Utility Of Bone Turnover Markers Research Articles

Effectiveness and Usefulness of Bone Turnover Marker in Osteoporosis Patients: A Multicenter Study in Korea

Background: This study aimed to investigate real-world data of C-terminal telopeptide (CTX), propeptide of type I collagen (P1NP), and osteocalcin through present multicenter clinical study, and retrospectively analyze the usefulness of bone turnover markers (BTMs) in Koreans. Methods: The study focused on pre- and post-menopausal patients diagnosed with osteoporosis and excluded patients without certain test results or with test intervals of over 1 year. The demographic data and 3 BTMs (CTX, P1NP, and osteocalcin) were collected. The patients were classified by demographic characteristics and the BTM concentrations were analyzed by the group. Results: Among women with no history of fractures, the levels of P1NP (N=2,100) were 43.544±36.902, CTX (N=1,855) were 0.373 ±0.927, and osteocalcin (N=219) were 10.81 ±20.631. Among men with no history of fractures, the levels of P1NP (N=221) were 48.498±52.892, CTX (N=201) were 0.370±0.351, and osteocalcin (N=15) were 7.868 ±10.674. Treatment with teriparatide increased the P1NP levels after 3 months in both men and women, with a 50% increase observed in women. Similarly, treatment with denosumab decreased the CTX levels after 3 months in both men and women, with a reduction of 50% observed in women. Conclusions: The results of this study can contribute to the accurate assessment of bone replacement status in Koreans. We also provide the P1NP level in the Korean population for future comparative studies with other populations.

Associated factors of osteoporosis and vascular calcification in patients awaiting kidney transplantation

IntroductionPretransplant osteoporosis and vascular calcification probably increase the risk of fractures and cardiovascular events after kidney transplantation. In the present study, we investigated the related risk factors of osteoporosis and vascular calcification among end-stage renal disease (ESRD) patients awaiting kidney transplantation.MethodsA total of 221 ESRD patients (age, 43.4 ± 14.3 years; 125 males and 96 females; median dialysis duration, 61.0 m) awaiting kidney transplantation were enrolled in this cross-sectional study. Serum levels of bone turnover markers and intact parathyroid hormone (iPTH) were analyzed from fasting morning blood samples. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD). Vascular calcification was evaluated by lateral abdominal radiography and plain radiographic films of the pelvis and hands.ResultsThe osteoporosis prevalence was 27.6% in this cohort of kidney transplantation candidates, and the prevalence of vascular calcification was 51.1%. The related factors for osteoporosis and vascular calcification were similar and included older age, longer dialysis duration, parathyroid hyperplasia, and higher levels of iPTH and bone turnover markers. In the multivariable regression model, age and iPTH were independent risk predictors of both vascular calcification and osteoporosis. There were strong, positive correlations between iPTH and all bone turnover markers. The moderate and severe hyperparathyroidism (iPTH 600–1499 pg/ml and iPTH 1500 pg/ml) were related to reduced serum albumin and hemoglobin levels.ConclusionThe involvement of high iPTH levels in vascular calcification, osteoporosis, and malnutrition indicated the need of treating hyperparathyroidism early in patients awaiting kidney transplantation. Prospective studies are needed to further examine the utility of bone turnover markers.

Utility of bone turnover markers in metabolic bone diseases

Bone turnover markers (BTMs) are biochemical indicators that provide information about the rate of bone remodeling, which involves the continuous process of bone formation and bone resorption. BTMs are measured in blood or urine samples and are used in the diagnosis, monitoring, and management of various metabolic bone diseases. They aid in the diagnosis of metabolic bone diseases by providing information about the bone turnover status. Abnormal levels of BTMs can indicate increased bone resorption or decreased bone formation, which are characteristic of certain conditions such as osteoporosis, osteomalacia, or Paget's disease. BTMs can provide insights into the severity of metabolic bone diseases. For example, in osteoporosis, elevated levels of bone resorption markers such as C-terminal telopeptide of type I collagen (CTX) or tartrate-resistant acid phosphatase 5b (TRACP-5b) indicate increased bone breakdown and higher fracture risk. Similarly, low levels of bone formation markers like procollagen type I N-terminal propeptide (PINP) or osteocalcin can indicate reduced bone formation and decreased bone strength. BTMs are valuable tools for assessing the response to treatment in metabolic bone diseases. Changes in BTM levels over time can indicate the effectiveness of interventions such as pharmacotherapy, lifestyle modifications, or surgical interventions. Decreased levels of bone resorption markers or increased levels of bone formation markers suggest a positive response to treatment, whereas persistent abnormal BTM levels may indicate the need for treatment adjustment.It's important to note that BTMs should be interpreted in conjunction with other clinical factors and imaging studies. They provide valuable information about bone turnover dynamics but should not be relied upon as standalone diagnostic or prognostic tools.

