Adverse effects of corticosteroids on bone metabolism: a review.Glucocorticoid GC exposure is the most common etiology of drug-induced secondary osteoporosis. Twenty percent of all cases of osteoporosis have been attributed to GC exposure. GCs are known steroids side effects osteoporosis inhibit bone remodeling and to increase fracture risk. GC exposure alters the fragile balance between osteoclast and osteoblast activity in bone osteopoorsis. GC stimulates osteoclast-mediated bone resorption and reduces osteoblast-mediated bone formation, which results in increased overall net bone resorption. Specifically, the 2 main effects of GCs on bone steroids side effects osteoporosis are 1 inducing apoptosis in osteoblasts and osteocytes, thereby decreasing bone formation, and 2 prolonging the lifespan of osteoclasts and increasing bone resorption. The risk of fracture decreases 3 months after cessation of GC therapy; thus, a 3-month period may be ideal between GC illegal anabolic steroids side effects in patients at high risk for the development of osteoporosis.
Corticosteroids cause osteoporosis and fractures in a high percentage of patients. There is a dose-dependent effect, which is difficult to define because of varying durations at each dose. The beneficial effects of steroids on the underlying disease may partially offset the detrimental effects on bone.
Because the effects are so variable and can be clinically severe, patients embarking on long-term steroid treatment should have bone density monitored, and measures taken to try to preserve bone.
The figure shows effects of steroids on bone. The yellow boxes are effects on osteoblasts or osteocytes; the blue boxes are effects on osteoclasts, and the white boxes are other effects which will secondarily cause bone loss. The trabecular bone is affected more rapidly than the cortical bone. Some patients suffer multiple vertebral compression fractures within a year of initiating steroid therapy. Diagnostic work-up Bone density should be measured in patients who are expected to remain on corticosteroids.
The same lab tests that are used for "ordinary" osteoporosis are indicated for steroid-induced osteoporosis. In males it is very important to remember to check the testosterone level. Females should be asked about amenorrhea which is probably a better indication of estrogen deficiency than estrogen levels. Measurement of LH or FSH will not be helpful in this situation, since the hypogonadism is usually hypogonadotropic, and thus low estrogen will not be associated with high FSH the way it is in a postmenopausal woman.
A hour urine calcium is indicated, because often these patients have hypercalciuria. I usually check a urine N-telopeptide, too, to get an idea of how much of the hyercalciuria is due to bone resorption. Low urine calcium is also seen, especially if patients have any other reason for malabsorption. Vigorous treatment with calcium and vitamin D is too frequently undertaken without checking the urine calcium, and this could worsen hypercalciuria. In patients with markedly low bone density, prevalent fractures, or high doses of steroids I usually also check a PTH and hydroxyvitamin D level.
In less severe cases I will just check these if the serum calcium or alkaline phosphatase is abnormal. Xrays of the spine are especially important in patients taking long-term corticosteroids, because sometimes the fractures are not clinically obvious, and if they are present the patient will need maximal therapy. Therapy The physiology of corticosteroid-induced osteoporosis is different than postmenopausal osteoporosis, so treatment cannot be expected to have the same results.
For example, anti-resorptive therapy does not result in the same degree of increase in bone mass as in postmenopausal osteoporosis. Greater amounts are unlikely to be beneficial, and it probably is better to get the calcium from dietary sources instead of tablets. The use of vitamin D in corticosteroid-treated osteoporosis is debated, and there is still not enough data to make strong recommendations. The most recent studies do not show a difference in bone density with active vitamin D metabolites or high doses of ergocalciferol.
In those cases with low urine calcium or clinical malabsorption or renal insufficiency the more potent vitamin D should be used such as calcitriol at 0. Gonadal steroids estrogen in women and testosterone in men should be replaced as appropriate unless there are contraindications. Anti-resorptive therapy can prevent some of the bone loss. Clinical trials using bisphosphonates have shown benefits after one to two years; long-term studies are still needed. These therapies should not be used in patients with low serum calcium, and adequate dietary intake should be assured before they are started.
Also avoid them in patients with reflux esophagitis, patients who are bedridden and can't be upright after taking the medication, and patients with renal insufficiency, and premenopausal women who may wish to become pregnant in the future. The bone resorption may be high when steroids are initiated, but with longer use the osteoclasts are inhibited by the steroids so it does not make as much sense to continue anti-resorptive therapy.
More recent studies comparing teriparatide to bisphosphonates have shown that there is significantly lower fracture rates in the patients treated with teriparatide. One of the studies lasted for 3 years and the P1NP was better than baseline throughout the study. Should bisphosphonates be used for long-term treatment of glucocorticoid-induced osteoporosis? Glucocorticoids and the osteoclast. Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: Teriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis.
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