We examined the hypothesis that exaggerating unloading-induced bone loss using a combination of hindlimb suspension (HLS) and exogenous injections of receptor activator of nuclear factor kappa-B ligand (RANKL) also exaggeratesgastrocnemius and quadriceps muscle loss. Forty, male C57Bl/6J mice (16 weeks) were subjected to HLS or normal ambulation (ground control, GC) for 14 days. Mice received 3 intraperitoneal injections of either human recombinant soluble RANKL or PBS as control (n=10/group) at 24 hour intervals starting on Day 1 of HLS. GC + RANKL and HLS mice exhibited similar decreases in trabecular bone volume and density in both proximal tibias and distal femurs. However, RANKL affected trabecular number, separation, and connectivity density, while HLS decreased trabecular thickness. The combination of RANKL and HLS exacerbated these changes. Similarly,GC + RANKL and HLS mice saw comparable decreases in cortical bone volume, thickness, and strength in femur midshafts, and combination treatment exacerbated these changes. Plasma concentrations of P1NP were increased in both groups receiving RANKL, while CTX concentrations were unchanged.HLS decreased gastrocnemius weight and was associated with a reduction in global protein synthesis, and no change in proteasome activity. This change was correlated with a decrease in S6K1 and S6 phosphorylation, but no change in 4E-BP1 phosphorylation. Injection of RANKL did not alter gastrocnemius or quadriceps muscle protein metabolism in GC or HLS mice.Our results suggest that injection of soluble RANKL exacerbates unloading-induced bone loss, but not unloading-induced gastrocnemius or quadriceps muscle loss. This article is protected by copyright. All rights reserved.

Keywords: Bone μCT; Bone-muscle interactions; Osteopenia; Sarcopenia; disuse; unloading.

Aims: Whey protein may improve bone turnover and have anti-osteoporotic effects. The aim of the present randomized, controlled, cross-over trial was to evaluate the effects of a whey protein pre-meal on bone turnover in people with type 2 diabetes and controls.

Methods: Two groups, matched on sex, age, and body mass index, comprising 12 participants with and 12 participants without type 2 diabetes were randomly given a pre-meal of whey protein (20g) or water, which was consumed 15 min before a fat-rich meal or a fat-rich meal supplemented with 20g whey protein. During a 360-min period, postprandial responses in bone turnover were examined.

Results: Osteocalcin, P-procollagen type 1 amino terminal propeptide (P1NP), C-terminal cross-linked telopeptide of type-I collagen (CTX), and parathyroid hormone (PTH) were lower at baseline and PTH, osteocalcin, and P1NP were lower during the entire postprandial phase in participants with type 2 diabetes than in participants without type 2 diabetes. We observed similar postprandial responses in bone turnover markers between persons with and without type 2 diabetes. We observed no effect of the whey protein or the water pre-meal on bone turnover markers. The changes were unrelated to secretion of hormones of the gut-bone axis.

Conclusion: Osteocalcin, P1NP, CTX, and PTH all decreased following meal ingestion. We observed no convincing effect of a whey protein pre-meal on bone turnover. However, these results confirm that people with type 2 diabetes have low bone turnover and that the decreased bone formation markers are also extend into the postprandial responses.

Keywords: Bone turnover; gastro-intestinal hormones; meal; type 2 diabetes.

BACKGROUND

Clinicians may use several biochemical markers of bone turnover to assess or guide the care of patients with chronic kidney disease (CKD). The aims of this study are to describe changes and correlations of markers of bone remodeling in patients with different stages of CKD.

METHODS

A total of 317 Chinese patients with advanced CKD (stage 3-5) were enrolled. We measured serum levels of intact-parathyroid hormone (iPTH), N-terminal midfragment (N-MID) osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP), β-isomerized C-terminal telopeptide (β-CTx), total alkaline phosphatase (ALP), and 25-hydroxyvitamin D (25[OH]D).

RESULTS

Levels of iPTH, N-MID osteocalcin, P1NP, and β-CTx and serum phosphorus were significantly different among patients with different stages of CKD. Serum levels of ALP and 25(OH)D were higher in hemodialysis (HD) patients than in peritoneal dialysis (PD) patients. Levels of ALP, osteocalcin, and P1NP were significantly higher in dialysis patients than in non-dialysis patients. Correlations between the levels of iPTH, ALP, N-MID os- teocalcin, P1NP, and β-CTx were statistically significant but weak. There was no correlation between 25(OH)D and iPTH or ALP.

CONCLUSIONS

Our results suggest that measurement of N-MID osteocalcin, P1NP, β-CTx, and iPTH may be useful for assessment of CKD-mineral bone disorder (MBD) in patients with CKD.

