Procollagen Type 1 N-terminal Propeptide Levels Research Articles

Assessment of muscle mass and bone density in elderly patients with type 2 diabetes mellitus depending on the level of glycated hemoglobin

Aim to assess the prevalence of low muscle mass and low bone density in elderly patients with type 2 diabetes (T2DM), depending on the level of glycated hemoglobin (HbA1c).
 Material and methods.The study included 187 patients (mean age 65.16 4.31 years), who were tested for fasting blood glucose, HbA1c, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), C-terminal type I collagen telopeptides (B-CTX), 25-hydroxyvitamin D, body composition and bone mineral density.
 Results.The prevalence of low muscle mass, osteopenia, and osteoporosis in elderly patients with T2DM was 35.8%, 38.5%, and 30.5%, respectively. The prevalence of low muscle mass was significantly higher in women with HbA1c 9.0% (p =0.035). Osteopenia and osteoporosis prevailed in men with HbA1c 9.0% (p=0.007 and p=0.048, respectively). The appendicular skeletal muscle index (ASMI), bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine, BMC and BMD of the thigh were significantly reduced in the osteoporosis and osteopenia groups (p0.05); while B-CTX, P1NP were significantly increased. In men, both ASMI (p=0.007) and P1NP levels (p=0.001) were important risk factors for osteopenia/osteoporosis, and in women such risk factor was ASMI (p=0.019).
 Conclusion.In T2DM patients, the high HbA1c levels were associated with higher rates of low muscle mass in women and osteoporosis in men, and ASMI was a risk factor for osteoporosis in both sexes.

A case of elevated P1NP levels: uncovering Paget's disease in a postmenopausal woman

INTRODUCTION: Procollagen type 1 N-terminal propeptide (P1NP) is a marker of bone formation that is frequently used in the diagnosis and management of osteoporosis. Elevated levels of P1NP may indicate increased bone turnover, which can be a sign of various bone disorders. Paget’s disease of bone is a chronic disorder characterized by excessive and disorganized bone remodeling. The exact cause of Paget’s disease is unknown, but it is thought to be related to genetic factors and viral infections.CASE REPORT: A 48-year-old postmenopausal woman presented with a six-month history of low back pain. Her DEXA scan showed osteopenia in the lumbar spine, and her serum P1NP level was markedly elevated. Further workup revealed a diagnosis of Paget’s disease of bone. The patient was treated with bisphosphonates, resulting in significant improvement in her symptoms and normalization of her P1NP level.CONCLUSIONS: This case highlights the importance of considering Paget’s disease as a potential cause of elevated P1NP levels. The use of bisphosphonates can be effective in treating Paget’s disease and improving bone health. Elevated P1NP levels can be seen in various bone disorders, and clinicians should be aware of its potential clinical implications. The measurement of P1NP is routinely included in the workup of patients with suspected bone disorders, and its levels are used to monitor response to treatment.

Hydroxyapatite-chitosan composites derived from sea cucumbers and shrimp shells ameliorate femoral bone defects in an albino rat model.

A bone defect is defined as a critically sized autologous bone and a bone gap. Bone grafting is one of the most commonly used surgical methods to enhance bone regeneration in orthopedic procedures. A composite of collagen, hydroxyapatite (HA), and chitosan (Ch) is suitable as a bone matrix and stimulates ossification. This study aimed to evaluate the use of natural HA-Ch composites derived from sea cucumbers and shrimp shells and quantify the levels of cytokines, polymorphonuclear neutrophils (PMNs), serum liver enzymes, calcium, phosphate, and procollagen type 1 N-terminal propeptide (PINP) in albino rats with femoral bone defects. A total of 48 albino rats with femoral bone defects were divided into 4 groups (n = 12 each): (C-) placebo, (C+) polyethylene glycol, (T1) HA, and (T2) HA-Ch groups. Each group was divided into two subgroups (n = 6 each), with euthanization on 7- and 42-day post-treatment, respectively. Procollagen Type 1 N-terminal propeptide and the cytokines interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor-alpha were quantified using enzyme-linked immunosorbent assay. Flow cytometry was performed to evaluate PMNs. A clinical chemistry analyzer was used to measure the serum levels of liver enzymes, calcium, and phosphate. There was a significant decrease in the level of IL-6 on 7 days and in the level of IL-10 on 42 days in the HA-Ch group. The level of PMNs also decreased significantly on 7 and 42 days in the HA-Ch group. Regarding serum liver enzymes, alkaline phosphatase (ALP) levels in the HA-Ch group increased significantly on 42 days. Calcium and phosphate levels increased significantly on 7 and 42 days in the HA and HA-Ch groups, and PINP levels increased significantly on 7 and 42 days in the HA-Ch group. The HA-Ch composite derived from sea cucumbers and shrimp shells ameliorated femoral bone defects in albino rats. The HA-Ch composite modulated the levels of IL-6, IL-10, PMNs, ALP, calcium, phosphate, and PINP on 7- and 42-day post-treatment.

