Bone Material Properties Research Articles

Prediction of bone ingrowth into a porous novel hip-stem: A finite element analysis integrated with mechanoregulatory algorithm.

Bone ingrowth into a porous implant is necessary for its long-term fixation. Although attempts have been made to quantify the peri-implant bone growth using finite element (FE) analysis integrated with mechanoregulatory algorithms, bone ingrowth into a porous cellular hip stem has scarcely been investigated. Using a three-dimensional (3D) FE model and mechanobiology-based numerical framework, the objective of this study was to predict the spatial distribution of evolutionary bone ingrowth into an uncemented novel porous hip stem proposed earlier by the authors. A CT-based FE macromodel of the implant-bone structure was developed. The bone material properties were assigned based on CT grey value. Peak musculoskeletal loading conditions, corresponding to level walking and stair climbing, were applied. The geometry of the implant-bone macromodel was divided into multiple submodels. A suitable mapping framework was used to transfer maximum nodal displacements from the FE macromodel to the cut boundaries of the FE submodels. CT grey value-based bone materials properties were assigned to the submodels. Thereafter, the submodels were solved and simulations of bone ingrowth were carried out using mechanoregulatory principle. A gradual increase in the average Young's modulus, from 1200 to 1500 MPa, of the bone tissue layer was observed considering all the submodels. The distal submodel exhibited 82% of bone ingrowth, whereas the proximal submodel experienced 65% bone ingrowth. Equilibrium in the bone ingrowth process was achieved in 7 weeks postoperatively, with a notable amount of bone ingrowth that should lead to biological fixation of the novel hip stem.

Computationally derived endosteal strain and strain gradients correlate with increased bone formation in an axially loaded murine tibia model

Osteoporosis is a common metabolic bone disorder characterized by low bone mass and microstructural degradation of bone tissue due to a derailed bone remodeling process. A deeper understanding of the mechanobiological phenomena that modulate the bone remodeling response to mechanical loading in a healthy bone is crucial to develop treatments. Rodent models have provided invaluable insight into the mechanobiological mechanisms regulating bone adaptation in response to dynamic mechanic stimuli. This study sheds light on these aspects by means of assessing the mechanical environment of the cortical and cancellous tissue to in vivo dynamic compressive loading within the mouse tibia using microCT-based finite element model in combination with diaphyseal strain gauge measures. Additionally, this work describes the relation between the mid-diaphyseal strains and strain gradients from the finite element analysis and bone formation measures from time-lapse in vivo tibial loading with a fluorochrome-derived histomorphometry analysis. The mouse tibial loading model demonstrated that cancellous strains were lower than those in the midshaft cortical bone. Sensitivity analyses demonstrated that the material property of cortical bone was the most significant model parameter. The computationally-modeled strains and strain gradients correlated significantly to the histologically-measured bone formation thickness at the mid-diaphyseal cross-section of the mouse tibia.

Bone mechanical properties were altered in a mouse model of multiple myeloma bone disease

Multiple myeloma bone disease (MMBD) is characterized by the growth of malignant plasma cells in bone marrow, leading to an imbalance in bone (re)modeling favoring excessive resorption. Loss of bone mass and altered microstructure characterize MMBD in humans and preclinical animal models, although, no study to date has examined bone composition or material properties. We hypothesized that MMBD alters bone composition, mineral crystal properties and mechanical properties in the MOPC315.BM.Luc model after intra-tibial injection of myeloma cells and three weeks of daily in vivo tibial loading. Decreased cortical bone elastic modulus and hardness measured by nanoindentation of tibiae were observed in MM-injected mice compared to PBS-injected mice, whereas cortical bone composition, mineral crystal properties measured by Fourier-transform infrared imaging or small angle X-ray scattering, respectively remained unchanged. However, MM-injected mice had thinner cancellous bone mineral particles compared to PBS-injected mice. Mechanical loading did not lead to altered cortical bone composition, mineral structure, or mechanical properties in the context of MM. Unexpectedly, we observed the intra-tibial injection itself altered the material composition of bone, manifested by increased matrix mineralization and crystal size of the hydroxyapatite crystals in the bone matrix. In conclusion, our data suggest that mechanical stimuli can be used as an adjuvant bone anabolic therapy in patients with MMBD to rebuild bone with unaltered composition and mineral structure to reduce subsequent fracture risk.