Introduction: We aimed to compare the efficacy after switching from either bisphosphonates (BPs) or non-BPs (NBPs) to combination therapies of denosumab (DMAb) or zoledronic acid (Zol) with eldecalcitol (ELD) in bone mineral density (BMD) and bone metabolism and investigate the prognostic and risk factors of side effects of this therapy.

Materials and methods: One-hundred forty-eight patients with postmenopausal osteoporosis were recruited; their therapy was switched from BPs or NBPs to Zol or DMAb plus ELD (BP-Zol: 43, NBP-Zol: 32, BP-DMAb: 35, and NBP-DMAb: 38). Longitudinal changes in bone metabolic markers (P1NP and TRACP-5b) and BMD were evaluated.

Results: In the BP-Zol group, P1NP did not change after 6 months and increased by 38.9% after 12 months. TRACP-5b decreased 15.8% after 6 months, but came back to baseline values 12 months after administration. In the rest of the groups, the bone metabolic markers remained suppressed after 6 and 12 months. Compared with baseline, all groups showed increase in BMD after 6 and 12 months. Bone metabolic markers at baseline were correlated with %change in lumbar spine BMD from baseline to 12 months. P1NP and 25-hydroxy vitamin D levels at baseline were identified as potential predictors of development of acute-phase reactions.

Conclusions: The combination therapy of Zol or DMAb and ELD may increase BMD at 12 months after the first administration in Japanese patients with postmenopausal osteoporosis, regardless of BPs pretreatment. Bone metabolic markers at baseline may be useful predictors for reaction to the therapy and side effects caused by these combination therapies in postmenopausal osteoporosis.

Keywords: Bone metabolic marker; Denosumab; Eldecalcitol; Postmenopausal osteoporosis; Zoledronic acid.

Introduction: Exercise acutely alters markers of bone resorption and formation. As risk of fracture is increased in patients with type 1 diabetes, understanding if exercise-induced bone turnover is affected within this population is prudent. We assessed bone turnover responses to acute exercise in individuals with long-duration type 1 diabetes and matched controls.

Research design and methods: Participants with type 1 diabetes (n=15; age: 38.7±13.3; glycosylated hemoglobin: 60.5±6.7 mmol/mol; diabetes duration: 19.3±11.4 years) and age-matched, fitness-matched, and body mass index-matched controls (n=15) completed 45 min of incline walking (60% peak oxygen uptake). Blood samples were collected at baseline and immediately, 30 min, and 60 min postexercise. Markers of bone resorption (β-C-terminal cross-linked telopeptide of type 1 collagen, β-CTx) and formation (procollagen type-1 amino-terminal propeptide, P1NP), parathyroid hormone (PTH), phosphate, and calcium (albumin-adjusted and ionized) were measured. Data (mean±SD) were analyzed by a mixed-model analysis of variance.

Results: Baseline concentrations of P1NP and β-CTx were comparable between participants with type 1 diabetes and controls. P1NP did not change with exercise (p=0.20) but β-CTx decreased (p<0.001) in both groups, but less so in participants with type 1 diabetes compared with controls (-9.2±3.7%; p=0.02). PTH and phosphate increased immediately postexercise in both groups; only PTH was raised at 30 min postexercise (p<0.001), with no between-group differences (p>0.39). Participants with type 1 diabetes had reduced albumin and ionized calcium at all sample points (p<0.01).

Conclusions: Following exercise, participants with type 1 diabetes displayed similar time-course changes in markers of bone formation and associated metabolites, but an attenuated suppression in bone resorption. The reduced albumin and ionized calcium may have implications for future bone health. Further investigation of the interactions between type 1 diabetes, differing modalities and intensities of exercise, and bone health is warranted.

Keywords: bone diseases; diabetes mellitus; exercise; metabolic; type 1.

Introduction: Accelerated bone loss and osteoporosis are multifactorial comorbidities related to HIV and its treatments; however, their mechanisms remain elusive. Identifying HIV treatments that are differentially linked to osteoporosis risk, and clinical factors associated with HIV-related osteoporosis may enable optimizing anti-retroviral treatment (ART) and anti-osteoporosis therapy in preventing or treating this debilitating complication. This study aims to evaluate the dynamics of bone turnover markers after initiation of two commonly used antiretroviral regimens.

Methods: A prospective matched cohort study. Thirty treatment-naïve male patients (mean age 40 ± 10y) who initiated treatment with truvada (tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)) + raltegravir or TDF/FTC + efavirenz were included in the study. Control group included 15 treatment-naive HIV patients. Serum morning fasting level of P1NP and CTX were measured 0, 1, 6, and 12 months after treatment initiation in the two study groups, and at 0, 6 and 12 months in the control group.