Procollagen type 1 N-terminal propeptide, neurofilament light chain, proinflammatory cytokines, and cognitive function in bipolar and major depressive disorders: An exploratory study of brain– bone axis and systemic inflammation

BackgroundHigher levels of neurofilament light chain (NfL) and proinflammatory cytokines (i.e., tumor necrosis factor [TNF]-α) were observed in patients with bipolar disorder (BD) and major depressive disorder (MDD). Procollagen type 1 N-terminal propeptide (P1NP), a bone turnover biomarker, is related to MDD. The association among the brain–bone axis, systemic inflammation, and cognitive function remains unclear in severe affective disorders. MethodsOverall, 25 patients with BD, 24 with MDD, and 29 matched controls were enrolled in the current study and underwent the measurements of the NfL, P1NP, and proinflammatory cytokine levels and 1-back and 2-back working memory tasks. Generalized linear models (GLMs) were used to examine the aforementioned biomarkers between the groups and clarify the association with each other. ResultsGLMs showed increased levels of NfL (p = 0.001, p = 0.020) and P1NP (p = 0.050, p = 0.032) in the patients with BD and MDD than in the controls and suggested significant correlations between the NfL level and the mean time of the 2-back working memory task (p = 0.038) and between P1NL and TNF-α levels (p < 0.001). DiscussionOur study revealed the dysregulated brain–bone axis, indicated by elevated NfL and P1NP levels, and related cognitive impairment and systemic inflammation in the patients with BD and MDD. Additional studies are necessary to elucidate definite pathomechanisms underlying those conditions.

N-MID, P1NP, β-CTX, and phosphorus in adolescents with condylar resorption

Condylar resorption (CR) is a temporomandibular joint disease that causes various physical or functional defects. We aimed to find the association between CR and bone metabolism levels. In this study, we recruited patients visiting the Orthodontic Clinic at Shanghai Ninth People's Hospital from January 2020 to September 2021. Patient characteristics, magnetic resonance imaging examination results, bone mineral density (BMD), Z-score, bone turnover markers, minerals, and hormones were collected and analyzed. The 89 participants were divided into CR (n=46) and normal (n=43) groups. Univariate logistic regression showed that N-terminal mid-fragment of osteocalcin (N-MID), procollagen type 1 N-terminal propeptide (P1NP), β-C-terminal telopeptide of type 1 collagen (β-CTX), and phosphorus (P < .001 for all) were protective factors, and BMD (P=.047) was a risk factor for CR. Multivariable logistic regression showed that N-MID, P1NP, β-CTX, and phosphorus (odds ratio <1, P < .05 for all) were protective factors for CR. Receiver operating characteristic curves showed these indicators to effectively predict CR occurrence (area under the curve >0.7; P < .001). Adolescents with low serum N-MID, P1NP, β-CTX, and phosphorus levels were associated with a higher risk of CR. We suggest that these indicators can guide clinicians in the early detection and prevention of CR in adolescents.

