Serum Bone Markers Research Articles

Compromised Volumetric Bone Density and Microarchitecture in Men With Congenital Hypogonadotropic Hypogonadism.

Men with congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) have both low circulating testosterone and estradiol levels. Whether bone structure is affected remains unknown. To characterize bone geometry, volumetric density and microarchitecture in CHH/KS. This cross-sectional study, conducted at a single French tertiary academic medical center, included 51 genotyped CHH/KS patients and 40 healthy volunteers. Among CHH/KS men, 98% had received testosterone and/or combined gonadotropins. High-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy x-ray absorptiometry (DXA), and measurement of serum bone markers were used to determine volumetric bone mineral density (vBMD) and cortical and trabecular microarchitecture. CHH and controls did not differ for age, body mass index, and levels of vitamin D and PTH. Despite long-term hormonal treatment (10.8 ± 6.8 years), DXA showed lower areal bone mineral density (aBMD) in CHH/KS at lumbar spine, total hip, femoral neck, and distal radius. Consistent with persistently higher serum bone markers, HR-pQCT revealed lower cortical and trabecular vBMD as well as cortical thickness at the tibia and the radius. CHH/KS men had altered trabecular microarchitecture with a predominant decrease of trabecular thickness. Moreover, CHH/KS men exhibited lower cortical bone area, whereas total and trabecular areas were higher only at the tibia. Earlier treatment onset (before age 19 years) conferred a significant advantage for trabecular bone volume/tissue volume and trabecular vBMD at the tibia. Both vBMD and bone microarchitecture remain impaired in CHH/KS men despite long-term hormonal treatment. Treatment initiation during adolescence is associated with enhanced trabecular outcomes, highlighting the importance of early diagnosis.

RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer

PurposeThis is the first prospective trial evaluating the efficacy of alpha emitter Radium-223 in patients with bone metastases from radioactive iodine (RAI) refractory (RAIR) differentiated thyroid cancer.MethodsRADTHYR is a multicenter, single-arm prospective Simon two-stage phase II trial (NCT02390934). The primary objective was to establish the efficacy of three administrations of 55 kBq/kg of Radium-223 by 18F-FDG PET/CT according to PERCIST criteria. Secondary objectives were to establish the efficacy of six administrations of Radium-223 by 18F-FDG PET/CT, 99mTc-HMDP bone scan and 18FNa PET/CT, clinical benefits, changes in serum bone markers, thyroglobulin levels, and safety.ResultsTen patients were enrolled between July 2015 and December 2017 (4 M; median age 74 years). Prior to Radium-223 administration, patients received a median RAI cumulative activity of 15 GBq (7.4–35.6), external radiation therapy (n = 9), bone surgery (n = 8), cimentoplasty (n = 5), and cryoablation (n = 2). 18F-FDG PET/CT showed stable disease (SD) in 4/10 and progressive disease (PD) in 6/10 cases after three administrations and SD in 4/10, PD in 5/10 cases, and 1/10 non-evaluable (NE) case after six administrations. After six injections, 99mTc-HMDP bone scan showed SD in 9 cases and was NE in 1 case; 18FNa PET/CT showed SD in 8 cases, partial response (PR) in 1 case, and was NE in 1 case. No significant clinical benefits were reported during the study. A skeletal event occurred in 6 patients (median time without skeletal event of 12.1 months). Seventy-seven adverse events were reported during treatment (7 of grade 3–4). Three patients developed an acute myeloid, a promyelocytic, and a chronic myeloid leukemia after the last Radium-223 administration considered as drug-related.ConclusionThe trial was stopped after interim analysis for lack of response of bone metastases from RAIR thyroid cancer to Radium-223. Severe hematological toxicity was observed in patients heavily pretreated with RAI and external radiation.Trial registration numberNCT02390934. Registration date 18.03.2015.

Circulating MiR-21 expression is upregulated after 30days of head-down tilt bed rest.

Circulating miRNAs (c-miRNAs) have potential as biomarkers of cellular activity, and they may play a role in cell-to-cell communication. The purpose of this study was to examine c-miRNA and bone marker responses to a 30-day six-degree head-down bed rest protocol at an ambient 0.5% CO2. Eleven participants (6 males/5 females, 25-50years) had fasting blood draws taken 3days before and immediately after completing the 30-day bed rest protocol at the Institute for Aerospace Medicine in Germany. Serum relative expression of miRNAs associated with bone function (miR-21-5p, -100-5p, -125b-5p, -126-3p) were analyzed using qPCR, and serum bone markers were quantitated using ELISA. Serum bone markers, sclerostin, and calcium significantly increased (p ≤ 0.036), and total hip aBMD significantly decreased (p = 0.003) post bed rest. Serum miR-21-5p relative expression was significantly upregulated (p = 0.018) post bed rest. Fold changes in miR-126-3p (r = 0.82, p = 0.002) and miR-21-5p (r = 0.62, p = 0.042) were positively correlated with absolute change in serum calcium. There were no sex differences in miRNA responses; women had greater percent increases in TRAP5b (37.3% vs. 16.9% p = 0.021) and greater percent decreases in total hip aBMD (- 2.15% vs. - 0.69%, p = 0.034) than men. c-miR-21-5p has potential as a biomarker of bone resorption and bone loss in an unloading condition. The upregulation of miR-21-5p may reflect an increase in osteoclast activity after bed rest, which is corroborated by the increase in TRAP5b.

