCs warrant further investigations as they may modulate some of the pathological processes responsible for the development of post-traumatic osteoarthritis following ACL reconstruction.Trial registrationClinicalTrials.gov (NCT01088191) registration date: March 11, 2010

Quantitative Assessment of Knee Effusion‐Synovitis in Older Adults: Association With Knee Structural Abnormalities

ObjectiveTo describe the natural history of quantitatively measured knee effusion‐synovitis and the longitudinal associations between effusion‐synovitis and knee structural factors, including cartilage defects, cartilage volume, subchondral bone marrow lesions, and meniscal pathology, in older adults.Methods A total of 406 subjects (with a mean age of 63 years, 50% women) were randomly selected at baseline and followed up 2.7 years later. T2‐ or T1‐weighted fat saturation magnetic resonance imaging was used to assess knee effusion‐synovitis maximal area, cartilage defects, cartilage volume, bone marrow lesions, and meniscal pathology at baseline and follow‐up. Multivariable generalized linear regression was performed to analyze the associations between the maximal area of effusion‐synovitis and other joint structural factors after adjustment for age, sex, body mass index, tibial bone area, and/or radiographic osteoarthritis (OA).ResultsOver 2.7 years of follow‐up, the size of effusion‐synovitis increased in 29%, remained stable in 50%, and decreased in 22% of the participants. Baseline effusion‐synovitis maximal area was significantly associated with changes in knee cartilage defects (β = 0.18 [95% confidence interval (95% CI)] 0.07, 0.29), bone marrow lesions (β = 0.17 [95% CI 0.05, 0.30]), and cartilage volume (β = −0.40 [95% CI −0.71, −0.09]) but not with change in meniscal pathology. In contrast, baseline structural measures were not associated with change or increase in effusion‐synovitis maximal area.ConclusionOur findings indicate that knee effusion‐synovitis is not static in older adults. It is predictive of, but not predicted by, other structural abnormalities, suggesting a potential role in early knee OA changes.

Association of physical activity and physical performance with tibial cartilage volume and bone area in young adults.

IntroductionPhysical activity has been recommended to patients with knee osteoarthritis for improving their symptoms. However, it is still controversial if physical activity has effects on joint structures including cartilage volume. The aim of this study was to describe the associations between physical activity and performance measured 5 years prior and tibial cartilage volume and bone area in young adults.MethodsSubjects broadly representative of the Australian population (n = 328, aged 31–41 years, female 47.3 %) were selected from the Childhood Determinants of Adult Health study. They underwent T1-weighted fat-suppressed magnetic resonance imaging (MRI) scans of their knees. Tibial bone area and cartilage volume were measured from MRI. Physical activity (measured using long international physical activity questionnaire (IPAQ)) and performance measures (long jump, leg muscle strength, physical work capacity (PWC170)) were measured 5 years prior.ResultsIn multivariable analyses, total physical activity (min/week) (β: 0.30 mm3, 95 % CI: 0.13,0.47), vigorous (β: 0.54 mm3, 95 % CI: 0.13,0.94), moderate (β: 0.34 mm3, 95 % CI: 0.01,0.67), walking (β: 0.40 mm3, 95 % CI: 0.07,0.72) and IPAQ category (β: 182.9 mm3, 95 % CI: 51.8,314.0) were positively associated with total tibial cartilage volume but not tibial bone area. PWC170, long jump and leg muscle strength were positively and significantly associated with both total tibial cartilage volume and total tibial bone area; and the associations with tibial cartilage volume decreased in magnitude but remained significant for PWC170 and long jump after further adjustment for tibial bone area.ConclusionWhile tibial bone area is affected only by physical performance, total tibial cartilage volume can be influenced by both physical activity and performance in younger adults. The clinical significance suggests a beneficial effect for cartilage but the bone area association was restricted to performance suggesting other factors rather than physical activity may be important.

Impact of Growth Hormone on Adult Bone Quality in Turner Syndrome: A HR-pQCT Study.

Women with Turner syndrome (TS) are known to be at risk of osteoporosis. While childhood growth hormone (GH) treatment is common in TS, the impact of this therapy on bone health has been poorly understood. The objective of this study was to determine the influence of childhood GH treatment on adult bone quality in women with TS. 28 women aged 17-45 with confirmed TS (12 GH-treated) agreed to participate in this cross-sectional study. Dual X-ray absorptiometry (DXA) of lumbar spine, hip, and radius and high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia were used to determine standard morphological and micro-architectural parameters of bone health. Finite element (FE) analysis and polar moment of inertia (pMOI) were used to estimate bone strength. GH-treated subjects were +7.4 cm taller (95% CI 2.5-12.3 cm, p = 0.005). DXA-determined areal BMD of hip, spine, and radius was similar between treatment groups. Both tibial and radial total bone areas were greater among GH-treated subjects (+20.4 and +21.2% respectively, p < 0.05), while other micro-architectural results were not different between groups. pMOI was significantly greater among GH-treated subjects (radius +35.0%, tibia +34.0%, p < 0.05). Childhood GH treatment compared to no treatment in TS was associated with an increased height, larger bones, and greater pMOI, while no significant difference in DXA-derived BMD, HR-pQCT micro-architectural parameters, or FE-estimated bone strength was detected. The higher pMOI and greater bone size may confer benefit for fracture reduction in these GH-treated patients.

