OBJECTIVE

To investigate the effects of low impact aerobic dance and fitball training on bone resorption in Thai working women.

METHODS

The samples of this study consisted of 47 females at the age from 35-45. The subjects were divided into two groups: A) 23 females in a low impact aerobic dance (20 min) and fitball (15 min) training group, and B) 24 females in a low impact aerobic dance training group (35 min). Both groups wore a heart rate monitor during the exercise training. The sessions in the training program over 12 weeks were performed a 3-day a week, 35-minute for work out per session at an intensity of 60-80% of maximum heart rate. Before and after the 12-week training program, bone resorption (Telopeptidecrosslinked: β-CrossLaps) and bone formation (N-terminal propeptine of procollagen type 1: P1NP) including physiological and fitness data were assessed. The data of pre and post trainings within and between the groups as well as the data of changes in dependent variables were compared and analyzed by using paired t-test and independent-test. The statistically significant difference was set at the 0.05 level.

RESULTS

Both the low impact aerobic dance and fitball training group and the low impact aerobic dance training group revealed their lower level of bone resorption (β-CrossLaps) while the first group showed statistically significant change (p < 0.05). In addition, there were no significant changes of bone resorption (β-CrossLaps) and bone formation (P1NP) between these two groups. However; both groups had not only a significant decrease in resting heart rate, systolic and diastolic pressure, but also an increase in muscular strength and endurance and maximum oxygen uptake when the training was completed. Flexibility ofthe group withfitball was increased significantly (p < 0.05).

CONCLUSIONS

Low impact aerobic dance and fitball training has the positive effect of slowing down bone resorption and is beneficial to healthy bones. They concurrently increase lower back flexibility.

OBJECTIVE

To evaluate systemic markers of collagen metabolism and vitamin C in female smokers with pelvic organ prolapse (POP). Secondary aims were to compare these levels in women based on prolapse or smoking history alone.

METHODS

This was a cross-sectional study with four groups: smokers with POP, non-smokers with POP, smokers without POP and non-smokers without POP. Subjects were age-matched based on smoking history and presence of POP. All underwent a fasting blood panel, including plasma procollagen 1-N propeptide (P1NP), matrix metalloproteinase 9 (MMP-9), and vitamin C.

RESULTS

Ninety-six subjects were enrolled. There were no differences for any demographics other than stage of prolapse, which was highest in non-smokers with POP. Significant variations in the levels of vitamin C and MMP-9 were noted among the four groups. Smokers with POP had lower levels of vitamin C and higher levels of MMP-9, compared to non-smokers with POP, but this relationship was not statistically significant. However, when contrasting smokers without POP to non-smokers without POP, significant differences in both vitamin C and MMP-9 were documented, confirming an impact of smoking on these markers. Notwithstanding, when evaluated independent of smoking status, vitamin C and MMP-9 levels in women with POP were similar to those of women without POP.

CONCLUSIONS

Lower vitamin C and higher MMP-9 among smokers confirms the usefulness of such markers in documenting the smoking's impact on collagen. However, the lack of a difference based on POP suggests these are poor measures for understanding the pathophysiology of this disorder.

OBJECTIVE

To evaluate the systemic effect of therapy with conjugated equine estrogen (CEE) vaginal cream on bone turnover markers in postmenopausal women.

METHODS

This study was conducted in 40 spontaneously menopausal women aged 40-60 years who complained of vulvovaginal symptoms. Subjects were instructed to self-administer 1 g CEE vaginal cream (CEE 0.625 mg) once daily for 12 weeks (continuous phase), then twice weekly for the next 12 consecutive weeks (intermittent phase). Serum levels of bone turnover markers and estradiol and the vaginal maturation index were evaluated at baseline, 12 and 24 weeks after treatment initiation.