Efficacy and Tolerability of Daratumumab with Ixazomib and Dexamethasone in Patients with One Prior Lenalidomide-Based Regimen: Preliminary Results of the Phase 2 Daria Study

Efficacy and Tolerability of Daratumumab with Ixazomib and Dexamethasone in Patients with One Prior Lenalidomide-Based Regimen: Preliminary Results of the Phase 2 Daria Study

Bone Development in Transgender Adolescents Treated With GnRH Analogues and Subsequent Gender-Affirming Hormones.

ContextHormonal interventions in adolescents with gender dysphoria may have adverse effects, such as reduced bone mineral accrual.ObjectiveTo describe bone mass development in adolescents with gender dysphoria treated with gonadotropin-releasing hormone analogues (GnRHa), subsequently combined with gender-affirming hormones.DesignObservational prospective study.Subjects51 transgirls and 70 transboys receiving GnRHa and 36 transgirls and 42 transboys receiving GnRHa and gender-affirming hormones, subdivided into early- and late-pubertal groups.Main Outcome MeasuresBone mineral apparent density (BMAD), age- and sex-specific BMAD z-scores, and serum bone markers.ResultsAt the start of GnRHa treatment, mean areal bone mineral density (aBMD) and BMAD values were within the normal range in all groups. In transgirls, the mean z-scores were well below the population mean. During 2 years of GnRHa treatment, BMAD stabilized or showed a small decrease, whereas z-scores decreased in all groups. During 3 years of combined administration of GnRHa and gender-affirming hormones, a significant increase of BMAD was found. Z-scores normalized in transboys but remained below zero in transgirls. In transgirls and early pubertal transboys, all bone markers decreased during GnRHa treatment.ConclusionsBMAD z-scores decreased during GnRHa treatment and increased during gender-affirming hormone treatment. Transboys had normal z-scores at baseline and at the end of the study. However, transgirls had relatively low z-scores, both at baseline and after 3 years of estrogen treatment. It is currently unclear whether this results in adverse outcomes, such as increased fracture risk, in transgirls as they grow older.

Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled study.

BackgroundInterest in herbal medicines and non-hormonal therapies for the treatment of menopausal symptoms has increased since the publication of adverse effects of estrogen replacement therapy. Vasomotor symptoms are the most characteristic and notable symptoms of menopause.ObjectiveTo investigate the changes in the frequency and severity of hot flush and associated vasomotor symptoms experienced by peri-menopausal and menopausal women supplemented with the herbal formulation (Nu-femme™) comprising Labisia pumila (SLP+®) and Eurycoma longifolia (Physta®) or placebo.DesignRandomised, double-blind, placebo-controlled, 24-week study enrolled 119 healthy women aged 41–55 years experiencing peri-menopausal or menopausal symptoms and supplemented with Nu-femme™ or placebo. The primary endpoint was comparative changes between treatment groups in the change in the frequency and severity of hot flushes. The secondary objectives were to assess the changes in the frequency and severity of joint pain, Menopause Rating Scale (MRS) and Menopause-Specific Quality of Life (MENQOL) questionnaire domain scores. Concentrations of serum hormone, lipid profile, bone markers, sleep quality and vitality were also studied as secondary objectives.ResultsAt week 12, significant (P < 0.01) improvements in hot flush symptoms were observed in Nu-femme™ and placebo groups. Even though there was no significant difference between groups, higher percentage of improvement, 65%, was seen in Nu-femme™ compared to 60% in placebo. Significant improvements (P < 0.001) in MRS and MENQOL scores at weeks 12 and 24 were observed in both groups, respectively. Luteinising hormone and follicle-stimulating hormone levels were significantly reduced (P < 0.05) at weeks 12 and 24, respectively, compared to baseline in the Nu-femme™ group, with no significant changes observed in the placebo group. There were significant (P < 0.05) reductions in serum low-density lipid and triglycerides levels at week 12 in Nu-femme™ group, but no changes seen in placebo group. At the end of week 24, changes in haematology and clinical chemistry parameters remained within normal clinical ranges in both groups.ConclusionHerbal formulation consists of L. pumila and E. longifolia (Nu-femme™) may support reduction in hot flushes and improvements in hormone and lipid profile in healthy peri-menopausal and menopausal women.

