Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the volume of bone tissue.1 It has been defined more explicitly as a disease characterized by low bone mass, microarchitectectural deterioration of bone tissue leading to increased bone fragility and consequential increase in fracture risk.2 Pulsed electromagnetic fields (PEMFs) stimulation has been in clinical use for over thirty years for patients with delayed fracture healing and non-unions.
Based upon multicenter, randomized and prospective clinical studies, the Food and Drug Administration, USA, approved PEMF as safe and effective method for treating nonunions and for osteoporosis therapy.3,4 Exogenously applied electromagnetic fields (EMF) affect bone metabolism, both in vivo and in vitro. It can improve bone mineral density (BMD) and biomechanical properties and decelerate the bone resorption process in vivo.5,6 While in vitro it can enhance osteoblast activity but cause significant reduction in osteoclast formation, activity and survival7,8 shifting the balance towards osteogenesis by affecting both pathways of bone metabolism. This review of the advances in the therapy for osteoporosis will briefly discuss the effect of PEMFs on chronic bony pain, bone mineral density, bone strength and biochemical markers of bone metabolism in the patients with osteoporosis.
EFFECT OF PEMFs ON PRIMARY OSTEOPOROSIS
Effect of PEMFs on chronic bony pain of patients with primary osteoporosis
Chronic bony pain is the most common symptom and cause of medical treatment in patients with primary osteoporosis which affects people’s quality of life.9 Therefore, many studies had concentrated in the analgesic effect of low-frequency pulsed electromagnetic fields.
Several observations10-14 and randomized controlled trials15,16 demonstrated that most patients with primary osteoporosis can get pain alleviation after 30-60 days treatment of PEMFs. This effect can even appear after therapy for two or three days and is significantly correlated with the number of therapies.17 One study10 that consisted of 126 subjects found that patients with type I osteoporosis got better effects than those with type II. Furthermore, PEMFs can significantly ease the pain in osteoporosis patients without joints degeneration; especially in the 40-60-year-old female patients with type I osteoporosis. And the pain of patients with type II osteoporosis, who were more than 70 years old and suffered from hyperostosis, was relieved slowly and may require more than ten treatments to reduce the general chronic pain. Another observation18 confirmed that PEMFs can not only ease chronic bony pain, but also lighten leg cramps, improve symptoms of insomnia or bad sleep, lower blood pressure, reduce the numbers of nocturia and eliminate edema in the lower extremities.
It is well accepted that PEMFs effectively relieves chronic bony pain20-22 without any side-effects10-11,13,14,20 after treatment of 40 minutes five times a week. The frequency of PEMFs was often below 50 Hz and the magnetic field intensity was different in each study but not more than 20 mT. Although the therapeutic parameters were not the same, the pain relief effect of PEMFs on primary osteoporosis was similar. Nevertheless, these results were not the best evidences because that fewer randomized controlled trials or multicenter studies were included and are meant only as recommendations of the clinical application of PEMFs for osteoporosis. Otherwise, the evaluation standard of pain relief were different, only one study12 applied the Visual Analogue Scale (VAS), which is a quantitative pain evaluation, the others used a qualitative evaluation. No study reported a blinded assessment which is recommended for pain relief evaluation. Further strict studies are needed to verify the pain relief effect of PEMFs.
Effect of PEMFs on bone mineral density of patients with primary osteoporosis
Bone mineral density is the gold standard for diagnosing osteoporosis and the best quantitative indicator for forecasting the risk of osteoporotic fracture, monitoring the natural course of osteoporosis and evaluating the effect of pharmacological intervention.9 Many studies at home and abroad have been concerned with altering BMD by treatment of PEMFs for patients with osteoporosis as well as considering chronic bony pain in the same study.11-13,15,20,21
There were three points of consideration of the impact of PEMFs on bone mineral density. First, some researchers considered that PEMFs enhanced bone mineral density. As early as 1990, Tabrah et al23 reported that PEMFs increased BMD of osteoporosis-prone women. They exposed the nondominant forearms of 20 subjects to 72 Hz PEMF 10 hours daily for a period of 12 weeks and found that the bone mineral densities of the treated radius increased significantly in the immediate area of the field during the exposure period and decreased during the following 36 weeks while a similar but weaker response occurred in the opposite arm. BMD of lumbar15,24 as well as femoral neck, Wards triangle and Trochiscus25 in 116 patients who received therapy with PEMFs was higher after six months of therapy than in the placebo group.
