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Reportedly, nausea or vomiting after heavy exercise was associated with post-exercise increased blood calcium (Ca) levels, which was correlated with enhanced bone resorption. We conducted a randomized, double-blind, placebo-controlled trial, enrolling 104 healthy trained male members of the Japan Ground Self-Defense Forces. Risedronate (17.5 mg) or placebo was prescribed 3 and 10 days before heavy exercise lasting approximately 5 h. The primary outcome was the severity of nausea or vomiting assessed by a visual analog scale during or post-exercise. The secondary outcomes included clinical symptoms associated with heat illness, post-exercise serum total Ca (tCa), whole blood ionized Ca (iCa), and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) levels. The mean age was 26 years. The exercise resulted in a 4.5% weight loss. The two groups were comparable in terms of the symptoms, including primary outcome. However, post-exercise tCa and TRACP-5b were significantly lower with risedronate. A similar result was observed for iCa. The post-exercise urinary Ca/Magnesium ratio and the incidence of hypercalcemia (defined as tCa or iCa levels ≥ each median value of all subjects) were significantly lower with risedronate (78.0% vs. 58.5%). A stronger treatment effect of risedronate on blood Ca levels was observed in participants who lost substantial body weight. Post-exercise hypercalcemia is attributed to enhanced bone resorption but not the cause of nausea.

Aside from existing drug therapies, certain lifestyle and nutritional factors are known to reduce the risk of osteoporosis. Among the nutritional factors, dried plum or prunes (Prunus domestica L.) is the most effective fruit in both preventing and reversing bone loss. The objective of the present study was to examine the extent to which dried plum reverses bone loss in osteopenic postmenopausal women. We recruited 236 women, 1–10 years postmenopausal, not on hormone replacement therapy or any other prescribed medication known to influence bone metabolism. Qualified participants (n 160) were randomly assigned to one of the two treatment groups: dried plum (100 g/d) or dried apple (comparative control). Participants received 500 mg Ca plus 400 IU (10 μg) vitamin D daily. Bone mineral density (BMD) of lumbar spine, forearm, hip and whole body was assessed at baseline and at the end of the study using dual-energy X-ray absorptiometry. Blood samples were collected at baseline, 3, 6 and 12 months to assess bone biomarkers. Physical activity recall and 1-week FFQ were obtained at baseline, 3, 6 and 12 months to examine physical activity and dietary confounders as potential covariates. Dried plum significantly increased BMD of ulna and spine in comparison with dried apple. In comparison with corresponding baseline values, only dried plum significantly decreased serum levels of bone turnover markers including bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b. The findings of the present study confirmed the ability of dried plum in improving BMD in postmenopausal women in part due to suppressing the rate of bone turnover.

Aim Preclinical studies suggested that insulin, incretin and thiazolidinediones had effect on regulation of bone metabolism. But clinical evidence is limited. We assessed the effects of these antihyperglycemic agents on bone metabolism in patients with newly diagnosed type 2 diabetes. Methods The present study was a two-center, randomized, parallel-group clinical trial. Sixty-two newly diagnosed and drug-naïve patients with type 2 diabetes were randomized to exenatide (EXE, n  = 20), mixed protamine zinc recombinant human insulin lispro injection (25R; INS, n  = 21) or pioglitazone (PIO, n  = 21) group for a 24-week treatment. Glycosylated hemoglobin A1c (HbA1c), body weight, body mineral density (BMD) and fasting serum concentration of bone turnover markers including osteocalcin (OC), C-telopeptide of type I collagen (CTX) and tartrate-resistant alkaline phosphatase 5b (TRAcP5b) were assessed at baseline and week 24. Results Baseline characteristics were similar among groups. At week 24, HbA1c improved in all patients (EXE:−2.4 ± 0.3 %, INS:−2.4 ± 0.3 %, PIO:−2.0 ± 0.2 %; p  > 0.05 among groups). Patients treated with exenatide lost body weight remarkably (−4.7 ± 0.8 kg). In spite of the amelioration of glucose control, no significant improvement of OC, CTX or TRAcP5b was observed at week 24 (EXE: OC −0.619 ± 0.728 ng/ml, CTX 0.147 ± 0.046 ng/ml, TRAcP5b 0.302 ± 0.149 U/L;INS: OC 0.637 ± 0.787 ng/ml, CTX −0.012 ± 0.074 ng/ml, TRAcP5b 0.124 ± 0.395 U/L; PIO: OC −0.150 ± 0.691 ng/ml, CTX 0.073 ± 0.094 ng/ml, TRAcP5b 0.586 ± 0.183 U/L; p  > 0.05), as well as BMD measurement, regardless of the treatments. Conclusions Twenty-four-week treatment with exenatide, insulin and pioglitazone improved glucose control in patients with newly diagnosed type 2 diabetes, but had no impact on bone turnover markers or BMD.

