Bone metabolism appears to influence insulin secretion and sensitivity, and insulin promotes bone formation in animals, but similar evidence in humans is limited. The objectives of this study are to explore if bone turnover markers were associated with insulin secretion and sensitivity and to determine if bone turnover markers predict changes in insulin secretion and sensitivity. The study population encompassed 576 non-diabetic adult men with normal glucose tolerance (NGT; n=503) or impaired glucose regulation (IGR; n=73). Baseline markers of bone resorption (CTX) and formation (P1NP) were determined in the fasting state and after a 2-h hyperinsulinaemic, euglycaemic clamp. An intravenous glucose tolerance test (IVGTT) and a 2-h oral glucose tolerance test (OGTT) were performed at baseline, and the OGTT was repeated after 3years. There were no differences in bone turnover marker levels between NGT and IGR. CTX and P1NP levels decreased by 8.0% (p<0.001) and 1.9% (p<0.01) between baseline and steady-state during the clamp. Fasting plasma glucose was inversely associated with CTX and P1NP both before and after adjustment for recruitment centre, age, BMI, smoking and physical activity. However, baseline bone turnover markers were neither associated with insulin sensitivity (assessed using hyperinsulinaemic euglycaemic clamp and OGTT) nor with insulin secretion capacity (based on IVGTT and OGTT) at baseline or at follow-up. Although inverse associations between fasting glucose and markers of bone turnover were identified, this study cannot support an association between insulin secretion and sensitivity in healthy, non-diabetic men.

Obese children have disadvantageous bone geometry, bone of low quality, and reduced strength at non-weight-bearing skeletal sites. The aim of our study was to investigate the role of parathormone (PTH) and the Wnt/β-catenin signaling pathway and its inhibitors, sclerostin and Dickkopf-1 (DKK1), as negative modulators of fat mass on bone. This was a cross-sectional observational study performed in 44 (26 males and 18 females) obese subjects, aged 11.41 ± 2.61 years. Thirty-seven normal-weight, healthy children (22 males and 15 females) of the same chronological age served as controls for the biochemical parameters and bone markers, while the data on bone geometry were evaluated according to our normative data obtained previously in a group of 325 control children. Digitalized X-rays were evaluated at the level of the second metacarpal bone for the determination of bone geometry: total cross-sectional area (TCSA), cortical area (CA), medullary area (MA), and bone strength (bending breaking resistance index [BBRI]). Serum bone markers (intact procollagen-1N-terminal propeptide [P1NP] and serum carboxy-terminal telopeptide of collagen-1 [CTX]), sclerostin, DKK1, PTH, 25-hydroxyvitamin D and were also measured. Data for TCSA, CA, MA, and BBRI are expressed as a standard deviation score in order to normalize them for age and sex. TCSA (mean ± SD, -2.92 ± 2.71), CA (-0.60 ± 0.82), MA (-0.45 ± 1.14), and BBRI (-2.65 ± 2.31) were all significantly smaller than in controls (p < 0.01). Serum PTH (36.27 ± 23.89 vs. 19.33 ± 11.37 pg/mL) and CTX (1.55 ± 0.44 vs. 1.34 ± 0.46 ng/mL) were significantly increased (p < 0.05) in the obese children compared to controls, while sclerostin was significantly decreased (24.67 ± 10.06 vs. 30.42 ± 11.01 pmol/L, p < 0.05). P1NP was also significantly increased (p < 0.01). PTH was negatively correlated with TCSA, CA, and BBRI. Bone turnover is higher in obese children than in controls, and this is associated with smaller and apparently weaker bones. Higher PTH and lower sclerostin levels may be responsible for these findings.

Canonical Wnt (Wingless/Integrated) signaling is crucial in bone development and the Wnt ligand can promote osteoblast differentiation from mesenchymal progenitor cells. Calcitriol, an active vitamin D3, is used clinically for treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients. The bone effects of calcitriol in SHPT remains uncertain. We hypothesized that calcitriol improves bone mass by suppressing osteoclast activity, and simultaneously promoting Wnt ligand secretion. We designed a cross-sectional study in maintenance hemodialysis patients to explore the effects of calcitriol on different bone turnover markers and specifically emphasized the Wnt 10b levels. Then, we explored the source of Wnt 10b secretion by using osteoclasts and osteoblasts treated with calcitriol in cell culture studies. Finally, we explored the effects of calcitriol on bone microarchitectures in CKD mice, using the 5/6 nephrectomy CKD animal model with analysis using micro-computed tomography. Calcitriol promoted the growth of both trabecular and cortical bones in the CKD mice. Wnt 10b and Procollagen 1 N-terminal Propeptide (P1NP) significantly increased, but Tartrate-resistant acid phosphatase 5b (Trap 5b) significantly decreased in the calcitriol-treated maintenance hemodialysis patients. Calcitriol enhanced Wnt 10b secretion from osteoclasts in a dose-dependent manner. Treatment of SHPT with calcitriol improved the bone anabolism by inhibiting osteoclasts and promoting osteoblasts that might be achieved by increasing the Wnt 10b level.

