tracp 5b
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Author(s):  
Etienne Cavalier ◽  
Pierre Lukas ◽  
Pierre Delanaye

Abstract Objectives Tartrate-resistant acid phosphatase, isoform 5b (TRACP-5b) is a bone resorption marker not influenced by renal function or food intake. TRACP-5b can be measured with Nittobo Medical enzymatic-immunoassay and IDS-iSYS automated immunoassay. We evaluated the Nittobo assay and established reference ranges for a Western-European population. We compared Nittobo and IDS results in different well-defined clinical populations. Methods We established the limits of detection and quantification (LOD-LOQ), linearity, imprecision and the reference ranges in 119 males, 50 women (<45 years) and 120 women (>60 years) for TRACP-5b with the Nittobo assay. We compared both assays in 30 hemodialyzed (HD), and 40 stage 3–5 patients suffering from chronic kidney disease (CKD), 40 patients suffering from rheumatoid arthritis and osteoporosis and 80 post-menopausal women. We measured TRACP-5b, β-crosslaps (β-CTX), bone alkaline phosphatase (B-ALP) and PTH in 20 hemodialyzed (HD) and 40 CKD patients. Results LOD and LOQ were 0.02 and 0.35 U/L. CV ranged from 8.3 to 4.3% (2/5 samples presenting CV > desirable CV). Method was linear up to of 11.3 U/L. Upper and lower limits of normality were 0.8–7.6 U/L in men, 0.9–4.7 U/L in women <45 and 0.9–7.1 U/L in women >60. The regression equation between the 2 methods was Nittobo = 1.13 (95% CI: 1.09–1.16) × iSYS − 0.4 (95% CI: −0.5; −0.3). TRACP-5b and b-ALP were in their respective reference ranges for most of CKD and HD patients. That was not the case for β-CTX, which increased with decreasing eGFR. Conclusions Nittobo TRACP-5b presents interesting analytical features and a good concordance with IDS iSYS. These methods could thus potentially be harmonized.


Endocrinology ◽  
2021 ◽  
Author(s):  
Karim Sahbani ◽  
Christopher P Cardozo ◽  
William A Bauman ◽  
Hesham A Tawfeek

Abstract Bone loss is one of the most common complications of immobilization after spinal cord injury (SCI). Whether TGF-β signaling plays a role in SCI-induced disuse bone loss has not been determined. Thus, 16-week-old male mice underwent sham or spinal cord contusion injury to cause complete hindlimb paralysis. Five days later, 10 mg/kg/day control (IgG) or anti-TGF-β1,2,3 neutralizing antibody (1D11) was administered twice weekly for 4 weeks. Femurs were examined by micro-computed tomography scanning (micro-CT) and histology. Bone marrow (BM) supernatants were analyzed by ELISA for levels of procollagen type 1 intact N-terminal propeptide (P1NP), tartrate-resistant acid phosphatase (TRAcP-5b), receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and prostaglandin E2 (PGE2). Distal femoral micro-CT analysis showed that SCI-1D11 mice had significantly (P&lt;0.05) attenuated loss of trabecular fractional bone volume (123% SCI-1D11 vs 69% SCI-IgG), thickness (98% vs 81%), and connectivity (112% vs 69%) and improved the structure model index (2.1 vs 2.7). Histomorphometry analysis revealed that osteoclast numbers were lower in the SCI-IgG mice than sham-IgG sham control. Biochemically, SCI-IgG mice had higher levels of P1NP and PGE2 but similar TRAcP-5b and RANKL/OPG ratio to the sham-IgG group. SCI-1D11 group exhibited higher levels of P1NP and RANKL/OPG ratio but similar TRAcP-5b and PGE2 to the sham-1D11 group. Furthermore, 1D11 treatment prevented SCI-induced hyperphosphorylation of tau protein in osteocytes, an event that destabilizes the cytoskeleton. Together, inhibition of TGF-β signaling after SCI protects trabecular bone integrity, likely by balancing bone remodeling, inhibiting PGE2 elevation, and preserving the osteocyte cytoskeleton.


2021 ◽  
pp. 1-22
Author(s):  
Jonathan M. Scott ◽  
Elizabeth A. Swallow ◽  
Corinne E. Metzger ◽  
Rachel Kohler ◽  
Joseph M. Wallace ◽  
...  

