Bone Resorption Markers Research Articles

The Effect of Endurance and Endurance-Strength Training on Bone Health and Body Composition in Centrally Obese Women-A Randomised Pilot Trial.

There is no consensus exercise programme to reduce body weight and improve body composition simultaneously preventing bone loss or stimulating osteogenesis. This pilot study compared the effect of endurance and endurance-strength training on body composition and bone metabolism in centrally obese women. Recruited subjects were randomly assigned to three-month endurance (n = 22) or endurance-strength training (n = 22). Body composition, bone mineral density (BMD) and content (BMC) were assessed before and after the intervention and markers of bone formation and resorption were measured. Both training significantly decreased fat mass; however, endurance-strength training had a more favourable effect on lean mass for the gynoid area (p = 0.0211) and legs (p = 0.0381). Endurance training significantly decreased total body BMC and BMD (p = 0.0440 and p = 0.0300), whereas endurance-strength training only reduced BMD (p = 0.0063). Changes in densitometric parameters did not differ between the groups but endurance training increased osteocalcin levels (p = 0.04845), while endurance-strength training increased tartrate-resistant acid phosphatase 5b concentrations (p = 0.00145). In conclusion, both training programmes were effective in the reduction of fat mass simultaneously negatively affecting bone health. However, endurance-strength training seemed to be more effective in increasing lean mass. The study protocol was registered in the ClinicalTrials.gov database under the number NCT03444207, date of registration: 23 February 2018 (retrospective registration).

Influence of Obesity on Bone Turnover Markers and Fracture Risk in Postmenopausal Women.

Background and aims: The relationship between obesity and bone metabolism is controversial. In recent decades, the protective role of obesity in the development of osteoporosis is questioned. The aims of this study are the following: to evaluate the differences in bone turnover markers between postmenopausal women with and without obesity and to compare the risk of fracture at five years between these groups. Methods: An observational longitudinal prospective cohort study of postmenopausal women with obesity (O) (body mass index (BMI) > 30 kg/m2) and non-obesity (NoO) (BMI < 30 kg/m2) is designed. 250 postmenopausal women are included in the study (NoO: 124 (49.6%) and O: 126 (50.4%)). It measures epidemiological variables, dietary variables (calcium intake, vitamin D intake, smoking, alcohol consumption, and physical activity), biochemicals (β-crosslap, type I procollagen amino-terminal peptide (P1NP), 25OH-vitamin D, and parathyroid hormone (PTH)), anthropometric variables, and fracture data five years after the start of the study. The mean age is 56.17 (3.91) years. Women with obesity showed lower levels of vitamin D (O: 17.27 (7.85) ng/mL, NoO: 24.51 (9.60) ng/mL; p < 0.01), and higher levels of PTH (O: 53.24 (38.44–65.96) pg/mL, NoO: 35.24 (25.36–42.40) pg/mL; p < 0.01). Regarding the bone formation marker (P1NP), it was found to be high in women without obesity, O: 45.46 (34.39–55.16) ng/mL, NoO: 56.74 (45.34–70.74) ng/mL; p < 0.01; the bone resorption marker (β-crosslap) was found to be high in women with obesity, being significant in those older than 59 years (O: 0.39 (0.14) ng/mL, NoO 0.24 (0.09) ng/mL; p < 0.05). No differences are observed in the risk of fracture at 5 years based on BMI (OR = 0.90 (95%CI 0.30–2.72); p = 0.85). Conclusions: Postmenopausal women with obesity showed lower levels of bone formation markers; older women with obesity showed higher markers of bone resorption.

Physical Activity in Late Prepuberty and Early Puberty Is Associated With High Bone Formation and Low Bone Resorption.