Association between P1NP and bone strength in postmenopausal women treated with teriparatide

ObjectiveTo evaluate the association between P1NP and bone strength in postmenopausal women treated with teriparatide. Materials and MethodsThis prospective study enrolled 248 postmenopausal women with severe osteoporosis treated with teriparatide. Procollagen type 1 N-terminal propeptide (P1NP) were assessed at baseline, 3, 6, and 12 months. Lumbar spine (LS), femoral neck (FN), and total hip (TH) bone mineral density (BMD) and LS trabecular bone score (TBS) were measured by Dual-energy x-ray absorptiometry at baseline and 12 months. ResultsWith teriparatide use, P1NP levels increase and peaked at 6 months. Significant increase in LS and hip BMD and LS TBS were also noted. The percentage change or absolute change >10 μg/L in PINP at 3 months was only related to changes in LS BMD at 12 months. With a median baseline P1NP level was 65.5 ng/mL, we found no correlation between P1NP and LS and hip BMD nor LS TBS. There was no association between LS TBS and axial BMD. After treatment, there was also no significance between the changes in TBS and axial BMD. Over the study period, 83.9% of the 248 participants were persistent with teriparatide at 3 months, 77.8% at 6 months, and 67.3% women at 12 months. ConclusionP1NP levels may provide a signal of osteoporosis risk but is not related to bone strength. Early changes in P1NP may offer information regarding subsequent BMD response so standardized monitoring of P1NP levels at baseline and at 3 months should be considered during osteoporosis therapy. As an additional benefit, serum level monitoring during treatment may also improve medication persistence.

Novel serological biomarker models composed of bone turnover markers, vitamin D, and estradiol and their auxiliary diagnostic value in girls with idiopathic central precocious puberty.

To establish serological biomarker models composed of bone turnover markers (BTMs), vitamin D (Vit D), and estradiol (E2) and to explore their auxiliary diagnostic value in girls with idiopathic central precocious puberty (ICPP). Ninety-three girls with ICPP and 93 healthy girls were included in the ICPP group and the control group, respectively. The serum levels of total procollagen type 1 N-terminal propeptide (P1NP), N-terminal midfragment of osteocalcin (N-MID), β-C-terminal telopeptide of type 1 collagen (β-CTX), Vit D, E2, and other biochemical parameters were detected in all participants. Serological biomarker models for assistance with ICPP diagnosis were established by logistic regression analyses. Serum P1NP, β-CTX, Vit D, and E2 levels differed significantly between the two groups (p<0.05). Three models were established. Model 1 consisted of P1NP and β-CTX, and had an area under curve (AUC) of 0.764, sensitivity of 74.19%, and specificity of 72.04%. Model 2 consisted of P1NP, β-CTX, and Vit D, and had an AUC of 0.840, sensitivity of 83.87%, and specificity of 72.04%. Model 3 consisted of P1NP, β-CTX, Vit D, and E2, and had an AUC of 0.917, sensitivity of 82.80%, and specificity of 86.02%. Serum P1NP, β-CTX, Vit D, and E2 levels may be effective indicators for auxiliary diagnosis of ICPP. Serological biomarker models composed of P1NP, β-CTX, Vit D, and E2 (models 1, 2, and 3) may have auxiliary diagnostic value for ICPP.

Abstract 12013: Procollagen Type 1 N-terminal Propeptide, a Collagen Synthesis Biomarker, is Associated With Adverse Clinical Outcome in Patients With Suspected Acute Coronary Syndrome

Introduction: Procollagen type 1 N-terminal Propeptide (P1NP) is a precursor protein of collagen type 1, a major component of cardiac extracellular matrix. The association of P1NP to clinical outcome in patients with suspected acute coronary syndrome (ACS) has so far not been investigated. The objective of the present study was to assess the predictive value of P1NP concerning adverse clinical outcome in patients admitted for suspected ACS. Methods: Plasma P1NP was measured with an enzyme immune assay in samples taken upon admission from patients enrolled in the Risk markers in Acute Coronary Syndrome (RACS) study (NCT00521976), a Norwegian single center study including patients with suspected ACS from November 2002 to September 2003. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), or stroke within 1 year. Additional analyzes included the composite and its individual components at 1, 2, and 7 years, and cardiac death at 1 and 2 years. Associations between quartiles of P1NP and the endpoints were assessed in both univariate analyzes and in stepwise multivariable Cox regression analyzes fitted with significant clinical variables, past medical history, medication, TnT, BNP, and eGFR before P1NP was introduced. Results: Samples were available from 813 patients (Mean age 69.6 years, 61.4 % males, 52.9% elevated TnT). Mean P1NP levels was 46.2 ng/mL (CI 44.8-47.6). In multivariable Cox analyzes, P1NP was found to be significantly associated with the composite of all-cause mortality, MI, or stroke at 1 year (HR [Q4vsQ1] 1.82, CI 1.12-2.98; p=0.017). This association did not remain significant beyond 1 year. No association was seen for any of the individual components, or cardiac death, at any timepoint, or in patients with elevated TNT (p&gt;0.05 for all). Conclusions: This first study on P1NP in suspected ACS revealed a significant association with adverse clinical outcome (all-cause death, MI, or stroke) at 1 year. However, no predictive value was found concerning outcome for the individual components of the primary endpoint, or cardiac death, at any timepoint, or in patients with elevated TNT.