Abstract In the US, as many as 20% of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop iron deficiency upon completion of training. Iron is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesized iron deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading. Three-week old female Sprague Dawley rats were assigned to one of four groups: iron adequate sedentary, iron deficient sedentary, iron adequate exercise, and iron deficient exercise. Exercise consisted of high-intensity treadmill running (54 min 3×/week). After 12-weeks, serum bone turnover markers, femoral geometry and microarchitecture, mechanical properties and fracture toughness, and tibiae mineral composition and morphometry were measured. Iron deficiency increased the bone resorption markers C-terminal telopeptide type I collagen and tartate-resistant acid phosphatase 5b (TRAcP 5b). In exercised rats, iron deficiency further increased bone TRAcP 5b, while in iron adequate rats, exercise increased the bone formation marker procollagen type I N-terminal propeptide. In the femur, exercise increased cortical thickness and maximum load. In the tibia, iron deficiency increased the rate of bone formation, mineral apposition, and zinc content. These data show that the femur and tibia structure and mechanical properties are not negatively impacted by iron deficiency despite a decrease in tibiae iron content and increase in serum bone resorption markers during 12-weeks of high-intensity running in young growing female rats.


2021 ◽  
pp. 074823372110489
Author(s):  
Nnenna L Nwobi ◽  
Joseph C Nwobi ◽  
Esther N Adejumo ◽  
Osahon S Usiobeigbe ◽  
Opeyemi A Adetunji ◽  
...  

Lead is an occupational toxicant and a recognised health threat particularly in developing countries. Hence, this study explored the interaction of blood lead level (BLL), a conventional marker of lead exposure, with indices of calcium metabolism and biomarkers of bone-turnover in 120 adult male automobile technicians (AT) with ≥ 1 year duration in professional practice. The AT as well as the control group, which comprised 120 age, body-size and socio-economically matched male administrative workers, were recruited from Sagamu, South West Nigeria. Levels of blood lead, serum indices of calcium metabolism [total calcium (tCa), ionised calcium (iCa), phosphate, albumin, magnesium (Mg) and 25-Hydroxycholecalceferol (25-OHCC)], biomarkers of bone formation [bone alkaline phosphatase (BALP) and osteocalcin (OC)] and biomarkers of bone resorption [tartarate-resistant acid phosphatase-5b (TACRP-5b) and urinary hydroxyproline (UHYP)] were determined in all participants. The BLL, 25-OHCC, TRACP-5b and UHYP significantly increased while tCa and iCa significantly reduced in AT compared to control. However, no significant difference was observed in phosphate, albumin, Mg, BALP and OC in AT compared to control. Interestingly, BLL demonstrated a significant negative association with tCa and iCa but a significant positive association with 25-OHCC, TRACP-5b and UHYP. However, BLL did not show significant association with phosphate, albumin, Mg, BALP and OC. Increased lead exposure as well as altered calcium metabolism and bone-turnover demonstrated by the automobile technicians may be suggestive of lead-induced accelerated bone demineralisation. These workers may be predisposed to high risk of increased susceptibility to bone diseases if this sub-clinical picture is sustained.


2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Nagato Kuriyama ◽  
Etsuko Ozaki ◽  
Teruhide Koyama ◽  
Daisuke Matsui ◽  
Isao Watanabe ◽  
...  

Abstract Background Bone mass was recently reported to be related to skeletal muscle mass in humans, and a decrease in cortical bone is a risk factor for osteoporosis. Since circulating myostatin is a factor that primarily controls muscle metabolism, this study examined the role of myostatin in blood in bone mass-skeletal muscle mass interactions. Methods The subjects were 375 middle-aged community residents with no history of osteoporosis or sarcopenia who participated in a health check-up. The subjects were divided into those with low cortical bone thickness (LCT) or low cancellous bone density (LBD) and those with normal values (NCT/NBD). Bone metabolism markers (BAP, TRACP-5b, etc.), skeletal muscle mass, serum myostatin levels, and lifestyle, were then compared between the groups. Results The percentage of diabetic participants and blood HbA1c, TRACP-5b, and myostatin levels were significantly higher, and the frequency of physical activity, skeletal muscle mass, grip strength, and leg strength were significantly lower in the LCT group than in the NCT group. The odds ratio of high myostatin in the LCT group compared with the NCT group was significant (2.26) even after adjusting for related factors. Significant differences were observed in the same items between the LBD and NBD groups as between the LCT and NCT groups, with no significant differences in skeletal muscle mass and serum myostatin levels. The serum myostatin level was significantly negatively correlated with cortical bone thickness and skeletal muscle mass. Conclusions Myostatin may regulate bone-skeletal muscle interactions and serve as a surrogate marker of cortical bone metabolism. Key messages The interaction between bone and skeletal muscle is reported to be important for preserving the activity of bone and muscle metabolism. Herein, we report for the first time that myostatin may regulate bone-skeletal muscle interactions and serve as a surrogate marker of cortical bone metabolism in adults.


