Cortical Bone Integrity Research Articles

Intramedullary Cylindrical Grafting for Nonunions of the Proximal Fifth Metatarsal

Fractures affecting the proximal fifth metatarsal constitute 25% of all metatarsal fractures, being particularly prevalent in sports due to stress-related incidents. Recognizing fracture patterns and implementing precise management are pivotal to mitigate potential complications, given the proclivity for suboptimal bone healing, and high incidence of nonunions (up to 4% in zone 2/3 fractures). Various methods for graft collection and application have been outlined, ranging from inlay grafts to the straightforward application of bone grafts at the nonunion site. However, the use of inlay grafts may pose challenges in size accuracy and donor site morbidity. We present and describe a novel grafting technique, which we describe as intramedullary bone grafting, exposing its capacity to promote bone healing by filling the medullary canal with cancellous bone. Developed for the treatment of delayed unions or nonunions in zone 2 and 3 fractures of the proximal fifth metatarsal, this innovative technique amalgamates the advantages of both inlay grafting and cancellous grafting. Employing a compacted cylindrical graft, tailored to match the reamed canal’s dimensions, replaces the entire medulla, facilitating the bone healing process. The technique establishes an intramedullary bone bridge across the nonunion site without compromising cortical bone integrity, extending significantly above and below the site. This presents a possible alternative to conventional methods. Furthermore, we illustrate a case involving a professional athlete with a Torg-3 fracture nonunion in zone 3, who underwent this grafting technique alongside anatomic plate fixation. Following a 4-month follow-up, a CT scan revealed complete bone healing, yielding a painless and functionally restored foot. This success enabled the athlete to resume regular practice. Level of Evidence: Level IV.

Risk factors for cement leakage after percutaneous vertebral augmentation for osteoporotic vertebral compression fractures: a meta-analysis.

Osteoporotic vertebral compression fractures (OVCF) may necessitate percutaneous vertebral augmentation (PVA), a procedure not without its risks. One notable complication is cement leakage (CL), which can cause significant distress in patients. Despite its clinical importance, there remains a paucity of meta-analyses investigating these complications and their management in the existing literature. We systematically reviewed PubMed, Cochrane Library, Embase, and Web of Science databases up to February 2024 to identify studies examining CL following PVA treatment in OVCF. We assessed the quality of eligible cohort studies using the Newcastle-Ottawa Scale (NOS), extracted data on incidence, identified risk factors for CL, and conducting meta-analysis with Revman 5.2 software. We calculated odd ratios (OR) and Mean Differences (MD) with 95% confidence interval (CI) applying random effects models. We identified twelve cohort studies that matched our strict inclusion criteria. These studies included a total of 2388 patients and 3392 vertebrae. CL was identified in 1132 vertebrae. Notable risk factors for CL included compromised cortical bone integrity (OR 5.00, 95% CI 3.01~8.29, P<0.00001), presence of intravertebral vacuum clefts (OR 1.68, 95% CI 1.07~2.65, P=0.03), basivertebral foramen sign (OR 1.77, 95% CI 1.09~2.89, P=0.02), and volume of cement used (MD 0.75, 95% CI 0.41~1.10, P<0.0001). Our findings underscore the significance of cortical bone integrity, intravertebral vacuum cleft, basivertebral foramen sign, and cement volume as principal determinants of CL risk in PVA for OVCF. These insights advocate for tailored surgical strategies to mitigate the risk of CL in this patient population.

