Effect of a bisphosphonate and selective estrogen receptor modulator on bone remodeling in streptozotocin-induced diabetes and ovariectomized rat model

Lee, Young‐Seok; Gupta, Rishab; Kwon, Jeong Taik; Cho, Dae Chul; Seo, Ye Jin; Seu, Sung Young; Park, Eui Kyun; Han, Inbo; Kim, Chi Heon; Sung, Joo Kyung; Kim, Kyoung‐Tae

doi:10.1016/j.spinee.2018.05.020

Cited by 10 publications

(5 citation statements)

References 38 publications

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“…This effect may be attributed to inhibition of bone turnover and bone loss and improvement of the SB microstructure by RAL. Our findings are also supported by several studies showing that RAL has anti-resorptive effects 38 , promoting bone formation 39 and thereby reversing the osteoporotic changes.…”

Section: Osteoarthritis Andcartilagesupporting

confidence: 88%

Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced - patellofemoral joint osteoarthritis

Bei

Tian

Xiao

et al. 2020

Osteoarthritis and Cartilage

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Objective: Abnormal remodeling of subchondral bone (SB) induced by estrogen deficiency has been shown to be involved in osteoarthritis (OA). Raloxifene (RAL) is commonly used to treat postmenopausal osteoporosis (OP). However, little is known about its effects on OA combined with estrogen deficiency. This study was performed to evaluate the efficacy of RAL on patella baja-induced patellofemoral joint OA (PFJOA) in an ovariectomized rat model. Design: Patellar ligament shortening (PLS) and ovariectomy (OVX) were performed simultaneously in 3month-old female SpragueeDawley rats, which were treated with RAL (10 mg/kg/day) or vehicle at 72 h postoperatively for 10 weeks. PFJOA was assessed by immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA), micro-computed tomography (mCT), histomorphology and behavioral analyses. Results: X-ray examinations showed that patella baja was successfully established by PLS. Histomorphological analysis revealed that PFJOA was significantly exacerbated by OVX and markedly alleviated by RAL. Moreover, RAL improved cartilage metabolism by decreasing MMP-13, ADAMTS-4, and caspase-3 and increasing Col-II and aggrecan at both the protein and mRNA levels. Furthermore, RAL markedly improved bone mass and SB microarchitecture and reduced osteoclast numbers and the serum osteocalcin and CTX-I levels. Although RAL showed a trend toward reducing pain sensitivity based on mechanical allodynia testing, this result was not statistically significant. Conclusion: These findings demonstrate that RAL treatment retards PFJOA progression in an ovariectomized rat model, suggesting that it may be a potential candidate for amelioration of the progression of PFJOA accompanied by postmenopausal OP.

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Section: Osteoarthritis Andcartilagesupporting

confidence: 88%

Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced - patellofemoral joint osteoarthritis

Bei

Tian

Xiao

et al. 2020

Osteoarthritis and Cartilage

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“…HE has also been reported to prevent the reduction of trabecular thickness due to estradiol deficiency and to reduce the number of osteoclasts in the tibial metaphysic [41]. CTX-1 is a bone resorption marker produced by the activity of osteoclasts [42]. Our findings show that the 3 : 1 complex inhibits bone resorption.…”

supporting

confidence: 58%

Combination of Red Clover and Hops Extract Improved Menopause Symptoms in an Ovariectomized Rat Model

Kim¹,

Kim²,

Yu³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Red clover and hops are already known for their alternative menopausal therapies; however, their combination has not yet been studied. This study aimed to evaluate the efficacy of the combination of red clover and hops extract (RHEC) for treating menopausal symptoms for the first time. A high-performance liquid chromatography (HPLC) method for RHEC was developed and validated for the analysis of biochanin A in red clover extract and xanthohumol in hops extract. An in vivo study was conducted using an ovariectomized rat model treated with RHEC (125, 250, and 500 mg/kg, p.o.) for a 12-week test period. Changes in body weight, tail skin temperature (TST), serum lipid profile, bone metabolism, antioxidants, and markers of vasorelaxation and uterus endometrium were evaluated. RHEC significantly inhibited body weight gain and decreased fat weight. Changes in TST associated with flashes were significantly inhibited in the RHEC groups. Other markers related to menopausal symptoms, such as blood lipid profile (total cholesterol and low-density-lipoprotein cholesterol), bone metabolism (serum alkaline phosphatase, osteocalcin, and c-terminal telopeptide type 1), antioxidants (superoxide dismutase and malondialdehyde), and vasorelaxants (endothelin-1 and nitric oxide), were significantly improved after the administration of RHEC. We also confirmed the safety of RHEC through histopathological observation of the endometrium. Our findings demonstrate that RHEC appears to have high potential for comprehensively improving various symptoms of menopause.