Material Homogenization of Human Femur Bone Material Using a New Weighted Approach

Abstract The design of efficient and safe biocompatible artificial implants for bone replacement and reconstructions requires a thorough understanding of natural bone material. A new homogenization approach is therefore used to predict effective material properties of the human femur bone. The bone structure is idealized as a functionally graded composite made of different quantities of a collagen protein matrix reinforced by hydroxyapatite mineral acting as the filler. Two distinct composite models were investigated, one where the mineral reinforcements were assumed to be randomly dispersed inclusions in a matrix of collagen, and a second model wherein the minerals were assumed to be unidirectional fibers. Predicted results for longitudinal and transverse elastic modulus from the models compare very well with range of values from published experimental data. It is also compared to those predicted using classical homogenization models. These material properties are then used to obtain the structural response of a bone plate section under transverse load.

Transmenopausal changes in cortical bone quality

Bone's resistance to fracture depends on its amount and quality, the latter including its structural and material/compositional properties. Bone material properties are dependent on bone turnover rates, which are significantly elevated immediately following menopause. Previously published data reported that following menopause, the amount of organic matrix synthesized at actively forming surfaces is significantly decreased, while glycosaminoglycan content was also modulated at resorbing surfaces, in the cancellous compartment.In the present study, we used Raman microspectroscopic analysis of paired iliac crest biopsies obtained before and shortly after menopause (1 year after cessation of menses) in healthy females to investigate changes in material/compositional properties due to menopause, in the cortical compartment. Specifically, the mineral/matrix ratio, the relative proteoglycan content, the mineral maturity/crystallinity, and the relative pyridinoline collagen cross-link content were determined at actively forming intracortical surfaces (osteons) as a function of tissue age, as well as in interstitial bone.Results indicated that it is the freshly synthesized organic matrix content that significantly declines following menopause, in agreement with what was previously reported for the cancellous compartment. This decline was not evident in the freshly deposited mineral content. None of the compositional/quality properties were altered following menopause either. Finally, no differences in any of the monitored parameters were evident in cortical interstitial bone.

Biomechanical analysis of various internal fracture fixation devices used for treating femoral neck fractures: A comparative finite element analysis

IntroductionSeveral internal fixation devices are available for treating Pauwels type I, II and III femoral neck fractures. The present study compared various fixation implants for all Pauwels fracture types using a CT-based subject-specific finite element model of the femur and determined the most effective implant for each fracture type. Materials and MethodsThe analysis included four different configurations of cannulated screw models, Femoral Neck System, Dynamic Hip Screw and Dynamic Condylar Screw (with and without anti-rotational screw). Ti-alloy was considered as the implant material. Heterogeneous bone material property was assigned based on CT grey value. Frictional contact was assumed in the contact interfaces. Peak loading corresponding to normal walking and stair-climbing were considered. Equivalent strain in bone, equivalent stress in the implants, femoral head deformation and rotation, micromotion in the contact interfaces, and strain-shielding in bone were evaluated for each implanted model. ResultsStresses generated in the implants were within the yield limit of the implant material. In Pauwels I and II, the micromotion predicted at the contact regions in all the implanted models was within 100 µm, which is suitable for bone integration. However, in Pauwels III fracture, most of the implanted models other than DHS with AR-screw model exhibited micromotion of more than 150 µm in the contact regions, which is expected to inhibit bone growth. ConclusionsThe DHS with AR-screw implanted model was identified as the most effective in treating Pauwels I and III fractures. However, for Pauwels type II, DCS with an AR-screw implant was deemed superior to the other configurations.

Aging alters the subchondral bone response 7 days after noninvasive traumatic joint injury in C57BL/6JN mice.

