Changes In Bone Morphology Research Articles

Changes in Skeletal Integrity and Marrow Adiposity during High-Fat Diet and after Weight Loss.

The prevalence of obesity has continued to rise over the past three decades leading to significant increases in obesity-related medical care costs from metabolic and non-metabolic sequelae. It is now clear that expansion of body fat leads to an increase in inflammation with systemic effects on metabolism. In mouse models of diet-induced obesity, there is also an expansion of bone marrow adipocytes. However, the persistence of these changes after weight loss has not been well described. The objective of this study was to investigate the impact of high-fat diet (HFD) and subsequent weight loss on skeletal parameters in C57Bl6/J mice. Male mice were given a normal chow diet (ND) or 60% HFD at 6 weeks of age for 12, 16, or 20 weeks. A third group of mice was put on HFD for 12 weeks and then on ND for 8 weeks to mimic weight loss. After these dietary challenges, the tibia and femur were removed and analyzed by micro computed-tomography for bone morphology. Decalcification followed by osmium staining was used to assess bone marrow adiposity, and mechanical testing was performed to assess bone strength. After 12, 16, or 20 weeks of HFD, mice had significant weight gain relative to controls. Body mass returned to normal after weight loss. Marrow adipose tissue (MAT) volume in the tibia increased after 16 weeks of HFD and persisted in the 20-week HFD group. Weight loss prevented HFD-induced MAT expansion. Trabecular bone volume fraction, mineral content, and number were decreased after 12, 16, or 20 weeks of HFD, relative to ND controls, with only partial recovery after weight loss. Mechanical testing demonstrated decreased fracture resistance after 20 weeks of HFD. Loss of mechanical integrity did not recover after weight loss. Our study demonstrates that HFD causes long-term, persistent changes in bone quality, despite prevention of marrow adipose tissue accumulation, as demonstrated through changes in bone morphology and mechanical strength in a mouse model of diet-induced obesity and weight loss.

Cortical Bone Morphological and Trabecular Bone Microarchitectural Changes in the Mandible and Femoral Neck of Ovariectomized Rats.

ObjectiveThis study used microcomputed tomography (micro-CT) to evaluate the effects of ovariectomy on the trabecular bone microarchitecture and cortical bone morphology in the femoral neck and mandible of female rats.Materials and MethodsTwelve female Wister rats were divided into two groups: the control and ovariectomized groups. The rats in the ovariectomized group received ovariectomy at 8 weeks of age; all the rats were sacrificed at 20 weeks of age, and their mandibles and femurs were removed and scanned using micro-CT. Four microstructural trabecular bone parameters were measured for the region below the first mandibular molar and the femoral neck region: bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp), and trabecular number (TbN). In addition, four cortical bone parameters were measured for the femoral neck region: total cross-sectional area (TtAr), cortical area (CtAr), cortical bone area fraction (CtAr/TtAr), and cortical thickness (CtTh). The CtTh at the masseteric ridge was used to assess the cortical bone morphology in the mandible. The trabecular bone microarchitecture and cortical bone morphology in the femoral necks and mandibles of the control group were compared with those of the ovariectomized group. Furthermore, Spearman’s correlation (rs) was conducted to analyze the correlation between the osteoporosis conditions of the mandible and femoral neck.ResultsRegarding the trabecular bone microarchitectural parameters, the BV/TV of the trabecular bone microarchitecture in the femoral necks of the control group (61.199±11.288%, median ± interquartile range) was significantly greater than that of the ovariectomized group (40.329±5.153%). Similarly, the BV/TV of the trabecular bone microarchitecture in the mandibles of the control group (51.704±6.253%) was significantly greater than that of the ovariectomized group (38.486±9.111%). Furthermore, the TbSp of the femoral necks in the ovariectomized group (0.185±0.066 mm) was significantly greater than that in the control group (0.130±0.026mm). Similarly, the TbSp of the mandibles in the ovariectomized group (0.322±0.047mm) was significantly greater than that in the control group (0.285±0.041mm). However, the TbTh and TbN trends for the mandibles and femoral necks were inconsistent between the control and ovariectomized groups. Regarding the cortical bone morphology parameters, the TtAr of the femoral necks in the ovariectomized group was significantly smaller than that in the control group. There was no significant difference in the TtAr, CtAr, or CtTh of the femoral necks between the control and ovariectomized groups, and no significant difference in the CtTh of the mandibles between the control and ovariectomized groups. Moreover, the BV/TV and TbSp of the mandibles were highly correlated with those of the femurs (rs = 0.874 and rs = 0.755 for BV/TV and TbSp, respectively). Nevertheless, the TbTh, TbN, and CtTh of the mandibles were not correlated with those of the femoral necks.ConclusionAfter the rats were ovariectomized, osteoporosis of the trabecular bone microarchitecture occurred in their femurs and mandibles; however, ovariectomy did not influence the cortical bone morphology. In addition, the parametric values of the trabecular bone microarchitecture in the femoral necks were highly correlated with those of the trabecular bone microarchitecture in the mandibles.