BackgroundPhysical activity (PA) increases bone mass, especially in late prepuberty and early puberty, but it remains unclear if and how PA affects both bone formation and bone resorption.Materials and MethodsWe included 191 boys and 158 girls aged 7.7 ± 0.6 (mean ± SD) in a population-based PA intervention study. The intervention group (123 boys and 94 girls) received daily physical education (PE) in school (40 min/day; 200 min/week) from study start and during the nine compulsory school years in Sweden. The controls (68 boys and 64 girls) received the national standard of 1–2 classes PE/week (60 min/week). During the intervention, blood samples were collected at ages 9.9 ± 0.6 (n = 172; all in Tanner stages 1–2) and 14.8 ± 0.8 (n = 146; all in Tanner stages 3–5) and after termination of the intervention at age 18.8 ± 0.3 (n = 93; all in Tanner stage 5) and 23.5 ± 0.7 (n = 152). In serum, we analyzed bone formation markers [bone-specific alkaline phosphatase (bALP), osteocalcin (OC), and N-terminal propeptide of collagen type 1 (PINP)] and bone resorption markers [C-terminal telopeptide cross links (CTX) and tartrate-resistant acid phosphatase (TRAcP 5b)]. Linear regression was used to compare age and sex-adjusted mean differences between intervention children and controls in these markers.ResultsTwo years after the intervention was initiated (at Tanner stages 1–2), we found higher serum levels of bALP and OC, and lower serum levels of TRAcP 5b in the intervention compared with the control group. The mean difference (95% CI) was for bALP: 13.7 (2.1, 25.3) μg/L, OC: 9.1 (0.1, 18.1) μg/L, and TRAcP 5b: −2.3 (−3.9, −0.7) U/L. At Tanner stages 3–5 and after the intervention was terminated, bone turnover markers were similar in the intervention and the control children.ConclusionDaily school PA in the late prepubertal and early pubertal periods is associated with higher bone formation and lower bone resorption than school PA 1–2 times/week. In late pubertal and postpubertal periods, bone formation and resorption were similar. Termination of the intervention is not associated with adverse bone turnover, indicating that PA-induced bone mass benefits gained during growth may remain in adulthood.

In patients with anorexia nervosa, myokine levels are altered but are not associated with bone mineral density loss and bone turnover alteration.

Objectives The two-fold aim of this study was: (i) to determine the effects of undernutrition on the myokines in patients with restrictive anorexia nervosa (AN) and (ii) to examine the potential link between myokines and bone parameters.Methods In this study, 42 young women with restrictive AN and 42 age-matched controls (CON) (mean age, 18.5 ± 4.2 years and 18.6 ± 4.2 years, respectively) were enrolled. aBMD and body composition were determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers and myokines (follistatin, myostatin and irisin) were concomitantly evaluated.Results AN patients presented low aBMD at all bone sites. REEm, bone formation markers, myostatin and IGF-1 were significantly lower, whereas the bone resorption marker and follistatin were higher in AN compared with controls. No difference was observed between groups for irisin levels. When the whole population was studied, among myokines, only myostatin was positively correlated with aBMD at all bone sites. However, multiple regression analyses showed that in the AN group, the independent variables for aBMD were principally amenorrhoea duration, lean tissue mass (LTM) and procollagen type I N-terminal propeptide (PINP). For CON, the independent variables for aBMD were principally LTM, age and PINP. Whatever the group analysed, none of the myokines appeared as explicative independent variables of aBMD.Conclusion This study demonstrated that despite the altered myokine levels in patients with AN, their direct effect on aBMD loss and bone turnover alteration seems limited in comparison with other well-known disease-related factors such as oestrogen deprivation.

Isoliquiritigenin Decreases Bone Resorption and Osteoclast Differentiation.

A dose-ranging study is performed using young estrogen-depleted rats to determine whether dietary isoliquiritigenin (ILQ) alters bone metabolism and if the effects are associated with estrogen receptor signaling. Six-week-old rats (ovariectomized at 4 weeks of age) are fed diets containing 0, 100, 250, or 750ppm ILQ (n = 5/treatment) for 7 days. Gene expression in femur and uterus, blood markers of bone turnover, body composition, and uterine weight and epithelial cell height are determined. Because ILQ lowers bone resorption, the effect of ILQ on in vitro differentiation of osteoclasts from bone marrow of mice is assessed. Treatment resulted in a dose-dependent increases in serum ILQ but no changes in serum osteocalcin, a marker of global bone formation. Contrastingly, ILQ administration results in reduced serum CTX-1, a marker of global bone resorption, and reduces tartrate resistant acid phosphatase expression in osteoclast culture. ILQ treatment and endogenous estrogen production had limited overlap on gene expression in femur and uterus. However, uterine epithelial cell hyperplasia is observed in two of five animals treated with 750ppm. In conclusion, dietary ILQ reduces bone resorption in vivo and osteoclast differentiation in vitro, by mechanisms likely differing from actions of ovarian hormones.

Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures

AimsBone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.MethodsA total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months.ResultsCTX and P1NP concentrations peaked at six weeks in all groups. Elevated six-week CTX and P1NP were associated with radiological healing at 12 weeks post-injury (odds ratio (OR) 10.5; 95% confidence interval 2.71 to 53.5, p = 0.002). We found no association between CTX or P1NP and functional healing. Baseline serum 25(OH)D showed a weak inverse relationship with P1NP (p = 0.036) and CTX (p = 0.221) at 12 weeks, but we observed no association between vitamin D supplementation and either BTM.ConclusionGiven the association between six-week BTM concentrations and three-month radiological fracture healing, CTX and P1NP appear to be potential surrogate markers of fracture healing.Cite this article: Bone Joint Res 2022;11(4):239–250.

The effect of maltobionic acid on bone metabolism markers in healthy Japanese postmenopausal women: A randomized double-blind placebo-controlled crossover study.

Osteoporosis is characterized by compromised bone strengthpredisposing to an increased risk of fracture and is a disease with a high incidence in postmenopausal women. Frequent estrogen deficiency, particularly in postmenopausal women, induces osteoclast activation and is a major contributor to reduced bone mineral density. Maltobionic acid (MB) reportedly promotes mineral resorption and maintains bone mineral density in human clinical trials, although no studies have confirmed that MB improves bone metabolism in humans. Therefore, this study aimed to investigate the effects of MB administration on bone‐resorption markers in healthy Japanese postmenopausal women. This was a randomized, double‐blind, placebo‐controlled, crossover trial. Twenty‐six healthy adult Japanese women who realized that they had passed through more than 1 year of natural menopause and were aged 40–69 years were categorized into three groups. The experimental groups were allowed to consume maltobionic acid syrup 4 g (MB syrup 4 g group), maltobionic acid syrup 2 g plus maltose syrup 2 g (MB syrup 2 g group), and maltose syrup 4 g (placebo group) for 4 weeks. All 26 participants completed the intervention. Continuous ingestion of MB syrup 2 g or 4 g for 4 weeks significantly reduced the levels of bone‐resorption markers deoxypyridinoline (DPD) and urinary N‐telopeptide (u‐NTx), and significantly increased the bone formation marker osteocalcin (OC) compared with the placebo group. Maltobionic acid (MB) intake may improve bone metabolism and reduce bone health problems, including osteoporosis, in postmenopausal, adult Japanese women. (UMIN‐CTR ID: UMIN000038627).

Effects of prior osteoporosis treatment on the treatment response of romosozumab followed by denosumab in patients with postmenopausal osteoporosis.

To investigate the effects of prior osteoporosis treatment on the response to treatment with romosozumab (ROMO) followed by denosumab (DMAb) in patients with postmenopausal osteoporosis. In this prospective, observational, multicenter study, treatment-naïve patients (Naïve; n = 55) or patients previously treated with bisphosphonates (BP; n = 37), DMAb (DMAb; n = 45) or teriparatide (TPTD; n = 17) (mean age, 74.6years; T-scores of the lumbar spine [LS] - 3.2 and total hip [TH] - 2.6) were switched to ROMO for 12months, followed by DMAb for 12months. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 24months. A BMD increase was observed at 12 and 24months in the following patients: Naïve (18.2% and 22.0%), BP (10.2% and 12.1%), DMAb (6.6% and 9.7%), and TPTD (10.8% and 15.0%) (P < 0.001 between the groups at both 12 and 24months) in LS and Naïve (5.5% and 8.3%), BP (2.9% and 4.1%), DMAb (0.6% and 2.2%), and TPTD (4.3% and 5.4%) (P < 0.01 between the groups at 12months and P < 0.001 at 24months) in TH, respectively. The BMD increase in LS from 12 to 24months was negatively associated with the levels of bone resorption marker at 24months. Incidences of major fragility fractures for the respective groups were as follows: Naïve (5.5%), BP (16.2%), DMAb (11.1%), and TPTD (5.9%). Previous treatment affected the BMD increase of following treatment with ROMO, although it did not affect that of following treatment with DMAb after ROMO.