OBJECTIVE

The objective of this study was to determine whether vitamin D and genistein supplementation had an additive beneficial effect on levels of vitamin D and bone markers and whether this effect was mediated by genes regulating isoflavone metabolism.

METHODS

We carried out a prospective study in postmenopausal women randomized to calcium and vitamin D supplementation or calcium, vitamin D, and genistein supplementation. Vitamin D, parathyroid hormone (PTH), cross-linked C-telopeptide (CTX), and procollagen 1 N-terminal (P1NP) were determined by electrochemiluminescence. Three SNPs - rs2231142 (ABCG2), rs358231 (cytosolic β-glucosidase [CBG]), and rs2273697 (ABCC2) - were determined.

RESULTS

We included 102 women. The effects on bone remodeling were similar: rises in vitamin D were significantly associated with reductions in PTH, CTX, and P1NP. Pharmacogenomic analysis of the genotypes showed that, in AT heterozygotes of the CBG1368T>A polymorphism, CTX and P1NP were not reduced.

CONCLUSIONS

Genistein added to calcium and vitamin D supplementation had no additional effect. The supplementation of individual AT heterozygotes of the CBG1368T>A polymorphism had no effect on markers of bone remodeling.

<AbstractText>Adults with type 1 diabetes (T1D) have increased risk of bone fractures and decreased bone mineral density (BMD). Alterations in bone turnover have been suggested as the link between T1D and the impaired bone health. Furthermore, bone turnover has been suggested to have beneficial effects on glucose metabolism. This study aimed at describing bone turnover markers (BTM), and the relationship with glycemic control, in children and adolescents with T1D.</AbstractText><AbstractText>173 (47% girls) children and adolescents aged 7.7-17.5 with T1D for more than one year were included. Participants were evaluated by BMD together with measurements of selected BTM; two formation markers: osteocalcin (OCN) and procollagen type-1 AMino-terminal propeptide (<em>P1NP</em>) and one resorption marker, C-terminal cross-linked telopeptide of type-1 collagen (CTX). BTM were converted into Z-scores utilizing new national references.</AbstractText><AbstractText>Mean OCN Z-score (-0.68 ± 1.31), <em>P1NP</em> Z-score (-0.33 ± 1.03) and CTX Z-score (-0.43 ± 1.10) were all significantly lower than the reference population (P < 0.001). No associations were seen between BTM and T1D duration. BMD Z-score was comparable to the reference population and associated to none of individual bone turnover markers. CTX Z-score was negatively associated to HbA1c (P = 0.007) independent of both exogeneous and residual endogenous insulin.</AbstractText><AbstractText>Markers of bone formation and resorption were decreased in children and adolescents with T1D. CTX Z-score associated negatively to HbA1c adjusted for insulin treatment and endogenous insulin production indicating a potential association between CTX and insulin sensitivity. The long-term consequences of decreased BTM on BMD needs further attention. This article is protected by copyright. All rights reserved.</AbstractText>

BACKGROUND

Cancer pathogenesis and resulting treatment may lead to bone loss and poor skeletal health in survivorship. The purpose of this investigation was to evaluate the influence of 26 weeks of combined aerobic and resistance-training (CART) exercise on bone mineral density (BMD) in a multi-racial sample of female cancer survivors.

METHODS

Twenty-six female cancer survivors volunteered to undergo CART for 1 h/day, 3 days/week, for 26 weeks. The Improving Physical Activity After Cancer Treatment (IMPAACT) Program involves supervised group exercise sessions including 20 min of cardiorespiratory training, 25 min of circuit-style resistance-training, and 15 min of abdominal exercises and stretching. BMD at the spine, hip, and whole body was assessed using dual-energy X-ray absorptiometry (DXA) before and after the intervention. Serum markers of bone metabolism (procollagen-type I N-terminal propeptide, P1NP, and C-terminal telopeptides, CTX) were measured at baseline, 13 weeks, and at study completion.