Association of Serum Periostin Level with Classical Bone Turnover Markers and Bone Mineral Density in Shanghai Chinese Postmenopausal Women with Osteoporosis.

BackgroundIt has been reported that serum periostin levels are significantly higher in postmenopausal patients with osteoporotic fractures. Nonetheless, the levels of serum periostin in postmenopausal women with different bone mass remain unclear.PurposeThe objective of the study was to identify the levels of serum periostin in Chinese postmenopausal women with different bone mass, and the correlations between the periostin levels and the classical bone turnover markers (BTMs), and bone mineral densities (BMDs) at different sites.Patients and MethodsThis study enrolled 331 Chinese postmenopausal women in Shanghai; their clinical features were collected; their levels of serum periostin and traditional BTMs were measured by ELISA or the fully automated immunoassay analyzer; their BMDs at different sites were measured by dual-energy X-ray absorptiometry (DXA).ResultsAccording to the T-value of bone mineral density (BMD), these postmenopausal women were divided into normal group (n=84), osteopenia group (n=126) and osteoporosis group (n=121). There was no significant difference in the serum periostin levels among the above three groups of subjects. In addition, Spearman correlation analysis also revealed that no correlation was observed between the value of serum periostin and those of traditional BTMs, and BMDs at different sites, respectively. The values of traditional BTMs were negatively correlated with those of BMDs at all measured sites. Furthermore, the receiver-operating characteristic (ROC) curves analysis indicated that among the periostin and traditional BTMs mentioned above, the best predictors for postmenopausal osteoporosis in Shanghai Chinese postmenopausal women were osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP) [the areas under the ROC curve (AUC)=0.746 and 0.761, respectively].ConclusionSerum periostin may not be used as a marker of systemic bone metabolism in Shanghai Chinese postmenopausal women without prior fracture. In addition, serum P1NP and OC levels may be the predictors of osteoporosis occurrence in Chinese postmenopausal women.

Efficacy of Daily Supplementation of Milk Fortified With Vitamin D2 for Three Months in Healthy School Children: A Randomized Placebo Controlled Trial

To evaluate the efficacy of daily supplementation of 200 mL milk fortified with 240 IU of vitamin D2 (ergocalciferol). Double-blind randomized controlled trial. School-based study in Delhi between October and December, 2019. 235 healthy children aged 10-14 years. Daily supplementation of 200 mL milk fortified with 240 IU of ergocalciferol in intervention group (n=119) and 200 mL of plain milk in control group (n =116) for 3 months. Change in serum 25 hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), bone formation and resorption markers, and urinary calcium creatinine ratio (U-Ca/CrR). The mean (SD) baseline serum 25(OH) D level in control and fortification groups was 11.9 (3.8) and 11.4 (3.6) ng/mL (P=0.23), respectively. The serum 25(OH)D levels did not increase post-intervention with the dose used for fortification, but were significantly higher in intervention group as compared to control group [10.8 (3.4) vs 6.7 (3.5) ng/mL; P<0.001]. A higher proportion of secondary hyperparathyroidism was observed post-intervention in control (39%) than in intervention group (13.3%); P<0.001. Serum carboxy-terminal telopeptide levels were similar in both groups but the serum procollagen type1 N-terminal propeptide levels were higher in the control than intervention group (P<0.007), following supplementation. Supplementation of milk fortified with approximately 240 IU vitamin D2 for three months did not achieve sufficient serum 25(OH)D levels in Indian children with vitamin D deficiency during winter.

