Therapies for Preventing Bone Loss with Glucocorticoid Treatment

Agarwal, Arnav; Adachi, Jonathan

doi:10.1007/s11914-020-00653-9

Cited by 3 publications

(1 citation statement)

References 51 publications

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“…They act in cell-type specific manner, and via cellular crosstalk mechanisms, which are still partially unknown. Currently, some drugs are applied to treat GIO by either inhibiting osteoclast activity (Bisphosphonates and Denosumab) or stimulating osteoblast activity (Teriparatide) ( 92 ). However, the utilization of drugs to treat unwanted effects caused by other drugs is not ideal for patients.…”

Section: Discussionmentioning

confidence: 99%

Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases

et al. 2022

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Glucocorticoids (GCs) are steroid hormones that respond to stress and the circadian rhythm. Pharmacological GCs are widely used to treat autoimmune and chronic inflammatory diseases despite their adverse effects on bone after long-term therapy. GCs regulate bone homeostasis in a cell-type specific manner, affecting osteoblasts, osteoclasts, and osteocytes. Endogenous physiological and exogenous/excessive GCs act via nuclear receptors, mainly via the GC receptor (GR). Endogenous GCs have anabolic effects on bone mass regulation, while excessive or exogenous GCs can cause detrimental effects on bone. GC-induced osteoporosis (GIO) is a common adverse effect after GC therapy, which increases the risk of fractures. Exogenous GC treatment impairs osteoblastogenesis, survival of the osteoblasts/osteocytes and prolongs the longevity of osteoclasts. Under normal physiological conditions, endogenous GCs are regulated by the circadian rhythm and circadian genes display oscillatory rhythmicity in bone cells. However, exogenous GCs treatment disturbs the circadian rhythm. Recent evidence suggests that the disturbed circadian rhythm by continuous exogenous GCs treatment can in itself hamper bone integrity. GC signaling is also important for fracture healing and rheumatoid arthritis, where crosstalk among several cell types including macrophages and stromal cells is indispensable. This review summarizes the complexity of GC actions via GR in bone cells at cellular and molecular levels, including the effect on circadian rhythmicity, and outlines new therapeutic possibilities for the treatment of their adverse effects.

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Section: Discussionmentioning

confidence: 99%

Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases

et al. 2022

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Challenges and Opportunities for Osteoporosis Care During the COVID-19 Pandemic

Cromer

2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Purpose The Coronavirus Disease 2019 (COVID-19) has both directly and indirectly affected osteoporosis diagnosis and treatment throughout the world. Methods This mini-review summarizes the available evidence regarding the effects of COVID-19, its treatment, and the consequences of the pandemic itself on bone health. Additionally, we review evidence and expert recommendations regarding putative effects of osteoporosis medications on COVID-19 outcomes and vaccine efficacy and summarize recommendations for continuation of osteoporosis treatment during the pandemic. Results The use of standard screening procedures to assess for osteoporosis and fracture risk declined dramatically early in the pandemic, while rates of fragility fractures were largely unchanged. COVID-19, its treatments, and public health measures to prevent viral spread are each likely to negatively affect bone health. Osteoporosis treatments are not known to increase risk of adverse events from COVID-19, and pre-clinical data suggests possible beneficial effects of some therapies. Vitamin D deficiency is clearly associated with adverse outcomes from COVID-19, but it remains unclear whether vitamin D supplementation may improve outcomes. Osteoporosis treatment should be continued whenever possible, and recommendations for substituting therapies, if required, are available. Conclusion The COVID-19 pandemic has decreased screening and disrupted treatment for osteoporosis. Osteoporosis medications are safe and effective during the pandemic and should be continued whenever possible. Further studies are needed to fully understand the impact of the COVID-19 pandemic on long-term bone health.

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Healing of sub-critical femoral osteotomies in mice is unaffected by tacrolimus and deletion of recombination activating gene 1

Liu¹,

Bartnikowski²,

Wu³

et al. 2021

eCM

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Clinical management of delayed healing or non-union of long bone fractures and segmental defects poses a substantial orthopaedic challenge. There are suggestions in the literature that bone healing may be enhanced by inhibiting the activities of T and B lymphocytes, but this remains controversial. To examine this matter in more detail, sub-critical-sized segmental defects were created in the femora of mice and it was assessed whether there might be a benefit from the administration of a Food and Drug Administration (FDA)-approved drug that blocks T cell activation (tacrolimus). Defects were stabilised using an internal plate. In certain groups of animals, 1 mg/kg or 10 mg/kg tacrolimus was delivered locally to the defect site for 3 or 7 d using an implanted osmotic pump with a silicon catheter directing drug delivery into the defect area. Healing was monitored by weekly X-ray and assessed at 12 weeks by mechanical testing, µCT and histology. Radiographic and histological evaluations revealed that 100 % of defects healed well regardless of tacrolimus dosage or duration. A comparison of healed C57BL/6 and Rag1−/− femora by µCT and ex vivo torsion testing showed no differences within mouse strains in terms of bone volume, tissue volume, bone volume/tissue volume ratio, shear modulus, torsional rigidity or torsional stiffness. These data failed to support an important role for tacrolimus in modulating the natural healing of segmental defects under those experimental conditions.

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Therapies for Preventing Bone Loss with Glucocorticoid Treatment

Cited by 3 publications

References 51 publications

Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases

Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases

Challenges and Opportunities for Osteoporosis Care During the COVID-19 Pandemic

Healing of sub-critical femoral osteotomies in mice is unaffected by tacrolimus and deletion of recombination activating gene 1

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