Эффективность применения золедроновой кислоты при лечении остеопороза у больных раком предстательной железы, получающих терапию агонистами ГнРГ

Introduction. It has been established that prolonged androgen-deprivation therapy (ADT) of prostate cancer leads to a decrease in bone mineral density (BMD) and increases the risk of fractures, which is an important medical and social problem. Zoledronic acid (ZA) is most often used for the prevention of osteoporosis against the background of ADT. The purpose of the study is to determine the efficacy and safety of ZA for the treatment and prevention of osteopo-rosis in non-metastatic prostate cancer against the background of ADT therapy with GnRH agonists. Materials and methods. The study included 45 men aged 54-81 years with morphologically verified prostate cancer (stages T2-4 N0-1 M0) who underwent surgical castration at least 6 months before inclusion or continuously received therapy with GnRH agonists. The blood level of CTX-1 was used as the main marker of bone resorption. To assess the BMD, the screening method of dual-band X-ray densitometry of the calcaneus with laser determination of the examination area – DXL using the CALSCAN apparatus and the DXL Calscan Workstation software was used. Patients were randomized into groups of 15 people each: Group 1 – received intravenous infusion of ZA at a dose of 4 mg at the beginning of the study and after 3 months of treatment; Group 2 received ZA at 2 mg in the same mode; Group 3 – control. For antire-sorptive therapy (ART), the drug Resorba (JSC «Pharm-Synthesis», Russia) was used. The duration of follow-up was 6 months. Results. In 13 out of 15 patients of Group 1, 3 months after the first administration of ZA, a decrease in the level of CTX-1 by 50% or more was observed, and after 6 months all 15 patients (100%) reached the age norm («complete answer»). Group 2 patients also responded to ART and by the 6th month 13 out of 15 (87%) had achieved a «complete response». In the control group by the 6th month the decrease in CTX-1 was not observed in any of the patients. Initially, the values of BMD in the studied groups did not differ. By the 3rd month of the study, the BMD index significantly increased only in Group 1. In Group 2 this indicator significantly increased by the 6th month of treatment. At the same time, in Group 1 after 6 months the BMD index reached higher values than in Group 2: an increase of 27% and 13%, respectively. In the control group, by the 6th month of observation, a significant decrease in BMD by 12% was noted. In Group 1, the number of patients with osteoporosis decreased to 6% and with a normal level of BMD – reached to 40%. Conclusion. High efficacy and sufficient safety of ZA in doses of 4 mg and 2 mg i/v one time in 3 months for anti-resorptive therapy in patients receiving long-term hormonal therapy with GnRH agonists has been demonstrated.

EFFECTS OF PROBIOTICS CONSUMPTION AND RESISTANCE EXERCISE ON BONE METABOLISM MARKERS IN PHYSICALLY INACTIVE YOUNG MALES

This study aims to investigate the effects of probiotics supplementation and resistance exercise on bone metabolism markers and parathyroid hormones in physically inactive young men. Fourty-one healthy participants completed the study. They were randomized into sedentary placebo control (C: n=10), probiotics (P: n=10), resistance exercise with placebo (E: n=12), and probiotics consumption with resistance exercise (PE: n=9) groups. Participants in the P and PE consumed multi-strain probiotics containing 3x1010 CFU of L. acidophilus BCMC® 12130, L. casei BCMC® 12313, L. lactis BCMC® 12451, B. bifidum BCMC® 02290, B. infantis BCMC® 02129 and B. longum BCMC® 02120 twice daily for 12 weeks. Participants in the E and PbE performed circuit training comprised of 10 resistance exercises 3 times/week. Body height and weight, blood pressure, resting heart rate and blood samples were collected at pre and post-tests. Blood samples were analysed for the concentration of bone formation markers [alkaline phosphatase (ALP) and osteocalcin (OC)], bone resorption marker [cross-linked carboxyterminal telopeptide of type 1 collagen (1CTP)] and parathyroid hormones (PTH). There were no significant differences (p&gt;0.05) in all measured parameters between groups and within each group (p&gt;0.05). Nevertheless, ALP and OC concentration exhibited increasing trends in PE group. There was a decreasing trend in PTH concentration in P and PE groups. As a conclusion, probiotics consumption with resistance exercise resulted in increased trends of bone formation markers and a small reduction in the bone resorption marker implying that this combination may elicit beneficial effects in improving bone formation in young physically inactive males.

Does the Rhythmic Gymnastics Training Affect Serum Bone Resorption and Oxidative Stress Markers?

