Low Bone Research Articles

Investigation of periodontal tissue regeneration using octacalcium phosphate and collagen composite

ObjectiveThis study aimed to investigate periodontal tissue regenerative potential of octacalcium phosphate (OCP) and collagen composite (OCPcol), recognized as excellent bone-regenerative materials, in artificial bone defect models using beagle dogs. This study specifically assessed the efficacy of OCPcol in periodontal soft-tissue regeneration. MethodsOCPcol was implanted in bone defects adjacent to the roots of the left mandibular third and fourth premolars in six beagle dogs (OCP group), while five dogs did not receive OCPcol (control group). The dogs were observed for 3 months. The specimens were evaluated radiologically and histologically. ResultsMicrocomputed tomography revealed bone regeneration originating from the lateral cortical bone surface adjacent to the created defect. The superficial layer of the regenerated bone was cortical bone-like and continuous with the upper and lower alveolar bone. The bone was regenerated by maintaining a continuous void in the periodontal ligament space above and below the dentinal defect. Dental defects of roots were not regenerated. The control group did not exhibit sufficient bone regeneration. Histologically, in the OCP group, formation of new cementum was observed on the outer surface of the root dentin, with connective tissue attachment and an oblique-running periodontal ligament in the space between the new bone and dentin. However, the dentinal defects were not regenerated． ConclusionsAlveolar bone and periodontal ligament regenerated when OCPcol was implanted into a bone and dentinal defect created around a natural tooth root. These results suggest that OCPcol effectively regenerates periodontal tissue, without ankylosis.

Quantitative metrics of bone quality determined at the distal radius using photon-counting CT.

To determine the accuracy of photon-counting-detector CT (PCD-CT) at deriving bone morphometric indices and demonstrate utility in vivo in the distal radius. Ten cadaver wrists were scanned using PCD-CT and high-resolution peripheral quantitative CT (HRpQCT). Correlation between PCD-CT and HRpQCT morphometric indices was determined. Agreement was assessed by Lin's concordance correlation coefficient (Lin's CCC). Wrist PCD-CTs of patients between 02/2022 and 08/2023 were also evaluated for clinical utility. Morphometric indices of the in vivo distal radii were extracted and compared between patients with or without osteoporosis. In cadavers, strong correlation between PCD-CT and HRpQCT was observed for cortical thickness (Spearman correlation, ρ, 0.85), trabecular spacing (ρ = 0.98), and trabecular bone volume fraction (ρ = 0.68). Moderate negative correlation (ρ = - 0.49) was observed for trabecular thickness. PCD-CT shows good agreement to HRpQCT for cortical thickness, trabecular spacing, and trabecular bone volume fraction (Lin's CCC = 0.80, 0.94, and 0.86, respectively) but poor agreement (Lin's CCC = - 0.1) for trabecular thickness. In forty participants (31 adults and 9 pediatric), bone morphometrics indices for cortical thickness, trabecular thickness, trabecular spacing, and trabecular bone volume fraction were 0.99mm (IQR, 0.89-1.06), 0.38mm (IQR, 0.25-0.40), 0.82mm (IQR, 0.72-1.05), and 0.28 (IQR, 0.25-0.33), respectively. Patients with osteoporosis had statistically significantly larger trabecular spacing (p = 0.025) and lower trabecular volumetric bone mineral density (p = 0.042). This study demonstrates the agreement of PCD-CT to HRpQCT in cadavers of most cortical and bone morphometrics examined and provide in vivo quantitative metrics of bone microarchitecture from routine clinical PCD-CT images of the distal radius.

Patients with TP53-Mutated Acute Myeloid Leukemia Receiving Intensive Induction Therapy Have Superior Outcomes Due to a Higher Rate of Salvage Therapy: A Single Institution, Retrospective Study.

