Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, n 22) and OC (MD: -0·610, n 24) with high heterogeneity and uNTX (MD: -8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 µg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

Reference intervals for CTX and P1NP in a multi-ethnic Malaysian cohort.

BACKGROUND: Well defined reference intervals are central to the utility of serum C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP), designated as reference markers in osteoporosis, and useful for monitoring therapeutic response in that condition. This study reports the reference intervals for plasma CTX and serum P1NP in a multi-ethnic Malaysian population. METHODS: Ethnic Malay, Chinese or Indian subjects aged 45-90 years old were recruited from Selangor, Malaysia from June 2016 to August 2018. Subjects with known medical conditions (e.g., bone disorders, malnutrition, immobilisation, renal impairment, hormonal disorders) and medications (including regular calcium or vitamin D supplements) that may affect CTX and P1NP were excluded. Additionally, subjects with osteoporosis or fracture on imaging studies were excluded. The blood samples were collected between 8 a.m. and 9 a.m. in fasting state. The CTX and P1NP were measured on Roche e411 platform in batches. RESULTS: The 2.5th-97.5th percentiles reference intervals (and bootstrapped 90%CI) for plasma CTX in men (n = 91) were 132 (94-175) - 775 (667-990) ng/L; in post-menopausal women (n = 132) 152 (134-177) - 1025 (834-1293) ng/L. The serum P1NP reference intervals in men were 23.7 (19.1-26.4) - 83.9 (74.0-105.0) µg/L, and in post-menopausal women, 25.9 (19.5-29.3) - 142.1 (104.7-229.7) µg/L. CONCLUSION: The reference intervals for plasma CTX and serum PINP for older Malaysian men and post-menopausal women are somewhat different to other published studies from the region, emphasising the importance of establishing specific reference intervals for each population.

Icariin attenuates thioacetamide­induced bone loss via the RANKL­p38/ERK­NFAT signaling pathway.

There is an increasing incidence of destructive bone disease caused by osteoclast proliferation. This is characterized by reduced bone mass and imbalance of bone homeostasis. Icariin (ICA), a flavonoid compound isolated from Epimedium, has anti­osteoporosis activity and inhibits the formation of osteoclasts and bone resorption. The purpose of the present study was to investigate the protective effect of ICA on osteoclastic differentiation induced by thioacetamide (TAA) and its possible mechanism in Sprague Dawley (SD) rats. In the present study, SD rats were intraperitoneally injected with TAA (300 mg/kg) for the bone loss model, treated with ICA (600 mg/kg, intragastric gavage) in the ICA group and TAA+ICA group for treatment of bone loss for 6 weeks. Indexes associated with bone metabolism, such as alkaline phosphatase, N­terminal telopeptide of type­I collagen (NTX­I), calcium (Ca), phosphorus (P) and magnesium (Mg) in the serum, were detected. Osteoclast differentiation of femoral tissues was detected by hematoxylin and eosin and tartrate­resistant acid phosphatase staining. The femoral bone mass was evaluated using a three­point bending test and micro computed tomography. Western blotting was used to detect the expression levels of osteoclast­related proteins in each group. In the rats treated with TAA, the serum concentrations of Ca, P and Mg were decreased, the serum concentration of NTX­I was increased, osteoclast differentiation of the femur was increased, femur bone stress and bone mass were decreased and the bone loss and osteoclast formation were reduced after ICA treatment. In addition, ICA inhibited the protein expression of receptor activator of nuclear factor κ­Β ligand (RANKL), receptor activator of nuclear factor κ­B (RANK), p38, ERK, c­Fos and nuclear factor of activated T cells 1 (NFATc1) in the femur of rats treated with TAA. The results suggested that ICA may inhibit osteoclast differentiation by downregulating the RANKL­p38/ERK­NFAT signaling pathway and prevent TAA­induced bone loss. The results are helpful to understand the mechanism of osteoclast differentiation induced by TAA, as well as the antiresorptive activity and molecular mechanism of ICA, and to provide new ideas for the treatment of osteolytic diseases.