RESULTS

Eighteen participants, with the average age of 63.0 ± 10.3 years, completed the program. Mean duration since completion of cancer treatment was 6.2 ± 10.6 years. Paired t-tests revealed significant improvements in BMD of the spine (0.971 ± 0.218 g/cm2 vs. 0.995 ± 0.218 g/cm2, p = 0.012), hip (0.860 ± 0.184 g/cm2 vs. 0.875 ± 0.191 g/cm2, p = 0.048), and whole body (1.002 ± 0.153 g/cm2 vs. 1.022 ± 0.159 g/cm2, p = 0.002). P1NP declined 22% at 13 weeks and 28% at 26 weeks in comparison to baseline (p < 0.01) while CTX showed a non-significant decrease of 8% and 18% respectively.

CONCLUSIONS

We report significant improvements in BMD at the spine, hip, and whole body for female cancer survivors who completed 26 weeks of CART. This investigation demonstrates the possible effectiveness of CART at improving bone health and reducing risk of osteoporosis for women who have completed cancer treatment. The IMPAACT Program appears to be a safe and feasible way for women to improve health after cancer treatment.

The present work was aimed to evaluate the effect of valproic acid(VPA), simvastatin (SIM)+VPA on Ti(titanium) rods osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. The MC3T3-E1 cells were co-cultured with VPA, SIM + VPA and induced to osteogenesis, and the cell viability, mineralization ability were observed by MTT and ALP staining, Alizarin Red staining and Western blotting. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: group OVX and VPA, SIM + VPA, and all the rats received Ti implants and animals belong to group VPA, SIM + VPA received valproic acid(300 mg/kg/day), valproic acid(300 mg/kg/day) plus SIM (25 mg/kg/day), respectively, treatment until death at 12 weeks. Micro-CT, histology, biomechanical testing, bone metabolism index and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and explore the possible mechanism. Results shown that VPA decreased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed combined application of systemic VPA showed harmful effects than OVX group on bone formation in osteopenic rats, with the worse effects on CTX-1, P1NP and microarchitecture as well as biomechanical parameters by down-regulated gene expression of Runx2, OCN, Smad1, BMP-2 and OPG, while up-regulated RANKL. However, after SIM treatment, the above indicators were significantly improved. The present study suggests that systemic use of VPA may bring harm to the stability of titanium implants in osteoporosis, SIM can reverse the negative effect of VPA on the osseointegration of titanium rods in ovariectomized rats.

Keywords: Osseointegration; Osteoporosis; Simvastatin; Titanium implants; Valproic acid..

Previous work has demonstrated that a single subcutaneous dose of salmon calcitonin leads to a transient decline in circulating levels of FGF23 in patients with X-linked hypophosphatemia (XLH). Since the calcitonin receptor is expressed on osteocytes, this raises the possibility that interdicting signals through that receptor could modulate circulating levels of FGF23 in XLH. In the present study, 21 subjects with XLH were randomly assigned to receive either placebo nasal spray or 400 IU of nasal salmon calcitonin daily for three months. On the first and last day of the study, serial measurements of FGF23, 1,25-dihydroxyvitamin D, and TmP/GFR were made over 27 h. At the beginning of Visit 2 (the first day of month 2) and the beginning of Visit 3 (the first day of month 3), single, first-morning, fasting measurements of these same parameters were made before the next administered dose of study drug. Following the initial or final dose of study drug, there were no differences in area under the curve, based on treatment assignment, for the three principal outcome variables. Similarly, there were no differences in the fasting measures taken at the beginning of Visit 2 or Visit 3 compared to the fasting values on either day 2 of Visit 1 or the fasting values on day 2 of Visit 4. There were also no significant changes over time in serum phosphorus, serum calcium, circulating levels of PTH, CTx, or P1NP. The reasons why nasal salmon calcitonin did not recapitulate the findings with subcutaneously administered drug may relate to the kinetics of drug delivery, the bioavailability of drug or peak drug dose achieved. It remains possible, however, that other means of altering calcitonin receptor signaling may still provide an opportunity for regulating FGF23 production.

OBJECTIVE

Epidemiological studies have associated proton pump inhibitor (PPI) therapy with osteoporotic fractures, but it is not clear if PPIs directly cause osteoporosis. We evaluated the effect of dexlansoprazole and esomeprazole on bone turnover, bone mineral density (BMD), true fractional calcium absorption (TFCA), serum and urine levels of minerals, and levels of parathyroid hormone (PTH) in healthy postmenopausal women.

METHODS

We performed a prospective, multicenter, double-blind study of 115 healthy, postmenopausal women (45 to 75 years of age) from November 4, 2010, through August 7, 2014. Women were randomized to groups given dexlansoprazole (60 mg), esomeprazole (40 mg), or placebo daily for 26 weeks. We measured plasma levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at 0 (baseline), 13, and 26 weeks. Primary outcomes were percent change in P1NP and CTX between weeks 0 and 26. We also measured changes in serum and urine levels of mineral, BMD, PTH (all subjects), and TFCA (n=30).