TP53 mutations (TP53m) define the most treatment-refractory acute myeloid leukemia (AML) subtype. Optimal treatment approaches have not been established in this setting. We reviewed our institutional experience to identify therapy sequencing, treatment response, and survival patterns in these patients. This study was a single-center, retrospective cohort analysis. Our cohort includes 86 TP53m and 337 TP53 wild-type (TP53wt) adult AML patients. TP53m AML patients presented with lower bone marrow and peripheral blasts; none presented with hyperleukocytosis. Patients who received intensive treatment up front demonstrated superior overall survival (OS) over those receiving first-line non-intensive therapy (2-year OS 22% versus 7%; p = 0.02). However, the complete remission (CR) rates among the first-line intensive and non-intensive therapy groups were comparable (21.9% and 29.4%, respectively, p = 0.49). The improved OS is therefore attributed to superior cumulative CR in the intensive group. First-line intensively treated patients were more likely to receive and respond to salvage, leading to a cumulative CR rate of 65.7% (versus 29.4%, p = 0.003). Achieving CR at any point is strongly associated with superior survival outcomes with 2-year OS of 31% versus 0% for those not achieving CR ever (p < 0.01). We find that TP53m AML rarely presents with oncological emergencies, suggesting that clinical trial enrollment is feasible in this group. Additionally, in our cohort, intensive induction therapies lead to superior survival outcomes attributed to successful salvage therapy. These data suggest that strategic therapy sequencing and salvage therapy may be important in optimizing outcomes for TP53m AML patients.

The association of combined vitamin C and D deficiency with bone mineral density and vertebral fracture

PurposeBoth vitamin C and D deficiencies are extremely common in clinical practice, especially in elderly population. Unfortunately, the role of vitamin C deficiency in osteoporosis related consequences is often neglected. The aim of the present study is to analyse if combined vitamin C and D deficiency would have an association with bone mineral density (BMD) and osteoporotic vertebral fracture (OVF).MethodsNinety-nine post-menopausal female patients admitted in the department of spine surgery of third affiliated hospital of Sun Yat-sen University were enrolled in the study. The participants were divided into four groups; vitamin D deficiency alone (comparator group), vitamin C deficiency alone and combined vitamin C and D deficiency as experimental group. The levels of vitamin C, vitamin D, calcium, phosphorous, BMD and condition of OVF were analysed.ResultsThere were statistically significant differences between the groups in terms of vitamin C and D levels. In terms of lumbar BMD, significant differences were observed between vitamin D deficiency alone and combined vitamin C and D deficiency. Only the combined vitamin C and D deficiency had a significant negative association with lumbar BMD and T-score. Similarly, combined vitamin C and D deficiency had a significant positive association with lumbar osteoporosis. None of the groups had any significant association with OVF. Combined vitamin C and D deficiency was found to be significantly associated with lower lumbar BMD and osteoporosis.ConclusionCombined vitamin C and D deficiency results in lower bone mineral density and higher risk of osteoporosis. We believe that existence of deficiencies of both vitamins could have a synergistic effect. Therefore, we recommend that vitamin C and D should be routinely measured in clinical practice.

How does orthodontic tooth movement influence the dental pulp? RNA-sequencing on human premolars.

The objective of this study is to analyse the gene expression profile of the dental pulp (DP) of human premolars subjected to 7 and 28 days of orthodontic force (OF) in vivo by using RNA sequencing. The maxillary and mandibular DP were additionally compared. Healthy patients requiring orthodontic premolar extractions were randomly assigned to one of the three groups: control (CG) where no OF was applied, 7 and 28 days, where premolars were extracted either 7 or 28 days after the application of a 50-100 g OF. Total RNA was extracted from the DP and analysed via RNA-seq. Differentially expressed genes (DEGs) were identified using a false discovery rate and fold change threshold of <0.05 and ≥1.5, respectively. Functional analysis was performed. After 7 days of OF, pulp reaction indicates immune response, hypoxia, DNA damage and epigenetic regulation. After 28 days, cell adhesion, migration, organization and tissue repair are evident. The maxillary and mandibular pulp tissues react differently to OF. The maxilla exhibits minimal alterations, mostly related to immune response at 7 days and tissue repair at 28 days, whereas the mandible shows mostly DNA damage and epigenetic regulation at 7 days and return to the original state at 28 days. This study demonstrates that the early reaction of the DP to OF is marked by immune response, hypoxia and DNA damage. In contrast, after 28 days, cell adhesion, migration, organization, tissue repair and dentine formation are observed. Maxillary and mandibular premolars react differently to OF: although the maxilla exhibits minimal alterations at both time points, the mandible mostly shows DNA damage, epigenetic regulation, and immune response at 7 days. These disparities could stem from different blood supplies or the lower maxillary bone density, potentially triggering faster biological changes. Our findings provide insights into the gene regulatory networks modulating DP response to OF.

