Objective We explored the effect of adjunctive acupuncture on secondary osteoporosis in patients with spinal cord injury (SCI).
Methods Patients with subacute SCI were recruited and divided into two groups by patient choice: group 1 patients received standard combination therapy and group 2 patients received combination therapy plus acupuncture for 3 months. The concentrations of IgG, IgM and tumour necrosis factor α (TNFα) in serum and the bone mineral density were measured before and after treatment.
Result The decrease in the concentration of TNFα and IgM in patients in group 2 compared with those in group 1 was statistically significant. The IgG level showed no significant change in either group. Bone mineral density increased more after adjunctive acupuncture, but the difference was not significant.
Conclusions Further research is needed to determine whether acupuncture as an adjunct to combination therapy can reduce osteoporosis in patients with subacute SCI.
Trial registration number P153-2008-36
- CLINICAL PHYSIOLOGY
- OSTEOPOROSIS ARTHRITIS
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Osteoporosis is a known complication of spinal cord injury (SCI), occurring predominantly in the pelvis and the lower extremities.1 ,2 The decline in bone mineral density (BMD) and bone mineral content has been amply documented in patients with acute and chronic SCI.3 ,4 Bone loss occurs rapidly in the acute phase of the injury and slows 2–3 years after injury.5 While the nature and magnitude of the effects of SCI on bone vary by skeletal site, sex and age,6 all individuals with motor complete SCI develop osteoporosis below the level of the injury.
The mechanism of osteoporosis in patients with SCI is complex. It has been reported that unloading, neuronal changes such as skeletal innervation, neuropeptide activity and hormonal changes such as parathyroid hormone and vitamin D are involved in the process of osteoporosis in patients with SCI7 ,8 and are relevant directly or indirectly in the treatment of osteoporosis in these patients.9–11
Acupuncture has been used for the treatment and prevention of disease in China for thousands of years. Clinical research has suggested that acupuncture could increase the bone mass density and alleviate pain in patients with primary osteoporosis.12–15 After SCI, leucocytes infiltrate the injured cord, causing significant damage and further impairing functional recovery; evidence suggests that acupuncture may enhance immune function after trauma in vitro and in vivo.16–18
In our study we observed the effect of acupuncture on cytokines (tumour necrosis factor α (TNFα), IgM and IgG) and investigated its effect on the BMD of the lumbar spine and intertrochanteric femur in patients with SCI.
The patients had an incomplete spinal cord lesion of sudden onset between C6 and T12 and were motor incomplete (grade C or D on the American Spinal Injury Association (ASIA) neurological impairment scale). The injury must have occurred between 1 and 6 months prior to recruitment. The patients were all inpatients who were receiving treatment in the department of rehabilitation.
Patients were excluded if they had contraindications for functional electrical stimulation such as cardiac pacemakers; skin lesions or rash at potential acupuncture sites; denervation of targeted muscles (except tibialis anterior, ST36; and peroneus longus, GB34); pressure ulcers anywhere on the lower extremities; uncontrolled hypertension; symptoms of orthostatic hypotension when standing for 15 min; or susceptibility to autonomic dysreflexia requiring medication.
The diagnostic criteria of osteoporosis followed section 6 of the diagnosis of secondary osteoporosis guideline published in 2011 by the Osteoporosis and Bone Mineral Disease branch of the Chinese Medical Association: a BMD <80% of the age-matched adult mean at the trabecular metaphysical-epiphyseal areas of the distal femur or the proximal tibia.
According to the principle of voluntary choice of patients and their families, a total of 40 patients in our department were recruited from January 2009 to April 2012. Their age ranged from 25 to 55 years, 27 cases were male and 13 were female (none menopausal). This was the number available during the study recruitment period. The participants were divided into two groups by choice: standard combination therapy was applied in group 1 patients and patients in group 2 received standard combination therapy plus 3 months of acupuncture treatment. The clinical and demographic characteristics of the patients are shown in table 1. Patients unwilling to accept acupuncture and moxibustion were assigned to group 1.
Before the study and during the 3-month study period, all patients received standard combination therapy following the routine procedure. Oral calcium amino acid chelate was administered (one capsule twice a day). Patients were asked to perform standing practice in an electric standing bed (SH Medical Equipment, Guangzhou, China) for 30 min twice a day. Massage was given along the GV meridian and ST foot Sanyang meridians 10 times during 3 months. Pulsed magnetic field therapy, which has been reported to benefit osteoporosis,19 was given. The patients lay supine on a pulsed magnetic field bed and pulsed magnetic field therapy with field strength 2–10 G and a frequency of 20 Hz was given to the whole body daily for 40 min each time for 3 months.
