Bone Sites Research Articles

Bone phenotypes in multiple endocrine neoplasia type 1: survey on the MEN1 Florentine database.

Multiple endocrine neoplasia type 1 (MEN1) is a rare, inherited cancer syndrome characterized by the development of multiple endocrine and non-endocrine tumors. MEN1 patients show a reduction of bone mass and a higher prevalence of early onset osteoporosis, compared to healthy population of the same age, gender, and ethnicity. During the monitoring and follow-up of MEN1 patients, the attention of clinicians is primarily focused on the diagnosis and therapy of tumors, while the assessment of bone health and mineral metabolism is, in many cases, marginally considered. In this study, we retrospectively analyzed bone and mineral metabolism features in a series of MEN1 patients from the MEN1 Florentine database. Biochemical markers of bone and mineral metabolism and densitometric parameters of bone mass were retrieved from the database and were analyzed based on age ranges and genders of patients and presence/absence of the three main MEN1-related endocrine tumor types. Our evaluation confirmed that patients with a MEN1 diagnosis have a high prevalence of earlyonset osteopenia and osteoporosis, in association with levels of serum and urinary markers of bone turnover higher than the normal reference values, regardless of their different MEN1 tumors. Fifty percent of patients younger than 26 years manifested osteopenia and 8.3% had osteoporosis, in at least one of the measured bone sites. These data suggest the importance of including biochemical and instrumental monitoring of bone metabolism and bone mass in the routine medical evaluation and follow-up of MEN1 patients and MEN1 carriers as important clinical aspects in the management of the syndrome.

Forearm Fractures in Overweight-Obese Children and Adolescents: A Matter of Bone Density, Bone Geometry or Body Composition?

Forearm fractures in children and adolescents are associated with increased body mass index (BMI). This bone site is non-weight-bearing and therefore is appropriate to explore the effect of BMI on bone mineral density (BMD) and bone geometry, avoiding the confounding effect of increased weight-associated mechanical loading. The aim of this review was to summarize available evidence on bone indices and body composition assessed by peripheral quantitative computed tomography (pQCT) or dual X-ray absorptiometry (DXA) at the forearm level in overweight (Ow) or obese (Ob) subjects. We conducted a review of the literature according to the PICOS model. A total of 46 studies were identified following the literature search. A final number of 12 studies were included in this review. pQCT studies evidenced that Ow and Ob children typically have normal or increased volumetric BMD (vBMD), total bone area and cortical area, with normal or reduced cortical thickness at the forearm. Outcomes from DXA evaluations are less conclusive. In almost all the studies fat mass and lean mass area at the forearm are increased. A higher fat-to-lean mass ratio has been observed in few studies. Bone strength was reported as normal or increased compared to normal weight peers. In Ow or Ob children-adolescents, vBMD, bone size and bone strength are not reduced compared to normal weight peers. The local higher fat-to-lean mass ratio may give a mismatch between bone strength and the load experienced by the distal forearm during a fall, resulting in increased risk of forearm fractures.

Evaluation of the Proximal Tibia as a Donor Site of Cancellous Bone for Intraoral Grafting Procedures-A Retrospective Study.

Background: Autogenous bone grafts remain the “gold standard” in maxillofacial reconstructive procedures. The objective of this study was to evaluate the proximal tibia as a donor site of cancellous bone for bone grafting procedures of the mandible on the basis of intraoperative parameters and clinical observations. Methods: The study was based on a medical record search of 40 patients who underwent surgical procedures because of benign pathological lesions of the jaws resulting in 3-wall bone defects of the mandible and qualified for surgical removal of the lesion with simultaneous bone grafting of the defect with autogenous cancellous bone harvested from the proximal tibia. Results: The use of the proximal tibia for bone grafting procedures enables large amounts of cancellous bone (15.09 cc in average) to be obtained. The procedure is characterized by a low risk of early and late complications, which include excessive bleeding, wound infection, lengthy healing time, scars, a loss of sensation around the scars, aching, a dip in bone, swelling and tenderness. Conclusions: The ability to obtain large amounts of cancellous bone and a low risk of intra- and postoperative complications make the proximal tibia an attractive donor site for the bone grafting procedures in maxillofacial surgery.