Apical periodontitis as an aggravating factor for the severity of rheumatoid arthritis: An animal study.

The present study investigated the influence of apical periodontitis (AP) on the severity of rheumatoid arthritis (RA) using a Wistar rat model. Forty male Wistar rats were distributed across four groups (n = 10) based on the induction of RA and AP: Control, RA, AP, and RA + AP. RA was induced through two immunisations with type II collagen emulsified in incomplete Freund's adjuvant, followed by one immunisation with complete Freund's adjuvant. After 21 days of RA induction, AP was induced by exposing the pulp of four molars. Animals were euthanized after 28 days of pulp exposure. Through the experiment, visual and behavioural assessments tracked RA development and the knees and hind paw joints were measured. Micro-computed tomography scans of knees and hind paws, as well as mandibles and maxillae, were conducted to evaluate RA severity and the presence of AP, respectively. Serum samples were collected to analyse proinflammatory cytokines (IL-1β, IL-2, IL-17, and TNF-α). Non-parametric data were analysed using the Kruskal-Wallis test followed by Student-Newman-Keuls test, while one-way anova followed by Tukey's test was performed for parametric data. A significance level of 5% was employed. All molars submitted to access cavity developed AP. All joints subjected to arthritis induction developed the disease, with AP + RA demonstrating a higher arthritis severity when compared to the RA group (p < .05). RA + AP group displayed a significantly larger hind paw and knee circumference compared to the RA group (p < .05). Micro-CT images of RA and RA + AP groups revealed joints with erosions and bone deformities, with a significantly lower bone surface density, lower trabecular number and higher trabecular separation in the hind paw and a significantly lower percent bone volume and higher trabecular separation in the knees of RA + AP group compared to RA group (p < .05). RA + AP group exhibited a significantly higher level of TNF-α and a lower level of IL-2 compared to all other groups (p < .05). Both RA and RA + AP groups had significantly higher IL-17 levels (p < .05), while there was no significant difference in IL-1β levels among the groups (p > .05). The findings from this study underscore a possible relationship between apical periodontitis and the exacerbation of rheumatoid arthritis.

Short-Term Celecoxib Promotes Bone Formation without Compromising Cefazolin Efficacy in an Early Orthopaedic Device-Related Infection: Evidence from a Rat Model.

Non-steroidal anti-inflammatory drugs (NSAIDs) are crucial components of multimodal analgesia for musculoskeletal injuries, targeting cyclooxygenase (COX) enzymes (COX-1 and/or COX-2 isoenzymes). Concerns exist regarding their potential interference with bone healing and orthopaedic device-related infections (ODRI), where data are limited. This study aimed to investigate whether the COX-selectivity of NSAIDs interfered with antibiotic efficacy and bone changes in the setting of an ODRI. In vitro testing demonstrated that combining celecoxib (a COX-2 inhibitor) with cefazolin significantly enhanced antibacterial efficacy compared to cefazolin alone (p < 0.0001). In vivo experiments were performed using Staphylococcus epidermidis in the rat proximal tibia of an ODRI model. Long and short durations of celecoxib treatment in combination with antibiotics were compared to a control group receiving an antibiotic only. The long celecoxib treatment group showed impaired infection clearance, while the short celecoxib treatment showed increased bone formation (day 6, p < 0.0001), lower bone resorption (day 6, p < 0.0001), and lower osteolysis (day 6, BV/TV: p < 0.0001; BIC: p = 0.0005) compared to the control group, without impairing antibiotic efficacy (p > 0.9999). Given the use of NSAIDs as part of multimodal analgesia, and considering these findings, short-term use of COX-2 selective NSAIDs like celecoxib not only aids pain management but also promotes favorable bone changes during ODRI.

Adolescent girls with type 1 diabetes develop changes in bone prior to evidence of clinical neuropathy.

