Clinical Presentations and Risk Factors of Gastrointestinal Bleeding in the Emergency Department: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Gastrointestinal bleeding is a major healthcare burden and is associated with significant morbidity and mortality. This study aimed to assess the prevalence, clinical presentation, and risk factors of patients presenting with gastrointestinal bleeding in the emergency department. MATERIALS AND METHODS: This retrospective study was conducted in two tertiary care hospitals in Riyadh, Saudi Arabia. The medical records of patients who presented to the emergency department with gastrointestinal bleeding between January 2010 and January 2020 were reviewed. Patients aged 18 years or older, with gastrointestinal bleeding (upper or lower) regardless of underlying cause, lifestyle, location of bleeding, health status, or medication use, were included. Demographic characteristics, initial vital signs, medical history, physical examination findings, comorbidities, medications, laboratory and radiological investigations, cause and stage of liver disease, management, and complications were recorded. Endoscopic findings and management of the bleeding site were collected according to the presenting symptoms. RESULTS: A total of 760 patients were included. The mean age was 62.7 ± 17.8 years, and 61.4% were males. The most common comorbidities at presentation were hypertension (54.1%), diabetes mellitus (51.2%), and ischemic heart disease (18.2%). The origins of the bleeding were lower gastrointestinal in 52% and upper gastrointestinal in 48% of patients. CONCLUSIONS: Lower gastrointestinal bleeding was found to be more common than upper gastrointestinal bleeding. Hemorrhoids, polyps, diverticular disease, and colonic ulcers were the major risk factors for lower gastrointestinal bleeding. In contrast, upper gastrointestinal bleeding was predominantly caused by esophageal varices, gastritis, and peptic ulcers.

Effectiveness of Topical Oxygen Therapy in Gingivitis and Periodontitis: Clinical Case Reports and Review of the Literature.

Gingivitis and periodontitis are common oral pathological conditions. Several optional adjunctive local therapies are used clinically. While antibiotics and chlorhexidine are the most common agents of choice, their long-term use is associated with several adverse effects. Some of these include staining of teeth and restorations, cellular cytotoxicity and hypersensitivity. Topical oxygen therapy has been recently introduced and could be clinically capable of inhibiting plaque bacterial biofilm growth. Available as a mouthwash, toothpaste and oral gel, this formulation comprises cellulose, glycerol and sodium peroxoborate, and releases topical oxygen in a controlled manner. Moreover, it releases topical oxygen, in a controlled manner, and lactoferrin, which are capable of antibacterial action and stimulation of bone cells, respectively. The aim of this paper is to report a case of gingivitis and another case of periodontitis, both of which were successfully treated clinically with adjunctive local oxygen therapy (blue®m). Additionally, this paper aims to review the relevant literature in terms of adjunct topical or local therapies used in the treatment of gingivitis and periodontitis, in order to understand how local therapies are helpful and to know if local oxygen therapy is a suitable clinical alternative.

Local Oxygen-Based Therapy (blue®m) for Treatment of Peri-Implant Disease: Clinical Case Presentation and Review of Literature about Conventional Local Adjunct Therapies.

Peri-implant diseases including peri-implant mucositis and peri-implantitis are among the major causes of failure of implant-supported dental restorations. They are characterized by progressive inflammation of the peri-implant mucosa, extending to the surrounding connective tissues and leading to bone loss and implant failure. Although strict oral hygiene practices help in preventing peri-implant diseases, plaque buildup around the implant restoration leads to chronic inflammation, due to the adherent bacterial biofilm. While mechanical debridement and non-surgical therapy to remove inflamed connective tissue (ICT) form the mainstay of treatment, additional local adjunctive therapies enhance clinical outcomes. Topical oxygen therapy is known to reduce inflammation, increase vascularity, and act as a bacteriostatic measure. The use of oxygen-based therapy (blue®m) products as a local adjunctive therapy for peri-implant mucositis and peri-implantitis can result in clinical outcomes similar to that of conventional local adjuncts such as chlorhexidine, antibiotics, and antibacterial agents. This report aims to present the clinical findings of patients with peri-implant mucositis and peri-implantitis, who were managed using local oxygen-based therapy as an adjunct to non-surgical therapy. In addition, a review of the literature about commonly used local adjuncts for peri-implant diseases has been included in the report to provide a means of comparison between conventional local adjunct therapy and topical oxygen-based therapy. Based on the reported findings and reviewed literature, local oxygen-based adjunct therapy was equally effective as conventionally used local adjuncts such as antibiotics, antibacterials, and probiotics, in treating patients with peri-implant diseases.

SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024.

ABSTRACT: Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.

Effectiveness of generic sofosbuvir in the treatment of chronic hepatitis C virus infection in Saudi patients.

OBJECTIVES: To assess the effectiveness of generic sofosbuvir (SOF) and branded daclatasvir (DCV) for the treatment of chronic hepatitis C virus (HCV)infected patients. METHODS: This retrospective study, performed in a single center in Saudi Arabia between August 2017 and July 2022, we enrolled 140 consecutive patients with HCV who received generic SOF and branded DCV. The primary outcome was sustained virologic response at week 12 (SVR12). RESULTS: The majority of the patients were female (62.1%), infected with genotype 4 (57.9%), and treatment-naïve in 120 (85.7%) patients with baseline cirrhosis in 55 (39.3%). The mean patient age was 61±13.6 years. In the intention-to-treat analysis, 131 (93.6%) patients achieved SVR12. Moreover, 85.7%, 100%, 100%, 88.9%, and 96.3% of genotypes 1a, 1b, 2, 3, and 4, respectively, achieved SVR12. In the per-protocol analysis, 131 (96.3%) patients achieved an SVR of 12. Additionally, 92.3%, 100%, 100%, 88.9%, and 98.7% of the patients with genotypes 1a, 1b, 2, 3, and 4, respectively, achieved SVR12. No HCV virologic breakthroughs occurred. In the subgroup analysis, SVR12 rates were comparable regardless of baseline characteristics, such as treatment history, cirrhosis, and hepatocellular carcinoma. Patients achieving SVR12 showed a significant improvement in post-treatment serum liver enzyme and total bilirubin levels. CONCLUSION: The findings of our study confirm the effectiveness of generic sofosbuvir as a treatment option for HCV infection.

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score.

BACKGROUND: Vietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years. METHODS: We plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data. DISCUSSION: The present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.

Would a 6-Month Wait Time for Patients With Hepatocellular Carcinoma Improve Organ Allocation in Centers With Active Living Related Liver Transplant Activity?

OBJECTIVES: The Model for End-Stage Liver Disease score is used to prioritize patients awaiting liver transplant. Since hepatocellular carcinoma does not affect the score, patients with hepatocellular carcinoma are given exception points to promote fairness. In the United States,this practice has resulted in overcorrection; hence, a 6-month delay to grant exceptions was implemented. A similar flaw may exist in Saudi Arabia. MATERIALS AND METHODS: We retrospectively reviewed data for 214 adults listed for liver transplant from January 2016 to July 2020 at King Abdulaziz Medical City, Riyadh. Data included diagnoses, Model for End-Stage Liver Disease scores, wait times, and outcomes. Comparative analyses were performed to contrast patients with hepatocellular carcinoma versus patients without hepatocellular carcinoma. RESULTS: Mean age was 55.2 ± 11.6 years, and 61% were male patients. Outcomes were that the patient received a transplant(77%; n = 165/214), dropped out (18%; n = 38/214), or remained on the wait (5%; n = 11/214). Of the hepatocellular carcinoma group, 84% (n = 56/68) received transplant versus 74% (n = 108/146) in the control group (P = .11). There was no significant difference in dropout rates (P = .33). Patients with hepatocellular carcinoma constituted 32% (n = 68/214) ofthe waitlist, yetthey received 40% of deceased organ offers (P = .015). Most patients in the hepatocellular carcinoma group received pretransplant bridging therapy for a median of 166 days (101-329.5 days). Median time from listing to transplant was shorter for the control group, 57 days versus 148 days (P < .001). Long-term outcomes were comparable between both groups. CONCLUSIONS: This study suggests that implementation of the 6-month wait time for patients with hepatocellular carcinoma before granting exception points may not be necessary for active living related liver transplant programs. Nevertheless, this remains a sound strategy to follow.

The use of portable OSL and IRSL measurements of NaCl in low dose assessments following a radiological or nuclear emergency.

During recovery phases following a nuclear or radiological incident analyses of doses received by members of the public and responders are often required. Several methods have been investigated for use at different timescales after the incident, including assessments based on measurements of materials present at the time of the incident. Common salt has previously been shown to have potential for retrospective dosimetry in the mGy dose range using laboratory instrumentation. This preliminary study investigates the use of portable instruments, with unprepared commercially sourced salt, in dose ranges below 100 µGy. Responses from pulsed IRSL and portable OSL instruments were compared. For OSL measurements, detection limits of 7 µGy have been demonstrated, with detection limits of 30-340 µGy for the other instruments investigated. Dose responses in the 0-500 µGy range were determined for the most sensitive systems, which show a linear response over this dose range with a non-zero intercept representing doses received from environmental sources since manufacture of the salt. For use as a dosimeter, methods of removing or accounting for inherited signals will be required in this low dose range. The results demonstrate that salt has considerable potential for use in retrospective dosimetry below 100 µGy, and that measurements can be conducted with portable OSL instruments.

Case Report: Dubin-Johnson Syndrome Presenting With Infantile Cholestasis: An Overlooked Diagnosis in an Extended Family.

Dubin-Johnson syndrome (DJS) is an often-missed diagnosis of neonatal cholestasis. We report two patients with DJS, who presented with neonatal cholestasis. The first patient underwent extensive investigations for infantile cholestasis with no definitive etiology reached; the diagnosis of DJS was missed until the age of 14 years old. The diagnosis was confirmed genetically with c.2273G > T, p.G758V mutation in exon 18 of the ABCC2 gene. The 2nd patient is a 7-day-old baby, the son of the 1st patient who gave birth to him at the age of 21 years old. He was diagnosed with DJS at the age of 2 weeks based on normal clinical and laboratory workup apart from direct hyperbilirubinemia. He had the same mutation as his mother in homozygous status. The husband was heterozygous for the same mutation. DJS is one of the often-missed differential diagnoses of neonatal cholestasis. It should be suspected in patients of infantile cholestasis, who have an, otherwise, normal physical examination, and laboratory investigations to avoid unnecessary lengthy, invasive, and expensive workups.

Lower prevalence of hepatic fibrosis in low viremic hepatitis B patients with fluctuating HBV DNA levels.

Background: In chronic hepatitis B virus (HBV) patients, fluctuations in HBV DNA serve as a "gray area" and impede the accurate identification of inactive carriers. We aimed to assess if such fluctuations impact the presence of significant hepatic fibrosis (Metavir F2-4) in chronic HBV patients. Methods: Consecutive, untreated HBeAg-negative carriers (n = 234) with fluctuating HBV DNA (n = 73) above or below a level of 2000 IU/mL were included and compared to those without fluctuations (n = 161). Patients without fluctuating HBV DNA were further analyzed based on those with persistently low (<2,000 IU/mL, n = 137) and higher HBV DNA (2,000-20,000 IU/mL, n = 24). Hepatic fibrosis (assessed by transient elastography) was correlated with virologic and biochemical profiles. Results: The mean age of the overall cohort was 47.8 ± 11.1 years, of whom 107 (45.7%) were male. During a median of 60 months (interquartile range [IQR] 34-82) of follow-up, 73 (31.2%) patients had a mean of 1.6 ± 0.9 fluctuations in HBV DNA. The median time to the first fluctuation was at 14.5 (IQR 5.0-33.7) months. Patients with fluctuating viremia had higher log10 qHBsAg (3.1 ± 0.8 vs. 2.7 ± 1.0, P = 0.022) and HBV DNA (3.4 ± 0.5 vs. 2.7 ± 0.8, P < 0.001) compared to those without fluctuations. Patients with fluctuant viremia were less likely to have F2-4 fibrosis (8.2%) compared to those without fluctuant viremia (18.2%, odds ratio [OR]: 0.407, 95% confidence interval [CI]: 0.161-1.030; P = 0.052). Males tended to have less fluctuation constituting 37.0% of patients with fluctuating HBV DNA (P = 0.071). Fluctuations occurred more frequently in those with predominantly higher HBV DNA levels (26.0%) compared to those without fluctuations (14.9%; P = 0.030). Conclusions: Fluctuating HBV DNA levels occur frequently but are not associated with significant fibrosis. Minor fluctuations in HBV DNA levels are unlikely to be of clinical relevance.

Surface Engineering for Dental Implantology: Favoring Tissue Responses Along the Implant.

Dental implants represent an illustrative example of successful medical devices used in increasing numbers to aid (partly) edentulous patients. Particularly in spite of the percutaneous nature of dental implant systems, their clinical success is remarkable. This clinical success is at least partly related to the effective surface treatment of the artificial dental root, providing appropriate physicochemical properties to achieve osseointegration. The demographic changes in the world, however, with a rapidly increasing life expectancy and an increase in patients suffering from comorbidities that affect wound healing and bone metabolism, make that the performance of dental implants requires continuous improvement. An additional factor endangering the clinical success of dental implants is peri-implantitis, which affects both the soft and hard tissue interactions with dental implants. In this study, we shed light on the optimization of dental implant surfaces through surface engineering. Depending on the region along the artificial dental root, different properties of the surface are required to optimize prevailing tissue response to facilitate osseointegration, improve soft tissue attachment, and exert antibacterial efficacy. As such, surface engineering represents an important tool for assuring the continued future success of dental implants. Impact Statement Dental implants represent a common treatment modality nowadays for the replacement of lost teeth or fixation of prosthetic devices. This review provides a detailed overview of the role of surface engineering for dental implants and their components to optimize tissue responses at the different regions along the artificial dental root. The surface properties steering immunomodulatory processes, facilitating osseointegration, and rendering antibacterial efficacy (at both artificial root and abutment region) are described. The review finally concludes that surface engineering provides a tool to warrant that dental implants will remain future proof in more challenging applications, including an aging patient population and comorbidities that affect bone metabolism and wound healing.

Histological evaluation of titanium fiber mesh-coated implants in a rabbit femoral condyle model.

OBJECTIVES: This study was aimed to comparatively evaluate new bone formation into the pores of a flexible titanium fiber mesh (TFM) applied on the surface of implant. METHODS: Twenty-eight custom made cylindrical titanium implants (4 ×10 mm) with and without a layer of two different types of TFM (fiber diameter of 22 µm and 50 µm, volumetric porosity ~70%) were manufactured and installed bilaterally in the femoral condyles of 14 rabbits. The elastic modulus for these two TFM types was ~20 GPa and ~5 GPa respectively, whereas the solid titanium was ~110 GPa. The implants (Control, TFM-22, TFM-50) were retrieved after 14 weeks of healing and prepared for histological assessment. The percentage of the bone area (BA%), the bone-to-implant contact (BIC%) and amount were determined. RESULTS: Newly formed bone into mesh porosity was observed for all three types of implants. Histomorphometric analyses revealed significantly higher (~2.5 fold) BA% values for TFM-22 implants (30.9 ± 9.5%) compared to Control implants (12.7 ± 6.0%), whereas BA% for TMF-50 did not significantly differ compared with Control implants. Furthermore, both TFM-22 and TFM-50 implants showed significantly higher BIC% values (64.9 ± 14.0%, ~2.5 fold; 47.1 ± 14.1%, ~2 fold) compared to Control (23.6 ± 17.4%). Finally, TFM-22 implants showed more and thicker trabeculae in the peri-implant region. SIGNIFICANCE: This in vivo study demonstrated that implants with a flexible coating of TFM improve bone formation within the inter-fiber space and the peri-implant region.

Peri-Implant bone response around porous-surface dental implants: A preclinical meta-analysis.

INTRODUCTION: This meta-analysis of relevant animal studies was conducted to assess whether the use of porous-surface implants improves osseointegration compared to the use of non-porous-surface implants. MATERIAL AND METHODS: An electronic search of PubMed (MEDLINE) resulted in the selection of ten animal studies (out of 865 publications) for characterization and quality assessment. Risk of bias assessment indicated poor reporting for the majority of studies. The results for bone-implant contact (BIC%) and peri-implant bone formation (BF%) were extracted from the eligible studies and used for the meta-analysis. Data for porous-surface implants were compared to those for non-porous-surface implants, which were considered as the controls. RESULTS: The random-effects meta-analysis showed that the use of porous-surface implants did not significantly increase overall BIC% (mean difference or MD: 3.63%; 95% confidence interval or 95% CI: -1.66 to 8.91; p = 0.18), whereas it significantly increased overall BF% (MD: 5.43%; CI: 2.20 to 8.67; p = 0.001), as compared to the controls. CONCLUSION: Porous-surface implants promote osseointegration with increase in BF%. However, their use shows no significant effect on BIC%. Further preclinical and clinical investigations are required to find conclusive evidence on the effect of porous-surface implants.

Clinical and Metabolic Characteristics of Non-Alcoholic Fatty Liver Disease Patients in Saudi Arabia: Data from the Systematic Observatory Liver Disease (SOLID) Registry.

BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in Saudi Arabia (SA), but descriptions of the clinical and metabolic characteristics of these patients are limited. The present study aims to fill this gap. METHODS: Demographic, clinical, and laboratory data of all NAFLD patients from 2009 to 2019 were retrieved from the Systematic Observatory Liver Disease Registry (SOLID) [n=832 (337 males; 495 females); mean (± standard deviation, SD) age was 42.6±13.6 years; mean body mass index (BMI) was 35.0±9.3kg/m2]. Non-invasive surrogate scores of fibrosis (eg AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4), and NAFLD fibrosis (NFS) scores) were calculated and analyzed. In addition, data from NAFLD patients with normal and high alanine aminotransferase (ALT) were compared using two different methods: the standard laboratory reference range which defines normal as ALT<61 IU/L, and the range proposed by a recent national study which sets upper limits of normal ALT at 33 IU/l for men and 22 IU/l for women. RESULTS: Hyperlipidemia was the most common comorbidity (41.7%), followed by type 2 diabetes mellitus (T2DM) (35.3%) and hypertension (28.4%). Prevalence of advanced fibrosis varied widely across definitions [FIB-4, N=19 (2.5%); APRI, N=21 (2.8%); NFS, N=62 (8.6%)] and exhibited sexual dimorphism with males having worse metabolic characteristics. NAFLD patients with normal ALT were more likely to be older, female, have a lower BMI, and have a higher prevalence of cirrhosis, DM, hypertension, hyperlipidemia, and renal dysfunction. CONCLUSION: Patients with NAFLD have metabolic characteristics associated with several comorbidities, including NAFLD patients with normal ALT. Mechanistic studies are needed to examine and analyze complex, interactive effects between sex, age, and other factors that may accelerate NAFLD disease progression.

Favorable response to carbamazepine therapy in genetically proven myoclonus-dystonia child.

BACKGROUND: Myoclonus dystonia (MDS) is a dominantly inherited genetic disorder caused by loss-of-function mutations in the epsilon sarcoglycan gene (SGCE). CASE PRESENTATION: We here in report a twenty months old Saudi boy who presented to us with a concern that the child is unable to walk properly. On assessment, he was flexing his left arm and left leg that usually followed by a back-ward fall. Diagnosis of dystonia induced with initiation of movement was suggested that later on proven genetically to be pathogenic mutation of sarcoglycan gene. Carbamazepine therapy was initiated with dramatic response. Response was maintained at 4 years follow up. CONCLUSIONS: Our patient and the other previously reported cases might highlight the response of SGCE mutations to carbamazepine therapy.

Histological and Histomorphometric Analyses of Bone Regeneration in Osteoporotic Rats Using a Xenograft Material.

We evaluated the effect of osteoporotic induction after eight weeks of initial healing of bone defects grafted with a xenograft material in a rat model. Bone defects were created in the femoral condyles of 16 female Wistar rats (one defect per rat). The defects were filled with bovine bone (Inter-Oss) granules. After eight weeks of bone healing, rats were randomly ovariectomized (OVX) or sham-operated (SHAM). At 14 weeks of bone healing, all animals were euthanized. Bone specimens were harvested and processed for histological and histomorphometric analyses to assess new bone formation (N-BF%), remaining bone graft (RBG%) and trabecular bone space (Tb.Sp%) within the defect area. After 14 weeks of bone healing, histological evaluation revealed a significant alteration in trabecular bone in OVX rats compared to SHAM rats. There was lower N-BF% in OVX rats (22.5% ± 3.0%) compared to SHAM rats (37.7% ± 7.9%; p < 0.05). Additionally, the RBG% was significantly lower in OVX (23.7% ± 5.8%) compared to SHAM (34.8% ± 9.6%; p < 0.05) rats. Finally, the Tb.Sp% was higher in OVX (53.8% ± 7.7%) compared to SHAM (27.5% ± 14.3%; p < 0.05) rats. In conclusion, within the limitations of this study, inducing an osteoporotic condition in a rat model negatively influenced bone regeneration in the created bone defect and grafted with a xenograft material.

Impact of Single or Combined Drug Therapy on Bone Regeneration in Healthy and Osteoporotic Rats.

Complications in bone regeneration in patients with systemic impaired bone metabolism (e.g., osteoporosis) represent a rapidly increasing clinical challenge. Alendronate and simvastatin are drugs commonly used to promote bone metabolism in osteoporotic conditions. The aim of this study was to evaluate initial bone regeneration within osseous defects grafted with beta-tricalcium phosphate (ß-TCP) in adjunction with systemic coadministrations of alendronate and simvastatin (i.e., daily subcutaneous injection for 3 weeks) in healthy and osteoporotic rats. Eighty Wistar female rats were ovariectomized (OVX; n = 40) or sham operated (n = 40). Six weeks later, osseous defects (a 3-mm critical-sized defect) were created in the left femoral condyles and then grafted with ß-TCP. From the day following graft installation, OVX and sham animals received for 3 weeks a daily subcutaneous injection of alendronate (50 µg/kg of body weight) and simvastatin (5 mg/kg of body weight), alone or in combination. A control group was included, which received subcutaneous saline administration. At the end of the 3 weeks, rats were euthanized and specimens (femoral condyles) were retrieved for histological evaluation and histomorphometric measurements, that is, bone area (BA%) and remaining bone graft (RBG%). In osteoporotic rats, 3 weeks of daily subcutaneous injection of combined therapy (alendronate plus simvastatin) led to a significant (p < 0.05) increase in BA% and a significant decrease in RBG% compared to healthy controls in osseous defects grafted with ß-TCP (BA%: 28.6 ± 12.0 vs. 18.2 ± 7.6, RBG% 61.3 ± 11.1 vs. 70.7 ± 7.3). No significant differences in BA% and RBG% were found in the OVX rats for single treatments. Furthermore, healthy controls showed similar BA% and RBG% upon single or combined therapy compared to nontreated control rats. Daily coinjections (for 3 weeks) of alendronate plus simvastatin result in a significant enhancement of bone regeneration within osseous defects grafted with ß-TCP in osteoporotic rats. Despite the expected effects on osteoporotic bone, our study did not confirm the hypothesized benefit of alendronate and simvastatin on bone regeneration in osseous defects in healthy conditions. The efficacy of the combination drug therapy on bone regeneration demands further investigation to elucidate molecular and cellular aspects underlying this therapy.

Histomorphometric Evaluation of Peri-Implant Bone Response to Intravenous Administration of Zoledronate (Zometa®) in an Osteoporotic Rat Model.

We evaluated the response to peri-implant bone placed in the femoral condyle of osteoporotic rats, following intravenous zoledronate (ZOL) treatment in three settings: pre-implantation (ZOL-Pre), post-implantation (ZOL-Post), and pre- + post-implantation (ZOL-Pre+Post). Twenty-four female Wistar rats were ovariectomized (OVX). After 12 weeks, the rats received titanium implants in the right femoral condyle. ZOL (0.04 mg/kg, weekly) was administered to six rats 4 weeks pre-implantation and was stopped at implant placement. To another six rats, ZOL was given post-implantation and continued for 6 weeks. Additional six rats received ZOL treatment pre- and post-implantation. Control animals received weekly saline intravenous injections. At 6 weeks post-implantation, samples were retrieved for histological evaluation of the percentage of bone area (%BA) and of the percentage of bone-to-implant contact (%BIC). BA% for ZOL-Pre (29.6% ± 9.0%) and ZOL-Post (27.9% ± 5.6%) rats were significantly increased compared to that of the controls (17.3% ± 3.9%, p < 0.05). In contrast, ZOL-Pre+Post rats (20.4% ± 5.0%) showed similar BA% compared to Saline controls (p = 0.731). BIC% revealed a significant increase for ZOL-Post (65.8% ± 16.9%) and ZOL-Pre+Post (68.3% ± 10.0%) rats compared with that of Saline controls (43.3% ± 9.6%, p < 0.05), while ZOL-Pre rats (55.6% ± 19%) showed a BIC% comparable to that of Saline controls (p = 0.408). Our results suggest that receiving intravenous ZOL treatment before or after implant placement enhances peri-implant bone responses in terms of bone area. However, the effect of different ZOL treatment regimens on BIC% was found to be inconclusive.