Evaluation of hematology, general serum biochemistry, bone turnover markers and bone marrow cytology in a glucocorticoid treated ovariectomized sheep model for osteoporosis research

Coelho, Catarina; Bordelo, João; Camassa, José Arthur de Abreu; Barros, Vera A; Babo, Pedro S.; Gomes, Manuela E.; Reis, Rui L.; Azevedo, Jorge Manuel Teixeira de; Requicha, João Filipe; Faísca, Pedro; Carvalho, Pedro P.; Viegas, Carlos; Dias, Isabel

doi:10.1590/0001-3765202020200435

Cited by 2 publications

(8 citation statements)

References 37 publications

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“…Amino acid and lipid metabolism was also found to be altered in ovariectomized and glucocorticoid treated sheep [ 7 ]. Similar changes have also been found in other ovine osteoporosis models [ 8 ].…”

Section: Introductionsupporting

confidence: 88%

Expression of Renal Vitamin D and Phosphatonin-Related Genes in a Sheep Model of Osteoporosis

Dittmer

Chernyavtseva

Marshall

et al. 2021

Animals

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Osteoporosis is a significant public health issue around the world, with post-menopausal osteoporosis due to estrogen deficiency resulting in approximately ¾ of cases. In this study, 18 aged Merino ewes were ovariectomized, and 10 were controls. Three of the ovariectomized ewes were treated weekly with 400 mg of methylprednisolone for 5 months and three were treated weekly for 2 months, followed by a 3-month recovery period. At 2 months, five control animals and six ovariectomized animals were euthanized. At 5 months, all the remaining ewes were euthanized. Kidney samples were collected postmortem for qPCR analysis of NPT1, PTH1R, NPT2a, NPT2c, Klotho, FGFR1IIIc, VDR, CYP24A1, CYP27B1, TRPV5, TRPV6, CalD9k, CalD28k, PMCA and NCX1. Ovariectomized sheep had significantly greater VDR expression compared with other groups. Ovariectomized sheep treated with glucocorticoids for 2 months followed by euthanasia at 5 months showed significant differences in TRPV5, CYP24A1 and klotho gene expression compared to other groups. Differences in klotho expression were most marked after adjustment for repeated measures (p = 0.1). Klotho is known as the “anti-aging” hormone and is involved in calcium and phosphorus metabolism. Klotho may be involved in the recovery of bone mineral density in ovariectomized sheep treated with glucocorticoids for 2 months followed by euthanasia at 5 months. Further research on the role of klotho is recommended.

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Section: Introductionsupporting

confidence: 88%

Expression of Renal Vitamin D and Phosphatonin-Related Genes in a Sheep Model of Osteoporosis

Dittmer

Chernyavtseva

Marshall

et al. 2021

Animals

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“…All animals had at least one-week acclimatization period prior to the OVX. General anesthesia was prevalently induced by intravenous injection of ketamine and propofol and prolonged with isoflurane in oxygen through an endotracheal tube [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Antibiotic prophylaxis was provided by intravenous injection at the time of anesthesia induction.…”

Section: Resultsmentioning

confidence: 99%

“…All the included studies had a control group in the 83% that was represented by unoperated animals while a total of 17% was represented by the sham group, i.e., a group where the procedure mimics the OVX in every way, including preprocedural routine, anesthesia, incisions, and postprocedural follow-up. Sham procedures are generally considered a more appropriate control than using no intervention since this procedure more clearly distinguishes whether a new treatment is effective beyond the placebo response that is due to the contextual cues of an invasive procedure [ 39 ]. However, from an ethical point of view, unmanipulated (unoperated) control animals minimize animal distress and unnecessary procedures.…”

Section: Resultsmentioning

confidence: 99%

“…The success of OVX in sheep was mostly confirmed by iliac crest and/or lumbar vertebra microcomputed tomography (CT) analyses [ 23 , 25 , 26 , 27 , 31 , 32 , 39 , 40 ] as well as by quantitative computed tomography (qCT), which measured the BMD using a X-ray CT scanner with a calibration standard to convert Hounsfield units (HU) of the CT image to bone mineral density values [ 24 , 28 , 29 ]. BMD was also measured by dual-energy X-ray absorptiometry (DXA) in iliac crest, femora, and lumbar spine [ 25 , 34 , 35 , 36 , 37 , 40 ].…”

Section: Resultsmentioning

confidence: 99%

“…BMD was also measured by dual-energy X-ray absorptiometry (DXA) in iliac crest, femora, and lumbar spine [ 25 , 34 , 35 , 36 , 37 , 40 ]. Same studies also evaluated OVX through analysis of biochemical markers of bone, such as osteocalcin, C-terminal cross-linked telopeptides of type I collagen (CTXI), alkaline phosphatase (b-ALP), and by changes in hormonal profile (circulating concentrations of estradiol) [ 27 , 28 , 36 , 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

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Osteoporosis Preclinical Research: A Systematic Review on Comparative Studies Using Ovariectomized Sheep

Salamanna

Contartese

Veronesi

et al. 2022

IJMS

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Sheep ovariectomy (OVX) alone or associated to steroid therapy, deficient diet, or hypothalamic–pituitary disconnection has proven to be of critical importance for osteoporosis research in orthopedics. However, the impact of specific variables, such as breed, age, diet, time after OVX, and other variables, should be monitored. Thus, the design of comparative studies is mandatory to minimize the impact of these variables or to recognize the presence of unwanted variables as well as to better characterize bone remodeling in this model. Herein, we conducted a systematic review of the last 10 years on PubMed, Scopus, and Web of Knowledge considering only studies on OVX sheep where a control group was present. Of the 123 records screened, 18 studies were included and analyzed. Results showed that (i) Merino sheep are the most exploited breed; (ii) 5–6 years of age is the most used time for inducing OVX; (iii) ventral midline laparotomy is the most common approach to induce OVX; (iv) OVX associated to steroid therapy is the most widely used osteoporosis model; and (v) success of OVX was mostly verified 12 months after surgery. In detail, starting from 12 months after OVX a significant decline in bone mineral density and in microarchitectural bone parameters as well as in biochemical markers were detected in all studies in comparison to control groups. Bone alteration was also site-specific on a pattern as follows: lumbar vertebra, femoral neck, and ribs. Before 12 months from OVX and starting from 3–5 months, microarchitectural bone changes and biochemical marker alterations were present when osteoporosis was induced by OVX associated to steroid therapy. In conclusion, OVX in sheep influence bone metabolism causing pronounced systemic bone loss and structural deterioration comparable to the situation found in osteoporosis patients. Data for treating osteoporosis patients are based not only on good planning and study design but also on a correct animal use that, as suggested by 3Rs principles and by ARRIVE guidelines, includes the use of control groups to be directly contrasted with the experimental group.

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Evaluation of hematology, general serum biochemistry, bone turnover markers and bone marrow cytology in a glucocorticoid treated ovariectomized sheep model for osteoporosis research

Cited by 2 publications

References 37 publications

Expression of Renal Vitamin D and Phosphatonin-Related Genes in a Sheep Model of Osteoporosis

Expression of Renal Vitamin D and Phosphatonin-Related Genes in a Sheep Model of Osteoporosis

Osteoporosis Preclinical Research: A Systematic Review on Comparative Studies Using Ovariectomized Sheep

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