Results: In both treatment groups, but not in the control group, both markers increased significantly over time with no difference in BTM between patients treated with raltegravir or efavirenz. Levels of P1NP were statistically higher at 6 and 12 months after treatment initiation in both treatment groups compared to the controls, while CTX during treatment increased in both treatment groups but was significantly higher only in the raltegravir treatment group after 12 months. The ratio of area under the curve of P1NP/CTX correlated with CD4 increment.

Conclusions: Treatment initiation with raltegravir or efavirenz combined with TDF/FTC is associated with increased bone turnover. Thus, therapy that optimize bone turnover is needed to reduce bone loss at this vulnerable period and improve long-term bone health.

Keywords: CTX; Efavirenz; HIV; P1NP; Raltegravir; Tenofovir/emtricitabine.

Context: Animal data and cross-sectional human studies have established that chronic hyponatraemia predisposes to osteoporosis; the effects of acute hyponatraemia on bone turnover have not been determined. Our objective was to test the hypothesis that acute hyponatraemia leads to dynamic effects on bone turnover.

Design: A prospective observational pilot study.

Methods: Bone turnover markers [C-terminal crosslinking telopeptide of type 1 collagen (CTX-1), N-propeptide of type 1 collagen (P1NP) and osteocalcin] were measured prospectively over one week in 22 eunatraemic patients with subarachnoid haemorrhage. Patients treated with glucocorticoids were excluded.

Results: Eight patients developed acute hyponatraemia, median nadir plasma sodium concentration 131 mmol/L (IQR 128-132), and 14 remained eunatraemic, nadir plasma sodium concentration 136 mmol/L (IQR 133-137). Significant main effects of hyponatraemia were found for P1NP (p=0.02) and P1NP:CTX-1 ratio (p=0.02), both fell in patients with acute hyponatraemia, with significant interaction between hyponatraemia and time from baseline for P1NP (p=0.02). Significant main effects of time from baseline (p<0.001) but not hyponatraemia (p=0.07) were found for osteocalcin. For CTX-1, significant main effects of time from baseline (p=0.001) but not hyponatraemia (p=0.65) were found. There was a positive correlation between change in P1NP:CTX-1 ratio and nadir plasma sodium concentration, r=+0.43, p=0.04. Median serum cortisol (measured on day 1, 3 and 7) was higher in the hyponatraemia group than in those who remained euntraemic, 545 nmol/L (IQR 373-778) versus 444 nmol/L (IQR 379-542) p=0.03.

Conclusion: These data suggest that acute mild hyponatraemia is associated with a reduction in bone formation activity.

Keywords: Hyponatraemia; bone; osteoporosis.

Chronic cadmium (Cd) toxicity is a significant health concern, and the mechanism of long-term low-dose Cd exposure on bone has not been fully elucidated yet. This study aimed to assess the association between long-term environmental Cd exposure and bone remodeling in women who aged over 50. A total of 278 non-smoking subjects from Cd-polluted group (n = 191) and non-Cd polluted group (n = 87) were investigated. Bone mineral density (BMD), the levels of three bone turnover markers (BTMs), including total procollagen type 1 amino-terminal propeptide (P1NP), collagen type 1 cross-linked C-telopeptide (β-CTX), bone-specific alkaline phosphatase (BALP), together with serum soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin (OPG) were determined. Early markers of renal dysfunction were measured as well. Urinary Cd concentrations ranged from 0.41 to 87.31 μg/g creatinine, with a median of 4.91 μg/g creatinine. Age, BMD, T-score, and prevalence of osteoporosis showed no statistical differences among the quartiles of urinary Cd concentrations, while serum levels of P1NP, β-CTX, and OPG were higher in the upper quartiles. Multivariate linear regression models indicated significantly positive associations of urinary Cd concentration with serum levels of P1NP, β-CTX, BALP, sRANKL, and OPG. A ridge regression analysis with T-score and the three BTMs, sRANKL, and OPG, adjusted for age and body mass index (BMI), indicated that except for age and Cd exposure, β-CTX was a predictor of T-score. These findings demonstrated that Cd may directly accelerate bone remodeling. Serum β-CTX might be an appropriate biochemical marker for evaluating and monitoring Cd-related bone loss. Capsule: Cadmium (Cd) may directly accelerate bone remodeling and serum β-CTX is a valuable biochemical marker for evaluating Cd-related bone loss.

Keywords: Bone remodeling; Cadmium exposure; Renal function; Serum β-CTX.

Objective: This study is aimed at analyzing the association between bone metabolism indices and diabetic retinopathy (DR) in elderly patients with type 2 diabetes mellitus.