Fengshi Qutong capsule ameliorates bone destruction of experimental rheumatoid arthritis by inhibiting osteoclastogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Bone destruction plays a key role in damaging the joint function of rheumatoid arthritis (RA). Fengshi Qutong capsule (FSQTC) consisting of 19 traditional Chinese medicines has been used for treating RA in China for many years. Preliminary studies show that FSQTC has analgesic activity and inhibits synovial angiogenesis of collagen-induced arthritis (CIA), but its role on bone destruction of RA is still unclear. AIM OF THE STUDY: To explore the effect of FSQTC on bone destruction of RA and the possible mechanism of osteoclastogenesis in vivo and in vitro. MATERIALS AND METHODS: LC-MS system was used to detect the quality control components of FSQTC. The anti-arthritic effect of FSQTC on CIA rats was evaluated by arthritis score, arthritis incidence and histopathology evaluation of inflamed joints. The effect of treatment with FSQTC on bone destruction of joint tissues was determined with X-ray and micro-CT quantification, and on bone resorption marker CTX-I and formation marker osteocalcin in sera were detected by ELISA. Then, osteoclast differentiation and mature were evaluated by TRAP staining, actin ring immunofluorescence and bone resorption assay both in joints and RANKL-induced RAW264.7 cells. In addition, RANKL, OPG, IL-1ß and TNFα in sera were evaluated by ELISA. The molecular mechanisms of the inhibitions were elucidated by analyzing the protein and gene expression of osteoclastic markers CTSK, MMP-9 and ß3-Integrin, transcriptional factors c-Fos and NFATc1, as well as phosphorylation of ERK1/2, JNK and P38 in joints and in RANKL-induced RAW264.7 cells using western blot and/or qPCR. RESULTS: In this study, 12 major quality control components were identified. Our data showed that FSQTC significantly increased bone mineral density, volume fraction, trabecular thickness, and decreased trabecular separation of inflamed joints both at periarticular and extra-articular locations in CIA rats. FSQTC also diminished the level of CTX-I and simultaneously increased osteocalcin in sera of CIA rats. The effects were accompanied by reductions of osteoclast differentiation, bone resorption, and expression of osteoclastic markers (CTSK, MMP-9 and ß3-Integrin) in joints. Interestingly, FSQTC treatment could reduce the protein level of RANKL, increase the expression of OPG, and decrease the ratio of RANKL to OPG in inflamed joints and sera of CIA rats. In addition, FSQTC inhibited the levels of pro-inflammatory cytokines implicated in bone resorption, such as IL-1ß and TNFα in sera. When RAW264.7 cells were treated with RANKL, FSQTC inhibited the formation of TRAP + multinucleated cells, actin ring and the bone-resorbing activity in dose-dependent manners. Furthermore, FSQTC reduced the RANKL-induced expression of osteoclastic genes and proteins and transcriptional factors (c-Fos and NFATc1), as well as phosphorylation of mitogen-activated protein kinases (MAPKs). CONCLUSION: FSQTC may inhibit bone destruction of RA by its anti-osteoclastogenic activity both in vivo and in vitro.

Effect of Vitamin E Supplement on Bone Turnover Markers in Postmenopausal Osteopenic Women: A Double-Blind, Randomized, Placebo-Controlled Trial.

Vitamin E is a strong anti-oxidative stress agent that affects the bone remodeling process. This study evaluates the effect of mixed-tocopherol supplements on bone remodeling in postmenopausal osteopenic women. A double-blinded, randomized, placebo-controlled trial study was designed to measure the effect of mixed-tocopherol on the bone turnover marker after 12 weeks of supplementation. All 52 osteopenic postmenopausal women were enrolled and allocated into two groups. The intervention group received mixed-tocopherol 400 IU/day, while the control group received placebo tablets. Fifty-two participants completed 12 weeks of follow-up. Under an intention-to-treat analysis, vitamin E produced a significant difference in the mean bone resorption marker (serum C-terminal telopeptide of type I collagen (CTX)) compared with the placebo group (-0.003 ± 0.09 and 0.121 ± 0.15, respectively (p < 0.001)). In the placebo group, the CTX had increased by 35.3% at 12 weeks of supplementation versus baseline (p < 0.001), while, in the vitamin E group, there was no significant change of bone resorption marker (p < 0.898). In conclusion, vitamin E (mixed-tocopherol) supplementation in postmenopausal osteopenic women may have a preventive effect on bone loss through anti-resorptive activity.