Endocrines ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 293-300
Author(s):  
Ikuko Ota ◽  
Yoshiaki Ota ◽  
Fuminori Taniguchi

A low dose of dienogest (DNG) 1 mg/day is useful for treating dysmenorrhea in young women. However, the effect of DNG on bone turnover during bone growth and formation, rather than at maturity, is currently unknown even at low doses. We investigated change in bone turnover after 3 months of DNG 1 mg/day. This retrospective cohort study included young women aged 10–24 years with dysmenorrhea and irregular menstruation. Gonadotropins and the bone metabolism markers TRACP-5b and BAP were compared before and at 3 months after administration of DNG 1 mg/day. There were no significant changes in TRACP-5b (before, 455.6 ± 323.6 mU/dL; 3 months after, 462.1 ± 346.1 mU/dL), BAP (before, 24.7 ± 19.0 μg/L; 3 months after, 25.2 ± 22.3 μg/L), or the TRACP-5b/BAP ratio (before, 22.1 ± 7.0; 3 months after, 21.5 ± 6.3). Administration of DNG 1 mg/day had no significant effect on bone turnover after 3 months during the bone-growth phase in young women.


Author(s):  
Yosuke Nakagawa ◽  
Hirotaka Komaba ◽  
Naoto Hamano ◽  
Hisae Tanaka ◽  
Takehiko Wada ◽  
...  

Abstract Context Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure, but its role in the pathogenesis of renal bone disease remains unknown. Objective To explore the association of serum sclerostin with bone metabolism in patients undergoing hemodialysis, with a particular focus on parathyroid hormone (PTH)-dependent and PTH-independent pathways. Design Cross-sectional and prospective cohort study. Setting and participants 654 patients undergoing hemodialysis at 10 facilities in Japan. Main outcome measures We employed multivariable linear regression to explore whether sclerostin levels were associated with metacarpal bone mineral density (BMD), intact PTH, bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b). We employed mediation analyses to explore whether and to what extent the association of PTH with bone turnover markers is mediated by sclerostin. We also compared sclerostin levels between patients with and without previous or incident fractures. Results The median sclerostin level in hemodialysis patients was 3–4-fold higher than that in healthy individuals. Higher sclerostin levels were associated with higher metacarpal BMD and lower levels of intact PTH, BAP, and TRACP-5b. However, the relationships of sclerostin with bone turnover markers were substantially attenuated after adjustment for PTH. Mediation analysis suggested that the effects of PTH on bone turnover markers were mainly direct rather than mediated by sclerostin. Sclerostin levels were not associated with previous or incident fractures. Conclusions These findings suggest that in patients undergoing dialysis, sclerostin has only a limited role in bone metabolism and may not mediate the effect of PTH on bone turnover.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Naoto Tominaga ◽  
Tomoki Yonaha ◽  
Masayuki Yamanouchi ◽  
Hirofumi Sumi ◽  
Yasuhiro Taki ◽  
...  

Abstract Background Parathyroid hormone (PTH) acts on bone to indirectly increase the number and activity of osteoclasts. Thus, PTH has a stimulatory effect on bone resorption and upregulates bone turnover. However, the responsiveness of bone to PTH varies widely among patients receiving dialysis. In fact, relative to the serum PTH level, the level of serum tartrate-resistant acid phosphatase-5b (TRACP-5b), a bone resorption marker derived from osteoclasts, varies as well. This study aimed to examine factors related to bone responsiveness to PTH in patients undergoing chronic hemodialysis (HD). Methods This study included patients receiving chronic HD in Kawasaki Municipal Tama Hospital (Kanagawa, Japan) and Yonaha Medical Clinic (Okinawa, Japan) and excluded patients who received HD for less than 6 months, those who received a combination of HD and peritoneal dialysis, and those who had cancer bone metastases or myeloma. The TRACP-5b/intact PTH (iPTH) ratio was created as an index of bone responsiveness to PTH, categorized into tertiles (low, medium, and high), and a cross-sectional study was conducted. P < 0.05 indicated statistically significant differences. Results One hundred and six patients were analyzed. Age (P = 0.010), body mass index (BMI) (P = 0.003), use of calcium-sensing receptor (CaSR) agonists (P = 0.008), use of vitamin D receptor activators (VDRAs) (P = 0.012), plasma iPTH level (P < 0.001), serum 1,25(OH)2D level (P = 0.003), and serum TRACP-5b level (P < 0.001) were significantly different among the three categories. In the single linear regression analysis, age (P = 0.016), corrected serum calcium level (P = 0.007), and ln [1,25(OH)2D] (P = 0.044) showed a significant positive correlation with ln [TRACP-5b/iPTH], whereas BMI (P = 0.026), use of CaSR agonists (P = 0.001), use of VDRAs (P = 0.009), and serum phosphorus level (P = 0.018) showed a significant negative correlation. Upon conducting multiple linear regression analysis incorporating significant variables in the single linear regression analysis, a significant negative correlation was observed between the TRACP-5b/iPTH ratio and intravenous administration of a CaSR agonist (etelcalcetide) and/or a VDRA (calcitriol or maxacalcitol) in all the adjusted models. Conclusions Bone responsiveness to PTH is negatively correlated with the intravenous administration of a CaSR agonist and/or a VDRA in patients undergoing chronic HD.