Methods: Data of 352 men and 284 postmenopausal women, aged more than 50 years, with type 2 diabetes mellitus were retrospectively analyzed. Patients were divided into three groups based on the degree of DR: nondiabetic retinopathy (NDR) group, background diabetic retinopathy (BDR) group, and proliferative diabetic retinopathy (PDR) group.

Results: (1) The diabetic duration and urinary albumin to creatinine ratio (UACR) were significantly higher in the PDR and BDR groups than in the NDR group (P < 0.05). The level of beta-C-terminal telopeptide (β-CTX) in male patients was lower in the PDR and BDR groups than in the NDR group (P < 0.05). In addition, the level of procollagen 1 intact N-terminal (P1NP) in female patients was higher in the PDR and BDR groups than in the NDR group (P < 0.05). (2) For men and postmenopausal women, the proportion of vitamin deficiency was higher in the PDR and BDR groups than in the NDR group (P < 0.05). (3) The logistic regression analysis in men and postmenopausal women showed that the diabetic duration and lower levels of UACR and 25(OH)D were independent risk factors for DR (P < 0.05). (4) The diabetic duration was also an independent risk factor for PDR (P < 0.05); however, no independent correlation was found between the level of 25(OH)D and PDR (P > 0.05).

Conclusions: A close association was observed between 25(OH)D level and DR in the elderly male patients and postmenopausal women with type 2 diabetes mellitus. P1NP and β-CTX levels might be closely related to DR in elderly male patients and postmenopausal women with type 2 diabetes mellitus.

Objective: Diabetes is a growing global public health concern with many significant disease complications. Multiple studies show that bone turnover markers (BTMs) are decreased in diabetes patients, indicating impaired bone metabolism in diabetes patients. A recent study also showed that in diabetes patients, BTMs are correlated with urine albumin to creatinine ratio, an indicator of nephropathy. However, whether BTMs are correlated with estimated glomerular filtration rate (eGFR) in diabetes remains unknown. This retrospective study accessed correlations between serum BTMs and eGFR in Chinese patients with diabetes and compare levels of BTMs and eGFR between diabetic patients and healthy individuals.

Methods: This study analyzed data from 221 diabetic patients (include type1 and type 2 diabetes) and 155 healthy individuals. Serum BTM levels and eGFR were compared between diabetic patients and healthy individuals. Pearson correlation analysis was used to assess correlations between BTMs and eGFR. Multiple logistic regression analysis adjusted for gender and age was performed to measure odd ratio (OR) and 95% confidence interval (95% CI) of BTMs on diabetes.

Results: Patients with diabetes had significant lower 25-hydroxyvitamin D (25(OH)D) levels (15.07 ± 6.20 ng/mL) than healthy group (17.89 ± 6.41 ng/mL) (P < 0.05). For patients with diabetes, eGFR was negatively correlated with osteocalcin (OC) (r = -0.434, P < 0.05), procollagen type 1 intact N-terminal propeptide (P1NP) (r = -0.350, P < 0.05), and β-carboxy-terminal cross-linking telopeptide of type I collagen (β-CTX) (r = -0.179, P < 0.05) levels. For healthy people, eGFR was negatively correlated with 25(OH)D (r = -0.290, P < 0.05) levels. Multiple logistic regression analysis adjusted for age and gender (mean age of diabetes was 64.9 years and the percentage of female was 66.9%, mean age of healthy people was 48.4 years and the percentage of female was 37.4%) showed that 25(OH)D (OR = 0.909, 95%CI = 0.862 - 0.959, P < 0.05) was protective factors for diabetes.

Conclusions: In the stage of diabetic nephropathy, bone turnover may accelerate. It is important to detect BTMs in the stage of diabetic nephropathy.

Study design: Prospective longitudinal study.

Objective: The aim of this study was to evaluate temporal changes of bone turnover markers (BTMs) after lumbar spinal fusion in patients without osteoporosis.

Summary of background data: Radiological studies are the standard method to monitor bony fusion, but they do not allow a timely assessment of bone healing. BTMs react rapidly to changes in bone metabolism during fusion process and could be an additional tool to monitor this process.

Methods: A total of 78 non-osteoporosis patients who had undergone one- or two-level transforaminal lumbar interbody fusion were included. Fusion status was assessed using CT sagittal and coronal images. Serum levels of bone specific alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) and osteocalcin (OC) were measured to assess bone formation, and tartrate-resistant acid phosphatase 5b (TRACP-5b) was measured to assess bone resorption. Serum samples were obtained before surgery and at 1, 2, 4, 8, 13, 26, 39, and 52 weeks after surgery.