Is There Difference of BMD between Non-Obese and Obese Children? - A Cross-Sectional Study in 194 Thai Children

Objective: To find the correlation between the presence of childhood obesity and bone mineral density (BMD). Materials and Methods: A cross-sectional study was conducted among children aged between 5 and 12 years old. After excluding children who had history of endocrinopathy, epilepsy, or cerebral palsy, all participants were divided into “obese group” (body mass index [BMI] at or above the 95 percentile of those with the same age and gender) and “control group” (BMI below the 95 percentile). Skeletal age, BMD, serum bone markers (osteocalcin and beta-crosslaps), and physical exercise were collected. Multivariate regression analysis was used for statistical analysis. Results: Ninety-six obese children and 98 controls were included in the present study. The average BMI was 28.5 kg/m² in obese group, and 16.6±1.9 kg/m² in controls (p&lt;0.001). BMDs of the spine and hip area were significantly higher in obese group compared to controls (p=0.002 and &lt;0.001, respectively). However, there was no significant difference of skeletal age or serum bone markers level between both groups (p&gt;0.05 all). Exercise was shown to significantly correlated with hip and distal radius BMD (p&lt;0.001 and 0.003, respectively). Conclusion: Obese children had significantly higher spine and hip BMD than non-obese children. Nevertheless, there were no differences between groups regarding skeletal age and bone markers. BMI and exercise activity might play an important role in higher BMD in children. Keywords: Bone mineral density, Children obesity

706-P: Recreational Soccer Training as a Tool Activity to Prevent Bone Issues in Type 2 Diabetes Patients

Bone formation is suppressed in the diabetic state, being the osteoporotic fractures a serious co-morbidity and complication of diabetes. A better lifestyle with proper diet and exercise have been linked to delay the progression of diabetes and may improve bone metabolism. With diabetes negatively affecting bone health we evaluated the impact of diet and exercise on serum bone markers, hormones and densitometry. This study assessed effects of twelve weeks of recreational soccer training combined with a caloric restricted diet (SO+D) vs. diet alone (D) in markers of bone health of type 2 diabetes (T2D) patients. Training sessions were performed for 40 min, 3 times per week for 12 weeks. We examined the following baseline and postprandial serum bone markers of formation: procollagen type 1 N-terminal propeptide (P1NP), and osteocalcin (OC); and C-terminal telopeptides of type I collagen (CTX) as bone resorption marker. Bone metabolic hormones such as parathyroid hormone (PTH) and 25-hydroxyvitamin D (25[OH]D) were also measured. Results: Compared to baseline levels, the first soccer session for SO+D induced acute increases of osteocalcin (35.0 ± 14.3 to 48.0 ± 26.3 ng/mL, P&amp;lt;0.05) and CTX remained unchanged. Osteocalcin, P1NP and CTX were lower in the D group (P&amp;lt;0.05). Compared to the D group, SO+D group resulted in increased osteocalcin (P&amp;lt;0.05), while P1NP and CTX levels did not alter. After 12 weeks, bone mineral density increased in both SO+D and D groups (P&amp;lt;0.05) and baseline levels of PTH remained unchanged, whereas 25[OH]D increased only in SO+D group (19.1±1.2 to 22.1 ± 1.4 ng/mL, P&amp;lt;0.05). Diet alone or combined with soccer training improved bone health status among T2D patients elicited by suppression on bone resorption marker and increased bone mineral density. However, recreational soccer training enhanced bone formation marker and vitamin D levels decreasing risk factors associated with osteoporosis and osteoporotic fractures in T2D patients better than diet alone. Disclosure M. Vieira de Sousa: None. M.R. da Silva: None. Funding Fundação de Amparo a Pesquisa do Estado de São Paulo (2012/01400-0)

Increasing Consumption of Vegetables Decreases Acid Excretion and Bone Turnover Among Adults with Overweight and Obesity: An 8-Wk Randomized Controlled Trial

