Tartrate-resistant Acid Phosphatase 5b Levels Research Articles

Abnormal bone mineral density and bone turnover marker expression profiles in patients with primary spontaneous pneumothorax.

To examine the bone mineral density (BMD) and the role of bone biomarkers, including bone formation marker procollagen type I aminoterminal propeptide (PINP) and N-terminal midmolecule fragment osteocalcin (N-MID), bone resorption marker b-C-telopeptides of type I collagen (b-CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) in the pathogenesis of PSP. Eighty-three consecutive primary spontaneous pneumothorax (PSP) patients (PSP group) and 87 healthy individuals (control group) were enrolled in this study. General data, including gender, age, height, weight, and body mass index (BMI), were recorded. Dual-energy X-ray absorptiometry, electrochemiluminescence immunoassay (ECLIA), and ELISA were used to evaluate bone mineral density and expression levels of bone metabolism markers, including PINP, b-CTX, TRACP5b, N-MID, and 25-hydroxyvitamin D (25-OH VD). Mean height was significantly greater in the PSP group compared with the control group, whereas weight and BMI were lower. Patients in the PSP group had significantly lower average bone mineral density, which mainly manifested as osteopenia (11/12, 91.7%); however, only one patient (8.3%) developed osteoporosis. Serum overexpression of PINP, b-CTX, TRACP5b, and N-MID were found in PSP patients. Expression of 25-OH VD was low in PSP patients. Bone resorption markers showed positive linear relationships with bone formation markers in all participants; whereas only TRACP5b expression negatively correlated with 25-OH VD. Expression levels of all bone turnover markers negatively correlated with BMI. Regression analysis identified risk factors of PSP as age, height, weight, and TRACP5b and 25-OH VD expression levels; whereas gender and PINP, b-CTX, and N-MID expression levels were not significantly associated with the onset of PSP. It had lower bone mineral density in PSP patients. Bone formation marker PINP, N-MID and bone resorption marker b-CTX, TRACP5b were upregulated in PSP patients. 25-OH VD expression was relatively low in this population of PSP patients. Age, height, weight, and expression levels of TRACP5b and 25-OH VD may be risk factors for PSP.

Different patterns of change in bone turnover markers during treatment with bone-modifying agents for breast cancer patients with bone metastases.

Bone-modifying agents are effective for treatment of breast cancer patients with bone metastases. Since their action is mediated through suppression of the osteoclast function, their efficacy can be determined by monitoring bone turnover markers. However, the clinical significance of these markers is yet to be compared. For this study, 52 breast cancer patients with bone metastases treated with zoledronic acid (n=36) or denosumab (n=22) were enrolled (6 patients were treated sequentially with both agents). Serum tartrate-resistant acid phosphatase-5b (TRACP-5b), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1CTP), N-terminal cross-linking telopeptides of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) were measured at pretreatment and 1, 3 and 6months after treatment. Serum TRACP-5b (p<0.0001), NTX (p=0.0007) and BAP (p=0.0032) decreased significantly after treatment. The baseline median value of TRACP-5b (457.5mU/dL, range 173-1630mU/dL) decreased to 137mU/dL (91-795mU/dL) 1month after treatment. Reduction in serum NTX and BAP was greatest after 3 and 6months, respectively. TRACP-5b, NTX and BAP were above normal levels at baseline in 62.5, 25 and 35.3% of patients, respectively, and nearly 80% of these patients attained normal levels during the treatment. Although bone-modifying agents reduced the baseline levels of TRACP-5b, NTX and BAP significantly, the reduction patterns differed. TRACP-5b appears to affect levels most quickly and sensitively, possibly due to its direct link to the number and activity of osteoclasts. These findings suggest that the efficacy of TRACP-5b is clinically significant when considering which bone-modifying agents to use for breast cancer patients with bone metastases.

Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious anabolic and anticatabolic effects. This study not only enriches our basic knowledge about bone quality and bone turnover mechanisms in leptin receptor-deficient animals, but also advances our understanding of the skeletal sensitivity of leptin-resistant db/db mice in response to external mechanical stimulation. © 2016 American Society for Bone and Mineral Research.

Changes in the Dickkopf-1 and tartrate-resistant acid phosphatase 5b serum levels in preschool children with nephrotic syndrome.