Posttraumatic osteoarthritis (PTOA) commonly develops following anterior cruciate ligament (ACL) injuries, affecting around 50% of individuals within 10-20 years. Recent studies have highlighted early changes in subchondral bone structure after ACL injury in adolescent or young adult mice, which could contribute to the development of PTOA. However, ACL injuries do not only occur early in life. Middle-aged and older patients also experience ACL injuries and PTOA, but whether the aged subchondral bone also responds rapidly to injury is unknown. This study utilized a noninvasive, single overload mouse injury model to assess subchondral bone microarchitecture, turnover, and material properties in both young adults (5 months) and early old age (22 months) female C57BL/6JN mice at 7 days after injury. Mice underwent either joint injury (i.e., produces ACL tears) or sham injury procedures on both the loaded and contralateral limbs, allowing evaluation of the impacts of injury versus loading. The subchondral bone response to ACL injury is distinct for young adult and aged mice. While 5-month mice show subchondral bone loss and increased bone resorption postinjury, 22-month mice did not show loss of bone structure and had lower bone resorption. Subchondral bone plate modulus increased with age, but not with injury. Both ages of mice showed several bone measures were altered in the contralateral limb, demonstrating the systemic skeletal response to joint injury. These data motivate further investigation to discern how osteochondral tissues differently respond to injury in aging, such that diagnostics and treatments can be refined for these demographics.

Femoral bone structure and mechanics at the edge and core of an expanding population of the invasive frog Xenopus laevis.

Understanding how living tissues respond to changes in their mechanical environment is a key question in evolutionary biology. Invasive species provide an ideal model for this as they are often transplanted between environments that differ drastically in their ecological and environmental context. Spatial sorting, the name given to the phenomenon driving differences between individuals at the core and edge of an expanding range, has been demonstrated to impact the morphology and physiology of Xenopus laevis from the invasive French population. Here, we combined a structural analysis using micro-CT scanning and a functional analysis by testing the mechanical properties of the femur to test whether the increased dispersal at the range edge drives differences in bone morphology and function. Our results show significant differences in the inner structure of the femur as well as bone material properties, with frogs from the centre of the range having more robust and resistant bones. This is suggestive of an energy allocation trade-off between locomotion and investment in bone formation, or alternatively, may point to selection for fast locomotion at the range edge. Overall, our results provide insights on the growth of the long bones and the formation of trabecular bone in frogs.

Degradation of the mechanical properties of cortical bone due to long duration storage

Understanding the behaviour and material properties of bone is critical in predicting the failure and fracture of bones in humans. To address this, mechanical tests have traditionally been conducted to characterize bone material and this has resulted in large body of literature. However, there appears to be a lack of complete information regarding the storage protocols used for bone specimens prior to conducting mechanical tests. For example, while storage methods are well described, parameters such as the time between donor death and bone retrieval, as well as time between specimen machining and testing, are seldom reported. As biological materials undergo degradation in storage after being removed from the donor, a clear understanding of this degradation behaviour would identify critical time frames in which previously stored cortical bone specimens should be tested such that they can still be considered representative of an in-vivo condition. In this paper, the results of an investigation to determine the effects of long duration storage on the measured mechanical properties of bovine cortical bone are reported. Three different storage protocols are compared; namely machined-refrigerated, machined-frozen and frozen-machined-frozen. Degradation effects are evident for both refrigerated and frozen specimens and the results demonstrate that testing bone specimens after more than one week in storage may not provide representative in-vivo properties. In addition, specimens exhibit severe degradation after six months in storage regardless of the storage protocol.

Effect of cement volume on biomechanical response of a spine segment treated with a PEEK polymer implant: a finite element comparative study with vertebroplasty.

In the current study, a 3D finite element study was performed to investigate the biomechanical response of an osteoporotic spine segment treated with a novel transpedicular implant (V-STRUT©, Hyprevention, France) made of PEEK (polyetheretherketone) material combined with either injections of 2, 3, 4, 5 and 6 cc of cement. The objective was to assess numerically the biomechanical performance of the implant in combination with different doses of the injected bone cement and to compare its performance with the gold standard vertebroplasty (VP) technique. A female (69yo) was selected and a 3D finite element model of an osteoporotic spine segment was built based on a Computed Tomography (CT) scan performed from T12 to L2 with corresponding intervertebral discs and ligaments. A heterogeneous distribution of bone material properties was assigned to the bone using grey scale levels. Bilateral ellipsoid geometries of the inserted cement were retained for the V-STRUT and VP models based on experimental observation performed on different patients treated with the V-STRUT device. The current study demonstrated an optimal dose of 4 cc of bilaterally injected cement for the V-STRUT and VP techniques to restore the treated segment and confirmed that the V-STRUT device in combination with bone cement is superior to VP alone in establishing the normal stiffness and in reducing the applied stress to the immediately adjacent vertebral levels.

