Glucocorticoids (GCs) have unparalleled anti-inflammatory and immunosuppressive properties, which accounts for their widespread prescription and use. Unfortunately, a limitation to GC therapy is a wide range of negative side effects including Cushing's syndrome, a disease characterized by metabolic abnormalities including muscle wasting and osteoporosis. GC-induced osteoporosis occurs in 30% to 50% of patients on GC therapy and thus, represents an important area of study.
Endogenous glucocorticoids (GCs) support normal bone development and bone mass maintenance, whereas long-term exposure to pharmacological dosages of GCs uncouples bone formation and resorption, resulting in GC-induced osteoporosis (GIOP). Heat shock protein 90 (HSP90) chaperoning glucocorticoid receptor (GR) signaling prompts us to speculate that HSP90 plays critical roles in GC-mediated bone formation and GIOP.
Prolonged glucocorticoid (GC) administration causes secondary osteoporosis (GIOP) and non-traumatic osteonecrosis. LLP2A-Ale is a novel bone-seeking compound that recruits mesenchymal stem cells to the bone surface, stimulates bone formation, and increases bone mass. The purpose of this study was to determine if treatment with LLP2A-Ale alone or in combination with parathyroid hormone (PTH) could prevent or treat GIOP in a mouse model.
Li Jian-min, Li Heng
Objective: To explore the influence of different-frequency glucocorticoid (GC) induction on morphological structures of humeri and soft tissues as well as immune system in rats.
Methods: A total of 32 specific pathogen-free (SPF) SD rats at the age of 3 months were selected and randomly divided into 4 groups, 8 cases in each group. The rats in control group were not given any treatment, while those in low-, moderate- and high-frequency groups were treated with intramuscular injection of dexamethasone 1 mg/kg per time for twice, 4 times and 6 times per week, respectively. All the rats were sacrificed on d30 to measure their body mass and qualities of soft tissues and immune organs, and bone histomorphometry was applied to analyze humeral bone mass and bone structural changes.
Results: Compared with control group, there was no change in cancellous bone mass and bone structures of upper humeri in low-frequency group, but serious loss of bone mass, significantly degenerated bone structure, markedly reduced trabecular thickness and number as well as notably increased trabecular separation was all observed in moderate- and high-frequency groups. The size of cortical bones, total size of bone structure, thickness of cortical bones and size percentage of cortical bones in middle humeri reduced apparently, while the size percentage of medullary cavity increased dramatically in high-frequency group. Growth plate thickness of upper humeri decreased in low-, moderate- and high-frequency groups, and the diameters of mastocytes diminished in moderate- and high-frequency groups. Compared with control group, body mass decreased obviously, qualities and indexes of spleen and thymus showed decreasing tendency along with the increase of drug administration frequency in low-, moderate- and high-frequency groups.
Conclusion: Low-frequency GC cannot change humeral morphology. The higher the frequency of drug administration is, the more the loss of cancellous bone mass is. When the frequency reaches to 6 times per week, the loss of cortical and cancellous bones is much severer. However, with the increase of drug administration frequency, thymic degeneration, splenic atrophy and immunosuppression can be induced. Therefore, the influence of different-frequency drug administration on bones and soft tissues in different locations as well as immune function should be fully considered and reasonable drug administration protocols should be designed for the establishment of SD rat models with osteoporosis.
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Glucocorticoids at pharmacological doses have been shown to interfere with fracture repair. The role of endogenous glucocorticoids in fracture healing is not well understood. We examined whether endogenous glucocorticoids affect bone healing in an in vivomodel of cortical defect repair.