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PERIODICUM BIOLOGORUM VOL. 117, No 1, 161–165, 2015
Non-pharmacological treatment of osteoporosis with
Nuclear Magnetic Resonance Therapy (NMR-Therapy)
Objectives: To demonstrate the long-term effects of the therapeutic use
of nuclear magnetic resonance (NMR) on bone mineral density (BMD) parameters in patients with osteoporosis. Methods: We enrolled 103 patients aged between 45 and 89 years who
1 Poliklinika K-CENTAR, Zagreb, Croatia had osteoporosis with a T-score of bone mineral density less than -2.5. All 2 Ludwig Boltzmann Cluster for Rheumatology, patients received an osteoporosis treatment with low field nuclear magnetic Balneology and Rehabilitation, Department for resonance using a special NMR device (MBST, MedTec, Germany) for one Rehabilitation, Saalfelden, Austria hour per day on 10 consecutive days. At baseline and 12 months after NMR 3 Private Consultant Surgeon, Deggendorf, Germany treatment the BMD was measured by DEXA. Additional y, the levels of the bone turnover markers osteocalcin and bone crosslaps (b-CTX; crosslinked telopeptides of collagen 1) were measured by immunoassays. Prof. Dr. Werner Kul ich Ludwig Boltzmann Department for Rehabilitation Results: BMD and serum levels of osteocalcin increased significantly
Thorerstrasse 26, 5760 Saalfelden, Austria from baseline to 12 months. b-CTX remained stable. Key words: Nuclear magnetic resonance therapy,
Conclusions: Under therapeutically use of NMR-Therapy, BMD-pa-
osteoporosis, bone mineral density, BMD, DXA, rameters increased during 12 months after a treatment block (10 x 1h). osteocalcin, crosslaps Therefore, NMR-Therapy can be considered a useful alternative or supple- ment to medical therapy in patients with osteoporosis. IntroductIonThe bone is metabolically active and constantly being repaired and The disorder osteoporosis is characterised by poor bone strength and increased risk of fractures due to structural deterioration of the bone.
Osteoporosis is getting more and more relevance in health policy.
Based on demographic changes (increase in older population) the amount of people with osteoporosis and its complications like vertebral body or femoral neck fracture will multiply, too. In addition to effective drug therapy non-pharmaceutical treatments with only few or even no side effects are interesting.
Osteoporosis can be prevented and treated. However, it remains un- derestimated, underdiagnosed and undertreated (1). Today bisphosphonates are the preferred drug therapy of osteoporo- sis. The use of bisphosphonates for the treatment of osteoporosis is de- scribed as a first-line therapy before any other treatment regime (2, 3). All bisphosphonates are associated with at least partially very harmful Received March 26, 2015.
side effects, primarily gastrointestinal and kidney diseases are not un- common in long-term treatment.
D. Krpan et al.
Non-pharmacological treatment of osteoporosis with NMR-Therapy
Effect of NMRT on Bone mineral density (DEXA).
12 months
Result of the BMD measurement by DEXA at baseline and 12 months after NMRT.
L1 – L4 = lumbar spine zone (L1, L2, L3, L4); neck = femoral neck; troch = trochanter; inter = intertrochanteric area; ward = Ward's triangle; mean plus standard deviation and median of T-scores, p indicates significant difference between baseline and 1 year Latest osteoporosis treatment is done by RANK ligand formation (8). Crosslinked degradation products of col- inhibitors – specific antibodies against signal transduction lagen serve as degeneration markers. These fragments of by „Receptor Activator of Nuclear factor Kappa B Li- collagen can be determined with ELISA (Enzyme Linked gand" (RANKL) of osteocytes – which support bone Immunosorbend Assay) as peptidbound crosslinks like CTx(BCTX//Cross Laps/Beta-CrossLaps. They describe Along with an increase in proliferation of osteoblasts the resorption activity in the bone. Increased BCTX val- and the associated bone formation a simultaneous de- ues in blood indicate enhanced bone degeneration.
crease in bone degeneration would be desirable.
The development of a noninvasive, nonpharmacologi- cal therapy which can provoke positive effects on bone 103 patients (male n = 10, female n = 93) with a mean cells, improve function and movement and reduce pain age of 68.4 years were included in this open trial. The would be valuable. Nuclear Magnetic Resonance (NMR) study was performed in the K-Center (Polyclinic / Centre as a therapeutic form of treatment has already been devel- oped more than 10 years ago; it characterizes a technol- for Osteoporosis and other bone- and joint disorders, ogy that uses NMR to activate cellular metabolism and head: Prof.Dr.Sc. Dalibor Krpan, Prim.Dr.Med, Zagreb, regenerative processes (4, 5). Clinical studies demonstrate effects of NMR-Therapy (NMRT) on pain relief in de- All enrolled patients suffered from osteoporosis, secured generative rheumatic diseases (6, 7). by DEXA measurement (T-score less than -2.5), and were The influence of therapeutic nuclear magnetic reso- treated 10 days with therapeutic NMRT (one hour treat- nance therapy (NMRT) on osteocytes depicts an interest- ment per day on 10 consecutive days; using MBST Osteo- ing, alternative active principle that is used since several System 700, MedTec Inc., Wetzlar, Germany).
All patients have been taking VitD3 800 I.j, continu- To verify the effect of the therapy of osteoporosis, two ously, started more than year before they did NMR treat- parameters can be determined: Bone density and markers ment. Patients never used other drugs for osteoporosis. for bone turnover.
Times of measurement was baseline and 12 months after Accurate determination of changes in bone density is possible by DEXA (Dual Energy X-ray Absorptiometry) Parameters of DEXA measurement: Changes of T- Score, Z-Score, Bone Mineral Density (BMD) of inter- trochanteric area, greater trochanter, ward's triangle, fe- Bone GLA Protein – also called Osteocalcin, a major noncollagenous bone matrix protein – is only known to mur neck and lumbar vertebra (L1 – L4).
be synthesized by bone forming cells. Osteocalcin can be All DXA measurements have been done on the same determined in serum by specific enzyme immunoassays device by same technician on the DXA device, Discovery, and has proved itself as a marker for bone turnover / bone QDR series (Hologic Inc., USA).
Period biol, Vol 117, No 1, 2015.
Non-pharmacological treatment of osteoporosis with NMR-Therapy
D. Krpan et al.
Laboratory measurement of Osteocalcin (Osteocalcin of cases. The median, which is independent of the rela- (OCN)-Elecsys) and Beta cross laps (Elecsys Bone Mark- tively broad distribution, also showed a clear enhancement er Assay CrossLaps have been done from serum by elec- of the osteocalcin concentrations from 14 to 18 ng/ml.
tro-chemoluminiscence immunoassays (ECLIA) on a cobas(Elecsys-analyzer (Roche Diagnostics International Interestingly, a decrease in BetaCrossLaps-Levels cor- Ltd., Switzerland).
relates with an increased T-score at the trochanter area.
Statistical analysis of data was done by the Ludwig Crosslaps are fragments of collagen. During bone re- Boltzmann Institute for Rehabilitation of Internal Dis- sorption in osteoporotic processes collagen is degraded eases Saalfelden using the program Sigma Plot 12.3 (SPSS and crosslaps (ß-CTX) are released into circulation. El- evated levels indicate increased bone loss. We investigated the effects of NMRT on ß-CTX in all study patients with osteoporosis. The serum concentrations of Beta-Crosslaps remained stable at 0.3 + 0.2 (baseline as well as after 12 months) and did not increase during 1 year, indicating A significance analysis with paired t-test resp. Wil- that there was no enhanced bone loss after NMRT.
coxon Signed Rank Sum Test showed a significant im- provement of T-scores of the lumbar vertebra (L1 – L4) in the patients with osteoporosis (male and female). T- scores at the femoral neck and the ward's triangle also A DEXA measurement, the „gold standard" in os- showed significant enhancement from baseline to 12 teodensitometry (9), offers good precision and low ra- months after NMRT (Table 1). Mean and median values diation exposure. The measurement points at the lumbar demonstrate an increase of bone density. No change of spine and the hip (proximal femur/trochanter area) are T-score could be depicted in greater trochanter and inter- the most prevalent used. Hence, these sites comprising trochanteric area.
femoral neck, intertrochantic area, ward's triangle and The change of the T-score at the ward's triangle cor- trochanter were included in the presented determina- related with a shift of the T-score in the intertrochanteric area and femoral neck. Improved T-score values of the Currently the WHO recommends measuring the trochanter area are associated with T-score levels of the BMD of the spine and proximal femur by DEXA to di- femoral neck and lumbar vertebra. The difference from agnose Osteoporosis (10). baseline to 12 months after NMRT of the T-score in the intertrochanteric area correlated with the T-scores of the Osteoporosis is a disorder that often leads to significant femoral neck and lumbar vertebra 3, but not with the morbidity when untreated.
residual lumbar vertebrae. An improvement of the T-score Denosumab, a monoclonal antibody to RANKL, values at the femoral neck correlated with all other en- given twice a year, reduces the risk of vertebral, non-ver- hancement of parameters.