The aim of the present study was to investigate the changes in the serum Dickkopf-1 (DKK-1) and tartrate-resistant acid phosphatase 5b (TRACP-5b) levels in preschoolers with nephrotic syndrome (NS). A total of 50 preschoolers (3-5 years old) with NS and 20 healthy preschoolers (control group) were enrolled in the prospective single-center study. The patients with NS received glucocorticoid treatment and the control group received no treatment. The levels of serum calcium, phosphorus, TRACP-5b, DKK-1 and 25-hydroxyvitamin D3 were measured at baseline and at 3 and 6 months in all the subjects. The levels of DKK-1 and TRACP-5b were significantly higher in the NS group prior to treatment when compared to the control group (P<0.05), but did not differ significantly between the two groups following treatment (P>0.05). Therefore, DKK-1 and TRACP-5b can be used as biomarkers of bone formation and bone resorption, respectively, in the early evaluation of bone metabolism.

Further significant effects of eldecalcitol on bone resorption markers and bone mineral density in postmenopausal osteoporosis patients having undergone long-term bisphosphonate treatment.

We investigated whether eldecalcitol has further significant effects on bone metabolic markers and bone mineral density (BMD) in osteoporosis patients having undergone long-term bisphosphonate treatment. Eldecalcitol treatment was initiated in 48 postmenopausal osteoporosis patients who had undergone bisphosphonate treatment with or without alfacalcidol treatment for more than 2years (average period 6.3years). Age, height, weight, total muscle volume, total fat volume, estimated glomerular filtration rate, and BMD at the lumbar spine, total hip, and distal third of the radius were measured as background data for each patient. Serum alkaline phosphatase, tartrate-resistant acid phosphatase5b, calcium, and phosphate levels were measured at the baseline and 3 and 12months after the initiation of eldecalcitol treatment, and BMD was measured at the baseline and 12months after the initiation of eldecalcitol treatment. Tartrate-resistant acid phosphatase5b level was significantly decreased at 3 and 12months after the initiation of eldecalcitol treatment in comparison with the baseline level. There were no significant changes in alkaline phosphatase, calcium, or phosphate levels in comparison with the baseline levels. In addition, the lumbar spine BMD at 12months after the initiation of treatment was significantly increased in comparison with the baseline level, although no significant changes in BMD at the total hip and distal third of the radius were observed. Eldecalcitol demonstrated significant effects in additionally decreasing the level of the bone resorption marker tartrate-resistant acid phosphatase5b and increasing BMD at the lumbar spine, even in osteoporosis patients having undergone long-term bisphosphonate treatment.

Antiosteoporotic activity of Du–Zhong–Wan water extract in ovariectomized rats

Context Eucommiae Cortex and Radix Dipsaci, occurring in a ratio of 1:1 in Du-Zhong-Wan (DZW), a Chinese herbal medicine, is available as a water extract followed by ethanol precipitation for the treatment of osteoporosis, fractures and menopausal syndrome.Objective This study investigates the protective effects of DZW in ovariectomy (OVX)-induced bone loss in a rat osteopenia model.Materials and methods Sixty Sprague–Dawley rats were randomly divided into the sham-operated group (SHAM) and five OVX subgroups: OVX with vehicle (OVX), 17β-estradiol (E2) and with three graded doses of DZW. Daily oral administration of the different samples started on the fifth week and lasted for 12 weeks, respectively. The body weight, uterus wet weight, serum biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture and immunohistochemistry were examined.Results Compared with the SHAM group, the DZW treatment significantly reversed the osteoporotic changes in OVX rats. The DZW-H group showed that serum tartrate-resistant acid phosphatase 5b (TRACP-5b) levels reduced by 152.25% (p < 0.01) and osteocalein (OCN) levels dose dependently increased by 118.43% (p < 0.01) as compared with the OVX group. Compared with the OVX group, the DZW at different three dosages of DZW evidently increased the right femur BMD by 112.43, 114.56 and 116.45%, and dramatically promoted bone quality and bone strength (p < 0.05). Further, immunohistochemical evaluation also showed that DZW administration increased ER expression in uteri (p < 0.01).Conclusions DZW exhibits an anti-osteoporotic effect, probably mediated via phyto-estrogenic effects. It might be a potential herbal alternative for the management of postmenopausal osteoporosis.

Comparison of the effects of eldecalcitol with either raloxifene or bisphosphonate on serum tartrate resistant acid phosphatase-5b, a bone resorption marker, in postmenopausal osteoporosis.

