Reduction In Bone Volume Fraction Research Articles

The effect of vitamin E incorporated into injectable platelet-rich fibrin on orthodontic tooth movement in rabbits.

To evaluate the effects of injectable platelet fibrin (iPRF) and combined vitamin E-iPRF on orthodontic tooth movement (OTM) rates in rabbits, 35 male New Zealand white rabbits were involved in this study using splitmouth design. OTM was carried out on the mandibular first premolar using 100g nickel titanium closing coil. Right side served as study group, isolated iPRF in one group and combined vitamin E-iPRF in other group was injected buccally and lingually (iPRF group, Vit E-iPRF group), and left side acted as positive control group (CG) by injecting normal saline (positive CG). The rate of OTM was measured using intra-oral scanner on days 7,14 and 21. Histological and Micro CT scan were examined on days 0, 7, 14 and 21. The iPRF and combined Vitamin E-iPRF demonstrated significant greater rate of OTM on days 7 and 14 in comparison to control group, only significant differences between iPRF and combined vitamin E-iPRF were seen on day 14. In all time intervals as compared to the CG, the number of osteoclasts was significantly higher in the isolated iPRF and combined vitamin E-iPRF groups. Significant reduction in bone volume fraction (BV/TV) was demonstrated in iPRF and combined vitamin E-iPRF groups in all time points, however, non-significant differences were found in trabecular thickness (Tb.Th) and trabecullar separation (Tb.Sp). Local injection of iPRF and combined vitamin E-iPRF showed temporary increase in the rate of OTM.

Hypobaric hypoxia deteriorates bone mass and strength in mice.

Mountaineers at high altitude are at increased risk of acute mountain sickness as well as high altitude pulmonary and cerebral edema. A densitometric study in mountaineers has suggested that expeditions at high altitude decrease bone mineral density. Surprisingly, the in vivo skeletal effects of hypobaric hypoxia are largely unknown, and have not been studied using advanced contemporary methods to assess bone microstructure. Eighty-four 22-week-old female mice were divided into seven groups with 12 mice in each group: 1. Baseline; 2. Normobaric, 4weeks; 3. Hypobaric hypoxia, 4weeks; 4. Normobaric, 8weeks; 5. Hypobaric hypoxia, 8weeks; 6. Normobaric, 12weeks; and 7. Hypobaric hypoxia, 12weeks. Hypobaric hypoxia mice were housed in hypobaric chambers at an ambient pressure of 500mbar (5500m altitude), while normobaric mice were housed at sea level atmospheric pressure for 4, 8, or 12weeks, respectively. Hypobaric hypoxia had a profound impact on femoral cortical bone and L4 trabecular bone, while the effect on femoral trabecular bone was less pronounced. Hypobaric hypoxia reduced the bone strength of the femoral mid-diaphysis and L4 at all time-points. At femoral cortical bone, hypobaric hypoxia reduced bone formation through fewer mineralizing surfaces and lower bone formation rate after 2weeks. In addition, bone strength decreased, and C-terminal telopeptide of type I collagen (CTX-I) increased independently of the duration of exposure to simulated high altitude. At L4, hypobaric hypoxia resulted in a substantial reduction in bone volume fraction, trabecular thickness, and trabecular number after 4weeks of exposure. Hypobaric hypoxia reduced bone strength and femoral bone mass, while femoral trabecular bone was much less affected, indicating the skeletal response to hypobaric hypoxia differ between cortical and trabecular bone. These findings provide initial preclinical support for future clinical studies in mountaineers to assess bone status and bone strength after exposure to prolonged high altitude exposure.

Reduction in Remote Site Bone Volume after Orthopedic Implant Surgery is Greater in Appendicular than Axial Skeleton

PurposeThe purpose of this study was to investigate trabecular bone volume at remote sites after orthopedic implant surgery and to determine if particle challenge to induce peri‐implant osteolysis, a major cause of aseptic implant failure, was contributory.MethodsIn this IACUC‐approved study that followed FASEB guidelines, male Sprague‐Dawley rats (398 ± 11.5 g; n=8–9/group) were randomly allocated to 5 groups. In 4 groups, bilateral titanium femoral implants were placed in the medullary space by drilling through the intercondylar groove (n=33). These rats received weekly intra‐articular injections containing vehicle as a control or particle solutions (clean‐ or lipopolysaccharide‐doped‐polyethylene or cobalt chromium) to stimulate peri‐implant osteolysis. A 5th group remained intact (no implant surgery, no intra‐articular injections, n=8). Rats were weighed at the commencement and at the 6 week conclusion of the study. Trabecular bone of the proximal humerus and L2 vertebral body was assessed by micro‐computed tomography. Data were analyzed by one‐way analysis of variance (ANOVA) for between‐group effects with Bonferroni corrected post‐hoc comparisons.ResultsTrabecular bone volume fraction in the proximal humerus was reduced by ~30% in each implant group compared to the intact group (ANOVA p<0.001, p≤0.002 for post‐hoc comparisons of each implant group to the intact group). There were no differences among the 4 implant groups. Although the L2 trabecular bone volume fraction varied among the 5 groups (ANOVA p=0.013), the post‐hoc comparisons showed only marginal reductions for cobalt chromium‐challenged rats compared to both intact (~20% reduction; p=0.054) and clean‐polyethylene‐challenged rats (~15% reduction; p=0.055). Weight was not different between groups at the start of the study (ANOVA p=0.809); however, at 6 weeks after surgery there was a significant group effect (ANOVA p <0.001) with the cobalt chromium‐challenged animals having gained ~25 or 35 g less weight than the vehicle‐control (p=0.013) and intact (p<0.001) rats, respectively.DiscussionPreviously, we showed that remote bone remodeling did not differ between vehicle and particle challenged rats that had received an implant, but in that study there was no intact control group [Ross RD et al., J Orthop Res, 2014]. In the present study in which an intact control group was included, we now show that there was a reduction in bone volume fraction at two remote sites following orthopedic implant surgery. Consistent with our previous study, bone volume fraction of the proximal humerus was reduced in all groups that underwent implant surgery, but there was no particle challenge effect. There was only marginal evidence that implant placement or particle challenge affected axial bone volume. These results suggest that surgical placement of an orthopedic implant may lead to a systemic increase in bone remodeling that more strongly affects the appendicular than the axial skeleton, but that the additional particle challenge was not contributory.Support or Funding InformationNIH R01AR066562