RESULTS

Between baseline and week 26, there were no significant within-group differences in markers of bone turnover; there was a nonsignificant increase in CTX levels in the dexlansoprazole group (0.12 ng/mL). The esomeprazole and dexlansoprazole groups had significantly increased levels of P1NP (18.2% and 19.2%, respectively) and CTX (22.0% and 27.4%, respectively) at week 26 compared with the placebo group, although these values remained within normal ranges. There were no statistically significant differences between groups in serum or urine levels of minerals, BMD, or PTH at week 26. PPI therapy did not reduce TFCA.

CONCLUSIONS

In a prospective study of postmenopausal women, we found significant increases in markers of bone turnover in women given PPI therapy compared with women given placebo, but levels remained within the normal reference range. We found no significant differences among groups in changes in BMD, PTH, serum or urine levels of minerals, or TFCA. Our findings indicate that 26 weeks of treatment with a PPI has no clinically meaningful effects on bone homeostasis. Clinicaltrials.gov no: NCT01216293.

Liraglutide (Lira), a long-acting glucagon-like peptide 1 receptor (GLP1R) agonist reduces glycosylated hemoglobin in type 2 diabetes mellitus patients. Lira is reported to have bone conserving effect in ovariectomized (OVX) rats. Here, we investigated the osteoanabolic effect of Lira and studied the underlying mechanism. In established osteopenic OVX rats, Lira completely restored bone mass and strength comparable to parathyroid hormone (PTH 1-34). Body mass index normalized bone mineral density of Lira was higher than PTH. The serum levels of osteogenic surrogate pro-collagen type 1 N-terminal pro-peptide (P1NP) and surface referent bone formation parameters were comparable between Lira and PTH. GLP1R, adiponectin receptor 1 (AdipoR1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) levels in bones were downregulated in the OVX group but restored in the Lira group whereas PTH had no effect. In cultured osteoblasts, Lira time-dependently increased GLP1R, AdipoR1 and PGC1α expression. In osteoblasts, Lira rapidly phosphorylated AMP-dependent protein kinase (AMPK), the cellular energy sensor. Exendin 3, a selective GLP1R antagonist and PKA inhibitor H89 blocked Lira-induced increases in osteoblast differentiation, and expression levels of AdipoR1 and PGC1α. Furthermore, H89 inhibited Lira-induced phosphorylation of AMPK and dorsomorphin, an AMPK inhibitor blocked the Lira-induced increases in osteoblast differentiation and AdipoR1 and PGC1α levels. Lira increased mitochondrial number, respiratory proteins and respiration in osteoblasts in vitro and in vivo, and blocking mitochondrial respiration mitigated Lira-induced osteoblast differentiation. Taken together, our data show that Lira has a strong osteoanabolic effect which involves upregulation of mitochondrial function.

Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation, low body weight, and elevated levels of bone marrow adipose tissue (BMAT). BMAT is negatively associated with BMD in AN and more than 85% of women with AN have low bone mass and an increased risk of fracture. Although a majority of women with AN are amenorrheic, which is associated with low BMD, oral contraceptive pills, containing supraphysiologic doses of estrogen, are not effective in increasing bone mass. We performed a 6-month, open-label study of transdermal estradiol (0.045 mg/day) + levonorgestrel (0.015 mg/day) in 11 women with AN (mean age ± SEM: 37.2 ± 2.3 years) to investigate the effects of transdermal, physiologic doses of estrogen on BMD and BMAT in women with AN. We measured change in BMD by DXA, change in BMAT at the spine/hip by ¹H-magnetic resonance spectroscopy, and change in C-terminal collagen cross-links (CTX), P1NP, osteocalcin, IGF-1, and sclerostin after 3 and 6 months of transdermal estrogen. Lumbar spine (2.0% ± 0.8%; p = 0.033) and lateral spine (3.2% ± 1.1%; p = 0.015) BMD increased after 6 months of transdermal estrogen. Lumbar spine BMAT decreased significantly after 3 months (-13.9 ± 6.0%; p = 0.046). Increases in lateral spine BMD were associated with decreases in CTX (p = 0.047). In conclusion, short-term treatment with transdermal, physiologic estrogen increases spine BMD in women with AN. Future studies are needed to assess the long-term efficacy of this treatment. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Women with breast cancer are often prescribed aromatase inhibitors, which can cause rapid loss of bone mass leading to significant potential for morbidity. Vibration training has been shown to be helpful in reducing bone turnover in postmenopausal women without cancer.

To examine the effect of vibration stimulus on markers of bone turnover in breast cancer patients receiving aromatase inhibitors.