Radiological Aspects of Temporo-Mandibular Joint Osteoarthritis

This article is about applications of computed tomography (CT) in diagnosis of inflammatory and degenerative disease of temporomandibular joint (TMJ). CT is highly informative method forvisualization of disease of temporomandibular joint. Finally, sections on other aspects of CT research related to the TMJ, clinical decision-making and concluding remarks are added. However, it should be emphasized that the diagnostic information obtained is limited to the morphology of the osseous joint components, cortical bone integrity and subcortical bonedestruction/production. Author of this research studied the frequency of radiological signs in different age group. In addition, there were studied frequency of isolated, combination types, and more and less localization sitesof radiological patterns of inflammatory and degenerative changes of temporo-mandibular joint

RF18 | PSAT162 Male Runners Have Impaired Tibial Cortical Bone Integrity and Strength Compared to Non-athletes

Abstract Female athletes with low energy availability are at risk for impaired bone microarchitecture and strength associated with hypogonadism. Data are lacking for bone outcomes in male athletes. We studied 31 men 16-30 years (n=15 runners with mean (±SD) mileage 43±4 miles/week, n=16 non-athlete controls). We assessed distal tibia and radius volumetric BMD (vBMD) and microarchitecture by high resolution peripheral quantitative CT (HRpQCT), estimated bone strength by microfinite element analysis and body composition by DXA. Testosterone, estradiol (by LC-MS) and leptin (by electrochemiluminescence) were measured. Groups did not differ for mean age (24.5±3.6y), BMI (22.2±2.6 kg/m2), lean mass, or testosterone or estradiol levels. Mean tibial cortical vBMD was lower and porosity higher in athletes than controls (p&amp;lt;0.01). In contrast, mean tibial trabecular vBMD and number were higher, and separation lower, in athletes (p&amp;lt;0.02). Athletes with BMI ≤ 21 kg/m2 had lower tibial failure load (bone strength estimate) than those with BMI &amp;gt;21 kg/m2 (p=0.007). Lean mass (R=0.85, p&amp;lt;0.0001), serum leptin (R=0.59, p=0.046) and estradiol (R=0.66, p=0.007), but not testosterone, were associated with tibial failure load in athletes. Athlete and control groups did not differ for HRpQCT variables at the radius. Despite weight-bearing activity, male runners have impaired tibial cortical BMD and microarchitecture, which may increase their risk for bone stress injuries. Lower leptin (reflecting lower fat mass) and estradiol (converted from testosterone in adipose tissue), as well as lean mass, are determinants of lower tibial strength in these athletes, suggesting that low energy availability is a risk factor for impaired bone strength in male runners. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m.

Further Imaging for Suspected Isolated Greater Trochanteric Fractures: Multiplanar Reformation Computed Tomography or Magnetic Resonance Imaging.

BackgroundMost isolated greater trochanter (IGT) fractures are treated conservatively. However, some require surgical fixation although indications for surgery have not yet been established. Many surgeons perform surgical fixation when the intertrochanteric extension crosses the midline on magnetic resonance (MR) images. Nevertheless, for mechanical strength, cortical bone integrity is more important than that of intramedullary cancellous trabeculae. We retrospectively evaluated the clinical usefulness of multiplanar reformation computed tomography (MPR CT) in determining treatment strategies for IGT fractures.MethodsWe evaluated 99 cases of suspected IGT fractures between October 2004 and December 2019. They were 66 women and 33 men with a mean age of 77 years. The mean follow-up period was 34 months. Most patients were evaluated with plain radiographs, followed by additional imaging study via MPR CT in 65 cases, magnetic resonance imaging (MRI) in 5 cases, and both in 17 cases. Typically, fractures were fixed surgically when a cortical breakage was detected in the intertrochanteric area on MPR CT, while fractures without evidence of cortical breakage on MPR CT were treated conservatively.ResultsIn 13 out of 82 cases evaluated by MPR CT, incomplete cortical breakage in the intertrochanteric area was detected, of which 10 were treated surgically. The remaining 3 cases were treated conservatively due to patient’s refusal, poor medical condition, and failure to detect breakage. Of 69 cases without cortical breakage, 61 cases were successfully treated conservatively. Among the 17 cases evaluated by both MPR CT and MRI, cortical breakage was detected in 3, of which the intertrochanteric extension crossed the midline on the MR image only in 1 case. Of the remaining 14 cases without breakage, the intertrochanteric extension crossed the midline in 5. Among these 5 cases, 3 were treated conservatively.ConclusionsThe results suggest that MPR CT is a useful imaging modality for further evaluation of IGT fractures. It was especially valuable in evaluating cortical bone integrity, which may be more critical for fracture stability.

