Serum C-terminal Cross-linking Telopeptide Research Articles

Changes of bone turnover markers and bone mineral density among postmenopausal Thai women with osteoporosis receiving generic risedronate

BackgroundOsteoporosis has been recognized as a significant health issue in Thailand. Pharmacological interventions are important way to prevent fracture. However, one of the main challenges in selecting a medication is high cost, particularly for brand-name drugs. Data on generic bisphosphonate use in Thai are still lacking. Therefore, our study aimed to assess the efficacy and safety of generic risedronate in postmenopausal Thai women with osteoporosis.MethodsThis prospective study was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from December 2022 to January 2024. Serum C-terminal cross-linking telopeptide of type I collagen (CTX) and procollagen type I N-propeptide (P1NP) were measured at baseline. All participants subsequently received 35 milligrams of oral risedronate once weekly for 52 weeks. Serum CTX and P1NP were remeasured at different time points. BMD was reevaluated at 52 weeks after risedronate treatment initiation.ResultsA total of 80 participants were included. The mean age was 65.2 ± 6.6 years. The mean body mass index (BMI) was 23.45 ± 3.49 kg/m2. The median (IQR) serum CTX level at 12 weeks was significantly lower than that at baseline (0.28 (0.16–0.46) ng/mL versus 0.44 (0.26–0.64) ng/mL, respectively; p value < 0.01). The suppression of serum CTX was confirmed at 52 weeks after treatment initiation. Compared with those at baseline, the serum P1NP levels were significantly lower at 24 weeks after treatment initiation (30.33 (19.19–39.58) ng/mL versus 41.90 (30.33–68.67) ng/mL, respectively; p value < 0.01). In terms of the BMD assessment at 52 weeks, significant improvements were observed in both areal BMD (g/cm2) and T scores at all measured sites compared with baseline. The lumbar spine, femoral neck, and total hip BMD increased from baseline by 4.76%, 3.84% and 4.54%, respectively.ConclusionPostmenopausal women with osteoporosis who were treated with generic risedronate demonstrated significant suppression of the bone remodelling process at 3, 6, and 12 months after treatment initiation. Additionally, significant improvements in the lumbar spine, femoral neck, and total hip BMD were observed at 12 months of therapy. These findings suggest that generic risedronate could be considered a reasonable and interesting option for treating postmenopausal women with osteoporosis in Thailand.

Evaluation of the protective dose-dependent effect of metformin for induced osteoarthritis in rats.

To evaluate the potential protective effect of metformin against osteoarthritis development in rats. The experimental study was conducted at the Iraqi Centre for Cancer Research and Medical Genetics, Mustansiriyah University, Baghdad, Iraq, from December 2021 to February 2022, and comprised male Sprague- Dawley mice who were divided into 5 equal groups: negative control group, osteoarthritis group subjected to monoiodoacetate induction, positive control group treated with celecoxib 30mg/kg, metformin 100mg/kg group, and metformin 200mg/kg group. Body mass index, inflammatory biomarkers, and serum C-terminal cross-linked telopeptide of type II collagen levels were noted for all the animals. Data was analysed using SPSS 24. Of the 35 mice, 7(20%) were in each of the 5 groups. Compared to the osteoarthritis group, metformintreated mice showed significantly reduced body mass index, inflammatory biomarker levels, and blood levels of Cterminal cross-linked telopeptide of type II collagen (p=0.05). Metformin 200mg/kg treatment had more beneficial effects than 100mg/kg dose on inflammatory biomarkers and serum C-terminal cross-linked telopeptide of type II collagen (p=0.05). A beneficial protective effect against the onset of osteoarthritis was produced by metformin in a dosedependent way. Additionally, metformin could lessen cartilage damage as demonstrated by a decrease in the serum levels of C-terminal cross-linked telopeptide of type II collagen in the osteoarthritis group.

Alteration of growth performance, glycolipid metabolism, and bone characteristics of broiler chickens in response to different inclusion levels of dietary wheat.

