Anabolic steroids for improving recovery after hip fracture in older people

Why anabolic steroids might help after a hip fracture

Hip fracture occurs mainly in older people, many of whom are frail. After surgery for their hip fracture, most patients suffer a loss of muscle mass and strength. Despite rehabilitation, most patients experience a long-term decline in mobility and function. Anabolic steroids, the synthetic derivatives of the male hormone testosterone, have been used in combination with exercise to improve muscle mass and strength in athletes. This review considers the evidence for the use of anabolic steroids aimed at improving outcomes after hip fracture in older people.

Description of the studies included in the review

We searched the medical literature until September 2013 and found three relevant studies that included a total of 154 women over the age of 65 years who had had hip surgery. Two studies were conducted in Sweden and one in Canada. The studies tested two comparisons. One study had three groups and contributed data to both comparisons.

Quality of the evidence
There were only three studies available and all three were small and at high risk of bias. We therefore judged the quality of the evidence to be very low, which means that we are uncertain how reliable the evidence is.

Summary of the evidence

Two very different studies compared anabolic steroid versus control (no anabolic steroid or placebo). One study conducted in the hospital ward compared weekly anabolic steroid injections versus placebo injections in 29 "frail elderly females". This study found no evidence that anabolic steroid resulted in better function, as measured by numbers discharged to a higher level of care or dead, or the time to mobilisation. The second study compared steroid injections given every three weeks for six months plus daily protein supplementation versus daily protein supplementation alone in 40 "lean elderly women". This study provided some evidence that anabolic steroids may result in better function, but they may also make no difference or result in worse function. Neither study found a difference in the incidence of individual adverse events in the two groups.

Two studies compared anabolic steroids combined with another nutritional intervention ('steroid plus') versus control (no 'steroid plus'). One study compared anabolic steroid injections every three weeks for 12 months in combination with daily supplement of vitamin D and calcium versus calcium only in 63 women who were living independently at home. The other study compared anabolic steroid injections every three weeks for six months and daily protein supplementation versus control in 40 "lean elderly women". Both studies found some evidence of better function in the steroid plus group. Pooled mortality data from the two studies showed no difference between the two groups at one year. Similarly, there was no evidence of between-group differences in individual adverse events. Three participants in the steroid group of one study reported side effects of hoarseness and increased facial hair. The other study reported better quality of life in the steroid plus group. None of the studies reported on patient acceptability of the intervention.

Conclusions

The quality of the evidence was very low, meaning that we are very uncertain about the direction and size of effect. Thus we are unable to say if anabolic steroids, either separately or in combination with nutritional supplements, improve recovery after hip fracture surgery in older people. Given that the results available point to the potential for more promising outcomes with a combined anabolic steroid and nutritional supplement intervention, we suggest that future research should focus on evaluating this combination.

Authors' conclusions: 

The available evidence is insufficient to draw conclusions on the effects, primarily in terms of functional outcome and adverse events, of anabolic steroids, either separately or in combination with nutritional supplements, after surgical treatment of hip fracture in older people. Given that the available data points to the potential for more promising outcomes with a combined anabolic steroid and nutritional supplement intervention, we suggest that future research should focus on evaluating this combination.

Read the full abstract...
Background: 

Hip fracture occurs predominantly in older people, many of whom are frail and undernourished. After hip fracture surgery and rehabilitation, most patients experience a decline in mobility and function. Anabolic steroids, the synthetic derivatives of the male hormone testosterone, have been used in combination with exercise to improve muscle mass and strength in athletes. They may have similar effects in older people who are recovering from hip fracture.

Objectives: 

To examine the effects (primarily in terms of functional outcome and adverse events) of anabolic steroids after surgical treatment of hip fracture in older people.

Search strategy: 

We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (10 September 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013 Issue 8), MEDLINE (1946 to August Week 4 2013), EMBASE (1974 to 2013 Week 36), trial registers, conference proceedings, and reference lists of relevant articles. The search was run in September 2013.

Selection criteria: 

Randomised controlled trials of anabolic steroids given after hip fracture surgery, in inpatient or outpatient settings, to improve physical functioning in older patients with hip fracture.

Data collection and analysis: 

Two review authors independently selected trials (based on predefined inclusion criteria), extracted data and assessed each study's risk of bias. A third review author moderated disagreements. Only very limited pooling of data was possible. The primary outcomes were function (for example, independence in mobility and activities of daily living) and adverse events, including mortality.

Main results: 

We screened 1290 records and found only three trials involving 154 female participants, all of whom were aged above 65 years and had had hip fracture surgery. All studies had methodological shortcomings that placed them at high or unclear risk of bias. Because of this high risk of bias, imprecise results and likelihood of publication bias, we judged the quality of the evidence for all primary outcomes to be very low.

These trials tested two comparisons. One trial had three groups and contributed data to both comparisons. None of the trials reported on patient acceptability of the intervention.

Two very different trials compared anabolic steroid versus control (no anabolic steroid or placebo). One trial compared anabolic steroid injections (given weekly until discharge from hospital or four weeks, whichever came first) versus placebo injections in 29 "frail elderly females". This found very low quality evidence of little difference between the two groups in the numbers discharged to a higher level of care or dead (one person in the control group died) (8/15 versus 10/14; risk ratio (RR) 0.75, 95% confidence interval (CI) 0.42 to 1.33; P = 0.32), time to independent mobilisation or individual adverse events. The second trial compared anabolic steroid injections (every three weeks for six months) and daily protein supplementation versus daily protein supplementation alone in 40 "lean elderly women" who were followed up for one year after surgery. This trial provided very low quality evidence that anabolic steroid may result in less dependency, assessed in terms of being either dependent in at least two functions or dead (one person in the control group died) at six and 12 months, but the result was also compatible with no difference or an increase in dependency (dependent in at least two levels of function or dead at 12 months: 1/17 versus 5/19; RR 0.22, 95% CI 0.03 to 1.73; P = 0.15). The trial found no evidence of between-group differences in individual adverse events.

Two trials compared anabolic steroids combined with another nutritional intervention ('steroid plus') versus control (no 'steroid plus'). One trial compared anabolic steroid injections every three weeks for 12 months in combination with daily supplement of vitamin D and calcium versus calcium only in 63 women who were living independently at home. The other trial compared anabolic steroid injections every three weeks for six months and daily protein supplementation versus control in 40 "lean elderly women". Both trials found some evidence of better function in the steroid plus group. One trial reported greater independence, higher Harris hip scores and gait speeds in the steroid plus group at 12 months. The second trial found fewer participants in the anabolic steroid group were either dependent in at least two functions, including bathing, or dead at six and 12 months (one person in the control group died) (1/17 versus 7/18; RR 0.15, 95% CI 0.02 to 1.10; P = 0.06). Pooled mortality data (2/51 versus 3/51) from the two trials showed no evidence of a difference between the two groups at one year. Similarly, there was no evidence of between-group differences in individual adverse events. Three participants in the steroid group of one trial reported side effects of hoarseness and increased facial hair. The other trial reported better quality of life in the steroid plus group.

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