Fam3c modulates osteogenic cell differentiation and affects bone volume and cortical bone mineral density.

Fam3c, a cytokine-like growth factor, has been suggested to have a role in epithelial-to-mesenchymal transition (EMT), tumor growth and metastasis. A single-nucleotide polymorphism affecting bone mineral density has been found in the first intron of the Fam3c gene in a study analyzing an Asian population cohort. Other independent studies on different population cohorts have found the fam3c locus to be associated with bone mineral density and fractures. In order to investigate the role of Fam3c in bone biology, we have generated a Fam3c knock-out (KO) mouse strain. The Fam3c KO mice were found to have normal appearance, behavior and fertility, but small changes in bone morphology and content were also observed. Micro-CT analysis of tibiae of the female mice revealed decreased number of trabeculae. In male mice the changes in the bone phenotype were smaller, but hematological changes were observed. Furthermore, there was a negative correlation between body weight and tibial trabecular and cortical bone volume in the male KO mice. There was a small increase in cortical bone mineral density, but in the lateral direction of tibiae the breaking strength was reduced. Fam3c KO bone marrow cells showed accelerated osteogenic differentiation and mineralization in vitro. The reduced number of bone trabeculae in Fam3c KO mice and the stimulated osteogenic differentiation indicate a role for Fam3c in osteoblast differentiation and bone homeostasis.

Correlation Between Stress Distributions and Biological Reactions in Bone Surrounding Implants That Support Cantilevers in Supraocclusal Contact in Rats.

To investigate the relationship between stress distributions and peri-implant bone reactions around maxillary implants that support cantilevers in supraocclusal contact. After molar extraction, 16 Wistar rats received a titanium implant unilaterally. After healing, 8 rats (control group) were killed and the others received implant-supported cantilever superstructures in supraocclusion (loaded group). After 5 days, they were killed. The maxillae of all rats were scanned by microcomputed tomography (μ-CT). Based on the μ-CT images, bone volumes were measured. For the loaded group, 3D finite element models were created and analyzed under 20-N vertical and 5-N lateral forces, successively. After μ-CT scanning, sections were prepared and observed histologically. When compared with the controls, the bone volume tended to decrease in the loaded group, but the difference was not statistically significant. On average, marginal bone resorption and stresses tended to be higher in 2 rats that occluded on the cantilever arm than in the others, which occluded right on the implant, nevertheless, calculated stress did not surpass the maximum elastic stress (yielding strength) of rat bone. However, at the implant-bone interface of these samples, partial bone resorption surrounded by signs of active resorption was histologically found. These findings suggest that in this occlusally loaded rat model, the stress distributions correlated to some extent with bone volume and morphological changes observed on μ-CT images and histological sections.

Chronic effects of stroke on hip bone density and tibial morphology: a longitudinal study.

The study aimed to quantify the long-term effects of stroke on tibial bone morphology and hip bone density. Only the trabecular bone mineral density and bone strength index in the hemiparetic tibial distal epiphysis showed a significant decline among individuals who had sustained a stroke 12-24months ago. This study aims to determine the changes in bone density and morphology in lower limb long bones during a 1-year follow-up period and their relationship to muscle function in chronic stroke patients. Twenty-eight chronic stroke patients (12-166months after the acute stroke event at initial assessment) and 27 controls underwent bilateral scanning of the hip and tibia using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively. Each subject was re-assessed 1year after the initial assessment. Twenty stroke cases and 23 controls completed all assessments. At the end of the follow-up, the paretic tibial distal epiphysis suffered significant decline in trabecular bone density (-1.8 ± 0.6%, p = 0.006) and bone strength index (-2.7 ± 0.6%, p < 0.001). More severe decline in the former was associated with poorer leg muscle strength (ρ = 0.447, p = 0.048) and motor recovery (ρ = 0.489, p = 0.029) measured at initial assessment. The loss in trabecular bone density remained significant among those whose stroke onset was 12-24months ago (p < 0.001), but not among those whose stroke onset was beyond 24months ago (p > 0.05) at the time of initial assessment. The changes of outcomes in the tibial diaphysis, except for cortical bone mineral content on the non-paretic side (-1.3 ± 0.3%, p = 0.003), and hip bone density were well within the margin of error for precision. There is evidence of continuous trabecular bone loss in the paretic tibial distal epiphysis among chronic stroke patients, but it tends to plateau after 2years of stroke onset. The steady state may have been reached earlier in the hip and tibial diaphysis.