The aim of this study was to evaluate the effects of different levels of wheat inclusion on growth performance, glycolipid metabolism, and tibial properties of broiler chickens. A total of 480 1-d-old male broiler chickens were initially fed identical starter diets until d 10. Subsequently, they were divided into 3 treatments consisting of 8 replicates with 20 birds per replicate, i.e., 1) low-level wheat addition group, with wheat ratios of 15% and 25% during the grower and finisher periods, respectively; 2) medium-level wheat inclusion group, incorporating 30% and 40% wheat in the grower and finisher diets, respectively; and 3) high-level wheat addition group, containing 55.8% and 62.4% wheat in the grower and finisher diets, until d 39. When compared to the low- and medium-level wheat diet, the high-level wheat inclusion in the diet increased feed intake and reduced the feed conversion ratio (both p<0.01), which was accompanied by a longer jejunum (p=0.031). Meanwhile, the high-level addition of wheat displayed a decreased abundance of Ruminococcin, Bacteroidetes, and Lactobacillus than the low-wheat group. With the increase of the proportion of wheat treatment, the contents of cholesterol, triglyceride, and high-density lipoprotein cholesterol were elevated in serum, whereas the concentration of serum C-terminal cross-linked telopeptide of type I collagen, a bone resorption marker, was decreased. In addition, the diet with medium and high levels of wheat improved the yield load of tibia, along with comparable bone dimension and weight. The medium- and high-level wheat additions increased serum glycolipid deposition and enhanced tibial mechanical properties, whereas the high-level wheat diet compromised the growth performance of broiler chickens, which might be associated with the alteration of gut microbiota.

Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature

SummaryVertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate.PurposeTumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods.MethodsThis was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center.ResultsVertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (β-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis.Conclusion68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

Liraglutide, a glucagon-like peptide-1 receptor agonist, inhibits bone loss in an animal model of osteoporosis with or without diabetes.

Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes. Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies. Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.

Management and Amelioration of Knee Joint Osteoarthritis in Adults Using a Novel High-Functional Bovine Collagen Peptide as a Nutritional Therapy: A Double-Blind, Prospective, Multicentric, Randomized, Active and Placebo Controlled, Five-Arm, Clinical Study to Evaluate the Efficacy, Safety, and Tolerability.

The various functionalities of collagen peptides have generated a large interest in utilizing the bioactive peptides as a nutritional therapy to ameliorate various physiological degenerative conditions. Collagen peptides are observed to reduce the pain and aligned difficulties with respect to osteoarthritis. Here we report the enhanced ameliorating property of novel high-functional "Wellnex" Type J collagen peptides following a double-blind randomized active and placebo-controlled 5-arm clinical trial (n = 100) by using it as a nutritional supplement in subjects with knee joint osteoarthritis in comparison with conventional bovine collagen peptides. The efficacy, safety, and tolerability were also studied. Dosages of 2.5, 5.0, and 10.0 g of high-functional Type J bovine collagen peptides, 10.0 g of conventional collagen peptides, and 10.0 g of placebo were given to the 5 groups for a period of 90 days. The Western Ontario McMaster Universities Arthritis Index (WOMAC) score, Pain Scale, Quality of Life (QoL), Physician's Impression of change Score (PICS), serum C-terminal cross-linked telopeptide of type II collagen (CTX-II) levels and Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) parameters were monitored. Type J 2.5 g showed significant improvement in WOMAC, QoL, CTX, and MOAKS and observed to be equivalent to conventional collagen peptide 10-g supplementation in terms of efficacy. The two significant outcomes of the study were that Type J 10.0 g, Type J 5.0 g, Type J 2.5 g and conventional collagen peptides 10.0 g supplementation were observed to be beneficial nutraceutical therapies for knee joint osteoarthritis, and Type J 2.5 g supplementation was equivalent to conventional collagen peptides 10.0-g supplementation in terms of efficacy.

A clinical retrospective study of implant as a risk factor for medication-related osteonecrosis of the jaw: surgery vs loading?