Implants in GBR-Augmented Sites in Patients Treated for Generalized Aggressive Periodontitis: A 10- to 20-Year Prospective Case Series.

The aim of this case series was to evaluate implants inserted in bone after guided bone regeneration (GBR). Fourteen patients with generalized aggressive periodontitis (GAP) who had lost one or two maxillary teeth in the incisor or premolar region were enrolled in the study. Due to bone resorption, the lateral width and vertical height of the bone were insufficient for implant placement. GBR was carried out in a staged approach using titanium-reinforced e-PTFE (expanded polytetrafluoroethylene) membranes. No bone grafts or bone substitute materials were used. After 6 to 8 months, turned-surface implants (n = 47) were inserted in augmented and nonaugmented bone sites and prosthetically treated with single crowns. All patients were examined during a 3- to 6-month recall schedule over a 10- to 20-year period, and clinical and radiographic examinations were performed. GBR yielded mean vertical and lateral bone gains of 4.5 and 7.0 mm, respectively. The implant survival rate was 100%, mucositis was present in 28.8% of sites, and peri-implantitis was not found. The annual bone loss at tooth sites was significantly higher than at implant sites in augmented bone (0.5% vs 0.2%, respectively; P = .000), and the adjacent teeth had significantly higher annual bone loss (0.8%; P = .000). Thus, severely periodontally compromised patients can be managed successfully in the long-term with the described clinical protocol.

Primary Diffuse Large B Cell Lymphoma of Bone: A Single-Center Experience.

BackgroundPrimary diffuse large B-cell lymphoma of the bone (PB-DLBCL) is a rare type of extra-nodal lymphoma. This study aimed to examine the clinical characteristics, outcomes, treatment modalities and risk of central nervous system relapse (CNSR) among adult Jordanian patients with PB-DLBCL.MethodsThis retrospective study included patients aged >16 years who were diagnosed with PB-DLBCL and treated at our hospital between 2002 and 2021. Clinical characteristics, treatment modalities, outcomes and CNSR events were extracted from the hospital’s data system and analysed. Patients were categorised into unifocal (UF) and multifocal (MF) PB-DLBCL groups according to the number of bone sites involved. The involvement of only one site was defined as UF, whereas the involvement of two or more sites was defined as MF.ResultsIn total, 12 patients were diagnosed with PB-DLBCL. Their median age was 47.5 years (range, 17–80 years). The male:female ratio was 1:1. There were eight patients in the UF PB-DLBCL group and four in the MF PB-DLBCL group. All patients received treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. In the UF PB-DLBCL group, the male:female ratio was 5:3, the median age was 41 years, and the follow-up duration was 9–135 (mean, 83.3) months. In the MF PB-DLBCL group, the male:female ratio was 1:3, the median age was 51.5 years, and the survival time was 3–11 (mean, 7) months. Three patients with vertebral UF PB-DLBCL underwent early vertebroplasty without complications. The most common site involved was the vertebral column. Most patients with UF PB-DLBCL achieved complete remission (CR), whereas no patients with MF PB-DLBCL achieved CR.ConclusionPB-DLBCL is rare in adult Jordanian patients. UF PB-DLBCL is more common than MF PB-DLBCL. Patients with UF PB-DLBCL had a good prognosis. Patients with MF PB-DLBCL had a high international prognostic index score, risk of CNSR and short survival time.

A Composite Deferoxamine/Black Phosphorus Nanosheet/Gelatin Hydrogel Scaffold for Ischemic Tibial Bone Repair.

