Bone Mineral Density Can Be Kept In Spinal Cord Injured Subjects Under Long Term NMES

Objective: Analyze the contribution of rehabilitation with neuromuscular electrical stimulation (NMES) assessing bone mineral density (BMD), quality of life aspects and demographic characteristics, after 10 years under treatment. Methods: Retrospective longitudinal study between 2008 and 2020, at Spinal Cord Injury Outpatient Clinic, University Hospital, with 24 individuals with spinal cord injury in rehabilitation with NMES. Identication questionnaire, Functional Independence Measure (FIM) and bone density exam were used for, respectively, demographic analysis, quality of life and BMD. Data from 2008 were catalogued as Pi and current data as Pa. Student’s T-test was used for statistical evaluation, being signicantly relevant when p < 0.05. Results: Mean age was 45.3 years old, with 22 male individuals; 14 are paraplegic and 10 are tetraplegic; 13 individuals presented injury by trac accident, 2 by fall from height, 4 by dive, 4 by rearm injury and 1 by tumor; 11 individuals with cervical-level injury and 13 thoracic-level injury, all with complete disability. FIM average Pi=80.2 and average Pa=84 (p=0.36); BMD of vertebrae L1-L4 average Pi=- 0.02 and average Pa=-0.17 (p=0.50); BMD of femoral neck average Pi=-2.1 and average Pa=-1.9 (p=0.12); outcomes: 2 osteopenia and 1 osteoporosis for L1-L4; 18 osteopenia and 4 osteoporosis for femoral neck. Conclusion: Demographic characteristics were compatible to literature, except for the age. FIM score and BMD remained similar to the beginning of treatment with NMES, concluding that there was stabilization of these parameters during treatment.


Introduction
People with spinal cord injury present motor, sensitive and autonomic disabilities 1 . In addition to the neurological loss, they could have problems related to self-esteem, loss of functional independence and social isolation. The costs to the national health system and to the government provident funds with diagnosis, treatment, recovery and rehabilitation are high.
Spinal cord trauma worldwide incidence is about 10-60 cases per million inhabitants depending on the country 2,3 . In Brazil, the incidence is estimated in around six to eight thousand new cases per year, 80% of which are male. Moreover, 60% of the victims are aged between 10 to 30 years old 1 .
Traumatic origin is the most prevalent cause of spinal cord injury according to the literature. Studies done in rehabilitation centres show that tra c accidents are the leading cause of trauma, followed by gunshot wounds. The non traumatic mechanisms, around 20% of spinal cord injuries cases, comprise infections, tumor growth, metastasis, herniated disc, autoimmune diseases and other etiologies 1 .
Reduction in bone mineral density (BMD) is signi cant in spinal cord injured people, with osteoporosis being a recurrent complication 4,5,6 . These individuals are known to be the population parcel who suffers the most with loss of bone mass, about 1% per week, in speci c regions of the body, in the rst months after injury 4,7 .. Neuromuscular electrical stimulation (NMES) is a rehabilitation strategy used in spinal cord injury 8 , which allows individuals to remain in the orthostatic position, also enabling movements, reducing contractures, spasticity, osteoporosis and deformities. There is an improvement in energy e ciency, which increases self-performance aiming to execute activities of daily living 9 , what can be quanti ed by The present study aims to analyze the contribution of rehabilitation with neuromuscular electrical stimulation (NMES) assessing bone mineral density (BMD), quality of life aspects and demographic characteristics, after 10 years under treatment. We hypothesized that there is alteration in BMD of spinal cord injured patients with NMES rehabilitation over the years.

Methods
Retrospective longitudinal study carried out between January 2008 and January 2020, approved by the Informed consent to publish identifying information/images was obtained from all participants. Informed consent to study participation was obtained from all participants.
Data from 2008 were catalogued as Pi and current data, after 10 years of evolution, as Pa. The inclusion criteria were: spinal cord injured individuals with intact lower motor neuron, minimum injury time of 1 year and beginning in rehabilitation programme.
Twenty four individuals from Spinal Cord Injury Outpatient Clinic at Unicamp were treated with NMES associated with a partial weight support system which supports bipedal gait through the use of walkers for paraplegia or suspension equipment for tetraplegia, both allowing for free movements of hip and knee joints 10 ( gures 1 and 2). The feet and ankle joints were protected with ankle-foot orthosis. The quadriceps and tibialis anterior muscles are stimulated towards gait. The stimulator uses four channels yielding a signal of 25 Hz with monophasic rectangular pulses of 300 microseconds at a maximum intensity of 150V (1 kilo Ohm load) along two weekly sessions lasting 20-30 minutes each.
Individuals were investigated about their demographic characteristics (age, sex, injury level, trauma mechanism), ASIA Impairment Scale 11 , FIM and bone density.
Bone density and functional independence measure data were compared at the beginning and throughout the rehabilitation period.
Demographic characteristics were outlined between January 2020 and March 2020.
The BMD was assessed through bone density exam of the lumbar spine and femoral neck using the dualenergy X-ray absorptiometry method (Luna DPX -Luna Radiation Corporation, Madson, WI). Results were analyzed comparing the standard deviation (SD) of young adult reference ranges (T-Score) 12 : up to -1.0 SD = normal; from -1 to -2.5 SD = osteopenia and; below -2.5 SD = osteoporosis.
Student's T-test was used for statistical evaluation among the groups and signi cant differences between the results when p < 0.05.

