This is the protocol for a review and there is no abstract. The objectives are as follows:
To assess the effects of physical therapy interventions for the prevention of fractures after spinal cord injury (SCI).
Description of the condition
Spinal cord injury (SCI) is an insult to the spinal cord resulting in a change, either temporary or permanent, in its normal motor, sensory, or autonomic functions (ASIA 2000). The main causes are road traffic injuries, falls, sport injuries and injuries related to violence (Lazo 2001).
Spinal cord injury has an incidence of 15 to 40 cases per million, with men being four times more affected than women. The worldwide prevalence is estimated at 700 to 900 million (Sekhon 2001). SCI often determines a profound and long-term disability that is life changing for the injured individual and his or her family. These injuries also have an important social cost, associated with expensive healthcare treatment, rehabilitation, and loss of productivity (Pickett 2006).
Osteoporosis is a disease of the skeletal system characterized by low bone mass and deterioration of bone tissue that leads to an increased risk of bone fracture. It is a known consequence of spinal cord injury in almost every SCI patient. It increases the risk of fracture mainly in the lower extremities. Some studies report fracture in up to 34% of patients with SCI (Lazo 2001), mostly caused by low intensity trauma such as during transfer from a bed to a chair (Vestergaard 1998). Fractures are associated with many other complications, such as pressure ulcers, spasticity, and deep venous thrombosis, which further increase morbidity, mortality, and healthcare costs.
The mechanism underlying osteoporosis in SCI patients is a dramatic reduction in bone density and bone mineral content, explained by immobility and several neuronal, vascular, and hormonal changes (Jiang 2006). The changes in bone lead to a high resorption rate, shown by erosioned surfaces and osteoclast activity. The levels of biochemical markers of resorption start increasing some weeks after injury and reach a maximum between week 10 to week 16. After one year, resorption markers remain high and bone formation markers are low. Some studies show that a steady state is achieved around the second year following injury but others note a continuous loss of bone (Maïmoun 2006).
Description of the intervention
Physical therapy interventions that are usually employed for spinal cord injury attempt to counteract some of the detrimental consequences of immobilization, the reduction in muscle contraction, and redistribution of the gravitational forces applied to bone segments that normally support weight (Maïmoun 2006).
There are several types of interventions that could theoretically be effective in the prevention of fractures. The most common are:
weight bearing by standing and walking (for example standing and treadmill walking using long leg braces, weight bearing while on a tilt table, and a gait rehabilitation program using orthoses);
exercise therapy (for example paraplegic sport players, wheelchair athletes, muscle stretching exercises, and resistance training);
exercise movement techniques (for example yoga and Tai Chi);
electrical stimulation (for example transcutaneous electrical nerve stimulation (TENS), vagus nerve stimulation, functional electrical stimulation cycling, functional electrical stimulation to quadriceps femoris and anterior tibial muscles, soleus muscle electrical stimulation, and electroacupuncture);
musculoskeletal manipulation (for example spinal manipulations, acupressure, motion therapy, and massage); and
other physical interventions (for example low-intensity pulsed ultrasound, impact vibration, hydrotherapy, hyperthermia, ammotherapy, diathermy, a steam bath, and myofunctional therapy).
How the intervention might work
There are several mechanisms that explain the potential benefits of physical therapies in the prevention of fractures in SCI patients. Some interventions (for example weight bearing by standing and walking and electrical stimulation) reduce muscle atrophy that occurs after a neurological lesion. Interventions aimed at providing early verticalization of the body can contribute to limiting the initial demineralization, through the maintenance of normal axial bone-loading by passive standing (for example with a standing frame or tilt-table) or by various aided-walking systems (Dauty 2000). Exercise has been shown to produce an osteogenic influence on bone sites submitted to weight-bearing or impact. The beneficial effect in the upper limbs was observed at any level of SCI, including quadriplegic patients (Dauty 2000). Intensive exercises such as skiing, quad rugby, wheelchair basketball, and weight training have a localized effect on the extremities involved (Jones 2002).
Functional electrical stimulation (FES) has generally been used to minimize muscle atrophy that occurs after a nerve injury and may help preserve bone mass in patients with SCI (Maïmoun 2004).
For many interventions the mechanism of benefit is not completely clear, but some theories exist. For instance, in vitro and in vivo studies have demonstrated that low-intensity pulsed ultrasound can provide an osteogenic stimulus (Naruse 2000). In many other cases (such as physiotherapy) the mechanism of action is still unknown (Biering-Sørensen 2009).
Why it is important to do this review
As discussed above, fractures in SCI patients result in a loss of or impaired function causing morbidity, mortality, deterioration in quality of life, and high cost to the health system. Thus, it is imperative to find the best way of treating people with SCI.
