Chronic plantar heel pain modifies associations of ankle plantarflexor strength and body mass index with calcaneal bone density and microarchitecture

Chronic plantar heel pain (CPHP) is associated with calcaneal bone spurs, but its associations with other calcaneal bone features are unknown. This study therefore aimed to determine associations between having CPHP and bone density and microarchitecture of the calcaneus. We assessed 220 participants with CPHP and 100 age- and sex-matched population-based controls. Trabecular bone density, thickness, separation and number, BV/TV, and cortical density, thickness and area were measured using a Scanco Xtreme1 HR-pQCT scanner at a plantar and mid-calcaneal site. Clinical, physical activity and disease history data were also collected. Associations with bone outcomes were assessed using multivariable linear regression adjusting for age, sex, physical activity, BMI and ankle plantarflexor strength. We assessed for potential effect modification of CPHP on these covariates using interaction terms. There were univariable associations at the plantar calcaneus where higher trabecular bone density, BV/TV and thickness and lower trabecular separation were associated with CPHP. In multivariable models, having CPHP was not independently associated with any bone outcome, but modified associations of BMI and ankle plantarflexor strength with mid-calcaneal and plantar bone outcomes respectively. Beneficial associations of BMI with mid-calcaneal trabecular density (BMI-case interaction standardised X/unstandardised Y beta -10.8(mgHA/cm3) (se 4.6), thickness -0.002(mm) (se 0.001) and BV/TV -0.009(%) (se 0.004) were reduced in people with CPHP. Beneficial associations of ankle plantarflexor strength with plantar trabecular density (ankle plantarflexor strength -case interaction -11.9(mgHA/cm3) (se 4.4)), thickness -0.003(mm) (se 0.001), separation -0.003(mm) (se 0.001) and BV/TV -0.010(%) (se 0.004) were also reduced. CPHP may have consequences for calcaneal bone density and microarchitecture by modifying associations of BMI and ankle plantarflexor strength with calcaneal bone outcomes. The reasons for these case-control differences are uncertain but could include a bone response to entheseal stress, altered loading habits and/or pain mechanisms. Confirmation with longitudinal study is required.

EphB3 as a potential mediator of developmental and reparative osteogenesis

The ephrin-B family of membrane-bound ligands is involved in skeletal patterning, osteogenesis, and bone homeostasis. Yet, despite the increasing collection of data affirming their importance in bone, the Eph tyrosine kinases that serve as the receptors for these ephrins in osteoblast stem cell niches remain unidentified. Here we report the expression of EphB3 at sites of bone growth in the embryo, especially at the calvaria suture fronts, periosteum, chondrocytes and trabeculae of developing long bones. Strong EphB3 expression persisted in the adult calvarial sutures and in the proliferative chondrocytes of long bones, both of which are documented niches for osteoblastic stem cells. We observed EphB3-positive cells in the tissue filling a created calvarial injury, further implying EphB3 involvement in bone healing. Genetic knockout of EphB3 caused an increase in the bone tissue volume as a fraction of total volume in six-week old calvaria and in femoral trabecular density, compared to wild type controls. This difference resolved by twelve weeks of age, when we instead observed an increase in the bone volume of femoral trabeculae and in trabecular thickness. Our data identify EphB3 as a candidate regulator of osteogenesis either alone or in combination with other bone-expressed Ephs, and indicate that it appears to function as a limiter of bone growth.

Effect of Curcumin on Alterations of Alveolar Bone Remodeling and Expression of Receptor Activator of Nuclear Factor-κ B Ligand in Rat Tooth During Tooth Movement

Objective: To evaluate the effect of Curcumin on Alterations of Alveolar Bone Remodeling and Expression of RANKL in Rat Tooth during Tooth Movement. Methods: 64 SD rats were randomly divided into 4 groups, Model, Adrb2, Cur and Cur + Pro groups. The rat orthodontic teeth movement models were established.The rats were injected corresponding reagents according to weight and were sacrificed on day 0, 7, 14 and 21. The movement distance of first molar of rats was measured by Vernier caliper.The numbers of osteoclasts were observed through TRAP staining. The change of micro-structure of alveolar bone was evaluated by Micro-CT. Results: The trends of the distance of teeth movement and numbers of osteoclast were the same: Cur group β Adrb2 group > Model groups Cur+Pro group (P < 0.05). Micro-CT scan showed that curcumin could reduce the bone volume fraction (BV/TV), bone trabecular density (MTPD), and increase the trabecular resolution (TB. SP). When propranolol was given at the same time, the effect of curcumin disappeared. Conclusion: Curcumin could promote the resorption of alveolar bone at the pressure side and increase the osteoclast numbers so that the alveolar bone became looser which was beneficial to the movement of orthodontic tooth.

