Tibial Cross Sections Research Articles

The Lacunocanalicular Network is Denser in C57BL/6 Compared to BALB/c Mice

The lacunocanalicular network (LCN) is an intricate arrangement of cavities (lacunae) and channels (canaliculi), which permeates the mineralized bone matrix. In its porosity, the LCN accommodates the cell network of osteocytes. These two nested networks are attributed a variety of essential functions including transport, signaling, and mechanosensitivity due to load-induced fluid flow through the LCN. For a more quantitative assessment of the networks’ function, the three-dimensional architecture has to be known. For this reason, we aimed (i) to quantitatively characterize spatial heterogeneities of the LCN in whole mouse tibial cross-sections of BALB/c mice and (ii) to analyze differences in LCN architecture by comparison with another commonly used inbred mouse strain, the C57BL/6 mouse. Both tibiae of five BALB/c mice (female, 26-week-old) were stained using rhodamine 6G and whole tibiae cross-sections were imaged using confocal laser scanning microscopy. Using image analysis, the LCN was quantified in terms of density and connectivity and lacunar parameters, such as lacunar degree, volume, and shape. In the same tibial cross-sections, the calcium content was measured using quantitative backscattered electron imaging (qBEI). A structural analysis of the LCN properties showed that spatially denser parts of the LCN are mainly due to a higher density of branching points in the network. While a high intra-individual variability of network density was detected within the cortex, the inter-individual variability between different mice was low. In comparison to C57BL/6J mice, BALB/c mice showed a distinct lower canalicular density. This reduced network was already detectable on a local network level with fewer canaliculi emanating from lacunae. Spatial correlation with qBEI images demonstrated that bone modeling resulted in disruptions in the network architecture. The spatial heterogeneity and differences in density of the LCN likely affects the fluid flow within the network and therefore bone’s mechanoresponse to loading.

Placing the tibial component of an ankle prosthesis: results of a CT-based simulation in healthy adults.

To characterize the 3D geometry of the distal tibia resection area from healthy individuals using CT-based digital implantation for proper preoperative sizing of TAA tibia component placement. Standardized CT images of healthy ankle joints serving as intra-individual references for treatment of contralateral injuries were identified. The tibial cross section dedicated to virtually host the tibial component was digitally prepared, and the size of the virtual contact surface was calculated. Finally, out of five prototypes the one fitting best in terms of size and alignment was identified. CT scans taken from 319 subjects were used for the virtual implantation procedure. Body height and size of the distal tibia contact area correlated (r = 0.49 and 0.42 in females and males, each p < 0.001). Prosthesis sizes 2 and 3 fit well for the vast majority of patients, while the smallest and largest sizes are rarely required. Digital implantation of the tibial component should be considered a valuable tool for preoperative planning as well as for the development of new implant types.

Digital Technology-Assisted "Z" Osteotomy lower limb corrective procedures.

Digital technology is a transformative product of the information age. z-osteotomy is a surgical procedure that corrects limb angulation and lengthens shortening deformities within a 40 mm difference in limb length.The purpose of this study is to Introduce the surgical technique of digitally assisted "Z" osteotomy for correction of angular and length deformities of the lower limbs and investigating its clinical efficacy. A retrospective study was conducted on five patients with multiplanar angular deformities of the lower extremity combined with limb shortening(n=5). The objective of the study was to assess the effectiveness of computer-assisted preoperative design planning and 3D-printed surgical guide fabrication in guiding precise orthopedic procedures. The study compared various parameters, including femoral or tibial cross-sections, coronal and sagittal deformities, limb length, modified Barthel Index, and post-operative complications. Five patients were granted 17.20±6.83 months of follow-up after surgery, with adequate correction of lower limb deformity, significant improvement in postoperative self-care ability improved Barthel index 90±3.08 points (P<0.05). One patient experienced postoperative wound pain at 3 months, which subsequently diminished significantly by the 4-month follow-up assessment., four cases had no complications. The new surgical method of digital technology-assisted "Z" osteotomy for correction of complex deformities of the lower limbs has remarkable clinical results, can accurately correct multi-planar angular deformities and realize limb lengthening at the same time, being safe and reliable.

