Prednisone prevents particle induced bone loss in the calvaria mouse model

Abstract

Introduction Glucocorticoids are essential in the treatment of many chronic inflammatory and malignant diseases but are known to have detrimental effects on bone. This study aimed to investigate the effects of prednisone on osteoclast functioning in vivo in the calvaria particle-induced bone loss mouse model. Methods 12-week-old male C57BL6/J mice received subcutaneously implanted prednisone (2.5 mg/d, 60 day release (n = 14)) or placebo pellets (n = 10). Osteolysis of the calvaria bone was induced two weeks later by application of ultra-high-molecular-weight polyethylene- (UHMWPE) particles to the dome (vs sham operation). The extent of osteolysis was determined histologically and by micro-computer tomography. Results Prednisone significantly inhibited particle-induced osteolysis in the skull. No significant difference in osteoclast numbers was seen in mice with prednisone vs placebo treatment. Prednisone treatment alone without particle application did not reduce bone mineral density or deterioration in bone microarchitecture parameters. Conclusions The calvaria particle-induced bone loss mouse model can be adapted to investigate osteoclast activity in vivo and the effect of prednisone on osteoclasts. In this preventive experimental design, the application of short-term low-dose prednisone has osteoprotective effects without measurable systemic side effects on bone parameters.

The osteocytic actions of glucocorticoids on bone mass, mechanical properties, or perilacunar remodeling outcomes are not rescued by PTH(1-34)

“…This study used FVB mice, which are the most susceptible strain to study GC-induced osteonecrosis, but at 13-weeks of age, they may be less sensitive to the catabolic action of GC on trabecular bone. Indeed, the effects of GC are age-dependent, such that others have shown that GC’s effect on trabecular bone is unchanged ( 70 , 72 , 75 , 76 ) or elevated ( 75 ) in younger mice. Another variable to consider is GC dosing effects, as shorter exposure to higher dose GC ( 77 ) or prolonged lower dose GC ( 40 ) treatment in younger mice can cause bone loss.…”

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases

“…In a recent investigation, a novel Keap-1 inhibitor, iKeap1, was shown to protect osteoblast from chemically generated oxidative assault and apoptosis by improving Nrf2-mediated expression of cytoprotective factors [ 123 ]. Treatment with a low dose of glucocorticoids, including dexamethasone (DEX), cortisone, and prednisolone, over a short time was shown to regulate bone remodeling and maintain homeostasis of the bone tissues [ 124 ]. However, administering the same drugs at a higher dosage over a long time elicited OP [ 125 ] and osteonecrosis via upregulation of glycogen synthase kinase-3β (GSK3β) gene expression and its enzyme activity [ 126 ].…”