Trabecular bone structure correlates with hand posture and use in hominoids

Bone is capable of adapting during life in response to stress. Therefore, variation in locomotor and manipulative behaviours across extant hominoids may be reflected in differences in trabecular bone structure. The hand is a promising region for trabecular analysis, as it is the direct contact between the individual and the environment and joint positions at peak loading vary amongst extant hominoids. Building upon traditional volume of interest-based analyses, we apply a whole-epiphysis analytical approach using high-resolution microtomographic scans of the hominoid third metacarpal to investigate whether trabecular structure reflects differences in hand posture and loading in knuckle-walking (Gorilla, Pan), suspensory (Pongo, Hylobates and Symphalangus) and manipulative (Homo) taxa. Additionally, a comparative phylogenetic method was used to analyse rates of evolutionary changes in trabecular parameters. Results demonstrate that trabecular bone volume distribution and regions of greatest stiffness (i.e., Young's modulus) correspond with predicted loading of the hand in each behavioural category. In suspensory and manipulative taxa, regions of high bone volume and greatest stiffness are concentrated on the palmar or distopalmar regions of the metacarpal head, whereas knuckle-walking taxa show greater bone volume and stiffness throughout the head, and particularly in the dorsal region; patterns that correspond with the highest predicted joint reaction forces. Trabecular structure in knuckle-walking taxa is characterised by high bone volume fraction and a high degree of anisotropy in contrast to the suspensory brachiators. Humans, in which the hand is used primarily for manipulation, have a low bone volume fraction and a variable degree of anisotropy. Finally, when trabecular parameters are mapped onto a molecular-based phylogeny, we show that the rates of change in trabecular structure vary across the hominoid clade. Our results support a link between inferred behaviour and trabecular structure in extant hominoids that can be informative for reconstructing behaviour in fossil primates

Local origins impart conserved bone type-related differences in human osteoblast behaviour

Osteogenic behaviour of osteoblasts from trabecular, cortical and subchondral bone were examined to determine any bone type-selective differences in samples from both osteoarthritic (OA) and osteoporotic (OP) patients. Cell growth, differentiation; alkaline phosphatase (TNAP) mRNA and activity, Runt-related transcription factor-2 (RUNX2), SP7-transcription factor (SP7), bone sialoprotein-II (BSP-II), osteocalcin/bone gamma-carboxyglutamate (BGLAP), osteoprotegerin (OPG, TNFRSF11B), receptor activator of nuclear factor-κβ ligand (RANKL, TNFSF11) mRNA levels and proangiogenic vascular endothelial growth factor-A (VEGF-A) mRNA and protein release were assessed in osteoblasts from paired humeral head samples from age-matched, human OA/OP (n = 5/4) patients. Initial outgrowth and increase in cell number were significantly faster (p < 0.01) in subchondral and cortical than trabecular osteoblasts, in OA and OP, and this bone type-related differences were conserved despite consistently faster growth in OA. RUNX2/SP7 levels and TNAP mRNA and protein activity were, however, greater in trabecular than subchondral and cortical osteoblasts in OA and OP. BSP-II levels were significantly greater in trabecular and lowest in cortical osteoblasts in both OA and OP. In contrast, BGLAP levels showed divergent bone type-selective behaviour; highest in osteoblasts from subchondral origins in OA and trabecular origins in OP. We found virtually identical bone type-related differences, however, in TNFRSF11B:TNFSF11 in OA and OP, consistent with greater potential for paracrine effects on osteoclasts in trabecular osteoblasts. Subchondral osteoblasts (OA) exhibited highest VEGF-A mRNA levels and release. Our data indicate that human osteoblasts in trabecular, subchondral and cortical bone have inherent, programmed diversity, with specific bone type-related differences in growth, differentiation and pro-angiogenic potential in vitro

Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men.

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment

Structure model index does not measure rods and plates in trabecular bone

Structure model index (SMI) is widely used to measure rods and plates in trabecular bone. It exploits the change in surface curvature that occurs as a structure varies from spherical (SMI = 4), to cylindrical (SMI = 3) to planar (SMI = 0). The most important assumption underlying SMI is that the entire bone surface is convex and that the curvature differential is positive at all points on the surface. The intricate connections within the trabecular continuum suggest that a high proportion of the surface could be concave, violating the assumption of convexity and producing regions of negative differential. We implemented SMI in the BoneJ plugin and included the ability to measure the amounts of surface that increased or decreased in area after surface mesh dilation, and the ability to visualize concave and convex regions. We measured SMI and its positive (SMI+) and negative (SMI-) components, bone volume fraction (BV/TV), the fraction of the surface that is concave (CF), and mean ellipsoid factor (EF) in trabecular bone using 38 X-ray microtomography (XMT) images from a rat ovariectomy model of sex steroid rescue of bone loss, and 169 XMT images from a broad selection of 87 species' femora (mammals, birds, and a crocodile). We simulated bone resorption by eroding an image of elephant trabeculae and recording SMI and BV/TV at each erosion step. Up to 70%, and rarely less than 20%, of the trabecular surface is concave (CF 0.155 – 0.700). SMI is unavoidably influenced by aberrations from SMI-, which is strongly correlated with BV/TV and CF. The plate-to-rod transition in bone loss is an erroneous observation resulting from SMI's close and artefactual relationship with BV/TV. SMI cannot discern between the distinctive trabecular geometries typical of mammalian and avian bone, whereas EF clearly detects birds' more plate-like trabeculae. EF is free from confounding relationships with BV/TV and CF. SMI results reported in the literature should be treated with suspicion. We propose that EF should be used instead of SMI for measurements of rods and plates in trabecular bone

Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength

Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites

Influence of obesity on microarchitecture and biomechanical properties in patients with hip fracture.