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“…Several studies on diabetic animals have provided solid evidence of a reduction in fracture risk with anti-osteoporotic treatments ( 53 , 54 ), based on their ability to increase BMD and bone strength. Although diabetes is characterized by low bone turnover, further reduction of bone turnover with antiresorptive therapies does not seem to negatively affect the potential to prevent fractures ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Alendronate Versus Denosumab on Major Osteoporotic Fracture Risk in Elderly Patients With Diabetes Mellitus: A Danish Retrospective Cohort Study

et al. 2022

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ObjectivePatients with diabetes mellitus have an increased risk of fractures; however, the underlying mechanism is largely unknown. We aimed to investigate whether the risk of major osteoporotic fractures in diabetes patients differs between subjects initiated with alendronate and denosumab, respectively.Methods and Research DesignWe conducted a retrospective nationwide cohort study through access to all discharge diagnoses (ICD-10 system) from the National Danish Patient Registry along with all redeemed drug prescriptions (ATC classification system) from the Health Service Prescription Registry. We identified all subjects with a diabetes diagnosis between 2000 and 2018 and collected data on the first new prescription of anti-osteoporotic treatment between 2011 and 2018. Exposure was defined as either alendronate or denosumab treatment initiated after diabetes diagnosis. Outcome information was collected by identification of all major osteoporotic fracture (MOF) diagnoses, i.e., hip, spine, forearm, and humerus, from exposure until 2018 or censoring by emigration or death. The risk of fracture was calculated as hazard ratios (HR) using multiply adjusted Cox proportional models with death as a competing risk.ResultsWe included 8,745 subjects initiated with either alendronate (n = 8,255) or denosumab (n = 490). The cohort consisted of subjects with a mean age of 73.62 (SD ± 9.27) years, primarily females (69%) and suffering mainly from type 2 diabetes (98.22%) with a median diabetes duration at baseline of 5.45 years (IQR 2.41–9.19). Those in the denosumab group were older (mean 75.60 [SD ± 9.72] versus 73.51 [SD ± 9.23] years), had a higher proportion of women (81% versus 68%, RR 1.18 [95% CI 1.13–1.24], and were more comorbid (mean CCI 2.68 [95% CI 2.47–2.88] versus 1.98 [95% CI 1.93–2.02]) compared to alendronate initiators. In addition, denosumab users had a higher prevalence of previous fractures (64% versus 46%, RR 1.38 [95% CI 1.28–1.48]). The adjusted HR for any MOF after treatment initiation with denosumab was 0.89 (95% CI 0.78–1.02) compared to initiation with alendronate.ConclusionThe risk of incident MOF among subjects with diabetes was similar between those initially treated with alendronate and denosumab. These findings indicate that the two treatment strategies are equally effective in preventing osteoporotic fractures in subjects with diabetes.

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Effect of a bisphosphonate and selective estrogen receptor modulator on bone remodeling in streptozotocin-induced diabetes and ovariectomized rat model

Cited by 10 publications

References 38 publications

Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced - patellofemoral joint osteoarthritis

Raloxifene retards cartilage degradation and improves subchondral bone micro-architecture in ovariectomized rats with patella baja-induced - patellofemoral joint osteoarthritis

Combination of Red Clover and Hops Extract Improved Menopause Symptoms in an Ovariectomized Rat Model

The Efficacy of Alendronate Versus Denosumab on Major Osteoporotic Fracture Risk in Elderly Patients With Diabetes Mellitus: A Danish Retrospective Cohort Study

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