Vertebral Bone Tissue Research Articles

Sclerotic Bone Adversely Affects Anti-Tuberculosis Drug Distribution in Patients with Spinal Tuberculosis: A Prospective Cross-Sectional Study.

The effects of sclerotic bone on anti-tuberculosis (anti-TB) drug distribution in the blood and in spinal tuberculosis (STB) lesions were investigated. Fifty-six patients with STB were prospectively enrolled from January 2020 to March 2023 and were divided into 2 groups: a group with sclerotic bone and a group without sclerotic bone, as identified on preoperative computed tomography (CT) scans. Individuals in the sclerotic bone group were further divided into fragmentary and non-fragmentary sclerotic bone groups. The patients underwent surgery, and blood was collected along with normal vertebral and STB-lesion-containing bone tissue samples. Following treatment, the samples were processed by a pharmacological laboratory in order to detect the concentrations of anti-TB drugs, including pyrazinamide, rifampicin, isoniazid, and ethambutol. Twenty-seven East Asian female and 29 East Asian male patients with STB were included in this study. The levels of anti-TB drugs showed a progressive decrease with increased circulatory distance, from blood to normal vertebral tissue to TB lesions, across all patient groups. Drug concentrations in TB lesions in the sclerotic bone group were significantly lower than those in the non-sclerotic bone group, as were concentrations in TB lesions in the non-fragmentary sclerotic bone group relative to those in the fragmentary sclerotic bone group. Drug levels in the blood and in normal vertebral bone tissue did not significantly differ between the sclerotic and non-sclerotic groups, nor between the fragmentary and non-fragmentary groups. Drug levels in the blood were linearly correlated with those in TB lesions in both the non-sclerotic bone group and the fragmentary sclerotic bone group. These results indicate that sclerotic bone negatively affects the dissemination of anti-TB drugs, with non-fragmentary sclerotic bone posing a greater obstacle than fragmentary sclerotic bone. In patients with STB without sclerotic bone or with fragmentary sclerotic bone, anti-TB drug levels in the blood were linearly correlated with drug levels in STB lesions. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Computer and experimental studies of the strength and durability of titanium nickelide prostheses and vertebral bone tissue in prosthetic intervertebral disk replacement in the cervical spine

The paper reports the results of the computer-aided analysis of the durability of porous cylindrical titanium nickelide prostheses intended for replace the intervertebral disk in the cervical spine segment and vertebral bone tissue of different density. Endoprostheses of different sizes were made of titanium nickelide obtained by self-propagating high-temperature synthesis. Experimental uniaxial compression load curves were obtained to assess the mechanical properties of the prostheses. The assessment of segment durability when the segment is tilted forward was carried out on the basis of stress state calculations of the segment with prostheses, as well as expressions approximating experimental data on porous samples cyclic loading made of titanium nickelide and bone tissue. The results of the study show the possibility of long-term operation of the implants in question and the absence of fatigue destruction of vertebral bone tissue throughout a person’s life.

Transient receptor potential vanilloid 4 regulates extracellular matrix composition and mediates load-induced intervertebral disc degeneration in a mouse model

Transient receptor potential vanilloid 4 (TRPV4) is a multi-modally activated cation channel that mediates mechanotransduction pathways by which musculoskeletal tissues respond to mechanical load and regulate tissue health. Using conditional Trpv4 knockout mice, we investigated the role of Trpv4 in regulating intervertebral disc (IVD) health and injury-induced IVD degeneration. Col2-Cre;Trpv4fl/f (Trpv4 KO) mice were used to knockout Trpv4 in all type 2 collagen-expressing cells. Effects of gene targeting alone was assessed in lumbar spines, using vertebral bone length measurement, histological, immunohistochemistry and gene expression analyses, and mechanical testing. Disc puncture was performed on caudal IVDs of wild-type (WT) and Trpv4 KO mice at 2.5- and 6.5-months-of-age. Six weeks after puncture (4- and 8-months-of-age at sacrifice), caudal spines were assessed using histological analyses. While loss of Trpv4 did not significantly alter vertebral bone length and tissue histomorphology compared to age-matched WT mice, Trpv4 KO mice showed decreased proteoglycan and PRG4 staining in the annulus fibrosus compared to WT. At the gene level, Trpv4 KO mice showed significantly increased expression of Acan, Bgn, and Prg4 compared to WT. Functionally, loss of Trpv4 was associated with significantly increased neutral zone length in lumbar IVDs. Following puncture, both Trpv4 KO and WT mice showed similar signs of degeneration at the site of injury. Interestingly, loss of Trpv4 prevented mechanically-induced degeneration in IVDs adjacent to sites of injury. These studies suggest a role for Trpv4 in regulating extracellular matrix synthesis and mediating the response of IVD tissues to mechanical stress.