Hormonal contraceptive use, bone density and biochemical markers of bone metabolism in British Army recruits

IntroductionHormonal contraceptive use might impair bone health and increase the risk of stress fracture by decreasing endogenous oestrogen production, a central regulator of bone metabolism. This cross-sectional study investigated bone...

Oral Estradiol Impact on Mitigating Unloading-Induced Bone Loss in Ovary-Intact Rats.

BACKGROUND: The impact of the spaceflight environment on endogenous estrogen production in female crewmembers and the resulting impact on other adaptations, like bone loss, is an under-investigated topic. Hence, we investigated the interaction of exogenous 17- estradiol (E2) treatment and disuse to test the hypothesis that E2 treatment would mitigate disuse-induced bone loss.METHODS: There were 40 virgin female Sprague-Dawley rats (5 mo old) randomized to placebo (PL; 0 ppm E2) or estrogen (E2; 10 ppm E2) treatments, delivered via custom-made rodent diets; half of each group was randomized to either weightbearing (WB) or hindlimb unloading (HU) for 39 d.RESULTS: We observed expected lower values after HU (615%) in volumetric BMD and cross-sectional areas at the proximal tibia metaphysis (PTM, by pQCT), 20% lower %BV/TV (nonsignificant) at the PTM, and 11% lower femoral neck maximal load; none of these HU-induced impacts were modified by E2. Impaired PTM periosteal expansion was observed in all E2-treated rats, with smaller (13 to 18%) cross-sectional areas. Midshaft tibial geometry was unaffected by E2 treatment, but large reductions (73 to 81%) in periosteal bone formation indices were observed in E2-treated rats.DISCUSSION: In summary, modest supplementation of exogenous E2 did not mitigate decrements in volumetric BMD, PTM cross-sectional geometry, or femoral neck strength observed with HU. However, numerous independent impacts of E2 treatment were observed, with significant suppression of periosteal bone formation indices. If maintained over time, this might impact negatively on cortical bone integrity during prolonged nonweightbearing.Mantri AV, Allaway HCM, Brezicha JE, Hogan HA, Bloomfield SA. Oral estradiol impact on mitigating unloading-induced bone loss in ovary-intact rats. Aerosp Med Hum Perform. 2021; 92(2):6574.

Connexin43 Gap Junctions and the Control of Skeletal Remodeling

Osteoblasts, osteoprogenitors, and osteocytes share and amplify signals through connexin43‐containing gap junctions, coordinating their function in response to local and systemic cues. Thus, connexin43 helps orchestrate bone formation and remodeling to maintain cortical bone integrity. Loss or defects in connexin43 lead to alterations in cortical bone quality and skeletal dysplasia. Using in vitro and in vivo models, our data show how connexin43 regulates the differentiation and activity of osteoblasts and development of skeletal elements through the control of signaling pathways that converge on Runx2, a transcriptional regulator of the osteoblast lineage. In addition, our data show how connexin43 can regulate signal transduction cascades by recruiting signaling complexes to the connexin43 C‐terminus, and how loss of this function can recapitulate many of the skeletal phenotypes caused by loss of connexin43 protein in bone. Work with chimeric connexins composed of connexin43 and connexin45, two connexins with opposing biological functions in bone, underscores that both the connexin channel (e.g., pore function) and connexin C‐terminal tail (e.g., signal complexing docking function) act in concert to regulate downstream signaling. Finally, our preliminary data shows that communication of the second messenger, cAMP, through connexin43 gap junctions spatially coordinates bone formation by linking cell populations across surprisingly large distances.Support or Funding InformationThis work was supported by a grant, R01‐AR063631 (JPS), from the National Institutes of Health/National Institute for Arthritis, Musculoskeletal and Skin Diseases.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Assessment of Temporomandibular Joint Diseases in Patients with Rheumatoid Arthritis by Panoramic Radiography and Magnetic Resonance Imaging