Identification of long-range ultrasonic guided wave characteristics in cortical bone by modelling

The propagation of ultrasonic guided waves in cortical bone has potential to inform medical caregivers about the condition of the bone structure. However, as waveguides, human long bones such as the tibia are complex in terms of their material behavior and their geometric features. They exhibit anisotropic elasticity and internal damping. For the first time, wave propagation is modelled in the irregular hollow tibial cross-section, which varies along its long axis. Semi-analytical, frequency domain, and time domain finite element analyses providing complimentary information about long-range wave propagation characteristics in such a waveguide are applied to the mid-diaphyseal region of a human tibia. Simulating the guided waves generated by a contact transducer, the signals received in axial transmission indicate the consistent presence of low phase velocity non-dispersive propagating modes. The guided waves capable of traveling long distances have strong potential for diagnosis of fracture healing.

Shear-Actuation and Vibrometer Reception of Penetrating Ultrasonic Guided Wave Modes in Human Tibia

The hollow long bones of the human appendicular skeleton are known to support the propagation of ultrasonic guided waves, whose potential for diagnosing bone health is being investigated. In this study, ultrasonic guided waves propagating in the diaphysis of human tibia are characterized experimentally and numerically in the frequency range around 200 kHz. The experiment involves a unique combination of omni-directional shear transducer-based excitation and detection using a 1D laser Doppler vibrometer. The cluster of phase velocities obtained from a linear array of time-history data using space-time Fourier transform is found to be in the non-dispersive low-phase velocity region of the dispersion curves obtained for a tibial cross-section. Time-domain finite element analysis revealed that the displacement components normal to the surface are significant, even though the loading is from a shear transducer. Furthermore, semi-analytical finite element analysis revealed that the wave structures of the wave modes contained within the cluster of low-phase velocity modes are consistent with the displacement profiles obtained from the time-domain analysis. The experimental results show that the low-phase velocity mode cluster has sufficient intensity to propagate axially at least 85 mm in the mid-diaphyseal region.

The Posterolateral Corner-Locked Technique Is Applicable in a Chinese Population Regarding the Tibial Component Rotation Alignment in Total Knee Arthroplasty.

Rotational malalignment between the femoral and tibial components in total knee arthroplasty (TKA) can affect clinical outcomes, but there is no consensus on how to best determine tibia tray orientation. The posterolateral corner-locked (PLCL) technique may be a new method. This study aims to assess the applicability of this technique in a Chinese population. Forty normal Chinese volunteers were recruited and underwent computed tomography (CT) of the lower limbs. Knee model reconstructions and simulated standard tibial osteotomy were conducted digitally. The transepicondylar axis (TEA), the Akagi line, and the line connecting the medial third of the tibial tubercle with the midpoint of the posterior cruciate ligament (PCL) were projected to the tibial cross-section and marked. The PLCL technique was applied using either symmetrical or asymmetrical tibial tray templates, and the anteroposterior (AP) axis of the tibial tray was marked. The angles between the TEA and these lines were calculated, and the statistical differences were analyzed. The angle between the TEA and the Akagi line and between the TEA and the line connecting the medial third of the tibial tubercle with the midpoint of the PCL were 96.90 ± 5.57 and 107.31 ± 5.95 degrees, respectively. The angles between the TEA and the AP axis of the symmetrical and the asymmetrical design tibial trays were 94.01 ± 4.21 and 96.65 ± 4.70 degrees, respectively. Except for the Akagi line and AP axis of the asymmetrical tibial tray, statistical differences were found between all lines (p < 0.05). The PLCL technique is principally suitable for Chinese patients requiring TKA when using the tibial component referred to in this study, although it may result in slight external rotation.