The Effect of Caloric Restriction with and without n-3 PUFA Supplementation on Bone Turnover Markers in Blood of Subjects with Abdominal Obesity: A Randomized Placebo-Controlled Trial.

Weight loss contributes to an increased risk of hip fracture, especially in postmenopausal women. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation could diminish the adverse effect of weight loss on bone health. The aim of this randomized, placebo-controlled, double-blind parallel trial was to investigate the effect of caloric restriction and n-3 PUFA supplement intake on osteogenic markers (carboxylated osteocalcin (Gla-OC); procollagen I N-terminal propeptide (PINP)), as well as a bone resorption marker (C-terminal telopeptide of type I collagen (CTX-I)) in a serum of 64 middle aged individuals (BMI 25-40 kg/m2) with abdominal obesity. Bone remodeling, metabolic and inflammatory parameters and adipokines were determined before and after 3 months of an isocaloric diet (2300-2400 kcal/day) or a low-calorie diet (1200 kcal/day for women and 1500 kcal/day for men) along with n-3 PUFA (1.8 g/day) or placebo capsules. CTX-I and adiponectin concentrations were increased following 7% weight loss independently of supplement use. Changes in CTX-I were positively associated with changes in adiponectin level (rho = 0.25, p = 0.043). Thus, an increase in serum adiponectin caused by body weight loss could adversely affect bone health. N-3 PUFAs were without effect.

Bisphosphonate use in children with cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is a heterogeneous group of non-progressive disorders of posture or movement, caused by a lesion of the developing brain. Osteoporosis is common in children with cerebral palsy, particularly in children with reduced gross motor function, and leads to an increased risk of fractures. Gross motor function in children with CP can be categorised using a tool called the Gross Motor Function Classification System (GMFCS). Bisphosphonate increases bone mineral density (BMD) and reduces fracture rates. Bisphosphonate is used widely in the treatment of adult osteoporosis. However, the use of bisphosphonate in children with CP remains controversial, due to a paucity of evidence and a lack of recent trials examining the efficacy and safety of bisphosphonate use in this population. OBJECTIVES: To examine the efficacy and safety of bisphosphonate therapy in the treatment of low BMD or secondary osteoporosis (or both) in children with cerebral palsy (GMFCS Levels III to V) who are under 18 years of age. SEARCH METHODS: In September 2020, we searched CENTRAL, MEDLINE, Embase, six other databases, and two trial registers for relevant studies. We also searched the reference lists of relevant systematic reviews, trials, and case studies identified by the search, and contacted the authors of relevant studies in an attempt to identify unpublished literature. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs), and quasi-RCTs, comparing at least one bisphosphonate (given at any dose, orally or intravenously) with placebo or no drug, for the treatment of low BMD or osteoporosis in children up to 18 years old, with cerebral palsy (GMFCS Levels III to V). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We were unable to conduct any meta-analyses due to insufficient data, and therefore provide a narrative assessment of the results. MAIN RESULTS: We found two relevant RCTs (34 participants). Both studies included participants with non-ambulatory CP or CP and osteoporosis. Participants in both studies were similar in severity of CP, age distribution, and sex distribution. The two trials used different bisphosphonate medications and different intervention durations, but further comparison of the interventions was not possible due to a lack of published data from one trial. One trial received funding and support from research, academic, and hospital foundations, with pharmaceutical companies providing components of the calcium and vitamin supplement; the other trial did not report sources of funding. We judged one study at an overall high risk of bias; the other as overall unclear risk of bias. PRIMARY OUTCOME: Compared to placebo or no treatment, both studies provided very low certainty evidence of improved BMD at least four months post-intervention in children treated with bisphosphonate. Only one study (12 participants) provided sufficient detail to assess a measure of the effect, and reported an improvement at six months post-intervention in lumbar spine z-score (mean difference (MD) 18%, 95% confidence interval (CI) 6.57 to 29.43; very low certainty evidence). SECONDARY OUTCOMES: Very low certainty evidence from one study found that bisphosphonate reduced serum N-telopeptides (NTX) more than placebo; the other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced NTX, but did not compare groups. One study reported inconclusive results between groups for serum bone-specific alkaline phosphatase (BAP). The other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced BAP, but did not compare groups. Neither study reported data for the effect of bisphosphonate treatment on changes in volumetric BMD in the distal radius or tibia, changes in fracture frequency, bone pain, or quality of life. One study reported that two participants had febrile events noted during their first dosing schedule, but no further adverse events were reported in either relevant study. AUTHORS' CONCLUSIONS: Based on the available evidence, there is very low certainty evidence that bisphosphonate treatment may improve bone health in children with cerebral palsy. We could only include one study with 14 participants in the assessment of the effect size; therefore, the precision of the effect estimate is low. We could only evaluate one planned primary outcome, as there was insufficient detail reported in the relevant studies. Further research from RCTs on the effect and safety of bisphosphonate to improve bone health in children with cerebral palsy is required. These studies should clarify the optimal standard treatment regarding weight-bearing exercises, vitamin D and calcium supplementation, and should include fracture frequency as a primary outcome.