BackgroundRisk factors for developing medication-related osteonecrosis of the jaw (MRONJ) include the general condition of the patient, smoking habit, poor oral hygiene, and the type, duration, and administration route of the drug, dentoalveolar surgery, such as implant placement. This study aimed to discuss whether implants may induce osteonecrosis in older patients receiving long-term medication and to analyze the radiological pattern of the bone necrosis.MethodsThis study included 33 patients diagnosed with dental implant-associated medication-related osteonecrosis of the jaw. Data regarding the medical history, type of medication used, durations of administration, laboratory test results, onset of bone necrosis since implant placement, type of opposing teeth, and radiological pattern of the bone necrosis on cone-beam computed tomography were recorded in patients with and without implants.ResultsThe most commonly used drug was bisphosphonate, with an average duration of use of 61.37 (± 53.72) months. The laboratory results showed average serum C-terminal cross-linking telopeptide (CTX) level of 0.23 ng/mL, vitamin D, 23.42 ng/mL, and osteocalcin, 4.92 ng/mL. Osteonecrosis occurred after an average of 51.03 (± 39.75) months following implant placement. Radiological evaluation revealed obvious sequestration in the implant-absent group, and the formation of a unit sequestration with an implant fixture (en bloc) was observed in the implant-present group. The patients underwent surgical treatment of sequestrectomy and explantation.ConclusionImplant placement, especially loading, may be considered a potential risk factor for the development of osteonecrosis in patients undergoing antiresorptive treatment.

Efficacy of sCOMP and sCTX-I in Diagnosis of Knee Osteoarthritis.

The aim of this study was to evaluate the efficacy of serum cartilage oligomeric matrix protein (sCOMP) and serum C-terminal cross-linked telopeptide of type I collagen (sCTX-I) in identifying disease severity in knee osteoarthritis (KOA) cases. A total of 150 individuals (100 cases and 50 controls) were recruited. They were assessed clinically and radiologically with WOMAC score and knee radiographsrespectively, while biochemical assessment was done by serum COMP and serum CTX-I level. There were significant differences in serum levels between healthy individuals and KOA patients of both, sCOMP (01.16 ± 0.39 vs 17.38 ± 4.99U/L; p = 0.01) and sCTX-I (0.35 ± 0.14 vs 4.59 ± 1.69; p = 0.02). There was a statistically significant difference between serum levels of CTX-I between K-L grade I and grade II (4.59 ± 1.69 vs 4.60 ± 1.17ng/mL; p = 0.03) but no significant difference was seen in the sCOMP levels between K-L grade I and grade II (14.60 ± 6.47 vs 17.47 ± 4.99U/L; p = 0.14). Our findings reveal that both sCOMP and sCTX-I are very effective in distinguishing between healthy adults and those affected by KOA. Only CTX-I was also able to distinguish between K-L grades I and II, while sCOMP failed. Further, use of these two biomarkers to differentiate between K-L grade II, III and IV is limited and lacks sufficient discriminating power, hence not recommended.

Dietary Zinc Glycine Supplementation Improves Tibia Quality of Meat Ducks by Modulating the Intestinal Barrier and Bone Resorption.

Leg problems characterized by gait abnormity and bone structure destruction are associated with a high risk of fractures and continuous pain in poultry. Zinc (Zn) acts a pivotal part in normal bone homeostasis and has proven to be highly effective in alleviating leg problems. Therefore, the effects of graded concentration of Zn on bone quality were evaluated in this study. A total of 512 1-d-old male ducks were fed 4 basal diets added 30mg/kg Zn, 60mg/kg Zn, 90mg/kg Zn, and 120mg/kg Zn as Zn glycine for 35 d. Tibia Zn content, ash percentage, and breaking strength linearly increased with dietary elevated Zn level (P < 0.05). Broken-line analysis revealed that the recommended level of Zn from Zn glycine was 55.13mg/kg and 64.48mg/kg based on tibia ash and strength, respectively. To further confirm the role of dietary Zn glycine addition on bone characteristics, data from birds fed either 60mg/kg Zn as Zn sulfate (ZnSO4), 30mg/kg Zn, or 60mg/kg Zn in the form of Zn glycine indicated that birds given 60mg/kg Zn from Zn glycine diet exhibited higher tibia ash, strength, and trabecular volume compared to those fed the 30mg/kg Zn diet (P < 0.05). Dietary 60mg/kg Zn as Zn glycine addition decreased intestinal permeability, upregulated the mRNA expression of tight junction protein, and increased the abundance of Lactobacillus and Bifidobacterium, which was companied by declined the level of inflammatory cytokines in both the ileum and bone marrow. Regarding bone turnover, the diet with 60mg/kg Zn from Zn glycine induced osteoprotegerin expression and thus decreased osteoclast number and serum bone resorption biomarker levels including serum tartrate-resistant acid phosphatase activity and C-terminal cross-linked telopeptide of type I collagen level when compared to 30mg/kg Zn diet (P < 0.05). Except for the upregulation in runt-related transcription factor 2 transcription, the experimental treatments did not apparently change the bone formation biomarker contents in serum. Additionally, Zn glycine displayed a more efficient absorption rate, evidenced by higher serum Zn level, and thus had potentially greater a protective role in the intestine barrier and tibia mass as compared to ZnSO4. Collectively, the dietary supplementation of 60mg/kg in the form of Zn glycine could suppress bone resorption mediated by osteoclast and consequently improve tibial quality of meat ducks, in which enhanced intestinal integrity and optimized gut microbiota might be involved.