The matching analysis of the tibial osteotomy and the imported prosthesis components of the Han and Uygur populations

Objective To compare the anatomical differences of tibia osteotomy between Han and Uygur populations and to analysis their compatibility with imported prosthesis component. Methods Two hundred patients (400 knees) were selected from the outpatients and healthy volunteers of the non-knee joint disease from September 1, 2012 to December 1, 2014, with 86 men (172 knees) and 114 women (228 knees). The average age is 44.6±10.8 years (range 21-68 years old). According to the populations, the subjects were divided into Han group and Uygur group. Furthermore, each group was divided into male subgroup and female subgroup. A full-length CT scan of the lower limb was conducted to reconstruct the knee joint in the workstation. The tibial osteotomy was simulated in total knee arthroplasty. The transverse diameter of the tibial cross section, the longitudinal depth of the medial platform and the depth of the lateral platform were measured. The front and back diameter and aspect ratio of the osteotomy were calculated. There parameters were compared between the Han and Uygur groups. Five mm tolerance range method was used to analysis the cover rate of the following three kinds of commercially imported prosthesis, namely Depuy, Link and Zimmer. Results The mean value of the tibial cross section were 72.3±4.3 mm, 50.7±3.1 mm, 47.8±3.0 mm, 49.3±2.9 mm and 0.682± 0.021 in Han group, while those were 74.5±4.8 mm, 51.4±3.0 mm, 48.6±2.8 mm, 50.0±2.9 mm and 0.672±0.020 in Uygur group, respectively. Except the aspect ratio, the average value of each parameter in Uygur group was greater than that in the Han group with statistically significant differences between the two populations. The cover rate of the three kinds of prosthesis tibial component were 53.0%, 37.0% and 40.0% for Han group, but 61.0%, 43.0% and 42.5% for Uygur group. Depuy prosthesis was fit for the Uygur population better. Conclusion The geometry and anatomy of proximal tibia in Chinese showed significant difference between Han and Uygur populations. The mean covering rates of the imported tibial components were low in the dimensions of the resected surface. We can improve the prosthesis and the matching degree by adjusting the parameters or increasing the model set. Key words: Tibia; Imaging, three-dimensional; Arthroplasty, replacement, knee; Prosthesis design

Phenamil, an amiloride derivative, restricts long bone growth and alters keeled-sternum bone architecture in growing chickens

“Broiler-type” chickens are fast-grow-ing, heavy-bodied birds with high demands on bone quality. Phenamil increased mineralization in cultured murine mesenchymal stem cells. Phenamil effects were tested in 2 groups of weight and gender matched day-old broiler chickens (n = 13). Oral administration of 30 mg phenamil/kg body weight d 1 to 13 reduced growth of chicks d 5 to 14 (P = 0.002); with phenamil-treated (PT) chick body weight being 84% of vehicle-treated (VT) chicks’ body weight on d 14. Tissues collected on d 15 showed that femur lengths and widths did not differ, but tibias from PT chicks were 6% shorter (P = 0.002) and 13% narrower (P = 0.012) with 18% thinner tibial cross-sections (P < 0.008) than in VT chicks. Angles of the caudal aspect of the anterior surface of keeled-sternums were 166° in PT chicks, flatter than the 148° found in VT chicks (P = 0.000). Total mineral content of both tibia and femur were lower in PT chicks (P = 0.005 for both). Bone Ca, P, and Mg (ppm) in ash were similar, but Ca:P was lower (1.70 vs 1.75) in PT versus VT chicks (P < 0.05). Osteocalcin was ∼20% lower (P = 0.020), PINP was ∼45% higher (P = 0.000) in PT chicks. Carboxy-terminal telopeptide type I collagen (ICTP) and cross-linked N-telopeptide of type I collagen (NTX1) were similar in the 2 groups. Phenamil had unexpected and detrimental effects on bone formation in growing broiler chicks, reducing linear skeletal growth and markedly changing bone architecture.

Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate

Odanacatib (ODN) is a selective and reversible inhibitor of cathepsin K which is an important enzyme for the degradation of collagen I. Aim of the present work was the head-to-head comparison between the effects of ODN and alendronate (ALN) on bone mineralization density distribution (BMDD), based on quantitative backscattered electron imaging in relation to changes in histomorphometric mineralizing surface per bone surface (MS/BS) in 12–22years old ovariectomized rhesus monkeys. Trabecular and cortical BMDD derived parameters from vertebrae and proximal tibiae were compared among vehicle (VEH, n=8), odanacatib low dose (ODN-L, n=8), odanacatib high dose (ODN-H, n=8), and alendronate (ALN, n=6) treated animals. Additionally, data from an intact, non-treated group of animals are shown (INT, n=8). In trabecular bone from the vertebra and metaphyseal tibia, the BMDD of the ODN and ALN treatment groups was shifted toward higher mineralization densities (p<0.001) consistent with the significant reduction of MS/BS (p<0.05 in ODN-H and ALN) compared to VEH. Vertebral trabecular CaMean (average degree of mineralization) was significantly higher in ODN-L (+6.5%), ODN-H (+6.1%), and ALN (+6.7%, all p<0.001). Tibial osteonal cortical bone revealed also significantly increased CaMean for ODN-L (+1.4%, p<0.05), ODN-H (+2.2%, p<0.05), and ALN (+3.4%, p<0.001) versus VEH, while primary cortical bone (devoid of secondary osteons) did not show any significant differences between the study groups. The percentage of primary bone area in the tibial cross-sections (on average 45±12%) was also not significantly different between the study groups (p=0.232). No significant differences in any BMDD parameters of all studied skeletal sites between ODN and ALN treatment were found. Correlation analysis revealed that MS/BS was highly predictive for trabecular BMDD in vertebral bone. The higher MS/BS, the lower was CaMean. Our findings are consistent with the inhibition of bone resorption of ODN and ALN in trabecular and osteonal compartments.

Effects of eldecalcitol on cortical bone response to mechanical loading in rats.

BackgroundMechanical loading of bones activates modeling and suppresses remodeling by promoting bone formation. Eldecalcitol is approved for the treatment of osteoporosis in Japan and is often used in patients undergoing exercise therapy. However, the effects of eldecalcitol on bone formation during mechanical loading are unknown. The aim of this study was to clarify the influence of eldecalcitol administration on bone response to mechanical loading using a four-point bending device.MethodsForty six-month-old female Wistar rats were randomized into four groups based on eldecalcitol dose (vehicle administration (VEH), low dose (ED-L), medium dose (ED-M), and high dose (ED-H)). Loads of 38 N were applied in vivo to the right tibia for 36 cycles at 2 Hz, by four-point bending, 3 days per week for 3 weeks. After calcein double-labeling, rats were sacrificed and tibial cross sections were prepared from the region with maximal bending at the central diaphysis. Histomorphometry was performed on the entire periosteal and endocortical surface of the tibiae, dividing the periosteum into lateral and medial surfaces.ResultsThe effects of external loading on bone formation parameters were significant at all three surfaces. Bone formation parameters were highest in the ED-H group, and the effects of eldecalcitol on bone formation rate were significant at the endocortical surface. In addition, the interaction between loading and eldecalcitol dose significantly affected bone formation rate at the endocortical surface.ConclusionsEldecalcitol enhanced the cortical bone response to mechanical loading and a synergistic effect was observed in a rat model.

