Calcium alone is insufficient to prevent rapid bone loss in patients starting corticosteroids. However, calcium and vitamin D3 (cholecalciferol) may blunt the continuing loss during long-term use of corticosteroids. A Cochrane meta-analysis compared patients taking calcium and vitamin D3 to patients using calcium alone or placebo.6
The studies were underpowered to detect statistically significant reductions in fracture risk, but revealed a trend towards a lower risk of fracture in patients treated with calcium and vitamin D3. All patients starting oral corticosteroid therapy are advised to take calcium (1000 mg/day) and vitamin D3 (at least 500 IU/day). In practice, the aim should be to maintain serum 25-hydroxyvitamin D3 levels greater than 50 ng/mL to prevent secondary hyperparathyroidism.
In addition to vitamin D3, randomised controlled trials DXA dual energy X-ray absorptiometry demonstrated that the hydroxylated derivatives of vitamin D3, for example 25-hydroxyvitamin D3 (calcidiol), 1-hydroxyvitamin D3 (alfacalcidol) or 1,25-dihydroxyvitamin D3 (calcitriol) administered together with calcium, were superior to calcium alone in reducing bone loss after corticosteroid therapy (Table 1). The risk of hypercalciuria or hypercalcaemia is higher with the hydroxylated vitamin D3 metabolites than with plain vitamin D3, especially when combined with calcium, and this must be monitored. Apart from calcitriol, vitamin D metabolites are not routinely available to Australian prescribers. Studies comparing the vitamin D metabolites in corticosteroid users have not been reported. Alendronate (10 mg/day) is more effective than alfacalcidol (1 microgram/day) in the prevention of costicosteroid-induced bone loss.7
However, calcitriol is at least as effective as alendronate in preventing bone loss in corticosteroid users.8
Table 1
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Vitamin D metabolites for prevention of corticosteroid-related bone loss
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Vitamin D derivative
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Dose range
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Cholecalciferol (vitamin D3)11
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500 IU/day-100 000 IU/week
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Calcidiol (25-hydroxyvitamin D3)12 *
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35-40 microgram/day
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Alfacalcidol (1-hydroxyvitamin D3)span>7 ,13 *
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0.5-1.0 microgram/day
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Calcitriol (1,25-dihydroxyvitamin D3)14
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0.5-1.0 microgram/day
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* not generally available in Australia
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Antiresorptive drugs
Although the effects of corticosteroids on bone formation predominate, antiresorptive drugs appear to reduce fracture risk both by reducing their effects on osteoclast-mediated bone remodelling and preventing the negative effects of corticosteroids on osteoblast and osteocyte viability. The active metabolites of vitamin D3, such as calcitriol (0.25-0.5 microgram/day), may effectively slow the rapid bone loss in patients starting corticosteroids. Bisphosphonates, such as alendronate and risedronate, also prevent bone loss in these patients and in those already taking chronic therapy.
A meta-analysis attempted to rank various antiresorptive drugs according to their effect on bone mineral density. It found that bisphosphonates had greater efficacy than no therapy or calcium (4.6% difference in percent change in the bone mineral density of the lumbar spine after one year). The efficacy of bisphosphonates was also enhanced when used in combination with vitamin D3 (6% difference in bone mineral density).9
While bisphosphonates are currently the most effective therapies for the management of corticosteroid-induced osteoporosis, few studies have measured fracture outcomes. The overall reduction in risk of morphometric (X-ray detected) vertebral fractures with bisphosphonates, such as risedronate, is approximately 37%, but there are no efficacy data about hip and other non-vertebral fractures in patients taking corticosteroids. The assumption is that the efficacy is similar to the 30-50% reduction in non-vertebral fractures seen in patients treated for postmenopausal osteoporosis, although this has not been rigorously tested. Further, no study has examined symptomatic vertebral fractures or back pain as a primary end point.
The intravenous bisphosphonates (pamidronate and zoledronic acid) are often used in patients who are intolerant of oral bisphosphonates. Zoledronic acid is effective in reducing vertebral and hip fractures in postmenopausal osteoporosis, and randomised studies in corticosteroid users are under way.
Anabolic drugs
Intermittent injections of parathyroid hormone have a bone anabolic effect. A randomised clinical trial showed that recombinant human parathyroid hormone injections could override corticosteroid-induced suppression of bone formation and increase bone mass.11
However, the precise role and cost-effectiveness of recombinant parathyroid hormone in postmenopausal and corticosteroid-induced osteoporosis has not been defined.
Fig. 1
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Fracture prevention for patients starting corticosteroids
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 |
DXA dual energy X-ray absorptiometry
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