Drinking Natural Mineral Water Maintains Bone Health in Young Rats With Metabolic Acidosis

IntroductionMetabolic acidosis affects bone health. It remains unclear whether drinking natural mineral water is better for maintaining bone health in the youth with metabolic acidosis.Materials and MethodsSixty young female rats (3-weeks-old) were randomly divided into three groups and drank purified water (PW, as control), bicarbonate-rich natural mineral water (Bic-NMW), or sulfate-rich natural mineral water (Sul-NMW), which, respectively, contained calcium (0.17, 155, and 175 mg/L), bicarbonate (0.1360, and 139 mg/L) and sulfate (0, 35.6, and 532 mg/L), for 16 weeks. In the last 3 weeks, metabolic acidosis was induced in 10 rats per group by adding NH4Cl (0.28 mM) to drinking water. The rats' blood, urine, and femur were collected for assessing acid-base status, calcium metabolism, bone microstructure, and strength. The difference between the three groups was determined using one-way ANOVA followed by the Student–Newman–Keuls test or Dunnett's T3 test.ResultsCompared with the PW rats, the Bic-NMW rats and the Sul-NMW rats had less urine net acid excretion (−1.51, 0.20 vs. 10.77, EQ/L), higher bone mineral density (442.50, 407.49 vs. 373.28, mg/mm3), growth cartilage width (271.83, 283.83 vs. 233.27, μm) and cortical trabecular area (9.33, 9.55 vs. 5.05, mm2), and smaller cortical marrow cavity area (5.40, 5.49 vs. 7.27, mm2) in the femur (P < 0.05). Besides, the Bic-NMW rats had less serum calcium (2.53 vs. 2.68, mmol/L) and C-terminal cross-linked telopeptide of type-I collagen (1.35 vs. 1.93, ng/mL), and higher serum calcitonin (0.61 vs. 0.39, μg/L), femoral trabecular thickness (0.10 vs. 0.09, μm), bone volume/total volume (0.42 vs. 0.34, %), cortical bone area (15.91 vs. 12.80, mm2), and ultimate stress (35.12 vs. 29.32, MPa) (P < 0.05). The Sul-NMW rats had more osteoclasts (22.50 vs. 11.54, cells/field) (P < 0.05).ConclusionsDrinking natural mineral water, especially bicarbonate-rich natural mineral water, is effective in improving bone health in young rats with metabolic acidosis. These benefits include maintaining bone mineral density, and improving bone microstructure and biomechanical properties via moderating metabolic acidosis.

Acidification of drinking water improved tibia mass of broilers through the alterations of intestinal barrier and microbiota.

ObjectiveDiet acidification supplementation is known to influence intestinal morphology, gut microbiota, and on phosphorus (P) utilization of broilers. Alterations in intestinal barrier and microbiota have been associated with systemic inflammation and thus regulating bone turnover. Hence the effect of acidifier addition to drinking water on tibia mass and the linkages between intestinal integrity and bone were studied.MethodsOne-d-old male broilers were randomly assigned to normal water (control) or continuous supply of acidified water (2% the blend of 2-hydroxy-4-methylthiobutyric acid, lactic, and phosphoric acid) group with 5 replicates of 10 chicks per replicate for 42 d.ResultsAcidification of drinking water improved the ash percentage and calcium content of tibia at 42 d. Broilers receiving acidified water had increased serum P concentration compared to control birds. The acidified group showed improved intestinal barrier, evidenced by increased wall thickness, villus height, the villus height to crypt depth ratio, and upregulated mucin-2 expression in ileum. Broilers receiving drinking water containing mixed organic acids had a higher proportion of Firmicutes and the ratio of Firmicutes and Bacteroidetes, as well as a lower population of Proteobacteria. Meanwhile, the addition of acidifier to drinking water resulted in declined ileal and serum proinflammatory factors level and increased immunoglobulin concentrations in serum. Concerning bone remodeling, acidifier addition was linked to a decrease in serum C-terminal cross-linked telopeptide of type I collagen and tartrate-resistant acid phosphatase reflecting bone resorption, whereas it did not apparently change serum alkaline phosphatase activity that is a bone formation marker.ConclusionAcidified drinking water increased tibia mineral deposition of broilers, which was probably linked with higher P utilization and decreased bone resorption through improved intestinal integrity and gut microbiota and through decreased systemic inflammation.