High Cortico-Trabecular Transitional Zone Porosity and Reduced Trabecular Density in Men and Women with Stress Fractures

To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.0 ± 1.6 years). Relative to controls, in men, at the distal radius, cases had smaller cortical cross sectional area (CSA) (p = 0.012), higher porosity of the outer transitional zone (OTZ) (p = 0.006), inner transitional zone (ITZ) (p = 0.043) and the compact-appearing cortex (CC) (p = 0.023) while trabecular vBMD was lower (p = 0.002). At the distal tibia, cases also had a smaller cortical CSA (p = 0.008). Cortical porosity was not higher, but trabecular vBMD was lower (p = 0.001). Relative to controls, in women, cases had higher distal radial porosity of the OTZ (p = 0.028), ITZ (p = 0.030) not CC (p = 0.054). Trabecular vBMD was lower (p = 0.041). Distal tibial porosity was higher in the OTZ (p = 0.035), ITZ (p = 0.009), not CC. Stress fractures are associated with compromised cortical and trabecular microstructure.

Severe bone microarchitecture impairment in women with pregnancy and lactation associated osteoporosis

Context Pregnancy and lactation-associated osteoporosis (PLO) is a rare condition characterized by fragility fractures, mostly vertebral, during the third trimester of pregnancy or the early postpartum. Objective The aim of this study was to evaluate bone microarchitecture in women with PLO in order to better understand the pathophysiology of this disease. Design and methods In this retrospective study, we included women with PLO referred to our bone center between November 2007 and July 2012. We assessed bone mineral density (BMD) by DXA, bone turnover markers and bone microarchitecture by HR-pQCT. Results were compared with a control group of healthy lactating women. Results Among the seven primiparous patients with PLO, six suffered vertebral fractures and one developed a hip fracture during the seventh month of gestation. Fractures occurred within the eighth month of pregnancy and the fourth month of postpartum; vertebral fractures were multiple in 85.7%. Major or minor risk factors for osteoporosis were present in 86% of our patients. Trabecular density, number and thickness were 34%, 20% and 22% lower than controls, (p &lt; 0.01, p = 0.01 and p = 0.01, respectively). Cortical parameters were also deteriorated but to a lesser extent. Conclusion In comparison with healthy lactating women, patients with PLO presented severe deterioration of bone trabecular and cortical microarchitecture. This significant compromise may explain the occurrence of multiple fractures in these otherwise healthy young women. Further prospective studies are needed in order to determine whether bone microarchitecture might be able to be restored in the future.

Mitochondrial Calcium Uniporter Deficiency in Zebrafish Causes Cardiomyopathy With Arrhythmia

Mitochondrial Ca2 + uptake influences energy production, cell survival, and Ca2 + signaling. The mitochondrial calcium uniporter, MCU, is the primary route for uptake of Ca2 + into the mitochondrial matrix. We have generated a zebrafish MCU mutant that survives to adulthood and exhibits dramatic cardiac phenotypes resembling cardiomyopathy and sinus arrest. MCU hearts contract weakly and have a smaller ventricle with a thin compact layer and reduced trabecular density. Damaged myofibrils and swollen mitochondria were present in the ventricles of MCU mutants, along with gene expression changes indicative of cell stress and altered cardiac structure and function. Using electrocardiography, we found that MCU hearts display conduction system defects and abnormal rhythm, with extended pauses resembling episodes of sinus arrest. Together, our findings suggest that proper mitochondrial Ca2 + homeostasis is crucial for maintaining a healthy adult heart, and establish the MCU mutant as a useful model for understanding the role of mitochondrial Ca2 + handling in adult cardiac biology.

Sex differences in cortical bone of humeral head region

Background Proximal humerus fractures are highly related to age, and are particularly high in women. The goal of this study was to investigate sex-related similarities and differences in humeral head structure. Methods Computed tomography (CT) scans of 147 healthy subjects (76 men /71 women) spanning a wide range of ages (20-88 years) were analyzed. Three groups of subjects were identified according to age: group A (aged 20-39 years), group B (aged 40-59 years), and group C (aged> 60 years). For each subject, cortical bone mapping (CBM) was applied to create color 3D thickness map for the proximal humerus. Regions of interest (ROI) were defined in three walls of humeral head which corresponded to the anterior, lateral and posterior aspects. Cortical parameters, including the cortical thickness (CTh), cortical mass surface density (CM), and the endocortical trabecular density (ECTD) were measured using CBM. Results In both sexes, the CTh value of proximal ROIs in lateral and anterior wall tended to decrease with age. No significant difference was detected between three age groups for each parameter in the posterior wall in men and women. In ROIs 1-9, the ECTD tended to show a notable decline with age in women. In contrast, the ECTD remained unchanged in men. When pooled across all decades, the CTh, CM and ECTD values of ROI 1-9 were approximately equivalent between men and women. Conclusions There was no sex difference in cortical bone parameters in the humeral head region. However, the endocortical trabecular density decreased significantly with age only in women.