This study analyzes whether concomitant raloxifene (RLX) or bisphosphonates (BP) plus eldecalcitol (ELD) has excessive suppressive effects on a bone resorption marker during the first 6 months of treatment in postmenopausal women in real-world setting. 285 postmenopausal osteoporotic patients who had been treated with RLX or BP plus ELD were evaluated the bone resorption marker, serum tartrate resistant acid phosphatase-5b (TRACP-5b), during the first 6 months of treatment. In drug-naïve group (not received osteoporosis medications before the administration, n=70), the concomitant RLX or BP with ELD significantly decreased levels of TRACP-5b without severe suppression. In vitamin D switch group [RLX or BP plus alfacalcidol (ALF) and then switched to RLX or BP plus ELD, n=215], the replacing ALF with ELD further and significantly decreased TRACP-5b and tertile analyses based on baseline values were significantly decreased far more in the highest, compared with the lowest tertile in the ELD+RLX and ELD+BP groups. ELD combined with RLX or BP administered for 6 months to postmenopausal women with osteoporosis who were drug-naïve or who had switched medications significantly reduced and maintained TRACP-5b values within the reference range.

Correlation between age-related changes of osseous metabolic markers and bone mineral density in females

Objective To investigate the age-related changes of osseous metabolic markers and their relationships to bone mineral density (BMD) in females. Methods A total of 309 females with different ages (25-84 years) were enrolled. The total collagen type I amino-terminal extension peptide (TPⅠNP) and beta collagen specific sequences (β-CTX) were measured by electrochemical luminescence method. 25-hydroxy vitamin D(25-OH-VitD) and tartrate-resistant acid phosphatase-5b(TRACP-5b) were measured using ELISA. BMD of femoral neck, lumbar spine 1-4 were measured with a bone densitometer (GE Lunar Prodigy dual energy X-ray absorptiometry, DXA). The differences among different age and BMD groups were compared by two-sample t test, one-way analysis of variance, χ2 test with SPSS 17.0 software. Results The serum TPⅠNP, β-CTX levels in the 45-54 years group were higher than those in the 35-44 years group: (55.63±19.24) μg/L vs (40.90±14.63) μg/L, (597.10±198.70) ng/L vs (404.79±147.22) ng/L (t=4.156, 5.319, both P<0.01), and decreased slightly with increasing age. The serum 25-OH-VitD level decreased with increasing age. The serum TRACP-5b in the 45-54 years group increased significantly compared to that in the 35-44 years group (t=5.934, P<0.01); and it reached the highest level of (5.05±1.63) U/L in the 55-64 years group, then decreased slightly. The serum levels of TPⅠNP, β-CTX, 25-OH-VitD, TRACP-5b in osteopenic and osteoporosis groups were significantly different from those in the normal group (F=225.908, 253.208, 252.927, 313.265, all P<0.01). The specificities and positive predictive values of all four osseous metabolic markers were all over 95% for the diagnosis of abnormal BMD. The sensitivities of both serum 25-OH-VitD and TRACP-5b levels were higher than those of TPⅠNP(91.47%(193/211), 88.15%(186/211) vs 65.40%(138/211); χ2=42.381, 30.621, both P<0.01) and β-CTX(51.66%(109/211); χ2=82.164, 66.783, both P<0.01). Negative predictive values of both serum 25-OH-VitD and TRACP-5b levels were higher than those of TPⅠNP(χ2=23.103, 15.367, both P<0.01) and β-CTX(χ2=38.126, 28.514, both P<0.01). Conclusions The osseous metabolic markers might be closely related to the changes of BMD and age in females. It was important to measure the bone metabolism markers in the early diagnosis of osteoporosis. Key words: Bone density; Age factors; Female; Type Ⅰ amino-terminal extention peptide; Beta collagen specific sequences; Calcifediol; Tartrate-resistant acid phosphatase

Effects of BIS076 in a model of osteoarthritis induced by anterior cruciate ligament transection in ovariectomised rats.

