Denervation induces rapid bone degeneration concurrent to neurovascular and mechanical changes

Bone · 2026-03-21

Denervation results in reduced bone quality, largely attributed to reduced loading due to concurrent muscle atrophy. However, sensory and sympathetic nerves also directly innervate bone, suggesting additional potential inputs into bone remodeling. A quantitative baseline of bone morphological and functional changes after nerve injury is lacking. We investigated structural, biomechanical, and immunohistochemical for time points up to three months following peripheral nerve injury. Our primary objective was to establish timelines over which bone and muscle structure and biomechanical function degraded after denervation. Additionally, we evaluated remodeling of bone innervation and vascularity and alterations in bone homeostatic markers after injury. Using a Lewis rat nerve injury model ( n = 60 total rats), our findings showed rapid bone deterioration following transection of sciatic nerves of both male and female rats. Biomechanical properties of bone, including three-point bending yield force ( p < 0.0001), ultimate force ( p < 0.0001), and stiffness ( p < 0.001), were significantly reduced as early as two weeks post-injury. At a slight delay compared to biomechanical changes, micro-CT and MRI revealed that bone mineral density (p < 0.0001) and cortical thickness ( p < 0.001) also declined and porosity increased ( p < 0.05) within three months. Immunohistochemical analysis revealed marked decreases in sensory (calcitonin gene related protein; CGRP) and sympathetic (Neuropeptide-Y; NPY) neuropeptides, reduced osteoblast density in periosteal regions, and increased vascular (CD-31) area fraction, accompanied by increased vascular fragmentation. These findings support the possibility that both muscle and neuronal influences underlie denervation-related bone atrophy, setting the stage for evaluation of bone health after nerve repair and targeted rehabilitative or therapeutic interventions. • Muscle atrophy-related unloading is believed to induce bone loss after nerve injury. • However, nerve injury also disrupts sensory and sympathetic innervation of bone. • Rat sciatic nerve injury causes rapid structural and mechanical changes to bone. • Neurovascular morphology and bone turnover markers are also altered with injury. • Both muscle and neuronal influences may underlie denervation-related bone atrophy.

Vitamin D Metabolite Ratio is a Marker of Osteoid in Persons Across the Spectrum of Kidney Diseases

Journal of the American Society of Nephrology · 2025-10-01

A randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy of the synbiotic medical food, SBD111, for the clinical dietary management of bone loss in menopausal women

Osteoporosis International · 2025-08-15 · 5 citations

This 12-month study in 286 early postmenopausal women evaluated the efficacy and safety of SBD111, a synbiotic medical food, in reducing bone loss. SBD111 did not significantly reduce bone loss for the full cohort, but did produce evidence of reduced bone loss in women with osteopenia and BMI ≥ 30. PURPOSE: To determine the efficacy of SBD111, a synbiotic medical food comprising probiotics and prebiotics, in reducing bone loss in women post-menopause, including prespecified subpopulations of women with osteopenia or elevated BMI. METHODS: colony forming units) or placebo (maltodextrin) capsules twice daily for 12 months. The primary endpoint was change in areal BMD at the lumbar spine (LS). Secondary endpoints included change in areal BMD at the femoral neck (FN) and total hip (TH), trabecular volumetric BMD at the LS, markers of bone turnover and inflammation, and safety. Changes in gut microbiome composition were exploratory. The hypotheses being tested were formulated before data collection. RESULTS: Two hundred eighty-six women [age 55 ± 3 years (mean ± standard deviation)] were enrolled, with 221 (77%) completing the study. For the primary outcome, SBD111 administration was not associated with significantly less bone loss in the LS after 12 months [0.15% (- 0.52%, 0.82%), mean effect size (95% CI) by linear mixed-effects regression]. However, SBD111 was associated with reduced BMD loss in the TH for women with BMI ≥ 30 [0.97% (0.015%, 1.925%)] and modestly reduced BMD loss in the FN for women with osteopenia [0.89% (- 0.277%, 2.051%)]. CONCLUSIONS: These findings indicate SBD111 did not significantly reduce BMD loss for the full cohort. However, the trial produced evidence that SBD111 reduced bone loss in women with osteopenia and BMI ≥ 30.

A randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy of the synbiotic medical food, SBD111, for the clinical dietary management of bone loss in menopausal women