Introduction: Rhythmic gymnastics training (RGT) includes intensive anaerobic loads, therefore it may cause oxidative stress (OS) and then consequently might negatively affect bone metabolism and nitric oxide (NO) levels which is related to vasodilation and bone metabolism. This study investigated the effects of chronic RGT on the markers of serum bone metabolism, OS, and NO levels together, which is yet unclear. Materials and methods: 16 girls rhythmic gymnasts (athletic group, AG; 10.33 ± 1.79, years) and 13 controls (CG; 9.23 ± 1.00 years) participated in this study. Type 1 collagen carboxy-terminal cross-linked telopeptide (ICTP) as bone resorption marker (using ELISA method), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), and growth hormone (GH) as bone metabolism markers; Total oxidant /antioxidant status ratio (TOS/TAS) as OS index (OSI) and NO levels; Troponin-I (Tn-I), and CK-MB levels, alanine aminotransferase (ALT), aspartate amino transferase (AST), creatine kinase (CK) as muscle injury markers; Some hematological parameters including hemogram were measured by standard methods. Results: Serum ICTP1 (p= 0.01) and GH (47.4 %) levels of AG were significantly higher than CG, whereas Ca level (p= 0.04) and body fat rate values was lower (p= 0.00). There is no significant difference between the groups for other parameters. Conclusions: The results suggest that RGT training did not significantly affect OS and NO levels that can cause anemia. But besides the increased GH levels, bone development can be affected negatively in child gymnasts due to the increased ICTP and decreased Ca levels. Thus, a calcium-rich diet and regular observation of bone metabolism markers are recommended. Keywords: Rhythmic gymnastics, Oxidative stress, Bone destruction, Nitric oxide.

Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib, Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment.

The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice.

Diagnostic yield of bone fragility gene panel sequencing in children and young adults referred for idiopathic primary osteoporosis at a single regional reference centre

AimTo describe the presenting features, bone characteristics and molecular genetics in a large monocentric cohort of children and young adults with idiopathic primary osteoporosis. MethodsSixty-six patients (19 children, 47 adults; 28 males, 38 females; age at referral: 3.8 to 65 years) diagnosed with primary osteoporosis were included in this study; patients with features of osteogenesis imperfecta or other known syndromes associated with osteoporosis were excluded. For each patient, the following data were collected by retrospective chart review: family and personal history of fracture and osteoporosis, mineral homeostasis parameters and markers of bone formation and resorption, bone mineral density (BMD) of the lumbar spine (LS-BMD), the total body less head (TB-BMD), and total hip levels (TH-BMD) measured by DXA. As part of the initial assessment process, a bone fragility gene panel sequencing was performed in all of these patients. ResultsThere was a higher predominance of males in the children (63%) and of females in the adults (66%) (p = 0.030). Compared to the adults, the children had a significantly lower frequency of vertebral fractures (26 vs 57%, p = 0.022) and a higher frequency of peripheral fractures (84 vs 53%; p = 0.019). Bone fragility gene panel sequencing allowed the identification of the heterozygous pathogenic variant in 27% of patients (most frequently in LRP5, WNT1 and COL1A1 or 2 genes) and the heterozygous p.(Val667Met) LRP5 variant in 11% of them. The frequency of pathogenic variants tended to be higher in the children compared to the adults without reaching statistical significance (42 vs 19%; p = 0.053). The frequency of the p.(Val667Met) LRP5 variant was similar in children and adults. No significant differences were found regarding the various clinical, biological and radiological characteristics of the patients according to genotype. ConclusionIn this study, we reported the presenting features and bone characteristics in a large cohort of children and young adults with idiopathic primary osteoporosis. Bone fragility gene panel sequencing allowed the identification of genetic variants in a significant proportion of these patients. Molecular diagnosis in these patients is important in order to be able to offer genetic counselling and organise patient management.

Effects of empagliflozin on markers of calcium and phosphate homeostasis in patients with type 2 diabetes – Data from a randomized, placebo-controlled study