Thirty-one breast cancer survivors undergoing treatment with aromatase inhibitors were randomized to vibration stimulus (n = 14) or usual care control (n = 17). Low-frequency and low-magnitude vibration stimulus (27-32 Hz, 0.3 g) was delivered in supervised sessions via standing on a vibration platform for 20 minutes, 3 times per week for 12 weeks. The primary outcome was blood markers of bone resorption (serum N-telopeptide X/creatine) and formation (serum type 1 procollagen N-terminal propeptide; P1NP). Other study outcomes body composition as well as measures of physical functioning. Outcomes were compared between groups using analysis of covariance adjusted for baseline values as well as time on aromatase inhibitors.

On average, participants were 61.5 years old and overweight (ie, body mass index = 28.5 kg/m2). Following vibration training, there was no significant difference between groups for bone resorption (adjusted group difference 0.5, P = .929) or formation (adjusted group difference 5.3, P = .286). There were also no changes in any measure of physical functioning body composition.

Short-term low-magnitude vibration stimulus does not appear to be useful for reducing markers of bone turnover secondary to aromatase inhibitors in breast cancer patients; nor is it useful in improving physical function or symptoms. However, further investigations with larger samples and higher doses of vibration are warranted.

Australian and New Zealand Clinical Trials Registry (ACTRN12611001094965).

Irisin, a myokine produced by skeletal muscle in response to physical exercise, promotes trans-differentiation of white adipose tissue into brown adipose tissue. Recent evidences suggested that irisin also plays an important role in the control of bone metabolism. This study aimed to ascertain the relationship between plasma irisin and bone mineral density (BMD) in Chinese population by adoption of an extreme sampling method. Based on a large and screened Chinese elderly population (N = 6308), two subgroups with extremely high and low hip BMD were selected for discovery (N = 80, high vs. low BMD = 44:36) and validation (N = 60, high vs. low BMD = 30:30), respectively. Plasma irisin, P1NP, and β-CTx were measured using commercially available ELISA kits. Other metabolic parameters (e.g., blood glucose, total cholesterol and triglycerides) were collected. Student's t test and Spearman correlation analyses were conducted in SPSS. Significant difference was discovered for plasma irisin between females and age-matched males (N = 80, male vs. female = 42:38, P = 0.002). The plasma irisin levels were significantly higher in high BMD subjects than in low BMD subjects, which was observed in both discovery (P = 0.012) and validation samples (P = 0.022). However, such observation was limited to males only. Further correlation analyses in males showed that plasma irisin was correlated with BMD (r = 0.362, P = 0.025) and triglyceride (r = - 0.354, P = 0.032). Plasma irisin levels were associated with hip BMD in Chinese elderly men. This study represented the first effort of investigating the relationship of plasma irisin and BMD in elderly population. The positive correlation between plasma irisin and BMD hints intrinsic communication between muscle and bone.

Background: Mineral and bone disorder (MBD) and growth impairment are common complications of pediatric chronic kidney disease (CKD). Chronic inflammation detrimentally affects bone health and statural growth in non-CKD settings, but the impact of inflammation on CKD-MBD and growth in pediatric CKD remains poorly understood. This study assessed associations between inflammatory cytokines with biomarkers of CKD-MBD and statural growth in pediatric CKD.

Methods: This is a cross-sectional study of children with predialysis CKD stages II-V. Cytokines (IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, interferon-γ), bone alkaline phosphatase (BAP), and procollagen type 1 N-terminal propeptide (P1NP) were measured at the same time as standard CKD-MBD biomarkers. Associations between cytokines, CKD-MBD biomarkers, and height z-score were assessed using linear regression analysis.

Results: Among 63 children, 52.4% had stage 3 CKD, 76.2% non-glomerular CKD etiology, and 21% short stature. TNF-α was the only cytokine associated with parathyroid hormone (PTH) independent of glomerular filtration rate. After stratification by low, medium, and high TNF-α tertiles, significant differences in PTH, serum phosphorus, alkaline phosphatase, BAP, P1NP, and height z-score were found. In a multivariate analysis, TNF-α positively associated with phosphorus, PTH, and alkaline phosphatase and inversely associated with height z-score, independent of kidney function, age, sex, and active vitamin D analogue use.

Conclusions: TNF-α is positively associated with biomarkers of CKD-MBD and inversely associated with height z-score, indicating that inflammation likely contributes to the development of CKD-MBD and growth impairment in pediatric CKD. Prospective studies to definitively assess causative effects of inflammation on bone health and growth in children with CKD are warranted.

Keywords: CKD-mineral and bone disorder; Chronic kidney disease; Inflammation; Pediatric; TNF-α.