Consequences of chromsome18q deletions.

Providing clinically relevant prognoses and treatment information for people with a chromsome18q deletion is particularly challenging because every unrelated person has a unique region of hemizygosity. The hemizygous region can involve almost any region of 18q including between 1 and 101 genes (30 Mb of DNA). Most individuals have terminal deletions, but in our cohort of over 350 individuals 23% have interstitial deletions. Because of this heterogeneity, we take a gene by gene approach to understanding the clinical consequences. There are 196 genes on 18q. We classified 133 of them as dosage insensitive, 15 (8%) as dosage sensitive leading to haploinsufficiency while another 10 (5%) have effects that are conditionally haploinsufficient and are dependent on another factor, genetic or environmental in order to cause an abnormal phenotype. Thirty-seven genes (19%) have insufficient information to classify their dosage effect. Phenotypes attributed to single genes include: congenital heart disease, minor bone morphology changes, central nervous system dysmyelination, expressive speech delay, vesicouretreral reflux, polyposis, Pitt-Hopkins syndrome, intellectual disability, executive function impairment, male infertility, aural atresia, and high frequency sensorineural hearing loss. Additionally, identified critical regions for other phenotypes include: adolescent idiopathic scoliosis and pectus excavatum, Virchow-Robin perivascular spaces, small corpus callosum, strabismus, atopic disorders, mood disorder, IgA deficiency, nystagmus, congenital heart disease, kidney malformation, vertical talus, CNS dysmyelination growth hormone deficiency and cleft palate. Together these findings make it increasingly feasible to compile an individualized syndrome description based on each person's individuated genotype. Future work will focus on understanding molecular mechanisms leading to treatment.

Activity intensity, assistive devices and joint replacement influence predicted remodelling in the proximal femur

Bone morphology and density changes are commonly observed following joint replacement, may contribute to the risks of implant loosening and periprosthetic fracture and reduce the available bone stock for revision surgery. This study was presented in the 'Bone and Cartilage Mechanobiology across the scales' WCCM symposium to review the development of remodelling prediction methods and to demonstrate simulation of adaptive bone remodelling around hip replacement femoral components, incorporating intrinsic (prosthesis) and extrinsic (activity and loading) factors. An iterative bone remodelling process was applied to finite element models of a femur implanted with a cementless total hip replacement (THR) and a hip resurfacing implant. Previously developed for a cemented THR implant, this modified process enabled the influence of pre- to post-operative changes in patient activity and joint loading to be evaluated. A control algorithm used identical pre- and post-operative conditions, and the predicted extents and temporal trends of remodelling were measured by generating virtual X-rays and DXA scans. The modified process improved qualitative and quantitative remodelling predictions for both the cementless THR and resurfacing implants, but demonstrated the sensitivity to DXA scan region definition and appropriate implant-bone position and sizing. Predicted remodelling in the intact femur in response to changed activity and loading demonstrated that in this simplified model, although the influence of the extrinsic effects were important, the mechanics of implantation were dominant. This study supports the application of predictive bone remodelling as one element in the range of physical and computational studies, which should be conducted in the preclinical evaluation of new prostheses.