Correlations of Maternal Serum Zinc Levels with Cord Blood Procollagen Type 1-N Terminal Propeptide Levels and Anthropometric Measurements of Newborns

Background: Zinc is an important micronutrient that is required for optimal fetal growth and development. Zinc deficiency during pregnancy may interfere with intrauterine fetal ossification. Fetal ossification can be measured with specific bone growth markers, such as procollagen type 1-N terminal propeptide (P1NP). This study aimed to investigate the mean maternal serum zinc levels and assess the correlations of maternal serum zinc levels with cord blood P1NP levels and anthropometric measurements of newborns. Methods: This cross-sectional study was conducted at Universitas Sumatera Utara Hospital and other hospitals in Medan, Indonesia, from April to October 2019. The statistical populations were pregnant mothers and their newborns who met the inclusion criteria. The participants were selected using a consecutive sampling technique. Maternal serum zinc levels and cord blood P1NP levels were measured before delivery; moreover, anthropometric measurements were conducted in this study. Results: A total of 42 subjects were included in this study with a mean maternal serum zinc level of 52.0±9.0 µg/dL. The proportion of pregnant mothers with low serum zinc levels was high (54.8%). According to the results, there was a significant correlation between maternal serum zinc levels and newborn birth weight (r=0.648) and length (r=0.656), as well as head circumference (r=0.578; P=0.001). There was also a significant and positive linear correlation between maternal serum zinc levels and cord blood P1NP levels (r=0.469; P=0.002). Conclusion: The mean maternal serum zinc levels during pregnancy were below normal. There were positive significant correlations between maternal serum zinc levels and cord blood P1NP levels with anthropometric measurements of newborns.

Examining zoledronic acid for the prevention of bone loss in patients receiving bariatric surgery

PurposeBariatric surgery is an effective treatment for severe obesity but causes substantial bone loss and increased risk of fractures. To date, there have been no studies examining whether pharmacologic treatments can prevent bone loss after bariatric surgery. We performed an exploratory study to examine the preliminary safety and efficacy of zoledronic acid (ZOL), a potent anti-resorptive bisphosphonate, to suppress bone turnover markers (BTM) and prevent declines in bone mineral density (BMD) after Roux-en-Y gastric bypass (RYGB) surgery. MethodsWe performed an open-label pilot study of pre-operative ZOL in postmenopausal women with obesity who were planning RYGB (n = 4). A single dose of zoledronic acid 5 mg was given intravenously prior to RYGB. Serum bone biochemistries including C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) were measured at multiple timepoints throughout the 24-week study. BMD was also obtained at the spine and hip by dual-energy x-ray absorptiometry (DXA) and at the trabecular spine by quantitative computed tomography (QCT) at pre-operative baseline and 24 weeks. Results were compared against pre-operative baseline and against changes among RYGB historical controls (n = 10). ResultsAt 2 weeks after RYGB, there was a nonsignificant trend for CTX and P1NP levels to be lower than baseline levels in the ZOL group. By 24 weeks after RYGB, however, participants who received ZOL had a significant increase in CTX above pre-operative baseline (+0.228 ± 0.117 ng/dL, p = 0.030) but this CTX rise was less than that observed in the controls (+0.601 ± 0.307 ng/dL, p = 0.042 between groups). Despite ZOL use, participants had significant areal BMD loss at the total hip as compared to pre-operative baseline (−4.2 ± 1.5%, p = 0.012) that was similar in magnitude to total hip BMD loss in the controls (−5.5 ± 3.9%, p = 0.005). There was a suggestion that the ZOL group might be protected against trabecular spine volumetric bone loss as compared to the control group (+4.8 ± 8.0% vs. -5.9 ± 7.0%, p = 0.075 between groups). Serum calcium, 25-hydroxyvitamin D, and parathyroid hormone did not change in either group. No hypocalcemia or serious adverse events were reported after ZOL. ConclusionIn this proof of concept study, a single dose of ZOL prior to RYGB appeared to transiently mitigate but not fully prevent high bone turnover in the acute postoperative period. At 24 weeks after RYGB, our preliminary data suggest that ZOL was not sufficient to prevent bone loss at the hip, although it may preserve bone density at the trabecular spine. Further prospective, controlled studies are needed to confirm our findings and to identify the best strategies for preventing bone loss in bariatric patients receiving RYGB.