IntroductionBone delay union is mostly caused by lack of blood supply. Although autografts, allografts and artificial bone have been widely used to treat bone delay union, the bone regeneration fails in the ischemic site accompanied by the bone donor site complications and disease transmission. Recently, there is a growing recognition of the importance of hydrogel scaffolds which are regarded as an eligible engineer tissue for bone repair. However, hydrogel is still limited in improving neovascularization.MethodsIn this work, black phosphorus nanosheet and deferoxamine (BPN-DFO) were loaded in the gelatin hydrogel to overcome the high risk of bone delay union and systemically investigated the regeneration capability of BPN-DFO hydrogel in vitro and vivo.ResultsThe resulting BPN-DFO hydrogel scaffold showed superior swollen, degradation and release rate, as well as satisfied biocompatibility. BPN-DFO hydrogel shown the significant up-expression of mRNA related to bone regeneration and cell proliferation. In vivo, the proposed BPN-DFO hydrogel significantly improved osteogenesis and neovascularization in the ischemic tibial bone site of SD rats with acute femoral artery occlusion. Both macroscopic and histological evaluation of new regenerated bone showed newly formed blood vessel and collagen using BPN-DFO hydrogel. The immunohistochemistry and RT-PCR revealed that the bone regeneration could be improved via BMP/Runx2 pathway.ConclusionThe BPN-DFO hydrogel possesses potential tissue engineer material for ischemic bone defect treatment. However, furthermore studies are needed to testify the safety and efficacy of BPN-DFO hydrogel.

Between-Subject and Within-Subject Variaton of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest.

To improve quantification of individual responses to bed rest interventions, we analyzed peripheral quantitative computer tomography (pQCT) datasets of the lower leg of 76 participants, who took part in eight different bed rest studies. A newly developed statistical approach differentiated measurement uncertainty UMeas from between-subject-variation (BSV) and within-subject variation (WSV). The results showed that UMeas decreased 59.3% to 80% over the two decades of bed rest studies (p < 0.01), and that it was higher for muscles than for bones. The reduction of UMeas could be explained by improved measurement procedures as well as a higher standardization. The vast majority (82.6%) of the individual responses pci exceeded the 95% confidence interval defined by UMeas, indicating significant and substantial BSV, which was greater for bones than for muscles, especially at the epiphyseal measurement sites. Non-significant to small positive inter-site correlations between bone sites, but very large positive inter-site correlation between muscle sites suggests that substantial WSV exists in the tibia bone, but much less so in the calf musculature. Furthermore, endocortical circumference, an indicator of the individual’s bone geometry could partly explain WSV and BSV. These results demonstrate the existence of substantial BSV bone, and that it is partly driven by WSV, and likely also by physical activity and dietary habits prior to bed rest. In addition, genetic and epigenetic variation could potentially explain BSV, but not WSV. As to the latter, differences of bone characteristics and the bone resorption process could offer an explanation for its existence. The study has also demonstrated the importance of duplicate baseline measurements. Finally, we provide here a rationale for worst case scenarios with partly effective countermeasures in long-term space missions.

Commensal oral microbiota induces osteoimmunomodulatory effects separate from systemic microbiome in mice.

Commensal microbes critically regulate skeletal homeostasis, yet the impact of specific microbiota communities on osteoimmune response mechanisms is unknown. To discern osteoimmunomodulatory effects imparted by the commensal oral microbiota that are distinct from the systemic microbiota, osteoimmunology studies were performed in both alveolar bone and nonoral skeletal sites of specific pathogen–free (SPF) versus germ-free (GF) mice and SPF mice subjected to saline versus chlorhexidine oral rinses. SPF versus GF mice had reduced cortical/trabecular bone and an enhanced pro-osteoclastic phenotype in alveolar bone. TLR signaling and Th17 cells that have known pro-osteoclastic actions were increased in alveolar BM, but not long BM, of SPF versus GF mice. MHC II antigen presentation genes and activated DCs and CD4+ T cells were elevated in alveolar BM, but not long BM, of SPF versus GF mice. These findings were substantiated by in vitro allostimulation studies demonstrating increased activated DCs derived from alveolar BM, but not long BM, of SPF versus GF mice. Chlorhexidine antiseptic rinse depleted the oral, but not gut, bacteriome in SPF mice. Findings from saline- versus chlorhexidine-treated SPF mice corroborated outcomes from SPF versus GF mice, which reveals that the commensal oral microbiota imparts osteoimmunomodulatory effects separate from the systemic microbiome.