Investigation of the Role of Osteoporotic Vertebra Degeneration on the Stability of the Lumbar Spine: In Silico Modelling under Compressive Loading.

An evaluation of the impact of osteoporosis on loss of spinal stability, with or without intervertebral disc degeneration, using computational analysis is presented. The research also investigates the correlation between osteoporosis and intervertebral disc degeneration. Three-dimensional finite element models of human lumbar spine segments were used to assess the influence of osteoporosis on spinal stability. Five different models of age-related degeneration were created using various material properties for trabecular bone and intervertebral discs. Calculation results indicate that in a spine with osteoporosis, the deformation of the intervertebral discs can increase by more than 30% when compared to a healthy spine. Thus, intervertebral disc deformation depends not only on the degree of degeneration of the discs themselves, but their deformation is also influenced by the degree of osteoporosis of the vertebrae. Additionally, the load-bearing capacity of the spine can decrease by up to 30% with osteoporosis, regardless of the degree of intervertebral disc deformation. In conclusion, osteoporosis can contribute to intervertebral disc degeneration.

Isotropic and orthotropic mechanical properties of in vivo mandible model: Assessment of computational modelling

This study assesses the various methodologies utilized in the literature for computational mandible modeling and their implications on research findings. Previous studies have explored diverse material properties for the mandible, whether modeled as a single entity, in pairs, or as multiple sub-regions. Within this framework, a finite element model of an intact mandible was created using sliced tomographic images to examine the dispersion of stress fields resulting from different sets of bone material properties sourced from specialized literature. This research introduces the methodology employed in mandible model development, strategies for achieving high precision, and the influence of mechanical properties. Through an evaluation of models proposed by different authors, significant dispersion was observed, leading to disparities ranging from 4.4% to 67.4% in stress field outcomes at the symphysis region. RMSE served as an estimator to assess the similarity between these models. The findings suggest that the Caraveo (2008) and Palka (2020) models exhibit notable convergence in predicting stress fields in the symphysis regions. By incorporating good modeling practices in the intact mandible model, a more reliable representation is ensured, laying the groundwork for future investigations involving nonlinear contact phenomena and topology optimization.

Osteomodulin deficiency in mice causes a specific reduction of transversal cortical bone size.

Skeletal growth, modeling, and remodeling are regulated by various molecules, one of them being the recently identified osteoanabolic factor WNT1. We have previously reported that WNT1 transcriptionally activates the expression of Omd, encoding Osteomodulin (OMD), in a murine mesenchymal cell line, which potentially explained the skeletal fragility of mice with mutational WNT1 inactivation, since OMD has been shown to regulate type I collagen fibril formation in vitro. In this study we confirmed the strong induction of Omd expression in a genome-wide expression analysis of transfected cells, and we obtained further evidence for Omd being a direct target gene of WNT1. To assess the in vivo relevance of this regulation, we crossed Omd-deficient mice with a mouse line harboring an inducible, osteoblast-specific Wnt1 transgene. After induction of Wnt1 expression for 1 or 3weeks, the osteoanabolic potency of WNT1 was not impaired despite the Omd deficiency. Since current knowledge regarding the in vivo physiological function of OMD is limited, we next focused on skeletal phenotyping of wild-type and Omd-deficient littermates, in the absence of a Wnt1 transgene. Here we did not observe an impact of Omd deficiency on trabecular bone parameters by histomorphometry and μCT either. Importantly, however, male and female Omd-deficient mice at the ages of 12 and 24weeks displayed a slender bone phenotype with significantly smaller long bones in the transversal dimension, while the longitudinal bone growth remained unaffected. Although mechanical testing revealed no significant changes explained by impaired bone material properties, atomic force microscopy of the femoral bone surface of Omd-deficient mice revealed moderate changes at the nanostructural level, indicating altered regulation of collagen fibril formation and aggregation. Taken together, our data demonstrate that, although OMD is dispensable for the osteoanabolic effect of WNT1, its deficiency in mice specifically modulates transversal cortical bone morphology.

Improving material properties of a poloxamer P407 hydrogel-based hydroxyapatite bone substitute material by adding silica-A comparative in vivo study.