Single-cell RNA landscape of osteoimmune microenvironment in osteoporotic vertebral compression fracture and Kümmell's disease.

Background: Single-cell RNA sequencing (scRNA-seq) enables specific analysis of cell populations at single-cell resolution; however, there is still a lack of single-cell-level studies to characterize the dynamic and complex interactions between osteoporotic vertebral compression fractures (OVCFs) and Kümmell's disease (KD) in the osteoimmune microenvironment. In this study, we used scRNA-seq analysis to investigate the osteoimmune microenvironment and cellular composition in OVCFs and KD. Methods: ScRNA-seq was used to perform analysis of fractured vertebral bone tissues from one OVCF and one KD patients, and a total of 8,741 single cells were captured for single-cell transcriptomic analysis. The cellularity of human vertebral bone tissue was further analyzed using uniform manifold approximation and projection. Pseudo-time analysis and gene enrichment analysis revealed the biological function of cell fate and its counterparts. CellphoneDB was used to identify the interactions between bone cells and immune cells in the osteoimmune microenvironment of human vertebral bone tissue and their potential functions. Results: A cellular profile of the osteoimmune microenvironment of human vertebral bone tissue was established, including mesenchymal stem cells (MSCs), pericytes, myofibroblasts, fibroblasts, chondrocytes, endothelial cells (ECs), granulocytes, monocytes, T cells, B cells, plasma cells, mast cells, and early erythrocytes. MSCs play an immunoregulatory function and mediate osteogenic differentiation and cell proliferation. The differentiation trajectory of osteoclasts in human vertebral bone tissue was also revealed. In addition, ECs actively participate in inflammatory infiltration and coupling with bone cells. T and B cells actively participate in regulating bone homeostasis. Finally, by identifying the interaction of ligand-receptor pairs, we found that immune cells and osteoclasts have bidirectional regulatory characteristics, have the effects of regulating bone resorption by osteoclasts and promoting bone formation, and are essential for bone homeostasis. It is also highlighted that CD8-TEM cells and osteoclasts might crosstalk via CD160-TNFRSF14 ligand-receptor interaction. Conclusion: Our analysis reveals a differential landscape of molecular pathways, population composition, and cell-cell interactions during OVCF development into KD. OVCFs exhibit a higher osteogenic differentiation capacity, owing to abundant immune cells. Conversely, KD results in greater bone resorption than bone formation due to depletion of MSCs and a relatively suppressed immune system, and this immune imbalance eventually leads to vertebral avascular necrosis. The site of action between immune cells and osteoclasts is expected to be a new therapeutic target, and these results may accelerate mechanistic and functional studies of osteoimmune cell types and specific gene action in vertebral avascular necrosis and pathological bone loss diseases, paving the way for drug discovery.

The Distribution Pattern of First-Line Anti-Tuberculosis Drug Concentrations between the Blood and the Vertebral Focus of Spinal Tuberculosis Patients.

Background: Anti-tuberculosis drug concentrations are critical for the treatment of spinal tuberculosis. The distribution pattern of anti-tuberculosis drugs between the blood and the vertebral focus needs to be further explored. Methods: A total of 31 spinal tuberculosis patients were prospectively included and then divided into a sclerotic group (15 cases) and a non-sclerotic group (16 cases) according to their preoperative CTs. All patients were treated with 2HERZ/6H2R2Z2 chemotherapy for 4 weeks before the operation. During the operation, blood, normal vertebral bone tissue, and vertebral focus tissue were obtained, processed, and sent to the pharmacology laboratory. The concentration values of four anti-tuberculosis drugs in each sample were obtained in a pharmacology laboratory. Results: There was no significant difference in the concentrations of the four anti-tuberculosis drugs in the blood and the normal vertebral bone tissue between the two groups; however, there was a significant difference in the vertebral focus tissue. There existed a linear correlation of four anti-tuberculosis drug concentrations between the blood and the focus in the non-sclerotic bone group. Conclusions: The existence of sclerotic bone hinders the anti-tuberculosis drug distribution. In the absence of sclerotic bone in the vertebral focus, there exists a linear relationship of the four anti-tuberculosis drug concentrations between the blood and the vertebral focus of spinal tuberculosis patients.