RESULTS

Levels of C-terminal cross-linked telopeptide of type I collagen (CTx) were significantly decreased at 12 weeks and 24 weeks when compared to baseline values (median (range) 0.435 (0.171-0.859) and 0.391 (0.122-0.714) vs. 0.562 (0.250-1.290) ng/ml (p < 0.001 and < 0.001), respectively), but there was no significant difference between the levels at 12 and 24 weeks. Levels of procollagen type I N-terminal propeptide (P1NP) and osteocalcin levels were significantly decreased after 24 weeks when compared to pretreatment levels (mean (standard deviation) 41.74 (11.76) vs. 50.02 (17.71) ng/ml (p = 0.002) for P1NP and 23.91 (7.11) vs. 27.54 (8.67) ng/ml (p < 0.001) for osteocalcin, respectively). Estradiol levels were significantly increased and the vaginal maturation index was significantly improved after 12 and 24 weeks when compared to baseline.

CONCLUSIONS

CEE vaginal cream significantly decreased the bone resorption marker (CTx) in postmenopausal women after completion of the continuous-treatment phase. There was no significant further decrease after the intermittent phase. The effects on the markers of bone formation and bone turnover (P1NP and osteocalcin) were apparent only at 24 weeks. The two treatment phases moderately increased serum estradiol levels and significantly improved the vaginal maturation index.

Cathepsin K plays an important role in bone resorption. The reports of the association of serum cathepsin K with bone mineral density (BMD) and bone turnover markers are conflicting and the role of serum cathepsin K as a bone turnover marker is unclear. The aims of the study were as follows: (1) to investigate the association of serum cathepsin K with BMD and markers of bone turnover and (2) to evaluate the correlations of single-nucleotide polymorphisms (SNPs) within the CTSK gene with serum cathepsin K, BMD, and markers of bone metabolism in postmenopausal Chinese women. A cross-sectional study was conducted with 1752 postmenopausal Chinese women. Four tagging SNPs (rs12085336, rs12746973, rs4379678, and rs10847) of the CTSK gene were genotyped. Serum cathepsin K of 768 and markers of bone metabolism of 1752 including serum intact PTH, 25-hydroxyvitamin D [25(OH)D], procollagen type 1 N-terminal propeptide (P1NP), and β-CrossLaps of type I collagen containing cross- linked C-telopeptide (β-CTX) were measured. The BMD of the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry (DXA). No significant relationship was detected between serum cathepsin K and age, BMI, BMD or bone metabolic markers (all P > 0.05) after adjustment for age and BMI. We failed to identify any significant association between the genotypes or haplotypes of CTSK and BMD, bone turnover markers, or serum cathepsin K. Neither serum cathepsin K nor CTSK gene polymorphisms was correlated with BMD or bone turnover markers. Genetic polymorphisms of CTSK may not be a major contributor to variations in the serum cathepsin K or BMD in postmenopausal Chinese women. The results implied that serum cathepsin K may not be viewed as a substitute for bone turnover markers.

Previously we reported the results of a 4-year extension of a 2-year randomized placebo-controlled trial showing that the antiresorptive effects of two annual 4-mg doses of zoledronate in HIV-infected men persisted for at least 5 years after the second dose. We set out to determine whether the effects on BMD and bone turnover persist beyond 10 years. We invited all participants in the original trial known to be alive and living in New Zealand to attend an additional visit approximately 12 years after trial entry and 11 years after their second dose of study medication. The outcome measures were BMD at the lumbar spine, proximal femur, and total body, and markers of bone turnover. Twenty-five of the 43 men originally enrolled in the trial attended the final visit, representing 25 of 31 (81%) participants alive and residing in New Zealand at the time. The average duration of follow-up was 12.4 years. At the final visit, BMD remained higher in the zoledronate group than the placebo group (lumbar spine 3.7%, 95% CI, 0.1 to 7.3; total hip 3.7%, 95% CI, 1.2 to 6.2; femoral neck 5.0%, 95% CI, 2.1 to 7.9; total body 2.4%, 95% CI, 0.7 to 4.0), and the between-group differences in BMD remained stable between 6 and 12 years. Serum CTx remained lower in the zoledronate group than the placebo group between 6 and 12 years and, at the final visit, was 45% lower (95% CI, 25 to 64) than the placebo group. P1NP was 26% (95% CI, 4 to 48) lower in the zoledronate group than the placebo group at the final visit. In summary, two annual 4-mg doses of zoledronate have effects on bone turnover and BMD in men that persist for at least 11 years after the second dose. © 2019 American Society for Bone and Mineral Research.