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

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

Characteristics of bone turnover markers in women with gestational diabetes mellitus

BackgroundBone turnover markers (BTMs) can be applied to the assessment of bone formation and bone resorption activity. The aim of this study was to investigate the changes in BTMs in women with gestational diabetes mellitus (GDM). MethodsOne hundred and five women with gestational diabetes mellitus defined as the GDM group and 46 healthy pregnant women with normal glucose tolerance selected as the control group were enrolled in this study. Serum samples were collected during regular obstetric examinations and the serum levels of total procollagen type 1 N-terminal propeptide (P1NP), N-terminal midfragment of osteocalcin (N-MID), and β-C-terminal telopeptide of type 1 collagen (β-CTX) were measured. An independent-sample t-test, the Mann–Whitney U test, and a Pearson correlation analysis were performed for data analyses. ResultsSerum β-CTX levels in the GDM group were significantly higher than those in the control group (296.00 [235.00–369.00] pg/mL vs. 218.5 [165.25–292.50] pg/mL, p < 0.05), while P1NP and N-MID levels did not differ between the two groups. The Pearson correlation analysis revealed that β-CTX level was correlated with blood glucose level. ConclusionsThe difference in β-CTX levels indicated that bone resorption in patients with GDM diabetes was higher than that in pregnant women with normal glucose tolerance. No obvious differences in bone formation markers P1NP and N-MID were found between the two groups.

Separate and Combined Effects of GIP and GLP-1 Infusions on Bone Metabolism in Overweight Men Without Diabetes.

The gut-derived incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) have been suggested to play a role in bone metabolism. Exogenous administration of GIP inhibits bone resorption, but the effect of GLP-1 is less clear. Furthermore, the combined effect of exogenous GIP and GLP-1 on bone metabolism is unknown. To investigate the effect of separate and combined infusions of the incretin hormones GIP and GLP-1 on bone resorption and formation. Randomized, double-blinded, placebo-controlled, crossover study including five study days. Seventeen overweight/obese men. On the first study day, a 50-g oral glucose tolerance test (OGTT) was performed. On the next four study days, isoglycemic IV glucose infusions (IIGI), mimicking the glucose excursions from the OGTT, were performed with concomitant infusions of GIP (4 pmol/kg/min), GLP-1 (1 pmol/kg/min), GIP+GLP-1 (4 and 1 pmol/kg/min, respectively), or placebo, respectively. Changes in bone resorption assessed by measurements of carboxy-terminal type I collagen crosslinks (CTX) and in bone formation as assessed by procollagen type 1 N-terminal propeptide (P1NP) concentrations. During the OGTT, CTX was significantly lowered by 54 ± 13% from baseline (mean ± SD) compared with 28 ± 12% during IIGI + saline (P < 0.0001). During IIGI+GLP-1 and IIGI+GIP, CTX was lowered by 65 ± 16% and 74 ± 9%, respectively, from baseline, whereas IGII+GIP+GLP-1 lowered CTX by 84 ± 4% from baseline. P1NP levels were unaffected by the interventions. Our data suggest that GLP-1, like GIP, may be involved in regulation of bone resorption and that GIP and GLP-1 together have partially additive inhibitory effects.

Serum 25(OH)D is associated with an altered bone turnover marker response after a hip fracture.

C-terminal telopeptide of type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) are bone turnover markers (BTMs) that are promising surrogate measures of fracture healing; however, it is unknown if their response is affected by other bone healing metabolites. Since 70% of fracture patients are reported to have insufficient serum vitamin D, we sought to determine if serum 25(OH)D levels are associated with differential changes in CTX and P1NP concentrations after hip fracture. This prospective cohort included hip fracture patients 65 years of age or older admitted to one of eight Baltimore-area hospitals. Serum samples were collected at baseline, 2-, 6-, and 12-month post-fracture. A mixed-effects repeated-measures analysis was used to determine the longitudinal association between vitamin D deficiency (25(OH)D < 20 ng/ml) and CTX and P1NP. Baseline lab values were obtained for 296 participants (mean age, 80.8 years; 51% male; 55% 25(OH)D < 20 ng/ml). During the acute fracture healing period P1NP concentrations increased by 14% (95%CI: 7-21%, p < 0.01) while CTX levels did not change (p = 0.07). Both CTX and P1NP decreased below baseline at 6 and 12 months. CTX levels were higher in participants with baseline 25(OH)D < 20 ng/ml (p = 0.01). There was no association between 25(OH)D < 20 ng/ml and P1NP levels over the study duration (p = 0.33). Data from this large, longitudinal cohort support claims that CTX and P1NP concentrations change during fracture healing; however, the differential response of CTX among vitamin D deficient patients highlights important questions for its utility as a reliable surrogate marker of fracture healing. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Mono- and Co-Activation of the GIP and GLP-1 Receptors Inhibits Bone Resorption