Intermittent Short-Term Infusion vs. Continuous Infusion of Piperacillin: Steady State Concentrations in Porcine Cervical Spine Tissue Evaluated by Microdialysis.

Background: Piperacillin is a central drug in the treatment of Pseudomonas aeruginosa spondylodiscitis. Intermittent short-term infusion (STI) remains standard treatment in most centres, although the application of continuous infusion (CI) has shown promising results in other clinical settings. We aimed to evaluate time above the minimal inhibitory concentration (fT > MIC) of the free fraction of piperacillin in steady state conditions in porcine cervical spine tissue following CI and STI using microdialysis with MIC targets of 4, 8, and 16 g/mL. Methods: 16 female pigs were randomized to receive piperacillin/tazobactam as STI (4/0.5 g every 6 h) or CI (4/0.5 g as a bolus followed by 12/1.5 g) for 18 h. Microdialysis catheters were placed for sampling of piperacillin concentrations from the intervertebral disc, vertebral cancellous bone, paravertebral muscle, and adjacent subcutaneous tissue during the third dosing interval (12–18 h). Blood samples were collected as reference. Results: CI resulted in fT > MIC > 82% across all compartments and targets, except for intervertebral disc (37%) and vertebral cancellous bone (28%) at MIC = 16 g/mL. In Group STI, >72% fT > MIC was reached for MIC = 4 g/mL in all investigated compartments, while for MIC = 16 g/mL only subcutaneous tissue exhibited fT > MIC > 50%. Conclusion: CI of piperacillin resulted in higher fT > MIC compared to STI infusion across the investigated tissues and targets. CI should therefore be considered in spondylodiscitis cases requiring piperacillin treatment.

Density and mechanical properties of vertebral trabecular bone-A review.

Being able to predict the mechanical properties of vertebrae in patients with osteoporosis and other relevant pathologies is essential to prevent fractures and to develop the most favorable fracture treatments. Furthermore, a reliable prediction is important for developing more patient‐ and pathology‐specific biomaterials. A plethora of studies correlating bone density to mechanical properties has been reported; however, the results are variable, due to a variety of factors, including anatomical site and methodological differences. The aim of this study was to provide a comprehensive literature review on density and mechanical properties of human vertebral trabecular bone as well as relationships found between these properties. A literature search was performed to include studies, which investigated mechanical properties and bone density of trabecular bone. Only studies on vertebral trabecular bone tissue, reporting bone density or mechanical properties, were kept.A large variation in reported vertebral trabecular bone densities, mechanical properties, and relationships between the two was found, as exemplified by values varying between 0.09 and 0.35 g/cm3 for the wet apparent density and from 0.1 to 976 MPa for the elastic modulus. The differences were found to reflect variations in experimental and analytical processes that had been used, including testing protocol and specimen geometry. The variability in the data decreased in studies where bone tissue testing occurred in a standardized manner (eg, the reported differences in average elastic modulus decreased from 400% to 10%). It is important to take this variability into account when analyzing the predictions found in the literature, for example, to calculate fracture risk, and it is recommended to use the models suggested in the present review to reduce data variability.

Determination of Residual Stress with Diffusion MR Method in Cortical and Trabecular Sections of Human Vertebral Bone Tissue

Determination of Residual Stress with Diffusion MR Method in Cortical and Trabecular Sections of Human Vertebral Bone Tissue

Microdialysis for the Assessment of Intervertebral Disc and Vertebral Cancellous Bone Metabolism in a Large Porcine Model.

It remains challenging to evaluate the in vivo pathophysiological biochemical characteristics in spine tissue, due to lack of an applicable model and feasible methods. The aim of this study was to apply microdialysis for the assessment of basic metabolites from the C3-C4 intervertebral disc, C3 vertebral cancellous bone and subcutaneous adipose tissue in a large porcine model. In 7 pigs, glucose, pyruvate, lactate and glycerol concentrations were evaluated in an 8-hour sampling period. The mean lactate/pyruvate (L/P) ratios for the intervertebral disc and vertebral cancellous bone were comparable and exceeded the ischemic cut-off value of 25 for the entire sampling interval. For subcutaneous adipose tissue, the L/P ratio was below the ischemic cut-off. This exploratory study confirms previous findings of ischemia in bone and the intervertebral disc. This encourages new microdialysis study designs in spine tissue employing large porcine models to create new knowledge and a greater understanding of the metabolism and pathogenesis in spine tissue.