Effects of Single versus Hypofractionated Focused Radiation Therapy on Vertebral Structure and Biomechanical Integrity

Introduction Stereotactic radiosurgery has shown great promise in the treatment of metastatic lesions within the spine. However, recent clinical studies have indicated that the procedure may increase the risk of developing vertebral compression fractions, particularly in osteoporotic patients (Rose et al, 2009. J Clinical Onc. 27(29):5075; Boehling et al, 2012. J Neurosurg Spine. 16:379). There is thus a critical need for research examining the effects of focused radiation on bone quality and mechanical properties. We have developed a rabbit model which enables the analysis of the effects of focused radiation on vertebral osteonecrosis, structure, and biomechanical integrity. Using this model, we are testing the hypothesis that fractionation of radiation dosing can reduce radiation osteonecrosis and preserve structural and biomechanical integrity of the spine. Material and Methods The L5 vertebral body of New Zealand White (NZW) rabbits was treated, under computerized tomography (CT) guidance, with either a single 24 Gy dose of radiation or three fractionated doses over 3 consecutive days of 8 Gy radiation via the small animal radiation research platform (SARRP) (Wong et al, 2008. Int J Radiat Oncol Biol Phys. 71(5): 1591). Effects of radiation treatment on L2, L4, L5, and L6 vertebral osteonecrosis, structure, and biomechanical integrity were evaluated 6 months postirradiation via high-resolution CT imaging (Skyscan, Bruker, Belgium), histology, and nondestructive biomechanical compression testing and were compared with nonirradiated controls. Vertebral bone volume over total volume (BV/TV), trabecular thickness (Tb.Th.), and trabecular spacing (TB.Sp) were evaluated from CT images via CTAn software (Bruker, Belgium). Result/Conclusion: Results till date suggest that a localized single dose of 24 Gy radiation leads to loss of vertebral bone volume and trabecular number and a subsequent increase in trabecular spacing. Similarly, hypofractionation of the radiation dose (3 × 8 Gy) leads to reduced trabecular number and increased trabecular spacing, yet preserves normalized bone volume. Whether these changes in bone morphology translate into reduced mechanical integrity is currently under analysis. Future work will utilize this model to evaluate the efficacy of various therapies, such as teriparatide (PTH [1–34]), in the prevention of radiation-induced osteonecrosis.

Architectural and biochemical adaptations in skeletal muscle and bone following rotator cuff injury in a rat model.

Injury to the rotator cuff can cause irreversible changes to the structure and function of the associated muscles and bones. The temporal progression and pathomechanisms associated with these adaptations are unclear. The purpose of this study was to investigate the time course of structural muscle and osseous changes in a rat model of a massive rotator cuff tear. Supraspinatus and infraspinatus muscle architecture and biochemistry and humeral and scapular morphological parameters were measured three days, eight weeks, and sixteen weeks after dual tenotomy with and without chemical paralysis via botulinum toxin A (BTX). Muscle mass and physiological cross-sectional area increased over time in the age-matched control animals, decreased over time in the tenotomy+BTX group, and remained nearly the same in the tenotomy-alone group. Tenotomy+BTX led to increased extracellular collagen in the muscle. Changes in scapular bone morphology were observed in both experimental groups, consistent with reductions in load transmission across the joint. These data suggest that tenotomy alone interferes with normal age-related muscle growth. The addition of chemical paralysis yielded profound structural changes to the muscle and bone, potentially leading to impaired muscle function, increased muscle stiffness, and decreased bone strength. Structural musculoskeletal changes occur after tendon injury, and these changes are severely exacerbated with the addition of neuromuscular compromise.

Bone morphological analyses in Spontaneously Diabetic Torii (SDT) fatty rats.

The Spontaneously Diabetic Torii (SDT) fatty rat, a model for obese type 2 diabetes, shows bone quantitative abnormalities, namely low bone mineral density (BMD). The objective of this study was to evaluate bone morphological changes, in particular identifying the bone qualitative abnormalities, in the SDT fatty rat. Male SDT fatty rats showed increases in total trabecular area and trabecular number and decreases in trabecular thickness in cancellous bones of the proximal tibia, indicating trabecular miniaturization. The SDT fatty rat is useful for investigation of pathophysiological changes in bone quality in diabetic osteoporosis.