Effects of bone-specific physical activity, gender and maturity on tibial cross-sectional bone material distribution: a cross-sectional pQCT comparison of children and young adults aged 5–29 years

Growth is the opportune time to modify bone accrual. While bone adaptation is known to be dependent on local loading and consequent deformations (strain) of bone, little is known about the effects of sex, and bone-specific physical activity on location-specific cross-sectional bone geometry during growth. To provide more insight we examined bone traits at different locations around tibial cross sections, and along the tibia between individuals who vary in terms of physical activity exposure, sex, and pubertal status. Data from 304 individuals aged 5–29years (172 males, 132 females) were examined. Peripheral quantitative computed tomography (pQCT) was applied at 4%, 14%, 38%, and 66% of tibial length. Maturity was established by estimating age at peak height velocity (APHV). Loading history was quantified with the bone-specific physical activity questionnaire (BPAQ). Comparisons, adjusted for height, weight and age were made between sex, maturity, and BPAQ tertile groups. Few to no differences were observed between sexes or BPAQ tertiles prior to APHV, whereas marked sexual dimorphism and differences between BPAQ tertiles were observed after APHV. Cross-sectional location-specific differences between BPAQ tertiles were not evident prior to APHV, whereas clear location-specificity was observed after APHV. In conclusion, the skeletal benefits of physical activity are location-specific in the tibia. The present results indicate that the peri- or post-pubertal period is likely a more favourable window of opportunity for enhancing cross-sectional bone geometry than pre-puberty. Increased loading during the peri-pubertal period may enhance the bone of both sexes.

Early urbanization and mobility at Tell Brak, NE Syria: the evidence from femoral and tibial external shaft shape

Urbanization at Tell Brak began in the late 5th millennium BCE and the site reached its maximum size in the Late Chalcolithic (LC) 3, ca. 3900–3600 BCE. During that time, a large midden was formed at the edge of the early city, now known as Tell Majnuna. Rescue excavations at Tell Majnuna revealed several clusters of commingled human remains and a cemetery on the top. Several human skeletons dated to the LC 3 and Early Bronze Age (EBA) were found also at Tell Brak itself and it was possible to investigate differences in cross-sectional femoral and tibial shaft shapes between LC 3 and EBA to test the hypothesis that rapid and extensive urbanization in the LC 3 induced increase in mobility. External midshaft and subtrochanteric measurements of at least 152 femora and measurements of 55 tibiae at the nutrient foramen were taken to investigate the differences in the level of terrestrial mobility between four LC 3 and one EBA chronological subsets. Also the correlation was examined between shaft cross-sectional shapes and frequency of linear enamel hypoplasia (LEH) in canines, as a proxy indicator of population stress. Due to post-mortem damage, sex assessment was based only on the size of measured bones. In spite of the limited quality of the gathered data, significant differences in femoral midshaft shape in males were observed between the LC 3 and EBA subsets and the average shape index scores appeared to be correlated with the LEH frequencies. No such result was obtained for females, suggesting that only males were more mobile in the LC 3 and their mobility level was associated with general population stress. In contrast, in females the average shape of subtrochanteric femoral cross-section was more variable between temporal subsets. The patterns of temporal differences in tibial cross-section at the nutrient foramen were not conclusive due to the small sample size. Obtained results suggest that males in the LC 3, the period of rapid urbanization, were more mobile than in the EBA, when the population size was considerably smaller. This mobility may have been related to need of searching for alternative resources for the overpopulated early city.

Ultrastructural evaluation of shrinkage artefacts induced by fixatives and embedding resins on osteocyte processes and pericellular space dimensions.