Residual Stress Levels on the Cortical Section of Vertebral Bone Tissue

Residual Stress Levels on the Cortical Section of Vertebral Bone Tissue

Formation of Hydroxyapatite via Transformation of Amorphous Calcium Phosphate in the Presence of Alginate Additives

Hydroxyapatite (HA) is the primary mineral of vertebral tooth and bone tissue; thus, it is often incorporated into synthetic composite materials designed for hard tissue engineering applications. U...

Evaluation of rapid GeneXpert MTB/RIF method using DNA tissue specimens of vertebral bones in patients with suspected spondylitis TB

To detect Mycobacterium tuberculosis DNA and rifampicin resistance in vertebral bone tissue specimens from spondylitis TB suspects. The rapid GeneXpert MTB/RIF and MGIT 960 liquid culture methods have been used in the specimens. Results from 70 suspects with spondylitis TB shown that 31.42% identified positive for spondylitis TB using culture method, while 88.57% shown positive results using rapid GeneXpert MTB/RIF method. The validity of GeneXpert MTB/RIF shown sensitivity value of 100%, specificity value of 16.6%, PPV of 35.48%, and NPV of 100%. GeneXpert has a high sensitivity but low specificity value in this study.

Peculiarities of Reparative Osteogenesis of Injured Thoracic and Lumbar Vertebral Bodies at Different Terms after Trauma

The analysis of the results of morphologic examination of vertebral body bone tissue obtained intraoperatively from 43 patients (20 - 67 years) with thoracic and lumbar spine injuries at different terms after trauma was performed. All patients were operated on via anterior approach to create ventral fusion. In the examined serial samples of vertebral body structures the quality and regeneration potential of bone tissue were assessed. It was shown that cell differentiation during the osteogenesis process was closely associated with angiogenesis. In the zones with active growth of microcirculatory bed vessels the normal cycle of osteoblast and osteocytes took place while hypoxia and acidosis resulted in pathologic osteogenesis. In patients under 50 years, both males and females) the full value consolidation time averaged 5 months. In patients over 50 years, independently of the gender, the decrease of spongy structures volume and bone mineral density was observed. The recommendations on surgical treatment tactics of patients with thoracic and lumbar vertebral body injuries were given.

The impact of metastasis on the mineral phase of vertebral bone tissue

The negative impact of metastases on the mechanical performance of vertebral bone is often attributed to reduced bone density and/or compromised architecture. However limited characterization has been done on the impact of metastasis on the mineralization of bone tissue and resulting changes in material behaviour. This study aimed to evaluate the impact of metastasis on micro and nano scale characteristics of the mineral phase of bone, specifically mineral crystal growth, homogeneity of mineralization and changes in intrinsic material properties. Female athymic rats were inoculated with HeLa or Ace-1 cancer cells lines producing osteolytic or mixed (osteolytic & osteoblastic) metastases respectively (N=17 per group). A maximum of 21 days was allowed between inoculation and sacrifice of inoculated rats and healthy age-matched uninoculated controls (N=11). X-ray diffraction was used to assess average crystal size in crushed L1-L3 vertebrae; backscatter electron microscopy and nanoindentation were utilized to evaluate modifications in bone mineral density distribution and material behaviour (tissue hardness and modulus) in sagittal-sectioned, embedded and polished L5 vertebrae. HeLa inoculated samples showed reduced mineral crystal width compared to healthy controls. While both types of metastatic involvement reduced tissue mineral content, pathological osteoblastic bone, specific to Ace-1 inoculated samples, significantly decreased tissue mineral homogeneity, whereas osteolytic bone from HeLa samples saw a slight increase in homogeneity. The modulus and hardness of pathological osteoblastic bone was diminished compared to all other bone. Elucidating changes in material behaviour and mineralization of bone tissue is key to defining bone quality in the presence of metastatic involvement.

