The Biomechanical Testing for the Assessment of Bone Quality in an Experimental Model of Chronic Kidney Disease

Oksztulska-Kolanek, Ewa; Znorko, Beata; Michałowska, Małgorzata; Pawlak, Krystyna

doi:10.1159/000442714

Cited by 24 publications

(10 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The bone strength in the course of CKD can be quantitatively measured by the biomechanical analysis based on the bone strength, stiffness and ability to absorb energy (Turner and Burr, 1993 ; Turner, 2006 ). The three-point bending test is commonly used to measure the bone properties of the cortical bone in rodents and other small animals (Oksztulska-Kolanek et al, 2016 ). In our study, stiffness, yield load, and ultimate load were significantly increased in older compared to younger animals.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

et al. 2017

Self Cite

View full text Add to dashboard Cite

The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD) represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx)-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD. The animals were sacrificed 1 and 3 months after 5/6 Nx or sham operation. Nephrectomized rats presented higher concentrations of serum creatinine, urea nitrogen, and parathyroid hormone both 1 and 3 months after nephrectomy. These animals revealed higher concentrations of kynurenine and 3-hydroxykynurenine in the serum and higher gene expression of aryl hydrocarbon receptor (AhR) as a physiological receptor for kynurenine and AhR-dependent cytochrome in the bone tissue. Furthermore, nephrectomy significantly increased the number of osteoclasts in the bone without affecting their resorptive activity measured in serum. These changes were particularly evident in rats 1 month after 5/6 Nx. The main bone biomechanical parameters of the tibia were unchanged between nephrectomized and sham-operated rats but were significantly increased in older compared to younger animals. A similar trend was observed for geometrical parameters measured with calipers, bone mineral density based on Archimedes' method and image of bone microarchitecture obtained from micro-computed tomography analyses of tibial cortical bone. In nephrectomized animals, peripheral kynurenine levels correlated negatively with the main parameters of bone biomechanics, bone geometry, and bone mineral density values. In conclusion, our data suggest that CKD-induced elevated levels of peripheral kynurenine cause pathological changes in bone structure via AhR pathway. This finding opens new opportunities for the treatment/prevention of osteoporosis in CKD.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Ultimate load is the maximum value of load attained during the bending test which is necessary to cause the fracture of the bone. Moreover, work to fracture represents the work that must be performed to fracture the bone (Turner, 2006 ; Oksztulska-Kolanek et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…The testing was performed using machine Zwick Roell Z.2.5 (Zwick, Stuttgart, Germany). Bone mechanical parameters included stiffness, the resistance of the tibia diaphysis to deformation (yield load), the resistance of the tibia diaphysis to fracture (ultimate load), their displacements, and work to fracture (Oksztulska-Kolanek et al, 2016). …”

Section: Methodsmentioning

confidence: 99%

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

Kałaska

Pawlak

Oksztulska-Kolanek

et al. 2017

PeerJ

Self Cite

View full text Add to dashboard Cite

BackgroundDisturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD.MethodsThirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites.ResultsSubtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry.DiscussionIn addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone changes in the course of CKD.

show abstract

“…According to the load-displacement curve, stiffness is measured in units of load per displacement (N/mm) and the slope of the elastic region represents the extrinsic stiffness, which is closely linked with the mineralization of the bone [ 18 , 19 ]. Toughness is a measure of the amount of energy needed to cause fracture [ 20 ]. It reflects work per unit of material needed to be done before fracture in mJ.…”

Section: Resultsmentioning

confidence: 99%

Vitamin D Auto-/Paracrine System Is Involved in Modulation of Glucocorticoid-Induced Changes in Angiogenesis/Bone Remodeling Coupling

Lisakovska

Shymanskyi

Labudzynskyi

et al. 2020

International Journal of Endocrinology

View full text Add to dashboard Cite

Osteoporosis is a devastating side effect of chronic glucocorticoid (GC) treatment. Despite the crucial role of vitamin D (VD) in bone homeostasis, the precise molecular mechanisms of its action on GC-induced disturbances of bone remodeling remain undefined. The study was performed to elucidate the relation of VD status to GC-induced changes of the angiogenesis/osteogenesis/bone resorption coupling in bone tissue. Female Wistar rats received prednisolone (5 mg/kg of b.w.) with or without VD3 (1000 IU/kg of b.w., for 30 days). Biomechanical parameters of rat femurs were assessed by the three-point bending test. The levels of calcium, inorganic phosphate, activity of total alkaline phosphatase (ALP), and its isoenzymes were determined spectrophotometrically. Vascular endothelial growth factor-A (VEGF-A) and caspase-3 protein levels were detected by western blotting. Vdr and Cyp27b1 mRNAs were measured by qRT-PCR. Receptor activator of nuclear factor κB (RANK) expression in bone sections was visualized immunohistochemically. Serum 25(OH)D was assayed by ELISA. GC administration led to a decrease in maximal load (by 1.2-fold) and stiffness and toughness (by 1.3-fold), which was accompanied by a 3-fold reduction of 25(OH)D level, an elevation of the ALP bone isoenzyme activity in serum, hypocalcaemia, and hypophosphatemia. Along with prednisolone-induced VD deficiency, an impaired synthesis of Vdr (−30%) and Cyp27b1 (+71%) mRNA was observed, reflecting deregulation of bone tissue VD-auto-/paracrine system. GC caused an increase in caspase-3 content, suppressed the synthesis of the osteoclastic marker RANK, and altered angiogenesis/osteogenesis coupling by significantly reducing the level of VEGF-A.VD3 treatment restored serum 25(OH)D content and the expression of key components of the VD-auto-/paracrine system. VD3 supplementation diminished cell apoptosis and strongly improved angiogenesis/osteogenesis coupling as well as mineral metabolism and biomechanical parameters of femurs in GC-administered rats. Thus, VD3 can have a beneficial effect on the correction of GC-induced pathological changes in bone remodeling.

show abstract

The Biomechanical Testing for the Assessment of Bone Quality in an Experimental Model of Chronic Kidney Disease

Cited by 24 publications

References 38 publications

Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

Vitamin D Auto-/Paracrine System Is Involved in Modulation of Glucocorticoid-Induced Changes in Angiogenesis/Bone Remodeling Coupling

Contact Info

Product

Resources

About