Unfortunately, there are not enough randomized controlled trials looking at the effects of physical therapy interventions, and the available studies are of low quality. For example, regarding the effect of weight bearing by standing and walking, a single study showed that early-period weight bearing did not increase bone mineral density (BMD); however, the therapy period was 12 weeks and only involved simple static weight-bearing. On the other hand, other patient-important outcomes, such as symptomatic fractures, were not considered (Ben 2005). For the evaluation of the effects of exercise, the quality of the available evidence is poor. One study found that the early restart of an athlete's career was significantly related to higher leg BMD (Miyahara 2008). Some studies show that there may be some effect of electrical stimulation (Maïmoun 2004). One randomized trial did not indicate any benefit from low-intensity pulsed ultrasound (Warden 2001). A systematic review on this topic found no conclusive indication of any effective interventions (Biering-Sørensen 2009).
There is a need to determine whether conservative interventions have a significant impact on the prevention of fractures after SCI.
To assess the effects of physical therapy interventions for the prevention of fractures after spinal cord injury (SCI).
Criteria for considering studies for this review
Types of studies
Randomized controlled trials (RCTs).
Types of participants
People with traumatic SCI resulting in some degree of transient or permanent loss of neurological functions. People of any gender or age group can be included in the review.
Types of interventions
Any trial assessing physical therapy interventions, as monotherapy or combined, compared with placebo or no treatment.
Some examples of physical therapy interventions are:
exercise movement techniques,
electrical stimulation therapy,
Types of outcome measures
Search methods for identification of studies
We will not restrict the search by date, language, or publication status.
The Cochrane Injuries Group Trials Search Co-ordinator will search the following electronic databases:
Cochrane Injuries Group Specialised Register (recent version);
Cochrane Central Register of Controlled Trials (The Cochrane Library) (recent issue);
Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to present);
Embase Classic + Embase (OvidSP) (1947 to present);
CINAHL Plus (1937 to present);
PEDro, Physiotherapy Evidence Database (http://www.pedro.org.au/) (1929 to present);
AMED, Allied and Complementary Medicine Database (Ovid) (1985 to present);
ISI Web of Science Science Citation Index Expanded (SCI-EXPANDED) (1970 to present);
ISI Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (1990 to present).
The MEDLINE strategy Appendix 1, which was formulated to retrieve studies for both this review and the review ‘Antiresorptive agents for the prevention of fractures after spinal cord injury’ (Montenegro 2013) will be adapted, as necessary, for each of the other databases.
Searching other resources
In order to identify articles potentially missed through the electronic searches, including grey literature and unpublished studies, the authors will perform an expanded search that includes the following:
Handsearch reference lists of all included studies and of relevant reviews retrieved by electronic searching to identify further relevant trials.
We will screen the proceedings of the 5th and 6th International Society of Physical and Rehabilitation Medicine World Congresses (http://www.isprm.org/meet/past-congresses/).
Authors of included studies and experts in the field will be contacted for any additional published or unpublished data.
In order to find additional literature we will run several Google Scholar searches using one term for a condition (spinal cord, paraplegia, quadriplegia) combined with one term describing non-pharmacological interventions (weight bearing, physical therapy, ultrasonic, short-wave, radio wave, electrical stimulation, magnetic field, vibration). The first 5 pages of each search will be reviewed.
We will search the following online trials registers: www.clinicaltrials.gov/, www.controlled-trials.com/, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) at http://apps.who.int/trialsearch/ using the search string in Appendix 1.
Data collection and analysis
We will work with the Cochrane Injuries Group Trials Search Co-ordinator to run the searches. We will collate the search results using bibliographic software such as EndNote and remove duplicates before two review authors (SV and AV) begin the screening process.
Selection of studies
Two authors (JG and MSV) will independently check the title or abstracts, or both, of the references. The full-text of all potentially eligible studies will be obtained to evaluate whether they fulfill our inclusion criteria. If there is disagreement, another author (CS) will help resolve discrepancies.
Data extraction and management
Two authors (JG and AV) will independently extract data onto pre-designed data extraction and validity assessment forms. A third author (CS) will act as an arbiter in case of disagreement.
The following data will be extracted where possible:
patient characteristics including mean age, age range, duration of spinal cord injury, neurological level (paraplegic versus tetraplegic), type of injury (complete versus incomplete);
Study authors will be contacted for further information if one of the authors requires clarification.
