Influence of glucocorticoid on bone in 3-, 6-, and 12-month-old rats as determined by bone mass and histomorphometry

Ogoshi, Tomofumi; Hagino, Hiroshi; Fukata, Satoru; Tanishima, Shinji; Okano, T.; Teshima, Ryota

doi:10.1007/s10165-008-0096-2

Cited by 20 publications

(15 citation statements)

References 26 publications

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“…The decreased TRACP 5b level can indicate both decreased bone resorption due to a lower osteoclast number, and a lower number of osteoclasts due to the bone loss induced by prednisolone treatment. In conclusion, 4-week prednisolone administration caused inhibition of both bone formation and resorption, consistent with a previous study [25].…”

Section: Discussionsupporting

confidence: 93%

“…A recent study of Ogoshi et al [25] demonstrated that 6-monthold female rats treated with 20 mg/kg prednisolone sodium succinate (sc) for 4 weeks were suitable models for glucocorticoid-induced osteoporosis, with a dominant cancellous bone decrease and reduced bone turnover, both formation and resorption. Our observations from the current study on male rats of a similar age (24 weeks) given prednisolone 21-hemisuccinate sodium salt at a dose of 7 mg/kg daily for 4 weeks are consistent with their results.…”

Section: Discussionmentioning

confidence: 99%

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Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats

Folwarczna

Pytlik

Śliwiński

et al. 2011

Pharmacological Reports

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Abstract:Glucocorticoid-induced osteoporosis is the most frequently occurring type of secondary osteoporosis. Antagonists of b-adrenergic receptors are now considered to be potential drugs under investigation for osteoporosis. The aim of the present study was to investigate the effects of propranolol, a nonselective b-receptor antagonist, on the skeletal system of mature male rats and on the development of bone changes induced by glucocorticoid (prednisolone) administration. The experiments were performed on 24-week-old male Wistar rats. The effects of prednisolone 21-hemisuccinate sodium salt (7 mg/kg, sc daily) or/and propranolol hydrochloride (10 mg/kg, ip daily) administered for 4 weeks on the skeletal system were studied. Bone and bone mineral mass in the tibia, femur and L-4 vertebra, length and diameter of the long bones, mechanical properties of tibial metaphysis, femoral diaphysis and femoral neck, bone histomorphometric parameters and turnover markers in serum were determined. Prednisolone-induced unfavorable skeletal changes led to disorders in bone mechanical properties. Propranolol not only did not improve bone parameters, but even caused deleterious effects on the skeletal system. Concurrent administration of propranolol with prednisolone did not counteract the changes induced by prednisolone. The results of this study may help to understand the equivocal results of human studies on the effects of b-blockers on the skeletal system. It is possible that the drugs exert biphasic effects on the skeletal system, both favorable and deleterious, depending on the dose or individual susceptibility.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats

Folwarczna

Pytlik

Śliwiński

et al. 2011

Pharmacological Reports

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“…CCs also have been reported to increase bone resorption, particularly during the early phase of treatment, by stimulating osteoclastic activity and survival through an effect on the RANKL/OPG signaling pathway 21–23. Consistent with these findings, studies in animals24 and in humans25–33 have shown that administration of GCs significantly reduce biochemical markers of bone formation but have no effect or even increase those of bone resorption. Remarkably, administration of prednisone to our patient decreased not only bone formation but also bone resorption within 4 weeks of starting of treatment.…”

Section: Discussionmentioning

confidence: 78%

Glucocorticoids are not always deleterious for bone

Lierop

Hamdy

Papapoulos

2010

Journal of Bone and Mineral Research

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A 23-year-old man with the rare sclerosing bone disorder van Buchem disease presented with progressively worsening headaches that eventually became persistent and associated with papilledema. Increased intracranial pressure was diagnosed, and the patient had a ventriculoperitoneal drain inserted as well as simultaneously receiving treatment with prednisone. Before starting treatment, there was biochemical evidence for increased bone turnover and for steady increases in bone mineral density (BMD) at the spine and total hip despite the patient having reached his peak height of 197 cm at the age of 19 years. Treatment with prednisone for 2 years resulted in biochemical and histologic suppression of bone formation as well as of bone resorption and arrest of further bone accumulation. Our data suggest that glucocorticoids (GCs) may represent an attractive alternative to the high-risk surgical approaches used in the management of patients with progressive sclerosing bone disorders. Our findings also suggest that whereas sclerostin may not be required for the action of GCs on bone formation, it may well be important for the action of GCs on bone resorption. The exact mechanism by which sclerostin may be involved in the regulation of bone resorption is as yet to be explored. ß

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“…Reductions in bone mineral density occur due to deficient calcium intake or corticosteroids both in humans and animals (Lill et al 2002). However, the reports remain contradictory, attributable to the fact that experimental glucocorticoid administration shows either increased BMD or decreased BMD in rats (Ogoshi et al 2008). However, the reports remain contradictory, attributable to the fact that experimental glucocorticoid administration shows either increased BMD or decreased BMD in rats (Ogoshi et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral, microarchitectural, biomechanical and matrix properties of rat bone

Govindarajan

Khassawna

Kampschulte

et al. 2013

Int J Experimental Path

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Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid-postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized-steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below -2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could be used in treatment.

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Influence of glucocorticoid on bone in 3-, 6-, and 12-month-old rats as determined by bone mass and histomorphometry

Cited by 20 publications

References 26 publications

Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats

Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats

Glucocorticoids are not always deleterious for bone

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral, microarchitectural, biomechanical and matrix properties of rat bone

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