1. Abstract 1.1.Objective: To assess the temporomandibular joint in patients with rheumatoid arthritis by both panoramic radiography and MRI. 1.2.Study design: Panoramic radiograph and MRI imaging were performed to forty joints of twenty patients from both sexes and varying ages, complaining of signs and/or symptoms of TMJ involvement. Diagnoses of Rheumatoid Arthritis were according to 1987 ACR criteria for RA. All images were analyzed and scored. 1.3.Results:Comparison between panorama and MRI revealed that there was statistically significant difference regard condyles position in panorama and condylar osseous changes in MRI, temporal cortical bone integrity in panorama and osseous condylar changes in MRIs and finally joints space narrowing in panorama and disc position, disc morphology, and joint effusion in MRIs. While, there was no statistically significant difference regard condyles morphology in panorama and osseous condylar changes in MRIs, and finally joint space narrowing in panorama and revealed retrodiscal band hyper intense signal detected in MR images. Conclusion:There is a significant relation between TMJ involvement and RA disease called TMD-RA. Early diagnosis and management of RA presents an important opportunity to alter the course of this progressive disease. MRI has a great role in detection of early involvement of TMJ in RA patients. This study recommends investigating TMJ in all diagnosed RA patients by MRI as a routine diagnostic tool due to its marvelous benefits.

Effect of stabilization splint therapy on glenoid fossa remodeling in temporomandibular joint osteoarthritis

PurposeThe aim of this study was to evaluate, by CBCT superimposition, bone changes (cortical bone intactness, sclerosis and subchondral cyst) in the glenoid fossa related to stabilization splint (SS) therapy for temporomandibular joint osteoarthritis (TMJ OA) patients and to compare the effects for two groups, one that had undergone SS therapy and the other that had not. MethodsThis case–control study included 36 TMJ OA patients, 10 that had undergone SS therapy (the SS group) compared with 26 that had not (the non-SS group). Osseous changes in the glenoid fossa were evaluated based on superimposed CBCT images before and after treatment. ResultsImprovements ranging from 57.5 to 100% were achieved in cortical bone integrity, sclerosis, and subchondral cyst for both groups, SS and non-SS. However, there were no statistically significant difference between the two groups (p>0.05). The non-SS group showed a significant decrease in the distances from the point of inflexion and the lowest point of the articular eminence to the reference line (p<0.05). On the other hand, the SS group showed an increase for the point of inflexion. The other measures showed no statistically significant differences in distance before treatment and after treatment, even though the average distance after treatment showed an overall increasing tendency. ConclusionSS therapy relieved excessive loading on the TMJ in the TMD OA patients, who showed, via CBCT superimposition, less bone resorption in the glenoid fossa.

Delayed Methicillin-Resistant Staphylococcus aureus Infection on a Mandibular Angle Fracture with Absorbable Plates.

Delayed Methicillin-Resistant Staphylococcus aureus Infection on a Mandibular Angle Fracture with Absorbable Plates.

Temporomandibular joint diagnostics using CBCT.

The present review will give an update on temporomandibular joint (TMJ) imaging using CBCT. It will focus on diagnostic accuracy and the value of CBCT compared with other imaging modalities for the evaluation of TMJs in different categories of patients; osteoarthritis (OA), juvenile OA, rheumatoid arthritis and related joint diseases, juvenile idiopathic arthritis and other intra-articular conditions. Finally, sections on other aspects of CBCT research related to the TMJ, clinical decision-making and concluding remarks are added. CBCT has emerged as a cost- and dose-effective imaging modality for the diagnostic assessment of a variety of TMJ conditions. The imaging modality has been found to be superior to conventional radiographical examinations as well as MRI in assessment of the TMJ. However, it should be emphasized that the diagnostic information obtained is limited to the morphology of the osseous joint components, cortical bone integrity and subcortical bone destruction/production. For evaluation of soft-tissue abnormalities, MRI is mandatory. There is an obvious need for research on the impact of CBCT examinations on patient outcome.