Peculiarities of Reparative Osteogenesis of Injured Thoracic and Lumbar Vertebral Bodies at Different Terms after Trauma

The analysis of the results of morphologic examination of vertebral body bone tissue obtained intraoperatively from 43 patients (20 - 67 years) with thoracic and lumbar spine injuries at different terms after trauma was performed. All patients were operated on via anterior approach to create ventral fusion. In the examined serial samples of vertebral body structures the quality and regeneration potential of bone tissue were assessed. It was shown that cell differentiation during the osteogenesis process was closely associated with angiogenesis. In the zones with active growth of microcirculatory bed vessels the normal cycle of osteoblast and osteocytes took place while hypoxia and acidosis resulted in pathologic osteogenesis. In patients under 50 years, both males and females) the full value consolidation time averaged 5 months. In patients over 50 years, independently of the gender, the decrease of spongy structures volume and bone mineral density was observed. The recommendations on surgical treatment tactics of patients with thoracic and lumbar vertebral body injuries were given.

Drug Release Characteristics and Tissue Distribution of Rifapentine Polylactic Acid Sustained-Release Microspheres in Rabbits after Paravertebral Implantation.

BackgroundRates of drug-resistant tuberculosis (TB) and TB associated with human immunodeficiency virus (HIV) infection have increased dramatically, intensifying challenges in TB control. New formulations of TB treatment drugs that control drug release and increase local drug concentrations will have a significant impact on mitigating the toxic side effects and increasing the clinical efficacy of anti-TB drugs.ObjectivesThe aim was to observe the sustained release characteristics of rifapentine polylactic acid sustained-release microspheres in vivo and the accumulation of rifapentine in other tissues following paravertebral implantation.MethodsThis study is a basic animal experimental study that began on July 17, 2014 in the Fifth Affiliated hospital of Xinjiang Medical University. One hundred and eight New Zealand white rabbits (weighing 2.8 - 3.0 kg, male and female, China) were randomly divided into three groups of 36 rabbits each. Blood and tissue samples from the liver, lungs, kidneys, vertebrae, and paravertebral muscle were collected at different time points post-surgery. High performance liquid chromatography (HPLC) analysis with a biological internal standard was used to determine the drug concentrations in samples.ResultsIn group A, no significant differences in rifapentine concentrations in the liver were detected between any two time points (P > 0.05). However, the differences in rifapentine concentrations between day 10 and day 21 were statistically significant (P < 0.05); for days 21, 35, 46, and 60, the differences in rifapentine concentrations between two sequential time points were not statistically significant (P > 0.05). In group B, the differences in rifapentine concentration between days 3 and 10 in vertebral bone and in paravertebral muscles were statistically significant (P < 0.05). Rifapentine was detected in the vertebral bone tissue in the group C animals. The rifapentine concentrations between two sequential time points were statistically significant (P < 0.05). Rifapentine could not be detected in the paravertebral muscles 46 days after the operation. The differences in rifapentine concentrations between two sequential time points among days 3, 10, 21, and 35 were statistically significant (P < 0.05).ConclusionsAfter paravertebral implantation of rifapentine polylactic acid sustained-release microspheres, the concentration of rifapentine in local vertebral bone tissues was maintained above the TB minimum inhibitory concentration for up to 60 days with no apparent accumulation of the drug in other tissues.

AGE AS A DETERMINANT OF VERTEBRAL TRABECULAR BONE STATUS IN HODGKIN LYMPHOMA PATIENTS AFTER COMPLETION OF CHEMOTHERAPY: A PROSPECTIVE STUDY

&lt;p&gt;Bone density alterations are often reported in patients with solid tumors and hematologic malignancies except cases of Hodgkin lymphoma, when this problem remains understudied. The aim of this study was to investigate the significance of patients’ age and ABVD standard chemotherapy regimen as the determinants of vertebral trabecular bone tissue status changes. The study included 40 HL patients of different age groups (median age 35.38 ± 2.22). Densitometric and structural parameters were obtained from pre-treatment and after chemo CT scans. Analysis of these parameters after chemotherapy compared to the initial values revealed significant decrease of bone density (maximum up to 24.9 %) in all age groups, as well as in patients who were treated with ABVD regimen. Structural parameters values (BV/TV, SMI, BS, FD, textural parameters) had also suggested trabecular transformation dependent on patients’ age and chemotherapy treatment. Age and ABVD standard chemotherapy may be considered as predisposing risk factors for trabecular bone structural alteration and there is a need for timely diagnosis and prevention.&lt;/p&gt;

Establishment of a comprehensive reference transcriptome for vertebral bone tissue to study the impacts of nutritional phosphorus deficiency in rainbow trout (Oncorhynchus mykiss, Walbaum)

