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Meta-analysis
ACE Report #7839

Network meta-analysis of current drug options for the treatment of osteoporosis in men


Study Type:Meta analysis
OE Level Evidence:1
Journal Level of Evidence:N/A

Comparison of Bone Mineral Density in Lumbar Spine and Fracture Rate among Eight Drugs in Treatments of Osteoporosis in Men: A Network Meta-Analysis

PLoS One. 2015 May 26;10(5):e0128032

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Synopsis

13 studies with a total of 3647 men were included in this meta-analysis to analyze the effect of eight drugs (alfacalcidol, alendronate, ibandronate, risedronate, zoledronate, strontium ranelate, teriparatide, and parathyroid hormone) on bone mass density (BMD) in the lumbar spine (LS) and fracture incidence in males with osteoporosis. Network meta-analysis based on direct and indirect comparisons demonstrated that zoledronate had the greatest efficacy in increasing BMD in LS when compared to placebo, and teriparatide had the greatest efficacy in reducing fracture rate when compared to placebo.

Publication Funding Details +
Funding:
Non-funded
Conflicts:
None disclosed

Risk of Bias

10/10

Reporting Criteria

19/20

Fragility Index

N/A

Were the search methods used to find evidence (original research) on the primary question or questions stated?

Was the search for evidence reasonably comprehensive?

Were the criteria used for deciding which studies to include in the overview reported?

Was the bias in the selection of studies avoided?

Were the criteria used for assessing the validity of the included studies reported?

Was the validity of all of the studies referred to in the text assessed with use of appropriate criteria (either in selecting the studies for inclusion or in analyzing the studies that were cited)?

Were the methods used to combine the findings of the relevant studies (to reach a conclusion) reported?

Were the findings of the relevant studies combined appropriately relative to the primary question that the overview addresses?

Were the conclusions made by the author or authors supported by the data and or analysis reported in the overview?

How would you rate the scientific quality of this evidence?

Yes = 1

Uncertain = 0.5

Not Relevant = 0

No = 0

The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.

4/4

Introduction

4/4

Accessing Data

4/4

Analysing Data

4/4

Results

3/4

Discussion

Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65

The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.

Why was this study needed now?

Osteoporosis is a common bone disease that results in decreased bone mass, and in turn significantly increases the risk of fracture. An improvement of bone mass density has been demonstrated to minimize the incidence of osteoporotic fractures. There have been a number of drugs which have been suggested to be efficacious in osteoporosis treatment, such as bisphosphonates (including alendronate, risedronate, ibandronate, and zoledronate), bone-anabolic drugs of parathyroid or teriparatide, strontium ranelate, and alfacalcidol, a vitamin D analog. Due to the wide range of drugs available, and conflicting results from many randomized controlled trials, the study sought to compare these options for primary treatment of osteoporosis.

What was the principal research question?

Between available drug therapies for osteoporosis (alfacalcidol, alendronate, ibandronate, risedronate, zoledronate, strontium ranelate, teriparatide, and parathyroid hormone) what is the hierarchy of efficacy with respect to improvement in bone mineral density of the lumbar spine and reduction of fracture rate?

Study Characteristics -
Data Source:
Amed (from 1985 to May 2014), British Nursing Index (from 1985 to May 2014), EMBASE (from 1974 to May 2014), PubMed (from 1966 to May 2014), the Cochrane Central Register of Controlled Trials (CENTRAL), Google scholar, SIGLE (System for Information on Grey Literature in Europe) and clinicaltrials.gov databases were searched for relevant articles. Additionally, the reference list of the included studies were reviewed for overlooked articles.
Index Terms:
Search terms and MeSH terms included: "alfacalcidol", "alendronate", "ibandronate", "risedronate", "zoledronate", "strontium ranelate", "teriparatide", "parathyroid hormone", "men or male" and "osteoporosis".
Study Selection:
Two authors independently selected the articles based on the title and abstract. Disagreements between the authors was resolved by a discussion or consultation with a third reviewer. Studies listed for inclusion were randomized controlled trials (RCTs) or quasi-RCTs that contained the following: men with primary or idiopathic osteoporosis; a follow-up period of greater than 12 months; therapy regimens that included one drug and a placebo, or two of alfacalcidol, alendronate, ibandronate, risedronate, zoledronate, strontium ranelate, teriparatide, and parathyroid hormone; report of bone mass density (BMD) in the lumbar spine (LS) and the fracture rate. 13 studies with 3647 male patients were included in this meta-analysis.
Data Extraction:
Two authors independently extracted the data for each included study.
Data Synthesis:
Stata software (version 12.0) was used for pairwise meta-analyses, and WinBUGS (version 1.4.3) was used to perform a network meta-analysis. Chi-squared tests and I^2 tests were used to calculate heterogeneity between studies. The Der-Simonian and Laird random effects model was used. Fracture rates were reported using dichotomous data as odds ratios (ORs) with 95% confidence intervals (CI) for direct comparisons and 95% credible intervals (CrI) for indirect comparisons. Standardized mean differences (SMD) were used, with a 95% CI or CrI for direct and indirect comparisons, for continuous data.

What were the important findings?

  • Compared to placebo, effect on lumbar spine BMD from greatest to lowest was zoledronate (SMD 13.48 [95% CrI 11.88 to 15.08]), alendronate (11.04 [9.68 to 12.41]), teriparatide (20mcg) + risedronate (10.98 [8.55 to 13.48]), risedronate (10.33 [8.68 to 12.01]), teriparatide (20mcg) (9.33 [6.87 to 11.76]), strontium ranelate (8.88 [7.51 to 10.24]), ibandronate (5.49 [3.82 to 7.16]), parathyroid hormone (4.89 [3.12 to 6.62]) and alfacalcidol (3.42 [1.7 to 5.2]).
  • With the exception of teriparatide (20mcg) + risedronate, zoledronate demonstrated a significantly greater effect size on LS BMD when compared to all other treatment options.
  • Compared to placebo, significantly lower fracture rates were demonstrated with treatment with teriparatide (20mcg) (4.04 [1.36 to 8.49]), teriparatide (40mcg) (3.5 [1.14 to 8.34]), zoledronate (2.92 [1.29 to 5.62]), and risedronate (OR 2.51 [95%CrI 1.23 to 4.24]).
  • Alfacalcidol was associated with significantly higher fracture rate than treatment with risedronate (7.66, 1.74 to 19.27), zoledronate (8.41, 2.12 to 20.03), strontium ranelate (5.21, 1.32 to 11.88), teriparatide (40mcg) (10.49, 1.83 to 30.47), or teriparatide (20mcg) (12.12, 2.17 to 33.84)

What should I remember most?

In osteoporosis treatment in men, zoledronate was associated with the greatest effect on lumbar spine bone mineral density relative to placebo treatment. Among the drug options, zoledronate, risedronate, and teriparatide (20 or 40mcg) demonstrated significant reductions in fracture incidence compared to placebo.

How will this affect the care of my patients?

The results of this study offer a preliminary analysis on the current evidence regarding effect of current drug options for osteoporosis on bone mineral density increase and fracture risk reduction. In general, zoledronate may be the most effective therapy drug for increasing lumbar BMD, whereas teriparatide may be associated with the greatest reduction in fracture rate. Nevertheless, results should be interpreted with careful consideration, as head-to-head comparisons between each drug are needed to ultimately conclude which treatment option offers the greatest efficacy for men with osteoporosis. Additional, future trials should consider safety analyses associated with the treatment options evaluated in the current study.

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