Results: A solid fusion was achieved in 71 of 78 patients (91%), and 7 patients resulted in pseudarthrosis. In the fusion group, the level of all BTMs once decreased at 1 postoperative week. Then, BAP and P1NP reached a peak at 4 weeks after surgery, and TRACP-5b and OC peaked at 8 weeks. Thereafter, the level of P1NP and TRACP-5b gradually got closer to the baseline over a year, and BAP kept high until 52 postoperative weeks. In the pseudarthrosis group, peak level of BTMs were significantly higher and the increased level of BAP and P1NP was kept until 52 weeks.

Conclusions: The current study demonstrated dynamics of BTMs after lumbar spinal fusion in patients without osteoporosis. These normal population data contribute as a baseline to evaluate the effect of osteogenic agents on bone metabolism after spinal fusion.Level of Evidence: 2.

Fosdagrocorat (PF-04171327), a dissociated agonist of the glucocorticoid receptor, has potent anti-inflammatory activity in patients with rheumatoid arthritis with reduced adverse effects on bone health. To identify fosdagrocorat doses with bone formation marker changes similar to prednisone 5 mg, we characterized treatment-related changes in amino-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC) with fosdagrocorat (1, 5, 10, or 15 mg) and prednisone (5 or 10 mg) in a phase II randomized trial (N = 323). The time course of markers utilized a mixed-effects longitudinal kinetic-pharmacodynamic model. Median predicted changes from baseline at week 8 with fosdagrocorat 5, 10, and 15 mg were -18, -22, and -22% (P1NP), and -7, -13, and -17% (OC), respectively. Changes with prednisone 5 and 10 mg were -15% and -18% (P1NP) and -10% and -17% (OC). The probability of fosdagrocorat doses up to 15 mg being noninferior to prednisone 5 mg for P1NP and OC changes was >90%.

Nutritional factors have been associated with osteoporosis and fractures. The intake of coffee may increase the risk of fracture whereas the intake of black and green tea is associated with its reduction. Recently, consumption of yerba mate was associated with increased bone mineral density in postmenopausal women. Nonetheless, its influence on fracture is not known. The aim of this study was to evaluate the effect of yerba mate tea intake on fractures, bone markers, calcium homeostasis, and oxidative stress in postmenopausal women. A case-control study was carried out in South Brazil, 46 women with fractures and 49 controls completed the study. There was no significant difference between the frequency of fractures in women who drank mate tea and women who did not (48.3% vs. 48.5%, p = .99). Moreover, there was no significant difference concerning the serum levels of total calcium, phosphorus, PTH, vitamin D, P1NP, and CTX in the subjects with the history of yerba mate use when compared to controls. Higher serum levels of NOx were found in women who drank the yerba mate infusion. In conclusion, the yerba mate intake is not associated with fracture, and it appears to have a neutral effect on the bone metabolism.

Background: Animal studies suggest that undercarboxylated osteocalcin may improve insulin sensitivity via its effect on testicular testosterone production. Human studies have been conflicting. Men undergoing androgen deprivation therapy (ADT) for prostate cancer experience profound hypogonadism resulting in increased insulin resistance. In a randomised controlled trial (RCT) of zoledronic acid versus placebo in men commencing extended-duration ADT, we aimed to examine the effects on fat mass and glucose metabolism. We hypothesised that zoledronic acid, which reduces osteocalcin concentrations, would worsen ADT-induced insulin resistance.

Methods: This was a prespecified secondary analysis of an RCT designed to evaluate the effects of zoledronic acid on bone microarchitecture in 76 men with non-metastatic prostate cancer undergoing curative radiotherapy combined with adjuvant ADT (n = 39 randomised to a single dose of zoledronic acid 5 mg, n = 37 randomised to matching placebo). Oral glucose tolerance tests to determine Matsuda Index were performed at 0, 3, 12 and 24 months. Using a mixed model, mean adjusted differences [MAD (95% confidence interval)] between the groups over time are reported.

Results: Over 24 months of ADT, fat mass increased and lean mass decreased for both groups, with no significant between group difference [MAD 401 g (-1307; 2103), p = 0.23 and -184 g (-1325; 955), p = 0.36 respectively]. Bone remodelling markers C-telopeptide [MAD -176 ng/l (-275; -76), p < 0.001 and P1NP -18 mg/l (-32; -5), p < 0.001] as a surrogate for osteocalcin, remained significantly lower in the zoledronic acid group, compared with placebo. There was no mean adjusted between-group difference for homeostatic model assessment 2 insulin resistance (HOMA2-IR) [-0.2 (-0.6; 0.2), p = 0.45], HbA1c [-0.1% (-0.3; 0.1), p = 0.64] or Matsuda Index [0.8 (-1.1; 2.7), p = 0.38]. The Matsuda Index decreased in both groups consistent with worsening insulin resistance with ADT.