Reducing dietary phosphorus (P) is a common approach to reduce effluent P outputs. The potential resulting P-deficiency is known to negatively impact fish bone condition and might result in vertebral deformities. To date, no large-scale study involving deep sequencing of the bone transcriptome has been conducted in salmonids and vertebral molecular changes remain poorly described. This study aims to provide the first comprehensive vertebral transcriptome for rainbow trout (Oncorhynchus mykiss) to allow functional and quantitative expression studies. Fish weighing 60.8±1.6g, were fed for 27weeks using two practical diets having 0.29% (deficient) and 0.45% (sufficient) available phosphorus (P), respectively. Deep sequencing was conducted using HiSeq2000 Illumina 100 paired-end technology from pooled P-deficient and P-sufficient fish and individuals displaying vertebral deformities. Over 140 million trimmed paired-end reads were assembled de novo with Trinity and resulted in 679,869 transcripts with a mean length of 542.5bp. From these sequences, 340,747 matched with referenced ESTs from rainbow trout. Furthermore, 141,909 and 117,564 sequences were functionally annotated against Nr and Uniprot databases, respectively. Interestingly, we observed putative homologue sequences for most of the key components involved in bone formation and turnover in mammals.

The role of hybrid chitosan membranes on scarring process following lumbar surgery: post-laminectomy experimental model

Objectives:Post-operative scarring process on lumbar surgery is object of several studies mainly because of the epidural fibrosis formation. Hybrid chitosan have shown promising effect on fibrosis prevention. The aim of this study was to determine the influence of chitosan-silane membrane on the lumbar surgery scarring process. These membranes have improved mechanical strength which makes them suitable to maintain a predefined shape.Methods:A two level lumbar laminectomy was performed in 14 New Zealand male rabbits. Laminectomy sites were randomly selected for biomaterial or control. Chitosan membranes were prepared and care was taken in order to make it adapted to the bone defect dimensions covering the totality of the defect including the bone margins. Histological analysis was performed by haematoxylin/eosin and by Masson’s trichrome staining four weeks after laminectomy.Results:Microscope observations revealed the presence of a well-organized regenerating tissue, integrated in the surrounding vertebral bone tissue with a regular and all-site interface on the chitosan sites, in clear contrast with the presence of a disorganized regenerating tissue with aspects consistent with the persistence of a chronic inflammatory condition, on control sites.Discussion:The results of this study clearly demonstrated that hybrid chitosan had an organizing effect on post-operative scarring process. The presence of the hybrid chitosan membrane resulted on a well-organized tissue integrated in the surrounding vertebral bone tissue with signs of regenerative bone tissue in continuity with native bone. This can be a major feature on the dynamics of epidural fibrosis formation.

Microdamage Caused by Fatigue Loading in Human Cancellous Bone: Relationship to Reductions in Bone Biomechanical Performance

Vertebral fractures associated with osteoporosis are often the result of tissue damage accumulated over time. Microscopic tissue damage (microdamage) generated in vivo is believed to be a mechanically relevant aspect of bone quality that may contribute to fracture risk. Although the presence of microdamage in bone tissue has been documented, the relationship between loading, microdamage accumulation and mechanical failure is not well understood. The aim of the current study was to determine how microdamage accumulates in human vertebral cancellous bone subjected to cyclic fatigue loading. Cancellous bone cores (n = 32) from the third lumbar vertebra of 16 donors (10 male, 6 female, age 76±8.8, mean ± SD) were subjected to compressive cyclic loading at σ/E0 = 0.0035 (where σ is stress and E0 is the initial Young’s modulus). Cyclic loading was suspended before failure at one of seven different amounts of loading and specimens were stained for microdamage using lead uranyl acetate. Damage volume fraction (DV/BV) varied from 0.8±0.5% (no loading) to 3.4±2.1% (fatigue-loaded to complete failure) and was linearly related to the reductions in Young’s modulus caused by fatigue loading (r2 = 0.60, p<0.01). The relationship between reductions in Young’s modulus and proportion of fatigue life was nonlinear and suggests that most microdamage generation occurs late in fatigue loading, during the tertiary phase. Our results indicate that human vertebral cancellous bone tissue with a DV/BV of 1.5% is expected to have, on average, a Young’s modulus 31% lower than the same tissue without microdamage and is able to withstand 92% fewer cycles before failure than the same tissue without microdamage. Hence, even small amounts of microscopic tissue damage in human vertebral cancellous bone may have large effects on subsequent biomechanical performance.