25-hydroxycholecalciferol reverses heat induced alterations in bone quality in finisher broilers associated with effects on intestinal integrity and inflammation

BackgroundAlterations in ambient temperature have been associated with multiple detrimental effects on broilers such as intestinal barrier disruption and dysbiosis resulting in systemic inflammation. Inflammation and 25-hydroxycholecalciferol (25-OH-D3) have shown to play a negative and positive role, respectively, in the regulation of bone mass. Hence the potential of 25-OH-D3 in alleviating heat induced bone alterations and its mechanisms was studied.ResultsHeat stress (HS) directly induced a decrease in tibia material properties and bone mass, as demonstrated by lower mineral content, and HS caused a notable increase in intestinal permeability. Treatment with dietary 25-OH-D3 reversed the HS-induced bone loss and barrier leak. Broilers suffering from HS exhibited dysbiosis and increased expression of inflammatory cytokines in the ileum and bone marrow, as well as increased osteoclast number and activity. The changes were prevented by dietary 25-OH-D3 administration. Specifically, dietary 25-OH-D3 addition decreased abundance of B- and T-cells in blood, and the expression of inflammatory cytokines, especially TNF-α, in both the ileum and bone marrow, but did not alter the diversity and population or composition of major bacterial phyla. With regard to bone remodeling, dietary 25-OH-D3 supplementation was linked to a decrease in serum C-terminal cross-linked telopeptide of type I collagen reflecting bone resorption and a concomitant decrement in osteoclast-specific marker genes expression (e.g. cathepsin K), whereas it did not apparently change serum bone formation markers during HS.ConclusionsThese data underscore the damage of HS to intestinal integrity and bone health, as well as that dietary 25-OH-D3 supplementation was identified as a potential therapy for preventing these adverse effects.

Oral Administration of Quercetin or Its Derivatives Inhibit Bone Loss in Animal Model of Osteoporosis.

Objectives. Quercetin (Q) and its derivatives are the major members of the naturally occurring flavonoid family, which possess beneficial effects on disease prevention including osteoporosis. The present study is aimed at further investigating the efficacy of the Q and its derivatives on bone pathology, bone-related parameters under imageology, bone maximum load, and serum bone metabolism indexes in animal model of osteoporosis. Potential mechanisms of Q and its derivatives in the treatment of osteoporosis as well as the existing problems regarding the modeling method and limitations of researches in this area were also summarized. Eight databases were searched from their inception dates to February 2020. Nineteen eligible studies containing 21 comparisons were identified ultimately. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. The results displayed the number of criteria met varied from 3/10 to 7/10 with an average of 5.05. The present study provided the preliminary preclinical evidence that oral administration of Q or its derivatives was capable of improving bone pathology, bone-related parameters under imageology and bone maximum load, increasing serum osteocalcin, alkaline phosphatase, and estradiol, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P < 0.05). No statistical difference was seen in survival rate, index of liver, or kidney function (P > 0.05). Q and its derivatives partially reverse osteopenia probably via antioxidant, anti-inflammatory, promoting osteogenesis, inhibiting osteoclasts, and its estrogen-like effect. The findings reveal the possibility of developing Q or its derivatives as a drug or an ingredient in diet for clinical treatment of osteoporosis.

Early changes in bone turnover predict longer-term changes in bone mineral density but not trabecular bone score in frail older women.