Identifying dental panoramic radiograph features for the screening of low bone mass in postmenopausal women

A retrospective cohort study was performed to evaluate the use of panoramic radiographs as a screening tool for low bone mass in postmenopausal women. Female subjects aged ≥50 years were included. The predictor variables were gonial angle, antegonial angle, mandibular cortical bone integrity, periodontal disease status, and number of remaining teeth. The primary outcome variable was bone mineral density status. Descriptive and logistic regression statistics were computed; P<0.05 was considered significant. The sample was composed of 273 subjects, aged 50–89 years. Visual assessment of mandibular cortical bone integrity demonstrated a statistically significant correlation with low bone mass diagnosis on univariate logistic regression (P=0.019), but lost significance on multivariate analysis with age, body mass index, and number of remaining teeth (P=0.6). A visual estimation of the mandibular cortical bone integrity from panoramic radiographs may be useful for identifying postmenopausal women at high risk for osteoporosis.

Increased resistance during jump exercise does not enhance cortical bone formation.

This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses. Sprague-Dawley rats (male, 6 months old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 wk. Load in the HRE group was progressively increased from 80 g added to a weighted vest (50 repetitions) to 410 g (16 repetitions). The LRE rats completed the same protocol as the HRE group (same number of repetitions), with only a 30-g vest applied. Low- and high-load jump RE resulted in 6%-11% higher cortical bone mineral content and cortical bone area compared with controls, as determined by in vivo peripheral quantitative computed tomography measurements. In the femur, however, only LRE demonstrated improvements in cortical volumetric bone mineral density (+11%) and cross-sectional moment of inertia (+20%) versus the CC group. The three-point bending to failure revealed a marked increase in tibial maximum force (25%-29%), stiffness (19%-22%), and energy to maximum force (35%-55%) and a reduction in elastic modulus (-11% to 14%) in both LRE and HRE compared with controls. Dynamic histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and HRE resulted in 20%-30% higher periosteal mineralizing surface versus the CC group. Mineral apposition rate and bone formation rate were significantly greater in animals in the LRE group (27%, 39%) than those in the HRE group. These data demonstrate that jump training with minimal loading is equally, and sometimes more, effective at augmenting cortical bone integrity compared with overload training in skeletally mature rats.

OP178: Progression of oral cancer from early to late stage after invasive dental treatments

Patients with oral cavity squamous cell carcinoma (OSCC) often present initially to a dentist complaining of a dental problem. These early cancerous changes are at times misdiagnosed as chronic infection resulting in invasive and often multiple dental procedures. This not only delays diagnosis and treatment, but also affects the integrity of cortical bone and promotes mandibular invasion, resulting in accelerated progression of the disease. A retrospective review of OSCC patients, presenting after multiple dental treatments, was performed. The clinical findings, imaging, treatment and pathology were reviewed. There were a total of 15 patients (nine females). The median duration of symptoms before their initial dental visit was 21 months (range: 6 months to 15 years). The presenting complaints included chronic oral lesions, ulcerations, swelling or jaw pain. Dental treatment, in the form of dental extractions, periodontal surgery or scaling and root planning without tissue biopsy, was the first treatment rendered on all of these patients. Nine patients (60%) were diagnosed with an OSCC within 6 months of the dental procedure, two were diagnosed within 1 year and the others over one year following the procedure. The primary tumors were located on the gingiva, floor of mouth or retromolar trigone. Eleven patients (73%) had bone involvement, eight patients (53%) had nodal metastases and five patients (33%) had perineural invasion at the time of diagnosis. Disrupting the mandibular periosteum in the proximity of an otherwise T1 lesion could facilitate bone invasion and thus accelerate the progression of OSCC to T4 tumor. If oral cancer is suspected, a biopsy should be performed prior to dental procedures such as extraction or periodontal surgery is initiated. This could expedite diagnosis, prevent treatment delays and potentially improve therapeutic outcome.