Neuropathy and fracture are prevalent complications of type 1 diabetes (T1D). Although correlated in the clinical literature, it remains unknown whether neuropathy contributes to the initiation of bone loss at the earliest stages of disease. We performed a single-center, cross-sectional study to quantify parameters of nerve and bone health in adolescent girls with T1D (n=21) and associated controls (n=12). Groups were well matched for age, height, strength, and physical activity. By HR-pQCT, participants with T1D had lower trabecular bone volume fraction at the distal radius (-14.6%, p-adj=0.095) and the tibia (-12.8%, p-adj=0.017) and decreased trabecular thickness (-8.3% radius, p-adj=0.007; -7.5% tibia, p-adj=0.034) after adjustment for body size. In the tibia only, cortical bone mineral density was increased by 8.6% (p-adj=0.024) and porosity was decreased by 52.9% with T1D (p-adj=0.012). There were no significant differences in bone density by DXA. Participants with T1D also had lower circulating levels of osteocalcin (-30%, p=0.057), and type I collagen cross-linked C-telopeptide (-36%, p=0.035), suggesting low bone formation and turnover in T1D. Based on the Michigan Neuropathy Screening Instrument, 9.5% of those with T1D had clinical evidence of diabetic peripheral neuropathy. However, consideration of neuropathy status failed to explain the widespread T1D-associated changes in bone. Our study defines early deficits in trabecular bone microarchitecture, decreased cortical porosity in the tibia, and suppression of biomarkers of bone turnover in adolescent girls with T1D, prior to the onset of symptomatic peripheral neuropathy. These findings inform our understanding of the rapid progression of skeletal disease in young girls with T1D and suggests that early detection and management strategies may help to prevent fracture and related co-morbidities later in life.

Sex differences in body composition and shock attenuation during running

Running-related impact shock is absorbed via biological tissue deformation. Given known sex differences in body composition, shock attenuation may also differ between sexes thereby influencing sex-specific running-related injury risk. This study examined sex differences in body composition and shock attenuation during running. Seventeen female (mean ± 1SD age: 34.7 ± 16.1) and twenty-one male runners (age: 29.0 ± 13.8) ran overground as inertial measurement units with triaxial accelerometers measured impact shock at the distal tibia and low-back. Frequency-domain axial and resultant shock attenuation were calculated between the low-back relative to the tibia using a transfer function of the power spectral density within 9–20, 21–35, and 36–50 Hz. Bone mineral density and content, fat and lean mass were measured in the lower extremity and pelvis/gynoid regions using dual x-ray absorptiometry. The association between sex and shock attenuation was tested using age-adjusted linear regression models, adjusted and unadjusted for body composition as a post-hoc analysis (α = 0.05). Body composition variables normalized to body mass were compared between sexes using independent samples t-tests (α = 0.05). Body composition differed between sexes (p-range: <0.001–0.01, Cohen’s d range: 0.17–2.41). Before adjusting for body composition, sex was not significantly associated with axial or resultant shock attenuation (p > 0.05), but adjusting for select body composition variables like lower extremity lean and bone mass revealed greater attenuation in females than males (β-range: −124.76 to −46.42, negative indicates greater attenuation; p-range = 0.004–0.04). Sex may not influence shock attenuation during running, but body composition must be accounted for to better understand this association and consequently sex-specific tissue capacities relative to applied loads.

Alveolar Ridge Preservation With Fibro-Gide or Connective Tissue Graft: A Randomized Controlled Trial of Soft and Hard Tissue Changes.

The aim of this study was to evaluate the effectiveness of a novel biomaterial (FG) for alveolar ridge preservation compared to CTG in terms of soft tissue thickness and bone dimensional changes. A randomized clinical trial was conducted on 30 patients who required extraction of 30 hopeless mandibular posterior teeth. All patients went through atraumatic tooth extraction, and then, they were randomly allocated to either a CTG, an FG, or a spontaneous healing (SH) group (1:1:1). All patients received a dental implant placed 6 months postoperatively. The soft tissue thickness and bone dimensional changes were measured before and 6 months after the procedure. The study's analysis revealed statistically significant differences in buccal gingival thickness and dimensional bone changes across the three examined groups after 6 months (p < 0.05). The SH group had lower gingival thickness (1.31 ± 0.65 mm) and higher vertical resorption (-1.46 ± 1.67 mm at the buccal aspect) compared with the CTG and FG groups. The CTG and FG groups had similar gingival thickness (2.42 ± 0.70 and 3.00 ± 0.71 mm, respectively) and bone width reduction (+0.86 ± 2.31 and +0.93 ± 2.38 mm, respectively), whereas the CTG group had lower vertical bone loss (-0.30 ± 1.09 mm at the buccal aspect) than the FG group (-0.47 ± 2.30 mm at the buccal aspect). FG and CTG demonstrate equivalent soft tissue thickness and comparable horizontal bone dimension outcomes in ARP.