We sought to examine the association between shorter-term changes in markers of bone turnover and longer-term changes in bone mineral density (BMD) and microstructure in a cohort of frail elderly women with multiple comorbid conditions including osteoporosis. We performed a secondary analysis of a 2-year zoledronic acid trial for osteoporosis in 155 women residents of long-term care communities (mean age 86.9 years). We examined the association of the 6-month change in serum C-terminal crosslinking telopeptide of type I collagen (CTX) and serum intact procollagen type I N propeptide (PINP) with the 12- and 24-month changes in BMD at the spine and hip and the trabecular bone score (TBS), an indirect measure of bone microstructure. For every 0.2-ng/ml 6-month CTX decrease, the corresponding increase in spine BMD at 12 and 24 months was 0.2% (p = 0.7210) and 1.1% (p = 0.0396), respectively; total hip BMD 1.1% (p = 0.0279) and 0.9% (p = 0.0716); and femoral neck BMD 1.7% (p = 0.0079) and 0.9% (p = 0.1698). Similarly, for every 20-ng/ml 6-month PINP decrease, the corresponding increase in spine BMD at 12 and 24 months was 0.9% (p = 0.0286) and 1.4% (p = 0.0012), respectively; total hip BMD 1.4% (p = 0.0005) and 1.4% (p = 0.0006); and femoral neck BMD 2.3% (p < 0.0001) and 2.0% (p < 0.0001). Bone marker changes were not consistently associated with TBS changes. Shorter-term 6-month changes in bone turnover markers are associated with the long-term changes in BMD over 1-2 years in the spine and hip but not with TBS.

Biochemical bone turnover markers in hormonal disorders in adults: a narrative review.

Hormonal disorders are often associated with abnormal levels of bone turnover markers (BTMs). N-terminal propeptide of type I procollagen (PINP) and serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) are the reference markers of bone formation and bone resorption, respectively. A comprehensive literature search within the MEDLINE and Web of Science databases was performed. Acromegaly is associated with higher BTM levels, which decrease during the remission after treatment. Adult-onset growth hormone deficiency is often associated with decreased BTM levels. Growth hormone replacement therapy stimulates bone turnover and increases BTM levels. Hypothyroidism is characterized by general slowing of bone metabolism which is reflected by lower BTM levels. The replacement thyroid hormone therapy increases the bone turnover rate and BTM levels increase. Patients with thyroid cancer receive a suppressive dose of thyroid hormones and may have slightly elevated BTM levels. Patients with overt hyperthyroidism had higher BTM levels and anti-thyroid therapy induces a rapid decrease in the BTM levels. Patients with overt primary hyperparathyroidism have higher BTM levels, whereas those with asymptomatic and normocalcemic hyperparathyroidism usually have normal BTM levels. Hypoparathyroidism is characterized by slightly decreased BTM levels. Cushing's syndrome is characterized consistently by markedly decreased osteocalcin concentration, whereas data on other BTMs are discordant. BTMs help us to better understand mechanisms of the impact of hormonal disorders and their treatment on bone metabolism. However, it is unknown whether BTMs may be used to monitor the effect of their treatments on bone in the clinical practice.

Higher concentration of serum C-terminal cross-linking telopeptide of type I collagen is positively related with inflammatory factors in postmenopausal women with H-type hypertension and osteoporosis.