BackgroundOsteoarthritis (OA) is the most frequent articular disease and a leading cause of disability. There is a need for effective treatments able to slow the progression of disease. Some of the available treatments are dietary supplements providing natural components. Recent studies have shown that estrogen deficiency contributes to the pathophysiological events of OA progression.MethodsWe have used the anterior cruciate ligament transection model of OA in ovariectomised rats to study the effects of BIS076, a new formulation of a natural porcine cartilage extract associated with hydroxyapatite (as a source of calcium) and vitamin D3. Cartilage degradation, proteoglycan depletion and synovitis were followed by histochemistry. Effects on bone microstructure were determined by μCT. The levels of biomarkers in serum and inflammatory mediators in knee homogenates were measured by luminex or ELISA.ResultsOral administration of BIS076 reduced articular cartilage damage and serum levels of cartilage degradation markers C-telopeptide of type II collagen and cartilage oligomeric matrix protein, as well as matrix metalloproteinase-3. The local inflammatory response was down-regulated by BIS076 with lower production of pro-inflammatory cytokines and prostaglandin E2 in joint tissues. In addition, BIS076 was effective on metaphyseal bone alterations as this formulation increased volumetric bone mineral density and improved bone micro-architecture. These effects were related to the modification of bone metabolism reflected by changes in bone biomarkers with reductions in the ratio receptor activator of nuclear factor κB ligand/osteoprotegerin and the levels of tartrate-resistant acid phosphatase-5b, suggesting an inhibitory activity of BIS076 on trabecular bone resorption.ConclusionsWe have demonstrated the protective properties of a new formulation (BIS076) on joint lesion and bone alterations in an experimental model of OA in ovariectomised rats. This study supports the interest of BIS076 in OA treatments.

Increased Bone Turnover and Possible Accelerated Fracture Healing in a Murine Model With an Increased Circulating C-Type Natriuretic Peptide.

Recent studies have revealed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth. Nevertheless, the effect of CNP on bone turnover has not yet been well studied. To elucidate this issue, we investigated the bone phenotype of a mouse model with elevated plasma CNP concentrations (SAP-CNP-Tg mice) in the present study. Microcomputed tomography (CT) analysis revealed less bone in femurs, but not in lumber vertebrae, of young adult SAP-CNP-Tg mice than that of wild-type mice. Bone histomorphometry of the tibiae from 8-week-old SAP-CNP-Tg mice showed enhanced osteoblastic and osteoclastic activities, in accordance with elevated serum levels of osteocalcin and tartrate-resistant acid phosphatase-5b, respectively. Next we performed an open and stabilized femoral fracture using 8-week-old SAP-CNP-Tg mice and compared the healing process with age-matched wild-type mice. An immunohistochemical study revealed that CNP and its receptors, natriuretic peptide receptor-B and natriuretic peptide clearance receptor, are expressed in hard calluses of wild-type mice, suggesting a possible role of CNP/natriuretic peptide receptor-B signaling in fracture repair, especially in bone remodeling stage. On micro-CT analysis, a rapid decrease in callus volume was observed in SAP-CNP-Tg mice, followed by a generation of significantly higher new bone volume with a tendency of increased bone strength. In addition, a micro-CT analysis also showed that bone remodeling was accelerated in SAP-CNP-Tg mice, which was also evident from increased serum osteocalcin and tartrate-resistant acid phosphatase-5b levels in SAP-CNP-Tg mice at the remodeling stage of fracture repair. These results indicate that CNP activates bone turnover and remodeling in vivo and possibly accelerates fracture healing in our mouse model.

Effects of novel multi‐nodal micro‐vibration at multiple frequencies on bone turnover markers and bone strengthen in ovariectomized rats

Osteoporosis is a bone disease characterized by low bone mass and structural deterioration. Whole body vibration (WBV) has been shown to have anti-osteoporotic effect. Current WBV devices use a fixed vibration frequency and displacement level. We developed a novel WBV device that simultaneously delivers multi-nodal micro-vibration displacements (1-4 mm) at multiple frequencies (20-130 Hz) (MVMF). The aim of this study was to test if MVMF technology prevents osteoporosis in ovariectomized (OVX) rats. Twenty three-month-old female Sprague Dawley rats were ovariectomized to induce osteoporosis, and another twenty rats underwent sham operation (SHAM). Two weeks after surgery, half of the rats in each group were treated with MVMF for 30 min/day, 3 day/week; the other half was untreated. After 12 weeks of treatment, rats were sacrificed and their blood and femur were harvested. Serum bone turnover markers were measured by enzyme-linked immunosorbent assay. The strength and stiffness of femur were measured by three-point bending. A 12-week treatment with MVMF had a tendency to increase maximal load of femur in both SHAM and OVX groups, although no statistical significance was found. Ovariectomy caused a significant increase in serum levels of osteocalcin and alkaline phosphatase (ALP), two bone formation markers, and tartrate-resistant acid phosphatase (TRAP) 5b, a bone resorption marker. Treatment with MVMF caused a significant decrease of osteocalcin, ALP, and TRAP 5b levels in OVX rats. The data suggests that the novel MVMF technology prevents OVX-induced increase in bone turnover, which has a potential to increase bone mass and strength in osteoporosis.