Fadiga óssea: causa de dor em joelhos na osteoartrite

A dor no joelho é o sintoma mais comum na osteoartrite, sendo a principal causa de incapacidade crônica em idosos e uma das principais fontes de morbidade atribuível à osteoartrite em geral. As causas de dor no joelho em pessoas com osteoartrite não são facilmente entendidas e o conhecimento sobre as causas da dor é fundamental para que futuramente sejam realizadas intervenções específicas. A fadiga óssea representa o remodelamento do osso subcondral na osteoartrite, levando a uma consequente alteração na forma do osso e/ou perda óssea. No entanto, a fadiga óssea não é algo facilmente interpretado, pois é de difícil detecção na ausência de defeitos claros da cortical e pela sobreposição de estruturas ósseas nas radiografias convencionais. A fadiga óssea está associada não apenas a dor no joelho, mas também a rigidez e incapacidade. Se a fadiga ocorre antes da osteoartrite avançada, isso sugere que alterações no osso subcondral podem ocorrer simultaneamente a alterações da cartilagem e que tratamentos visando sua preservação podem não ser eficazes. Lesões com padrão de edema ósseo estão associadas e são fatores preditivos para fadiga óssea. Este trabalho tem por objetivo rever a literatura mostrando a importância da fadiga óssea e de como diagnosticar esta alteração nos exames de imagem.

Is peak bone mass achieved following recovery from reduced energy availability?

We previously demonstrated focal bone loss and disrupted metabolic hormone levels in sedentary (SED) and exercising (EX) rats after 12 wks of reduced energy availability (EA; energy intake minus exercise energy expenditure). We hypothesized that peak bone mass (total bone mineral content, totBMC) at 12 mo of age would be diminished by 12 wks reduced EA, even after 12 wks of recovery (REC). After acclimation to AIN‐93M purified diet, 5‐ mo‐old female rats (n=72) were randomized into SED and EX groups; half of each group was designated −25% EA. During REC, all rats were fed ad lib and exercise volume was halved. After 12 wks REC, fat mass was 30% lower in −25EA SED vs. ADLIB SED; however, there were no differences in lean mass. After 4 wks REC, totBMC (by DXA) in −25EA SED was 15% lower vs. ADLIB SED; after 12 wks REC it matched ADLIB SED values. TotBMC for −25EA EX was higher than −25EA SED rats at all time points. Serum IGF‐1 and leptin, reduced after 12 wks of − 25EA, rebounded quickly with regain of fat mass, except for lower leptin in −25EA SED. After 12 wks REC, mineralizing surface on mid‐shaft tibia (by histomorphometry) was low only in ADLIB EX. These data suggest that cortical bone integrity and metabolic hormones recover from stringent reductions in EA when energy balance is re‐established in both SED and EX conditions. Whether the same recovery potential exists for cancellous bone compartments after reduced EA has yet to be determined.Grant Funding Source : Department of Defense #WSIXWH‐06‐1‐0479

Finite Element Analysis of 2 Immediate Loading Systems in Edentulous Mandible: Rigid and Semirigid Splinting of Implants

The objective of this study was to evaluate the stress on the cortical bone around single body dental implants supporting mandibular complete fixed denture with rigid (Neopronto System-Neodent) or semirigid splinting system (Barra Distal System-Neodent). Stress levels on several system components were analyzed through finite element analysis. Focusing on stress concentration at cortical bone around single body dental implants supporting mandibular complete fixed dentures with rigid (Neopronto System-Neodent) or semirigid splinting system (Barra Distal System-Neodent), after axial and oblique occlusal loading simulation, applied in the last cantilever element. The results showed that semirigid implant splinting generated lower von Mises stress in the cortical bone under axial loading. Rigid implant splinting generated higher von Mises stress in the cortical bone under oblique loading. It was concluded that the use of a semirigid system for rehabilitation of edentulous mandibles by means of immediate implant-supported fixed complete denture is recommended, because it reduces stress concentration in the cortical bone. As a consequence, bone level is better preserved, and implant survival is improved. Nevertheless, for both situations the cortical bone integrity was protected, because the maximum stress level findings were lower than those pointed in the literature as being harmful. The maximum stress limit for cortical bone (167 MPa) represents the threshold between plastic and elastic state for a given material. Because any force is applied to an object, and there is no deformation, we can conclude that the elastic threshold was not surpassed, keeping its structural integrity. If the force is higher than the plastic threshold, the object will suffer permanent deformation. In cortical bone, this represents the beginning of bone resorption and/or remodeling processes, which, according to our simulated loading, would not occur.