Sports ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 82
Author(s):  
Tatsuya Ishizu ◽  
Eri Takai ◽  
Suguru Torii ◽  
Motoko Taguchi

The aim of the present study was to clarify the influence of inulin and lactulose-fortified prebiotic food intakes on bone metabolism turnover among Japanese female athletes. The participants included 29 female athletes aged 18–25 years. They were requested to consume their habitual foods or drinks with one pack of prebiotic food every day for 12 weeks. Dietary intake, training time, body composition, blood sample, and fecal microbiota were assessed during this intervention period. Body composition, total energy intake, and training time of the participants revealed no significant changes during the intervention period. The occupation ratio of Bifidobacterium spp. was significantly increased at 3 and 4 weeks (18.0 ± 8.3% and 17.6 ± 8.5%, respectively) compared to that of pre-intervention (11.7 ± 7.3%) (p = 0.019 and p = 0.035, respectively). The serum TRACP-5b level was significantly decreased at 12 weeks (363 ± 112 mU/dL) compared to that at baseline (430 ± 154 mU/dL) (p = 0.018). These results suggest that the prebiotic food used in this study might have beneficial effects on bone health and gut microbial environment among female athletes. Further studies are warranted to identify the mechanism of the prebiotics–gut–bone axis.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 59.1-60
Author(s):  
Y. Kanayama ◽  
R. Sugimoto

Background:Romosozumab (ROMO), a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. And although it is a novel therapeutic agent for osteoporosis, which has shown high effects of increasing bone density and inhibiting fragile fracture in overseas clinical trials. However the clinical efficacy for rheumatoid arthritis complicated with osteoporosis (RA-OP) is unknown.Objectives:To evaluate the clinical efficacy of ROMO in patients with RA-OP for 12 months.Methods:RA patients diagnosed according to the 2010 ACR/EULAR criteria. All patients met at least one of the following criteria were eligible; a bone mineral density T score of -2.5 or less at the lumber spine or total hip and either one or more moderate or severe vertebral fractures or two or more mild vertebral fractures. All patients were initiated ROMO from between March and December, 2019. The total number of patients was 13 cases. The ROMO dose was 210mg at once every 1 months. In all cases native or activated vitamin D has been used. We reviewed the results for 12 months about the increase and decrease of bone mineral density (BMD) of lumbar spine(LS) and total hip(TH) by DEXA and bone turnover markers, intact n-terminal propeptide type I procollagen(PINP) and tartrate-resistant acid phopshatate form 5b(TRACP-5b).Results:The gender was all female. The mean age was 73.2 ± 7.6; disease duration was 20.5 ± 16.9 years; the body mass index was 19.7 ± 3.0 and the FRAX was 40.5 ± 16.2. Clinical findings related to RA-OP at baseline were as follows; CRP 1.29 ± 1.66; DAS-CRP 3.43 ± 0.96; HAQ 1.59 ± 0.97 and, bone turnover markers and bone mineral density at baseline were as follows; P1NP 58.1 ± 33.5; TRACP-5b 438 ± 216; LS-BMD and T-score 0.81 ± 0.15 g/cm2 and -2.63 ± 1.05 and TH-BMD 0.54 ± 0.08 g/cm2 and -3.22 ± 0.64 g/cm2. The rate of increased P1NP from baseline to 1, 3, 6 and 12 months were each 114.3 ± 90.6% at 1 month, 131.6 ± 134.3% at 3 month, 122.6 ± 174.3% at 6 month and 80.4 ± 181.6% at 12 month and decreased TRAC-5b were -10.7 ± 20.8% at 1 month, 7.9 ± 36.9% at 3 month, 25.5 ± 64.6% at 6 month and 32.5 ± 77.0% at 12 month. The rate of increased LS-BMD from baseline to 6 and 12 months were 8.6 ± 8.0%, 12.5 ± 11.1% and TH-BMD were 4.3 ± 5.0%, 6.8 ± 6.9% (Fig. 1, 2).Conclusion:Clinical efficacy of ROMO for RA-OP was extremely effective and has the high potential to be an important option in the treatment of RA-OP.References:Disclosure of Interests:None declared


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