Objective: The aim is to analyze the fracture risk in rheumatic patients by fracture risk assessment tool (FRAX), which is recommended by World Health Organization (WHO), so that we can prevent the occurrence of osteoporotic fracture earlier. Methods: Totally 617 participants, 204 out-patients with rheumatism, 204 in-patients with rheumatism and 209 healthy controls, from March to October in 2018 of Fourth Medical Center of PLA General Hospital, Jishuitan Hospital and China-Japan Friendship Hospital, were enrolled in this study. The probability of hip fracture (PHF) and major osteoporotic fracture (PMOF) in 10 years with FRAX were compared, and the differences between taking sleroids or not and with or without bone mass density (BMD) of femoral neck were evaluated. Correlation analysis was conducted between PHF, PMOF and clinical information, including age, disease duration, gender, steroid usage, osteocalcin, P1NP and β-crosslaps. Results: There was no significant difference in PMOF within 10 years (3.455±2.690 vs 2.973±2.149 vs 3.323±1.828) among the three groups (P>P<P<P>P1NP among in-patients. Conclusion: The prevalence of 10-year hip fracture calculated by FRAX in rheumatism patients is higher than that of healthy group. FRAX can be used to calculate fracture risk without BMD. Combination of FRAX and bone turnover markers may be more effective in prediction of osteoporotic fracture in rheumatic patients.

Context: In healthy individuals, glucose-dependent insulinotropic polypeptide (GIP) enhances insulin secretion and reduces bone resorption by up to 25% estimated by absolute placebo-corrected changes in carboxy-terminal type 1 collagen crosslinks (CTX) during GIP and glucose administration. In patients with type 2 diabetes (T2D), GIP's insulinotropic effect is impaired and effects on bone may be reduced.

Objective: To investigate GIP's effect on bone biomarkers in patients with T2D.

Design: Randomized, double-blinded, crossover study investigating 6 interventions.

Patients: Twelve male patients with T2D.

Interventions: A primed continuous 90-minute GIP infusion (2 pmol/kg/min) or matching placebo (saline) administered at 3 plasma glucose (PG) levels (i.e., paired days with "insulin-induced hypoglycemia" (PG lowered to 3 mmol/L), "fasting hyperglycemia" (mean PG ~8 mmol/L), or "aggravated hyperglycemia" (mean PG ~12 mmol/L).

Main outcome measures: Bone biomarkers: CTX, procollagen type 1 N-terminal propeptide (P1NP) and PTH.

Results: On days with insulin-induced hypoglycemia, CTX was suppressed by up to 40 ± 15% during GIP administration compared with 12 ± 11% during placebo infusion (P < 0.0001). On days with fasting hyperglycemia, CTX was suppressed by up to 36 ± 15% during GIP administration, compared with 0 ± 9% during placebo infusion (P < 0.0001). On days with aggravated hyperglycemia, CTX was suppressed by up to 47 ± 23% during GIP administration compared with 10 ± 9% during placebo infusion (P = 0.0005). At all glycemic levels, P1NP and PTH concentrations were similar between paired days after 90 minutes.

Conclusions: Short-term GIP infusions reduce bone resorption by more than one-third (estimated by absolute placebo-corrected CTX reductions) in patients with T2DM, suggesting preserved bone effects of GIP in these patients.

Précis: Short-term GIP infusions reduce the bone resorption marker CTX by one-third in patients with type 2 diabetes independent of glycemic levels.

Keywords: Gastric inhibitory polypeptide; bone markers; carboxy-terminal collagen type 1 crosslinks (CTX); glucose-dependent insulinotropic polypeptide (GIP); procollagen type 1 N-terminal propeptide (P1NP).

BACKGROUND

We aimed to investigate the bone turnover markers in coronary artery disease (CAD) patients with and without type 2 diabetes (T2DM) in comparison with control subjects without CAD and T2DM.