Synthesis and evaluation of bifunctional DFO2K: a modular chelator with ideal properties for zirconium-89 chelation.

The synthesis and evaluation of the newest generation of our DFO2 chelator family-DFO2K-is described. DFO2K was designed with a simple synthetic route to access different bifunctional derivatives, with each derivative having similar metal ion coordination spheres and high denticity (up to 12 coordinate) to ensure stable coordination of zirconium-89. The high denticity could potentially enhance stability with other large oxophilic radiometals. Zirconium-89 is the most popular radionuclide to pair with large macromolecules such as antibodies (immunoPET) for positron emission tomography applications. Although clinically successful, the stability of the "gold standard" chelator desferrioxamine B (DFO) can be improved as significant bone uptake is observed in animal models, despite no obvious stability issues in humans. Following the synthesis of DFO2K we assessed its radiolabeling efficiency with zirconium-89 and compared with DFO, which revealed rapid and nearly identical radiolabeling kinetics to DFO. The resultant [89Zr]Zr-DFO2K complex showed improved stability over [89Zr]Zr-DFO in different in vitro stability assays such as hydroxyapatite and 1000-fold molar excess EDTA challenges. Furthermore, biodistribution studies of the non-bifunctional chelators in healthy mice showed that [89Zr]Zr-DFO2K had a similar distribution profile and clearance to [89Zr]Zr-DFO. The bifunctional derivative p-SCN-Ph-DFO2K was conjugated to a non-specific human IgG antibody and evaluated after 2 weeks circulating in healthy female CD1 mice. Mice administered [89Zr]Zr-DFO2K-IgG showed substantially lower bone uptake in PET-CT images than [89Zr]Zr-DFO-IgG, with PET ROI data and ex vivo biodistribution revealing a statistically significantly lower bone uptake for DFO2K. Overall, owing to its high denticity, ease of synthesis, improved solubility over DFO2 and DFO2p, and stable chelation of zirconium-89, DFO2K appears to be an improved alternative chelator to DFO for zirconium-89 chelation.

Analysis of the relationship between solar greenhouse operation and occupational high incidence diseases

Objective: To understand the health status of solar greenhouse workers, to provide scientific basis for the development of occupational high incidence diseases prevention and control strategies. Methods: In July 2019, a random cluster sampling method was used to select 245 workers engaged in solar greenhouse vegetable cultivation in Daba Village, Jingyuan County, Baiyin City, Gansu Province as the solar greenhouse operation group. Matched by gender, age, marital status, body mass index (BMI), 282 people from adjacent Shaliang Village who did not engage in solar greenhouse operation were selected as the control group. Field investigation and health examination were carried out among the study subjects. The general situation, facial features examination results, ophthalmic examination results, bone and joint examination results and skin examination results were compared between the two groups. And the multiple logistic regression analysis was used to analyze the influencing factors of abnormal bone and joint examination (upper limbs, lower limbs, hands and spine bone joints) in study subjects. Results: There were statistically significant differences in smoking age and alcohol consumption between the two groups (P<0.001). Compared with the control group, the abnormal detection rates of nose examination, throat examination, slit lamp examination, conjunctival examination, lower limb bone joint examination, hand bone joint examination, spine examination, head and neck skin examination, trunk skin examination, upper limb skin examination, and lower limb skin examination in the solar greenhouse operation group were higher, and the differences were statistically significant (χ(2)=11.53, 7.94, 9.92, 27.93, 79.32, 81.42, 9.43, 6.79, 9.76, 4.34, 8.29, P<0.05). Multivariate logistic regression analysis showed that after adjusting for gender, age, marital status, education level, BMI, compared with the control group, solar greenhouse operation was a risk factor for abnormal bone and joint examination (OR=1.178, 95%CI: 1.151-2.143, P=0.001) . Conclusion: Solar greenhouse operation has a certain harmful effect on health of workers, and solar greenhouse workers have an increased risk of abnormal diseases of upper limbs, lower limbs, hands and spine bone joints.

Application of topical 5-Fluorouracil to reduce the recurrence of odontogenic keratocyst: A prospective study with 2-year follow-up

ObjectivesThe purpose of this prospective study was to evaluate the effect of topical 5-Fluorouracil as an adjunct therapy in reducing the recurrence of odontogenic keratocyst. MethodsForty-eight patients with proven incisional biopsy as odontogenic keratocyst were included in this clinical study. The patients were divided into two equal groups, the test group patients were treated with 5-Fluorouracil cream after cyst enucleation. However, the control group patients were treated with cyst enucleation only. Recurrence (yes/no) was the primary outcome variable evaluated by clinical signs of inflammation, swelling, or pain within a 2-year follow-up. The pain was measured on a visual analogue scale, and swelling was measured pre-surgically using vertical and horizontal references, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months. Computed tomography was performed pre-surgically and 24 hours post-surgically, at 12-month, and 24-month intervals to evaluate local bone density. The T-test was used to compare between two studied groups. ResultsPost-surgical follow-up showed uneventful wound healing in both groups with no clinical signs of recurrence or swelling, pain results demonstrated that patients have decreased records throughout the observation periods with no significant difference between both groups. Normal sensation was encountered in all patients except for one patient in the control group who showed no sensation (score 2). Post-surgical radiographic findings revealed a considerable shift in bone density in all patients of both groups at the site of excised lesions during the follow-up periods compared with immediate post-surgical radiographs. However, the test group patients demonstrated a significant increase of bone density between different evaluation periods (P = 0.001) than the control group. ConclusionConservative enucleation of odontogenic keratocyst combined with topical application of 5-Fluorouracil is an effective treatment with lower recurrence rates, less morbidity, and normal bone healing.

Bone and muscle differences in children and adolescents with type 1 diabetes: The mediating role of physical activity

Children with type 1 diabetes (T1D) experience an increased risk of fracture, which may be related to altered bone development. We aimed to assess differences in bone, muscle and physical activity (PA), and explore if better muscle and PA measures would mitigate bone differences between children and adolescents with T1D and typically developing peers (TDP). We matched 56 children and adolescents with T1D (mean age 11.9 yrs) and 56 TDP (11.5 yrs) by sex and maturity from 171 participants with T1D and 66 TDP (6-17 yrs). We assessed the distal radius and tibia with high-resolution peripheral quantitative computed tomography (HR-pQCT), and the radius and tibia shaft bone and muscle with pQCT. We also measured muscle function from force-related measures in neuromuscular performance tests (push-up, grip test, countermovement and long jump). We compared PA based on questionnaire scores and accelerometers between groups. Bone, muscle, and neuromuscular performance measures were compared using MANOVA. We used mediation to explore the role of PA and muscle in bone differences. Children and adolescents with T1D had 6–10 % lower trabecular density, bone volume fraction, thickness and number at both distal radius and tibia, and 11 % higher trabecular separation at the distal radius than TDP. They also had 3–16 % higher cortical and tissue mineral density, and cortical thickness at the distal radius, 5–7 % higher cortical density and 1–3 % higher muscle density at both shaft sites compared to TDP. PA mediated the between-group difference in trabecular number (indirect effect −0.04) at the distal radius. Children and adolescents with T1D had lower trabecular bone density and deficits in trabecular micro-architecture, but higher cortical bone density and thickness at the radius and tibia compared to TDP. They engaged in less PA but had comparable muscle measures to those of TDP. PA participation may assist in mitigating deficit in trabecular number observed in children and adolescents with T1D.

Oncological and functional outcomes of pathological fractures of lower extremities in patients with malignant bone tumors.

As managing pathological fractures of the extremities can be difficult, the present study aimed to present a treatment algorithm for lower extremity bone malignancies. A total of 38 patients with impending and pathological fractures were treated at the Department of Orthopedic Surgery in Kindai University Hospital. Age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcomes, follow-up period and the MSTS scores and ECOG-PS were compared in cases of primary malignant tumors and those cases of metastatic malignant tumors were retrospectively surveyed. Post-treatment MSTS scores in cases of impending and pathological fractures were compared between intramedullary nail fixation and non-intramedullary nail fixation procedures. Disease sites included the sub-trochanteric femur in 10 patients, trochanteric femur in 8, femoral diaphysis in 7, femoral neck in 5, bilateral trochanteric femur in 3, proximal tibia in 3 and distal femur in 2 patients. A total of 10 patients had metastases between 3-20 sites. The median pre-fracture ECOG-PS score was 1. Adjuvant radiotherapy was administered to 5, chemotherapy to 8 and radiotherapy with chemotherapy to 10 patients. Surgical procedures included intramedullary nails in 18 patients, tumor arthroplasty in 4, plate fixation in 3, artificial head replacement in three, compression hip screw (CHS) in 3, conservative treatment in 2, bilateral intramedullary nail fixation in 2 and artificial bone stem with combined intramedullary nail and plate fixation, right-sided artificial head replacement and left-sided CHS in 1 patient each. The MSTS score was 19.9±8.95 for intramedullary nail fixation and 24.3±7.45 for other procedures, with a negative association between the MSTS score and pre-fracture ECOG-PS. The median follow-up period was 8 months. The outcomes were as follows: Alive with disease, 23 patients; continued disease-free, 1 patient; and dead due to disease, 14 patients. The 1-year postoperative overall survival rate was 60.5%. Moreover, the group with metastatic malignant tumors, which had significantly worse ECOG-PS, had significantly lower MSTS scores than the group with primary malignant tumors. The authors' treatment algorithm for malignant bone tumors of the lower extremity was shown to be useful.

Jaboticaba Peel Extract Attenuates Ovariectomy-Induced Bone Loss by Preserving Osteoblast Activity.

Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Since jaboticaba peel extract (JPE) added to the culture medium enhanced the osteogenic potential of mesenchymal stem cells (MSCs) derived from osteoporotic rats, we hypothesized that JPE prevents the development of ovariectomy-induced osteoporosis. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy. Then, the femurs were subjected to microcomputed tomography and histological analyses, and the osteoblast and adipocyte differentiation of MSCs was evaluated. JPE attenuated ovariectomy-induced bone loss, as evidenced by higher bone volume/total volume and trabecular number, along with lower trabecular separation and bone marrow adiposity. These protective effects of JPE on bone tissue are due to its ability to prevent the imbalance between osteoblast and adipocyte differentiation of MSCs, since, compared with MSCs derived from ovariectomized rats treated with vehicle, MSCs treated with JPE exhibited higher gene and protein expression of osteogenic markers and extracellular matrix mineralization, as well as lower gene expression of adipogenic markers. These data highlight the potential therapeutic use of JPE to prevent osteoporosis.

A microtomographic and histopathological evaluation of dental cements as late-stage peri-implant complication in a rat model

Cement mediated peri-implantitis accounts for 1.9–75% of dental implant failures associated with peri-implant diseases. This study evaluated the biological impact of dental cements on osseointegrated implants using Lewis rats. Twenty-two rats were distributed into 6 groups: negative control (NC) soft diet (SD), and hard diet (HD); positive control SD and HD (n = 3); Implant + bio-ceramic Cement (BC) SD and HD which included contralateral Sham sites (n = 5). Titanium implants were placed on either side of the maxillae and allowed to heal for 14 days. Later, both sides of experimental groups underwent a re-entry surgery to simulate clinical cementation. The right side received 0.60 mg of BC. At 14 days post cement application, maxillae were harvested for clinical, microtomographic, and histological evaluations. Clinical and microtomographic evaluations indicated evidence of extensive inflammation and circumferential bone resorption around BC implants in comparison to NC. Histology revealed cement particles surrounded by inflammatory infiltrate in the implant area accompanied by biofilm for SD groups. Both sides of BC indicated intensive bone resorption accompanied by signs of osteolysis when compared to NC. Cemented groups depicted significantly lower bone to implant contact when compared to NC. In conclusion, residual cement extravasation negatively impacted osseointegrated implants after re-entry surgeries.

Calorie restriction in mice impairs cortical but not trabecular peak bone mass by suppressing bone remodeling.