Fructus Ligustri Lucidi aqueous extract promotes calcium balance and short-chain fatty acids production in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL) is an edible herb with anti-osteoporotic activity, yet whether and how the aqueous extract of this herb affect calcium metabolism in preservation of bone quality remain unclear. AIM OF THE STUDY: To investigate the effects of FLL aqueous extract on calcium balance and short-chain fatty acids (SCFAs) production in ovariectomized (OVX) rats. MATERIALS AND METHODS: OVX rats were daily and orally administrated with FLL aqueous extract (3.5 g/kg) for 14 weeks. The levels of N-terminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTx-I) in rat serum were evaluated by ELISA assays. The concentration of calcium in serum, urine, and feces were determined by biochemical assays. Bone quality was determined by Micro-CT, a three-point bending assay, and Fourier Transform Infrared (FTIR) Spectrometry. The expressions of Calbindin D28K and Calcium-sensing receptor (CaSR) in kidney as well as the Vitamin D receptor (VDR), the transient receptor potential vanilloid receptor 6 (TRPV6), Calbindin D9k in the duodenum were measured by immunohistochemistry, western blotting, or real-time PCR. The short-chain fatty acids (SCFAs) levels in the feces of the cecum were tested by gas chromatograghy. RESULTS: The administration of FLL to OVX rats resulted in a significant improvement in bone mineral density and biomechanical strength as well as in maintaining bone microstructures and material quality. Meanwhile, the decreased levels of PINP and increased levels of CTx-I in OVX rats were restored by FLL treatment. Additionally, FLL treatment increased calcium absorption, upregulated VDR, TRPV6, Calbindin D9k expressions in the duodenum, Calbindin D28K in kidney, and down-regulated CaSR expression in the kidney, as well as enhanced SCFAs levels in the feces of OVX rats. CONCLUSIONS: FLL aqueous extract may preserve bone quality through regulation of the calcium balance and intestinal SCFAs production in OVX rats. This offers translational value of FLL into osteoporosis clinical trial.

The effect of Cornus mas extract consumption on bone biomarkers and inflammation in postmenopausal women: A randomized clinical trial.

The drastic decrease in estrogen levels in menopausal women can elevate bone resorption and osteoporosis. Cornus mas extract (C. mas extract) is a potential candidate for treating menopausal-related bone complications because of its phytoestrogen and anti-inflammatory contents. It was an interventional double-blind placebo-controlled randomized study. Eighty-four women aged 45-60 years old were randomly allocated to either the extract group receiving 3 capsules of 300 mg C. mas extract or the placebo group receiving 3 capsules of 300 mg of starch powder per day for 8 weeks. Then, venous blood was used to measure bone-specific alkaline phosphatase (BAP), osteocalcin (OC), C-terminal telopeptide (TC) as well as serum levels of PTH and hsCRP. Our results indicated the decrease in alkaline phosphatase, PTH, and as an inflammation biomarker, hsCRP, between two groups at the end of the study. No statistically significant difference was observed in telopeptide C, osteocalcin, and calcium between the placebo and extract groups after 8 weeks of intervention. In conclusion, the results indicate that the C. mas extract supplement of 900 mg/day may decrease levels of BAP, PTH, and hsCRP. However, this intervention had no beneficial effect on OC and TC in healthy postmenopausal women.

Elevated Urate Levels Do Not Alter Bone Turnover Markers: Randomized Controlled Trial of Inosine Supplementation in Postmenopausal Women.