tebral and hip fractures in osteoporosis parallel to a per- The serum levels of the bone turnover marker osteocal- cent range in BMD of 6 % (lumbar spine) respectively 3 cin increased significantly within the 12 months, in average % (total hip) after 12 months therapy (11). The significant about 55% (Figure 2). Female patients (90%) outweighed improvements of BMD by bisphosphonates amount to males. In the group of male patients (n = 10) no significance 2.4 – 3.7 % (risedronate or alendronate) at the hip resp. for this marker could be detected due to the low number 4.2 – 6 % at the lumbar spine after 24 (not 12!) months Figure 1. DEXA assessment of BMD (T-score) in 103 patients with
Figure 2. Osteocalcin levels in serum of patients with osteoporosis at
osteoporosis before and 12 months after NMRT. * indicates sig- baseline and 12 months after NMRT in the total group and devi- nificant changes ded in males and females; Period biol, Vol 117, No 1, 2015.
D. Krpan et al.
Non-pharmacological treatment of osteoporosis with NMR-Therapy
(12). During one year surprisingly, the NMR therapy en- differs to those using only static or pulsed magnetic fields. hanced the BMD by the same percentage range or more The easy-to-use therapeutic method for regenerative stim- (up to 10 %). Ipso facto, in any case the physiological bone ulation of disturbed and irreparable cell processes is di- loss up to 4 % can be more than offset by NMRT! rectly based on the technology behind NMR imaging 12 months after NMRT, the bone density (DEXA) (=MRI). The biological effect of this technology is based was significantly higher and the bone formation param- on the knowledge that cell functions are only possible if eter Osteocalcin increased as well (Figure 1, 2). Osteocal- energy supply is assured. Deficient energy flow in endog- cin levels are consistently related to the level of bone for- enous regeneration processes unavoidably leads to cell mation and therefore it is a sensitive marker in death. To prevent such conditions, the incurred energy deficit has to be compensated by suitably measures (e.g. osteoporosis (13). In most cases of osteoporosis normal or nuclear magnetic resonance).
slightly reduced values of Osteocalcin are found and the discrimination between different groups is rather poor, The application of 1 hour NMR-Therapy a day on 10 but a clear correlation exists with spontaneous bone loss consecutive days has been found to be efficient.
Although in Germany NMR-Therapy is successfully It is not routinely recommended to use bone turnover adapted for the treatment of osteoporosis already more markers (BTMs) but baseline measurements of bone than 10 years, only a few clinical studies exist.
markers can be checked 3-6 months later to monitor re- A comparable study to our investigations with DEXA sponse to treatment (8). measurements is a trial of a German group who explored It is interesting that one year after NMR therapy there the bone density with QCT (quantitative computer tom- could be observed a significant increase of the Osteocalcin ography) 6 months after whole-body-NMRT (10 x 1h). levels (p < 0.001) in the total population as well as in fe- After 6 months, a significant growth of the bone mineral male patients who account for 90 % of the total col ective.
content (p < 0.05) was manifested in the NMR group but not with bisphosphonates in the comparison group. Paral- The small changes of Cross-Laps indicate unaltered lel, the scores Osteoporosis Quality of Life Questionnaire, bone degeneration.
Fairbank Score and Roland & Morris Disability Question- A large body of evidence indicates that pulsed electro- naire were reduced significantly under NMR-therapy (22). magnetic fields, a safe and non-invasive method, could To access NMRT on cellular processes, investigations promote osteogenesis. The FDA, USA approved therapy of our own research group could demonstrate in microar- with pulsed electromagnetic fields as an effective method ray experiments modulating NMR effects on the regula- for osteoporosis therapy (16). Therapy with PEMF is fre- tion of NFAT (Nuclear Factor of Activated T-cells) me- quently confused with nuclear magnetic resonance ther- tabolism and the Ca2+ release in osteosarcoma cell lines apy which varies physically significant from PEMF by another magnetic field structure and the additional radio frequency. PEMF could also prevent bone loss through As the annual bone loss amounts physiologically to 0.5 regulating the cytokine expression of RANKL and OPG – 1 % and can rise up to 4 % postmenopausally (24), a in bone cells (17). non-drug therapy like NMRT which has shown (by DEXA measurement) to improve significantly decreased In a recent study the inhibitory effects of PEMF on bone density can be a useful alternative or supplement to osteopenia in rats with disuse-induced bone loss could be medical therapy in osteoporosis.
demonstrated by increased mineral apposition and bone formation rates over promotion of the genes of Wnt1, However, a randomized double blinded controlled OPG, Osteocalcin, LRP5 and others (18). In contrast trial is warranted to confirm the effects of NMR-Therapy other research groups found no support for the use of on osteoporosis.
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Non-pharmacological treatment of osteoporosis with NMR-Therapy
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