Abstract Objectives To investigate the extent to which increased vegetable consumption affects urinary acid excretion and serum bone markers. Epidemiological studies suggest vegetable intake is positively associated with bone health through several mechanisms such as reducing oxidative stress and inflammation or diet-induced metabolic acidosis. We hypothesized that increasing intake of vegetables to the amounts and types recommended by the Dietary Guidelines for Americans (DGA) is beneficial to bone health by suppressing bone turnover. Methods One-hundred and ten adults with overweight or obesity were recruited in a two-arm, parallel-designed, randomized controlled community-based 8-wk feeding intervention trial. The two arms included (1) attention control arm, and (2) active intervention arm during which participants received a variety of pre-packaged, minimally prepared fresh or frozen vegetables. Blood and urine samples were collected. One hundred-two participants completed the study. Results At baseline, there were no differences in urine pH (6.17 ± 0.42 vs 6.18 ± 0.41), urine titratable acid (21.0 ± 7.3 vs 20.7 ± 9.0 mEq/d), urine ammonia (324 ± 197 vs 348 ± 175 mg/d), serum N-terminal propeptide of type I procollagen (PINP, a bone formation marker, 27.8 ± 8.9 vs 26.3 ± 10.5 ng/ml), serum C-terminal telopeptide of type I collagen (CTX, a bone resorption marker, 0.36 ± 0.18 vs 0.34 ± 0.15 ng/ml), between the control and the intervention groups, respectively. There were no differences in the above parameters between the baseline and at the end of 8-wk for the control group. Compared to the baseline, increased intake of vegetables increased urine pH (6.33, P &amp;lt; 0.05) and serum PINP (29.7 ± 13.6 ng/ml, P &amp;lt; 0.05), and decreased urine titratable acid (17.0 ± 9.4 mEq/d, P &amp;lt; 0.05), urine ammonia (279 ± 151 mg/d, P &amp;lt; 0.05), and serum CTX (0.29 ± 0.11 ng/ml, P &amp;lt; 0.01). Conclusions These data demonstrate that increased vegetable consumption of the types and amounts recommended by the DGA decreases urinary acidity and has positive effects on bone turnover markers. Funding Sources This work was supported by the Agricultural Research Service of the United States Department of Agriculture, #3062–51,000-053–00D.

Tibolone, alendronate, and simvastatin enhance implant osseointegration in a preclinical in vivo model.

The objective of the study was to evaluate and compare the effect of different drugs such as simvastatin, alendronate, and tibolone for titanium implant osseointegration enhancement. Eighty female albino Wistar rats were equally divided into five groups: Group I (ovariectomy), Group II (sham ovariectomy), Group III (alendronate+ovariectomy), Group IV (simvastatin+ovariectomy), and Group V (tibolone+ovariectomy). Three months after ovariectomy, we performed bilateral titanium intramedullary nailing in all groups, followed by oral administration of alendronate, simvastatin, or tibolone for 12weeks. Examinations included micro-CT, mechanical pull-out test, histology, and bone serum markers. Peri-implant micro-CT analysis showed a significantly higher overall bone tissue in tibolone compared to the ovariectomy group, while no significant difference was found between the treatment groups. Sham ovariectomy, alendronate, and tibolone groups had a higher body mass density compared to ovariectomy and simvastatin groups. All treatment groups had a greater thickness of the peri-implant compact bone layer compared to ovariectomy group, but the results were not statistically significant. Tibolone presented the highest values in pull-out test, but alendronate showed more consistently positive results compared to other groups. Osteocalcin had in the tibolone group almost three times the value in the ovariectomy group, but the results were not statistically significant. The hypothesis that alendronate, simvastatin, and tibolone enhance the osseointegration process of intramedullary titanium implants in ovariectomized rats has been accepted, while tibolone could offer the best results.

Serum bone markers and risk of osteoporosis and fragility fractures in women who received endocrine therapy for breast cancer: a prospective study.

Osteoporosis and fragility fracture are major bone toxicities of aromatase inhibitors (AIs) for postmenopausal hormone receptor-positive breast cancer. Except for a few small studies on bone turnover markers and reduced bone mineral density after AI treatment, data on the associations of bone markers and risk of osteoporosis or fracture from prospective studies are lacking. In a prospective study of 1709 women on AIs, two bone turnover markers, BALP and TRACP, and two bone regulatory markers, RANKL and OPG, were measured and examined in relation to risk of osteoporosis and fragility fractures during a median follow-up time of 6.1years. Higher levels of BALP and TRACP were both associated with increased risk of osteoporosis and higher BALP/TRACP ratios were associated with lower risk of osteoporosis, but no associations were observed for fracture risk. Higher levels of OPG were associated with increased risk of fracture, whereas higher levels of RANKL were associated with lower risk. As a result, OPG/RANKL ratios were positively associated with fracture risk [hazard ratio (HR) = 2.49, 95% confidence interval (CI) 1.34-4.61]. After controlling for age and fracture history, the associations became non-significant but a suggestive trend remained (HR = 1.80, 95% CI 0.96-3.37). Our study provides suggestive evidence for the potential utility of OPG/RANKL ratios in predicting risk of fracture in women treated with AIs for breast cancer. Further validation may be warranted.

Changes in serological bone turnover markers in bisphosphonate induced osteonecrosis of the jaws: A case control study.