OBJECTIVE: Observational studies have consistently demonstrated that serum urate level positively correlates with bone mineral density (BMD). We undertook this study to determine whether moderate hyperuricemia induced by inosine supplements influences bone turnover markers in postmenopausal women over a 6-month period. METHODS: One hundred twenty postmenopausal women were recruited for a 6-month randomized, double-blind, placebo-controlled trial. Key exclusion criteria were osteoporosis, previous fragility fracture, bisphosphonate therapy, gout, kidney stones, and a urine pH level of ≤5.0. Participants were randomized in a 1:1 ratio to receive placebo or inosine. The coprimary end points were change in levels of N-propeptide of type I procollagen (PINP) and change in levels of ß-C-telopeptide of type I collagen (ß-CTX). Change in BMD, as measured by dual x-ray absorptiometry, was an exploratory end point. RESULTS: Administration of inosine led to a significant increase in serum urate concentration over the study period (P < 0.0001 for all follow-up time points). At week 26, the mean change in serum urate concentration was +0.13 mmoles/liter (+2.2 mg/dl) in the inosine group and 0.00 mmoles/liter (0 mg/dl) in the placebo group. There was no difference in PINP or ß-CTX levels between groups over the 6 months. There were no significant changes in bone density between groups over the 6 months. Adverse events and serious adverse events were similar between the 2 groups. CONCLUSION: This clinical trial shows that although inosine supplementation leads to sustained increases in serum urate levels over a 6-month period, it does not alter markers of bone turnover in postmenopausal women. These findings do not support the concept that urate has direct biologic effects on bone turnover.

Effectiveness of electroacupuncture as a treatment for osteoporosis: A systematic review and meta-analysis.

BACKGROUND: Osteoporosis (OP) results in an increased risk of fragility fractures, representing a major public health problem. In preventing OP, complementary and alternative medicine, such as acupuncture, was recommended because of the low efficiency and side effects of medications. Recently, there is insufficient evidence on electroacupuncture as an effective therapy for OP management. Hence, we evaluated the effectiveness of electroacupuncture for OP treatment. METHODS: We conducted a systematic review and meta-analysis of clinical studies on patients with OP. Five databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang) were searched from the earliest publication date to March 12, 2020. Randomized controlled trials (RCTs) were included if electroacupuncture was applied as the sole treatment or as an adjunct to other treatments compared with medications in patients with OP. The measurement outcomes included serum aminoterminal propeptide of type I procollagen (PINP) and C-telopeptide of type I collagen (CTX) levels, bone mineral density (BMD) of lumbar, and visual analog scale scores for OP-related pain. Acupoints were extracted when available. RESULTS: In total, 11 RCTs involving 731 participants were included for further meta-analysis. The meta-analysis showed that the use of electroacupuncture as a sole treatment or as an adjunct to other treatments could relieve OP-related pain compared with medications [mean difference (MD) =  -0.58, 95% confidence interval (CI); MD =  -0.97 to -0.19, P = .003, I2 = 88%; MD =  -1.47, 95% CI = -2.14 to -0.79, P < .001, I2 = 96%). Meanwhile, the results showed a favorable effect of electroacupuncture on decreasing serum beta-CTX levels. However, there were no significant differences in serum PINP levels and BMD of lumbar. Shenshu (BL23) was the most frequent acupoint stimulation among these studies. CONCLUSIONS: The application of electroacupuncture as an independent therapy or as an adjunct to other treatments might attenuate OP-related pain and serum beta-CTX levels. However, to overcome the methodological shortcomings of the existing evidence, due to a small size of samples and high risk of bias in these included RCTs, further rigorous studies are required.

A Dairy Product to Reconstitute Enriched with Bioactive Nutrients Stops Bone Loss in High-Risk Menopausal Women without Pharmacological Treatment.