Background and aimSodium-glucose cotransporter-2 (SGLT2) inhibitors, glucose-lowering drugs that increase urinary glucose excretion have been shown to reduce CV events in patients with type 2 diabetes (T2D). Furthermore, several studies have demonstrated that treatment with SGLT2 inhibitors affect calcium and phosphate homeostasis, but the effect of empagliflozin on these biomarkers is hitherto not investigated in detail. Therefore, this analysis of the EMPA hemodynamics study examined effects of empagliflozin on calcium and phosphate homeostasis. MethodsIn this placebo-controlled, randomized, double-blind study patients with T2D were randomized to empagliflozin 10 mg (n = 20) or placebo (n = 22). Biomarkers of calcium and phosphate homeostasis were assessed before, and after 3 days and 3 months of treatment. ResultsAfter 3 days of treatment empagliflozin significantly increased serum levels of phosphate (baseline: 1.10 ± 0.21 mmol/L; day 3: 1.25 ± 0.23 mmol/L; p = 0.036), parathyroid hormone (PTH) (baseline: 57.40 ± 30.49 pg/mL; day 3: 70.23 ± 39.25 pg/mL; p = 0.025), fibroblast growth factor 23 (FGF23) (baseline: 77.92 ± 24.31 pg/mL; day 3: 109.18 ± 58.20 pg/mL; p = 0.001) and decreased 1,25-dihydroxyvitamin D (baseline: 35.01 ± 14.01 ng/L; day 3: 22.09 ± 10.02 mg/L; p < 0.001), while no difference of these parameters was recorded after 3 months of treatment. Empagliflozin had no significant effects on serum calcium and markers of bone resorption (collagen type 1 β-carboxy-telopeptide = β-CTX) or formation (osteocalcin) after 3 days and 3 months of treatment. ConclusionsEmpagliflozin treatment of patients with T2D transiently increases serum phosphate, PTH and FGF23, and decreases 1,25-dihydroxyvitamin D. This might reflect a temporal increase of sodium driven phosphate reabsorption in the proximal tubule of the kidney caused by increased sodium availability in response to SGLT2 inhibition.

Bone Turnover Markers After Six Nights of Insufficient Sleep and Subsequent Recovery Sleep in Healthy Men.

The goal of this study was to determine the bone turnover marker (BTM) response to insufficient and subsequent recovery sleep, independent of changes in posture, body weight, and physical activity. Healthy men (N = 12) who habitually slept 7-9h/night were admitted to an inpatient sleep laboratory for a baseline 8h/night sleep opportunity followed by six nights of insufficient sleep (5h/night). Diet, physical activity, and posture were controlled. Serum markers of bone formation (osteocalcin, PINP) and resorption (β-CTX) were obtained over 24 h at baseline and on the last night of sleep restriction, and on fasted samples obtained daily while inpatient and five times after discharge over 3weeks. Maximum likelihood estimates in a repeated measures model were used to assess the effect of insufficient and subsequent recovery sleep on BTM levels. There was no statistically or clinically significant change in PINP (p = 0.53), osteocalcin (p = 0.66), or β-CTX (p = 0.10) in response to six nights of insufficient sleep. There were no significant changes in BTMs from the inpatient stay through 3weeks of recovery sleep (all p [Formula: see text] 0.63). On average, body weight was stable during the inpatient stay (Δweight = - 0.55 ± 0.91kg, p = 0.06). No significant changes in serum BTMs were observed after six nights of insufficient or subsequent recovery sleep in young healthy men. Changes in weight and physical activity may be required to observe significant BTM change in response to sleep and circadian disruptions. Clinical Trials Registration Registered at ClinicalTrials.gov (NCT03733483) on November 7, 2018.

Changes in Bone Mineral Density and Serum Lipids across the First Postpartum Year: Effect of Aerobic Fitness and Physical Activity.

This study evaluated the changes in bone mineral density (BMD) and serum lipids across the first postpartum year in lactating women compared to never-pregnant controls, and the influence of physical activity (PA). The study also explored whether N-telopeptides, pyridinoline, and deoxypyridinoline in urine serve as biomarkers of bone resorption. A cohort of 18 initially lactating postpartum women and 16 never pregnant controls were studied. BMD (dual energy X-ray absorptiometry), serum lipid profiles, and PA (Baecke PA Questionnaire) were assessed at baseline (4–6 weeks postpartum), 6 months, and 12 months. Postpartum women lost 5.2 ± 1.4 kg body weight and BMD decreased by 1.4% and 3.1% in the total body and dual-femur, respectively. Furthermore, BMDdid not show signs of rebound. Lipid profiles improved, with increases in high-density lipoprotein-cholesterol (HDL-C) and decreases in low-density lipoprotein cholesterol (LDL-C) and the cholesterol/HDL-C ratio at 12 months (vs. baseline). These changes were not influenced by lactation, but the fall the Cholesterol/HDL-C ratio was influenced by leisure-time (p = 0.051, time X group) and sport (p = 0.028, time effect) PA. The decrease in BMD from baseline to 12 months in total body and dual femur, however, was greater in those who continued to breastfeed for a full year compared to those who stopped at close to 6 months. Urinary markers of bone resorption, measured in a subset of participants, reflect BMD loss, particularly in the dual-femur, and may reflect changes bone resorption before observed changes in BMD. Results provide support that habitual postpartum PA may favorably influence changes in serum lipids but not necessarily BMD. The benefit of exercise and use of urinary biomarkers of bone deserves further exploration.

