Amino-terminal Telopeptide Research Articles

Effect of Odanacatib on the release of NTX (Amino Terminal Telopeptide) from LPS contaminated type I dentin collagen.

To evaluated the Odanacatib inhibitor treatment on lipopolysaccharide (LPS) contamination effect on cathepsin-K mediated dentin degradation by analysis of type I collagen C- and N-termini telopeptides. Pulverized and disks of human dentin were demineralized and LPS contaminated, or stored in deionized water (DW) for 12h. Samples were challenged with lactic acid (LA). Aliquots of dentin powder were treated with 1mL Odanacatib or stored in DW for 30min. Dentin collagen degradation was determined by sub-product release of C-terminal (ICTP and CTX) and N-terminal (NTX) telopeptides, normalized to total protein (tp) concentration (n=3). Dentin matrix was evaluated for gravimetric (n=8) and ultrastructural changes. Data were analyzed by Student t-test, one-way ANOVA and Tukey's test (α=5 %). LA incubation significantly increased telopeptide release compared with DW (p<0.05). In untreated groups, significantly higher CTXtp, NTXtp telopeptide rates were observed for LA+LPS samples compared with DW (p<0.01). Odanacatib significantly reduced ICTPtp, CTXtp, and NTXtp telopeptide release for LPS, LA, and LA+LPS conditions. In untreated groups, LPS and LA+LPS challenge significantly increased dentin weight loss (p=0.02). Within each storage condition, Odanacatib treatment did not affect weight change (p>0.05) of dentin disks. This study showed that LPS contamination resulted in significantly higher rates of NTX than CTX from dentin matrix. Odanacatib significantly reduced telopeptide release rates of LPS contaminated dentin matrix.

Long-term effect of full-body pulsed electromagnetic field and exercise protocol in the treatment of men with osteopenia or osteoporosis: A randomized placebo-controlled trial

Background: Osteoporosis is the most prevalent metabolic disease affecting bones. Objective: To investigate the long-term effect of pulsed electromagnetic field (PEMF) combined with exercise protocol on bone mineral density (BMD) and bone markers in men with osteopenia or osteoporosis. Methods: Ninety-five males with osteopenia or osteoporosis (mean age, 51.26 ± 2.41 years; mean height, 176 ± 2.02 cm; mean weight, 83.08 ± 2.60 kg; mean body–mass index (BMI), 26.08 ± 1.09 kg/m2) participated in the study, and they were randomly assigned to one of three groups: Group 1 received a full-body PEMF and exercise protocol (PEMF +EX), Group 2 received a placebo full-body PEMF and exercise protocol (PPEMF +EX), and Group 3 received a full-body PEMF alone (PEMF). PEMF was applied for the whole body using a full-body mat three times per week for 12 weeks, with an exercise protocol that includes flexibility, aerobic exercise, strengthening, weight-bearing, and balance exercises followed by whole-body vibration (WBV) training. Outcome measures include BMD of total hip and lumbar spine and bone markers [serum osteocalcin (s-OC), Serum amino-terminal cross-linking telopeptide of type I collagen (s-NTX), Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX), Parathyroid hormones (PTH), Bone-specific Alkaline Phosphatase (BSAP), and 25-hydroxy vitamin D (Vit D)]. Results: The BMD of total hip and lumbar spine was significantly increased post-treatment in all groups, and more so in Group 1 and Group 2 than Group 3. There was a significant difference in bone markers in all groups, more so in Group 1 and Group 2 than in Group 3. Conclusion: PEMF combined with exercise protocol exerts a potent role for treating OP, is more effective than exercise and PEMF alone for increasing BMD and enhancing bone formation, and suppresses bone-resorption markers after 12-weeks of treatment with the impact lasting up to 6 months.

Efficacy and Safety of Oral Ibandronate versus Intravenous Zoledronic Acid on Bone Metabolism and Bone Mineral Density in Postmenopausal Japanese Women with Osteoporosis.