Antibiotic-Loaded Polymeric Barrier Membranes for Guided Bone/Tissue Regeneration: A Mini-Review.

Polymeric membranes are frequently used for bone regeneration in oral and periodontal surgery. Polymers provide adequate mechanical properties (i.e., Young’s modulus) to support oral function and also pose some porosity with interconnectivity to permit for cell proliferation and migration. Bacterial contamination of the membrane is an event that may lead to infection at the bone site, hindering the clinical outcomes of the regeneration procedure. Therefore, polymeric membranes have been proposed as carriers for local antibiotic therapy. A literature search was performed for papers, including peer-reviewed publications. Among the different membranes, collagen is the most employed biomaterial. Collagen membranes and expanded polytetrafluoroethylene loaded with tetracyclines, and polycaprolactone with metronidazole are the combinations that have been assayed the most. Antibiotic liberation is produced in two phases. A first burst release is sometimes followed by a sustained liberation lasting from 7 to 28 days. All tested combinations of membranes and antibiotics provoke an antibacterial effect, but most of the time, they were measured against single bacteria cultures and usually non-specific pathogenic bacteria were employed, limiting the clinical relevance of the attained results. The majority of the studies on animal models state a beneficial effect of these antibiotic functionalized membranes, but human clinical assays are scarce and controversial.

Molecular alterations across sites of metastasis in patients with renal cell carcinoma (RCC).

287 Background: RCC has a distinct pattern of metastatic spread with common sites of metastasis including the lung, bone, and liver. Less common sites include the brain, adrenal gland, and pancreas. While the pattern of metastatic spread has prognostic significance, the biology driving tropism to specific organ sites has not been fully characterized. We utilized a multi-institutional real-world dataset to examine genomic alterations and transcriptional signatures across the spectrum of metastatic sites in patients with RCC. Methods: RCC tissue specimens derived from the kidney and distant metastatic sites were sequenced utilizing a commercially available Clinical Laboratory Improvement Amendments (CLIA)-certified assay by Caris Life Sciences. Whole exome and transcriptome sequencing was performed. Molecular subgroups were defined according to the IMmotion151 metastatic RCC subtypes, with subgroups determined by a weighted average of gene expression levels. Molecular analysis and PD-L1 expression (SP142) were described by metastasis site. Results: 657 RCC samples from 653 patients underwent molecular profiling. The median age was 62 years (range 14-90) and the majority were male (70.6%). The most common histology was clear cell RCC (n = 509, 77.5%), followed by papillary (n = 63, 9.6%), chromophobe (n = 30, 4.6%), medullary (n = 8, 1.2%), collecting duct (n = 6, 0.9%), and mixed (n = 41, 6.2%). Specimen source included the kidney (n = 340, 51.8%), lung (n = 75, 11.4%), bone (n = 45, 6.8%), lymph nodes (n = 34, 5.2%), liver (n = 28, 4.3%), endocrine glands (adrenal, pancreas, and thyroid; n = 23, 3.5%), brain/CNS (n = 16, 2.4%), and other metastatic sites (n = 96, 14.6%). Compared to kidney, several genes were mutated at higher rates for select metastatic sites, including PBRM1 (59.5% bone, 59.1% endocrine, and 45.9% lung vs 33.8% kidney, p&lt; 0.05) and KDM5C (27.8% endocrine, 29.2% lymph nodes, and 35.3% soft tissue vs 9.3% kidney, p&lt; 0.05). When evaluating metastatic specimens versus kidney specimens, bone metastases had a significantly higher proportion of tumors classified as ‘Angio/stromal’ (n = 19, 42.2%; vs n = 52, 15.4%; p&lt; 0.0001), while liver metastases had a higher proportion of the ‘complement/Ω-oxidation’ subgroup (n = 17, 60.7%; vs n = 48, 14.1%; p&lt; 0.0001). PD-L1 expression in metastatic sites (range 6.8%-21.7%, with exception of 0% in GI; p= 0.09 to 0.99) was not significantly different from the kidney (16.6%). Conclusions: In our contemporary real-world analysis, we demonstrate differential patterns of molecular alterations among sites of metastasis in RCC. Our observations elucidate the biology underlying heterogeneous disease outcomes associated with site of metastasis. Application of predictive signatures by site of metastasis may help inform personalized therapy strategies in advanced RCC. Further studies are warranted to validate our findings.