The structure and handling properties of a P407 hydrogel-based bone substitute material (BSM) might be affected by different poloxamer P407 and silicon dioxide (SiO2) concentrations. The study aimed to compare the mechanical properties and biological parameters (bone remodeling, BSM degradation) of a hydroxyapatite: silica (HA)-based BSM with various P407 hydrogels in vitro and in an in vivo rat model. Rheological analyses for mechanical properties were performed on one BSM with an SiO2-enriched hydrogel (SPH25) as well on two BSMs with unaltered hydrogels in different gel concentrations (PH25 and PH30). Furthermore, the solubility of all BSMs were tested. In addition, 30 male Wistar rats underwent surgical creation of a well-defined bone defect in the tibia. Defects were filled randomly with PH30 (n = 15) or SPH25 (n = 15). Animals were sacrificed after 12 (n = 5 each), 21 (n = 5 each), and 63 days (n = 5 each). Histological evaluation and histomorphometrical quantification of new bone formation (NB;%), residual BSM (rBSM;%), and soft tissue (ST;%) was conducted. Rheological tests showed an increased viscosity and lower solubility of SPH when compared with the other hydrogels. Histomorphometric analyses in cancellous bone showed a decrease of ST in PH30 (p = .003) and an increase of NB (PH30: p = .001; SPH: p = .014) over time. A comparison of both BSMs revealed no significant differences. The addition of SiO2 to a P407 hydrogel-based hydroxyapatite BSM improves its mechanical stability (viscosity, solubility) while showing similar in vivo healing properties compared to PH30. Additionally, the SiO2-enrichment allows a reduction of poloxamer ratio in the hydrogel without impairing the material properties.

Gut hormone analogues and skeletal health in diabetes and obesity: Evidence from preclinical models

Diabetes mellitus and obesity are rapidly growing worldwide. Aside from metabolic disturbances, these two disorders also affect bone with a higher prevalence of bone fractures. In the last decade, a growing body of evidence suggested that several gut hormones, including ghrelin, gastrin, glucose-dependent insulinotropic polypeptide (GIP), glucagon, and glucagon-like peptide-1 and 2 (GLP-1 and GLP-2, respectively) may affect bone physiology. Several gut hormone analogues have been developed for the treatment of type 2 diabetes and obesity, and could represent a new alternative in the therapeutic arsenal against bone fragility. In the present review, a summary of the physiological roles of these gut hormones and their analogues is presented at the cellular level but also in several preclinical models of bone fragility disorders including type 2 diabetes mellitus, especially on bone mineral density, microarchitecture and bone material properties. The present review also summarizes the impact of GLP-1 receptor agonists approved for the treatment of type 2 diabetes mellitus and the more recent dual or triple analogue on bone physiology and strength.

Combining anabolic loading and raloxifene improves bone quantity and some quality measures in a mouse model of osteogenesis imperfecta

Osteogenesis imperfecta (OI) increases fracture risk due to changes in bone quantity and quality caused by mutations in collagen and its processing proteins. Current therapeutics improve bone quantity, but do not treat the underlying quality deficiencies. Male and female G610C+/− mice, a murine model of OI, were treated with a combination of raloxifene and in vivo axial tibial compressive loading starting at 10 weeks of age and continuing for 6 weeks to improve bone quantity and quality. Bone geometry and mechanical properties were measured to determine whole bone and tissue-level material properties. A colocalized Raman/nanoindentation system was used to measure chemical composition and nanomechanical properties in newly formed bone compared to old bone to determine if bone formed during the treatment regimen differed in quality compared to bone formed prior to treatment. Lastly, lacunar geometry and osteocyte apoptosis were assessed. OI mice were able to build bone in response to the loading, but this response was less robust than in control mice. Raloxifene improved some bone material properties in female but not male OI mice. Raloxifene did not alter nanomechanical properties, but loading did. Lacunar geometry was largely unchanged with raloxifene and loading. However, osteocyte apoptosis was increased with loading in raloxifene treated female mice. Overall, combination treatment with raloxifene and loading resulted in positive but subtle changes to bone quality.

Explaining and predicting the increased thorax injury in aged females: age and subject-specific thorax geometry coupled with improved bone constitutive models and age-specific material properties evaluated in side impact conditions.

