12In whom and how to prevent glucocorticoid-induced osteoporosis
Section snippets
Epidemiology
In a large retrospective cohort study evaluating the relationship between oral glucocorticoid use and fracture risk in the UK, it was estimated that approximately 0.9% of the total adult population (around 409 000 people) were using oral glucocorticoids at any one time.5 While the majority were taking doses of 2.5–7.5 mg prednisolone daily, an estimated 93 000 people were taking doses >7.5 mg, and had done so for more than 6 months.5 A significant dose-response was observed for vertebral and hip
Pathophysiology
Bone loss resulting from glucocorticoid therapy is believed to occur through a number of mechanisms. Glucocorticoids decrease intestinal calcium absorption and increase renal calcium elimination through a mechanism that remains unclear.2, 16 This purportedly leads to secondary hyperparathyroidism; however, measurements of parathyroid hormone (PTH) have led to conflicting results, with at least one study reporting reduced levels.17 Others have reported that glucocorticoids enhance the action of
Management
In general, it is recommended that any patient currently prescribed or about to initiate glucocorticoid therapy be assessed for risk factors for osteoporosis and advised on lifestyle modification tactics to reduce the risks. This would include limiting cigarette smoking and alcohol consumption, reducing caffeine intake, participating in weight-bearing activities, and taking precautions to reduce the risk of falls. Particularly in the elderly, in whom the risk of osteoporosis and falls are
Drug therapy
To help understand the terminology, treatment studies are those which assess the efficacy of a medication to stabilize bone mass, and if possible increase bone mass and reduce the risk of fractures in a person already on chronic glucocorticoid therapy and in whom bone loss has already occurred. Prevention studies examine the efficacy of a drug to prevent bone loss in a patient about to initiate treatment with glucocorticoids.
Anabolic therapy (Table 4)
Three randomized controlled trials have used anabolic therapy in the treatment of GIOP (Table 4).64, 65, 66 One study examined human parathyroid hormone, one examined testosterone, and one examined nandrolone decanoate. While the testosterone study examined men, the other two enrolled postmenopausal women. Results of the studies indicated that BMD of the lumbar spine64, 65 and forearm66 increased in the treatment groups, whereas it decreased in the placebo groups following therapy. No effect
Calcium, vitamin D and its analogues (Table 5)
A recent meta-regression analysis demonstrated that vitamin D and its analogues offered a modest benefit in preserving bone density in individuals receiving glucocorticoid treatment, compared to no therapy or calcium-alone therapy.67 Of the prevention studies, Adachi et al8 failed to find any benefit on lumbar spine BMD over a 3-year study period between individuals initiating glucocorticoid therapy of >10 mg/day and treated with 1000 mg/daily of calcium and either placebo or 50 000 IU/week of
Summary of therapeutic options
It appears clear that bisphosphonates offer the greatest protection for the prevention and treatment of GIOP. In addition to maintaining bone density and preventing further losses in individuals who have already sustained complications of glucocorticoids, these medications have also been demonstrated to reduce the risk of fractures. Data are far more compelling for the bisphosphonates than for any other agent. While hormone replacement therapy was extensively used in the past for the treatment
Clinical approach
As always, a patient's individual risk factors should be carefully reviewed when initiating glucocorticoid therapy. Since the evidence indicates that bone loss is most rapid at the onset of glucocorticoid therapy (within the first 3–6 months), preventative measures should be initiated concurrently with the glucocorticoids. Risk factors that should be considered include BMD at the lumbar spine and femoral neck at the onset of glucocorticoid therapy, family history, hormonal status, fracture
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