This study was aimed to compare the outcomes of two operational methods used for the fixation of calcaneal fracture, the open reduction using a plate and the minimally invasive cannulated screw fixations. Thus, we attempted to find out as to which of these fixation regimens was therapeutically superior by assessing improvement in the restoration of foot functioning and estimating the biochemical indices that reflect bone recovery. A total of 492 calcaneal fracture patients admitted in our hospital from February, 2008 to February, 2012 were selected for the study and randomly divided into two groups of 246 cases each. They were treated with either open reduction using a plate or minimally invasive cannulated screw fixation procedures. After the operations, patients were followed up for 2 years and the outcomes including functional restoration of calcaneus, the post-operational complications, and measure of the biochemical indicators of bone recovery were compared. The patients who underwent plate fixation procedure showed the excellent and good rate of 76.8 %. The minimally invasive cannulated screw fixation led to the excellent and good rate of 82.5 %. The angle, width, and height of calcaneus observed in the last follow-up were also improved significantly in the two groups ( p  < 0.05); however, these outcomes of the two techniques were not significantly different from each other ( p  > 0.05). The post-operative complications occurred with the rates of 14.2 and 4.9 % in the patients treated with the plate and the minimally invasive cannulated screw fixations, respectively. The length of stay and hospitalization costs in the plate fixation group were 9.16 ± 0.83 days and 12,639.74 ± 2,573.82 Chinese Yuan, respectively. In comparison, in cannulated screw fixation group, the length of hospital stay (7.03 ± 0.52 days) and its cost (6,795.01 ± 996.53 Chinese Yuan) were significantly lower. Serum bone alkaline phosphatase and tartrate-resistant acid phosphatase-5b levels measured at the last follow-up examination were significantly altered ( p  < 0.05) in the two groups. However, the difference between the outcomes of the two methods was not statistically significant ( p  > 0.05). Plate screw and the cannulated screw fixations showed equally good therapeutic effect and significantly improved patients’ mobility. However, the cannulated screw fixation was superior in terms of post-operative infection-free recovery and economical burden to the patients.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options. Tartrate-resistant acid phosphatase 5 (ACP5) performs a variety of functions. However, its role in IPF remains unclear. Here, we demonstrate that the levels of ACP5 are increased in IPF patient samples and mice with bleomycin (BLM)-induced pulmonary fibrosis. In particular, higher levels of ACP5 are present in the sera of IPF patients with a diffusing capacity of the lungs for carbonmonoxide (DLCO) less than 40% of the predicted value. Additionally, Acp5 deficiency protects mice from BLM-induced lung injury and fibrosis coupled with a significant reduction of fibroblast differentiation and proliferation. Mechanistic studies reveal that Acp5 is upregulated by transforming growth factor-β1 (TGF-β1) in a TGF-β receptor 1 (TGFβR1)/Smad family member 3 (Smad3)-dependent manner, after which Acp5 dephosphorylates p-β-catenin at serine 33 and threonine 41, inhibiting the degradation of β-catenin and subsequently enhancing β-catenin signaling in the nucleus, which promotes the differentiation, proliferation and migration of fibroblast. More importantly, the treatment of mice with Acp5 siRNA-loaded liposomes or Acp5 inhibitor reverses established lung fibrosis. In conclusions, Acp5 is involved in the initiation and progression of pulmonary fibrosis and strategies aimed at silencing or suppressing Acp5 could be considered as potential therapeutic approaches against pulmonary fibrosis. Idiopathic pulmonary fibrosis is a fatal lung disease with limited treatment options. Here the authors show that tartrate-resistant acid phosphatase 5 (Acp5) promotes lung fibrosis by enhancing beta-catenin signaling and that inhibition of Acp5 can reverse stablished pulmonary fibrosis.

The periosteum, a thin tissue that covers almost the entire bone surface, accounts for more than 80% of human bone mass and is essential for bone regeneration. Its osteogenic and bone regenerative abilities are well studied, but much is unknown about the periosteum. In this study, we found that macrophage-lineage cells recruit periosteum-derived cells (PDCs) for cortical bone formation. Knockout of colony stimulating factor-1 eliminated macrophage-lineage cells and resulted in loss of PDCs with impaired periosteal bone formation. Moreover, macrophage-lineage TRAP+ cells induced transcriptional expression of periostin and recruitment of PDCs to the periosteal surface through secretion of platelet-derived growth factor-BB (PDGF-BB), where the recruited PDCs underwent osteoblast differentiation coupled with type H vessel formation. We also found that subsets of Nestin+ and LepR+ PDCs possess multipotent and self-renewal abilities and contribute to cortical bone formation. Nestin+ PDCs are found primarily during bone development, whereas LepR+ PDCs are essential for bone homeostasis in adult mice. Importantly, conditional knockout of Pdgfrβ (platelet-derived growth factor receptor beta) in LepR+ cells impaired periosteal bone formation and regeneration. These findings uncover the essential role of periosteal macrophage-lineage cells in regulating periosteum homeostasis and regeneration.