METHODS

This cross-sectional study was performed on 45 subjects undergoing elective heart surgery; either for coronary artery bypass grafting or for valve surgery. According to angiographic results, participants were grouped in two groups with CAD (n = 33) and without CAD (n = 12). The serum levels of osteocalcin (OC), procollagen I aminoterminal propeptide (P1NP) and carboxy-terminal collagen crosslinks (CTX), as bone turnover markers, as well as serum levels of 25 (OH) vitamin D3, PTH, and common metabolic factors were analyzed in all participants.

RESULTS

Serum levels of bone markers did not differ in patients with CAD compared to non-CAD subjects. Regarding metabolic factors, serum levels of FBG had invert correlation with OC in CAD patients (p = 0.004). The data of subgroup analysis showed serum levels of OC and CTX were statistically significant lower in CAD-DM than CAD-non DM (p < 0.05). There were not any significant differences in the P1NP levels between groups.

CONCLUSIONS

Our data suggest that CTX and OC would be used as suitable bone markers in CAD patients with T2DM. However, further clinical studies need to establish the role of these markers in CAD patients with diabetes.

<AbstractText>Both thyroid dysfunction and levothyroxine therapy (LT4) have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded conflicting results.</AbstractText><AbstractText>To assess the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with SHypo.</AbstractText><AbstractText>Planned nested substudy of the double-blind placebo-controlled TRUST trial. Participants with SHypo were randomized to LT4 with dose titration vs. placebo with computerized mock titration.</AbstractText><AbstractText>196 community-dwelling adults over 65 years enrolled at the Swiss TRUST sites had baseline and 1-year follow-up bone examinations; 4 participants withdrew due to adverse events not related to treatment.</AbstractText><AbstractText>One-year percent changes of BMD, TBS, and two serum BTMs (sCTX and <em>P1NP</em>). Student's t-test for unadjusted analyses, and linear regression adjusted for clinical center and sex, were performed.</AbstractText><AbstractText>Mean age was 74.3y ± 5.7, 45.4% were women, and 19.6% were osteoporotic. The unadjusted 1-year change in lumbar spine BMD was similar between LT4 (+0.8%) and placebo-treated groups (-0.6%; between-groups difference +1.4%: 95%CI -0.1 to 2.9, p=0.059). Likewise, there were no between-group differences in 1-year change in TBS (-1.3%: 95%CI -3.1 to 0.6, p=0.19), total hip BMD (-0.2%: 95%CI -1.1 to 0.1, p=0.61), or BTMs levels (sCTX +24.1%: 95%CI -7.9 to 56.2, p=0.14), or after adjustment for clinical centers and sex.</AbstractText><AbstractText>Over one-year levothyroxine had no effect on bone health in older adults with SHypo.</AbstractText><AbstractText>ClinicalTrial.gov NCT01660126 and NCT02491008.</AbstractText>

<AbstractText>Bone health in SLE is adversely affected by vitamin D deficiency, inflammatory cytokines and glucocorticoid use. We hypothesised that vitamin D supplementation would increase markers of bone formation and decrease markers of bone resorption in SLE subjects.</AbstractText><AbstractText>We studied 43 vitamin D-deficient SLE subjects who participated in a 12-week randomised controlled trial of 2000-4000 IU/day vitamin D supplementation versus placebo. Subjects had inactive SLE (SLE Disease Activity Index ≤4) and were taking <20 mg prednisone daily at baseline. We assayed baseline and week 12 serum 25-hydroxyvitamin D, N-terminal propeptide of type 1 collagen (<em>P1NP</em>) and C-telopeptide (CTX). We tested the effect of vitamin D versus placebo on change (Δ) in <em>P1NP</em> and ΔCTX in an intention-to-treat analysis. Secondary analyses evaluated whether vitamin D affected bone turnover among subjects achieving vitamin D repletion (≥30 ng/mL) or currently taking glucocorticoids.</AbstractText><AbstractText>28 subjects were randomised to vitamin D and 15 to placebo. Mean age was 39 years and 40% were using glucocorticoids at enrolment. Repletion was achieved by 46% in the vitamin D group versus none in the placebo group. Changes in bone turnover markers were not significantly different in the vitamin D group versus placebo group (median Δ<em>P1NP</em> -0.2 vitamin D group vs -1.1 placebo group (p=0.83); median ΔCTX +3.5 vitamin D group vs -37.0 placebo group (p=0.50)). The effect of vitamin D did not differ based on achieving vitamin D repletion or baseline glucocorticoid use.</AbstractText><AbstractText>Vitamin D supplementation did not affect the 12-week change in bone turnover markers among SLE subjects in this trial.</AbstractText>