There are no published clinical reports comparing ibandronate (IBN) treatment and zoledronic acid (ZOL) treatment in Japanese postmenopausal osteoporotic patients. This investigation therefore compared the efficacy and safety of the drugs on improving bone metabolism and bone mineral density (BMD) in Japanese postmenopausal women with primary osteoporosis. Eighty-two treatment-naïve primary osteoporotic female patients were randomly divided into IBN-treated or ZOL-treated groups. Bone turnover markers and BMD were examined immediately prior to treatment (baseline) and at 6, 12, 18, 24, and 30 months of therapy. Compared with baseline levels, the values of type 1 procollagen N-terminal propeptide, bone-specific alkaline phosphatase (BAP), urinary type-I collagen amino-terminal telopeptide (NTX), and tartrate-resistant acid phosphatase 5b were all significantly decreased at every time point in both groups apart from BAP at 30 months in the ZOL group, urinary NTX at 12 months in the ZOL group and at 24 and 30 months in both groups. Lumbar BMD values were significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6 and 12 months in the ZOL group compared with pre-treatment levels. Hip BMD values were also significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6, 12, and 18 months in the ZOL group compared with baseline values. The percentage changes of hip BMD at 18 and 24 months in the ZOL group were significantly higher than those in the IBN group (both p < 0.05). No remarkable adverse events were noted in either group. In conclusion, both IBN and ZOL significantly and safely improved bone turnover markers and BMD during 30 months of treatment in Japanese osteoporosis patients. The ZOL group tended to exhibit greater gains in BMD as compared with the IBN group, which merits further investigation.

Long-term effect of full-body pulsed electromagnetic field and exercise protocol in the treatment of men with osteopenia or osteoporosis: A randomized placebo-controlled trial

Background: Osteoporosis is the most prevalent metabolic disease affecting bones. Objective: To investigate the long-term effect of pulsed electromagnetic field (PEMF) combined with exercise protocol on bone mineral density (BMD) and bone markers in men with osteopenia or osteoporosis. Methods: Ninety-five males with osteopenia or osteoporosis (mean age, 51.26 ± 2.41 years; mean height, 176 ± 2.02 cm; mean weight, 83.08 ± 2.60 kg; mean body–mass index (BMI), 26.08 ± 1.09 kg/m2) participated in the study, and they were randomly assigned to one of three groups: Group 1 received a full-body PEMF and exercise protocol (PEMF +EX), Group 2 received a placebo full-body PEMF and exercise protocol (PPEMF +EX), and Group 3 received a full-body PEMF alone (PEMF). PEMF was applied for the whole body using a full-body mat three times per week for 12 weeks, with an exercise protocol that includes flexibility, aerobic exercise, strengthening, weight-bearing, and balance exercises followed by whole-body vibration (WBV) training. Outcome measures include BMD of total hip and lumbar spine and bone markers [serum osteocalcin (s-OC), Serum amino-terminal cross-linking telopeptide of type I collagen (s-NTX), Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX), Parathyroid hormones (PTH), Bone-specific Alkaline Phosphatase (BSAP), and 25-hydroxy vitamin D (Vit D)]. Results: The BMD of total hip and lumbar spine was significantly increased post-treatment in all groups, and more so in Group 1 and Group 2 than Group 3. There was a significant difference in bone markers in all groups, more so in Group 1 and Group 2 than in Group 3. Conclusion: PEMF combined with exercise protocol exerts a potent role for treating OP, is more effective than exercise and PEMF alone for increasing BMD and enhancing bone formation, and suppresses bone-resorption markers after 12-weeks of treatment with the impact lasting up to 6 months.

Low bone mass and hypovitaminosis D in haemophilia: A single‐centre study in patients with severe and moderate haemophilia A and B

Haemophilia (H) is frequently associated with a multifactorial reduction in bone mineral density (BDM), but little is known about possible differences between HA and HB according to their severity. To evaluate the association between low bone mineral density (BMD), 25-hydroxyvitamin D [25(OH)D] concentrations and bone turnover markers in patients with HA and HB younger or older than 50years. In 78 patients <50years and 33 patients >50years with severe (S) or moderate (M) HA and HB, BMD was measured by dual-energy X-ray absorptiometry at femoral neck (FN) and lumbar spine and then correlated to annual bleeding rate (ABR), World Federation of Haemophilia orthopaedic joint scale (WFH score), 25(OH)D concentrations, parathyroid hormone (PTH), amino-terminal telopeptide of type 1 collagen (NTx), urinary pyridinolines, osteocalcin and bone-specific alkaline phosphatase. Overall, a high prevalence of hypovitaminosis D was diagnosed. In patients <50years, low FN-BMD was significantly more frequent in HA than in HB, while PTH, pyridinolines, ABR and WFH score were associated with H type and severity. In patients >50years, similarly low FN-BMD was observed in HA and HB, while ABR and WFH score were associated with H type and severity, being milder in HB. Low bone mass is a frequent comorbidity in haemophilic patients of all ages, apart from those with MHB. Clinical and laboratory assessments confirm a higher bone impairment and faster bone resorption in HA compared with HB. Looking at H type and severity, MHB seems to have a normal bone metabolism and a less severe disease.

BONE REMODELING MARKERS AS PREDICTORS OF BONE METABOLIC CHANGES IN MALES WITH DIABETIC OSTEOPATHY

Diabetic osteopathy is one of the little studied complications of diabetes mellitus (DM), which leads to common lowtrauma fractures and, as a consequence, disability and death. The level of insulin is connected with bone functional and morphological changes followed by decreased bone mineral density (BMD) in the early stages of diabetic osteopathy. Objective: to study bone morphofunctional properties in males with type 1 and 2 DM (T1DM and T2DM). Subjects and methods. Examinations were made in 41 male patients with T1DM and 52 male patients with T2DM without a history of fractures. Their age varied from 40 to 70 years (mean age, 55.8±0.7 years and 58.4±0.9 years, respectively). A control group consisted of 34 patients (mean age, 55.9±0.9 years) without a history of DM. Patients with other endocrine disorders, end-stage complications, or chronic liver and kidney diseases were excluded from the investigation. BMD was determined by dual-energy X-ray absorptiometry (DXA). Serum bone remodeling markers (procollagen type 1 amino-terminal propeptide and C-terminal telopeptide), as well as 25(OH)D, parathyrin, insulin, glycated hemoglobin (HbA1c), and electrolytes (Ca2+, P+) were evaluated. Results and discussion. An association of BMD with renal function, HbA1c, and body mass index was observed in patients with T2DM. In the T1MD group, BMD was closely related to insulin deficiency and was significantly lower than that in the control group. In patients with vitamin D deficiency, BMD was significantly lower than in those with normal vitamin D levels (p&lt;0.05). The patients with T1DM displayed both a decrease in BMD (p&lt;0.05) and a pronounced change in the levels of bone markers (p&lt;0.05). Those with T2DM had impaired bone remodeling processes, which was determined by the level of these markers (p&lt;0.05) and observed in the presence of normal BMD due to the complex pathophysiology of the underlying disease. Conclusion. Vitamin D deficiency, insufficient and decreased insulin sensitivity, hyperglycemia, and overweight are important causes of osteopathy in patients with DM. The markers of bone remodeling may become promising indicators for diagnosing osteopathy, but additional studies are needed to elaborate recommendations for their use in routine practice in order to predict and prevent this complication of DM.

A Preliminary Study of the Effect of Hyperadrenocorticism on Calcium and Phosphate Concentrations, Parathyroid Hormone and Markers of Bone Turnover in Dogs.

Reports on the effects of hyperadrenocorticism (HAC) on bone turnover in dogs are largely confined to radiographic studies. The aim of this study was to more accurately assess bone turnover in dogs with HAC by measuring circulating total and ionized calcium and phosphate concentrations, both intact and whole parathyroid hormone (PTH) concentrations and markers of both osteoblastic (osteocalcin) and osteoclastic [carboxyterminal cross-linked telopeptide of type 1 collagen (ICTP) and urine aminoterminal telopeptide of type 1 collagen (NTX) activity]. Dogs with HAC and a control group were prospectively enrolled for comparison. Results from 49 dogs with HAC were compared with 39 dogs from a hospital control population. Plasma intact and whole PTH concentrations were determined using a human immunoradiometric assay. Serum osteocalcin and NTX concentrations were measured using human enzyme linked immunosorbent assays. Serum ICTP concentration was measured using a human radioimmunoassay. Total calcium concentrations in dogs with HAC (2.67 ± 0.25 mmol/L) were not significantly different than in the control group (2.67 ± 0.14 mmol/L). By contrast, phosphate concentrations were significantly (P = 0.0143) higher in dogs with HAC (1.46 ± 0.30 mmol/L) compared to the control group (1.28 ± 0.33 mmol/L). The median intact PTH concentration in HAC dogs was 9.25 (range, 1.34–95.45) pmol/L, which was significantly (P < 0.0001) higher than in the control group [median, 3.88 (range, 2.01–10.31) pmol/L]. Whole PTH concentrations were also significantly (P < 0.0001) higher in the HAC group [median, 4.61 (range, 0.56–125.16) pmol/L] compared to the control group [median, 1.83 (range, 0.88–6.81) pmol/L]. Serum osteocalcin and urine NTX concentrations were not significantly different between the two groups of dogs. The median ICTP concentration in dogs with HAC was 2.98 (range, 1.15–6.62) ng/mL which was significantly (P < 0.0001) lower than in the control dogs [median, 7.30 (range, 3.68–21.25) ng/mL]. Both whole and intact PTH concentrations are increased in dogs with HAC compared to a hospital control population. This does not however appear to be associated with a decrease in bone formation (as assessed by osteocalcin) or an increase in bone resorption (as assessed by ICTP and urine NTX).

Serum Biomarkers Related to Glucocorticoid-Induced Osteonecrosis of the Femoral Head: A Prospective Nested Case-Control Study.

Early diagnosis and prevention of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) continues to be a challenging problem for clinicians and researchers. However, the role of circulating biomarkers for GC-induced ONFH, which may reveal individual susceptibility and facilitate earlier diagnosis, remains to be determined. The aim of this study was to identify potential biomarkers that may predict early GC-induced ONFH. A total of 123 patients scheduled for initial systemic GC therapy were enrolled in this prospective nested case-control study. The serum concentrations of 13 potential biomarkers were measured in seven patients with GC-induced ONFH, diagnosed instantly after short-term use of GCs and in 20 controls who did not develop osteonecrosis despite similar GC therapy. Biomarkers were measured both before and after taking GCs to identify any differences in marker levels and the changes during GC therapy between two groups. Type I collagen cross-linked C-telopeptide (β-CTX; p = 0.000) was significantly lower, high-density lipoprotein cholesterol (p = 0.092) and apolipoprotein (apo)-B/apo-A1 (p = 0.085) tended to be lower and higher, respectively, before GC treatment in osteonecrosis group. After GC therapy, β-CTX (p = 0.014) was significantly lower and amino terminal telopeptide of procollagen type I (PINP; p = 0.068) tended to be lower in the osteonecrosis group. As secondary outcomes, we observed remarkable changes in nine potential biomarkers following short-term GC therapy in both groups. In conclusion, we found that β-CTX, could potentially be used to predict GC-induced ONFH before GC therapy. Lower β-CTX and PINP are promising biomarkers for the early diagnosis of GC-induced ONFH. These findings need to be confirmed in large-scale prospective studies. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2348-2357, 2019.

Efficacy and Safety of Denosumab Therapy for Osteogenesis Imperfecta Patients with Osteoporosis-Case Series.

Osteogenesis imperfecta (OI) is a connective tissue disorder that is characterized by low bone density leading to recurrent fractures. The efficacy of the anti-resorption drug denosumab for OI with osteoporosis is still largely unknown. We herein describe the clinical outcomes of eight osteoporotic cases of OI to examine the effects and safety of denosumab. This retrospective, consecutive case series included eight patients respectively aged 42, 40, 14, 22, 3, 51, 37, and 9 years. We measured the bone mineral density (BMD) of the lumbar 1–4 spine (L-BMD) and bilateral hips (H-BMD), bone-specific alkaline phosphatase, urinary type I collagen amino-terminal telopeptide, and tartrate-resistant acid phosphatase 5b before and during denosumab therapy. Despite multiple pretreatment fractures in the cohort, no fractures or severe side effects, such as hypocalcemia, were observed during the observational period apart from a fracture in a young pediatric girl. Both L-BMD and H-BMD were increased by denosumab in seven of eight cases. Bone turnover markers were inhibited in most cases by denosumab therapy. Denosumab treatment could generally raise BMD without any adverse effects. The agent therefore represents a good therapeutic option for OI with osteoporosis.

Congenital hypophosphataemia in adults: determinants of bone turnover markers and amelioration of renal phosphate wasting following total parathyroidectomy

Congenital hypophosphataemia (CH) is a collection of disorders that cause defective bone mineralisation manifesting with rickets in childhood and osteomalacia in adulthood. Bone turnover markers (BTMs) are surrogate measures of metabolic bone disease severity. We explored the utility of BTMs in 27 adults with CH: 23 had X-linked hypophosphataemia (XLH), of whom 2 were hypoparathyroid post-total parathyroidectomy (PTx); 2 had autosomal dominant hypophosphataemic rickets (ADHR), and 2 had none of the known mutations. We measured the renal tubular maximum reabsorption rate of phosphate (TmP/GFR), C-terminal fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), ionised calcium, 1,25-dihydroxyvitamin D [1,25(OH)2D], and a panel of BTMs: serum bone-specific alkaline phosphatase (bone ALP), osteocalcin (Oc), total procollagen type I amino-terminal propeptide (PINP), and carboxy-terminal telopeptide of type I collagen (CTX); and urine amino-terminal telopeptides of type I collagen (uNTX). After excluding 2 patients with XLH and PTx, the frequency of abnormal elevation in BTMs was: bone ALP (96%); CTX (72%); PINP (52%); uNTX (48%); Oc (28%). The strongest association with bone ALP was TmP/GFR. Those patients receiving phosphate supplements and alfacalcidol had significant elevation in CTX. The 2 patients with XLH and PTx had normalisation of TmP/GFR and near normalisation of BTMs post-operatively, despite marked elevation in both C-terminal and intact FGF23. In conclusion, BTMs in our CH patients indicated that most have abnormalities consistent with osteomalacia and many have mild secondary hyperparathyroidism; and the normalisation of TmP/GFR after total PTx in 2 cases of XLH remains unexplained, but possible causes are speculated.

Efficacy of denosumab therapy for neurofibromatosis type I with osteoporosis and history of fractures: a case report

BackgroundThe natural history and pathogenesis of the skeletal abnormalities found in neurofibromatosis type 1 (NF1) are poorly understood, and the therapeutic options for these manifestations remain limited. This report first describes the clinical outcomes of denosumab treatment for a patient with NF1 suffering from osteoporosis.MethodsWe enrolled a patient with NF1 under denosumab treatment for osteoporosis, prior fractures, and no improvement in bone mineral density (BMD) over 3 years of alendronate therapy. BMD was monitored by dual-energy X-ray absorptiometry. Tested laboratory data included bone-specific alkaline phosphatase, urinary type I collagen amino-terminal telopeptide, tartrate-resistant acid phosphatase 5b, 1-alpha, 25-dihydroxyvitamin D3, and parathyroid hormone. BMD and laboratory data were evaluated before, between 2 and 4 months, and at 6, 12, 18, and 24 months of treatment.Case presentationDuring 2 years of denosumab therapy for osteoporosis in a 58-year-old female NF1 patient with prior fractures, BMD increased by 6.5% in the lumbar spine and 10.6% in the total hips, and bone turnover markers were notably improved. No fractures occurred during the latter half of treatment.ConclusionDenosumab represents an effective treatment option for osteoporosis in NF1 patients.

Effects of blood flow restriction exercises on bone metabolism: a systematic review.

This study analysed the effect of low-intensity (LI) exercises with blood flow restriction (BFR) on bone metabolism compared with high-intensity (HI) exercises without BFR. The following databases were searched using the keywords therapeutic occlusion training OR BFR training OR vascular occlusion training OR KAATSU training OR ischaemia training AND osteogenesis OR bone biomarkers OR bone metabolic marker OR bone mass OR bone turnover OR osteoporosis OR osteopenia: PubMed, Web of Science, SPORTDiscus, CINAHL, Science Direct, Cochrane and Google Scholar. Two researchers, independently and blindly, selected the studies based on established inclusion and exclusion criteria. Electronic and manual searches located 170 articles published in English; after screening, only four studies showed that BFR training increases the expression of bone formation markers (e.g. bone-specific alkaline phosphatase) and decreases bone resorption markers (e.g. the amino-terminal telopeptides of type I collagen) after both aerobic and anaerobic exercise across several populations. The results of this study show that few studies have confirmed the positive effect of exercise with BFR on bone metabolism, formation and resorption. Furthermore, no methodological standardization of the samples, exercise type, intervention frequency or duration was observed.

Bone metabolism markers and angiogenic cytokines as regulators of human hematopoietic stem cell mobilization.

Hematopoietic stem cell (HSC) mobilization involves cleavage of ligands between HSC and niche components. However, there are scarce data regarding the role of bone cells in human HSC mobilization. We studied biochemical markers of bone metabolism and angiogenic cytokines during HSC mobilization in 46 patients' sera with lymphoma and multiple myeloma, by ELISA. Significant changes between pre-mobilization and collection samples were found: (1) Bone alkaline phosphatase (BALP) increased, indicating augmentation of bone formation; (2) Receptor activator of Nf-κB ligand/osteoprotegerin ratio (RANKL/OPG) increased, showing osteoclastic differentiation and survival; however, there was no evidence of increased osteoclastic activity; and (3) Angiopoietin-1/Angiopoietin-2 ratio (ANGP-1/ANGP-2) decreased, consistent with vessel destabilization. Poor mobilizers had significantly higher carboxy-terminal telopeptide of collagen type I (CTX) and lower ANGP-1 at pre-mobilization samples, compared to good ones. CTX, amino-terminal telopeptide of collagen type I (NTX) and ANGP-1 pre-mobilization levels correlated significantly with circulating CD34+ peak cell counts. Our results indicate that bone formation and vessel destabilization are the two major events during human HSC mobilization. Osteoblasts seem to be the orchestrating cells, while osteoclasts are stimulated but not fully active. Moreover, ANGP-1, CTX and NTX may serve as predictors of poor mobilization.

Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and bone mineral density in post-menopausal women with type 2 diabetes: a randomized controlled trial

BackgroundSeveral antidiabetic therapies affect bone metabolism. Sulfonylureas have the lowest impact on bone among oral antidiabetics. The objective of this study is to compare the effects of vildagliptin and gliclazide modified release (MR) on bone turnover markers (BTMs) and bone mineral density (BMD) in postmenopausal women with uncontrolled type 2 diabetes (T2D).MethodsForty-two postmenopausal women with uncontrolled T2D were randomly allocated into vildagliptin or gliclazide MR (control) groups. The primary endpoint was the change in the BTMs in months 6 and 12 compared with the baseline. The secondary endpoint was the variation in the BMD, which was assessed via dual-energy X-ray absorptiometry at the lumbar spine, femoral neck and total hip at baseline and month 12.ResultsAfter a 12-month treatment, the BTM serum carboxy-terminal telopeptide of type 1 collagen increased 0.001 ± 0.153 ng/mL in the vildagliptin group versus 0.008 ± 0.060 ng/mL in the gliclazide MR group (p = 0.858). The serum osteocalcin, serum amino-terminal propeptide of procollagen type I and urinary amino-terminal telopeptide of type 1 collagen remained stable in both groups, and there was no statistically significant difference between the effect of vildagliptin and gliclazide MR on these variables. The lumbar spine BMD did not change in the vildagliptin or gliclazide MR groups after a 12-month treatment (0.000 ± 0.025 g/cm2 versus −0.008 ± 0.036, respectively, p = 0.434). Furthermore, there was a similar lack of change in the femoral neck and total hip BMD values in both treatments.ConclusionsBone turnover markers and BMD remained unchanged after a 12-month treatment in both groups, which suggests that vildagliptin has the same safety profile as gliclazide MR on bone metabolism.Trial Registration ClinicalTrials.gov number NCT01679899

Effect of Atorvastatin on Bone biochemical markers in dyslipidemic patients, Basra, Iraq

&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Objective: The aim of the study was to estimate the action atorvastatin(20mg/day) on bone biochemical markers dyslipidemic men. Methodology: This study was conducted between May 2015 and November 2015 in Al-Basrah General hospital in Basra, Iraq, to evaluate important role of atorvastatin (20mg/day)(Lipitor® Pfizer Pharma GmbH.Germany) on bone biochemical markers. Thirty men patients who had been admitted for a variety of medical problems included in the study. All the patients had previously been diagnosed with Dyslipidemia by specialist physician in internal medicine and all patients age below 55 years . the inclusion criteria for the experimental group was use of atorvastatin for at least three months; the study group was then compared to age-matched healthy men .bone biochemical markers were compared between groups. Results are expressed mean ± SD; statistically Student’s t test was used to compare variables. Results: The mean age of the statin group was 44.5 ± 5.9 and control group was 45.7 ± 4.4.After 3 months treatment with atorvastatin, as in table (1) and figures (1-8) Surprisely level of serum total cholesterol remain significantly higher than value of normal healthy group. LDL value significantly reduced by treatment but still significantly higher than values of normal group. HDL value were significantly higher than that of its initial values, but level of HDL ;after treatment; was not significantly different from that of normal group. Triglycerides was not significantly changed by treatment and its value still significantly higher than normal group. Vit D level was not significantly change by treatment and its value was significantly lower than normal group. Osteocalcin was elevated significantly by treatment; and this elevation was significantly as compared with its initial value and with that of normal group. Amino Terminal telopeptide procollagen type I (NTX-I) was not significantly change by treatment and its value still significantly higher than normal group and before treatment values. Also body mass index value was not significantly changed by treatment. Recommendations: Further studies are recommended to confirm the positive effects of atorvastatin and other statins on bone biochemical markers with larger number of patients and longer period of follow up. Also other bone formation and resorption markers are recommended to determine the expected mechanisms of action of statins on bone remodeling processes.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Treatment of osteoporosis with eldecalcitol, a new vitamin D analog: a comprehensive review and meta-analysis of randomized clinical trials.

ObjectiveEldecalcitol (ELD) is an active form of vitamin D analog that has been approved for the treatment of osteoporosis in Japan. Over recent years, a number of multicenter, randomized controlled clinical trials have been conducted. Our goal is to comprehensively summarize the results from these studies.MethodsWe searched the databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials up to February 28, 2015. Each database was searched using search terms “Eldecalcitol” and “ED-71” and the results were combined. The retrieved data from three independent clinical trials included a total of 1,332 patients with osteoporosis. After the data were pooled from three trials, RevMan software was used to conduct meta-analyses to determine the effects of ELD on bone mineral density (BMD) and bone turnover marker (BTM) type I collagen amino-terminal telopeptide (NTX). Effects of ELD on some of the bone formation and bone resorption parameters, incidence of vertebral fractures at the lower spine, and health-related quality of life (HRQOL) in patients with osteoporosis were also summarized.ResultsWith a test for overall effectZ=6.35, ELD could increase lumbar BMD (P<0.00001). In comparison with alphacalcidol, ELD suppressed the NTX level to a greater degree (test for overall effectZ=3.82,P<0.0001). ELD was also found to suppress bone alkaline phosphatase (BALP) by 19% (P<0.01) and osteocalcin by 19% (P<0.01) at the dose of 0.75 μg/day. Compared to alfacalcidol, ELD showed higher potency in suppressing serum BALP (26±9 vs 32±11 U/L,P<0.05) and amino-terminal propeptide of procollagen I (PINP) (42±15 vs 59±23 ng/mL,P<0.05). In addition, ELD was found to be more effective in reducing the incidence of vertebral fractures at the lower spine (P=0.029).ConclusionOur meta-analysis showed that ELD was more potent than alphacalcidol in reducing BTM (NTX). Clinical data together suggest that ELD is efficient in treating osteoporosis by increasing lumbar BMD; suppressing BTMs, including NTX, BALP, osteocalcin, and PINP; resulting in the reduction in the incidence of vertebral fractures at the lower spine; and increasing the HRQOL in patients with osteoporosis.

Green tea and exercise interventions as nondrug remedies in geriatric patients with rheumatoid arthritis.

This study aimed to evaluate the effects of green tea and supervised exercise training interventions on improvement of disease activity and bone metabolism markers in rheumatoid arthritis patients. [Subjects and Methods] One-hundred and twenty subjects who had a mean age of (60.7 ± 2.53 years) and had been diagnosed with rheumatoid arthritis at least ten years previously were randomly included in this study. Patients were treated with infliximab, green tea, or a supervised exercise program for six months. Disease activity markers as well as antioxidant activity of green tea extracts were estimated before supplementation using in vitro assays. [Results] Rheumatoid arthritis patients treated with green tea for 6 months alone or in combination with infliximab or an exercise program showed significant improvement in disease activity parameters, including C-reactive protein, and erythrocyte sedimentation rate, swollen and tender joints counts, and modified Stanford Health Assessment Questionnaire score, along with an increase in serum levels of bone resorption markers, i.e., deoxypyridinoline, amino-terminal telopeptide of type 1 collagen, and bone alkaline phosphatase, at 6 months of after initial treatment. The European League Against Rheumatism and American College of Rheumatology scores revealed more clinical improvement in the disease activity of rheumatoid arthritis patients treated with green tea along with exercise compared with rheumatoid arthritis patients treated with infliximab or exercise combinations. This may have been due to the higher potential antioxidant activity of green tea (89.6% to 96.5%). [Conclusion] Both exercise and green tea interventions appeared to be beneficial as nondrug modulates for rheumatoid arthritis disorders.

Comparison of clinical cut-points and treatment targets for urine NTX and plasma βCTX-I in osteoporosis

ObjectiveWe undertook to identify levels for plasma β isomerised carboxy-terminal telopeptides of type I collagen (p-βCTX-I) that are comparable to currently used urine amino-terminal telopeptides of type I collagen (u-NTX) cut-points and treatment targets in osteoporosis. Design and methodsFasting morning samples were collected from patients attending tertiary hospitals and clinics for investigation of metabolic bone disease. Patients with Paget's disease or <20years of age were excluded. Second void spot urine for NTX and plasma (EDTA) samples were utilised. Urine was analysed routinely and plasma stored at −20C until analysis by enzyme-linked immunosorbent assay (ELISA) (Immunodiagnostic Systems plc), E170 (Roche Diagnostics) and IDS-iSYS (Immunodiagnostic Systems plc) methods. The relationship of u-NTX with each p-βCTX-I method's results was assessed by Passing and Bablok regression, and p-βCTX-I levels equivalent to u-NTX cut-points and targets were interpolated. ResultsOne hundred and forty six patients were included. Spearman correlation coefficients ranged from 0.71 to 0.75 for the three βCTX-I assays. The equivalent βCTX-I concentrations for NTX/Cr values of 21 (fracture risk reduction target following risedronate therapy), 27 (healthy pre-menopausal women's mean value), and 38 (threshold for reduction of BMD on calcium alone) nmol BCE/mmol were 230, 312 and 462ng/L for the automated Roche assay and 271, 395 and 624ng/L for the automated IDS i-SYS assay respectively. ConclusionsThe p-βCTX-I equivalent to the only available fracture outcome based absolute treatment threshold of 21nmol BCE/mmol established for u-NTX, is close to 250ng/L but will vary between p-βCTX-I assays.

Preliminary Report on the Investigation of the Association Between BPPV and Osteoporosis Using Biomarkers.

To test the hypothesis that levels of a BPPV biomarker, otolin-1, correlate with those of osteoporosis markers, aminoterminal propeptide of protocollagen type I (P1NP), and aminoterminal telopeptides of collagen (NTX), thus further supporting a link between the two diseases. Prospective pilot clinical trial (Level of Evidence: 2b). Postmenopausal women with BPPV. Diagnostic. Serum levels of otolin-1, P1NP, NTX, vitamin D, and calcium were examined in relation to each other, age, and DEXA scan T-scores. There was a strong, negative correlation between T-scores and otolin-1 levels. Although P1NP and NTX levels were strongly correlated, neither had statistical correlations with otolin-1. Despite a strong correlation between DEXA scan results and otolin-1 levels, there were no significant correlations between otolin-1 and P1NP or NTX. This suggests that the association between osteoporosis and BPPV is complex, but not likely to be causal. Although more work is needed to elucidate these relationships, this preliminary finding has important practical implications for BPPV in that proactive management of osteoporosis, per se, would not be expected to have benefits in management of BPPV.

Biochemical markers of bone collagen type I metabolism.

This review focuses on the analysis of diagnostic value of the major bone remodeling markers, in particular synthesis and degradation markers of collagen type I. These include carboxy- and aminoterminal telopeptide, carboxy- and aminoterminal propeptide of procollagen type I, hydroxyproline, hydroxylysine, pyridinoline and deoxypyridinoline. Their measurement allows evaluating the structural and functional conditions and also the rate of metabolic processes in the bone tissue. The advantages and disadvantages of determination of these markers in the condition of different bone diseases were examined. It is shown that determination of bone collagen type I metabolism markers is the most informative for assessment of bone resorption, formation and turnover.