Bone remodeling is the continual process to renew the adult skeleton through the sequential action of osteoblasts and osteoclasts. Nuclear factor RANK, an osteoclast receptor, and its ligand RANKL, expressed on the surface of osteoblasts, result in coordinated control of bone remodeling. Inflammation, a feature of illness and injury, plays a distinct role in skewing this process toward resorption. It does so via the interaction of inflammatory mediators and their related peptides with osteoblasts and osteoclasts, as well as other immune cells, to alter the expression of RANK and RANKL. Such chemical mediators include TNFα, glucocorticoids, histamine, bradykinin, PGE2, systemic RANKL from immune cells, and interleukins 1 and 6. Conditions, such as periodontal disease and alveolar bone erosion, aseptic prosthetic loosening, rheumatoid arthritis, and some sports related injuries are characterized by the result of this process. A thorough understanding of bone response to injury and disease, and ability to detect such biomarkers, as well as imaging to identify early structural and mechanical property changes in bone architecture, is important in improving management and outcomes of bone related pathology. While gut health and vitamin and mineral availability appear vitally important, nutraceuticals also have an impact on bone health. To date most pharmaceutical intervention targets inflammatory cytokines, although strategies to favorably alter inflammation induced bone pathology are currently limited. Further research is required in this field to advance early detection and treatments.

Purpose To quantify bulk bone water to test the hypothesis that bone water concentration (BWC) is negatively correlated with bone mineral density (BMD) and is positively correlated with age, and to propose the suppression ratio (SR) (the ratio of signal amplitude without to that with long-T2 suppression) as a potentially stronger surrogate measure of porosity, which is evaluated ex vivo and in vivo. Materials and Methods Human subject studies were conducted in compliance with institutional review board and HIPAA regulations. Healthy men and women (n = 72; age range, 20–80 years) were examined with a hybrid radial ultrashort echo time magnetic resonance (MR) imaging sequence at 3.0 T, and BWC was determined in the tibial midshaft. In a subset of 40 female subjects, the SR was measured with a similar sequence. Cortical volumetric BMD (vBMD) was measured by means of peripheral quantitative computed tomography (CT). The method was validated against mi-cro-CT–derived porosity in 13 donor human cortical bone specimens. Associations among parameters were evaluated by using standard statistical tools. Results BWC was positively correlated with age (r = 0.52; 95% confidence interval [CI]: 0.22, 0.73; P = .002) and negatively correlated with vBMD at the same location (r = −0.57; 95% CI: −0.76, −0.29; P < .001). Data were suggestive of stronger associations with SR (r = 0.64, 95% CI: 0.39, 0.81, P < .001 for age; r = −0.67, 95% CI: −0.82, −0.43, P < .001 for vBMD; P < .001 for both), indicating that SR may be a more direct measure of porosity. This interpretation was supported by ex vivo measurements showing SR to be strongly positively correlated with micro-CT porosity (r = 0.88; 95% CI: 0.64, 0.96; P < .001) and with age (r = 0.87; 95% CI: 0.62, 0.96; P < .001). Conclusion The MR imaging–derived SR may serve as a biomarker for cortical bone porosity that is potentially superior to BWC, but corroboration in larger cohorts is indicated.

Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12–25 years) a median of 9.7 (4.3–19.3) years after alloHSCT compared to 25 age-, race-, and sex-matched healthy controls. Vertebral MR spectroscopic imaging and tibia micro-MRI were used to quantify marrow adipose tissue (MAT) and trabecular microarchitecture. Additional measures included DXA whole-body fat mass (WB-FM), leg lean mass (Leg-LM), trunk visceral adipose tissue (VAT), and CT calf muscle density. Insulin resistance in alloHSCT survivors was estimated by HOMA-IR. AlloHSCT survivors had lower Leg-LM (p<0.001), and greater VAT (p<0.01), MAT (p<0.001) and fat infiltration of muscle (p=0.04) independent of WB-FM, vs. matched-controls; BMI did not differ. Survivors had lower bone volume fraction and abnormal microarchitecture including greater erosion and more rod-like structure vs. controls (all p=0.04); 14 had vertebral deformities and two had compression fractures. Greater WB-FM, VAT, MAT and muscle fat infiltration were associated with abnormal trabecular microarchitecture (p<0.04 for all). AlloHSCT HOMA-IR was elevated, associated with younger age at transplantation (p<0.01), and positively correlated with WB-FM and VAT (both p<0.01). In conclusion, the markedly increased marrow adiposity, abnormal bone microarchitecture, and abnormal fat distribution highlight the risks of long-term treatment-related morbidity and mortality in alloHSCT recipients after TBI. Trabecular deterioration was associated with marrow and visceral adiposity. Furthermore, long-term survivors demonstrated sarcopenic obesity, insulin resistance, and vertebral deformities. Future studies are needed to identify strategies to prevent and treat metabolic and skeletal complications in this growing population of childhood alloHSCT survivors.

Purpose To develop a method to assess volumetric cortical bone porosity in clinically practical acquisition times by measuring the signal decay at only two echo times (TEs) as part of a single three-dimensional ultrashort TE (UTE) magnetic resonance (MR) examination. Materials and Methods The study was approved by the institutional review board and complied with HIPAA guidelines. Written informed consent was obtained from all subjects. A marker of cortical bone porosity called porosity index was defined as the ratio of UTE image intensities at a long and short TE, and the results were compared with biexponential analysis. Porosity index of midtibia cortical bone samples obtained from 16 donors was compared with ground-truth porosity by using micro–computed tomographic (CT) imaging and bone mineral density by peripheral quantitative CT scanner. Reproducibility of porosity index were tested in volunteers and clinical feasibility evaluated in postmenopausal women. Interparameter associations were assessed by using Pearson or Spearman correlation coefficient. Results Bone specimen porosity index was correlated with micro-CT imaging porosity (R2 = 0.79) and pore size (R2 = 0.81); age (R2 = 0.64); peripheral quantitative CT scanner density (R2 = 0.49, negatively); and pore water fraction (R2 = 0.62) and T2* (R2 = 0.64) by biexponential analysis. The reproducibility study yielded a coefficient of variation of 2.2% and intraclass correlation coefficient of 0.97. The study that involved postmenopausal women showed a wide range of porosity index (15%–38%). Conclusion A two-point MR imaging method to assess cortical bone porosity in humans was conceived and validated. This approach has the potential for clinical use to assess changes in cortical bone porosity that result from disease or in response to therapy.

The mechanical properties of bone estimated by micro-finite element (µFE) analysis on the basis of in-vivo micro-MR images (µMRI) of the distal extremities provide a new tool for direct assessment of the mechanical consequences of intervention. However, the accuracy of the method has not previously been investigated. Here, we compared µFE-derived mechanical parameters obtained from µMR images at 160 µm isotropic voxel size now achievable in vivo with those derived from 25 µm isotropic (reference) µCT images of thirty cadaveric tibiae from fifteen donors (4 females, 11 males, 55–84 yrs.). Elastic and shear moduli estimated from (5 mm)3 sub-volumes of trabecular bone (TB) derived from µMR images were significantly correlated with those derived from volume-matched reference µCT images (R2 = 0.60–0.67). Axial stiffness of whole-bone sections (including both cortical and trabecular compartments) derived from µMR-based models were highly correlated (R2 = 0.85) with those from high-resolution reference images. Further, µFE models generated from µCT images after downsampling to lower resolutions relevant to in-vivo µMRI (100–160 µm), showed mechanical parameters to be strongly correlated (R2 > 0.93) with those derived at reference resolution (25 µm). Incorporation of grayscale image information into the µMR-based µFE model yielded slopes closer to unity than binarized models (1.07±0.15 vs. 0.71±0.11) when correlated with reference sub-regional elastic and shear moduli. The work suggests that elastic properties of distal tibia can be reliably estimated by µFE analysis from µMR images obtainable at in-vivo resolution.