We investigated the effect of mono- and co-administration of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) on bone resorption and formation. Seventeen overweight/obese men without diabetes were included in a randomized, double-blinded, placebo-controlled, cross-over study and subjected to a 50g oral glucose tolerance test (OGTT) and four isoglycemic intravenous glucose infusions (IIGI), mimicking the glucose excursions from the OGTT, with concomitant infusions of GIP (4 pmol/kg/min), GLP-1 (1 pmol/kg/min), GIP+GLP-1 (4 and 1 pmol/kg/min, respectively) or placebo. Bone resorption and formation were assessed by measurements of carboxy-terminal type 1 collagen crosslinks (CTX), and procollagen type 1 N-terminal propeptide (P1NP), respectively. Suppression of CTX is shown in Fig. 1. During OGTT the baseline subtracted area under the curve (bsAUC) was significantly lower than during IIGI+saline infusion (-9,117±566 (mean±SEM) vs. -4,333±583 %×min, P&amp;lt;0.0001). Infusion of GLP-1 and GIP significantly potentiated CTX suppression to -10,751±799 %×min and 13,714±440 %×min, respectively. Co-administration of GIP+GLP-1 suppressed CTX to -15,466±268 %×min. P1NP levels were unaffected. Our data suggest that GLP-1, like GIP, may be involved in bone homeostasis and that co-administration of GIP+GLP-1 inhibits bone resorption more than each hormone alone. Disclosure N.C. Bergmann: Employee; Self; Zealand Pharma A/S. A.B. Lund: Other Relationship; Self; Novo Nordisk A/S. S.M. Heimbürger: Research Support; Self; Novo Nordisk A/S. L. Jessen: Employee; Self; Zealand Pharma A/S. Stock/Shareholder; Self; Zealand Pharma A/S, Novo Nordisk A/S. M.B. Christensen: None. T. Vilsbøll: Advisory Panel; Self; Amgen Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, AstraZeneca, MSD K.K., Sanofi, Novo Nordisk A/S. Consultant; Self; Amgen Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, AstraZeneca, MSD K.K., Sanofi, Novo Nordisk A/S. Speaker's Bureau; Self; Amgen Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, AstraZeneca, MSD K.K., Sanofi, Novo Nordisk A/S. Research Support; Self; Eli Lilly and Company, Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp.. Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Consultant; Self; Amgen Inc.. Advisory Panel; Self; MedImmune, Sanofi. Consultant; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi.

Naringin protects against bone loss in steroid-treated inflammatory bowel disease in a rat model

We observed the effects of naringin on bone loss in glucocorticoid-treated inflammatory bowel disease (IBD) in a rat model. The IBD model was established in Sprague-Dawley rats by administering 5.0% dextran sodium sulfate. Dexamethasone (DEX) and naringin were given at the second week. Blood, colon and bone samples were collected for biomarker assay, histological analysis or microCT analysis. Superoxide dismutase, catalase and malonaldehyde were measured in bone. A significant decrease of procollagen type 1 N-terminal propeptide (P1NP) level was observed in DEX-treated IBD groups compared with the control (p < 0.05). P1NP levels were dose-dependently increased in the presence of naringin intervention. Bone loss and decreased bone biomechanical properties were observed in DEX-treated IBD rats compared with control rats (p < 0.01). Naringin intervention protected against bone loss and decreased bone biomechanical properties. Bone formation related gene mRNA expressions were significantly decreased in DEX-treated IBD rats compared with control rats. Naringin administration reversed the down-regulation of the expressions of those genes. Naringin treatment reduced the oxidative stress in bone from DEX-treated IBD rats. Our data indicated that naringin may have great potential for the treatment of bone loss in glucocorticoid-treated IBD patients via blocking oxidative stress and promoting bone formation.

