Chronic glucocorticoid excess hasdeleterious effects on bone thatcan lead to osteoporosis andfractures.
GLUCOCORTICOIDS AND BONE PHYSIOLOGY Glucocorticoids reduce bone formation and increase bone resorption. Glucocorticoids exert their effects on gene expression via cytoplasmic glucocorticoid receptors. In adult bone, glucocorticoid receptors are found in stromal cells & osteoblasts
Decreased bone formation — The predominant effect of glucocorticoids on the skeleton is reduced bone formation. The decline in bone formation may be mediated by direct inhibition of osteoblast proliferation and by stimulation of apoptosis of osteoblasts .
Decreased calcium absorption — Glucocorticoids decrease intestinal calcium absorptionIncreased calcium excretion — Glucocorticoids increase renal calcium excretion by decreasing calcium reabsorptionThe effects are pronounced with daily therapy, may be less with alternate-day therapy.
CLINICAL ASPECTS OF GLUCOCORTICOID- INDUCED BONE LOSS A prospective, longitudinal study found that patients beginning high-dose glucocorticoid therapy (mean dose 21 mg/day) lost a mean of 27% of their lumbar spine bone density during the first year. There is a substantial increase in fracture risk in patients receiving glucocorticoid therapy that appears within three to six months of initiating treatment. Fracture risk appears to be related to the dose and duration of therapy.
Bone density usually increases after discontinuation of exogenous glucocorticoids
Prevention and treatment of glucocorticoid-induced osteoporosisGENERAL MEASURES — Attempts to reverse the glucocorticoid excess by decreasing the dose of exogenous glucocorticoid The glucocorticoid dose and the duration of therapy should be as low as possible.
When glucocorticoids are given, topical therapy (such as inhaled glucocorticoids for asthma & glucocorticoid enemas for bowel disease) is preferred. Consider short-term high-dose pulse therapy instead of continuous therapy for weeks or months . Patients should be encouraged to do weight- bearing exercises for at least 30 minutes each day . Patients should avoid smoking and excess alcohol.
CALCIUM AND VITAMIN DThe American College of Rheumatology (ACR) recommends the following Maintain a calcium intake of 1000 to 1500 mg/day Vitamin D intake of 800 IU/day
BISPHOSPHONATES - (Eg- ALENDRONATE, ETIDRNATE) These drugs prevent glucocorticoid-induced bone loss by prolonging the lifespan of osteoblasts. Total body bone density increased significantly with the alendronate treatment.
The American College of Rheumatology (ACR) guidelines recommends the following interventions in patients initiating prednisone in a dose of 5 mg/day or higher for more than three months and for patients receiving long term glucocorticoids in whom the BMD T-score is below -1.0. • Bisphosphonate therapy alendronate 35 mg/week for prevention, 70 mg/week for treatment Consideration of calcitonin therapy if bisphosphonates are contraindicated or not tolerated.( dose of 200 IU/day)
SIDE-EFFECTS Peptic ulceration Abdominal pain & distension Dyspepsia & regurgitation Osteonecrosis of the jaw
Patient information Drugs need to be taken in the morning on an empty stomach with a full 8 oz glass of plain water. The person must then wait for at least half an hour before eating or taking any other medications. These dosing instructions help to reduce the risk of side effects and potential complications.