Osteoporosis is a disease where increased bone weakness increases the risk of a broken bone. Until a broken bone occurs, there are typically no symptoms. Osteoporosis affects more than 75 million people in the United States, Europe and Japan. The diagnosis of osteoporosis is primarily determined by measuring bone mineral density using dual-energy X-ray absorptiometry, but for men under 50 years of age, premenopausal women should not be made on the basis of densitometric criteria alone. Bone biomarkers are a useful tool in detecting osteoporotic. A two-step dual-label time-resolved fluorescence immunoassay (TRFIA) was developed for the simultaneous detection of serum C-terminal telopeptide (β-CTX) and amino-terminal propeptide (P1NP) of Type I procollagen in a single run. The performance of this assay was first evaluated using clinical serum samples, and then compared with commercialized kits. The sensitivity of this assay for β-CTX was 1 ng/L (dynamic range, 0-1000 ng/L), and the sensitivity for P1NP detection was 1 μg/L (dynamic range, 1-1000 μg/L). High correlation coefficients (R) were obtained between the present dual-label TRFIA and commercially available kits (R = 0.99 for β-CTX and P1NP). The present dual-label TRFIA has high sensitivity, specificity and accuracy in clinical sample analysis. It is a good alternative to the single-label diagnostic methods.

Objective: To investigate the mechanism underlying systemic lupus erythematosus (SLE)-related bone loss by evaluating the bone mineral density (BMD) and bone turnover markers (BTMs) in premenopausal patients with new-onset SLE without any treatment.

Methods: BMD and BTMs of 106 premenopausal patients with new-onset SLE and 64 gender-, age- and body mass index (BMI)-matched healthy controls were analyzed. BMD was determined using dual energy X-ray absorptiometry (DXA). Serum BTMs were measured.

Results: Hip and lumbar spine BMD in premenopausal patients with new-onset SLE was significantly decreased compared with healthy controls. Higher rate of osteoporosis was observed in new-onset SLE patients (25% vs. 1%). Moreover, uncoupled bone remodeling evidenced by an increase in bone resorption marker β-CTX (685.9 ± 709.6 pg/mL vs. 395.4 ± 326.0 pg/mL, P < 0.05) and decrease in bone formation markers PINP (37.4 ± 33.0 ng/mL vs. 46.1 ± 20.9 ng/mL, P < 0.05) and OC (11.4 ± 9.8 ng/mL vs. 18.2 ± 8.6 ng/mL, P < 0.05) was observed in premenopausal patients with new-onset SLE compared with healthy controls. Univariate correlation analyses showed negative correlations between OC and SLE Disease Activity Index (SLEDAI), and positive correlations between β-CTX and SLEDAI. SLE patients positive for dsDNA, nucleosome showed lower OC and higher β-CTX.

Conclusion: Premenopausal patients with new-onset SLE had decreased BMD and abnormal bone metabolism with increased β-CTX and decreased OC and P1NP levels, indicating uncoupled bone remodeling in new-onset SLE patients. Disease activity and abnormal immunity, especially the amount of antibodies in SLE patients, were strongly associated with abnormality of bone metabolism.

Keywords: Premenopausal systemic lupus erythematosus; bone formation; bone mineral density; bone resorption.

Real-world data on the new anti-sclerostin antibody drug, romosozumab, remain scarce. There is a strong need to accumulate and analyze data on romosozumab treatment for such conditions as osteoporosis. The purpose of this study was to investigate the therapeutic and adverse effects of romosozumab for osteoporosis treatment in clinical practice. Of the 230 osteoporosis patients prescribed romosozumab from September 2019 in this prospective multicenter cohort study, 204 patients completed 12 months of treatment. The primary outcome of interest was the rate of change in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck as measured by dual-energy X-ray absorptiometry. Secondary outcomes included changes in bone turnover markers and serum-corrected calcium level as well as the incidence of adverse events. At 6 and 12 months of romosozumab treatment, the respective percentage change in BMD from baseline was 7.4% and 12.2% for the lumbar spine, 1.8% and 5.8% for the total hip, and 2.9% and 6.0% for the femoral neck, all of which were significantly higher (P < 0.001) than baseline values. Patients who switched from another osteoporosis regimen exhibited significantly lower lumbar spine BMD gains versus treatment-naïve patients, especially for cases switching from denosumab. P1NP was significantly increased at 6 months (58.9%; P < 0.01), while TRACP-5b was significantly decreased at 6 months (-14.7%; P < 0.001) and 12 months (-18.8%; P < 0.001) versus baseline values. The largest rate of decrease in serum-corrected calcium was 3.7% at 12 months. Sixty-four (27.8%) of 230 patients experienced an adverse event, and 7 (3.0%) new fractures were recorded. In sum, romosozumab treatment for 12 months significantly improved lumbar spine, total hip, and femoral neck BMD according to real-world data.