Serum Levels of NTx and TRACP5b in Giant Cell Tumor of Bone and its Clinical Implications.

To investigate the serum levels of N-terminal telopeptide of type I collagen (NTx) and tartrate-resistant acid phosphatase 5b (TRACP5b) in giant cell tumor of bone (GCT) patients and the clinical implications. 56 GCT patients (29 males and 27 females, 15 to 60 years old with a median age of 28.0 years old) with clinicopathological characteristics of GCT were enrolled in the Department of Bone Cancer, the Affiliated Cancer Hospital of Xinjiang Medical University from October 2008 to October 2014. The enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of NTx and TRACP5b in the patients. Compared with 21 patients who had a GCT of < 5 cm, the serum levels of NTx and TRACP5b in the 35 patients with a GCT of ≥ 5 cm were significantly increased (p < 0.05). Compared with those GCT patients who had a grade I tumor, the levels of NTx and TRACP5b in grade II patients were not increased (p > 0.05), but the levels of NTx and TRACP5b were significantly increased in grade III patients (p < 0.05). Moreover, compared with the patients in histologic stage I, the levels of NTx and TRACP5b in stage II GCT patients were not increased (p > 0.05), whereas the levels in grade III patients were significantly increased (p < 0.05). In addition, the location of the tumor had a significant effect on the serum levels of NTx and TRACP5b (p < 0.05). Our study suggests that serum NTx and TRACP5b are sensitive and simple biomarkers to indicate aberrant bone metabolism in GCT patients, and they may have a clinical significance in GCT diagnosis. Combined examination for both markers helps in the classification of clinicopathological stages of GCT patients and in the prognosis of the disease.

Vitamin K3 increased BMD at 1 and 2 months post-surgery and the maximum stress of the middle femur in the rat

The therapeutic effects of vitamin K3 (VK3) on osteoporosis are still unknown. In this study, we hypothesized that VK3 possesses therapeutic effects on osteoporosis; to verify this hypothesis, the ovariectomized rat was used as an osteoporosis model. Fifty-six Sprague-Dawley female rats aged 8 to 9 months were randomly assigned to 4 groups: sham surgery, ovariectomy with saline, ovariectomy with low-dose VK3, and ovariectomy with high-dose VK3. Intramuscular injection of VK3 was performed every other day beginning 1 month postoperatively. The therapeutic effects of VK3 on osteoporosis were evaluated by measurement of bone mineral density (BMD), bone biochemical markers, biomechanical properties, and bone morphometric parameters. The overall average BMD in VK3-treated groups increased to a level between those of the ovariectomy group and the sham surgery group. The procollagen I N-terminal peptide level peaked at 2 months after surgery in all groups except in the group that had undergone ovariectomy with low-dose VK3. The tartrate-resistant acid phosphatase 5b level increased more slowly at 4 months after surgery than at 2 months after surgery in the VK3-treated groups. The ovariectomy with high-dose VK3 group had the highest maximum stress of the middle femur of all groups. With VK3 treatment, the trabecular bone area percentage increased. All morphometric indicators for the middle tibia in the VK3-treated groups reached the levels found in the sham surgery group. In summary, VK3 therapy increased BMD at 1 and 2 months postsurgery and the maximum stress of the middle femur. In addition, VK3 therapy slowed the increase in bone turnover in ovariectomized rats. Furthermore, VK3 can improve morphometric indicators for the middle tibia. Our preliminary study indicates that VK3 has a potential therapeutic effect on osteoporosis and is worthy of further investigation.