In addition to the combination therapy described above, patients recruited to the acupuncture group received acupuncture treatment according to Traditional Chinese Medicine (TCM) principles. The acupuncture point selections were based on TCM theory to treat Bi and Lou syndrome based on previous clinical reports.20 ,21 Acupuncture and moxibustion therapy were performed by two certified physicians with more than 5 years of experience in acupuncture treatment. The acupuncture treatment was divided into two alternating treatments: treatment 1 was applied at GV14 Dazhui, GV4 Mingmen, BL11 Dazhu (bilateral), BL23 Shenshu (bilateral), BL20 Pishu (bilateral) and BL21 Weishu (bilateral) and treatment 2 was applied at ST36 Zusanli, SP6 Sanyinjiao (bilateral), KI3 Taixi (bilateral) and GB34 Yanglingquan (bilateral). Needles 5 cm long with a diameter of 0.25 mm (Huanqiu Acupuncture Medical Appliance, Suzhou, China) were inserted to a depth of 0.6 cun with a twisting reducing and reinforcing technique and retained for 20 min. The two alternating treatments were applied on alternate days. Acupuncture treatment 2 included electroacupuncture (EA) (2 cun needle) at SP6 (bilateral), KI3 (bilateral) and GB34 (bilateral) using a BT701-B EA apparatus. EA treatment was performed using alternating 50 and 100 Hz for 30 min. Each course lasted 10 days followed by 2 days of rest; a total of 10 courses were given.
During the acupuncture treatment a moxa stick moxibustion was supplied at CV8 Shenque for 30 min at a distance of 4 cm with a temperature of 45°C at night.
Blood samples were taken from both groups of patients by standard venepuncture on recruitment and after 3 months of treatment. The separated samples were allowed to clot for 30 min and centrifuged at 3400 rpm for 10–15 min. They were then separated into plastic vials and frozen at −20°C or colder until just prior to immunoassay using a commercial ELISA kit (Becton Dickinson). A cytometric bead assay was employed to measure levels of TNFα, IgM and IgG in plasma according to the manufacturer's instructions.
Densitometry was performed to evaluate the treatment effect of acupuncture. The BMD (g/cm2) of the lumbar spine and intertrochanteric femur were measured using dual energy X-ray absorptiometry (Hologic QDR 1000) after recruitment and at the end of treatment after 3 months.
The results are expressed as means±SE. Data were compared using the t test and χ2 test, respectively. A p value <0.05 was considered as significant. SPSS V.19.0 statistical software was used.
During the treatment period no serious acupuncture- and moxibustion-related adverse reactions occurred. The most common adverse effects were needle site bleeding and subcutaneous bleeding, all of which were effectively controlled. All patients completed 3 months of treatment, and all the patients in the acupuncture group received all 100 acupuncture treatments.
Change in TNFα level after treatment
As shown in table 2, TNFα levels in both groups decreased after treatment, but the change was only statistically significant in group 2 who received combination plus acupuncture therapy (p<0.01). The TNFα level was significantly lower in the acupuncture group than in the group who received combination therapy alone (p=0.028).
Change in IgM and IgG after treatment
For the group who received combination therapy, the mean IgM level showed minimal change after treatment but was significantly lower in the group receiving acupuncture therapy (p<0.01 compared with before treatment). After treatment IgM was significantly reduced in the group who received acupuncture compared with those receiving combination therapy alone (p=0.002, table 2).
The IgG level in both groups decreased but the change was not statistically significant.
Bone mineral density
After treatment for 3 months the BMD values of L2–3 lumbar spine and intertrochanteric femur in both groups were increased. The change was not significant (p=0.061 and p=0.124 for L2–3 lumbar spine and intertrochanteric femur, respectively) in patients who received combination therapy, but the increase was significant in the group who received combination plus acupuncture therapy (p=0.000 and p=0.000 for L2–3 lumbar spine and intertrochanteric femur, respectively). The difference between groups was not statistically significant (p=0.253 and p=0.314 for L2–3 lumbar spine and intertrochanteric femur, respectively; figure 1).
In this study on the effect of acupuncture and moxibustion on secondary osteoporosis in patients with SCI we found significantly greater reductions in TNFα and IgM in the group who received acupuncture, moxibustion and combination therapy than in those who received only combination therapy, but no significant difference in IgG or BMD.