Conclusion: A single dose of zoledronic acid does not appear to influence glucose metabolism in men newly commencing ADT. Further study to evaluate the endocrine relationship between bisphosphonates, bone and glucose metabolism is required.

Trial registration number: [ClinicalTrials.gov identifier: NCT01006395].

Keywords: androgen deprivation; bisphosphonates; diabetes; insulin resistance; prostate cancer.

Objective: The characteristics of bone metabolism in T2DM are still controversial. This study aims to recognize bone turnover features in patients with newly diagnosed T2DM who have never been treated with anti-diabetic drugs and further explore the possible factors contributing to their impaired bone turnover.

Materials and methods: An analytic sample of 88 patients with newly diagnosed T2DM and 152 non-diabetic control individuals were studied. All the participants were postmenopausal women. Demographics variables and clinical history were recorded. We measured lipid profile, glucose metabolism, bone turnover markers indices as well as their related hormones, serum calcium and phosphorus. Bone mineral density was detected by dual-energy X-ray absorptiometry. We compared the differences in bone turnover markers and their regulating hormones between two groups and further analyzed the factors related to bone turnover in T2DM.

Results: Compared to the control group, patients with T2DM had a higher level of bone alkaline phosphatase (BALP), lower levels of procollagen type I intact N-terminal (P1NP), osteocalcin (OC) and parathyroid hormone (PTH). Multiple linear regression analysis showed that in patients with T2DM, HbA1c was negatively correlated to P1NP and OC. For patients without diabetes, HbA1c was negatively related to BALP and OC.

Conclusions: Patients with newly diagnosed T2DM may have impaired osteoblastic maturation and bone formation, which may be mainly attributed by hyperglycemia.

Keywords: bone formation; bone metabolism; fracture; postmenopausal women; type 2 diabetes.

The preventive and therapeutic mechanisms of CDBE on osteoporosis were studied by observing the serum bone-related biochemical indicators, bone trabecular micro-structure and intestinal flora in ovariectomized osteoporosis model mice, in order to provide a scientific theoretical basis for the further study on the effect of CDBE on osteoporosis, and the prevention and treatment of osteoporosis with clinical traditional Chinese medicines. The components in CDBE were detected by UHPLC-MS. A mouse osteoporosis model was established by the bilateral ovariectomy in female ICR mice. The biochemical indicators related to osteoporosis were detected, the right proximal tibia was scanned by Micro-CT, the intestinal microflora in the colon contents were examined, and the changes of microflora were taken as the main target to evaluate the effect of CDBE on the intestinal microflora in the model mice. A total of 16 compounds were obtained by the combined application of UHPLC-MS. CDBE could significantly increase the contents of E2, Ca²⁺ , CT, HyP, OCN, FOXP3, P1NP and CTX-II, in the model mice. CDBE could significantly improve the trabecular micro-structure, Tb.N, Tb.Sp, SMI and Conn.D. CDBE could make the intestinal flora of osteoporosis model mice tend to healthy mice in species and quantity. CDBE can improve the symptoms of postmenopausal osteoporosis in mice, with a positive effect on the intestinal flora of postmenopausal mice. Its mechanism of regulating the symptoms of osteoporosis may be related to the regulation of bone-related biochemical indicators in the serum of mice. PRACTICAL APPLICATIONS: This research has a positive impact on the development of functional food with anti-osteoporosis in the future.

Keywords: compound deer bone extract; intestinal flora; osteoporosis.

Background: Bone is thought to be the reservoir of the human lead burden, and vitamin D is associated with bone turnover. We aimed to explore whether exposure to lower 25-hydroxy vitamin D (25(OH)D) levels was associated with higher blood lead levels (BLLs) by increasing the bone turnover rate in individuals with type 2 diabetes.

Methods: A total of 4103 type 2 diabetic men and postmenopausal women in Shanghai, China, were enrolled in 2018. Their 25(OH)D, β-C-terminal telopeptide (β-CTX), N-MID osteocalcin and procollagen type 1 N-peptide (P1NP) levels were detected. Their BLLs were determined by atomic absorption spectrometry. Mediation analyses were performed to identify the possible role that bone turnover played in the underlying mechanisms.

Results: In both the men and postmenopausal women, all three bone turnover markers were inversely associated with 25(OH)D and positively associated with the BLL (all P<0.01) after adjusting for age, current smoking habits, metabolic parameters, duration of diabetes, vitamin D intake, and use of anti-osteoporosis medication. In the mediation analyses, none of the direct associations between 25(OH)D and BLL was significant for the three bone turnover markers, but all three bone turnover markers were found to be significant mediators of the indirect associations between 25(OH)D and BLL.