Trabecular bone recovers from mechanical unloading primarily by restoring its mechanical function rather than its morphology

Upon returning to normal ambulatory activities, the recovery of trabecular bone lost during unloading is limited. Here, using a mouse population that displayed a large range of skeletal susceptibility to unloading and reambulation, we tested the impact of changes in trabecular bone morphology during unloading and reambulation on its simulated mechanical properties. Female adult mice from a double cross of BALB/cByJ and C3H/HeJ strains (n=352) underwent 3wk of hindlimb unloading followed by 3wk of reambulation. Normally ambulating mice served as controls (n=30). As quantified longitudinally by in vivo μCT, unloading led to an average loss of 43% of trabecular bone volume fraction (BV/TV) in the distal femur. Finite element models of the μCT tomographies showed that deterioration of the trabecular structure raised trabecular peak Von-Mises (PVM) stresses on average by 27%, indicating a significant increase in the risk of mechanical failure compared to baseline. Further, skewness of the Von-Mises stress distributions (SVM) increased by 104% with unloading, indicating that the trabecular structure became inefficient in resisting the applied load. During reambulation, bone of experimental mice recovered on average only 10% of its lost BV/TV. Even though the addition of trabecular tissue was small during reambulation, PVM and SVM as indicators of risk of mechanical failure decreased by 56% and 57%, respectively. Large individual differences in the response of trabecular bone, together with a large sample size, facilitated stratification of experimental mice based on the level of recovery. As a fraction of all mice, 66% of the population showed some degree of recovery in BV/TV while in 89% and 87% of all mice, PVM and SVM decreased during reambulation, respectively. At the end of the reambulation phase, only 8% of the population recovered half of the unloading induced losses in BV/TV while 50% and 49% of the population recovered half of the unloading induced deterioration in PVM and SVM, respectively. The association between morphological and mechanical variables was strong at baseline but progressively decreased during the unloading and reambulation cycles. The preferential recovery of trabecular micromechanical properties over bone volume fraction emphasizes that mechanical demand during reambulation does not, at least initially, seek to restore bone's morphology but its mechanical integrity.

Bone morphology changes around two types of bone‐level implants installed in fresh extraction sockets – a histomorphometric study in Beagle dogs

Minimizing crestal bone loss following immediate implant placement is considered the most challenging aspect in implant therapy. Implant surface topography and chemical modifications have been shown to influence the success of Osseointegration. The Straumann Bone Level implant, featuring SLActive surface, has been introduced with the aim of enhancing bone apposition. Similarly, the OsseoSpeed implants from Astra Tech claim to have an enhanced osseointegration. Because of the specific features in the implant design, both companies claim that crestal resorption is minimal with these implants. To evaluate the osseointegration and crestal bone level following immediate placement of Straumann Bone Level implant and OsseoSpeed implants in fresh extraction sockets in Beagle dogs. The distal roots of the second, third and fourth premolars were extracted in both sides of the mandible. The distal roots were removed using a dental elevator. A total of 60 fixtures were installed in 10 Beagle dogs. Two types of implants were used: Straumann Bone-Level implants, which were 8 × 3.3 mm in size, and Astra Tech OsseoSpeed 3.5 S MicroThread implants, which were 8 × 3.5 mm in size. The histomorphometrical evaluation was performed at the end of 4- and 12-week healing. The implant-bone contact and bone volume percentage were assessed. The bone-to-implant contact (BIC) and the bone volume did not show any significant changes for both types of implants. The OsseoSpeed™ implants showed 67.4% and 65.3% BIC, respectively, at 4 and 12 weeks compared with 71.7 and 73.1 for the Straumann Bone-Level implants. The bone volume around both types of implants did not differ significantly at both time periods. The crestal bone resorption was observed for both types of implants. The first BIC at buccal side and lingual side of the implants also did not differ significantly for both implant systems. This study showed that Straumann Bone Level and OsseoSpeed implants induced similar bone response after immediate implantation at 4 and 12 weeks. The immediate implant placement resulted in peri-implant crestal bone-level changes for both types of implants.

Patient care services: What pharmacists do

Patient care services: What pharmacists do

APhA honors outstanding achievements at Annual Meeting

Each year, APhA recognizes exceptional contributors to the profession at the Annual Meeting. The following award winners will be honored at APhA2014 in Orlando.

Change of mechanical vertebrae properties due to progressive osteoporosis: combined biomechanical and finite-element analysis within a rat model

For assessing mechanical properties of osteoporotic bone, biomechanical testing combined with in silico modeling plays a key role. The present study focuses on microscopic mechanical bone properties in a rat model of postmenopausal osteoporosis. Female Sprague-Dawley rats were (1) euthanized without prior interventions, (2) sham-operated, and (3) subjected to ovariectomy combined with a multi-deficiencies diet. Rat vertebrae (corpora vertebrae) were imaged by micro-CT, their stiffness was determined by compression tests, and load-induced stress states as well as property changes due to the treatment were analyzed by finite-element modeling. By comparing vertebra stiffness measurements with finite-element calculations of stiffness, an overall microscopic Young's modulus of the bone was determined. Macroscopic vertebra stiffness as well as the microscopic modulus diminish with progression of osteoporosis by about 70%. After strong initial changes of bone morphology, further decrease in macroscopic stiffness is largely due to decreasing microscopic Young's modulus. The micromechanical stress calculations reveal particularly loaded vertebra regions prone to failure. Osteoporosis-induced changes of the microscopic Young's modulus alter the fracture behavior of bone, may influence bone remodeling, and should be considered in the design of implant materials.

