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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review of randomised, controlled trials

JA Knopp, BM Diner, M Blitz, GP Lyritis, and BH Rowe.

Review published: 2005.

CRD summary

This review concluded that calcitonin appeared effective in the management of acute pain associated with acute osteoporotic vertebral compression fractures. The reporting of the review methodology suggests that this was a well-conducted review. However, poor reporting of the individual study data means that it is not possible to confirm the reliability of the authors' conclusion.

Authors' objectives

To compare the efficacy of calcitonin with placebo for the treatment of acute pain from recent, stable, osteoporotic vertebral compression fractures.


The Cochrane Musculoskeletal Group's Specialised Register, the Cochrane Controlled Trials Register (Issue 3, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), LILACS, Dissertation Abstracts and Index to Theses were searched up to April 2003. Bibliographies of relevant articles were reviewed and conference proceedings were sought. Contact was made with the primary author of included studies, experts in the field and the manufacturer of calcitonin. Published and unpublished studies written in any language were eligible for inclusion.

Study selection

Study designs of evaluations included in the review

Randomised placebo-controlled trials (RCTs) were eligible for inclusion. All of the included studies were double-blind.

Specific interventions included in the review

Studies that compared calcitonin (via any administration route) with placebo were eligible for inclusion. Calcitonin was administered at a dose of 100 international units (IU) intramuscularly for 14 days, 200 IU for 28 days intranasally, or 200 IU via rectal suppository for 28 days.

Participants included in the review

Studies of patients with acute pain from a recent, clinically diagnosed, osteoporotic vertebral compression fracture were eligible for inclusion. Patients managed in hospital or community settings were eligible, with most studies assessing hospitalised patients. The mean age of the patients was 71.6 years.

Outcomes assessed in the review

The primary outcome of interest was the analgesic effect of calcitonin as determined by a descriptive pain scale (e.g. a visual analogue scale) at rest, sitting, standing and walking. Concomitant analgesic use and adverse events were also assessed.

How were decisions on the relevance of primary studies made?

Two independent reviewers assessed the eligibility of studies.

Assessment of study quality

The studies were assigned a quality score (maximum possible score 5) based on the Jadad instrument, which assesses the reporting of randomisation, blinding, withdrawals and drop-outs. Concealment of allocation was also assessed as either adequate, inadequate or unclear. Two independent reviewers performed the validity assessment.

Data extraction

Two independent reviewers extracted data from the individual studies. Sufficient data were extracted to enable the calculation of a mean difference with 95% confidence interval (CI). When standard deviations (SDs) were not reported, an estimate based on the weighted average of SDs reported for all included studies was imputed. Data on the occurrence of side-effects were also extracted.

Methods of synthesis

How were the studies combined?

Studies that used comparable visual analogue scale and concomitant analgesic use were pooled to give a weighted mean difference (WMD) with 95% CI using a fixed-effect meta-analysis. Publication bias was assessed using a funnel plot and the rank correlation test.

How were differences between studies investigated?

Statistical heterogeneity was assessed using the chi-squared statistic. A sensitivity analysis was performed to assess the effect of imputed SDs. Subgroup analyses were performed according to the route of administration. Additional analyses based on age, gender, severity of osteoporosis based on bone density, and dose of calcitonin were planned but could not be carried out because of insufficient data. Potential sources of heterogeneity were investigated where necessary.

Results of the review

Five RCTs (n=246) were included. Four were included in the meta-analysis.

In terms of methodological quality, one study scored the maximum of 5 and four studies scored 4. Three studies reported adequate concealment of allocation. The authors also noted that most studies appeared to have used convenience samples to recruit trial participants.

Calcitonin was associated with a statistically significant improvement in resting pain after 1 week of treatment compared with placebo (WMD 3.08, 95% CI: 2.64, 3.52); the effect was sustained at weekly intervals up to 4 weeks (WMD 4.03, 95% CI: 3.70, 4.35). Similar results were obtained for sitting, standing and walking. The subgroup analysis based on route of administration suggested that patients given calcitonin intramuscularly (n=28) initially experienced superior pain control and could mobilise faster than those given calcitonin intranasally. However, the authors advised caution because of the small number of studies. The sensitivity analysis suggested that the use of imputed SDs did not influence the results.

The side-effects reported in the calcitonin group (n=122) were mild enteric disturbances (n=20), facial flushing and anorexia (n=7), mild headache (n=3) and mild dizziness (n=7). The side-effects reported in the placebo group (n=124) were mild dizziness (n=1), mild enteric disturbances (n=10) and headache (n=3). The overall withdrawal rate was 2.8%.

Calcitonin was associated with statistically significantly less frequent analgesic use (paracetamol tablets used per patient) compared with placebo by week 1 (WMD 2.72, 95% CI: 2.31, 3.13). The results were similar up to week 4.

Authors' conclusions

Calcitonin appears effective in the management of acute pain associated with acute osteoporotic vertebral compression fractures by shortening time to mobilisation. Intramuscular administration may have produced a more rapid analgesic effect, although this requires conformation.

CRD commentary

The review addressed a clear research question and the inclusion criteria were well defined. A comprehensive search strategy was performed, with attempts made to limit language and publication bias. Methods were used to minimise reviewer error and bias in the study selection, data extraction and validity assessment processes. Methodological quality was assessed, the scores suggesting that included studies were of a high methodological quality.

Adequate details about the characteristics of the included studies were given. Methods used only to combine the results of studies using comparable outcome measures would appear appropriate. Differences between the studies were explored and potential sources of heterogeneity were investigated. The authors considered the limitations in the available evidence relating to, for example, the generalisability of the results and the reporting of included studies. They also noted that three of the included studies were conducted by the same principal investigator. The methodology used in this review was well documented. However, the primary outcome data for individual studies were not reported, thus making it difficult to verify the authors' conclusion.

Implications of the review for practice and research

Practice: The authors stated that calcitonin should be considered an adjunctive analgesic for the treatment of acute pain associated with recent, osteoporotic vertebral compression fractures. Research: The authors stated that future research should focus on effective dose range and duration of response, long-term efficacy and, particularly, postmenopausal women. A cost analysis comparing calcitonin with conventional therapies, which incorporates health-related quality of life, length of time to mobilisation and length of hospital stay, is also needed. Trials should also consider comparing calcitonin with other analgesics and in combination with other analgesics.


Emergency Medicine Research Group.

Bibliographic details

Knopp JA, Diner BM, Blitz M, Lyritis GP, Rowe BH. Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review of randomised, controlled trials. Osteoporosis International 2005; 16(10): 1281-1290. [PubMed: 15614441]

Indexing Status

Subject indexing assigned by NLM


Acute Disease; Aged; Analgesics /therapeutic use; Back Pain /drug therapy /etiology; Bone Density Conservation Agents /therapeutic use; Calcitonin /therapeutic use; Female; Fractures, Compression /etiology; Humans; Male; Osteoporosis /complications; Randomized Controlled Trials as Topic; Spinal Fractures /etiology



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 15614441


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