There are a lot study confirmed the relationship of bone serum markers changes and skeletal irregularities. But there is no sufficient case control studies about the role of these markers on bisphosphonate induced osteonecrosis of jaws (BRONJ). The aim of this study is to find out if there is any derangement of bone markers in bisphosphonate-treated patients with ONJ. We obtained serum bone markers and other relevant endocrine assays on 20 patients with osteonecrosis of the jaw (ONJ) and 20 randomized healthy volunteers. All of the ONJ group treated with zoledronic acid and had been withdrawn from bisphosphonate for at least 6 months. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. The biochemical assays were performed on N-Telopeptides of type I collagen (NTX), bone-specific alkaline phosphatase (ALP), calcitonin, osteocalcin, intact parathyroid hormone (PTH), T3, T4, TSH, and Vitamin D 25 hydroxy (Vit-D). In ONJ group, PTH level is statistically higher and TSH, Vit-D, osteocalcin and NTX levels statistically lower compared to control group. We conclude that these changes in PTH, Vit-D, TSH, osteocalcin and NTX levels maybe have a role in the pathophysiology of BRONJ. But the data need to be confirmed by future studies.

Differences in Osteoimmunological Biomarkers Predictive of Psoriatic Arthritis among a Large Italian Cohort of Psoriatic Patients.

(1) Background: In literature it is reported that 20–30% of psoriatic patients evolve to psoriatic arthritis over time. Currently, no specific biochemical markers can either predict progression to psoriatic arthritis or response to therapies. This study aimed to identify osteoimmunological markers applicable to clinical practice, giving a quantitative tool for evaluating pathological status and, eventually, to provide prognostic support in diagnosis. (2) Methods: Soluble (serum) bone and cartilage markers were quantified in 50 patients with only psoriasis, 50 psoriatic patients with psoriatic arthritis, and 20 healthy controls by means of multiplex and enzyme-linked immunoassays. (3) Results: Differences in the concentrations of matrix metalloproteases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), receptor activator of nuclear factor kappa-B- ligand (RANK-L), procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTx-I), dickkopf-related protein 1 (DKK1), and sclerostin (SOST) distinguished healthy controls from psoriasis and psoriatic arthritis patients. We found that MMP2, MMP12, MMP13, TIMP2, and TIMP4 distinguished psoriasis from psoriatic arthritis patients undergoing a systemic treatment, with a good diagnostic accuracy (Area under the ROC Curve (AUC) > 0.7). Then, chitinase-3-like protein 1 (CHI3L1) and MMP10 distinguished psoriasis from psoriatic arthritis not undergoing systemic therapy and, in the presence of onychopathy, MMP8 levels were higher in psoriasis than in psoriatic arthritis. However, in these latter cases, the diagnostic accuracy of the identified biomarkers was low (0.5 < AUC < 0.7). (4) Conclusions. By highlighting never exploited differences, the wide osteoimmunological biomarkers panel provides a novel clue to the development of diagnostic paths in psoriasis and psoriasis-associated arthropathic disease.

877P - Serum biomarkers of bone metabolism in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with radium-223 (Ra223): Results from a prospective multicentre study