Predicting and understanding thorax injury is fundamental for the assessment and development of safety systems to mitigate injury risk to the increasing and vulnerable aged population. While computational human models have contributed to the understanding of injury biomechanics, contemporary human body models have struggled to predict rib fractures and explain the increased incidence of injury in the aged population. The present study enhanced young and aged human body models (HBMs) by integrating a biofidelic cortical bone constitutive model and population-based bone material properties. The HBMs were evaluated using side impact sled tests assessed using chest compression and number of rib fractures. The increase in thoracic kyphosis and the associated change in rib angle with increasing age, led to increased rib torsional moment increasing the rib shear stress. Coupled with and improved cortical bone constitutive model and aged material properties, the higher resulting shear stress led to an increased number of rib fractures in the aged model. The importance of shear stress resulting from torsional load was further investigated using an isolated rib model. In contrast, HBM chest compression, a common thorax injury-associated metric, was insensitive to the aging factors studied. This study proposes an explanation for the increased incidence of thorax injury with increasing age reported in epidemiological data, and provides an enhanced understanding of human rib mechanics that will benefit assessment and design of future safety systems.

A Finite Element Model to Investigate the Stability of Osteochondral Grafts Within a Human Tibiofemoral Joint

Osteochondral grafting has demonstrated positive outcomes for treating articular cartilage defects by replacing the damaged region with a cylindrical graft consisting of bone with a layer of cartilage. However, factors that cause graft subsidence are not well understood. The aim of this study was to develop finite element (FE) models of osteochondral grafts within a tibiofemoral joint, suitable for an investigation of parameters affecting graft stability. Cadaveric femurs were used to experimentally calibrate the bone properties and graft-bone frictional forces for use in corresponding image-based FE models, generated from µCT scan data. Effects of cartilage defects and osteochondral graft repair were measured by examining contact pressure changes using further in vitro tests. Here, six defects were created in the femoral condyles, which were subsequently treated with osteochondral autografts or metal pins. Matching image-based FE models were created, and the contact patches were compared. The bone material properties and graft-bone frictional forces were successfully calibrated from the initial tests with good resulting levels of agreement (CCC = 0.87). The tibiofemoral joint experiment provided a range of cases that were accurately described in the resultant pressure maps and were well represented in the FE models. Cartilage defects and repair quality were experimentally measurable with good agreement in the FE model pressure maps. Model confidence was built through extensive validation and sensitivity testing. It was found that specimen-specific properties were required to accurately represent graft behaviour. The final models produced are suitable for a range of parametric testing to investigate immediate graft stability.

Regional variation of the cortical and trabecular bone material properties in the rabbit skull.

The material properties of some bones are known to vary with anatomical location, orientation and position within the bone (e.g., cortical and trabecular bone). Details of the heterogeneity and anisotropy of bone is an important consideration for biomechanical studies that apply techniques such as finite element analysis, as the outcomes will be influenced by the choice of material properties used. Datasets detailing the regional variation of material properties in the bones of the skull are sparse, leaving many finite element analyses of skulls no choice but to employ homogeneous, isotropic material properties, often using data from a different species to the one under investigation. Due to the growing significance of investigating the cranial biomechanics of the rabbit in basic science and clinical research, this study used nanoindentation to measure the elastic modulus of cortical and trabecular bone throughout the skull. The elastic moduli of cortical bone measured in the mediolateral and ventrodorsal direction were found to decrease posteriorly through the skull, while it was evenly distributed when measured in the anteroposterior direction. Furthermore, statistical tests showed that the variation of elastic moduli between separate regions (anterior, middle and posterior) of the skull were significantly different in cortical bone, but was not in trabecular bone. Elastic moduli measured in different orthotropic planes were also significantly different, with the moduli measured in the mediolateral direction consistently lower than that measured in either the anteroposterior or ventrodorsal direction. These findings demonstrate the significance of regional and directional variation in cortical bone elastic modulus, and therefore material properties in finite element models of the skull, particularly those of the rabbit, should consider the heterogeneous and orthotropic properties of skull bone when possible.

Aging impairs the osteocytic regulation of collagen integrity and bone quality

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRIIocy−/−) that suppresses PLR. The control aged bone displayed decreased TGFβ signaling and PLR, but aging did not worsen the existing PLR suppression in male TβRIIocy−/− bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFβ. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.