Early detection and quantification of murine melanoma bone metastases with magnetic resonance imaging

Bone metastases occur in approximately 80% of patients with advanced cancer and cause significant morbidity. There are currently no established means by which to identify the early growth of micro-metastatic cells or their effects on bone at a time when curative therapy might be initiated. We postulated that high-resolution magnetic resonance imaging (MRI) could detect and quantify the growth and destructive effects of bone micrometastases. Using a mouse model for metastasis of malignant melanoma, we have examined the ability of MRI to quantify cortical bone destruction and the percentage of the medullary cavity occupied by tumour, trabecular bone, and marrow. The results from MRI were compared to histomorphometry (the reference standard) and to radiographs. In vivo gradient-echo and spin-echo MRI demonstrated that metastatic melanoma replaced the marrow space but that the cortical bone integrity was preserved (P < or = 0.001). The smallest detectable micrometastasis had an area of 0.323 mm(2). In contrast, we observed no trends after quantifying the radiograph data. These approaches delineated the limits of MRI in its ability to quantify tumour burden and the effect on bone in this model. Given the increasing use of MRI as a non-invasive clinical diagnostic method, the present findings may be applicable in detecting bone metastases in the clinical setting at an early and potentially treatable stage.

Quantitative trait loci that modulate femoral mechanical properties in a genetically heterogeneous mouse population.

The goal of this study was to investigate genetic effects on mechanical properties of the mouse femur. We found evidence for QTL on eight chromosomes that affect mechanical traits. Some of these QTL may have primary effects on body weight or femoral geometry, and others seem to affect bone quality directly. Previous studies have shown a dependence of fragility-related fracture risk on genetic background. Although many of these studies investigated the effect of genetics on BMD, basic measures of bone geometry and mechanical integrity may provide a more comprehensive characterization of the genetic effects on bone fragility. The purpose of this study was to identify quantitative trait loci (QTL) that affect mechanical and material properties of cortical bone in a genetically heterogeneous mouse population. A total of 486 female UM-HET3 mice was used for this study. UM-HET3 mice are produced as the offspring of (BALB/cJ x C57BL/6J) F(1) females and (C3H/HeJ x DBA/2J) F(1) males. Femurs from 18-month-old mice were tested to failure in four-point bending to assess mechanical properties of cortical bone; these properties were compared with genotype data from 185 biallelic loci. A permutation-based test was used to detect significant associations between genetic markers and mechanical traits. This test generates p values that account for the effect of testing multiple hypotheses. Throughout the experiment, p < or = 0.05 was considered statistically significant. Analysis of covariance was used to examine possible effects of body weight and femoral geometry. We found evidence for genes on maternal chromosomes 11 and 13 and paternal chromosomes 2, 4, 7, 10, 11, and 17 that affect mechanical and material properties of femoral bone. The total variance explained by genetic effects on each mechanical trait ranges from 2.9% to 15.4%. Most of the identified polymorphisms influence mechanical traits even after adjustment for body weight. Adjustment for femoral geometry reduces the effects of some of the QTL, but those on chromosomes 2 and 10 do not seem to be influenced by femoral geometry. Many genes and chromosomes are involved in the genetic control over mechanical integrity of cortical bone. QTL on paternal chromosomes 4 and 11 may mediate mechanical properties, at least in part, by modulation of femoral geometry. Other QTL identified here may directly affect bone tissue quality.