BackgroundRa223 is a life-prolonging alpha-emitter bone targeted therapy for mCRPC patients with bone metastases. However, evidence on biomarkers that may help us in patient selection are lacking. Total ALP (tALP) appeared to be a potential marker of Ra223 effect in early studies (Sartor, Ann Oncol, 2017). Other bone-related markers, as bone-specific ALP (BALP), have demonstrated its prognostic value in mCRPC patients with bone metastases (Fizazi K, Eur Urol, 2015; Lara PN, J Natl Cancer Inst, 2014). MethodsPRORADIUM (NCT022925702) is a prospective multicentre cohort study in mCRPC patients treated with Ra223. The primary aim was to assess the impact of baseline serum biomarkers of bone formation (BALP and C-terminal of type 1 collagen propeptide [CICP]) on overall survival (OS). Secondary aims include the correlation of progression-free survival (PFS), time to PSA progression (TTPP) and skeletal-related events free-survival (SRE-FS) with serum bone markers. Results142 out of 168 pts enrolled in the study were included in this preliminary analysis. Median age was 74 yrs, 85.5% pts had ECOG 0-1, 52% pts completed 5-6 cycles of Ra223. Higher baseline levels of BALP and CICP were associated to number of metastases in bone-scan (p=0.007 and p=0.016, respectively) and baseline pain (p=0.014 and p=0.050, respectively). After a median follow-up of 18 months, 91 deaths were observed, with a median OS of 11.5 months (95%CI: 9.1-13.9). Patients with baseline BALP and CICP values above the median showed a trend to shorter TTPP (BALP: 2.8 vs 3.1 m, p=0.016; CICP: 2.8 vs 3.0 m, p=0.091) and PFS (BALP: 4.4 vs 5.1 m, p=0.070; CICP: 4.2 vs 5.5 m, p=0.281), respectively. The elevation of bone markers above the median was significantly associated with worse OS (BALP: 8.8 vs 17.9 m, p<0.001; CICP: 9.4 vs 16.8 m, p=0.001). There were not associations found with SRE-FS. ConclusionsOur results suggest that baseline serum markers of bone formation may serve as biomarkers for prognosis in mCRPC patients treated with Ra233. Clinical trial identificationNCT022925702. Legal entity responsible for the studyIBIMA and CNIO. FundingBayer, CRIS Cancer Foundation, Grant from Instituto de Salud Carlos III (PI16/01565). DisclosureN. Romero Laorden: Honoraria (self), Travel / Accommodation / Expenses: Bayer, Astellas Pharma, Janssen-Cilag, Sanofi-Aventis, PharmaMar, MSD, Roche. R. Lozano Mejorada: Honoraria (self): Roche, Janssen-Cilag, Bayer; Research grant / Funding (institution): Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Roche, Janssen-Cilag, Astellas Pharma. E. Almagro Casado: Honoraria (self): MSD; Travel / Accommodation / Expenses: BMS. E. Gonzalez Billalabeitia: Travel / Accommodation / Expenses: BMS, Pfizer, Janssen-Cilag, Astellas Pharma, Sanofi. A. Montesa: Advisory / Consultancy: Janssen-Cilag, Pfizer, Sanofi, Astellas Pharma; Travel / Accommodation / Expenses: Pfizer. G.A. De Velasco Oria de Rueda: Honoraria (self), Advisory / Consultancy: Pfizer, Novartis, Ipsen, Astellas Pharma, BMS, Bayer, MSD, Roche. R. Morales Barrera: Honoraria (self): MSD, Sanofi, AstraZeneca, Janssen, Roche/Genentech; Advisory / Consultancy: MSD, Sanofi, AstraZeneca, Janssen, Roche/Genentech; Speaker Bureau / Expert testimony: MSD, Sanofi, AstraZeneca, Asofarma, Janssen; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, INC, Astellas Pharma, AstraZeneca, Aveo Pharmaceuticals, Bayer, Blueprint Medicines Corporation, BN Immunotherapeutics, Boehringer Ingelheim España, BMS, Clovis Oncology, Cougar Technology, Deciphera Pharmaceuticals LL; Travel / Accommodation / Expenses: MSD, Roche, Lilly, Clovis Oncology, Bayer, Janssen-Cilag, Astellas Pharma, AstraZeneca. D. Lorente: Honoraria (self): Janssen-Cilag, Bayer, Astellas Pharma, Sanofi; Advisory / Consultancy: Janssen-Cilag, Bayer, Sanofi; Travel / Accommodation / Expenses: Sanofi, Astellas, Janssen-Cilag, Celgene. E. Castro: Honoraria (self): Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer; Advisory / Consultancy: Bayer, Janssen-Cilag; Research grant / Funding (institution): Janssen-Cilag, AstraZeneca, Bayer, Genentech, Roche, Pfizer, Astellas Medivation, Tokai Pharmaceuticals; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, Astellas Pharma. D. Olmos Hidalgo: Honoraria (self): Janssen-Cilag, Bayer, Sanofi; Advisory / Consultancy: Bayer, Janssen-Cilag, AstraZeneca, Clovis Oncology; Research grant / Funding (institution): Bayer, Janssen, AstraZeneca, Roche/Genentech, Medivation/Pfizer, Astellas, Tokai, MSD, GSK; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Ipsen. All other authors have declared no conflicts of interest.

Effect of low-intensity resistance training with blood flow restriction on serum VEGF level, bone markers and bone mineral density in elderly women

Purpose The purpose of this study was to investigate the effects of low-intensity resistance training with blood flow restriction on serum VEGF, bone markers and bone mineral density in elderly women. Methods The subjects were divided into three groups: low-intensity resistance training with blood flow restriction(BFR-LRT, n=8); high intensity resistance training(HRT, n=8); low- intensity resistance training (LRT, n=5). Both the BFR-LRT and LRT groups worked out knee extension and leg curl exercises at 20% of each estimated one-repetition maximum(1RM) and HRT group worked out knee extension and leg curl exercises at 70% of each estimated 1RM 3 days per week for 12 weeks. Results As a result after 12 weeks, serum VEGF level have increased significantly among BFR-LRT group compared to HRT and LRT groups. Serum Bone ALP level have increased significantly among BFR-LRT and HRT groups compared to LRT group. Calcaneus BMD have increased significantly among BFR-LRT and HRT groups compared to LRT group. Conclusions In conclusion, despite using low-intensity load, BFR-LRT is a efficient training alternative to HRT for improving bone metabolism in older women.

Anomalous bone changes in ovariectomized type 2 diabetic rats: inappropriately low bone turnover with bone loss in an estrogen-deficient condition.