Novel diagnostic model for bone metastases in renal cell carcinoma patients based on bone scintigraphy analyzed by computer-aided diagnosis software and bone turnover markers

BackgroundComputer-assisted diagnosis (CAD) systems for bone scans have been introduced as clinical quality assurance tools, but few studies have reported on its utility for renal cell carcinoma (RCC) patients. The aim of this study was to assess the diagnostic validity of the CAD system for bone scans and to construct a novel diagnostic system for bone metastases in RCC patients.MethodsWe evaluated bone scan images of 300 RCC patients. Artificial neural network (ANN) values, which represent the probability of abnormality, were calculated by BONENAVI, the CAD software for bone scans. By analyzing ANN values, we assessed the diagnostic validity of BONENAVI. Next, we selected 108 patients who underwent measurements of bone turnover markers and assessed the combined diagnostic validity of BONENAVI and bone turnover markers.ResultsForty-three out of 300 RCC patients had bone metastases. The AUC of ANN values was 0.764 and the optimum sensitivity and specificity were 83.7 and 62.7%. By logistic analysis of 108 cases, we found that ICTP, a bone resorption marker, could be a diagnostic marker. The AUC of ICTP was 0.776 and the optimum sensitivity and specificity were 57.1 and 86.8%. Subsequently, we developed a novel diagnostic model based on ANN values and ICTP. Using this model, the AUC was 0.849 and the optimum sensitivity and specificity were 76.2 and 80.7%.ConclusionBy combining the high sensitivity provided by BONENAVI and the high specificity provided by ICTP, we constructed a novel, high-accuracy diagnostic model for bone metastases in RCC patients.

Once daily calcium (1000mg) and vitamin D (1000IU) supplementation during military training prevents increases in biochemical markers of bone resorption but does not affect tibial microarchitecture in Army recruits.

Basic combat training (BCT) is a period of novel physical training including load carriage resulting in higher risk of stress fracture compared to any other time during military service. Prior trials reported a 20% reduction in stress fracture incidence with Ca and vitamin D (Ca+D) supplementation (2000mg Ca, 800IU vitamin D), and greater increases in tibia vBMD during BCT compared to placebo. The primary objective of this randomized, double-blind, placebo-controlled trial was to determine the efficacy of a lower dose of Ca (1000mg/d Ca, 1000IU vit D) on PTH, bone biomarkers and tibial microarchitecture during BCT. One hundred volunteers (50 males, 50 females; mean age 21.8±3.5 y) were block randomized by race and sex to receive a daily Ca+D fortified food bar or placebo. Anthropometrics, dietary intake, fasted blood draws and high resolution pQCT scans of the distal and mid-shaft tibia were obtained at the start of BCT and 8 wks later at the conclusion of training. As compliance was 98% in both treatment groups, an intent-to-treat analysis was used. At the distal tibia, total vBMD, Tb.vBMD, Tb.N, Th.Th and Tb.BV/TV increased (+1.07 to 2.12% for all, p<0.05) and Tb.Sp decreased (0.96 to 1.09%, p<0.05) in both treatment groups. At the mid-shaft, Ct.Pm increased (+0.18 to 0.21%, p=0.01) and Ct.vBMD decreased (-0.48 to -0.77%, p<0.001) in both groups. Ca+D prevented increases in CTX and TRAP, which were observed in the placebo group (group-by-time, p<0.05). Mean circulating 25OHD, BAP, P1NP and iCa increased and PTH decreased in both treatment groups (p<0.05). These results, in agreement with other studies, suggest that bone microarchitectural changes indicative of bone formation occur during BCT. While Ca+D supplementation at lower doses than those tested in previous studies prevented increases in biochemical markers of bone resorption in this study, there were no significant changes in bone tissue after 8 wks of Army BCT.

Characterization, pharmacokinetics, and pharmacodynamics of anti-Siglec-15 antibody and its potency for treating osteoporosis and as follow-up treatment after parathyroid hormone use.