Results
BMD assessment for L1-L4 vertebrae resulted in Pi with an average of -0.02 (varying from -2.1 to 3.5) and Pa with an average of -0.17 (varying from -2.6 to 4.4), where p was 0.50, not having, thus, statistically differences between the paired samples.
The analysis of the 24 bone density exams of the femoral neck had Pi with an average of -2.1 (varying from -4.4 to -0.1) and Pa with an average of -1.9 (varying from -4.2 to -0.9), where p was 0.12, not having statistically difference between the paired samples. The analysis of subjects' individual SD, in most recent bone density exams (Pa), resulted in the following classi cation: 21 individuals as normal, two as osteopenia and one as osteoporosis for lumbar spine; two individuals as normal, 18 as osteopenia and four as osteoporosis for femoral neck (Table 1).  . In relation to the mechanism of trauma, 13 individuals presented injury by tra c accidents (motorcycle or automobile accident or being run over), 2 by fall from height, 4 by dive in shallow water, 4 by rearm injury and 1 by bone tumor ( Table 1). The average time of injury was 14.8 years (varying from seven to 25 years).
Regarding the evolution of treatment over 10 years, those individuals analyzed by FIM obtained Pi with an average of 80.2 (varying from 25 to 124) and Pa with an average of 84 (varying from 66 to 106), with p being 0.36, without existing statistically differences between the paired samples. Studies show that spinal cord injury is associated with higher prevalence of cervical-level injury 14,15,16,17 .

Discussion
However, the present study differs from those, presenting 13 individuals (54%) with thoracic-level injury and 11 (44%) with cervical-level injury.
The literature points out that the higher increase of FIM scores occurs in the rst years after injury and, after approximately ve years, the scores stabilizes, existing little improvement in independence level, because it is understood that the maximum level of independence was obtained according to the level injury 18 . Data obtained from the study agree with literature, because there was stabilization of the scores of most individuals.
Regarding bone mass quality, in this study, it was found 79% of osteopenia prevalence and 21% of osteoporosis, on any of the structures analyzed (lumbar spine and femoral neck). These data illustrate how much this population is affected by high degrees of bone loss. Some studies point out that these individuals lose up to 50% of bone density in the rst year of injury, which tends to stabilize after the second year 19 .
Although the pathophysiological mechanisms of this process are not yet totally elucidated, sublesionals central and peripheral neural denervations seem to have strong in uence on bone mass loss, once they act on osteoanabolic metabolism 4 . Other possible mechanisms which may be responsible for this event include the gravity change due to immobilization, the loss of anabolic factors (for example, testosterone and/or circulating growth hormones), the factors in bone local environment (paracrine in uences of muscle atrophy) and the presence of catabolic factors at the time of injury (such as administration of high doses of methylprednisolone within a few hours after the acute and/or systemic event and/or the local production of in ammatory mediators or cytokines) 4,19 .
In this study, it was also evidenced that femur is the most affected region by bone loss, with the prevalence of osteopenia approximately 75% and of osteoporosis 17% for femoral neck; and 8% of osteopenia and 4% of osteoporosis for lumbar spine.
In the study of Sabo et al 20 , the authors also found BMD reduced in proximal femur, but not in lumbar spine. This is justi ed because, in order to avoid bone loss, it is necessary to have normal muscular function and load, variables practically absent in the femur and partially present in the lumbar spine, which supports the load of individual's body while using the wheelchair 21 .
In relation to the effects of NMES treatment on bone density of spinal cord injured individuals, literature does not show a consensus. Studies that investigated its effects on bone are con icting 22 . Several methodological limitations restrict the capability to con rm the utility of this intervention in order to improve the skeletal status 22 . In Forrest et al 23 the authors observed a decrease of total BMD (1.54%) and regional BMD (legs: 6.72%).
In Giangregorio et al's study 24 , authors concluded that this intervention is not enough to prevent bone loss, as it was evidenced by BMD reduction for all individuals varying in magnitude from 1.2 to 26.7% for lower limb and 0.2 to 7.4% for lumbar spinal.
On the other hand, in the study carried out by Mohr et al 25 , a 10% increase of BMD for proximal tibia was described, but no difference for femoral neck and spine. In the study of Coupaud et al 13 , it was also veri ed an increase of BMD for distal tibia (5% for right leg and 20% for left leg). However, the results were insigni cant for proximal tibia and for the femur. In this study, improvement of BMD of the femoral neck and worsening of BMD of the lumbar spine were found. Even though, data obtained were not statistically signi cant, preventing us from making statements and comparisons with other studies.
Limitations of this study include the small sample of 24 individuals and their di culty to maintain 10years follow-up treatment because of socioeconomic and psychological reasons, functional dependence and comorbidities due to the level of the spinal cord injury. Larger studies should be carried out for better future analysis and adjustments in these factors would help to continue the treatment of these patients.
The demographic pro le of patients was compatible to the one found in literature in the characteristics analyzed, except for the age, which is higher among patients in this study. About functional independence measure score and bone mineral density, they remained similar to the beginning of the treatment with neuromuscular electrical stimulation (NMES), concluding that there has been stabilization of these parameters during 10 years of treatment.. Our long term results do show that it is feasible to preserve BMD thus avoiding bone fractures, due to disuse osteoporosis in spinal cord injury subjects. Use of walker for paraplegics to perform NMES