Metastasis patterns and prognosis of octogenarians with metastatic breast cancer: A large-cohort retrospective study.

BackgroundBreast cancer may differ biologically in patients aged over 80 years. The objective of the current study was to analyze the metastasis patterns and prognosis of elderly patients with metastatic breast cancer (MBC) and compare it to patients of other ages.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was utilized to select MBC patients from 2010 to 2015. Chi-squared test was used to compare clinicopathological characteristics among different aged groups. The Kaplan-Meier method and multivariate Cox model were utilized for survival analysis.ResultsA total of 10479 MBC patients were included, among which 1036 (9.9%) patients were aged over 80 years. Compared with other aged group, the elderly patients tended to have a higher proportion of HR+/Her2- subtype, white race, lower tumor differentiation, and receive less treatment, including surgery, chemotherapy and radiotherapy (P< 0.001). MBC patients with different age presented with distinctive metastatic patterns. The older patients were more likely to have lung metastasis, but less likely to have bone, brain, liver and multiple sites metastasis than the younger group (P <0.001). The proportion of TNBC subtype increased substantially in the older patients with brain metastasis, compared to the younger and middle-aged group. The old age was demonstrated to significantly associate with worse prognosis of MBC patients. Additionally, our findings also showed that older MBC patients could achieve dramatical overall survival benefit from surgery (HR = 0.58; P <0.001) and chemotherapy (HR = 0.59; P <0.001), but not the radiotherapy (HR = 0.96; P = 0.097).ConclusionThe elderly MBC patients presented with distinctive metastatic patterns, clinical characteristics, and prognostic outcomes compared with younger patients. Our findings could assist clinicians in making appropriate therapeutic decision.

Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection

Orthopedic implants account for 99% of orthopedic surgeries, however, orthopedic implant-related infection is one of the most serious complications owing to the potential for limb-threatening sequelae and mortality. Current antibiotic treatments still lack the capacity to target bone infection sites, thereby resulting in unsatisfactory therapeutic effects. Here, the bone infection site targeting efficacy of D6 and UBI29-41 peptides was investigated, and bone-and-bacteria dual-targeted nanoparticles (NPs) with D6 and UBI29-41 peptides were first fabricated to target bone infection site and control the release of vancomycin in bone infection site. The results of this study demonstrated that the bone-and-bacteria dual-targeted mesoporous silica NPs exhibit excellent bone and bacteria targeting efficacy, excellent biocompatibility and effective antibacterial properties in vitro. Furthermore, in a rat model of orthopedic implant-related infection with methicillin-resistant Staphylococcus aureus, the growth of bacteria was evidently inhibited without cytotoxicity, thus realizing the early treatment of implant-related infection. Hence, the bone-and-bacteria dual-targeted molecule-modified NPs may target bacteria-infected bone sites and act as ideal candidates for the therapy of orthopedic implant-related infections.