Induction of bone loss in DBA/1J mice immunized with citrullinated autologous mouse type II collagen in the absence of adjuvant

Joint damage in rheumatoid arthritis (RA) is characterized by cartilage and bone loss resulting in pain, deformity, and loss of joint function. Anti-citrullinated protein antibody (ACPA) has been implicated in RA pathogenesis and predicts radiographical joint damage and clinical severity. Therefore, the purpose of this study was to assess bone loss by micro-CT, histological joint damage, and ACPA levels using a mouse model of RA. Arthritis was induced by immunizing DBA/1 mice with autologous citrullinated type II mouse collagen (CIT-CII) weekly for 4 weeks. Mice immunized with autologous CII served as controls. At week 5, mice were killed, ACPA levels determined, and micro-CT performed to quantitatively analyze bone damage. Micro-CT analysis revealed significant loss of bone density, volume, and surface (p < 0.05) in bone peripheral to the inflamed joints of CIT-CII animals compared to CII controls. Histological staining demonstrated cartilage, proteoglycan, joint collagen, and bone collagen loss in the CIT-CII group compared to CII. Serum ACPA levels were increased (p = 0.03) in the CIT-CII group compared to CII, and these levels were inversely correlated with bone quantity and quality. In this study, we demonstrate that immunization with autologous CIT-CII initiates significant systemic bone and articular cartilage loss in the absence of adjuvant. Significant inverse correlations of circulating ACPA and bone quality/quantity were present. ACPA levels predict the adverse bone morphological changes in this model of early RA.

Evaluation of the morphological changes in the mandible for dentate and totally edentate elderly population using cone-beam computed tomography

The loss of teeth considerably modifies the mandibular shape. The aim of this study was to compare the morphological changes in the mandible for dentate and totally edentate elderly subjects using cone-beam computed tomography. In total, 50 cone-beam computed tomography patients (25 dentate, 25 edentate) without any maxilla-mandibular dysmorphosis were analyzed retrospectively. Panoramic representations of the mandible with superimposed axial slices and cross-sectional slices were developed with the cone-beam computed tomography scans. Values of the mandibular cortical index, bone quality index, gonial angle, antegonial angle, antegonial depth and condyle angle in the left and right side were measured. There was a significant difference in the mandibular cortical index between the total edentate group and the dentate group in the left side of the mandible (p<0.001). There was a significant difference in the bone quality index between the total edentate group and the dentate group in the right side and the left side (p<0.001). There was a significant difference in the bone quality index between the right side and the left side (p<0.005). When comparing gender, there was only a difference in the right side (p<0.05). Our study concluded that the mandibular basal bone morphology changes as a consequence of tooth loss. Cone-beam computed tomography is shown to be a good tool in investigating and achieving these results.

Protein Antigens Increase the Protective Efficacy of a Capsule-Based Vaccine against Staphylococcus aureus in a Rat Model of Osteomyelitis

Staphylococcus aureus is an invasive bacterial pathogen, and antibiotic resistance has impeded adequate control of infections caused by this microbe. Moreover, efforts to prevent human infections with single-component S. aureus vaccines have failed. In this study, we evaluated the protective efficacy in rats of vaccines containing both S. aureus capsular polysaccharides (CPs) and proteins. The serotypes 5 CP (CP5) and 8 CP (CP8) were conjugated to tetanus toxoid and administered to rats alone or together with domain A of clumping factor A (ClfA) or genetically detoxified alpha-toxin (dHla). The vaccines were delivered according to a preventive or a therapeutic regimen, and their protective efficacy was evaluated in a rat model of osteomyelitis. Addition of dHla (but not ClfA) to the CP5 or CP8 vaccine induced reductions in bacterial load and bone morphological changes compared with immunization with either conjugate vaccine alone. Both the prophylactic and therapeutic regimens were protective. Immunization with dHla together with a pneumococcal conjugate vaccine used as a control did not reduce staphylococcal osteomyelitis. The emergence of unencapsulated or small-colony variants during infection was negligible and similar for all of the vaccine groups. In conclusion, addition of dHla to a CP5 or CP8 conjugate vaccine enhanced its efficacy against S. aureus osteomyelitis, indicating that the inclusion of multiple antigens will likely enhance the efficacy of vaccines against both chronic and acute forms of staphylococcal disease.