Keywords: Adverse event; Bone mineral density; Bone turnover marker; Osteoporosis; Romosozumab.

Objectives: A proof of concept cross-sectional study investigating changes in myocardial abnormalities across stages of chronic kidney disease (CKD). Characterizing noninvasive markers of myocardial fibrosis on cardiac magnetic resonance, echocardiography, and correlating with biomarkers of fibrosis, myocardial injury, and functional correlates including exercise tolerance.

Background: CKD is associated with an increased risk of cardiovascular death. Much of the excess mortality is attributed to uremic cardiomyopathy, defined by increased left ventricular hypertrophy, myocardial dysfunction, and fibrosis. The prevalence of these abnormalities across stages of CKD and their impact on cardiovascular performance is unknown.

Methods: A total of 134 nondiabetic, pre-dialysis subjects with CKD stages 2 to 5 without myocardial ischemia underwent cardiac magnetic resonance (1.5-T) including; T₁ mapping (biomarker of diffuse fibrosis), T₂ mapping (edema), late gadolinium enhancement, and assessment of aortic distensibility. Serum biomarkers including collagen turnover (P1NP, P3NP), troponin T, and N-terminal pro-B-type natriuretic peptide were measured. Cardiovascular performance was quantified by bicycle cardiopulmonary exercise testing and echocardiography.

Results: Native myocardial T₁ times increased incrementally from stage 2 to 5 (966 ± 21 ms vs. 994 ± 33 ms; p < 0.001), independent of hypertension and aortic distensibility. Left atrial volume, E/e', N-terminal pro-B-type natriuretic peptide, P1NP, and P3NP increased with CKD stage (p < 0.05), while effort tolerance (% predicted VO₂Peak, %VO₂VT) decreased (p < 0.001). In multivariable linear regression models, estimated glomerular filtration rate was the strongest predictor of native myocardial T₁ time (p < 0.001). Native myocardial T₁ time, left atrial dilatation, and high-sensitivity troponin T were independent predictors of % predicted VO₂Peak (p < 0.001).

Conclusions: Imaging and serum biomarkers of myocardial fibrosis increase with advancing CKD independent of effects of left ventricular afterload and might be a key intermediary in the development of uremic cardiomyopathy. Further studies are needed to determine whether these changes lead to the increased rates of heart failure and death in CKD. (Left Ventricular Fibrosis in Chronic Kidney Disease [FibroCKD]; NCT03176862).

Keywords: T(1) mapping; myocardial fibrosis; uremic cardiomyopathy.

BACKGROUND

Intestinal bacteria influence bone remodeling in rodents, and antibiotic manipulation of the rodent gut microbiota increases bone formation and prevents ovariectomy-induced bone loss. In theory, these effects may be mediated by changes in sex hormone biotransformation in the gut, gut serotonin secretion or nutrition-induced secretion of glucagon-like peptide 2 (GLP-2) and glucose-dependent insulinotropic hormone (GIP). Antibiotics change the human gut microbiota, but the effect of antibiotic treatment on human bone turnover is unknown.

METHODS

We analyzed serum levels of bone turnover markers, serotonin, GLP-2 and sex hormones before, immediately after, and eight, 42 and 180 days after a 4-day per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in twelve healthy adult males. Fasting and meal-stimulated procollagen type I amino-terminal propeptide (P1NP), C-telopeptide of type I collagen (CTX) and osteocalcin levels were measured.

RESULTS

While the antibiotic course reduced the stool abundance and composition of anaerobic bacteria as confirmed by cultivation studies, neither short nor long-term alterations in serum P1NP, CTX and osteocalcin were observed. Furthermore, we did not observe any changes in levels of serum GLP-2, serotonin or sex hormones.

CONCLUSIONS

Eradication of anaerobic bacteria from healthy adult males had no effect on serum bone turnover markers.

Purpose: To investigate the effect of supplementary energy on bone formation and resorption during arduous military training in energy deficit.

Methods: Thirty male soldiers completed an 8-week military combat course (mean ± SD, age 25 ± 3 years, height 1.78 ± 0.05 m, body mass 80.9 ± 7.7 kg). Participants received either the habitual diet (control group, n = 15) or an additional 5.1 MJ·d to eliminate the energy deficit (supplemented group, n = 15). Circulating markers of bone formation and resorption, and reproductive, thyroid, and metabolic status, were measured at baseline, and week 6 and 8 of training.