Tartrate-resistant acid phosphatase 5b is a potential biomarker for rheumatoid arthritis: a pilot study in Han Chinese

Background Bone damage around the joints is one of the major pathophysiological mechanisms that leads to rheumatoid arthritis (RA) chronic disability. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) is secreted by osteoclasts, its activity can be used as a clinically relevant bone resorption marker. The aim of this study was to test whether the measurement of serum levels of TRACP-5b in patients with RA would correlate with measures of disease activity and with responses to therapy. Methods Fifty-six patients were randomly assigned to receive recombinant human cytotoxic tlymphocyte-associated antigen-4 immunoglobulin (RhCTLA4-Ig), infliximab or methotrexate (MTX). The clinical and serologic indicators of RA activity were evaluated at baseline and at 24 weeks. Serum TRACP-5b was measured by Enzyme-linked Immunosorbent Assay (ELISA) at 0, 12 and 24 weeks. Hand X-rays were obtained at baseline. Results At baseline, the levels of TRACP-5b correlated with the severity of X-ray damage, disease duration (r=0.332, P=0.012), and tender joint count (r=0.408, P=0.002). The 24 weeks values of TRACP-5b for RhCTLA4-Ig group and infliximab group differed significantly from the baseline values in each group (P &lt;0.05; P &lt;0.05), whereas only the value for RhCTLA4-Ig group differed significantly from the 24 weeks value for the MTX group (P &lt;0.01). Considering the two biologics-treated groups together, the TRACP-5b levels at 24 weeks differed significantly from the baseline values only in those patients who reached an ACR70 level (P &lt;0.05). Conclusions Measurement of serum TRACP-5b in RA patients reflects clinical and radiological measures of disease activity, treatment with certain biologics, and degree of response to therapy. TRACP-5b should be investigated further as a potential biomarker to predict response to therapy, including slowing of radiographic progression.

Effects of Er-Zhi-Wan on microarchitecture and regulation of Wnt/β-catenin signaling pathway in alveolar bone of ovariectomized rats

Recent studies have shown that Er-Zhi-Wan (EZW), a traditional Chinese medicine consisting of Herba Ecliptae (HE) and Fructus Ligustri Lucidi (FLL), had a definite antiosteoporotic effect on osteoporotic femur, but its effect on osteoporosis of alveolar bone remains unknown. In the present study, we investigated the effects of Er-Zhi-Wan (EZW) on the microarchitecture and the regulation of Wnt/β-catenin signaling pathway in the alveolar bone of ovariectomized rats. Thirty Sprague-Dawley rats were randomly divided into three groups: sham operation group (sham, n=10), ovariectomy (OVX) group (n=10), and OVX with EZW treatment group (EZW group, n=10). From one week after ovariectomy, EZW (100 mg/mL) or vehicle (distilled water) was fed (1 mL/100 g) once per day for 12 weeks until the sacrifice of the rats. The body weights were measured weekly. After sacrifice, the sera and mandible were collected and routinely prepared for the measurement of alveolar trabecular microarchitecture, serum levels of E2, bone-specific alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase 5b (TRAP5b), as well as mandibular mRNA expression of Wnt/β-catenin signaling pathway molecules wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5), β-catenin and dickkopf homolog 1 (DKK1). The results showed that EZW treatment significantly prevented the body weight gain, degradation of alveolar trabecular microarchitecture and alveolar bone loss in the OVX rats. Furthermore, we observed that EZW could increase the serum levels of E2 and BALP, and decrease levels of serum TRAP5b in EZW group compared with vehicle group. In addition, RT-PCR results revealed that EZW upregulated the expression levels of wnt3a, LRP5 and β-catenin, and reduced the expression of DKK1 in OVX rats. Taken together, our results suggested that EZW may have potential anti-osteoporotic effects on osteoporotic alveolar bone by stimulating Wnt/LRP5/β-catenin signaling pathway.

One-year changes in bone mineral density and bone turnover markers in premenopausal amateur runners: a prospective study.

A prospective study was conducted to clarify the 1-year changes in lumbar spine and hip bone mineral density (BMD) and bone turnover markers in premenopausal amateur runners and to determine whether jumping and muscle-strengthening exercises have additive effects on the bone parameters in these runners. Thirty-six premenopausal amateur runners were recruited and were divided into the following two groups: a jumping plus muscle-strengthening exercise group (n =21) and a control group (n =15). All participants continued their running practice for 1 year, and the lumbar spine and total hip BMD and bone turnover markers were monitored. For all participants, the lumbar spine and total hip BMD increased modestly after 1 year (1.31% and 1.54%, respectively) in addition to increases in the bone-specific alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase 5b levels (13.2%-27.8%), indicating mild effects of running activity on bone turnover and BMD at clinically relevant skeletal sites. Jumping plus muscle-strengthening exercises did not significantly influence any bone parameters; however, it was difficult to draw definite conclusions because compliance was poor. These results suggest that long-distance running at the recreational level may be useful in maintaining bone health in premenopausal women.