Previous exposure to simulated microgravity does not exacerbate bone loss during subsequent exposure in the proximal tibia of adult rats

Extended periods of inactivity cause severe bone loss and concomitant deterioration of the musculoskeletal system. Considerable research has been aimed at better understanding the mechanisms and consequences of bone loss due to unloading and the associated effects on strength and fracture risk. One factor that has not been studied extensively but is of great interest, particularly for human spaceflight, is how multiple or repeated exposures to unloading and reloading affect the skeleton. Space agencies worldwide anticipate increased usage of repeat-flier crewmembers, and major thrust of research has focused on better understanding of microgravity effects on loss of bone density at weightbearing skeletal sites; however there is limited data available on repeat microgravity exposure. The adult hindlimb unloaded (HU) rat model was used to determine how an initial unloading cycle will affect a subsequent exposure to disuse and recovery thereafter. Animals underwent 28days of HU starting at 6months of age followed by 56days of recovery, and then another 28days of HU with 56days of recovery. In vivo longitudinal pQCT was used to quantify bone morphological changes, and ex vivo μCT was used to quantify trabecular microarchitecture and cortical shell geometry at the proximal tibia metaphysis (PTM). The mechanical properties of trabecular bone were examined by the reduced platen compression mechanical test. The hypothesis that the initial HU exposure will mitigate decrements in bone mass and density for the second HU exposure was supported as pre- to post-HU declines in total BMC, total vBMD, and cortical area by in vivo pQCT at the proximal tibia metaphysis were milder for the second HU (and not significant) compared to an age-matched single HU (3% vs. 6%, 2% vs. 6%, and 2% vs. 6%, respectively). In contrast, the hypothesis was not supported at the microarchitectural level as losses in BV/TV and Tb.Th. were similar during 2nd HU exposure and age-matched single HU. Recovery with respect to post-HU values and compared to aging controls for total BMC, vBMD and cortical area were slower in older animals exposed to single or double HU cycles compared to recovery of younger animals exposed to a single HU bout. Despite milder recovery at the older age, there was no difference between unloaded animals and controls at the end of second recovery period. Therefore, the data did not support the hypothesis that two cycles of HU exposure with recovery would have a net negative effect. Mechanical properties of trabecular bone were affected more severely than densitometric measures (35% loss in trabecular bone ultimate stress vs. 9% loss in trabecular vBMD), which can be attributed most prominently to reductions in trabecular bone density and tissue mineral density. Together, our data demonstrate that initial exposure to mechanical unloading does not exacerbate bone loss during a subsequent unloading period and two cycles of unloading followed by recovery do not have a cumulative net negative effect on total bone mineral content and density as measured by pQCT at the proximal tibia metaphysis.

Microradiography and microcomputed tomography comparative analysis in human bone cores harvested after maxillary sinus augmentation: a pilot study

The aim of this study was to compare microradiography (MR) and microcomputed tomography (μCT) analysis of bone samples following maxillary sinus augmentation at different time periods and determine the relationships between measured area and volume fractions. Lateral window sinus grafts were performed on 10 patients using a mineralized human bone allograft (MHBA). At implant placement, 5-13 months after surgery, 10 bone core biopsies were harvested. Prior to histologic sectioning, bone samples were evaluated with μCT. The morphometric parameters computed by MR and μCT were compared using Pearson's correlation and Bland and Altman analysis and included hard tissue fraction (HV/TV:%), soft tissue fraction (SV/TV:%), vital bone fraction (BV/TV:%) and residual graft fraction (GV/TV:%). Strong positive correlation between MR and μCT was found for HV/TV and SV/TV and BV/TV [r = 0.84, 0.84 and 0.69, respectively] but weak for GV/TV [r = 0.10]. μCT technology shows promising potential as an indicator of bone morphology changes; however, caution should be used in interpreting morphometric parameters, as the different methods reveal important biases.