ObjectiveTo investigate the changes of inflammatory factors and bone metabolism markers in postmenopausal women with H‐type hypertension and to assess the relationship between them.MethodsPostmenopausal women who were diagnosed with osteoporosis were selected as observation objects. Participants were divided into three groups: only osteoporosis group (osteoporosis group), hypertension combined with osteoporosis group (hypertension group), and H‐type hypertension combined with osteoporosis group (H‐type hypertension group). The changes in bone mineral density and bone metabolic markers (osteocalcin [OC], procollagen type I N‐terminal propeptide (PINP), and C‐terminal cross‐linking telopeptide of type I collagen [CTX]) and inflammatory factors (interleukin‐6 [IL‐6] and tumor necrosis factor‐α [TNF‐α]) were compared among three groups.ResultsIn the hypertension group and the H‐type hypertension group, the bone mineral density of the lumbar spine (0.647 ± 0.038 vs 0.638 ± 0.034 vs 0.668 ± 0.047, P < 0.05) and the femoral neck (0.567 ± 0.047 vs 0.552 ± 0.053 vs 0.618 ± 0.059, P < 0.05) was significantly lower than that in the osteoporosis group. The concentrations of CTX (266.61 ± 64.65 vs 293.09 ± 72.34 vs 235.48 ± 62.85, P < 0.05), IL‐6 (44.36 ± 6.45 vs 48.05 ± 8.04 vs 39.06 ± 7.95, P < 0.05) and TNF‐α (30.53 ± 6.28 vs 34.52 ± 7.15 vs 28.66 ± 6.19, P < 0.01) in the hypertension group and in the H‐type hypertension group were significantly higher than those in the osteoporosis group. The concentrations of OC (30.59 ± 6.43 vs 27.10 ± 6.51, P < 0.05) and PINP (36.36 ± 6.16 vs 33.16 ± 6.77, P < 0.05) in the H‐type hypertension group were increased dramatically. The concentration of CTX was positively correlated with the concentration of IL‐6 (r = 0.587, P < 0.01) and TNF‐α (r = 0.474, P < 0.01) and negatively related with the concentration of OC (r = −0.591, P < 0.01) and PINP (r = −0.646, P < 0.01) and the bone mineral density of the lumbar spine (r = −0.470, P < 0.01) and the femoral neck (r = −0.509, P < 0.01).ConclusionHigher concentration of serum CTX is found in postmenopausal women with H‐type hypertension, which is positively correlated with inflammatory factors. Besides, H‐type hypertension could further enhance the activity of osteoclasts and increase the expressions of inflammatory factors, resulting in the aggravation of osteoporosis.

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.

Prevalence and Risk Factors of Low Bone Mineral Density and Fractures of Young Thalassemia Patients

▪Background: Thalassemia is a common cause of anemia in Thailand. Blood transfusion and iron chelation lengthen life span of thalassemia patients. As a result, these patients are experiencing an emerging long-term complications including thalassemia-associated osteoporosis (TAO). However, prevalence of TAO and TAO-associated fractures in this population is uncertain.Objective: To investigate the prevalences of TAO and fractures among thalassemia patients and to identify clinical and laboratory factors that are associated with these conditions.Methods: Consecutive males (18-50 years) or premenopausal females with thalassemia who were followed up in the hematologic clinic at ChiangMai University from November 2017 to June 2018, were screened for TAO using the dual energy X-ray absorptiometry (DXA) for measuring bone mineral density (BMD) and vertebral fracture assessment (VFA). TAO was defined as low BMD (Z-score ≤ -2.0 SD) or presence of vertebral fractures from VFA. We collected clinical data and, determined laboratory investigation including fasting plasma glucose, serum testosterone or estradiol, thyroid function test, serum calcium, serum insulin like growth factor-1, serum C-terminal crosslinking telopeptide of type I collagen (CTX), serum procollagen type I N-terminal propeptide (P1NP), serum 25-hydroxy vitamin D (25-OHD), viral hepatitis B and C, and serum ferritin and non-transferrin-bound iron (NTBI; toxic form of iron). Outcomes were prevalence of TAO and fractures.Results: A total of 140 thalassemia patients were screened (89 transfusion-dependent thalassemia; TDT and 51 non-transfusion-dependent thalassemia; NTDT). Most patients received routine calcium (elemental calcium 600 mg/day) and vitamin D supplement (vitamin D2 20,000 IU/week). The prevalence of TAO was 75.7% (TDT 83.1%, NTDT 62.7%). The prevalence of vertebral fractures from VFA was 22.8% (TDT 24.7%, NTDT 19.6%). Among 106 patients with TAO, only 50 patients participated in this study (TDT 70%). Factors associated with lower mean BMD Z-score were current smoking, splenectomy history, vitamin D deficiency, diabetes mellitus, low IGF-1 level and serum NTBI above 2.2 uM. Fractures were common in patients with TDT than those with NTDT (51% vs. 20%, p=0.039). The prevalence of sub-optimal vitamin D level among Thai thalassemia patients was high at 50% even with vitamin D supplement. Factors associated with bone fractures were male sex (RR 1.66, 95%CI 1.02-2.70), hemoglobin level below 8 g/dl (RR 2.73, 95%CI 1.00-7.46), hypogonadism (RR 1.67, 95%CI 1.11-2.50), low IGF-1 level (RR 1.75, 95%CI 0.97-3.14) and serum NTBI above 1.5 uM (RR 6.14, 95%CI 0.96-39.47). Type of iron chelation, serum ferritin and the 2 bone turnover markers level (CTX and P1NP) were not associated with BMD or fractures.Conclusion: TAO is common among Thai thalassemia patients. We observed high prevalence of suboptimal vitamin D level in these patients. Male sex, high disease severity (low hemoglobin level and high serum NTBI) and secondary endocrinopathies may predict TAO and fractures. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study