medRxiv · 2025-05-21 · 2 citations

Summary: This 12-month study in 286 early postmenopausal women evaluated the efficacy and safety of SBD111, a synbiotic medical food, in reducing bone loss. SBD111 did not significantly reduce bone loss for the full cohort, but did produce evidence of reduced bone loss in women with osteopenia and BMI ≥ 30. Purpose: To determine the efficacy of SBD111, a synbiotic medical food comprising probiotics and prebiotics, in reducing bone loss in women post-menopause, including prespecified subpopulations of women with osteopenia or elevated BMI. Methods: colony forming units) or placebo (maltodextrin) capsules twice daily for 12-months. The primary endpoint was change in areal BMD at the lumbar spine (LS). Secondary endpoints included change in areal BMD at the femoral neck (FN) and total hip (TH), trabecular volumetric BMD at the LS, markers of bone turnover and inflammation, and safety. Changes in gut microbiome composition were exploratory. The hypotheses being tested were formulated before data collection. Results: 286 Women [age 55 ± 3 years (mean ± standard deviation)] were enrolled, with 221 (77%) completing the study. For the primary outcome, SBD111 administration was not associated with significantly less bone loss in the LS after 12-months [0.15% (-0.52%, 0.82%), mean effect size (95% CI) by linear mixed effects regression]. However, SBD111 was associated with reduced BMD loss in the TH for women with BMI ≥ 30 [0.97% (0.015%, 1.925%)] and modestly reduced BMD loss in the FN for women with osteopenia [0.89% (-0.277%, 2.051%)]. Conclusions: These findings indicate SBD111 did not significantly reduce BMD loss for the full cohort. However, the trial produced evidence that SBD111 reduced bone loss in women with osteopenia and BMI ≥ 30.

Ultrashort echo time quantitative magnetization transfer (UTE-qMT) MRI distinguishes human diabetic bones from healthy ones

Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2024-11-26

Motivation: There is no standardized method to probe bone quality, a key determinant of bone fracture risk of type 2 diabetes patients. Goal(s): We tested whether UTE quantitative MT (UTE-qMT) imaging and UTE-based water pool measurement can distinguish diabetic bones from healthy ones. Approach: Twenty-two ex vivo human diabetic bones and 13 healthy ones were scanned with UTE-MT, proton density UTE, and inversion recovery UTE sequences to measure qMT parameters and fractions of pore and bound water pools. Results: The proton exchange rates from UTE-qMT showed a significant decrease in diabetic bones. Impact: The proton exchange rate measured via UTE-qMT can distinguish diabetic bones from healthy ones. UTE-qMT may provide insight into molecular-scale bone quality that explains the increased fracture risk in type 2 diabetes patients despite the increased bone mineral density.

Deep Convolutional Neural Network for Dedicated Regions-of-Interest Based Multi-Parameter Quantitative Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of the Knee Joint

Journal of Imaging Informatics in Medicine · 2024-03-28 · 3 citations

Quantitative MRI of cartilage in ACL reconstructed patients using 3D ultrashort echo time T1 (UTE-T1) and magnetization transfer ratio (UTE-MTR)

Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2024-11-26

Motivation: Post traumatic osteoarthritis is a common complication of ACL injury. There is limited research on the early degenerative changes in cartilage of ACL injured knees. Goal(s): To develop novel biomarkers for identifying early cartilage damage in ACL reconstructed knees. Approach: We employed ultrashort echo time magnetization transfer ratio (UTE-MTR) and UTE-T1 sequence to study the knee articular cartilage in ACL reconstructed patients. Results: UTE-T1 and UTE-MTR can be used as quantitative biomarkers for assessing cartilage damage. Reduced MTR and increased T1 values indicate cartilage damage which is otherwise not appreciated on morphological imaging. Impact: UTE-T1 and UTE-MTR sequences can detect early cartilage damage, which could help us better understand the development of post-traumatic osteoarthritis.

Extra axial bone ablation with augmentation

Techniques in vascular and interventional radiology · 2024-08-24

ROI based Multi-parameter Quantitative Network(RMQ-Net) with Uncertainty-awareness for Quantitative UTE MRI Study of Cartilage

Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2024-11-26

Motivation: Quantitative MRI (qMRI) studies of cartilage regions need both regional segmentation and pixel-wise fitting analysis, which can be time-consuming and subject to inter-individual variability. Goal(s): To design a deep neural network for simultaneous qMRI mapping and accurate tissue segmentation. Approach: By leveraging different scan sequences, we proposed a RMQ-net with Uncertainty-awareness(UA) module, or UA-QMR-net. A majority-voting strategy was applied for robust cartilage segmentation and accelerated qMRI analysis. Results: The results demonstrated that the UA-RMQ-net achieved higher performance than the original RMQ-net for both UTE-T1 and UTE-T1r analyses of articular cartilage. Impact: By leveraging information from different scan sequences, the proposed UA-RMQ-net could obtain higher performance for accelerated qMRI analysis.

Bone Biomarkers Based on Magnetic Resonance Imaging

Seminars in Musculoskeletal Radiology · 2024-02-01 · 1 citations

Magnetic resonance imaging (MRI) is increasingly used to evaluate the microstructural and compositional properties of bone. MRI-based biomarkers can characterize all major compartments of bone: organic, water, fat, and mineral components. However, with a short apparent spin-spin relaxation time (T2*), bone is invisible to conventional MRI sequences that use long echo times. To address this shortcoming, ultrashort echo time MRI sequences have been developed to provide direct imaging of bone and establish a set of MRI-based biomarkers sensitive to the structural and compositional changes of bone. This review article describes the MRI-based bone biomarkers representing total water, pore water, bound water, fat fraction, macromolecular fraction in the organic matrix, and surrogates for mineral density. MRI-based morphological bone imaging techniques are also briefly described.