<AbstractText>In rodents, Osteocalcin (OCN) stimulate insulin production and insulin sensitivity, both important factors during partial remission in humans with type 1 diabetes (T1D). However, decreased OCN has reported in both adult and pediatric T1D. This study aims at investigating bone turnover and partial remission in children and adolescents with recent onset T1D.</AbstractText><AbstractText>99 individuals (33% girls) were recruited within 3 months of T1D onset and examined three times, 6 months apart. Outcome variables were bone formation markers OCN and procollagen type-1 amino-terminal propeptide (<em>P1NP</em>) and the bone resorption marker C-terminal cross-linked telopeptide of type-1 collagen (CTX). Dependent variables included IDAA1c (surrogate marker of partial remission), total-body bone mineral density (BMD) and stimulated C-peptide as representative of endogenous insulin production.</AbstractText><AbstractText>OCN- and <em>P1NP</em> Z-scores were significantly decreased throughout the study, whereas CTX Z-scores were increased. None of the bone turnover markers changed significantly between visits. Total body BMD Z-score did not change during the study but was significantly higher than the reference population at visit 2 (P=0.035). There were no differences in the bone turnover markers for those in partial remission as defined by either C-peptide or IDAA1c at any visit. The individual change in CTX Z-score was negatively associated with the increase of IDAA1c (P=0.030) independent of C-peptide decline (P=0.034).</AbstractText><AbstractText>Bone turnover markers indicate increased bone resorption and decreased bone formation during the first year of T1D. The negative association between bone resorption and IDAA1c might represent compensatory mechanisms affecting insulin sensitivity. This article is protected by copyright. All rights reserved.</AbstractText>

Runx2 is an essential transcription factor for osteoblast differentiation. However, its functions after the commitment into osteoblasts are controversial and remain to be clarified. We generated enhanced green fluorescent protein (EGFP)-Cre transgenic mice driven by the 2.3-kb Col1a1 promoter, and Runx2 was deleted in osteoblasts and odontoblasts in Runx2^fl/flCre mice. The sutures and fontanelles were more widely opened in Runx2^fl/flCre newborns than in Runx2^fl/fl newborns. Runx2^fl/flCre mice exhibited dwarfism with shorter incisors and 37% had irregularly aligned incisors. The volume of trabecular bone in femurs and vertebrae and their bone mineral density (BMD), in addition to the cortical thickness and BMD were reduced in Runx2^fl/flCre mice compared with Runx2^fl/fl mice in both sexes. The bone formation of both trabecular and cortical bone, osteoblast number, osteoclast surface, osteoblast proliferation, and the serum levels of P1NP, TRAP5b, and CTX1 were reduced in Runx2^fl/flCre mice. The expression of major bone matrix protein genes, including Col1a1, Col1a2, Spp1, Ibsp, and Bglap&Bglap2, and of Tnfsf11 was lower in Runx2^fl/flCre mice than in Runx2^fl/fl mice. The expression of Runx2 target genes, including Ihh, Fgfr1, Fgfr2, Fgfr3, Tcf7, Wnt10b, Pth1r, Sp7, and Dlx5, was also reduced. Osteoblasts in Runx2^fl/fl mice were cuboidal and contained abundant Col1a1, whereas those in Runx2^fl/flCre mice were deflated and contained a small amount of Col1a1. Runx2 activated the reporter activity of the 2.3-kb Col1a1 promoter and bound the region around the Col1a1 transcription start site. The deletion of Runx2 by Cre-expressing adenovirus in Runx2^fl/fl primary osteoblasts impaired osteoblast differentiation and the expression of genes encoding major bone matrix proteins, and osteoclastogenesis was inhibited due to the reduction of Tnfsf11 expression in the osteoblasts. This study demonstrated that Runx2 is required for the expression of the major bone matrix protein genes and Tnfsf11 after commitment into osteoblasts in mice. This article is protected by copyright. All rights reserved.

Scaffold implantation for the repair of oral bone defects involves an interplay between the scaffold biomaterial and the microenvironment. However, previous studies on this subject have only considered the effects of the immune system and largely ignored those of the oral microbiota. Accordingly, in the present study, we prepared composite scaffolds comprising a three-dimensional poly(l-lactide-co-glycolide) matrix with a superparamagnetic iron oxide nanoparticle (SPION) coating and used a rat model to evaluate their palate-bone-regenerating effects and their interaction with the oral microbiota. It was found that the SPION coated scaffold induced better bone regeneration than that achieved by the controls. Furthermore, it significantly decreased the operational taxonomic units (OTU) numbers as determined by 16 s rRNA gene sequencing, and also resulted in decreased Chao and ACE alpha diversity indexes compared with those of the controls. However, it had no effect on beta diversity. SPION coated scaffolds caused a shift in oral bacterial composition characterized by a decrease in the Clostridium spp. population, and the dominant flora being Proteobacteria. Furthermore, SPION coated scaffolds upregulated the concentration of serum iron, hepcidin, and P1NP. Thus, SPION coated scaffolds enhanced bone regeneration, and this effect was partly related to alteration of the oral microbiota by the antibacterial effects of SPION. Our findings provide a better understanding of the role of oral microbiota in oral bone regeneration and how SPION coated scaffolds can be used to enhance it.

Keywords: 3D printing; Bone regeneration; In vivo; Oral microbiota; Superparamagnetic iron oxide nanoparticle.

This study aimed to explore the risk factors attributed to osteoporosis in newly type 2 diabetes mellitus (T2DM) patients. This study aimed to recruit 244 T2DM patients and 218 non-diabetic controls. We collected demographic characteristics, medical history, bone mineral density and biomarkers including bone specific alkaline phosphatase (BALP), osteocalcin, N-terminal peptide of type I procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRCAP-5b), β-Cross Laps of type I collagen-containing cross-linked C-telopeptide (β-CTX), 25-hydroxyvitamin D, parathyroid hormone were recorded or detected. Bone mineral density (BMD) was our primary outcome. Based on the result of BMD, we divided both the control group and T2DM group into three subgroups: normal bone mass, osteopenia and osteoporosis. In control group, we found age, sex, menopausal status, BMI, P1NP, BALP, TRACP-5b, osteocalcin, and corrected serum calcium are differential among three subgroups. In T2DM group, we found age, sex, menopausal status, drinking status, BMI, HbA1c, TRACP-5b and OC were differential among three subgroups. In T2DM and control groups, age, female, postmenopausal status, BALP, TRACP-5b and osteocalcin were positively correlated while BMI was negatively correlated with osteoporosis. In control group, β-CTX was positively correlated with osteoporosis. In T2DM group, HbA1c and corrected serum calcium concentration were positively correlated with osteoporosis. After further adjustment of age, BMI in male, TRACP-5b was positively correlated with the risk of osteoporosis in newly diagnosed T2DM. After adjusted of age, BMI and menopausal status in female, OC was positively correlated with the risk of osteoporosis in newly diagnosed T2DM and controls. In female T2DM, BALP and P1NP were positively correlated with the risk of osteoporosis. In conclusion, age, BMI and menopausal status are common risk factors for osteoporosis in diabetic and non-diabetic patients, however TRACP-5b, BALP and osteocalcin are special risk factors for osteoporosis in newly diagnosed T2DM patients but not non-diabetic patients, which may be applied to identify osteoporosis risk in T2DM patients, but this result needs to be proven with fracture data.

Keywords: TRACP-5b; bone specific alkaline phosphatase; osteocalcin; osteoporosis; risk assessment; type 2 diabetes mellitus.

Elagolix is a novel, oral gonadotropin-releasing hormone receptor antagonist indicated for the management of moderate to severe pain associated with endometriosis and heavy menstrual bleeding associated with uterine fibroids. Consistent with its mechanism of action, elagolix exhibited dose-dependent suppression of estradiol (E2) in clinical studies. A dose-response model that describes the relationship between elagolix dosages and average E2 levels was combined with a previously published quantitative systems pharmacology (QSP) model of calcium homeostasis to predict bone mineral density (BMD) changes during and following elagolix treatment. In the QSP model, changes in E2 levels were linked to downstream changes in markers of bone resorption (carboxyterminal cross-linked telopeptide of type 1 collagen [CTX]), formation (N-terminal propeptide of type 1 procollagen [P1NP]) and BMD. The BMD, CTX, and P1NP predictions by the QSP model were validated against observed data from four phase III clinical trials of elagolix in premenopausal women with endometriosis. BMD, CTX, and P1NP were successfully described by the QSP model, without any model fitting, suggesting that the model was validated for further predictions of elagolix effects on BMD. Simulations using the validated QSP model demonstrated that elagolix 150 mg once daily dosing for 24 months is predicted to result in -0.91% change from baseline in lumbar spine BMD. The QSP model simulation results were part of the totality of evidence to support the approved duration of therapy for elagolix 150 mg once daily in patients with endometriosis.

The pathogenesis for low-trauma wrist fractures in men is not fully understood. This study found that these men had evidence of significantly higher bone turnover compared with control subjects. Bone turnover markers were negative predictors of bone mineral density and were a predictor of fracture.

Introduction: Men with distal forearm fractures have reduced bone density, an increased risk of osteoporosis and of further fractures. The aim of this study was to investigate whether or not men with distal forearm fractures had evidence of altered bone turnover activity.

Methods: Fifty eight men with low-trauma distal forearm fracture and 58 age-matched healthy control subjects were recruited. All subjects underwent a DXA scan of the forearm, both hips, and lumbar spine, biochemical investigations, and health questionnaires. Measurements of beta crosslaps (βCTX), procollagen type I N-terminal propeptide (PINP), sclerostin, Dickkopf-1 (Dkk1), and fibroblast growth factor 23 (FGF 23) were made.

Results: Men with fracture had significantly higher PINP than controls at 39.2 ng/ml (SD 19.5) versus 33.4 ng/ml (SD13.1) (p<0.001). They also had significantly higher βCTX at 0.45 ng/ml (SD 0.21) versus 0.37 ng/ml (SD 0.17) (p= 0.037). Fracture subjects had significantly lower aBMD and PINP was a negative predictor of aBMD at the total hip and βCTX a negative predictor of forearm aBMD. Sclerostin was a positive predictor of aBMD at the lumbar spine and hip sites. Sex hormone binding globulin (SHBG) at 37nmol/L (SD 15.0) was lower in fracture cohort compared to 47.9 nmol/L (SD 19.2) (p=0.001) in control. Multiple regression revealed that the best model for prediction of fracture included SHBG, P1NP, and ultra-distal forearm aBMD. The likelihood of distal forearm fracture was decreased by 5.1% for each nmol/L increase in SHBH and by 1.4% for every mg/cm² increase in ultra-distal forearm aBMD, but increased by 6.1 % for every ng/ml increase in P1NP. Men in the highest quartile of PINP had a significantly greater likelihood of distal forearm fracture than those in the lowest quartile.

Conclusion: The fracture group had significantly higher PINP and βCTX compared with the control group, and these markers were negative predictors of aBMD at the total hip and forearm sites, respectively. Sclerostin was a positive predictor of the variance of spinal and hip aBMD. Likelihood of forearm fracture was best predicted by a combination of SHBG, PINP, and ultra-distal forearm aBMD. Findings of such cross-sectional data should be treated with caution, as longitudinal studies would be required to confirm or refute them.

Keywords: Bone turnover markers; Forearm fracture; Male; Osteoporosis.

