You are referred a 75 year old man with longstanding ulcerative colitis who has been treated with many recurrent courses of oral steroids. He complains of back and hip pain. Plain X-rays show evidence of marked osteoporosis. He asks if there is anything he can do to help his bone problems.
You formulate the question, in a man with steroid-induced osteoporosis, does treatment with bisphosphonates reduce bone pain, fracture rate and improve bone mineral density? You search the Cochrane Library using the terms “steroid” and “osteoporosis” and find the following systematic review: Bisphosphonates for steroid induced osteoporosis (CDSR 1999;issue 1)
Read the article and decide:
- Is the evidence from this systematic review valid?
- Is this valid evidence from this systematic review important?
- Can you apply this valid and important evidence from this systematic review in caring for your patient?
Completed Systematic Reviews Worksheet for Evidence-Based Gastroenterology and Hepatology
Citation
Homik J, Cranney A, Shea B, et al. Bisphosphonates for steroid induced osteoporosis. CDSR 1999;issue 1.
Are the results of this systematic review of therapy valid?
- Is it a systematic review of randomised trials of the treatment you’re interested in?
- All trials included were Controlled Trials, randomisation was not a specific criterion for inclusion. However a sensitivity analysis was performed comparing the results of randomised and nonrandomized controlled trials and little difference was detected (nonrandomized studies underestimated the effect).
- Were all patients who entered the trial accounted for at its conclusion?
- And were they analysed in the groups to which they were randomised?
- Yes
- Does it include a methods section that describes finding and including all the relevant trials?
- Yes
- Does it include a methods section that describes assessing their individual validity?
- Yes
- Were the results consistent from study to study?
- Broadly consistent results were found. Several sensitivity analyses were performed, for methodological differences as well as primary vs. secondary prevention, but no major differences could be detected.
Are the valid results of this systematic review important?
| Odds Ratios | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 0.9 | 0.85 | 0.8 | 0.75 | 0.7 | 0.65 | 0.6 | 0.55 | 0.5 | ||
| Patient’s Expected Event Rate (PEER) | 0.05 | 209 | 139 | 104 | 83 | 69 | 59 | 52 | 46 | 41 |
| 0.10 | 110 | 73 | 54 | 43 | 36 | 31 | 27 | 24 | 21 | |
| 0.20 | 61 | 40 | 30 | 24 | 20 | 17 | 14 | 13 | 11 | |
| 0.30 | 46 | 30 | 22 | 18 | 14 | 12 | 10 | 9 | 8 | |
| 0.40 | 40 | 26 | 19 | 15 | 12 | 10 | 9 | 8 | 7 | |
| 0.50 | 38 | 25 | 18 | 14 | 11 | 9 | 8 | 7 | 6 | |
| 0.70 | 44 | 28 | 20 | 16 | 13 | 10 | 9 | 7 | 6 | |
| 0.90 | 101 | 64 | 46 | 34 | 27 | 22 | 18 | 15 | 12 | |
Can you apply this valid, important evidence about a treatment in caring for your patient?
Do these results apply to your patient?
- Is your patient so different from those in the systematic review that its results can’t help you?
- no
How great would the potential benefit of therapy actually be for your individual patient?
- Method I: In the table on page 1, find the intersection of the closest odds ratio from the overview and the CER that is closest to your patient’s expected event rate if they received the control treatment (PEER)
$$quad text{In the $SR$ the authors present weighted mean differences in bone mineral density between $\\$treatment and placebo groups. This is the}\\
\\ qquad mathit{Absolute~Risk~Reduction}\\
qquad = 4.3% \\[10pt]
qquad mathit{NNT} \\
qquad = 1/0.043 \\
qquad = 23
$$ - Method II: $$text{To calculate the $NNT$ for any $OR$ and $PEER$} \\
qquad mathit{NNT} =frac{1-[mathit{PEER})times(1-OR)]}{(1-mathit{PEER})timesmathit{PEER}times(1-mathit{OR})}
$$
Are your patient’s values and preferences satisfied by the regimen and its consequences?
- Do your patient and you have a clear assessment of their values and preferences?
- Needs to be assessed in each patient but this patient has specifically asked what can be done to reduce his pain.
- Are they met by this regimen and its consequences?
- Needs to be assessed in each patient. It must be recognised that this study used bone mineral density as a surrogate for pain and fractures. Although there is a correlation, and other studies have confirmed the efficacy of bisphosphonates in reducing fracture rates, this evidence is not directly applicable to pain and fracture rates.
Should you believe apparent qualitative differences in the efficacy of therapy in some subgroups of patients?
Only if you can say “yes” to all of the following:
- Do they really make biologic and clinical sense?
- Is the qualitative difference both clinically (beneficial for some but useless or harmful for others) and statistically significant?
- Was this difference hypothesised before the study began (rather than the product of dredging the data), and has it been confirmed in other, independent studies?
- Was this one of just a few subgroup analyses carried out in this study?
Additional Notes
This systematic review is directly applicable to the patient. The outcome measure (bone mineral density) is of very little interest to the patient who is concerned with pain and fracture rate. Although there is a relationship between BMD and pain and fractures this has been addressed in other studies that have not concentrated on steroid induced osteoporosis. However it seems likely that if there is concordance between the BMD changes in steroid and non steroid groups, then the impact of bisphosphonates on fractures and pain in the steroid group will also be the same as that seen in the non steroid induced osteoporotic patients.
Steroid Induced – Osteoporosis Bisphosphonates Improves Bone Mineral Desity
Clinical Bottom Line
Bisphosphonates improve bone mineral density in patients with steroid induced osteoporosis.
Citation
J, Cranney A, Shea B, et al. Bisphosphonates for steroid induced osteoporosis. CDSR 1999;issue 1.
Clinical Question
In a patient with steroid induced osteoporosis, does treatment with bisphosphonates reduce bone pain, fracture rate and improve bone mineral density?
Search Terms
“osteoporosis” and “steroids” in Cochrane Library
The Study
Systematic review of controlled trials that studied the effect of bisphosphonates on steroid induced osteoporosis. Bone mineral density was taken as the only outcome measure.
The Evidence
| Outcome | ARR (weighted) | NNT (95% CI) |
|---|---|---|
| Bone mineral density increase | .043 | 23 (17 to 37) |
Comments
The authors state that there is a relationship between BMD, and pain and fracture rates, but emphasise that the results do not permit us to draw conclusions about the efficacy of bisphosphonates in preventing fractures in steroid induced osteoporosis.