Summary Inhibition of sympathetic signaling to bone reduces bone resorption in rodents. In contrast, we show that pharmacological reduction of the sympathetic tone increases bone resorption in humans in vivo. This effect does not appear to be mediated via a direct pharmacological effect on the osteoclast. Introduction Inhibition of sympathetic signaling to bone reduces bone resorption in rodents. It is uncertain whether a similar role for the sympathetic nervous system exists in humans. The sympathetic tone can be reduced by clonidine, which acts via alpha-2-adrenergic receptors in the brainstem. Our objective was to determine the effect of clonidine on bone turnover in humans. Methods The acute effect of a single oral dose of 0.3 mg clonidine on serum bone turnover markers (C-terminal cross-linking telopeptides of collagen type I (CTx), a marker for bone resorption, and procollagen type 1 N propeptide (P1NP), a marker for bone formation) was determined in a randomized crossover design in 12 healthy volunteers, aged 18–70 years. In addition, we assessed the effect of clonidine on the number of tartrate-resistant acid phosphatase–positive multinucleated cells (TRAcP + MNCs) and bone resorption. Results CTx concentrations increased after clonidine treatment compared to the control condition ( p  = 0.035). P1NP concentrations were not affected by clonidine ( p  = 0.520). In vitro, clonidine had no effect on the number of TRAcP + MNCs ( p  = 0.513) or on bone resorption ( p  = 0.996). Conclusions We demonstrated that clonidine increases bone resorption in humans in vivo. This effect does not appear to be mediated via a direct effect on the osteoclast.

Arbuscular mycorrhizal fungi (AMF) transfer plant photosynthate underground which can stimulate soil microbial growth. In this study, we examined whether there was a potential link between carbon (C) release from an AMF and phosphorus (P) availability via a phosphatesolubilizing bacterium (PSB). We investigated the outcome of the interaction between the AMF and the PSB by conducting a microcosm and two Petri plate experiments. An in vitro culture experiment was also conducted to determine the direct impact of AMF hyphal exudates on growth of the PSB. The AMF released substantial C to the environment, triggering PSB growth and activity. In return, the PSB enhanced mineralization of organic P, increasing P availability for the AMF. When soil available P was low, the PSB competed with the AMF for P, and its activity was not stimulated by the fungus. When additional P was added to increase soil available P, the PSB enhanced AMF hyphal growth, and PSB activity was also stimulated by the fungus. Our results suggest that an AMF and a free-living PSB interacted to the benefit of each other by providing the C or P that the other microorganism required, but these interactions depended upon background P availability.

Effects of whole-body cryostimulation on lysosomal enzyme activity: acid phosphatase (AcP), arylsulphatase (ASA) and cathepsin D (CTS D), as well as on the creatine kinase (CK), and the cortisol concentration in the serum of kayakers during training were studied. Additionally, the effect of a single cryostimulation treatment in untrained men was evaluated. The kayakers were subjected to a ten-day training cycle, in which training sessions were preceded by whole-body cryostimulation at a temperature ranging from -120 to -140 degrees C, and to a control training without cryostimulation. Blood samples were taken from the kayakers before the training and after the sixth and tenth day of training and from untrained men before and after cryostimulation. The single cryostimulation caused a 30% (P < 0.05) decrease in the CK activity in untrained men. After the sixth day of training with cryostimulation, the activity of ASA was 46% (P < 0.001), AcP 32% (P < 0.05) and CK 34% lower (P < 0.05) than after the sixth day of training without cryostimulation. The results support that preceding training with whole-body cryostimulation alleviates exertion stress by a stabilisation of lysosomal membranes.

Summary Phosphate (Pi) deficiency in soil system is a limiting factor for rice growth and yield. Majority of the soil phosphorus (P) is organic in nature, not readily available for root uptake. Low Pi‐inducible purple acid phosphatases (PAPs) are hypothesized to enhance the availability of Pi in soil and cellular system. However, information on molecular and physiological roles of rice PAPs is very limited. Here, we demonstrate the role of a novel rice PAP, OsPAP21b in improving plant utilization of organic‐P. OsPAP21b was found to be under the transcriptional control of OsPHR2 and strictly regulated by plant Pi status at both transcript and protein levels. Biochemically, OsPAP21b showed hydrolysis of several organophosphates at acidic pH and possessed sufficient thermostability befitting for high‐temperature rice ecosystems with acidic soils. Interestingly, OsPAP21b was revealed to be a secretory PAP and encodes a distinguishable major APase (acid phosphatase) isoform under low Pi in roots. Further, OsPAP21b‐overexpressing transgenics showed increased biomass, APase activity and P content in both hydroponics supplemented with organic‐P sources and soil containing organic manure as sole P source. Additionally, overexpression lines depicted increased root length, biomass and lateral roots under low Pi while RNAi lines showed reduced root length and biomass as compared to WT. In the light of these evidences, present study strongly proposes OsPAP21b as a useful candidate for improving Pi acquisition and utilization in rice.