Effects of letrozole on bone biomarkers and femur fracture in female rats

Yönden, Zafer; Aydın, Mehmet; Alcin, E; Keleştemur, Mehmet Halidun; Kutlu, Selim; Yılmaz, Bayram

doi:10.1007/bf03180579

Cited by 8 publications

(6 citation statements)

References 25 publications

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“…Letrozole pretreatment for 1 month in ovotoxic mice resulted in further reduction in ALP and HxP and enhanced TRAP activity in both femoral epiphysis and lumbar vertebrae indicating significantly enhanced bone turnover. This is in agreement with clinical and preclinical studies showing bone loss with letrozole. While ALP is a bone formation marker and represent osteoblastic activity , both TRAP and HxP are considered markers of bone resorption .…”

Section: Discussionsupporting

confidence: 92%

“…Because exemestane also reduced ALP in the femoral epiphysis, it is discernible that it may impair bone formation in femoral epiphysis while having no effect on bone resorption. Thus, there seems to be a differential profile of the two aromatase inhibitors on bone biomarkers which is also in agreement with some previous reports [6,45]. However, our results differ from the study by McCloskey and co-workers (2007) which reported all three aromatase inhibitors viz.…”

Section: Discussionsupporting

confidence: 89%

“…The third generation nonsteroidal (anastrozole and letrozole) and steroidal (exemestane) aromatase inhibitors inhibit the aromatase enzyme by 96–99% thereby produces an oestrogen deficient environment . Low serum estradiol (E2) levels are associated with decreased bone mineral density (BMD) and increased fracture risk in women as well as in ovariectomized animals . Postmenopausal women receiving aromatase inhibitors are at further increased risk of developing oestrogen deprived state due to diminished secretion from the ovaries and therefore high risk of bone loss .…”

Section: Introductionmentioning

confidence: 99%

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Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice

Kalam

Talegaonkar

Vohora

2016

Fundamemntal Clinical Pharma

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The third generation aromatase inhibitors are currently the drugs of choice for treatment of early and advanced breast cancer in postmenopausal women. One of the significant limiting factor during therapy is their negative impact on bone health. In the present study, we compared the effects of a non-steroidal (letrozole) and a steroidal aromatase inhibitor (exemestane) on bone mineral density and markers of bone turnover including alkaline phosphatase (ALP), tartrateresistant acid phosphatase (TRAP), hydroxyproline (HxP), receptor activator of nuclear factor kappa-B ligand (RANKL), sclerostin and dickkopf-1 (DKK-1) in vinlycyclohexene di epoxide (VCD)-induced ovotoxic female mice. VCD administration for 15 days mimicked a postmenopausal state with reduced serum estradiol levels. Ovotoxicity was accompanied by reduced ALP, HxP and enhanced TRAP, sclerostin and DKK-1 activity in femoral epiphysis and lumbar vertebrae of mice. While letrozole (1mg/kg) administration for one month enhanced bone turnover in ovotoxic mice, exemestane (3.25 mg/kg) was devoid of such effects in both normal and ovotoxic mice. The latter, however, reduced ALP in femoral epiphysis of ovotoxic mice.Letrozole depleted estradiol levels in ovotoxic mice and enhanced RANKL activity while exemestane neither affected estradiol nor RANKL in both normal and ovotoxic mice, and enhanced sclerostin and DKK-1 in femoral epiphysis only. The study indicates that the two aromatase inhibitors possesses differential profile in terms of their effects on bone and that exemestane could be a better option for the treatment of breast cancer in postmenopausal women at least in terms of its effects on bone.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice

Kalam

Talegaonkar

Vohora

2016

Fundamemntal Clinical Pharma

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“…In the present study, microCT-scanning results indicated that following 4 and 6 weeks post-surgery, the fracture repair indices, including BV/TV, BS/BV, TB.TH, TB.N and TB.SP, were significantly improved in the PDLLA group compared with the control group. ALK and OPG were expressed in the bone tissue, specifically in osteoblastic lineages and their serum concentrations were considered as the markers for the evaluation of osteogenesis during development and bone formation throughout fracture healing (23,24). The results of the current study indicate that at weeks 4 and 6 following intramedullary fixations for osteotomy, the serum levels of ALK and OPG were significantly increased in the PDLLA group, compared with the control.…”

Section: Discussionmentioning

confidence: 58%

Increased Runx2 expression associated with enhanced Wnt signaling in PDLLA internal fixation for fracture treatment