Estrogen deprivation accelerates bone resorption, leading to imbalance of bone remodeling and osteoporosis in postmenopausal women. In the elderly, type 2 diabetes mellitus (T2DM) frequently coexists as an independent factor of bone loss. However, little is known about the skeletal changes in a combined condition of estrogen deficiency and T2DM. Herein, we performed ovariectomy (OVX) in nonobese Goto-Kakizaki (GK) T2DM rats to examine changes associated with calcium and phosphate metabolism and bone microstructures and strength. As expected, wild-type (WT) rats subjected to ovariectomy (OVX-WT) had low trabecular bone volume and serum calcium with increased dynamic histomorphometric and serum bone markers, consistent with the high turnover state. T2DM in GK rats also led to low trabecular volume and serum calcium. However, the dynamic histomorphometric markers of bone remodeling were unaffected in these GK rats, indicating the distinct mechanism of T2DM-induced bone loss. Interestingly, OVX-GK rats were found to have anomalous and unique changes in bone turnover-related parameters, i.e., decreased osteoblast and osteoclast surfaces with lower COOH-terminal telopeptide of type I collagen levels compared with OVX-WT rats. Furthermore, the levels of calciotropic hormones, i.e., parathyroid hormone and 1,25(OH)2D3, were significantly decreased in OVX-GK rats. Although the OVX-induced bone loss did not further worsen in GK rats, a three-point bending test indicated that OVX-GK bones exhibited a decrease in bone elasticity. In conclusion, T2DM and estrogen deficiency both led to microstructural bone loss, the appearance of which did not differ from each factor alone. Nevertheless, the combination worsened the integrity and suppressed the turnover, which might eventually result in adynamic bone disease.

Bone disorders in chronic kidney disease patients: A teaching hospital based study in central India

Background: Kidneys and bones are the major metabolic buffer systems in our body that help us to maintain the internal milieu. Disease in one naturally is going to affect the other in long term. The association between the two has long been known but not brought into the limelight till the recent decades. This increase in the importance being given to the mineral abnormalities is due to its high association with the cardiovascular disease and death due to CVD. Chronic kidney disease (CKD) is a progressive loss in renal function which involves in deterioration in mineral homeostasis with disruption of normal serum and tissue concentration of phosphorus and calcium. Also changes in circulating levels of hormones parathyroid hormone (PTH), calcitriol (1, 25(OH) 2 D), and fibroblast growth factor-23 (FGF-23). Here our aim is to study the prevalence of markers associated with MBD in CKD stage 3-5 patients. Patients with CKD stage 3-5 were included in this observational study with all necessary parameter. X-RAY abdomen and echocardiography was done to look for evidence of vascular and valvular calcification respectively. Aims and Objectives: To evaluate the bone disorders in chronic kidney disease patients.Material and Methods: This retrospective study was conducted in Department of Medicine, RKDF Medical College Hospital & Research Center, Bhopal, Madhya Pradesh, India. All CKD patients from stage 3-5 were included. Likewise Patients having pre-existing systemic diseases like SLE/RA, liver disease, patients on steroids or other drugs which have effect on bone metabolism like calcium, phosphate binders, vit D, bisphosphonates, patients with primary bone diseases, patients on maintenance hemodialysis and h/o fracture in last. Statistical analysis was done using SPSS software.Results and Observations: A total of 175 patients (132 males, 43 females) (M:F = 3:1) were included in this study with a mean age of 50.54 years. Among CKD stages 3 to 5, the prevalence of hypocalcemia was 21.5%, 33.9% & 48.9%, hyperphosphatemia was 11.1%, 25.5% & 63%, hyperparathyroidism was 48.1%, 67.3% & 89.1%, high total alkaline phosphatase was 0%,5.9% & 45.7%, low 25-OH-vit D was 59.2%, 70.6% & 79.4% respectively. Low 25 (OH) D levels, hyperparathyroidism, and hyperphosphatemia were the noticeable markers of CKD-MBD in our patients. Mineral bone disorder are common in CKD patients which start in early CKD stages & worsen with disease progression that causes morbidity and decreased quality of life.Conclusion: Diabetic and Non-diabetic CKD-MBD are not different and hence need not be addressed separately. Serum bone marker assay should be included in CKD-MBD screening. The screening should begin in the early stage of CKD. In conclusion, we observed Low 25 (OH) D levels, hyperparathyroidism, and hyperphosphatemia were the noticeable markers of CKD-MBD in our patients. Mineral bone disorder are common in CKD patients which start in early CKD stages & worsen with disease progression that causes morbidity and decreased quality of life. Hence, this shows the importance of early recognition, understanding of their patho-physiological consequences & planning management strategies to prevent their progression, thereby reducing the cardiovascular morbidity & mortality.

Serum bone markers in ROD patients across the spectrum of decreases in GFR: Activin A increases before all other markers .