Recent studies have established the idea that Siglec-15 is involved in osteoclast differentiation and/or function, and it is anticipated that therapies suppressing Siglec-15 function can be used to treat bone diseases such as osteoporosis. We have produced rat monoclonal anti-Siglec-15 antibody (32A1) and successively generated humanized monoclonal anti-Siglec-15 antibody (DS-1501a) from 32A1. Studies on the biological properties of DS-1501a showed its specific binding affinity to Siglec-15 and strong activity to inhibit osteoclastogenesis. 32A1 inhibited multinucleation of osteoclasts and bone resorption (pit formation) in cultured mouse bone marrow cells. 32A1 also inhibited pit formation in cultured human osteoclast precursor cells. Maximum serum concentration and serum exposure of DS-1501a in rats were increased in a dose-dependent manner after single subcutaneous or intravenous administration. Furthermore, single administration of DS-1501a significantly suppressed bone resorption markers with minimal effects on bone formation markers and suppressed the decrease in bone mineral density (BMD) of the lumbar vertebrae in ovariectomized (OVX) rats. In histological analysis, the osteoclasts distant from the chondro-osseous junction of the tibia tended to be flattened, shrunken, and functionally impaired in 32A1-treated rats, while alkaline phosphatase-positive osteoblasts were observed throughout the metaphyseal trabeculae. In addition, we compared the efficacy of 32A1 with that of alendronate (ALN) as follow-up medicine after treatment with parathyroid hormone (PTH) using mature established osteoporosis rats. The beneficial effect of PTH on bone turnover disappeared 8weeks after discontinuing the treatment. The administration of 32A1 once every 4weeks for 8weeks suppressed bone resorption and bone formation when the treatment was switched from PTH to 32A1, leading to the maintenance of BMD and bone strength. Unlike with ALN, the onset of suppression of bone resorption with 32A1 was rapid, while the suppression of bone formation was mild. The improvement of bone mass, beneficial bone turnover balance, and suppression of osteoclast differentiation/multinucleation achieved by 32A1 were supported by histomorphometry. Notably, the effects of 32A1 on bone strength, not only structural (extrinsic) but also material (intrinsic) properties, were significantly greater than those of ALN. Since the effect of 32A1 on BMD was moderate, its effect on bone strength could not be fully explained by the increase in BMD. The beneficial balance of bone turnover caused by 32A1 might, at least in part, be responsible for the improvement in bone quality. This is the first report describing the effects of anti-Siglec-15 antibody in OVX rats; the findings suggest that this antibody could be an excellent candidate for treating osteoporosis, especially in continuation therapy after PTH treatment, due to its rapid action and unprecedented beneficial effects on bone quality.

Does the Rhythmic Gymnastics Training Affect Serum Bone Resorption and Oxidative Stress Markers?

Introduction: Rhythmic gymnastics training (RGT) includes intensive anaerobic loads, therefore it may cause oxidative stress (OS) and then consequently might negatively affect bone metabolism and nitric oxide (NO) levels which is related to vasodilation and bone metabolism. This study investigated the effects of chronic RGT on the markers of serum bone metabolism, OS, and NO levels together, which is yet unclear. Materials and methods: 16 girls rhythmic gymnasts (athletic group, AG; 10.33 ± 1.79, years) and 13 controls (CG; 9.23 ± 1.00 years) participated in this study. Type 1 collagen carboxy-terminal cross-linked telopeptide (ICTP) as bone resorption marker (using ELISA method), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), and growth hormone (GH) as bone metabolism markers; Total oxidant /antioxidant status ratio (TOS/TAS) as OS index (OSI) and NO levels; Troponin-I (Tn-I), and CK-MB levels, alanine aminotransferase (ALT), aspartate amino transferase (AST), creatine kinase (CK) as muscle injury markers; Some hematological parameters including hemogram were measured by standard methods. Results: Serum ICTP1 (p= 0.01) and GH (47.4 %) levels of AG were significantly higher than CG, whereas Ca level (p= 0.04) and body fat rate values was lower (p= 0.00). There is no significant difference between the groups for other parameters. Conclusions: The results suggest that RGT training did not significantly affect OS and NO levels that can cause anemia. But besides the increased GH levels, bone development can be affected negatively in child gymnasts due to the increased ICTP and decreased Ca levels. Thus, a calcium-rich diet and regular observation of bone metabolism markers are recommended. Keywords: Rhythmic gymnastics, Oxidative stress, Bone destruction, Nitric oxide.