Osteoporosis is a multifactorial disease characterized by the loss of bone mass and deterioration of the internal structure of the bone, increasing the risk of fractures, and is becoming an economic and social problem. The main treatment is pharmacological, however, the population demands other therapies, such as foods with nutrients beneficial to bone health. Seventy-eight healthy menopausal women at risk of osteoporosis or untreated osteopenia were recruited for a randomized, parallel, double-blind clinical trial with two intervention groups: one group consumed a serving a day of the experimental enriched product (experimental group (EG)) and the other group (control group (CG)) consumed the same product without enrichment. The main objective was to compare the effect of consuming a dairy preparation to reconstitute, similar to yogurt when prepared, enriched in calcium, vitamin D, vitamin K, vitamin C, zinc, magnesium, L-leucine and probiotic (Lactobacillus plantarum 3547) on bone metabolism markers for 24 weeks. The EG showed a significantly increased bone mass compared to the CG (0.01 ± 0.03 vs. -0.01 ± 0.03 kg; p < 0.05). In addition, the EG maintained their bone mineral density (BMD) compared to the CG, whose BMD significantly decreased at the end of the study. For biochemical markers, the EG significantly increased the serum levels of the N-terminal propeptide of type I collagen (P1NP) bone formation marker (13.19 ± 25.17 vs. -4.21 ± 15.62 ng/mL; p < 0.05), and decreased the carbo-terminal telopeptide of type I collagen (CTx) bone resorption marker compared to the CG (-0.05 ± 0.19 vs. 0.04 ± 0.14 ng/mL; p < 0.05). On the other hand, the EG exhibited a significantly decreased systolic and diastolic blood pressure compared to the start of the study. Finally, the EG significantly increased their dietary calcium and vitamin D intake compared to the CG. In conclusion, the regular consumption of a dairy product to reconstitute enriched with bioactive nutrients improves bone health markers in menopausal women at risk of osteoporosis without pharmacological treatment.

Effects of whole-body vibration training on bone density and turnover markers in adolescent swimmers.

Background Whole-body vibration training has recently been proposed as a complementary training modality to improve the bone health of adolescent swimmers. However, there is no longitudinal study regarding the effects of this training combination on bone metabolism. Therefore, the main goal was to analyze the effects of swimming and vibration training on bone turnover markers during adolescence. Methods The present study included 68 adolescent swimmers and 41 normoactive controls (CON). Swimmers were randomly selected to either continue with their regular swimming training (SWI) or participate in an additional vibration protocol (VIB). Anthropometric measurements and serum level determinations of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide crosslaps (CTX) were performed before and after the 6-month intervention. Results Statistically significant group by time interactions were found for both bone formation markers. VIB showed a decrease over time in OC (baseline: 101.4 µg/mL, follow-up: 82.8 µg/mL, p < 0.05) and P1NP (baseline: 528.4 µg/mL, follow-up: 389.0 µg/mL, p < 0.05) and SWI had analogous reductions in P1NP (baseline: 685.8 µg/mL, follow-up: 542.0 µg/mL, p < 0.05), whereas CON experienced an increase in OC levels (baseline: 94.4 µg/mL, follow-up: 103.4 µg/mL, p < 0.05). After stratifying the sample according to the pubertal status, similar interactions were observed. Conclusions The combination of swimming training and this particular vibration protocol led to a decrease in bone formation markers, especially during early puberty. Whole-body vibration might not induce an osteogenic stimulus in adolescent swimmers.

Imaging, biomarker and invasive assessment of diffuse left ventricular myocardial fibrosis in atrial fibrillation.

BACKGROUND: Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. METHODS: LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. RESULTS: On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression. CONCLUSION: LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker.

Effect of continuous long-term treatment for 10 years with bisphosphonate on Japanese osteoporosis patients.

INTRODUCTION: In terms of the balance between benefits and risks of long-term treatment with bisphosphonate, uncertainties remain regarding the optimal treatment duration. We investigated effects of continuous long-term treatment for 10 years with bisphosphonate in postmenopausal osteoporosis patients. MATERIALS AND METHODS: Fifty five patients in the outpatient clinic of our hospital have been continuously treated with alendronate or risedronate for 10 years. All data were retrospectively collected. The age, height, weight, total muscle volume, total fat volume, and BMD at the lumbar spine, total hip and distal 1/3 radius, alkaline phosphatase (ALP), urinary type I collagen cross-linked N-telopeptide (uNTX) and tartrate-resistant acid phosphatase-5b (TRAP5b), calcium (Ca) and phosphate (P) levels were measured pre- and after the start of 10-year continuous treatment. RESULTS: BMD at the lumbar spine increased continuously over the 10-year period, while BMD at the total hip slightly but significantly decreased, and that at the 1/3 radius did not show any significant change over the 10 years. Serum Ca value was significantly decreased after the start of treatment, and became stable within the reference range from the second year. Bone resorption markers such as uNTX and TRAP5b significantly decreased from the second year after the start of treatment and no significant changes were observed thereafter. There were no serious medical adverse events including atypical femoral fractures and osteonecrosis of the jaw. CONCLUSION: We believe that the continuous use of alendronate and risedronate for 10 years could be an option for the treatment of postmenopausal osteoporosis patients.

Effect of vitamin D fortified foods on bone markers and muscle strength in women of Pakistani and Danish origin living in Denmark: a randomised controlled trial.

BACKGROUND: Deficient and insufficient vitamin D status (defined as serum 25(OH)D < 30 nmol/L and > 50 nmol/L) is prevalent worldwide and associated with decreased muscle strength and poor bone health. We aimed to investigate the effect of vitamin D fortification on bone markers and muscle strength among younger adult women at risk of vitamin D deficiency. METHODS: A 12-week randomised double-blinded placebo-controlled winter intervention trial, providing 30 µg vitamin D3/day through fortified yoghurt, cheese, eggs and crisp-bread or similar placebo products. Participants were 143 women of Danish and Pakistani origin 18-50 years of age, living in Denmark, randomised into four groups stratified by ethnicity. Serum 25-hydroxyvitamin D (25(OH)D) by LC-MS/MS and the secondary endpoints: four specific bone markers (osteocalcin (OC), Bone specific Alkaline Phosphatase (BALP), Procollagen type 1 amino-terminal propeptide (P1NP), C-terminal crosslinked telopeptide of type 1 collagen (CTX)) and three muscle strength measures (handgrip, knee extension strength, chair-standing), were assessed using one-way ANOVA, Tukey HSD and subsequent linear ANCOVA models, adjusted for relevant covariates. RESULTS: Significantly increased serum 25(OH)D concentration from 53.3 (17) to 77.8 (14) nmol/L and from 44.5 (21) to 54.7 (18) nmol/L among Danish and Pakistani women in the fortified groups, respectively (P <  0.05). The bone turnover markers OC, BALP, P1NP and CTX did not change significantly. Muscle strength by handgrip, knee extension and chair-standing test did not change significantly following the intervention. CONCLUSIONS: Consumption of vitamin D fortified foods for 12 weeks did not result in significant changes of the bone turnover markers OC, BALP, P1NP and CTX. Muscle strength measured as hand grip strength, knee extension strength and chair-standing did not change significantly following the intervention.

Effects of resveratrol supplementation on bone biomarkers: a systematic review and meta-analysis.

The current study presents a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) on resveratrol and bone health biomarkers. PubMed, Scopus, and Web of Science (until September 2018) were searched to identify the potential RCTs with information on resveratrol supplementation and bone metabolism biomarkers. Mean differences (MD) were analyzed using a random-effects model. Pooling six RCTs (eight treatment arms with 264 subjects) together identified no significant reduction of serum Ca, osteocalcin, C-terminal telopeptide of type I collagen, and procollagen I N-terminal propeptide values after resveratrol supplementation over placebo treatment. However, a significant increase in serum alkaline phosphatase (ALP) (MD: 5.69 mg/mL, 95% CI: 3.58-7.80, I2  = 95.7%, P < 0.001) and bone alkaline phosphatase (BAP) (MD: 10.57 mmHg, 95% CI: 5.36-15.78, I2  = 99.2%, P < 0.001) values was observed after resveratrol treatment relative to placebo. The findings of this study indicate that resveratrol supplementation increased some key bone biomarkers, such as ALP and BAP. Further precise clinical trials of the effects of resveratrol supplementation on bone health should be conducted.

Effects of Short-Term Dried Plum (Prune) Intake on Markers of Bone Resorption and Vascular Function in Healthy Postmenopausal Women: A Randomized Crossover Trial.

