Effects of long-term administration of pantoprazole on bone mineral density in young male rats

Matuszewska, Agnieszka; Nowak, Beata; Rzeszutko, Marta; Zduniak, Krzysztof; Szandruk, Marta; Jędrzejuk, Diana; Landwójtowicz, Marcin; Bolanowski, Marek; Pieśniewska, Małgorzata; Kwiatkowska, J; Szeląg, Adam

doi:10.1016/j.pharep.2016.06.012

Cited by 18 publications

(14 citation statements)

References 23 publications

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“…The topic remains a matter of debate. A positive, albeit modest, association between PPIs and OP was reported in animal [ 262 , 263 , 264 ] and numerous of human studies. Many studies and meta-analyses suggested that acid inhibitors, especially the PPIs, moderately increase risk of fractures, particularly in older adults (who are already at higher fracture risk); the risk increases with longer durations of PPI use, often only in the presence of at least one other RF for OP such as older age, female gender and a higher comorbidity score [ 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 , 289 , 290 ].…”

Section: Hpi-induced Upper Gut Diseases and Osteoporotic Fracturesmentioning

confidence: 95%

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

Fisher

Smith

2020

JCM

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Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world’s population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI–OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.

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Section: Hpi-induced Upper Gut Diseases and Osteoporotic Fracturesmentioning

confidence: 95%

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

Fisher

Smith

2020

JCM

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“…By contrast, Matuszewska et al (2016) did not detect any changes in bone microstructure of Wistar rats treated with pantoprazole (3 mg/kg for 84 days). 28 Similarly, Veggar et al (2017) did not observe changes in femoral trabecular and cortical structures of mice with impaired mobility and treated with pantoprazole (100 mg/kg bw daily, 3 weeks). However, they reported a marginally higher lumbar Tb.Th in these mice compared with the untreated mice.…”

Section: Discussionmentioning

confidence: 92%

<p>Effects of Calcium and Annatto Tocotrienol Supplementation on Bone Loss Induced by Pantoprazole in Male Rats</p>

Chin

Thong

Kamalulloh

et al. 2020

DDDT

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Prolonged use of proton pump inhibitors may cause bone loss, and limited therapeutic agents are available to prevent this skeletal side effect. The combination of annatto tocotrienol, a bone anabolic agent, with calcium presents a novel strategy to prevent bone loss caused by proton pump inhibitors. This study aims to compare the effects of calcium alone and in combination with annatto tocotrienol or vitamin D 3 (Caltrate Plus) in preventing bone loss caused by pantoprazole. Methods: Three-month-old Sprague Dawley male rats (n=30) were randomised into five groups (n=6/group). Bone loss was induced by pantoprazole (3 mg/kg p.o.) in four groups, and they were treated concurrently with either calcium carbonate (77 mg p.o.), calcium carbonate (77 mg p.o.) plus annatto tocotrienol (60 mg/kg p.o.) or Caltrate Plus (31 mg p.o.) for 60 days. The rats were euthanised at the end of the experiment, and their femurs were harvested for X-ray micro-computed tomography, bone cellular histomorphometry and bone mechanical strength analysis. Results: Pantoprazole caused significant deterioration of trabecular bone microstructures but did not affect other skeletal indices. Calcium supplementation with or without annatto tocotrienol prevented the deterioration of trabecular microstructures at the femur but did not improve other skeletal indices. Annatto tocotrienol did not enhance the skeletal actions of calcium, whereas Caltrate Plus did not affect the bone health indices in these rats. Conclusion: Calcium supplementation per se can prevent the deterioration of bone trabecular microstructures in rats receiving long-term treatment of pantoprazole.

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“…Clinical meta-analyses have also shown that PPI use increases the risk of hip, spine, or vertebral fracture (Ito and Jensen 2010 ; Yu et al 2011 ; van der Hoorn et al 2015 ; Chen et al 2016 ; Poly et al 2018 ), and patients treated with PPIs for two years are more likely to have a hip fracture (OR = 1.30, CI = 1.21–1.39) (Corley et al 2010 ). In addition, animal experiments showed that pantoprazole treatment for 12 weeks had a negative effect on bone metabolism in young male rats (Matuszewska et al 2016 ), and pantoprazole (100 mg/kg/day) could affect fracture healing in mice (Histing et al 2012 ; Menger et al 2020 ). However, there have been few studies on the molecular mechanism of the effect of PPIs on osteocytes in vitro.…”

Section: Introductionmentioning

confidence: 99%

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways

Cheng

Sun

et al. 2022

Mol Med

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Background Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine model of chronic oral PPI administration to verify whether PPIs caused bone metabolic impairment and investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 murine osteoblasts. Methods A lansoprazole-induced bone loss model was used to investigate the damaging effects of PPIs. In vivo, immunohistochemistry, Hematoxylin–Eosin (HE) staining, micro-CT analysis, and blood biochemical analyses were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects of lansoprazole and related signaling pathways in MC3T3-E1 cells were investigated by CCK-8 assays, EdU assays, flow cytometry, laser confocal microscopy, patch clamping, reverse transcription-quantitative polymerase chain reaction and Western blotting. Results After 6 months of lansoprazole gavage in ICR mice, the micro-CT results showed that compared with that in the vehicle group, the bone mineral density (BMD) in the high-dose group was significantly decreased (P < 0.05), and the bone microarchitecture gradually degraded. Biochemical analysis of bone serum showed that blood calcium and phosphorus were both decreased (P < 0.01). We found that long-term administration of lansoprazole impaired skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOCE pathway, effectively blocked increase in calcium caused by LPZ, thus protecting cell viability. Conclusions Longterm administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium increases in osteoblasts in a concentration-dependent manner. Intracellular calcium ([Ca2+]i) persisted at a high concentration, thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblast apoptosis.

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Effects of long-term administration of pantoprazole on bone mineral density in young male rats

Abstract: We observed that PPIs might have a negative impact on bone formation in growing rats mainly due to their inhibitory effects on the gastric proton pump, with probable deterioration of calcium absorption and decrease in growth plate thickness.

Cited by 18 publications

References 23 publications

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

<p>Effects of Calcium and Annatto Tocotrienol Supplementation on Bone Loss Induced by Pantoprazole in Male Rats</p>

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways

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