Conclusion: The association between vitamin D and BLL was fully mediated by bone turnover markers in type 2 diabetic patients (mediation effect). This finding suggested that vitamin D may protect against blood lead exposure from the bone reservoir by decreasing bone turnover in individuals with type 2 diabetes.

Background: Previous studies have proposed that osteogenic and apoptotic processes of valve interstitial cells contribute to the mineralization and then calcification of the aortic valve. Osteoblast-like cells subsequently mediate calcification of the aortic valve as part of a highly regulated process analogous to skeletal bone formation. The objective of this study was to evaluate the pathogenesis of the sclerotic/calcific changes in the aortic valve from histological and biological findings, and investigate the role of osteoblasts in the calcified pathway of aortic stenosis.

Methods: Preoperative echocardiography in 550 consecutive patients with osteoporotic hip fracture were retrospectively examined (475 females, mean 25th-75th, 89 [85-93] years). One hundred sixteen patients were under medical treatment with anti-osteoporosis drugs. We evaluated the prevalence and degree of degenerative changes in the aortic valve and examined the associations of bone turnover biomarkers N-terminal pro-peptide of type 1 collagen (P1NP) and serum tartrate-resistant acid phosphatase (TRACP-5b) with degenerative calcific changes in the aortic valve.

Results: Of 550 patients, 112 patients (20.9%) showed no leaflet calcification; 296 (53.8%), 1 leaflet calcification; and 142 (25.8%), 2 ≥ leaflets calcification. Significant (peak velocity ≥ 3.0m/s) Aortic stenosis was found in 43 patients (7.8%). In patients who were not taking anti-osteoporotic drugs, P1NP was higher in the 2 ≥ leaflets calcification group than in the other groups (p < 0.01). TRACP-5b was not significantly different among the three groups (p = 0.15).

Conclusions: Degenerative changes in the aortic valve were related to bone biomarker activation in osteoporotic hip fracture patients.

Keywords: Degenerative aortic valve disease; Osteoblast; Osteoporosis.

Background: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted in response to food ingestion, and they have been suggested to regulate bone turnover. In humans, exogenous GIP and GLP-2 acutely inhibit bone resorption as measured by circulating levels of carboxy-terminal type 1 collagen crosslinks (CTX).

Objective: The objective was to study the individual and combined acute effects of GIP and GLP-2 on bone turnover in postmenopausal women during nighttime - a period of increased bone resorption.

Methods: Using a randomized, placebo-controlled, double-blinded, crossover design, each participant (n = 9) received on four separate study days: GIP, GLP-2, GIP+GLP-2, and placebo (saline) as subcutaneous injections at bedtime. Main outcomes were levels of CTX and procollagen type 1 N-terminal propeptide (P1NP).

Results: Compared with placebo, GIP and GLP-2 alone significantly inhibited bone resorption (measured by CTX). GIP rapidly reduced CTX levels in the period from 45 to 120 minutes after injection, while GLP-2 had a more delayed effect with reduced CTX levels in the period from 120 to 240 minutes after injection. Combining GIP and GLP-2 showed complementary effects resulting in a sustained inhibition of CTX with reduced levels from 45 to 240 minutes after injection. Furthermore, GIP acutely increased bone formation (measured by P1NP).

Conclusion: Both GIP and GLP-2 reduced CTX during the night and had complementary effects when combined.

Keywords: CTX; Glucose-dependent insulinotropic polypeptide (GIP); P1NP; bone turnover; glucagon-like peptide-2 (GLP-2); gut-bone axis.

Aims: To explore the relationships of procollagen type 1 N-terminal propeptide (P1NP) and β cross-linked C-telopeptide of type 1 collagen (β-CTX) with bone mineral density (BMD) in postmenopausal women.

Methods: All postmenopausal women were selected from a community-based case-control study. The anteroposterior L1-L4 and left proximal femur BMD were measured. P1NP and β-CTX were also collected and tested. The main correlation analysis was applied to explore the relationships of BMD, P1NP, and β-CTX.

Results: The total 1055 postmenopausal women were enrolled. The BMD at all sites kept a decrease continually with age (P < 0.01). In addition, the level of β-CTX increased significantly from 45 to 50 years old and remained at a high level in the later stage, while the level of P1NP changed little or even decreased with age. Logistic regression model showed that β-CTX has better ability to predict BMD than P1NP, as demonstrated by an area under the curve (AUC) of 0.63.

Conclusion: P1NP and β-CTX are important markers to monitor bone metabolism. This trial is registered with ChiCTR-SOC-17013090. The date of registration is Oct. 23, 2017.

Objective: We evaluated longitudinal trends and associations between bone mass, bone turnover and inflammatory markers among South African children living with HIV (CLHIV) and controls.