Effects of angiotensin-converting enzyme inhibitor, captopril, on bone of mice with streptozotocin-induced type 1 diabetes

There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin-angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-β and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice.

Effects of Fluoride and Cadmium co-Exposure on Bone in Male Rats

Although cadmium (Cd) and fluoride may both have adverse effects on bone, most studies focus on a single agent. In this study, we investigated the effects of cadmium and fluoride on bone at a relative low level. Sprague-Dawley male rats were assigned randomly into four groups which were given sodium chloride, cadmium (50mg/L), and fluoride (20mg/L) alone, or in combination via drinking water. At the 12th week, urine, blood, and bone tissues were collected for biomarker assay, biomechanical assay, and histological assay. Cadmium had significantly adverse effects on bone mineral density, bone biomechanical property, and bone microstructure. Fluoride slightly increased vertebral bone mineral density but negatively affected bone biomechanical property and bone microstructure. Fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium but could not improve the damage of bone biomechanical property and microstructure caused by cadmium. Tartrate-resistant acid phosphatase 5b levels in rats treated with cadmium and fluoride or in combination were 1-2.5 folds higher than the control. Our data suggest that low level of fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium exposure but has no influence on appendicular skeleton damage caused by cadmium.

Plasma osteopontin is correlated with bone resorption markers in rheumatoid arthritis patients

To assess whether any form of osteopontin (OPN) is correlated with bone resorption markers or treatment effects in rheumatoid arthritis (RA). Subjects comprised 119 patients with RA. RA disease activity was evaluated by Disease Activity Score (DAS) 28, erythrocyte sedimentation rate (ESR), and levels of C-reactive protein (CRP), rheumatoid factor (RF) and matrix metalloproteinase (MMP)-3. OPN levels in plasma and urine were measured by enzyme-linked immunosorbent assay (ELISA). Levels of tartrate-resistant acid phosphatase (TRACP) 5b in serum and C-terminal telopeptide of type 1 collagen (CTX)-1 in urine were measured by ELISA. Patients were divided into responder and nonresponder groups, and OPN levels were compared at baseline and after treatment. Levels of full-length OPN in plasma (P-fOPN) were significantly correlated with levels of TRACP 5b (r=0.44, P<0.001), urine CTX-1 (r=0.26, P=0.004) and MMP-3 (r=0.34, P<0.001). Levels of TRACP 5b were significantly correlated with age (r=0.25, P=0.007), but levels of P-fOPN were not. After treatment, plasma OPN levels were significantly decreased in responders (P=0.003). Levels of full-length or thrombin-cleaved forms of OPN in urine were not correlated with TRACP 5b or CTX-1. Our results suggest that plasma OPN may reflect inflammatory bone destruction in RA patients.

The clinical utility of serum tartrate‐resistant acid phosphatase 5b in the assessment of bone resorption in patients on peritoneal dialysis

Serum tartrate-resistant acid phosphatase 5b (TRACP5b) is a bone resorption marker used in the assessment of bone metabolic status. The present study was designed to determine the clinical characteristics and utility of measuring serum TRACP5b levels in peritoneal dialysis (PD) patients. Cross-sectional study. Forty-one patients receiving PD treatment in a single centre. Serum levels of the bone turnover markers TRACP5b, N-terminal cross-linking telopeptide of type 1 collagen (NTX), bone-specific alkaline phosphatase (BAP), and parathyroid hormone (PTH) were simultaneously measured. The correlation of serum TRACP5b with other established bone markers was analysed after logarithmic transformation. Multivariate linear regression analysis was performed to examine the effects of both renal and peritoneal Kt/V (an index for solute clearance) for urea on bone markers using age, sex, body mass index, and PTH as covariates. Bone markers were also measured in three patients before and after treatment with cinacalcet hydrochloride, alphacalcidol, and raloxifene hydrochloride. Log TRACP5b was significantly correlated with log NTX, log BAP and log PTH. In the multivariate analysis, peritoneal Kt/V was not correlated with log NTX, log BAP or log TRACP5b. In contrast, renal Kt/V was significantly correlated with log NTX only. Responses to drug treatment were more accurately determined from serum TRACP5b and BAP than from serum NTX. Serum TRACP5b and BAP are potentially useful biomarkers for the evaluation of bone turnover in PD patients because they correlate well with other established bone markers and they are not influenced by renal and peritoneal clearances.