Childhood Physical Performance Measures and Adulthood Knee Cartilage Volume and Bone Area: A 25-Year Cohort Study.

We aimed to determine the associations between childhood physical performance measures and tibial cartilage volume and tibial bone area in adults 25 years later. Participants (n = 330, ages 31-41 years, female 47%) were selected from the Australian Schools Health and Fitness Survey of 1985. The participants underwent T1-weighted fat-suppressed magnetic resonance imaging (MRI) of their knees. Tibial bone area and cartilage volume were measured from MRI. Childhood measures, including physical work capacity at 170 beats per minute (PWC170 ), leg strength, number of sit-ups, long-run, and short-run were measured in 1985. PWC170 and leg strength measures were repeated after 20 years in their adulthood. Linear regression analysis was used to determine the association of performance measures with cartilage volume. There were consistent positive associations of all childhood measures, including PWC170 (β = 0.38 cm(2) per 10 watts, 95% confidence interval [95% CI] 0.15, 0.60), leg strength, long-run, short-run, and sit-ups with adult medial and total tibial bone area. Similarly, there was an association of PWC170 and sit-ups with adult medial tibial cartilage volume. After further adjustment for tibial bone area, the association between PWC170 and medial and total (β = 0.08 cm(3) per 10 watts, 95% CI 0.02, 0.10) tibial cartilage volume decreased in magnitude but remained significant. Childhood physical performance measures, especially PWC170 , were associated with knee tibial bone area and cartilage volume in adulthood. The associations with cartilage volume appeared to be partially mediated by bone area. This suggests physical performance measures in childhood can independently influence adult knee structures.

Association between popliteal artery wall thickness and knee cartilage volume loss in community-based middle-aged women without clinical knee disease

ObjectiveIncreasing evidence suggests a role of vascular pathology in the pathogenesis of osteoarthritis. This study examined the association between popliteal artery wall thickness, a surrogate marker of cardiovascular disease, and knee cartilage volume loss in an asymptomatic cohort of women. Study designProspective cohort study of 170 women with no significant knee pain, injury, or history of clinical knee disease. Participants underwent knee magnetic resonance imaging at baseline and 2 years later. Popliteal artery wall thickness was assessed using validated methods. Main outcome measuresTibial cartilage volume assessed using validated methods. Results142 women (83.5%) completed 2-year follow-up. After adjusting for age, body mass index and tibial bone area, greater popliteal artery wall thickness was associated with increased rate of medial tibial cartilage volume loss. With increasing tertiles of popliteal artery wall thickness, the mean (standard error) of annual medial tibial cartilage volume loss was 1.62 (0.45)%, 2.18 (0.43)%, and 2.98 (0.48)%, respectively, p for trend=0.04. No significant association was observed in lateral tibial cartilage. ConclusionIn community-based women greater popliteal artery wall thickness is associated with increased rate of tibial cartilage volume loss over 2 years. These findings suggest an adverse effect of vascular pathology on articular knee cartilage, supporting the hypothesis that there might be a vascular contribution to the development of knee osteoarthritis. Although needing to be confirmed in other studies, these results suggest that targeting vascular pathology may provide a potential target for the prevention and early treatment of knee osteoarthritis in women.

Association between popliteal artery wall thickness and knee structure in adults without clinical disease of the knee: a prospective cohort study.

There is evidence of a vascular contribution to the pathogenesis of osteoarthritis (OA). The aim of this study was to examine the association between popliteal artery wall thickness, which was previously shown to be associated with the risk of OA, and structural changes in the knee in an asymptomatic cohort. A total of 297 adults with no significant knee pain, injury, or history of clinical knee disease were recruited. Participants underwent magnetic resonance imaging of the knee at baseline and 2 years later. Popliteal artery wall thickness, knee cartilage volume, and bone marrow lesions (BMLs) were assessed. Of 278 participants with valid popliteal artery wall thickness measurements, 254 (91.4%) completed the 2-year followup assessment. After adjusting for age, sex, body mass index, and tibial bone area, increased popliteal artery wall thickness was found to be associated with a reduced medial tibial cartilage volume (B = -6.7 [95% confidence interval (95% CI) -12.9, -0.6], P = 0.03) and an increased rate of medial tibial cartilage volume loss (B = 0.06 [95% CI 0.01, 0.12], P = 0.03). There was a trend toward worsening of medial tibiofemoral BMLs in relation to increased popliteal artery wall thickness (odds ratio 1.07 [95% CI 0.99, 1.15]; P = 0.07). No significant associations with the lateral tibiofemoral compartment were observed. Increased popliteal artery wall thickness was associated with adverse changes in knee structure, as evidenced by reduced medial tibial cartilage volume, increased rate of cartilage volume loss, and a trend toward worsening of BMLs over 2 years. These findings suggest an association between vascular pathology and early structural changes in the knee, which supports the hypothesis that vascular health may play a role in the development of knee OA.