Osteoporosis and cardiovascular disease are global health burdens, with postmenopausal women being at great risk. Dried plums/prunes (DPs) have been reported to provide bone health benefits in animal models, which is consistent with in vitro models. Data from human studies suggest that DP intake can enhance lipid metabolism, anti-inflammatory, and oxidant defense systems, which can impact cardiovascular health. We tested the hypothesis that short-term consumption of low and reasonable levels of DPs augments bone resorption and vascular function. Twenty-seven healthy, postmenopausal women were randomly assigned to consume six DPs (∼42 g) or two DPs (∼14 g) per day for 2 weeks, then a 2-week washout period and then crossed over. Serum C-telopeptide, beta-crosslinked (CTX) was used as a measure of bone resorption. Peripheral artery tonometry (PAT) was used to assess microvascular function. The pattern of changes in CTX in the second 2-week period (no change or decline) differed significantly from the pattern in the first 2 weeks (increases in both groups; F = 9.26, P = .006), suggesting a trend in CTX reduction (i.e., a decrease in bone resorption) in those consuming six DPs per day in the second phase. No effects on vascular function were noted. A significant interaction was observed for the augmentation index, a measure of arterial stiffness, between treatment and years after menopause (P = .045). The results suggest a potentially favorable impact of DPs on bone health when assessed with a short-term, crossover study design in postmenopausal women. Given the novel assessments used in this study, follow-up studies are warranted.

Temporal Change in Biomarkers of Bone Turnover Following Late Evening Ingestion of a Calcium-Fortified, Milk-Based Protein Matrix in Postmenopausal Women with Osteopenia.

The diurnal rhythm of bone remodeling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of bedtime ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or maltodextrin (CON) on acute (0-4 h) blood and 24-h urinary change in biomarkers of bone remodeling in postmenopausal women with osteopenia. In CON, participants received 804 ± 52 mg calcium, 8.2 ± 3.2 µg vitamin D and 1.3 ± 0.2 g/kg BM protein per day. MBPM increased calcium intake to 1679 ± 196 mg, vitamin D to 9.2 ± 3.1 µg and protein to 1.6 ± 0.2 g/kg BM. Serum C-terminal cross-linked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), and urinary N-telopeptide cross-links of type I collagen (NTX), pyridinoline (PYD) and deoxypyridinoline (DPD) was measured. Analyzed by AUC and compared to CON, a -32% lower CTX (p = 0.011, d = 0.83) and 24% (p = 0.52, d = 0.2) increase in P1NP was observed for MBPM. Mean total 24 h NTX excreted in MBPM was -10% (p = 0.035) lower than CON. Urinary PYD and DPD were unaffected by treatment. This study demonstrates the acute effects of bedtime ingestion of a calcium-fortified, milk-based protein matrix on bone remodeling.

Relationship between plasma levels of sclerostin, calcium-phosphate disturbances, established markers of bone turnover, and inflammation in haemodialysis patients.

PURPOSE: Data concerning the relation between increased levels of circulating sclerostin (a physiological inhibitor of bone formation) and bone turnover in patients with chronic renal failure (CRF) are limited. Therefore, the aim of this study was to evaluate associations between plasma sclerostin levels and calcium-phosphate disturbances, markers of bone turnover as well as inflammation in haemodialysis (HD) patients. METHODS: In plasma samples obtained in 150 stable HD patients (92 men) aged 40-70 years, levels of sclerostin, fibroblast growth factor (cFGF23), osteocalcin, the N-terminal propeptide of type I procollagen, C-terminal telopeptide of the alpha chain of type I collagen (ß-CTx), and inflammatory markers (IL-6 and TNF-α) in addition to routine parameters (calcium, phosphorus, parathyroid hormone-iPTH, 25-OH-D, alkaline phosphatase) were measured. RESULTS: Plasma sclerostin concentrations were significantly higher in HD men than women (2.61 vs. 1.88 ng/mL, p < 0.01). Patients with sclerostin levels above median were characterized by lower iPTH and IL-6, but higher cFGF23 and TNF-α (significantly only in men) concentrations. Plasma sclerostin concentration positively correlated with serum 25-OH-D (τ = 0.204), phosphorus (τ = 0.1482), and TNF-α (τ = 0.183) and inversely with iPTH (τ = - 0.255), alkaline phosphatase (τ = - 0.203), IL-6 (τ =- 0.201), and ß-CTx (τ = - 0.099) levels. In multivariate regression analysis, variability of sclerostin levels was explained by sex and 25-OH-D and phosphorus levels. CONCLUSIONS: Increased circulating sclerostin levels seem to reflect slower bone turnover in HD patients. Low levels of sclerostin are associated with vitamin D deficiency and good phosphates alignment.