A New Clinically Relevant T-Score Standard to Interpret Bone Status in a Sheep Model

Heiß, Christian; Kern, Stefanie; Malhan, Deeksha; Böcker, Wolfgang; Engelhardt, Markus; Daghma, Diaa Eldin S.; Stoetzel, Sabine; Schmitt, J.; Ivo, M.; Kauschke, Vivien; Lips, Katrin Susanne; Tushtev, Kamen; Rezwan, Kurosch; Khassawna, Thaqif El

doi:10.12659/msmbr.905561

Cited by 7 publications

(7 citation statements)

References 28 publications

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“…The regions of interest (ROI) of the left proximal femurs and lumbar spines 4–6 of each animal ( n = 5, respectively) were set 2 days before sacrifice, as described elsewhere [21], and scanned using dual-energy X-ray absorptiometry (DXA) (InAlyzer, MEDIKORS Inc., Seoul, Korea). BMC (bone mass, g), BMD (BMC / unit area, g/cm 2 ), and BV (cm 3 ) were measured using the InAlyzer software (MEDIKORS Inc., Seongnam, Korea).…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of Melon Extracts on Bone Strength, Mineralization, and Metabolism in Rats with Ovariectomy-Induced Osteoporosis

et al. 2019

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A polyphenolic extract from melon (Cucumis melo L.), as a potential source of natural antioxidants, has been reported to have a positive effect on osteoblast activity. In this study, the protective effects of heat-treated melon extract (ECO-A) on bone strength, mineralization, and metabolism were examined in osteoporotic rat models. Osteoporosis was induced by ovariectomy (OVX) in female rats and then maintained for 8 weeks, along with the ingestion of phosphate-buffered saline (PBS, OVXP) or ECO-A (OVXE) for an additional 4 weeks. At a pre-determined timepoint, bone strengths, as well as bone mineral contents (BMC) and the density (BMD) of femurs and/or lumbar spines extracted from each animal, were measured by a mechanical test and dual-energy X-ray absorptiometry, respectively. Moreover, several biochemical markers for bone turnover were analyzed by respective colorimetric assay kits in addition to clinical analyses. The maximum load and stiffness of femurs from the OVXE group were found to be significantly higher than the other groups. Furthermore, the OVXE group showed significantly higher BMC, BMD, and bone volume than the OVX and OVXP groups, which were comparable to the non-OVX (sham) group. The levels of bone formation and resorption markers in the OVXE group were similar to the sham group, but significantly different from other groups. In conclusion, these results suggest that ECO-A can play potentially positive roles in the protection of bone loss in rats with OVX-induced osteoporosis.

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Section: Methodsmentioning

confidence: 99%

Protective Effects of Melon Extracts on Bone Strength, Mineralization, and Metabolism in Rats with Ovariectomy-Induced Osteoporosis

et al. 2019

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“…In earlier studies a connection between BMD, osteoporosis and increased fat content in the bone could be observed (Heiss et al, 2017;Rosen & Bouxsein, 2006;Sekiya et al, 2004). Age also influences the bone density of the animals (Reinwald & Burr, 2011).…”

Section: Factors Influencing Bmdmentioning

confidence: 85%

DXA reference values of the humanoid sheep model in preclinical studies

Biehl

Schmitt

Stoetzel

et al. 2021

PeerJ

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Background Merino land sheep are a popular pre-clinical large animal model in research on systemic skeletal diseases such as osteoporosis. Interpretation of studies is difficult because many reference parameters are missing or not established. This study aims to determine the reference parameters of the skeletal system (peak bone mass = PBM, T-Score). A defined standard allows an easier comparison of the study data of the animal model with human studies (T-Score). Materials and methods A total of 116 Dual Energy X-ray Absorptiometry DXA measurements were performed on 74 untreated sheep. The average age of the animals was 57 months. The BMD, BMC, and fat content of the sheep were determined by the relevant human region of interest (ROI). From this, the PBM and from this the T-score for each of the animals were calculated. Results Using 682 DXA measurements BMD and BMC were determined to provide an indication to PBM. For BMD a significant correlation to the age of the animals was observed (p = 0.043). A significant correlation was also seen for BMC (B) (p ≤ 0.001). In the age-dependent analysis, a widespread of values above the linear regression line was measured for both BMD and BMC between the 50th and 90th months of life. From an age of about 90 months, a wider spread of values below the linear regression line was found, although the average values continued to rise. Discussion The evaluation of the 116 DXA measurements allowed the determination of the PBM for merino land sheep. With the help of the PBM, a T-score was calculated for each animal. The statistical analysis shows significant differences in BMD values between the different animal groups in each of the four ROIs investigated. Individual control or sham groups per study are therefore not sufficient. To improve comparability, an independent reference group should be established. Conclusion An independent reference group for PBM and a T-score was established from four to six-year-old animals. The bone density increases with the age of the animals. Around the fourth year of life, a first peak could be observed. Also, after the seventh year of life, a further peak with the beginning plateau phase was observed. When compiling a group of animals for an osteoporosis model, animals from the age of seven years should, therefore, be used.

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“…However, it is important to underline that at sexual maturity, the sheep is not mature from the skeletal point of view yet, and growth ends a long time after puberty, such as in the vertebral body epiphysis where the closing times of the ossification centers are around 4–5 years of age. In this review, the age of the animals ranged from 3 to 10 years with some studies using animals with a wide age range [ 34 , 36 , 38 ]. The age reported in all studies are those at which the animals underwent bilateral OVX that was always performed through a ventral midline laparotomy under general anesthesia ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

“…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%

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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A New Clinically Relevant T-Score Standard to Interpret Bone Status in a Sheep Model

Cited by 7 publications

References 28 publications

Protective Effects of Melon Extracts on Bone Strength, Mineralization, and Metabolism in Rats with Ovariectomy-Induced Osteoporosis

Protective Effects of Melon Extracts on Bone Strength, Mineralization, and Metabolism in Rats with Ovariectomy-Induced Osteoporosis

DXA reference values of the humanoid sheep model in preclinical studies

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

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