Bone Marrow Adipose Tissue Deficiency Increases Disuse-Induced Bone Loss in Male Mice

Bone marrow adipose tissue (MAT) is negatively associated with bone mass. Since osteoblasts and adipocytes are derived from the same precursor cells, adipocyte differentiation may occur at the expense of osteoblast differentiation. We used MAT-deficient KitW/W−v (MAT-) mice to determine if absence of MAT reduced bone loss in hindlimb-unloaded (HU) mice. Male MAT- and wild-type (WT) mice were randomly assigned to a baseline, control or HU group (n = 10 mice/group) within each genotype and HU groups unloaded for 2 weeks. Femurs were evaluated using micro-computed tomography, histomorphometry and targeted gene profiling. MAT- mice had a greater reduction in bone volume fraction after HU than did WT mice. HU MAT- mice had elevated cancellous bone formation and resorption compared to other treatment groups as well as a unique profile of differentially expressed genes. Adoptive transfer of WT bone marrow-derived hematopoietic stem cells reconstituted c-kit but not MAT in KitW/W−v mice. The MAT- WT → KitW/W−v mice lost cancellous bone following 2 weeks of HU. In summary, results from this study suggest that MAT deficiency was not protective, and was associated with exaggerated disuse-induced cancellous bone loss.

Identification and Characterization of a Synthetic Osteogenic Peptide.

Osteoporosis is the most common metabolic bone disorder and its management represents a tremendous public health encumbrance. While several classes of therapeutics have been approved to treat this disease, all are associated with significant adverse effects. An algorithm was developed and utilized to discover potential bioactive peptides, which led to the identification of an osteogenic peptide that mapped to the C-terminal region of the calcitonin receptor and has been named calcitonin receptor fragment peptide (CRFP). In vitro treatment of human mesenchymal stem cells with CRFP resulted in dose-specific effects on both proliferation and osteoblastic differentiation. Similarly, in vitro treatment of rat RCJ3.1C5.18 cells led to dose- and species-specific effects on proliferation. A rat ovariectomy (OVX) model was used to assess the potential efficacy of CRFP in treating osteoporosis. MicroCT analysis of distal femoral samples showed that OVX rats treated with CRFP were significantly protected from losses of 55 % in trabecular bone volume fraction (BVF), 42 % in connectivity density, and 18 % in trabecular thickness in comparison to vehicle-treated controls. MicroCT analyses of vertebrae revealed CRFP to significantly prevent a 25 % reduction in BVF. MicroCT evaluation of femoral and vertebral cortical bone found a significant reduction of 2 % in vertebral bone mineral density. In summary, our in vitro studies indicate that CRFP is both bioactive and osteogenic and our in vivo studies indicate that CRFP is skeletally bioactive. These promising data indicate that further in vitro and in vivo evaluation of CRFP as a new treatment for osteoporosis is warranted.

Mechanical consequence of trabecular bone loss and its treatment: a three-dimensional model simulation

Age-related changes in the microstructure of trabecular bone, such as decreases in trabecular number and trabecular thickness, lead to reductions in mechanical properties, such as Young’s modulus and strength. Current drug therapy, such as bisphosphonate or parathyroid hormone, improves the mechanical properties of bone mainly by increasing the trabecular thickness, but not increasing the trabecular number. However, the mechanical efficacy of these treatments has not been fully quantified using trabecular bone models. In this study, we used an idealized three-dimensional (3D) microstructural model of trabecular bone to create bone loss either through trabeculae thinning or random removal of trabeculae, and simulated treatment by increasing the trabeculae thickness of the remaining trabeculae. The reduction in either the Young’s modulus or the strength due to trabeculae loss was proportional to a much higher power of reduction in bone volume fraction than due to trabeculae thinning. This indicates that bone loss due to trabeculae loss is much more detrimental to Young’s modulus and strength of trabecular bone than due to trabeculae thinning, indicating the importance of trabecular number and connectivity in the mechanical integrity of trabecular bone. In general, treatments by increasing the trabecular thickness of remaining trabeculae after trabeculae loss cannot fully recover the initial mechanical properties of intact bone, even if bone loss is fully recovered, whereas trabecular thickening can fully restore the mechanical properties after bone loss by trabeculae thinning. The results also show that the residual loss in mechanical properties is dependent on the extent of trabeculae loss.