The significance of osteoporosis after SCI is that it results in skeletal fragility and an increased risk of fractures. Complications from fractures lead to an increase in the associated morbidity and mortality and also in the healthcare costs that they generate.22
There is some evidence that different acupuncture points stimulate different cerebral areas and conditioned reactions.23 ,24 In a SCI study, after EA stimulation the gene expression of calcitonin gene-related polypeptide and neuropeptide Y were upregulated and functionally correlated with the recovery of sensory functions.25 Han et al reported that EA decreased water channel aquaporin-4 expression in SCI rats and increased hind limb functional recovery, and concluded that EA inhibits oedema of the spinal cord, eliminating secondary injury, preserving the remnants of the normal spinal cord tissue and promoting nerve tissue reconstruction.26 Ikjma et al reported that acupuncture treatment regulated the expression of TNFα in a postmenopausal osteoporosis rat; moreover, this study reported that moxibustion therapy had a similar effect.27 Our results were consistent with these results.
Evidence from mouse models has demonstrated that EA or acupuncture stimulation at ST36 can modulate the immune response.28 ,29 Recent studies have shown that EA at ST36 could regulate the neuroendocrine immune network.30 BL23 and BL20 are commonly used acupuncture points to improve bone mass and structure in osteoporosis. Zhang et al demonstrated that acupuncture at BL23 and BL20 promoted bone formation and also suppressed the bone resorption induced by ovariectomy in osteoporotic rats.31 Using other points, we showed that secondary osteoporosis in patients with subacute SCI improves after acupuncture, and the results are consistent with other studies in primary osteoporosis.32 ,33
SCI causes significant damage and is followed by inflammatory reactions; these inflammatory cells may induce immune responses, resulting in changes in a large number of inflammatory mediators such as IgM, IgG and TNFα. Davies et al34 indicated that serum levels of the proinflammatory cytokines interleukin and IgG and IgM in patients with SCI were much higher than matched healthy controls, and concluded that this could indicate a protective autoimmunity or may simply be a consequence of occult or evident infection or evidence of cytokine dysregulation that may contribute to an immune-mediated impairment of axonal conduction. Our study suggests that these factors are influenced by combination therapy and adjunctive acupuncture. Acupuncture treatment is commonly used in TCM hospitals for patients with SCI, but there are few research studies of the changes in related factors.
A number of animal experiments have shown that targeted interventions on the above factors in the acute or subacute setting can play a therapeutic role.35–37 In this study we selected the therapeutic window as 1–6 months after SCI for these patients because raised levels of immunoglobulins and TNFα are typical characteristics of patients with SCI.38 Early intervention and treatment is important for the recovery of these patients.
Osteoporosis is typically a disease of women, and most osteoporotic fractures occur among postmenopausal women.39 ,40 In our study we analysed the effect of acupuncture in male and female patients separately and found no differences between them, although the study was not designed for this purpose and the sample size was not sufficient to be definitive. This finding needs to be verified in clinical trials with a larger number of patients. Generally, there is a different baseline for male and female propensities to osteoporosis but, in the present study, none of the female patients was menopausal. Unloading and disuse are still the two main reasons for osteoporosis in patients with SCI, and there was no significant difference between male and female patients at baseline in the present study (data not shown).
Osteoporosis is one of the most frequent complications following SCI, resulting from an imbalance in bone formation and resorption. Although unloading after SCI is considered to be the most important factor in the development of osteoporosis, other factors are involved in this process. Thus, it was hypothesised that the neural lesion itself after SCI may play a pivotal role in the pathogenesis of osteoporosis by a direct role in denervation on bone or indirectly by disrupting vasoregulation. The effect of acupuncture on the regulation of immunoglobulins and TNFα during the acute stage of SCI needs further study in properly randomised trials.
There are several limitations in the present study, such as the small numbers, group allocation by patient choice and short follow-up. There are also limitations in the measurement of BMD which is subject to 10% error and may not really be relevant over such a short period as 3 months. We will extend the follow-up period in a possible future study to test for prevention of osteoporosis in the acute post-traumatic period.
Acupuncture has been reported to have an effect in osteoporosis.
We compared the effect of adjunctive acupuncture in patients with spinal cord injury.
There were significant reductions in TNFα and IgM after acupuncture, but not in IgG or bone mineral density.
QM and XL contributed equally.
Contributors TZ defined the research theme. QM and XL designed the methods and experiments, carried out the study, analysed the data, interpreted the results and wrote the paper. QS and PY co-worked on associated data collection and their interpretation. FZ and JL co-designed the experiments and discussed the analyses, interpretation and presentation.
Competing interests None.
Ethics approval This observational study was registered at the Institute of Orthopaedics and Traumatology of Chinese PLA, General Hospital of Jinan Military Area Command and was approved by the hospital Ethics Committee (P153-2008-36). All work was undertaken following the provisions of the Declaration of Helsinki.
Patient consent All participants signed a written informed consent form.
Provenance and peer review Not commissioned; externally peer reviewed.
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