La obesidad y la osteoporosis (OP) son dos patologías muy prevalentes en nuestra sociedad actual. El efecto de la obesidad sobre la calidad ósea se encuentra en debate en la actualidad. Objetivo: Valorar el efecto del peso corporal sobre la microestructura y las propiedades biomecánicas de hueso trabecular procedente de biopsias de extremidad proximal de fémur de pacientes con fractura de cadera por fragilidad. Material y método: Estudio transversal de 16 pacientes con fractura de cadera. 2 grupos según su IMC: (A) sujetos normopeso y (B) con obesidad. Recogimos biopsias de hueso trabecular de cabeza femoral. Valoramos determinaciones bioquímicas (PTH, 25(OH) vitamina D e IGF-1), marcadores de remodelado óseo (PINP,CTX), masa ósea (DMO cuello y cadera total), microestructura ósea y estudio biomecánico (µCt). El análisis estadístico: t-Student (SPSS 22.0) significación p<0,05. Resultados: Todos los pacientes presentaron DMO de cadera en rango osteoporótico. El grupo de obesos presentó niveles superiores de PTH e inferiores de IGF-1, vitamina D y PINP. No encontramos diferencias en los parámetros relacionados con el metabolismo óseo. El grupo de obesos presentó mejores índices microestructurales alcanzando la significación: mayor volumen óseo (BV/TV: 36,6±12,7 vs. 19,4±11,4%, BS/TV: 5,5±1,1 vs. 3,9±1,3%), mayor número de trabéculas (Tb.N: 1,6±0,4 vs. 1,01±0,4), mayor anchura de trabéculas (Tb.Th: 0,22±0,003 vs. 0,17±0,05) y menor separación trabecular (Tb.Sp: 0,51±0,12 vs. 0,66±0,16). Los parámetros biomecánicos confirman una mayor resistencia del hueso trabecular en pacientes obesos. Conclusión: La obesidad puede ser un factor protector de la calidad ósea en la región femoral y tiene menos efecto sobre la densidad mineral ósea.Obesity and osteoporosis (OP) are two very prevalent diseases in our society today. The effect of obesity on bone quality is currently a subject under discussion. Objective: To assess the effect of body weight on the microstructure and biomechanical properties of trabecular bone biopsies from the proximal end of the femur in patients with hip fracture fragility. Material and methods: Cross-sectional study of 16 patients with hip fracture. The 2 groups are divided according to their BMI: (A) normal weight individuals and (B) those with obesity. We collected biopsies of cancellous bone from the femoral head and assessed biochemical determinations (PTH, 25 (OH) vitamin D and IGF-1), bone remodeling markers (PINP, CTX), bone mass (BMD neck and total hip), bone microstructure and biomechanical study (µCt). Statistical analysis: Student's t test (SPSS 22.0) significance p<0.05. Results: All patients had hip BMD in osteoporotic range. The obese group had higher levels of PTH and lower IGF-1, vitamin D and PINP. We found no differences in the parameters related to bone metabolism. The obese group showed better indices reaching microstructural significance: increased bone volume (BV/TV: 36.6±12.7 vs 19.4±11.4%, BS/TV: 5.5±1.1 vs 3.9±1.3%), higher trabecular number (Tb.N: 1.6±0.4 vs 1,01±0,4), greater trabecular width (Tb.Th: 0.22±0.003 vs 0.17±0.05) and lower trabecular separation (Tb.Sp: 0.51±0.12 vs 0.66±0.16). Biomechanical parameters confirm greater strength of trabecular bone in obese patients. Conclusion: Obesity may be a protective factor of bone quality in the femoral region and has less effect on bone mineral density

Prolonging disuse in aged mice amplifies cortical but not trabecular bones’ response to mechanical loading

Objective: Short-term neurectomy-induced disuse (SN) has been shown to restore load responses in aged mice. We examined whether this restoration was further enhanced in both cortical and trabecular bone by simply extending the SN. Methods: Following load: strain calibration, tibiae in female C57BL/J6 mice at 8, 14 and 20 weeks and 18 months (n=8/group) were loaded and bone changes measured. Effects of long-term SN examined in twenty-six 18 months-old mice, neurectomised for 5 or 100 days with/without subsequent loading. Cortical and trabecular responses were measured histomorphometrically or by micro-computed tomography. Results: Loading increased new cortical bone formation, elevating cross-sectional area in 8, 14 and 20 week-old (p <0.05), but not 18 month-old aged mice. Histomorphometry showed that short-term SN reinstated load-responses in aged mice, with significant 33% and 117% increases in bone accrual at 47% and 37%, but not 27% of tibia length. Cortical responses to loading was heightened and widespread, now evident at all locations, following prolonged SN (108, 167 and 98% at 47, 37 and 27% of tibial length, respectively). In contrast, loading failed to modify trabecular bone mass or architecture. Conclusions: Mechanoadaptation become deficient with ageing and prolonging disuse amplifies this response in cortical but not trabecular bone

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p\u3c0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure