Systemic administration of omeprazole interferes with bone healing and implant osseointegration: an in vivo study on rat tibiae (original) (raw)

Biomechanical and biochemical evaluation of the effect of systemic application of omeprazole on the osseointegration of titanium implants

International Journal of Implant Dentistry

Background This study aimed to investigate the effects of systemic omeprazole treatment on the osseointegration of titanium implants. Material and methods After surgical insertion of titanium implants into the metaphyseal part of rats’ both right and left tibial bones, the animals were randomly divided into three equal groups: control (n = 8), omeprazole dosage-1 (n = 8) (OME-1), and omeprazole dosage-2 (n = 8) (OME-2) and totally 48 implants were surgically integrated. The rats in the control group received no treatment during the four-week postoperative experimental period. In the OME-1 and OME-2 groups, the rats received omeprazole in doses of 5 and 10 mg/kg, respectively, every 3 days for 4 weeks. After the experimental period, the rats were euthanized. One rat died in each group and the study was completed with seven rats in each group. Blood serum was collected for biochemical analysis, and the implants and surrounding bone tissue were used for biomechanical reverse-torque ana...

Effects of long-term administration of omeprazole on bone mineral density and the mechanical properties of the bone

Revista Brasileira de Ortopedia (English Edition), 2015

Objectives: Epidemiological studies have shown a relationship between long-term use of proton pump inhibitors and bone metabolism. However, this relationship has not yet become established. The aim of the present study was to analyze the mechanical properties and bone mineral density (BMD) of rats that were subjected to long-term omeprazole use. Methods: Fifty Wistar rats weighing between 200 and 240 g were divided equally into five groups: OMP300 (omeprazole intake at a dose of 300 moL/kg/day); OMP200 (200 moL/kg/day); OMP40 (40 moL/kg/day); OMP10 (10 moL/kg/day); and Cont (control group; intake of dilution vehicle). The solutions were administered for 90 consecutive days. After the rats had been sacrificed, their BMD, the mechanical properties of the dissected femurs and their serum Ca++ levels were analyzed. Results: The BMD of the OMP300 group was lower than that of the controls (p = 0.006). There was no difference on comparing the OMP200, OMP40 and OMP10 groups with the controls. The maximum strength and rigidity of the femur did not differ in the experimental groups in comparison with the controls. The OMP300 group had a statistically lower serum Ca++ concentration than that of the controls (p = 0.049), but the other groups did not show any difference in relation to the controls. Conclusion: Daily intake of 300 moL/kg/day of omeprazole decreased the BMD of the femur, but without changes to the rigidity and strength of the femur in adult rats.

Kinas M, Bilal Ö, Kıvrak A. Effect of Omeprazole on Fracture Healing in the RandomPatterned Rat Tibial Fracture Model: An Experimental Study. J Clin Pract Res 2023; 45(5): 447–55.

Journal of Clinical Practice and Research, 2023

Objective: Fractures represent one of the most common pathologies encountered in orthopedic practice. Various factors can impact fracture healing, both negatively and positively. This study aimed to investigate the influence of omeprazole, a proton pump inhibitor prescribed to mitigate the side effects of non-steroidal anti-ınflammatory drugs (NSAIDs) used for pain management post-fracture treatment and for deep vein thrombosis (DVT) prophylaxis, on fracture union through an animal experiment. Materials and Methods: The study utilized 40 male Wistar-Albino rats obtained from the Experimental Research Laboratory. Employing the simple randomization method, the animals were divided into experimental and control groups, with tibia fractures induced and subsequently fixed intramedullarily. At the conclusion of the sixth week, comprehensive histological, radiological, and biomechanical assessments were conducted to compare fracture union and bone biomechanical strength with the control group. Results: Histological and radiological evaluations were conducted on the tibias of 40 male Wistar-Albino rats. In terms of biomechanical analysis, 14 tibias from the control group and 16 tibias from the study group were examined. Remarkably, the study group exhibited superiors union compared to the control group both histologically (p=0.033), radiologically (AP1 view; p=0.040, AP2 view; p=0.036, LAT1 view; p=0.081, LAT2 view; p=0.03), and biomechanically (p=0.047), following omeprazole use. Conclusion: The administration of omeprazole as a proton pump inhibitor following fracture treatment contributes positively to the process of fracture healing.

Postoperative Administration of the Acetylcholinesterase Inhibitor, Donepezil, Interferes with Bone Healing and Implant Osseointegration in a Rat Model

Biomolecules

Donepezil is an acetylcholinesterase inhibitor commonly used to treat mild to moderate Alzheimer’s disease. Its use has been associated with increased bone mass in humans and animals. However, the effect of postoperative administration of donepezil on bone healing remains unknown. Therefore, this study aimed to assess the impact of postoperative injection of donepezil on bone healing, titanium-implant osseointegration, and soft tissue healing. Twenty-two Sprague-Dawley rats were randomly assigned to receive a daily dose of either donepezil (0.6 mg/kg) or saline as a control. In each rat, a uni-cortical defect was created in the right tibia metaphysis and a custom-made titanium implant was placed in the left tibiae. After two weeks, rats were euthanized, and their bones were analysed by Micro-CT and histology. The healing of bone defect and implant osseointegration in the rats treated with donepezil were significantly reduced compared to the saline-treated rats. Histomorphometric ana...

Does locally delivered Zoledronate influence peri-implant bone formation? – Spatio-temporal monitoring of bone remodeling in vivo

Biomaterials, 2014

Bisphosphonates are known for their strong inhibitory effect on bone resorption. Their influence on bone formation however is less clear. In this study we investigated the spatio-temporal effect of locally delivered Zoledronate on peri-implant bone formation and resorption in an ovariectomized rat femoral model. A cross-linked hyaluronic acid hydrogel was loaded with the drug and applied bilaterally in predrilled holes before inserting polymer screws. Static and dynamic bone parameters were analyzed based on in vivo microCT scans performed first weekly and then biweekly. The results showed that the locally released Zoledronate boosted bone formation rate up to 100% during the first 17 days after implantation and reduced the bone resorption rate up to 1000% later on. This shift in bone remodeling resulted in an increase in bone volume fraction (BV/TV) by 300% close to the screw and 100% further away. The double effect on bone formation and resorption indicates a great potential of Zoledronateloaded hydrogel for enhancement of peri-implant bone volume which is directly linked to improved implant fixation. . Bone formation rate measured in 4 layers around the screw, the gray asterisks indicate the significant differences between ZoleGel-group and Gel-group, the black ones between Control-group and ZoleGel-group.

The Evaluation of omeprazole effect on the sensitivity of 99mTc-MDP bone-seeking to detect simulated closed fracture in the rat’s foot

iranian journal of nuclear medicine, 2017

Introduction: Omeprazole (OP) is one the proton pump inhibitor (PPI) agents, and available over the counter in generic formulations. Epidemiological investigations have been confirmed a relationship between long term use of PPI agents and bone metabolism. Bone scintigraphy is commonly used for analysing the bone metabolism in clinical practice. This study was conducted to assess the effect of omeprazole on the sensitivity of bone imaging to distinguish simulated closed fracture in the rat's foot. Methods: A total number of 32 adult, male NMRI were chosen. The animals were divided into two principle groups equally for four and eight weeks experiment. Each group was equally divided into four groups. These subgroups included the standard or control rats (4W S and 8W S) not receiving omeprazole and the others that received 25 (4W OP 25 and 8W OP 25), 50 (4W OP 50 and 8W OP 50), 100 (4W OP 100 and 8W OP 100) mg/kg of the drug. Reproducible closed fracture was created in the rat's...

Short-Term Omeprazole Treatment Does Not Influence Biochemical Parameters of Bone Turnover in Children

Calcified Tissue International, 2002

Gastric proton pump inhibitors are widely used in the treatment of dyspeptic problems and for the eradication of H. pylori infection. Data are not available on whether omeprazole, a representative of proton pump inhibitors, in¯uences the function of osteoclastic H + -pump in children. We studied the impact of shortterm omeprazole administration on the biochemical parameters of bone turnover in pediatric patients. Urinary calcium excretion, serum total alkaline phosphatase activity, collagen type 1 crosslinked C-telopeptide, and osteocalcin levels were determined in 34 children [20 girls (9 prepubertal) and 14 boys (6 prepubertal)] before and after 2 weeks of omeprazole treatment at a dose of 20 mg/day. The measured parameters were within the healthy reference range in each patient. None of them altered during the study in any age or in any gender. We conclude that omeprazole, at a dose of 20 mg/day, does not signi®cantly in¯uence the investigated biochemical parameters of osteoclast and osteoblast function in pediatric patients.

Short-Term Omeprazole Use Does Not Affect Serum Calcium Concentrations and Bone Density in Horses

Journal of Equine Veterinary Science, 2015

Omeprazole is used to treat gastric ulcers in horses. In some human and experimental animal studies, proton pump inhibitor use has been associated with a change in bone density or fracture risk. This study evaluated the effects of administration of omeprazole for 60 days and its effects on serum total calcium, ionized serum calcium, bone mineral content (BMC), and bone mineral density (BMD) in horses. Blood samples and bone biopsies from the tibia were collected from 10 geldings aged 2 and 3 years old before beginning treatment. Horses were administered either 4 mg/kg omeprazole paste or an equal volume of vehicle only paste orally once per day for 60 days. Blood samples were taken at days 7, 14, 21, 28, 35, 42, 49, 56, and 60. Serum total calcium and ionized calcium were measured on all samples. Horses were euthanized on day 60, and bone was harvested from all horses from the contralateral tibia. In addition, the third metacarpal bones and proximal femurs were harvested from each subject. Bone samples were evaluated for BMD and BMC using peripheral quantitative computed tomography (pQCT). Serum total calcium and ionized calcium concentrations were not significantly different between treated and control groups. Bone density and composition were also not significantly different when compared between control and treatment groups. Short-term administration of omeprazole does not significantly affect serum total calcium and ionized serum calcium concentrations nor does it affect bone density or BMC in normal horses as measured with pQCT.

Effect of Meloxicam and Diclofenac Sodium on Peri-Implant Bone Healing in Rats

Journal of Periodontology, 2008

Background: This study evaluated the effects of diclofenac sodium and meloxicam on peri-implant bone healing. Methods: Thirty male rats were divided into three groups: the control group (CG) received no drug; the diclofenac sodium group (DSG) received 1.07 mg/kg twice a day for 5 days; and the meloxicam group (MG) received 0.2 mg/kg daily for 5 days. A screw-shaped titanium implant was placed in the tibia. Fluorochromes, oxytetracycline (OxT), calcein (CA), and alizarin (AL), were injected at 7, 14, and 21 days, respectively, after implantation, and the animals were sacrificed 28 days after implant placement. The percentages of OxT-, CA-, and ALlabeled bone as well as the percentages of bone-to-implant contact (BIC), cortical bone area (CBA), and trabecular bone area (TBA) within the implant threads were evaluated. Results: Bone healing was delayed in the DSG during the first 14 days after implant placement (OxT-labeled bone: DSG: