Markers of Bone and Cartilage Turnover.

Over the past few decades, scientists have been trying to identify tissue-specific markers that would help to better understand the pathogenesis of bone and cartilage diseases and could be used clinically for the screening, diagnosis and follow-up of bone or joint diseases. Historically, only a few components known to be involved in bone, mineral or cartilage turnover were available for this purpose (e. g., urine hydroxyproline, serum and urine calcium and phosphate levels). However, since most if not all of these substances have wider biological functions beyond bone, mineral and cartilage metabolism, their clinical value as tissue-specific markers was limited. Hence, there was a need to identify more specific indices of bone and cartilage metabolism. Since the 1980s, a number of collagenous and non-collagenous breakdown products as well as cell-specific enzymes have been discovered and developed into markers of musculoskeletal tissue metabolism. This review describes their chemical and biological function, available analytical methods and possible clinical applications.

Inhibition of cancer cell mitosis by reducing the availability of phosphate.

The addition of phosphate groups is an essential requirement for the proper functioning of cyclin and cyclin dependent kinase which control various stages in the mitotic division of cancer cells. Thus limiting the availability of phosphate is likely to interfere with the metabolism of rapidly growing malignant cells. The human hormone glucagon and the anti metabolite mithramycin reduce serum phosphate by increasing phosphaturia and are both very effective in treating Paget's disease of bone, a precancerous condition. In this disorder large doses of glucagon given intravenously relieve bone pain and cause serum phosphate and alkaline phosphatase as well as urine hydroxyproline to fall, indicating a marked reduction in bone turnover. A constant iv infusion of glucagon was given to each of three patients all of whom had secondary malignant bone deposits. Two of the patients had primary prostate cancer and one had a squamous cell lung tumour. All three patients had relief of bone pain and a fall in serum alkaline phosphatase. Serum acid phosphatase also fell in the two patients with prostate cancer. It is proposed that the marked drop in serum phosphate due to glucagon causes intracellular phosphate to fall. This in turn disrupts the addition and removal of phosphate groups essential for the proper functioning of cyclin and cyclin dependent kinase. These two proteins control the transition from G1 to S (DNA synthesis phase) and G2 to M (mitotic phase) in the dividing cycle of malignant cells. Depriving a tumour of an essential ingredient used in phosphorylation reactions will disrupt its growth. It is also proposed that, by the same mechanism, glucagon induced hypophosphataemia renders malignant cells more sensitive to established chemotherapeutic agents and radiation waves. If this hypothesis proves to be correct, lowering intracellular phosphate may become an useful tool in cancer therapy. However extensive studies are necessary to determine whether mitosis in cancer cells can be advantageously disrupted by glucagon induced hypophosphataemia.

Experimental study of the effect on bone metabolism and bone histomorphometry of osteoporosis rats with birdpecking and revolving moxibustion on twelve back-shu points.

The aim of the study was to explore the effect of birdpecking and revolving moxibustion on twelve back shenshu points on the bone metabolism and bone histomorphometry of osteoporosis rats. The 50 female rats of 8 months old that did not pregnant were collected and randomly divided into sham-operation group, model group, moxibustion group, moxibustion and estrogen group, and estrogen group. All the rats, except for the rats in the sham-operation group, received ovarian surgery to establish the models. After 10 days postoperatively (healing), the rats received moxibustion and estrogen therapy. According to the different groups, the rats received rat femur in vivo bone mineral density assessment at 90 days after surgery. After that, the rats were sacrificed, and then the left femoral bones were collected for bone histomorphometry test; blood was taken for bone alkaline phosphatase (BALP) testing, and urine was collected for hydroxyproline testing. The urine hydroxyproline was tested once at 24 h after ovarian surgery. At 24 h after ovarian surgery, the urine hydroxyproline in the ovariectomy group was significantly higher than that in the sham-operation group (P < 0.05), indicating that after ovarian surgery, the collagen broke down which accelerated the process of osteoporosis. After the intervention therapy with moxibustion and estrogen, the BALP, urinary hydroxyproline and femoral bone histomorphometry were comparatively analyzed, and the results showed that the intervention groups were higher than the model group (P < 0.05). But when compared with the sham-operation group, the indexes in the intervention groups were decreased, and the differences were significant (P < 0.05), indicating that intervention could only delay the incidence of osteoporosis. The Chinese traditional measure of "birdpecking and revolving moxibustion on twelve back-shu points" can effectively prevent the recession of bone metabolism of osteoporosis rats, and slow down the degeneration of bone morphology, which can be used to delay the incidence of osteoporosis.

[Metabolism of collagen in patients with Dupuitren's contracture].

Results of investigation of collagen metabolism in Dupuitren's contracture (DC) were summarized. The patients were operated for calculous cholecystitis and DC stages II - III. The changes revealed witnessed about more expressed degradation of collagen and affection of the elastin components of connective tissue. On background of the pathological process progress in palmar aponeurosis in patients, suffering DC, a content of oxyproline have enhanced trustworthy in urine and reduced in tissue of a changed palmar aponeurosis.

Impact of omeprazole on bone remodeling in normal and ovariectomized Wistar rats.

BACKGROUND: Several epidemiologic studies have suggested the association between therapy with proton pump inhibitors (PPIs) and bone fractures. AIM: This study aimed at evaluating the effect of omeprazole on bone in normal and ovariectomized Wistar rats and the possible mechanisms involved. MATERIALS AND METHODS: 56 rats were divided into 3 main groups. Normal group; further subdivided into normal control group and two groups which were treated with omeprazole in two doses (20, 40 mg/kg/day i.p). Sham operated group. Ovariectomized group; further subdivided into ovariectomized control group, and two groups which were treated with omeprazole in two doses (20, 40 mg/kg/day i.p). Rats were treated for the last 4 weeks of the total 8 weeks of the experiment. Urine hydroxyproline, serum osteocalcin, TNF-α and IL-6 and bone mineral content were assessed. Omeprazole effects on the endothelial dependent and independent relaxation were determined. RESULTS: Omeprazole in normal and ovariectomized rats produced significant reduction in bone formation, tibia calcium content and serum TNF-α and IL-6. Omeprazole in ovariectomized rats produced a dose dependent decrease in bone resorption. Isolated aortic rings from ovariectomized/omeprazole treated rats exhibited reversal of the endothelial dysfunction that observed with ovariectomized rats. CONCLUSIONS: PPIs might induce both positive and negative effects on bone remodeling. Although these drugs might have the potential to inhibit bone resorption, through suppression of pro-inflammatory cytokines and improvement of endothelial function, yet these effects are counteracted by their inhibitory effects on the gastric proton pump with reduction in calcium absorption and bone formation.

Suppression of NF-κB p65 nuclear translocation and tumor necrosis factor-α by Pongamia pinnata seed extract in adjuvant-induced arthritis.

Pongamia pinnata is a plant known for its therapeutic usage in Indian traditional medicine. Despite the controversy regarding toxic flavonoid and erucic acid content, the seed of this plant is consumed in tribal medicine and its oil is used in Ayurveda to treat psoriasis and arthritis. This study explored the potential anti-arthritic effects of a P. pinnata seed (hexane) extract (PSE) at non-lethal doses in an adjuvant-induced arthritic rat model; possible mechanisms of any observed effects were also explored. After establishing the lethal doses arising from oral exposure to the extract, the material was administered per os daily at two doses (0.3 g/kg/day; 0.5 g/kg/day) to arthritic rats. Other rats received indomethacin or vehicle (control). Treatments were performed for a total of 14 days. One day after the final exposure, the rats were euthanized to permit harvest of various cells, blood, and tissues for analyses. Paw diameter and tissue myeloperoxidase activity in the paws were evaluated as indices for edema and neutrophil infiltration into the tissue. The severity of arthritis in the experimental rats was assessed via measures of urinary hydroxyproline (HP) and glucosamine, and of serum pro-inflammatory TNFα and anti-inflammatory IL-10. The extent of NF-κB p65 nuclear translocation in peritoneal macrophages harvested from naïve rats and then treated in vitro was also assessed. The results indicated that exposure to PSE significantly decreased paw diameter, tissue myeloperoxidase level, and levels of urinary HP and glucosamine, as well as of serum TNFα and IL-10 in adjuvant-injected (arthritic) rats. In vitro PSE treatment also resulted in a marked inhibition of NF-κB p65 nuclear translocation in primary cultures of peritoneal macrophages. Thus, PSE appears to be able to prevent experimental arthritis, in part, by helping to maintain the balance between pro- and anti-inflammatory cytokines and by inhibiting NF-κB activation.

A Surgeon's guide to advances in the pharmacological management of acute Charcot neuroarthropathy.

Acute Charcot neuroarthropathy is a devastating condition and, its incidence is increasing. Currently, treatment consists of immobilisation and off-loading of the involved extremity. Outcomes are frequently poor and novel treatments are being sought urgently. This review aims to outline advances in the pharmacological treatment of this, condition. PubMed and the Cochrane Database of systematic reviews were searched. Relevant papers were cross referenced. Eleven original studies were identified. The limited data available suggest pamidronate, alendronate and calcitonin provide some clinical and biochemical improvements while zoledronic acid is deleterious and, increases off-loading times. However, the data is not robust enough to convincingly demonstrate clinically meaningful effects. The studies were predominantly low quality and heterogeneous. They differed markedly in study type, pharmacological agent used, dosing regimen, disease, aetiology/stage/location, concurrent off-loading regimen, outcomes and, follow-up. Few were rigorous in controlling for associated confounding variables and none investigated long term outcomes. The routine use of pharmacological treatment modalities for this condition is not recommended in the United States by the Food and Drug Administration or in the United Kingdom by the National Institute for Health and Clinical Excellence. Given the evidence available this is justified and further higher quality research is required.

Zinc as a nutritional approach to bone loss prevention in an ovariectomized rat model.

OBJECTIVE: In this study, we have investigated the role of zinc supplementation (a nutritional antioxidant) in an ovariectomized osteopenic rat model. METHODS: Forty-eight female Wistar rats were assigned to four groups: control, zinc, ovariectomy (OVX), and OVX + zinc. Analysis was performed to compare the study groups on bone metabolism markers, bone antioxidant enzymes, and zinc and copper levels in serum and bone tissues. Electron microscopy was also performed to assess morphological changes. RESULTS: Estradiol levels decreased and tartarate-resistant acid phosphatase 5b levels increased in the OVX group. In the OVX + zinc group, these levels were regulated; however, estradiol levels were still significantly lower than those in controls. The OVX group showed significantly higher urinary excretion of hydroxyproline, which recovered upon zinc supplementation but was higher than normal levels. The activities of catalase and superoxide dismutase decreased in ovariectomized animals and up-regulated upon zinc supplementation. Zinc supplementation in the OVX group revoked reduced glutathione levels and elevated malondialdehyde levels. Reduction in zinc and copper levels was observed in the bone tissues and serum of the OVX group. Zinc administration restored these levels to normal. Electron microscopic studies revealed a looser structure and resorbed areas in ovariectomized rat cortical bone. Zinc administration restored bone tissue morphology. CONCLUSIONS: These findings suggest that changes in cortical bone attributed to estrogen deficiency are arrested by zinc supplementation, which can be a sustainable approach to improving bone health.

Antiosteoporotic activity of echinacoside in ovariectomized rats.

PURPOSE: Echinacoside (ECH), isolated from Cistanche tubulosa (Schrenk) R. Wight stems, has been reported to enhance bone regeneration in MC3T3-E1 cells in vitro. The objectives of this study were to investigate the antiosteoporotic effect of ECH on bone metabolism in the ovariectomized (OVX) rat model of osteoporosis in vivo. METHODS: Fifty-six aged 6 months female Sprague-Dawley rats were randomly assigned into sham-operated group (SHAM) and six OVX subgroups (n=8 each). The OVX rats were then subdivided into six groups treated with vehicle (OVX), Xian-ling-gu-bao (XLGB, 0.5 g/kg body weight/day, orally), 17ß-estradiol (E2, 50 µg/kg body weight/day, orally) or ECH (30, 90, and 270 mg/kg body weight, daily, orally) for 12 weeks respectively. We evaluated the pharmacological effects of E2, XLGB and ECH against osteoporosis by evaluating the body weight, uterus wet weight, serum and urine biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture, bone histomorphology and uterus immunohistochemistry. RESULTS: In OVX rats, the increases of body weight, serum hydroxyproline (HOP) levels, and the decreases of uterus wet weight and BMD were significantly reversed by ECH treatment. Moreover, three dosages of ECH completely corrected the increased urine concentration of calcium (Ca), inorganic phosphorus (P), and HOP observed in OVX rats. Furthermore, Micro-CT analysis results of distal femur showed that all ECH-treated groups notably enhanced bone quality compared to OVX group (p<0.05). Consistent with this finding, total femur BMD and biomechanical strength of tibia were significantly improved (p<0.05) after 12 weeks ECH administration. Histological results also showed the protective activity of ECH through promotion of bone formation and suppression of bone resorption. In addition, the ECH administration also significantly enhanced the expression of ER in the uteri according to immunohistochemical evaluation (p<0.05). Those findings, based on the serum and urine biochemical, BMD, Micro-CT, biomechanical test, histopathological and immunohistochemical parameters, showed that ECH has a notable antiosteoporotic effect, similar to estrogen, especially effective for prevention osteoporosis induced by estrogen deficiency. CONCLUSION: These results suggest that ECH, as a new class of phytoestrogen, has a remarkable antiosteoporotic activity, and may be a promising candidate for treatment of postmenopausal osteoporosis induced by estrogen deficiency in a natural way through herbal resources.

Effect of non-steroidal anti-inflammatory drugs on bone turnover: an evidence-based review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for acute and chronic pain control and treatment of inflammation, osteoarthritis and rheumatoid arthritis. NSAIDs have been shown to inhibit bone healing in animal studies due to the inhibition of prostaglandin synthesis. However, little evidence exists regarding the effect of NSAID exposure on human bone metabolism. This systematic review summarizes the current literature of randomized controlled trials (RCTs) investigating NSAIDs with bone remodeling-related outcomes in humans. After performing computerized searches in the most widely indexed databases, study selection, data abstraction and risk of bias assessment were conducted in duplicate. The results were controversial regarding the association of NSAID with bone formation or resorption. Increased bone mineral density following NSAID exposure was reported by some studies. Based on the levels of biochemical markers, no effect was seen on bone formation, while some evidence was found for a decreased rate of bone resorption in NSAID patients. Trials investigating the effects of NSAID treatment on bone metabolism outcomes of human patients are limited. Further research is required to confirm or refute the findings of this systematic review.

[Biochemical indices of connective tissue metabolism in patients with chronic hepatitis B and C].

37 patients with chronic hepatitis B and C were examined. Patients were divided into 3 groups depending on the degree of connective tissue dysplasia. We investigated: free and protein-bounded hydroxyproline, collagenase activity, total alkaline phosphatase and its bone fraction, creatinine, calcium and phosphorus content in the blood serum and urine. It has been found the dependence of collagen synthesis from the state of connective tissue. The higher is the degree of dysplasia, the more intensive is the process of collagen synthesis (P < 0.05). The index of corellation between protein-bounded and free fraction can be used as a biochemical marker for determination the stage of pathological process in the liver and for monitoring the effectiveness of therapy.

A high molecular weight protein extract of Mastobranchus indicus (Mi-64) having antiarthritic activity in experimental animals.

Mi-64, a high molecular weight protein (130 kDa), obtained from the tissue homogenate of marine polychaete (Mastobranchus indicus) collected from the Indian Sunderban has antiarthritic activity in experimental animals. The FCA-induced arthritis model was developed in Wistar albino rats to evaluate the antiarthritic effects of Mi-64. After FCA induction, the rats were treated with Mi-64 (0.25 and 0.5 mg kg(-1) body weight) for 10 days. We have determined the paw/ankle swellings, urinary hydroxyproline and glucosamine, serum acid and alkaline phosphatases to assess the antiarthritic activity. The levels of interleukin-1 beta (IL-1ß), IL-6, cytokine-induced neutrophil chemoattractant-1 (CINC-1), tumor necrosis factor-alpha (TNF-α), and IL-10 were measured by ELISA. Results showed that Mi-64 significantly reduced paw/ankle swellings and restored the urinary hydroxyproline/glucosamine and serum phosphatases. Mi-64 significantly inhibited the overproduction of IL-1ß, IL-6, CINC-1, and TNF-α and augmented IL-10 production. The data suggest that Mi-64 produced significant antiarthritic effects that may be mediated by balancing the pro- and anti-inflammatory cytokines.

Variability in the measured response of bone to teriparatide.

UNLABELLED: Apparent failures of bone mineral density (BMD) response to teriparatide at spine or hip occur even in a high compliance context (15% spine and 55% hip). Apparent non-responders nevertheless show good biomarker response, suggesting that apparent BMD non-response is due to measurement imprecision. Calcium intake may be an important determinant of hip response. INTRODUCTION: Individuals vary in response to bone active agents, but that variability is poorly quantified and its basis is not well understood. The study included 203 postmenopausal women with moderately severe osteoporosis, all treated with teriparatide, calcium, and vitamin D. The study was performed at the Creighton University Medical Center, a single site. METHODS: This is a prospective study of change in bone mineral density and resorption biomarkers over a 12-month treatment period. BMD response at spine and total hip was quantified by computing slopes for each participant's values, and biomarker change by the difference in values across the 12-month study period. RESULTS: Of the total number of participants, 85.2% exhibited a significant spine BMD response, while only 44.8% had a significant change at the hip. However, mean biomarker response was marginally larger for the BMD non-responders at either site than for the responders, indicating biological, if not measurable densitometric, activity of teriparatide in essentially all participants. CONCLUSIONS: Occasional apparent failures of BMD response in patients receiving teriparatide are probably not due to failure of response at the level of the bone remodeling apparatus, but instead reflect a combination of measurement imprecision and variable bone remodeling balance. The reason for the latter remains unclear.

ELISA measurement for urinary 3-hydroxyproline-containing peptides and its preliminary application to healthy persons and cancer patients.

BACKGROUND/AIM: We reported that endogenous urinary 3-hydroxyproline (3-Hyp) is useful for cancer screening because cancer invasion involves the destruction of basement membrane. A simple and sensitive assay is desired. PATIENTS AND METHODS: An ELISA method using a specific antibody against a synthetic peptide of 10 amino acids including 3-Hyp corresponding to the amino acid sequences of collagen type IV alpha chain was applied to urine samples from 180 healthy controls and 22 cancer patients. RESULTS: The values in controls were 2.44+/-1.90 (SD) mg peptide/g creatinine for 52 men and 2.87+/-2.01 for 128 women, while the values in 22 cancer patients were very low at 0.110+/-0.137 (p<0.001). DISCUSSION: The discrepancy in the data between our previous and present studies is based on the difference of targets measured. 3-Hyp-containing peptides in cancer patients might be destroyed by the elevated peptidase levels found in these patients. CONCLUSION: This ELISA assay may be useful for cancer screening.

Peptide bound hypohydroxyprolinuria in Handigodu Disease: a familial syndrome of spondylo epi(meta)physeal dysplasia.

Handigodu Disease (HD) is disorder of the osteoarticular system prevalent in few villages of two districts of the state Karnataka in southern India. 24 hrs urinary excretions of proline (Pro) and 4-hydroxyproline (Hyp) were analyzed by HPLC. Decreased peptide bound Hyp excretions (mumole/24 hrs) were found in patient group when compared with controls (Nonaffected; 113.02 +/- 67.96, Type-I; 36.22 +/- 20.76, Type-II; 45.74 +/- 14.95, Type-III; 40.46 +/- 22.68) and without significant difference in Pro excretions. Significant increased peptide bound Pro to Hyp ratio were found in patient group compared to control (Nonaffected n=63: 2.02 +/- 1.65, Type-I n=18: 3.144 +/- 1.42, Type-II n=28: 4.21 +/- 1.95, Type-III n=8: 8.60 +/- 6.55). 24 hrs urinary excretions of deoxypyridinoline (DPD) crosslinks were found without significant difference among affected and control, hence HD ruled out from general bone reduction. These results suggest hypohydroxyprolinuria may be because of reduced bone turnover or defective hydroxylation of prolyl residues during post translational modification of collagen biosynthesis.

[Biochemical diagnosis of immobilization osteoporosis].

The authors have ascertained informative laboratory tests for diagnosis of immobilization osteoporosis and prognostic tests of reparative osteogenesis in its presence. A study was conducted in 97 patients (mean age 39.8 +/- 9.5 years) with bone nonunion and immobilization osteoporosis diagnosed densitometrically (DPXA, Lunar, USA). The proposed procedures are topical if no densitometric study is available and the prediction of osteogenesis on the basis of the phosphatase index is of informative value at the X-ray negative stage (1 month after surgery). The procedures are available and cost-effective; their sensitivity is 75-77%.

Atypical thyrotropin-secreting pituitary microadenoma revealed by severe osteoporosis in a young man.

For 10 years, a young man was followed for a severe osteoporosis associated with a considerable reduction in height and a massive weight loss. The constant increase of signs of tissue impregnation with thyroid hormones and the molar ratios of alpha-TSH suggested an inappropriate secretion of thyrotropin. Magnetic resonance imaging finally revealed a thyrotropic microadenoma of the pituitary gland. This case gives some new additional information on thyrotropin-induced osteoporosis. To our knowledge such a case has never been reported in the literature.