Effect of isolated vitamin D supplementation on bone turnover markers in younger postmenopausal women: a randomized, double-blind, placebo-controlled trial.

The purpose of this study is to evaluate the effect of VD supplementation alone on bone turnover markers in younger postmenopausal women. In this double-blind, placebo-controlled trial, 160 women were randomized into the VD group (supplementation with 1000IU of vitamin D3/day, orally; n = 80) or placebo group (n = 80). Women aged 50-65years with amenorrhea ≥ 12months and normal bone mineral density were included. The intervention lasted 9months, and the participants were assessed at the beginning and end of treatment. Serum levels of total calcium, parathormone (PTH), alkaline phosphatase (AP), and 24-h urine calcium were determined. Serum C-terminal telopeptide of type I collagen (s-CTX) and procollagen type 1 N-terminal propeptide (P1NP) were measured by immunoassay as markers of bone resorption and formation, respectively. Plasma 25-hydroxyvitamin-D [25(OH)D] concentrations were measured by HPLC. Intention-to-treat analysis was performed using ANOVA, Student's t test, Tukey's test, and gamma distribution. Over the period of 9months, 25(OH)D concentrations increased from 15.0 ± 7.5 to 27.5 ± 10.4ng/mL (+ 45.4%) in the VD group and decreased from 16.9 ± 6.7 to 13.8 ± 6.0ng/mL (- 18.5%) in the placebo group (p< 0.001). There was a decrease (- 21.3%) of PTH levels in the VD group with a significant difference between groups at the end of the study (p< 0.001). No significant differences were observed in the other laboratory parameters (total calcium, AP, and calciuria) in either group (p> 0.05). A comparison of bone turnover markers showed a significant reduction in of s-CTX (- 24.2%, p< .0001) and P1NP (- 13.4%, p= 0.003) levels in the VD group. No significant variations in bone turnover markers were observed in the placebo group (s-CTX, - 6.9%, p= 0.092 and P1NP, - 0.6%, p= 0.918). In younger postmenopausal women with VD deficiency, isolated supplementation with 1000IU of vitamin D3 for 9months is associated with a reduction in bone turnover markers. However, any between-group differences was not observed in bone turnover markers.

Bone Mineral Density and Physical Performance of Female Patients 27 Years or Longer after Surgery for Adolescent Idiopathic Scoliosis.

Study DesignRetrospective cohort study.PurposeTo assess bone mineral density (BMD) and bone metabolism ≥27 years after surgery in female patients who underwent spinal fusion for adolescent idiopathic scoliosis (AIS) during adolescence and to determine their associations with physical performance. Overview of LiteratureThere are no studies investigating postsurgical BMD in middle-aged AIS patients.MethodsThis study included 23 patients who provided informed consent among 229 female patients with AIS who underwent spinal fusion from 1968 until 1988. Average age at the time of observation was 48.8 years. BMD was measured at the left femoral neck, and the levels of two bone metabolism markers–procollagen type 1 N-terminal propeptide (P1NP) and tartrate-resistant acid phosphatase 5b (TRACP-5b)–were measured from blood samples. Physical performance was measured using grip strength, sit-ups, sit-and-reach, side step, and standing long jump.ResultsMean BMD was 0.784 g/cm2. According to the World Health Organization diagnostic criteria, one subject (4.3%) had osteoporosis, whereas nine subjects (39.1%) had osteopenia. In patients with osteoporosis or osteopenia, P1NP and TRACP-5b levels were high, and BMD loss was because of high metabolic turnover. All calculated standard scores for physical performance were lower in the study cohort than in healthy individuals. There was a positive correlation between BMD and the standard score for grip strength, whereas there were weak positive correlations between BMD and the standard scores for side step and standing long jump.ConclusionsIn female AIS patients who underwent spinal fusion in adolescence, 4.3% and 39.1% had osteoporosis and osteopenia, respectively, ≥27 years after surgery. Exercise performance of these patients was poor compared with the national standards. In these patients, increased physical activity should be encouraged to prevent BMD loss in middle age.