BACKGROUND It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). MATERIAL AND METHODS We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. RESULTS During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. CONCLUSIONS Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation.

Improving patient health-related quality of life (HRQOL) and prevention of bone fracture are important components of the treatment of osteoporosis. Our aim in this study was to evaluate the effect of denosumab treatment in improving HRQOL among patients with osteoporosis. Our analysis was based on 332 patients with osteoporosis, followed for 24 months. All patients received denosumab (60 mg) subcutaneously every 6 months. Bone mineral density (BMD) was assessed at the distal radius, with serum concentration of calcium, phosphate, P1NP, and TRACP5b also measured. HRQOL assessment included pain (visual analogue scale [VAS]) and the EQ-5D questionnaire. A multivariate analysis was performed to identify the possible confounders associated with deterioration in the EQ-5D utility score in response to denosumab treatment. Denosumab treatment yielded a 3.4% increase in BMD at 24 months. Serum levels of TRACP5b and P1NP decreased significantly, from baseline, at 6 months, with no effect on calcium and phosphate levels. Pain VAS and EQ-5D utility score improved significantly, from baseline, at 6 months, with the EQ-5D utility score correlating with the BMD at all time points of measurement over the 24-month period of observation. Knee osteoarthritis and multiple comorbidities were significantly associated with a worse HRQOL in response to denosumab treatment. Denosumab treatment increased BMD, with improvements in BMD correlating with improved HRQOL, supporting a possible benefit of using denosumab for the treatment of osteoporosis. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

French maritime pine bark extract (FMPBE; Oligopin®), a dietary supplement, is rich in procyanidin. The objective of this study was to determine the effects of FMPBE on bone remodeling in postmenopausal osteopenic women. This randomized, double-blinded, placebo-controlled clinical trial was conducted on 40 postmenopausal osteopenic women. Individuals were randomly assigned to either FMPBE (250 mg/day, n = 21) or placebo (250-mg starch/day, n = 19) for 12 weeks. Biochemical indices, including bone remodeling marker, were assessed before and after the intervention. After the 12-week intervention, that is, FMPBE supplementation, a significant increase in bone alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) levels and a significant decrease in C-terminal telopeptide of type I collagen (CTx1) were observed. Compared with the control group, FMPBE supplementation resulted in a significant increase in P1NP (0.015), BAP levels (0.001), and BAP/CTx1 ratio (p = 0.001) and a significant decrease in CTx1 levels (0.006). FMPBE supplementation for 12 weeks in postmenopausal osteopenic women produced favorable effects on bone markers. Meanwhile, further research is needed to determine whether FMPBE supplements can be used as a preventive strategy for bone loss in postmenopausal osteopenic women.

The article presents the results of structural change and functional state of bone in patients with diabetes mellitus. Total of 235 patients aged 40 to 70 years, of these, 98 (41 men, 57 women) type 1 and 137 (52 men, 85 women) type 2 diabetes patients were included in the study. DM1 duration 16,6±0,6 years, BMI: 26,1±0,2 kg/m2 and DM2: 8,1±0,7 years, BMI: 30±0,4 kg/m2. Investigated the level of 25(OH)D, PTH, serum bone remodeling markers (ALP, PINP, b-CTx) and DXA. The results of the study demonstrated that the content of serum bone remodeling markers in patients with DM1 and DM2, in comparison to the control group, indicate pathological processes in bone remodeling with decrease bone formation marker PINP in patients with DM1 by 16%, with DM2 by 12% in comparison with the control and an increase bone resorption marker b-CTx by 32% with DM1 and in 25% patients with DM2, of whom of women were 1,5 times more than men. Patients with DM2 had lower b-CTx values and a relatively higher level of P1NP, which reflects a less pronounced change in bone turnover compared to patients with DM1, regardless of age and duration of disease. T-score BMD of L1-L4 area was reduced in 64 and 44% of patients with DM1 and DM2; T-score BMD of femoral neck area - in 41 and 36% of patients. These results suggest that bone disorders and related fractures, is a clinically significant and commonly underestimated problem in diabetes.