Design: We previously reported decreased bone mass among CLHIV independent of marked inflammation and increased bone turnover. The goal of this study was to evaluate longitudinal changes in bone mass, bone turnover and inflammation over two years.

Methods: Longitudinal analyses were conducted among 220 CLHIV and 220 controls. Anthropometric measurements, physical activity, antiretroviral regimen, virologic and immunologic status, whole body (WB) and lumbar spine (LS) bone mineral content (BMC) and bone mineral density (BMD) were collected (enrollment, 12 and 24 months). Bone turnover markers including C-telopeptide of type I collagen (CTx) and procollagen type I N-terminal propeptide (P1NP) and inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble CD14 and high-sensitivity C-reactive protein (hsCRP) were collected at enrollment and 24 months.

Results: Compared with controls, CLHIV had significantly lower mean WB-BMC, WB-BMD, WB-BMC Z-scores, LS-BMC and LS-BMD as well as lower bone formation (P1NP) and resorption (CTx), and higher hsCRP and soluble CD14 over 24 months. CLHIV on efavirenz (EFV) had consistently lower TNF-alpha and IL-6 compared with those on ritonavir-boosted lopinavir (LPV/r) at all time points.

Conclusions: Over two years of follow-up, South African CLHIV had persistently lower bone mass, bone turnover, and macrophage activation. Lower bone mass and higher pro-inflammatory cytokine profiles were consistently observed among those on LPV/r-based compared to EFV-based regimens.

Two cases of advanced alkaptonuria (AKU) with co-existing osteoporosis are described. Case 1 developed multiple non-vertebral fragility fractures, while Case 2 developed vertebral fragility fractures, both refractory to bisphosphonates. Difficulties in diagnosing osteoporosis in AKU complicated by extensive calcifying and ossifying spondylosis are discussed. Both patients continued to fracture despite nitisinone therapy for metabolic control of AKU, as well as bisphosphonate antiresorptive therapy for osteoporosis. Subsequently the patients were treated with teriparatide 20 μg subcutaneous injections daily for two years, leading to reduction in fractures soon after commencing therapy in both cases. Markers of bone remodelling P1NP and CTX were stimulated. No complications due hypercalcaemia or calcification were encountered in either case. We conclude that teriparatide is an effective adjunct in the treatment of AKU when bisphosphonates prove ineffective.

Keywords: Alkaptonuria; Bisphosphonates; CTX; CTX, C terminal telopeptide; CtBMD; CtBMD, cortical bone mineral density; DEXA; DEXA, dual-energy X-ray absorptiometry; Fractures; Homogentisic acid; Nitisinone; Ochronosis; Osteoporosis; P1NP; P1NP, procollagen type 1 N-terminal propeptide; PTH; PTH, parathryoid hormone; Teriparatide.

Purpose: The research aimed to compare the therapeutic effect of teriparatide (TPTD) and zoledronic acid (ZOL) therapy on bone formation and spinal fusion in patients with osteoporosis (OP) who underwent transforaminal lumbar interbody fusion (TLIF).

Methods: On the basis of different anti-OP treatment options, the TPTD group was treated daily with TPTD (20 μg. ih. qd) for at least 6 months, while the ZOL group was treated with a single dose of ZOL (5 mg. ivgtt. st) postoperatively. The visual analogue scale (VAS), Oswestry Disability Index (ODI), bone mineral density (BMD), and concentration of bone turnover markers before, 6, and 12 months after surgery were evaluated. X-ray and three-dimensional computed tomography scans were performed at 6 and 12 months postoperatively to assess interbody fusion.

Results: The number of patients in the TPTD and ZOL groups was 29 and 38 patients, respectively. The VAS and ODI scores in both groups were significantly reduced at 6 and 12 months after TLIF. Compared with that of baseline, the lumbar spine BMD of TPTD patients increased significantly from 0.716±0.137 g/cm² to 0.745±0.124 g/cm² and 0.795±0.123 g/cm² at 6 and 12 months, respectively, and was significantly higher than that of the ZOL group at 12 months (0.720±0.128 g/cm²). The bone formation marker, P1NP, in the TPTD group increased significantly (145.48±66.64 ng/mL and 119.55±88.27 ng/mL) compared with baseline (44.67±25.15 ng/mL) and in the ZOL group (28.82±19.76 ng/mL and 29.94±20.67 ng/mL) at 6 and 12 months, respectively. The fusion rates in the TPTD and ZOL groups were 57% and 45% at 6 months, without statistical significance. However, TPTD had a more statistically significant positive influence on fusion rate than ZOL at 12 months (86% vs 70%).

Conclusion: TPTD was more efficient than ZOL in bone formation and spinal fusion in OP patients who underwent TLIF.

Keywords: TLIF; osteoporosis; teriparatide; zoledronic acid.