One randomized controlled trial26 compared three months of estrogen therapy and estrogen combined with PEMFs with PEMFs alone on bone mineral density of patients with postmenopausal osteoporosis. The bone mineral density was greater in the combined group, estrogen therapy and PEMFs, than before. But what is regrettable is that there was no comparison among the three groups. Another randomized controlled trial suggested a similar result comparing PEMFs plus calcitonin with calcitonin alone in 64 subjects after treatment for 65 days.27 But in another randomized controlled trial28 that compared PEMFs to an integrated pharmacological therapy (calcitonin, diphosphonic acid salt and fluoride et al), while both groups accepted the same treatment of calcium and alfacalcidol, there was no significant change between PEMFs and the integrated pharmacological therapy. It was speculated that the two methods had a similar effect, however there was no equivalent test. Recently, one study22 that contained 300 subjects suggested that PEMFs increased BMD 2-3 months after therapy. But it was not a randomized controlled trial.
Another finding was that PEMFs did not affect bone mineral density of patients with osteoporosis. Giordano et al29 lead a randomized single-blind controlled trial to observe the effect of 100 Hz PEMFs on bone mineral density, serum osteocalcin and procollagen type I C-terminal propeptide (ICTP). The bone mineral density was not increased significantly after PEMFs treatment for 60 minutes per day, three times a week which lasted 6 months. A study of 16 subjects by Chen et al11 suggested that after 60 day therapies the BMD was greater than before but with no statistical significance. Yang et al12 assessed the BMD again 3 months after PEMFs treatment and found no significant improvement. This may relate to the small sample size of cases, short duration and high frequency used.
The third view was that PEMFs can improve bone mineral density of the hip and femoral neck but not the lumbar spine. Gao et al13 evaluated the bone mineral density 2 months after treatment and found that the bone mineral density of the hip and femoral neck had increased significantly while the difference of mean bone mineral density of L2-4 had not. The small sample (18 subjects) may have influenced the results.
There were also reports about the long-term effects of PEMFs on bone mineral density of osteoporosis patient from home and abroad. Tabrah et al30 remeasured the bone density of radii after eight years and found no long-term changes. Zhou et al24 found that the bone mineral density increased significantly 2-6 months after three 30-day periods of therapy. Liu et al21 observed that BMD was still higher than the control group 3-4 months after 30 days of therapy. Thus we inferred that the improved BMD effect of PEMFs can last for at least 3-4 months which indicated that osteoporosis patients would not be treated every day. But the long-term effect and safety of PEMFs, when comparing PEMFs alone or in combination with exercise and pharmacologic agents such as bisphosphonates and hormones, should be further studied because that osteoporosis develops with aging.
Although the effect of PEMFs on improving bone mineral density is still uncertain, an improving trend occurred. Low frequency, which is often below 50 Hz 20 mT, appropriated length of PEMFs therapy, which is at least 30 days,20,21,24 would be good for osteoporosis patients. Otherwise further studies with more subjects will be needed to confirm whether PEMFs can enhance bone mineral density and at which sites bone miner density can be improved. The appropriate sample size and duration must also be considered. Most current researches were focusing on the change of bone mineral density before and after treatment which reduces the strength of the evidence due to many interfering factors. Thus randomized double-blind controlled trails are needed to determine the effect of PEMFs on bone mineral density.
Effect of PEMFs on bone strength in patients with osteoporosis
Zhang et al16 assessed the bone strength by ultrasound of group receiving PEMFs and drug treatment and a group receiving pharmacological therapy alone. They found that after treatment with PEMFs and drug, the broadband ultrasound attenuation (BUA), speed of sound (SOS) values of the right calcaneus were statistically greater than before while the values in pharmacological therapy group were not. But there was no comparison between the two groups.
Effect of PEMFs on biochemical markers of bone metabolism for primary osteoporosis
Biochemical markers of bone metabolism9 are the metabolites in the process of bone metabolism produced by osteoblast and osteoclast which indicate the activity of bone formation and bone resorption. Biochemical markers can reflect the condition of bone remodeling, diagnose metabolic bone diseases early, indicate bone loss and fractures and monitor pharmacological effect.