Assessment of risk of bias in included studies
The risk of bias in the included studies will be assessed according to the 'risk of bias table' recommended in Chapter 8 of the Cochrane Handbook (Higgins 2011). We will provide a description and judgements about the following domains for each study: adequacy of sequence generation, allocation concealment, blinding, addressing of incomplete outcome data, likelihood of selective outcome reporting, and other potential sources of bias (for example if co-interventions are present).
One review author will prepare risk of bias tables, and a second review author will check the data for accuracy.
Measures of treatment effect
We will report pooled outcomes as risk ratio (RR) with 95% confidence interval (CI) for dichotomous outcomes, and as mean difference (MD) with 95% CI for continuous outcomes. If different measures are used for continuous outcomes (for example different measures of BMD) we will pool outcomes as standardised mean differences (SMD) with 95% CIs.
Unit of analysis issues
The unit of analysis will be a person with spinal cord injury. Considering the type of intervention, it is likely that only parallel RCTs will be included, so each patient will have received only one intervention. In studies where more than two interventions had been compared (intervention 1 versus intervention 2 versus placebo), extra care will be taken to avoid double counting of patients in the meta-analysis.
Dealing with missing data
We will contact authors of studies not reporting data on the primary outcome. If a response is not received, and for the analysis of secondary outcomes, we will analyse the available data. We will address the potential impact of missing data on the findings of the review in the discussion section using a worst-case and a best-case scenario. In case authors did not report an intention-to-treat analysis (ITT), or have reported a modified ITT analysis, we will reanalyse data following this principle when possible. If not possible we will address the issue in the discussion section of the review.
Assessment of heterogeneity
We will evaluate clinical heterogeneity and combine comparable studies in a meta-analysis where appropriate. To assess statistical heterogeneity within a meta-analysis, we will use a formal statistical test (Q statistic) and the I2 statistic. Statistically significant heterogeneity will be defined as at least one positive test (either P < 0.10 using the Mantel-Haenszel Chi2 test, or > 50% using the I2 statistic).
Assessment of reporting biases
We will investigate the presence of publication bias visually with the use of funnel plots if at least 10 trials are included. We will base evidence of asymmetry on P < 0.10 and present intercepts with 90% CIs. Other reporting biases, including outcome reporting bias, will be evaluated through discrepancies between the registered protocol and the final publication. In case we can not find the record of a study in the WHO ICTRP or other prospective registers, we will contact authors for more information.
We will perform statistical analysis in accordance with the guidelines for statistical analysis described in the Cochrane Handbook (Higgins 2011). We will use a random-effects model for the analyses.
Subgroup analysis and investigation of heterogeneity
The influence of the following factors on the outcomes will be assessed by subgroup analyses.
Duration of spinal cord injury (less than one year versus more than one year).
Neurological level (paraplegic versus tetraplegic).
Type of injury (complete versus incomplete).
We will perform sensitivity analyses to address the impact of allocation concealment.
We would like to thank Marcela Rivera and Romina Torres who provided great support and assistance in the development of the search strategies; and Emma Sydenham and other members of the Cochrane Injuries Group who provided us with invaluable help.
Appendix 1. Search strategies
1. exp Spinal Cord Injuries/
2. exp Spinal Cord Ischemia/
3. exp Central Cord Syndrome/
4. (myelopathy adj3 (traumatic or post-traumatic)).ab,ti.
5. ((spine or spinal) adj3 (fracture* or wound* or trauma* or injur* or damag*)).ab,ti.
6. (spinal cord adj3 (contusion or laceration or transaction or trauma or ischemia)).ab,ti.
7. central cord injury syndrome.ab,ti.
8. central spinal cord syndrome.ab,ti.
9. exp Cervical Vertebrae/in [Injuries]
10. exp Spinal Cord/
12. exp Paraplegia/
13. exp Quadriplegia/
14. (paraplegia* or quadriplegia* or tetraplegia*).ab,ti.
16. exp Osteoporosis/
17. exp Bone Density/
18. exp Osteoporotic Fractures/
19. exp Absorptiometry, Photon/
20. exp Densitometry/
21. exp Fracture Fixation/
23. (Osteoporo* or Absorptiometry or Densitometry).ab,ti.
24. (Bone* adj3 (break* or broke* or density or "mineral content")).ab,ti.
26. 15 and 25
28. randomized controlled trial.pt.
29. controlled clinical trial.pt.
31. clinical trials as topic.sh.
34. 27 or 28 or 29 or 30 or 31 or 32 or 33
35. (animals not (humans and animals)).sh.
36. 34 not 35
37. 26 and 36
"spinal cord" OR SCI OR quadriplegia OR paraplegia
Contributions of authors
All authors contributed to the protocol.
Maria Soledad Villagra and Andrea Velasco will join as authors on the full review.