Crowding teeth and alveolar bone of mandibular central incisors in adults

Objectives: To study the correlation between alveolar bone morphology of mandibular central incisors and crowding of the six anterior mandibular teeth by using little’s Irregularity Index in adults. Materials and Methods: A total of 44 adults' cases (22 females and 22 males), aged 18-38 years. Patients were scanned by CBCT. We evaluated the morphology of alveolar bone around mandibular central incisors, calculated Little’s Irregularity Index of the anterior lower dental arch, analyzed data, performed the statistical analysis, and studied the correlation. Results: The current study showed statistically significant differences according to gender between some sites of alveolar bone surrounding central incisors and found no confirmed correlations between the studied variables. Conclusion: The potential risks, which may occur as a result of orthodontic treatment for adults, require individual planning of each tooth movement after assessing its condition and position within the dental arch, as well as a continuous evaluation of the surrounding alveolar bone, in order to achieve safe treatment results that ensure the integrity of the periodontal tissues.

MR Imaging Provides Practical Information for Preoperative Assessment of Radial Polydactyly with Bifurcation at the Metacarpophalangeal Joint Level.

PurposeWe aimed to evaluate the use of magnetic resonance imaging (MRI) to visualize unossified bone sites that are often not visible with radiography in pediatric radial polydactyly patients with bifurcation at the metacarpophalangeal (MP) joint level. The MRI validation could help in planning for surgical procedures.Patients and MethodsA total of 141 thumbs in 139 pediatric patients with bifurcation at the MP joint on radiography were included in this study. All the patients had undergone MRI with proton density-weighted fat-suppressed fast spin-echo (FS PDWI) sequence and fast fat-suppressed 3D spoiled gradient-recalled echo (FS 3D SPGR) sequence. The MR images of the cartilaginous structure and joint characteristics at the MP joint were evaluated and categorized by two experienced radiologists.ResultsOur analysis demonstrated that MR imaging, especially the FS 3D SPGR sequence, yields better visibility of the cartilaginous structure and shows clearer joint characteristics that could not be detected by radiography. The abnormalities included a cartilaginous connection on the base of duplicated proximal phalanx, cartilaginous joint connection and the shape of articular cartilage on the head of metacarpal and soft tissue band. Radiologically encountered duplications at the MP joint level were successfully classified into six types based on the MRI-detected structural changes. The distribution of the six types was 17.7% (25/141) in type 1, 53.9% (76/141) in type 2, 2.8% (4/141) in type 3, 9.9% (14/141) in type 4, and 13.5% (19/141) in type 5.ConclusionThis data showed that MR imaging provides practical information on the anatomic characteristics in radial polydactyly with bifurcation at the MP joint level that could aid surgical decision-making processes. Thus, the FS 3D SPGR sequence could be used as a MR imaging technique in radial polydactyly.

The relationship between chemerin, bone metabolism, the RANKL/RANK/OPG system, and bone mineral density in girls with anorexia nervosa

Based on recent studies in humans, chemerin has been classified as an adipokine that might be associated with osteoporosis and BMD. Bone loss is common in adolescents with anorexia nervosa (AN). Moreover, dysfunction in the production of chemerin has also been shown. Therefore, we carried out a comparative analysis between chemerin, bone metabolism, the RANKL/RANK/OPG system, and BMD in girls with AN. Plasma chemerin, OC, CTx, OPG, and sRANKL were determined by ELISA in 75 girls with AN aged 12.6-17.8 years. BMD was assessed by DXA and expressed as Z-score according to the lumbar spine (s) and total body (TB) sites. According to the s-BMD- and TB-BMD Z-score, girls with AN were divided into two subgroups with parallel analyses used: normal (Z-score > -2.0) and low (Z-score ≤ -2.0) s-BMD, and normal (Z-score > -2.0) and low (Z-score ≤ -2.0) TB-BMD. Mean OC and the OPG/sRANKL ratio were markedly lower in the low s-BMD subgroup compared to the normal s-BMD subgroup. The s-Z-score values (both low and normal) correlated significantly and positively with the OPG/sRANKL ratio. Only in the low s-BMD subgroup did chemerin correlate significantly and positively with all nutritional indices and the OPG/sRANKL ratio. In the low TB-BMD subgroup the mean OC and the OPG/sRANKL ratio were lower than in the normal TB-BMD subgroup. The TB-Z-score values (both normal and low) correlated significantly and positively with all nutritional indices and the OPG/sRANKL ratio. The low TB-Z-score values correlated significantly and positively also with chemerin. In the low TB-BMD subgroup chemerin correlated significantly and positively with weight and BMI (expressed as absolute values), Cole index, the duration of the disease, and OPG/sRANKL ratio while its correlation with age was negative. Undernutrition and associated deficit of adipose tissue may result in inadequate chemerin production and skeletal disorders in girls with AN. Chemerin acts as a coordinator of the dynamic balance between bone metabolism and the OPG/RANK/RANKL system and, in turn, may contribute to the loss of bone mass in girls with AN. The cortical bone site seems to be more severely responsive to chemerin actions than the trabecular bone site.