Serum osteocalcin and alkaline phosphatase are the main markers of osteoblastic activity. Studies showed that PEMFs increased the level of serum osteocalcin after one13 or two15 months of treatment. But the difference in serum total alkaline phosphatase (ALP) level was not significantly changed before and after treatment which are affected by the ratio of bone ALP. But one study28 demonstrated that PEMFs increased the level of serum ALP. The change of ALP may be caused by pharmacological effect.
However, the effect of PEMFs on bone resorption activity that was reported was controversial. The concentrations of urine hydroxyproline did not change significantly in either the PEMFs combined with calcium group or in the calcium alone group.15 It suggested that PEMFs had no effect on bone resorption. However, the investigation of Gao et al14 showed that PEMFs effectively increased serum ICTP. Xiong et al31 also observed that PEMFs increased or maintained bone mineral density by inhibiting the bone resorption activity. Hydroxyproline also existed in other tissues and was influenced by food; the change of urine hydroxyproline can not represent the activity of bone resorption. Experiments demonstrated that PEMFs increased bone formation and decreased bone resorption,5-8 further clinical trails that confirm the effect of PEMFs on bone formation and resorption are warranted.
Effect of PEMFs on bone mineral density of patients with secondary osteoporosis after spinal cord injury
After spinal cord injury bone metabolism changed rapidly resulting in bone loss, bone structure damage and increased risk of fractures. The markers of bone metabolism become abnormal just one week after spinal cord injury; BMD and bone structure changed 2 to 6 weeks after injury which mainly occurred in cancellous bone and was characteristic of active bone resorption in animal and human studies. Cross comparative studies showed that the impact of SCI on bone metabolism and bone strength was greater than that of estrogen deficiency. The secondary osteoporosis caused by SCI was different from endocrine disorders and from disuse.32,33
Garland et al34 lead a study that consisted of 6 male patients with complete spinal cord injury of a minimum of 2 years duration. The time of therapy of PEMFs continued for 6 months and at 3 months BMD increased in the stimulated knees by 5.1% and declined in the control knees by 6.6% (P <0.05 and P <0.02, respectively). By 6 months the BMD returned to near baseline values and at 12 months both knees had lost bone at a similar rate. It was demonstrated that PEMFs can delay bone loss and there may exist both a local and a systemic response. Another study35 consisted of 24 patients with SCI who were then divided into two groups, BMD of the total proximal femur and trochanter of patients in the treatment group were increased significantly compared with the control group. Both of the trials indicated that the increase in BMD effects of PEMFs may relate to the features of the subjects. People with spinal cord injury are younger than osteoporosis patients, the osteoblasts and osteoclasts of patients with spinal cord injury may be more sensitive to the PEMFs stimulation than that of the old people.
SIDE EFFECT OF PEMFs
Ten studies10,11,13,14,20,23-25,28,31 observed no side effects of PEMFs stimulation by describing treatment response and testing blood, serum, liver and kidney function along with levels of serum calcium and phosphorus. None of them reported other side effects, thus PEMFs is approved as safe for osteoporosis by short term application.
PEMFs have been developed as a non-drug treatment for osteoporosis in recent years. Clinical studies have shown the therapeutic efficacy of PEMFs in primary and secondary osteoporosis which can relieve chronic bony pain quickly and efficiently with no side effects. But it is still controversial whether PEMFs enhanced the bone mineral density of patients with primary osteoporosis. The effect of PEMFs on biochemical markers of bone metabolism confirmed that PEMFs promoted bone formation which may partly elucidate the mechanism of PEMFs for osteoporosis. However, reports of the effects on bone resorption were not consistent. Furthermore, the long-term efficacy, prevention of osteoporotic fracture, effect on daily life and quality of life and safety need further study. Moreover, the intensity, frequency and therapeutic course have not been standardized. As many studies were observational which were not the best studies as required by the evidence-based medicine, more randomized double-blinded controlled trials are warranted to confirm the effects of PEMFs on osteoporosis as well as the interaction with other pharmacological therapy.
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