Get access

Calcitonin for preventing and treating corticosteroid-induced osteoporosis

  • Review
  • Intervention

Authors


Abstract

Background

Corticosteroid-induced osteoporosis is a cause of morbidity in patients with chronic obstructive lung disease, asthma, and rheumatologic disorders. Corticosteroid treatment causes bone loss by a variety of complex mechanisms. It has been shown that bone mineral loss at the hip averages 14% in the first year after starting corticosteroid therapy.

Objectives

To review the efficacy of calcitonin (subcutaneous or nasal) for the treatment and prevention of corticosteroid-induced osteoporosis.

Search methods

We conducted a search of Medline, the Cochrane Controlled Trials Register and Embase using the Cochrane Musculoskeletal Group search strategy for randomized controlled trials (RCTs) up to May 1998. We also searched bibliographic references and consulted content experts.

Selection criteria

Two independent reviewers selected RCTs which met predetermined inclusion criteria.

Data collection and analysis

Two reviewers independently extracted data using predetermined forms and assessed methodological quality of randomization, blinding and dropouts. For dichotomous outcomes, relative risks (RR) were calculated. For continuous data, weighted mean differences (WMD) of the percent change from baseline were calculated. We decided a priori to use random effects models for all outcomes, because of uncertainty about whether a consistent true effect exists in such different populations.

Main results

Nine trials met the inclusion criteria, including 221 patients randomized to calcitonin and 220 to placebo. The median methodologic quality was two out of a maximum of five points. Calcitonin was more effective than placebo at preserving bone mass at the lumbar spine after six and 12 months of therapy with a WMD of 2.8% (95% CI: 1.4 to 4.3) and 3.2% (95% CI: 0.3 to 6.1). At 24 months, lumbar spine BMD was not statistically different between groups: WMD 4.5% (95% CI: -0.6 to 9.5)]. Bone density at the distal radius was also higher with calcitonin after six months of therapy, but bone density at the femoral neck was not different between placebo and calcitonin treated groups. The relative risk of fractures was not significantly different between calcitonin and placebo with a relative risk (RR) of 0.71 (95% CI: 0.26 to 1.89) for vertebral and 0.52 (95% CI: 0.14 to 1.96) for non vertebral fractures. The subgroup analyses of methodological quality and duration of corticosteroid therapy were confounded. Trials of patients who had been taking steroids for greater than three months (which were of low methodologic quality) demonstrated a larger effect of calcitonin on spine bone density (about 6%) than prevention trials (about 1%). There was no consistent effect of different dosages (50-100 IU compared to 200-400 IU). However, subcutaneous calcitonin showed substantially greater prevention of bone loss. Withdrawals due to side effects were higher in the calcitonin-treated groups: RR 3.19 (95%CI: 0.66 to 15.47). Important side effects included nausea and facial flushing.

Authors' conclusions

Calcitonin appears to preserve bone mass in the first year of glucocorticoid therapy at the lumbar spine by about 3% compared to placebo, but not at the femoral neck. Our analysis suggests that the protective effect on bone mass may be greater for the treatment of patients who have been taking corticosteroids for more than three months. Efficacy of calcitonin for fracture prevention in steroid-induced osteoporosis remains to be established.

摘要

背景

Calcitonin 預防及治療類固醇引起的骨質疏鬆症

類固醇引起的骨質疏鬆症是造成慢性肺氣腫、氣喘、及風濕病合併症的原因之一。類固醇治療經由複雜機制造成骨質流失。研究顯示,開始使用類固醇治療第一年髖部骨質礦物平均流失量為14%。

目標

回顧calcitonin (皮下或噴鼻) 預防及治療類固醇引起的骨質疏鬆症之效果。

搜尋策略

搜尋包括Medline, Cochrane Controlled Trials Register and Embase之隨機對照控制臨床研究 (直到1998年5月)。同時手動搜尋所選文章之參考文獻及徵詢專家。

選擇標準

兩位作者獨立進行合乎收錄文章之資料摘錄。

資料收集與分析

兩位作者使用預製表格獨立進行資料摘錄,並對每篇試驗研究的隨機分配、盲性評估及病患流失率之品質評估。二分法資料以相對風險﹝RR﹞,連續性資料則計算基礎值改變百分比之加權平均差異(weighted mean difference, WMD)做評估。因不確定在如此不同族群一致真實效果是否存在,因而事先決定使用隨機效應模式做分析。

主要結論

9個研究包含221例病患使用calcitonin,220例病患使用安慰劑。研究方法品質中位數為2﹝最高分為5﹞。Calcitonin在治療6及12個月後,在腰椎骨質密度保留方面比安慰劑有效﹝WMD 4.5% [95% CI: −0.6 to 9.5]﹞。在治療6個月後,橈骨遠端骨質密度比安慰劑組高。但在股骨頸骨質密度則無顯著差異。 Calcitonin治療組與安慰劑組在骨折相對風險並無統計上顯著差異﹝脊椎骨折RR 0.71, 95% CI 0.26 to 1.89;非脊椎骨折RR 0.52, 95% CI 0.14 to 1.96﹞。次群分析顯示研究方法品質及類固醇使用時間為干擾因子。使用類固醇已超過3個月以上者﹝研究方法品質低﹞,Calcitonin使用對脊椎骨質密度效用較安慰劑高﹝約6%﹞,高於預防研究試驗﹝約1%﹞。不同劑量(50 – 100 IU比上200 – 400 IU)之效果並無一致性。但皮下使用calcitonin預防骨質流失能力較強。因副作用而停用,在Calcitonin治療組相對風險為3.19 (95%CI: 0.66 to 15.47)。重要副作用包括噁心與臉潮紅。

作者結論

使用類固醇治療的第1年,Calcitonin與安慰劑相比,骨質流失在腰椎減少3%,但股骨頸未有顯著差異。建議使用類固醇超過3個月以上者,Calcitonin預防骨質疏鬆症效果較顯著。使用Calcitonin預防類固醇引起骨鬆骨折之效果有待確立。

翻譯人

本摘要由林口長庚醫院余光輝翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

長期類固醇治療使用包括許多原因,包括發炎性腸炎、慢性肺氣腫、類風濕性關節炎。 9個研究包含221例病患使用calcitonin,220例病患使用安慰劑。研究顯示Calcitonin治療第一年,在腰椎及前臂使骨質流失減少3%, 在髖骨質密度則無顯著差異。預防類固醇引起脊椎及長骨之骨鬆骨折在Calcitonin治療組與安慰劑組並無顯著差異。Calcitonin組比安慰劑組副作用高4倍,並主要為噁心與臉潮紅。

Plain language summary

Calcitonin for preventing and treating corticosteroid-induced osteoporosis

Long-term corticosteroids are prescribed for a number of reasons, including inflammatory bowel disease, chronic obstructive lung disease and rheumatoid arthritis. Steroids cause bone loss by a variety of complex mechanisms. Calcitonin is an anti-resorptive therapy that has been approved for the treatment of established osteoporosis. The purpose of this review was to evaluate calcitonin as a means of preventing bone loss with corticosteroid therapy. Nine randomized controlled trials were included in the review, with 221 patients randomized to calcitonin and 220 to placebo. The results showed that calcitonin prevents bone loss at the spine and forearm by about 3% after the first year of therapy. There was no effect on bone loss at the hip. Calcitonin was not statistically different from placebo at preventing fractures of the spine and long bones, such as hip fractures. Calcitonin was associated with four times the side effects of placebo, and these were mostly nausea and facial flushing.

Get access to the full text of this article

Ancillary