The Chronic Effects of a Quantified Jump-Landing Program on Bone Health, Body Composition and Performance Parameters in Premenopausal Women

The primary purpose of this study was to determine the effects of a 12-month quantified jump-landing program at clinically relevant bone sites in premenopausal women. Secondary measures of interest included; lower body explosive power, muscle reactivity, balance performance parameters and body composition. A longitudinal controlled trial was implemented to determine the effect of utilizing previously quantified jumps and hops with specific cues provided for jump-landings. Participants; Fifty-seven women (age, 42.4 ± 5.50 y; body mass, 70.2 ± 11.5 kg; height, 165.4 ± 0.10 cm; body fat, 31.5 ± 6.20%) were assigned to a jump (JL) or control (CON) group. The JL performed periodized jumping-landing exercises up to five times per week for 12-months. Linear mixed model regression analysis was used to determine if differences existed between the JL and CON. Significant group main effects (P&lt;0.01) in favour of the JL (↑0.41 - ↑3.72%) were observed for bone mineral density and bone mineral content at the femoral neck, total hip and lumbar spine. Significant group main effects (P&lt;0.01) for cross-sectional area, cortical thickness and section modulus at the femoral narrow neck were also in favour of the JL (↑2.78 - ↑3.84%). For ground contact time, improvements in the JL over the CON between baseline and 12-months were apparent (↑21.9% vs. ↓8.86%) with significant group and time effects (P&lt;0.01) being observed. A longitudinal quantified periodized jumplanding program performed 2-3 mins/day; 4-5 times a week is osteogenically effective in improving bone strength at clinically relevant lower body sites associated with osteoporosis in premenopausal women.

Bone-Specific Enhancement of Antibody Therapy for Breast Cancer Metastasis to Bone.

Despite the rapid evolution of therapeutic antibodies, their clinical efficacy in the treatment of bone tumors is hampered due to the inadequate pharmacokinetics and poor bone tissue accessibility of these large macromolecules. Here, we show that engineering therapeutic antibodies with bone-homing peptide sequences dramatically enhances their concentrations in the bone metastatic niche, resulting in significantly reduced survival and progression of breast cancer bone metastases. To enhance the bone tumor-targeting ability of engineered antibodies, we introduced varying numbers of bone-homing peptides into permissive sites of the anti-HER2 antibody, trastuzumab. Compared to the unmodified antibody, the engineered antibodies have similar pharmacokinetics and in vitro cytotoxic activity, but exhibit improved bone tumor distribution in vivo. Accordingly, in xenograft models of breast cancer metastasis to bone sites, engineered antibodies with enhanced bone specificity exhibit increased inhibition of both initial bone metastases and secondary multiorgan metastases. Furthermore, this engineering strategy is also applied to prepare bone-targeting antibody–drug conjugates with enhanced therapeutic efficacy. These results demonstrate that adding bone-specific targeting to antibody therapy results in robust bone tumor delivery efficacy. This provides a powerful strategy to overcome the poor accessibility of antibodies to the bone tumors and the consequential resistance to the therapy.