Introduction: Renal osteodystrophy (ROD) develops early in chronic kidney disease (CKD) and progresses with loss of kidney function. While intact parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3 (1,25D), and fibroblast growth factor-23 (FGF-23) levels are usually considered the primary abnormalities in ROD development, the role of serum activin A elevations in CKD and its relationships to ROD have not been explored. The aims of this study were to evaluate serum activin A at different CKD stages, and to establish the relationships between activin A, bone biomarkers, and bone histomorphometric parameters. Materials and methods: 104 patients with CKD stages 2 – 5D underwent bone biopsies. We measured in the serum activin A, BSAP, DKK1, FGF-23, α-Klotho, intact PTH, sclerostin, TRAP-5b, and 1,25D. Biochemical results were compared across CKD stages and with 19 age-matched controls with normal kidney function. Results: Median activin A levels were increased in all stages of CKD compared to controls from 544 pg/mL in CKD 2 (431 – 628) to 1,135 pg/mL in CKD 5D (816 – 1,456), compared to 369 pg/mL in controls (316 – 453, p < 0.01). The increase of activin A in CKD 2 (p = 0.016) occurred before changes in the other measured biomarkers. Activin A correlated with intact PTH and FGF-23 (r = 0.65 and 0.61; p < 0.01) and with histomorphometric parameters of bone turnover (BFR/BS, Acf, ObS/BS and OcS/BS; r = 0.47 – 0.52; p < 0.01). These correlations were comparable to those found with intact PTH and FGF-23. Conclusion: Serum activin A levels increase starting at CKD 2 before elevations in intact PTH and FGF-23. Activin A correlates with bone turnover similar to intact PTH and FGF-23. These findings suggest a role for activin A in early development of ROD.

Chocolate and chocolate constituents influence bone health and osteoporosis risk.

Bone loss resulting in increased risk for osteoporosis is a major health issue worldwide. Chocolate is a rich source of antioxidant and antiinflammatory flavonoids and dietary minerals with the potential to benefit bone health. However, other chocolate constituents such as cocoa butter, sugar, and methylxanthines may be detrimental to bone. Human studies investigating the role of chocolate consumption on serum bone markers and bone mineral density (BMD) have been inconsistent. A contributing factor is likely the different composition and thereby the nutrient and bioactive content among chocolate types. White and milk chocolate are high in sugar and low in flavonoids and most minerals. Dark chocolate (45-85% cocoa solids) is high in flavonoids, most minerals, and low in sugar with ≥70% cocoa solids resulting in higher fat and methylxanthine content. The aim of this review was to examine the relationship between chocolate consumption and its constiuents, including flavonoid content, on bone health and osteoporosis risk. Studies showed postmenopausal women had no bone effects at moderate chocolate intakes, whereas adolescents consuming chocolate had greater longitudinal bone growth. Based on flavonoid and mineral content, unsweetened cocoa powder appeared to be the best option followed by dark chocolate with higher cocoa content in terms of supporting and preserving bone health. Determining dietary recommendations for chocolate consumption relative to bone health is important because of the growing popularity of chocolate, particularly dark chocolate, and an expected increase in consumption owing to suggestions of health benefits against various degenerative diseases.

Revisiting predictive biomarkers of musculoskeletal injury in thoroughbred racehorses: longitudinal study in polish population

BackgroundHigh prevalence of musculoskeletal disorders in racehorses and its impact on horse welfare and racing economics call for improved measures of injury diagnosis and prevention. Serum biomarkers of bone and cartilage metabolism have previously shown promise in prediction of musculoskeletal injuries in horses. This study aimed to re-evaluate usability of the predictive serum biomarkers identified in North American Thoroughbred racehorses in a geographically distinct group of Polish Thoroughbreds.ResultsSerum concentrations of bone and cartilage biomarkers: osteocalcin, c-terminal telopeptide of type I collagen, total glycosaminoglycans (GAG), chondroitin sulfate epitope and c-propeptide of type II procollagen (CPII) were evaluated in the beginning and the next 3 months of one racing season in a cohort of twenty-six 2-year-old Polish racehorses. Exit criteria were diagnosis of musculoskeletal injury, leading to > 5 days off training (n = 8), or completion of 3 study months with no training interruptions (n = 18). Normalized results and matching archival data from 35 2-year-old North American racehorses was used for logistic regression analysis to identify universal predictors of injury. Mean GAG and CPII levels were lower in injured group comparing to control, which is consistent with previous findings in racehorses. These biomarkers were also identified as predictors of injury in the mixed population model. Population origin had no significant effect on predictive value of evaluated biomarkers (Wald test p = 0.137). Decreased osteocalcin and increased c-terminal telopeptide of type I collagen levels in injured horses comparing to controls were specific for Polish population and signalized disruption in bone turnover homeostasis.ConclusionsChanges in serum GAG and CPII in racehorses at risk of injury appear to be similar across distinct populations while dynamics of serum bone marker is more population-specific.