BackgroundIndividuals with Diabetes Mellitus (DM) are at increased risk for fracture due to the decrease in bone strength and quality. Serum procollagen type I intact N-terminal (P1NP) and serum C-terminal cross-linking telopeptide of type I collagen (CTX) as markers of bone formation and resorption, respectively, have been reported to be decreased in T2DM. It remains unclear whether diabetes-associated alterations in the bone turnover of T2DM individuals are related to the longer duration of the disease or may occur earlier. Furthermore, previous studies on BTMs in T2DM individuals have mostly been done in postmenopausal women with T2DM, which might have masked the DM-induced alterations of bone turnover with concurrent estrogen deficiency. This study aims to assess the levels of serum P1NP and CTX as markers of bone turnover in premenopausal women with and without T2DM.MethodsThis cross-sectional study involves 41 premenopausal women with T2DM, and 40 premenopausal women without DM. Sampling was done consecutively. P1NP and CTX measurement was done using the electrochemi-luminescence immunoassay (ECLIA) method. Other data collected include levels of HbA1C, ALT, creatinine, eGFR and lipid profile.ResultsMedian (interquartile range) P1NP in T2DM is 29.9 ng/ml (24.7–41.8 ng/ml), while in non-DM is 37.3 ng/ml, (30.8–47.3 ng/ml; p = 0.007). Median (interquartile range) CTX in T2DM is 0.161 ng/ml (0.106–0.227 ng/ml), while in non-DM is 0.202 ng/ml (0.166–0.271 ng/ml; p = 0.0035). Levels of P1NP and CTX in the T2DM group did not correlate with the duration of disease, age, BMI or the levels of HbA1C.ConclusionsPremenopausal women with T2DM indeed have lower bone turnover when compared with non-DM controls. This significantly lower bone turnover process starts relatively early in the premenopausal age, independent of the duration of DM. Gaining understanding of the early pathophysiology of altered bone turnover may be key in developing preventive strategies for diabetoporosis.

Water extract of Uncaria sinensis suppresses RANKL-induced bone loss by attenuating osteoclast differentiation and bone resorption

BackgroundThe hooks and stems of Uncaria sinensis have been used to mitigate cardiovascular and central nervous system disorders in Asia traditional medicine. Regulation of osteoclast differentiation and activity is a major target for preventing and treating pathological bone diseases. MethodsTartrate-resistant acid phosphatase (TRAP) activity and the number of TRAP-stained multinucleated cells were used to examine receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. The activation of RANKL-induced signaling pathways and the expression of transcription factors were investigated by western blot analysis and quantitative real-time polymerase chain reaction. The bone resorption activity of osteoclast was studied using a plate coated with hydroxyl-apatite. Trabecular bone destruction was investigated using a RANKL-induced trabecular bone loss mouse model. ResultsWe found that water extract of the hooks and stems of U. sinensis (WEUS) inhibits RANKL-induced differentiation of murine bone marrow macrophages and RAW264.7 cells into osteoclasts. WEUS inhibited the activation of NF-κB and the expression of nuclear factor of activated T-cells, cytoplasmic 1. In addition, WEUS suppressed the bone resorbing activity of mature osteoclasts without affecting their survival. Furthermore, oral administration of WEUS suppressed RANKL-induced bone loss with a significant amelioration of trabecular bone micro-structures. WEUS also reduced RANKL-induced increase in serum TRAP5b activity and C-terminal cross-linked telopeptide of type I collagen levels. ConclusionThe present study demonstrates that WEUS has a pharmacological activity that inhibits osteoclast-mediated bone destruction by suppressing osteoclast differentiation and function. These results suggest that U. sinensis could be a promising herbal candidate for preventing and treating bone diseases such as osteoporosis.