Ling

Wu²,

Shi

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Poly-D-L lactide (PDLLA) biodegradable implants to heal fractures are widely applied in orthopedic surgeries. However, whether the process of fracture healing is regulated differently when PDLLA is used compared with traditional metal materials remains unclear. Runt-related transcription factor 2 (Runx2) and canonical Wnt signaling are essential and may interact reciprocally in the regulation of osteogenesis during bone repair. In the present study, a rat femoral open osteotomy model was used to compare the curative efficacy of a PDLLA rod and Kirschner wire under intramedullary fixation for fracture treatment. The dynamic expression of Runx2 and key components of the canonical Wnt signaling in callus tissue during fracture healing was also investigated. The results of the current study indicate that at weeks 4 and 6 following fixation, the callus bone structural parameters of microCT were significantly improved by PDLLA rod compared to that of Kirschner wire. In addition, at weeks 4 and 6 after fixation, the protein and mRNA expression of Runx2 and the positive regulators of canonical Wnt signaling, such as Wnts and β-catenin, were significantly increased. However, the protein and mRNA expression levels of the negative regulators of canonical Wnt signaling, such as glycogen synthase kinase-3β, were significantly decreased in callus tissue when treated with PDLLA rod compared with Kirschner wire. Collectively, these data indicate that compared to the traditional metal material, using PDLLA internal fixation for fracture treatment may further improve bone formation, which is associated with the increased expression of Runx2 and the enhancement of canonical Wnt signaling. IntroductionSince the use of biodegradable implants to heal fractures by Rokkanen et al in 1985, the method of using biodegradable materials has been widely applied in orthopedic surgeries (1-3). Biodegradable materials exhibit various advantages in the treatment of fractures compared with the use of traditional metal implants, including the elimination of implant removal, reduction of the 'stress shielding' effect, improvement of biocompatibility, reduction of radiological artifacts and utilization of magnetic resonance imaging assessment following surgery (4,5). Poly-D-L lactide (PDLLA) is a material with an intermediate degradation time (PDLLA begins to degrade at ~12 weeks) and may be completely replaced by bone tissue following surgery, thus, it is considered to be one of the most effective biodegradable materials for the treatment of fractures (6-8). However, with the exception of clinical outcomes, the differences in the biological processes following the use of PDLLA and metal fixation to treat a fracture remain unknown.The fracture healing process has been widely accepted to comprise a series of overlapping phases; these include inflammation, repair and remodeling events (9). This multistage repair process involves a variety of complex and well-orchestrated cellular and molecular processes, and should be considered as a special...

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“…Kumru et al ( 12 ) suggested that neither anastrozole nor letrozole had clear effects on bone mass density (both vertebral and femoral) of intact female rats. On the other hand, Yonden et al ( 13 ) observed that letrozole increased the risk of femoral fracture and of bone biomarkers, including alkaline phosphatase and phosphate.…”

Section: Introductionmentioning

confidence: 99%

Assessment of bone metabolism and biomechanical properties of the femur, following treatment with anastrozole and letrozole in an experimental model of menopause

et al. 2017

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The aim of the present study was to investigate the impact of anastrozole and letrozole supplementation following surgically induced menopause on bone metabolism and biomechanical properties. A total of 45 Wistar rats underwent ovariectomy and were then randomly allocated to receive no treatment, anastrozole or letrozole. At 2 and 4 months following the initiation of the present study, the serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined, and the animals were sacrificed at the end of the 4-month period to assess the biomechanical properties of the femoral bones. The applied force and the deflection of the central section were recorded during the test. Taking advantage of these quantities, the fracture force, the stiffness of the bone and the energy absorbed until fracture were determined. At 2 months following the initiation of the experimental protocol, the mean OPG levels were significantly increased in the control group compared with the anastrozole-treated group (P<0.01). Similarly, RANKL levels were significantly increased in the control rats compared with the anastrozole-treated animals (P<0.001) and animals that received letrozole (P<0.05). Notably, these trends were not observed at the end of the experiment (4 months). A biomechanical study of the femoral bones revealed significantly decreased stiffness among animals that received anastrozole (P<0.05) and letrozole (P<0.01) compared with their control counterparts. The results of the present study indicate that treatment with anastrozole and letrozole significantly increases the levels of OPG and RANKL in bone, an effect that appears to be directly associated with the biomechanical properties of bones.

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Effects of letrozole on bone biomarkers and femur fracture in female rats

Cited by 8 publications

References 25 publications

Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice

Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice

Increased Runx2 expression associated with enhanced Wnt signaling in PDLLA internal fixation for fracture treatment

Assessment of bone metabolism and biomechanical properties of the femur, following treatment with anastrozole and letrozole in an experimental model of menopause

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