The integrity of the interface between the osteocyte (Ot) process and the canalicular wall was investigated in terms of change in the lateral dimensions of the Ot process in relation to the canalicular width, i.e., widening of the pericellular space. This has been interpreted as shrinkage of the Ot process relative to the canalicular wall during sample preparation stages of fixation, dehydration, and resin embedding. Sprague-Dawley rat tibial cross-sections were prepared for transmission electron microscopy (TEM). Four different fixative preparations: paraformaldehyde (PF), modified Karnovsky's (MK), glutaraldehyde (GRR) with ruthenium red (GRR), and zinc formalin (ZF); and two different embedding resins: LR Gold (LRG) and Epon812 (Epon) were evaluated. It was found that for LRG embedding, formalin-only fixatives (PF and ZF) induced lower shrinkage than GRR-containing fixatives (MK and GRR). In contrast, for Epon embedding, MK showed the highest shrinkage, while no differences were found between the remaining fixatives (PF, ZF, and GRR). All formalin-containing fixatives (MK, PF, and ZF) induced similar shrinkage in both embedding media. The most dramatic difference was for GRR fixation, which in combination with LRG embedding showed ∼ 62% more shrinkage than with Epon embedding, suggesting that the combination of GRR fixation and LRG embedding synergistically amplifies Ot shrinkage. These differences likely suggest a role of the resin in secondarily influencing the tissue structure following fixation. Further, the work confirms LRG as a poor embedding medium for bone specimens, as it causes large variations in shrinkage depending on fixation.

Effects of minodronate on cortical bone response to mechanical loading in rats

The effects of BPs on bone formation during mechanical loading are still unknown. In this study, we evaluated the effect of minodronate on the cortical bone response to mechanical loading applied using a 4-point bending device. We used six-month old female Wistar rats and randomized into five groups (N=10/group): Vehicle administration (VEH), low dose minodronate administration (MIN-L, 0.01mg/kg BW), middle dose minodronate administration (MIN-M, 0.1mg/kg BW), high-dose minodronate administration (MIN-H 1mg/kg BW), and very high-dose minodronate administration (MIN-VH, 10mg/kg BW). Minodronate or vehicle was administered orally using the feeding needle at a dosage 3 times/week for 3weeks. Loads on the right tibia at 38N for 36cycles at 2Hz were applied in vivo by 4-point bending on the same day for 3weeks. After calcein double labeling the rats were sacrificed and tibial cross sections were prepared from the region with maximal bending at the central diaphysis. Histomorphometry was performed at the entire periosteal and endocortical surface of the tibiae, dividing the periosteum into lateral and medial surfaces. The formation surface was reduced significantly in MIN-H and MIN-VH groups at the medial surface, and in MIN-VH group at the endocortical surface of the loaded tibia (p<0.01 vs. VEH). The mineral appositional rate was reduced significantly in MIN-H and MIN-VH groups at the endocortical surface of the loaded tibia (p<0.01 vs. VEH). The bone formation rate was significantly reduced in MIN-H group at the medial surface, and in MIN-H and MIN-VH groups at the endocortical surface of the loaded tibia (p<0.01 vs. VEH). However, no significant differences were observed in any parameters between the VEH group and either the MIN-L or MIN-M groups for both the loaded and non-loaded tibiae. Based on previous preventive studies in OVX rats, the optimal dose of minodronate for the treatment of osteoporosis would be 0.03mg/kg (0.21mg/kg/week). Therefore, we used 0.1mg/kg of minodronate 3 times/week (0.30mg/kg/week) that was close to 0.21mg/kg/week. In conclusion, minodronate does not reduce the cortical bone response to mechanical loading at the optimal dose for the treatment of osteoporosis in rat model.

Bone’s Structural Diversity in Adult Females Is Established before Puberty

Bone must be rigid for leverage yet light for mobility. We studied how bone modeling and remodeling fashioned differences in bone size, shape, and mass during growth to achieve these properties in adulthood. We measured the structural features of a tibial cross-section using quantitative computed tomography and markers of remodeling in 258 10- to 13-yr-old girls during 2 yr and in 108 of their mothers. Tibia total cross-sectional area and mass correlated between daughters and their mothers (r = 0.34 and 0.44, respectively, both P < 0.01). The location of a daughter's tibial total cross-sectional area, medullar area, and bone mass in the lower, middle, or upper part of the sample distribution was established before puberty and tracked during 2 yr (r = 0.84-0.94 first vs. last measurements' ranking). Tibial cross-sectional area correlated with medullar area (r = 0.69). Both areas correlated inversely with volumetric bone mineral density (r = -0.32 and -0.67, respectively; all P < 0.001), so larger cross-sections had a lower volumetric bone mineral density. The amount of bone deposited on the anterior and posterior periosteal surface during 2 yr was twice that deposited medially and laterally (P < 0.001), increasing strength more in the former than in the latter principal axis. Differences in skeletal size, shape, and mass in adulthood are likely to be largely established before puberty. We infer that bone fragility in advanced age has its structural antecedents partly established in early life.

Joint loading-driven bone formation and signaling pathways predicted from genome-wide expression profiles

Joint loading is a recently developed loading modality that induces anabolic responses by lateral loads applied to a synovial joint such as an elbow and a knee. The present study extended this loading modality to an ankle and addressed a question: does ankle loading promote bone formation in the tibia? If so, what signaling pathways are involved in the anabolic responses? Using C57BL/6 female mice as a model system, lateral loads of 0.5 N were applied to the ankle at 5 Hz for 3 min/day for 3 consecutive days and load-driven bone formation was evaluated at three tibial cross-sections (the proximal, middle, and distal diaphysis). Furthermore, total RNA was isolated for 3 pairs of microarray experiments as well as quantitative real-time PCR analyses. The histomorphometric results revealed that in all cross-sections ankle loading elevated the cortical area and thickness as well as the calcein-labeled surface. Signaling pathway analysis from microarray-derived whole-genome mRNA expression profiles and quantitative real-time PCR predicted that molecules in phosphoinositide 3-kinase (PI3K), ECM-receptor interactions, TGFβ signaling, and Wnt signaling were involved in the joint-loading driven responses. Since ankle loading stimulates bone formation throughout the tibia both in the endosteum and the periosteum, it may provide a non-pharmacological approach to effectively activate molecular signaling necessary for preventing bone loss.

Tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys ( Macaca mulatta)

The acyclic nucleoside phosphonate analog, 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA; Tenofovir; Gilead Sciences, Inc., Foster City, CA), has been shown to effectively inhibit simian immunodeficiency virus (SIV) replication in rhesus macaques by blocking reverse transcription. However, chronic long-term tenofovir treatment at 30 mg/kg/day, intended to reduce viral replication and illness, has been shown to result in bone deformities and spontaneous fractures in rhesus monkeys. Based on these findings, we studied the effects of tenofovir treatment and pathogenic SIV infection on cortical bone remodeling in rhesus monkeys. Tibiae from tenofovir-treated or untreated, SIV-infected or uninfected, rhesus macaques were evaluated for bone microdamage and remodeling. We found that tenofovir treatment had a significant effect on osteoid (unmineralized bone) seam width in tibial cross-sections. Regardless of SIV infection status, half of the tenofovir-treated animals had significantly increased osteoid seam widths in tibial cortical bone resulting in an osteomalacia-like condition. Pathogenic SIV infection significantly increased tibial resorption cavity density, and this increase was normalized by tenofovir treatment. These results suggest that tenofovir treatment at 30 mg/kg/day inhibits mineralization of newly formed bone. SIV infection results in increased tibial resorption cavity density, while tenofovir treatment tends to minimize this increase. Both defective mineralization of newly formed bone and increased resorption cavity density may result in greater bone fragility.

Effect of parathyroid hormone on cortical bone response to in vivo external loading of the rat tibia.

Cortical bone responses following administration of parathyroid hormone (PTH) were evaluated using a four-point bending device to clarify the relationship between the effect of PTH and mechanical loading. Female Wistar rats, 6-months-old, [corrected] were used. Rats were randomized into three groups (n = 10/group), namely PTH-5 (5 microgram PTH/kg body weight), PTH-30 (30 microgram PTH/kg body weight), and PTH-v (vehicle). PTH (human PTH (1-34)) was injected subcutaneously three times/week for 3 weeks. Loads on the right tibia were applied in vivo at 29.1 +/- 0.3 N for 36 cycles at 2 Hz 3 days/week for 3 weeks using four-point bending. The administration of PTH and tibial mechanical loading were performed on the same day. After calcein double labeling, rats were killed and tibial cross-sections were prepared from the region with maximal bending at the central diaphysis. Histomorphometry was performed over the entire periosteal and endocortical surfaces of the tibiae, dividing the periosteum into lateral and medial surfaces. The in vivo average peak tibial strains (predicted) on the lateral periosteal surface were 1392.4, 1421.8 and 1384.7 (mu)strain in PTH-v, PTH-5 and PTH-30 groups, respectively, showing no significant difference among the three groups. Significant loading-related increases in the bone formation surface, mineral apposition rate, and bone formation rate were observed at the periosteal and endocortical surfaces. Significant differences between PTH groups were also seen. Interaction between mechanical loading and PTH was significant at both periosteal and endocortical surfaces. It is concluded that PTH has a synergistic effect on the cortical bone response to mechanical loading.

2D calculation method based on composite beam theory for the determination of local homogenised stiffnesses of long bones

A calculation method using the finite element technique is presented. Its main objective was to determine strains, stresses and more particularly stiffnesses in any cross section of a tibia, thus enabling the localisation of tibial torsion in vivo. Each tibial cross section was considered to be a non-uniform cross section of a composite beam with arbitrary orientation of fibres. The determination of stresses, strains and stiffnesses within a composite beam cross section has been defined by solving a variational problem. The validation of this method was performed on a tibial diaphysis of which each cross section was assumed to be the cross section of a composite beam made of orthotropic materials with orthotropic axes of any orientation with respect to the principal axis of the bone. The comparison of the results, from our model and that of a three-dimensional one, was performed on each nodal value (strains, stresses) of the meshed cross section as it was impossible to obtain local stiffnesses by experimentation. The good agreement between the results has validated our finite element program. Actually, this method has enabled to treat directly 2D geometric reconstructions from CT scan images with a good accuracy to determine locally the homogenised mechanical characteristics of human tibia in vivo, and particularly to quantify torsional tibial abnormalities of children without approximation of the shape of the cross section and by calculating the real moment of inertia J. The importance of the fibre orientation with regards to the stiffness values has been emphasised. This 2D method has also allowed to reduce CPU time of the 3D modelling and calculation.

Systemic administration of rhIGF-I or rhIGF-I/IGFBP-3 increases cortical bone and lean body mass in ovariectomized rats

The purpose of this study was to compare dose-related effects on cortical bone and lean body mass following subcutaneous administration of rhIGF-I alone, or bound to an equimolar amount of rhIGFBP-3 to adult Ovx rats. At the age of 16 weeks, rats were ovariectomized or sham-operated and were allowed 8 weeks to develop osteopenia. After being divided into control (saline treated) or treatment groups, rats were injected daily during an 8-week period with 0.9 and 2.6 mg/kg of rhIGF-I, or with 0.9, 2.6, and 7.5 mg/kg of rhIGF-I bound to rhIGFBP-3. Fluorescent bone markers were given 9 and 2 days prior to necropsy. Body weights and lean body mass were monitored throughout the experiment. Cortical bone histomorphometry was performed on tibial cross-sections at the tibiofibular junction, and endochondral bone growth was measured at the distal femoral metaphysis. All rats treated with rhIGF-I or the rhIGF-I/IGFBP-3 complex had increased body weights, corresponding to a dose-dependent increase in lean body mass. Endochondral growth was slightly increased in all experimental groups, but was not dose-dependent. A dramatic increase in periosteal, modeling-dependent formation, coupled with decreased or unchanged resorption on the endocortical envelope resulted in a dose-dependent increase in cortical thickness and cross-sectional area in groups treated with the complex of rhIGF-I/IGFBP-3. This complex appeared to be more effective in promoting positive musculoskeletal changes than rhIGF-I alone.(ABSTRACT TRUNCATED AT 250 WORDS)