Clinical and biochemical response of TNFRSF11A-mediated early-onset familial Paget disease to bisphosphonate therapy.

Early-onset familial Paget disease of bone (EoPDB) is a rare condition caused by a 27-bp insertion mutation affecting the signal peptide of TNFRSF11A, which encodes RANK. EoPDB shows phenotypic overlap to both familial expansile osteolysis and expansile skeletal hyperphosphatasia, which are caused by similar mutations in TNFRSF11A. Although EoPDB is characterized by elevated bone turnover, there is no published information on the response of this condition to antiresorptive therapy. Here, we describe the clinical and biochemical response to bisphosphonate therapy in three patients with EoPDB. In all cases, treatment with the first-generation bisphosphonate etidronate at high doses reduced biochemical markers of bone turnover but the response was incomplete and short-lived. In contrast, treatment with aminobisphosphonates resulted in greater suppression of biochemical markers of bone turnover with an extended duration of response. From a clinical perspective, the results were less impressive and there was no clear benefit from antiresorptive treatment in terms of bone deformity, deafness, and tooth loss, although bone pain improved in one patient. We conclude that intravenous aminobisphosphonate therapy may be the preferred mode of treatment for EoPDB to provide long-term suppression of bone turnover. The long-term clinical effects of treatment on the natural history of the bone disease remain uncertain however, and this will require further study.

Comparação dos efeitos do TENS e dos exercícios terapêuticos sobre os níveis de hidroxiprolina na urina em síndrome do impacto no ombro / Comparison of the effects of TENS and exercises therapy effects on hydroxyproline levels in urine on shoulder pain

Objetivo: Comparar os efeitos da neuroestimulação elétrica transcutânea (TENS) e cinesiologia aplicada, assim como esta isolada, na excreção urinária em indivíduos com a síndrome do impacto do ombro (SIO). Métodos: Participaram do estudo dois grupos de 35 indivíduos cada, sendo 30 mulheres e 40 homens, com idade entre 45 e 60 anos. O grupo controle realizou a cinesiologia aplicada e o grupo experimental realizou o tratamento TENS associado à cinesiologia aplicada. Para a mensuração da hidroxiprolina na urina foi utilizado o protocolo de colorimetria. A coleta urinária foi feita na 1ª, 5ª e 10ª sessão. O tratamento foi realizado em 10 sessões de 55 minutos. O tratamento estatístico utilizado foi feito através da análise de variância One Way (ANOVA). Resultado: Não houve melhora significativa como indicado por F = 0,662, p > 0,05. Conclusão: Os resultados mostraram não haver interação significativa entre os tipos de tratamento com a excreção urinária de hidroxiprolina. Contudo, os resultados obtidos das variáveis mostraram uma forte tendência à melhora, apresentando um resultado mais efetivo no grupo que utilizou somente a cinesiologia aplicada até a quinta sessão e, posteriormente, com uma tendência mais efetiva no grupo que utilizou a cinesiologia aplicada + TENS. O estudo mostrou, também, um resultado mais eficiente do grupo que utilizou apenas a cinesiologia aplicada como tratamento.

Objective: To compare the transcutaneous electrical nerve stimulator (TENS) effects associated to the kinesiology applied, and only the kinesiology applied on the hydroxiproline (HP) excretion on individuals with shoulder pain, during 10 physical therapy sessions with duration of 55 minutes each session for both treatments. Methods: The individuals were divided into two groups of 35 people each, being 30 women and 40 men; aged between 40 and 65 years old. The control group underwent only applied kinesiology and the experimental group applied kinesiology associated to TENS. It was used the colorimetric protocol to measure urinary excretion of HP. Three samples of each variable were carried out on the first, fifth and tenth sessions. The ANOVA test with repeated measures to analyze the HP was used for the statistics. Results: There were no significance as indicated by F = 0.662, p > 0.05. Conclusion: We concluded that the study showed a strong benefit tendency for both groups due to HP decrease levels. As a better result before the 5th session for the group applied kinesiology and after the 5th - 10th session of treatment, for the applied kinesiology + TENS group, although there was no significance based on the statistics. And, also, it showed a better result for the group who practiced only applied kinesiology