Results: Bone ALP decreased in controls (-4.4 ± 1.9 μg·L) and increased in the supplemented group (16.0 ± 6.6 μg·L), between baseline and week 8 (P < 0.001). P1NP increased between baseline and week 6 for both groups (5.6 ± 8.1 μg·L, P = 0.005). βCTX decreased between baseline and week 8 for both groups (-0.16 ± 0.20 μg·L, P < 0.001). Prolactin increased from baseline to week 8 for the supplemented group (148 ± 151 IU·L, P = 0.041). The increase in adiponectin from baseline to week 8 was higher in controls (4.3 ± 1.8 mg·L, P < 0.001) than the supplemented group (1.4 ± 1.0 mg·L, P < 0.001). IGF binding protein-3 was lower at week 8 than baseline for controls (-461 ± 395 ng·mL, P < 0.001).

Conclusion: The increase in bone ALP, a marker of bone formation, with supplementation supports a role of energy in osteoblastic activity; the implications for skeletal adaptation and stress fracture risk is unclear. The mechanism is likely through protecting markers of metabolic, but not reproductive or thyroid, function.

OBJECTIVE

This report from the Japan Fracture Observational Study (JFOS) describes the design of the study, baseline characteristics of the patients, and interim results.

METHODS

This is an interim analysis from an ongoing observational study of male and female patients with osteoporosis initiating daily teriparatide treatment observed at baseline, 3, 6 and 12 months. There was no control group. Baseline data were collected on demographic characteristics, medical and osteoporosis history, prior use of medications and health-related quality of life (HRQoL). This interim analysis includes preliminary information concerning incidence of clinical fractures, bone mineral density (BMD), procollagen type 1 aminoterminal propeptide (P1NP), back pain, HRQoL, and adverse events.

RESULTS

Baseline observations were completed for 1810 patients; 90.1% were female. Compared with osteoporotic patients treated with teriparatide in other observational studies, those in JFOS were older but had fewer osteoporosis risk factors. The incidence of clinical fractures was 2.9% at 6 months and 3.7% at 12 months. At 12 months, mean BMD was 8.9% higher at the lumbar spine and 0.8% higher at the total hip compared to baseline. At 6 months, the median serum concentration of P1NP was 187.7% higher than at baseline. At 12 months, back pain scores assessed by visual analog scale (VAS) were lower and HRQoL scores were higher than at baseline. No new safety signals were observed.

CONCLUSIONS

This is the first report from an observational study of daily teriparatide in Japanese osteoporotic patients at high risk of fractures. Patients in JFOS were older but had fewer osteoporosis risk factors than those treated with teriparatide in other observational studies. The interim analysis suggests that the clinical profile of teriparatide in the real world is similar to that observed in clinical trials and observational studies conducted in Europe and the United States.

<AbstractText>Cystic fibrosis(CF) related diabetes(CFRD) and osteoporosis are prevalent in adult patients with CF. We aimed to evaluate if CFRD and markers of glucose metabolism and inflammation are associated with bone turnover in CF.</AbstractText><AbstractText>Cross sectional study at the adult section at the Copenhagen CF Center from January-October 2017. Fasting blood samples, including bone turnover markers(BTMs) and cytokines, Dual-x-ray absorptiometry scan and oral glucose tolerance test were performed. Lung-transplanted participants and patients in antiosteoporotic treatment were excluded from analyses.</AbstractText><AbstractText>102 patients were included of whom 19 had a prior CFRD diagnosis. CFRD patients had lower procollagen type 1 N-terminal propeptide(<em>P1NP</em>) and C-Terminal cross-linked Telopeptide(CTX) levels compared to CF patients without diabetes (median[IQR]) 49.5 μg/l [29.6,57.1] vs 56.9 μg/l [38.2,74.3], p = .03 and 0.2 μg/l [0.1,0.3] vs 0.4 μg/l [0.3,0.6], p < .01, respectively. Fasting plasma glucose(FPG) was negatively associated with the bone formation markers <em>P1NP</em> and osteocalcin and bone resorption marker CTX. In multivariate linear regression FPG remained a significant predictor of <em>P1NP</em> -1.07 [-1.09;-0.01] and CTX -1.13 [-1.21;-1.06]. Bone mineral density Z-score was not different between patients with and without CFRD but FPG was negatively associated with hip and femoral neck Z-score. There was no consistent association between inflammatory cytokines and BTMs.</AbstractText><AbstractText>Bone turnover markers are reduced in CF patients with CFRD and negatively associated with glucose levels. Extra attention towards frequent hyperglycemia in CF patients should be taken when evaluating decreased BMD. Glycemia may be a future target for improving outcome in CFBD.</AbstractText>