Implant Stability Following Osseointegration of Dental Implants in Bone Sites Reconstructed with Novel Porous Titanium Scaffold

Porous titanium (porous Ti) possesses excellent mechanical strength and three-dimensional structure. Therefore, it enables bone formation due to its good osteoconduction abilities. Osseointegration can be achieved at the implant site after bone reconstruction with porous Ti. This study aimed to assess implant stability following osseointegration at sites reconstructed with porous Ti. Hollow-shaped porous Ti were placed in the tibiae of six New Zealand white rabbits. Ti dental implants were placed 4 weeks later. Implant placed at the parent bone sites, without porous Ti, served as the controls. Histological and histomorphometric assessments of the porous Ti and control sites were performed 4 weeks later. There was no significant difference in the insertion torque between the porous Ti and control groups. The primary and secondary implant stability quotient value was higher in the porous Ti group than that in the control group. Histologically, bone reconstruction was achieved with porous Ti through osteoconduction into the original bone region and bone marrow region, as osseointegration of implants was achieved even in the bone marrow region. The bone-implant contact ratio was similar in both the groups; however, the bone-implant contact was mainly in the cortical region in the control group. In the present study, the reconstructed bone site with porous Ti showed favorable osseointegration ability when the dental implant was placed. Porous Ti is expected to be a suitable material for bone material before implant placement.

A facile aqueous production of bisphosphonated-polyelectrolyte functionalized magnetite nanoparticles for pH-specific targeting of acidic-bone cells.

Bone malignancy treatment is being hindered due to the insufficient selectivity of therapeutic nanoparticles towards malignant bone sites. Polyelectrolyte functionalized magnetic nanoparticles having dually specific pH-sensing ability and bisphosphonate moieties, can be an effective solution for selective targeting of bone malignancies. First, polyelectrolyte was prepared via N-carboxycitraconyzation of chitosan (NCCS) followed by successive functionalization with alendronic acid (AL) and fluorescein isothiocyanate (FITC). Then, Fe3O4-NCCS-FITC-AL nanoparticles were synthesized by a facile one-step microwave-assisted aqueous method via in situ surface functionalization. The formation, crystal structure, and surface conjugation of Fe3O4 nanoparticles with polyelectrolytic stabilizer were confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analyses. Synthesized Fe3O4-NCCS-FITC-AL nanoparticles were superparamagnetic, colloidally stable and highly hemocompatible under physiological conditions. Moreover, at pH 5.0, Fe3O4-NCCS-FITC-AL nanoparticles formed a precipitate due to inversion of their surface charge. This pH-dependent charge-inversion drastically changed the interactions with erythrocytes and bones. Selective membranolysis of erythrocytes occurred at pH 5.0. The designed nanoparticles showed enough potential for selective targeting of pathological bone sites in early-stage magnetofluorescent imaging and as a therapeutics carrier to treat malignant bone diseases.

Fractal dimension analysis on CBCT scans for detecting low bone mineral density in postmenopausal women.

PurposeThe aim of this study was to compare the fractal dimension (FD) measured at 2 bone sites (second cervical vertebra and mandible) on cone-beam computed tomography (CBCT). The research question was whether FD could serve as an accessory tool to refer postmenopausal women for densitometric analysis. Therefore, the reliability and accuracy of FD were evaluated.Materials and MethodsIn total, 103 postmenopausal women were evaluated, of whom 52 had normal bone mineral density and 51 had osteoporosis, according to dual X-ray absorptiometry of the lumbar spine and hip. On the CBCT scans, 2 regions of interest were selected for FD analysis: 1 at the second cervical vertebra and 1 located at the mandible. The correlations between both measurements, intra- and inter-observer agreement, and the accuracy of the measurements were calculated. A P value less than 0.05 was considered to indicate statistical significance for all tests.ResultsThe mean FD values were significantly lower at the mandibular region of interest in osteoporotic patients than in individuals with normal bone mineral density. The areas under the curve were 0.644 (P=0.008) and 0.531 (P=0.720) for the mandibular and vertebral sites, respectively.ConclusionFD at the vertebral site could not be used as an adjuvant tool to refer women for osteoporosis investigation. Although FD differed between women with normal BMD and osteoporosis at the mandibular site, it demonstrated low accuracy and reliability.