Calorie restriction (CR) can lead to weight loss and decreased substrate availability for bone cells. Ultimately, this can lead to impaired peak bone acquisition in children and adolescence and bone loss in adults. But the mechanisms that drive diet-induced bone loss in humans are not well characterized. To explore those in greater detail, we examined the impact of 30% CR for 4 and 8wk in both male and female 8-wk-old C57BL/6J mice. Body composition, areal bone mineral density (aBMD), skeletal microarchitecture by micro-CT, histomorphometric parameters, and in vitro trajectories of osteoblast and adipocyte differentiation were examined. After 8wk, CR mice lost weight and exhibited lower femoral and whole-body aBMD vs ad libitum (AL) mice. By micro-CT, CR mice had lower cortical bone area fraction vs AL mice, but males had preserved trabecular bone parameters and females showed increased bone volume fraction compared to AL mice. Histomorphometric analysis revealed that CR mice had a profound suppression in trabecular as well as endocortical and periosteal bone formation in addition to reduced bone resorption compared to AL mice. Bone marrow adipose tissue was significantly increased in CR mice. In vitro, the pace of adipogenesis in bone marrow stem cells was greatly accelerated with higher markers of adipocyte differentiation and more oil red O staining, whereas osteogenic differentiation was reduced. qRT-PCR and western blotting suggested that the expression of Wnt16 and the canonical β-catenin pathway was compromised during CR. In sum, CR causes impaired peak cortical bone mass due to a profound suppression in bone remodeling. The increase in marrow adipocytes in vitro and in vivo is related to both progenitor recruitment and adipogenesis in the face of nutrient insufficiency. Long-term CR may lead to lower bone mass principally in the cortical envelope, possibly due to impaired Wnt signaling.

Bone mineral density assessment in patients with cystinuria.

Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine. Clinical features of cystinuria mainlyinclude nephrolithiasis and its complications, although cystinuric patients may present with other comorbidities. There are currently no data on bone features of patients with cystinuria. Our aim is to characterize bone mineral density (BMD) in cystinuria. Our study included adult cystinuric patients with estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73m2 followed at 3 specialized outpatient clinics in Italy (Rome, Naples and Verona). Markers of bone turnover were analyzed in a centralized laboratory. Clinical, biochemical and dual-energy X-ray absorptiometry (DEXA) data were collected from September 2021 to December 2022. Linear regression models were used to evaluate statistically significant deviations from zero of Z-scores. Twenty-seven patients were included in the study. Mean (SD) age was 37 (15) years, 41% were women. Mean estimated glomerular filtration rate was 99mL/min/1.73m2. Serum parameters associated with bone turnover (parathyroid hormone, FGF23, calcium and phosphate) were all in the normal range, with only 4 patients showing mild hypophosphatemia. Prevalence of low bone mineral density, defined as Z-score ≤ - 2 at any site, was 15%. Average Z-scores were negative across most sites. Our study suggests that cystinuric patients have lower bone mineral density compared with individuals of the same sex and age, even when theirkidney functionis normal.

A Morphological Study of Distal Femoral Varus Deformity.

Background In the management of medial compartment knee osteoarthritis via around-knee osteotomy (AKO) and total knee arthroplasty (TKA), evaluating the lateral distal femoral angle (LDFA) is crucial. This angle reflects the presence of distal femoral varus deformity. This study aims to explore the relationship between LDFA and lower extremity bone morphology and identify factors contributing to a high LDFA. Methods A retrospective analysis was conducted on 59 patients who underwent AKO or TKA at our hospital. Alignment of the lower extremity was assessed using X-rays, and bone morphology was investigated through computed tomography (CT) employing the ZedKnee® system(LEXI, Tokyo, Japan). Each measured parameter was analyzed. Results Our findings indicate a significant correlation between LDFA and several parameters, including age, femoral tibial angle (FTA), hip knee ankle angle (HKA), percentage of mechanical axis (% MA), femoral bowing angle, femoral tibial joint torsion, and the height of lateral and medial femoral condyles. A multiple-regression analysis determined that the most significant influences on LDFA were the heights of the femoral condyle, age, and HKA. Conclusion LDFA is significantly affected by the heights of the medial and lateral femoral condyles and tends to increase with age, possibly as a result of attrition of the medial femoral condyle. Given its significance, LDFA should be carefully considered as a preoperative indicator in AKO and TKA to guide surgical caution when LDFA is elevated.