The Phenotype of Bone Turnover in Patients with Fragility Hip Fracture: Experience in a Fracture Liaison Service Population.

Background: Hip fragility fractures are becoming one of the main health care problems in countries with an aging population. This study aimed to evaluate the clinical characteristics and the usefulness of bone turnover markers in patients with a hip fracture. Methods: In a cohort of 363 patients (84.1 ± 9.2 years) with hip fractures we measured 25-hydroxyvitamin D (25OHD), bone alkaline phosphatase, type I collagen β carboxy telopeptide (βCTX), and parathyroid hormone (PTH). We recorded patients’ Charlson Comorbidity Index (CCI) and previous history of fragility fractures. Results: Vitamin D and PTH levels were inversely correlated (r = −024; p < 0.001). The prevalence of 25OHD deficiency was 57.8%, the PTH levels greater than 65 pg/mL was in 47.0 %, and in those who had βCTX values the upper limit was 61.8%. Moreover, 62% of patients with a fragility hip fracture had a history of a previous fracture. The 25OHD serum levels were inversely associated with CCI and a previous fragility fracture. On the contrary, PTH and βCTX serum levels showed a positive significant correlation with CCI and previous fragility fractures. Conclusion: This study confirmed the usefulness of a bone turnover markers assessment, along with the comorbidities and history of previous fragility fractures in order to better identify the risk of hip fracture.

Clinical utility of bone turnover markers in patients with chronic kidney disease.

The burden of fractures is very high in patients with chronic kidney disease (CKD). It is increasingly recognized that knowledge of bone turnover is of paramount importance in guiding mineral metabolism and osteoporosis therapy in CKD. Bone histomorphometry is the gold standard to assess bone turnover, but is seldomly performed in clinical practice. Bone turnover markers (BTMs) may be the long awaited noninvasive diagnostic that may help to close the therapeutic gap in patients with advanced CKD presenting with bone fragility. Mounting evidence indicates that BTMs may be useful in skeletal and nonskeletal risk stratification, in guiding mineral metabolism and osteoporosis therapy, and in monitoring the therapeutic response. BTMs provide information that is complementary to other clinical tests. It may be envisioned that in the near future, the assessment of nonkidney cleared BTMs may become part of routine clinical evaluation and monitoring of bone health in CKD patients, integrated with clinical risk factors, imaging data and, eventually, bone histomorphometry. Panels of BTMs will likely be more informative than single markers, and the same might hold true for trends as opposed to single time point data.

Determining Bone Turnover Status in Patients With Chronic Liver Disease.

IntroductionHepatic osteodystrophy is an osteoporotic bone disease that occurs in chronic liver disease patients. The global prevalence of osteoporosis in patients with chronic liver disease is 30% to 40%. The pathogenesis of hepatic bone disease is not clear, but it occurs due to unstable bone remodeling with increased bone resorption and decreases bone formation. There has been an interest in determining the clinical utility of bone turnover markers (BTMs) in the assessment of osteoporosis in chronic liver patients.MethodsThis was a cross-sectional study conducted in patients with chronic liver disease at the section of chemical pathology, department of pathology and laboratory medicine, Aga Khan University (AKU). A total of 50 patients with age >8 years and a history of liver disease >6 months were recruited from January to October 2019. Liver function tests, i.e. aspartate aminotransferase (AST), alanine transaminase (ALT), albumin, and bilirubin, along with clinical signs of liver disease chronicity, were noted. The samples for BTMs, i.e. total serum alkaline phosphatase (ALP) and serum C-terminal telopeptide of type-1 collagen (CTX) were withdrawn and analyzed on Microlab (ELItech Group, Puteaux, France) and ADVIA Centaur (Siemens Diagnostics, NY), respectively.ResultsThe majority of patients were males (n=34, 68%). Twenty-four (48%) patients suffered from fibrosis while 26 (52%) were without fibrosis. Median platelet count (68×109/L (102.5-50)) and median cholesterol levels (102.5 mg/dl (147-99.5)) were decreased, whereas gamma-glutamyl transferase (GGT) levels were higher in the fibrosis group as compared to the non-fibrosis group. The median levels of total ALP were 91.5 IU/L (103-82), and the median levels of CTX were 0.24 pg/ml (0.34-0.21).ConclusionIn the present study, no significant difference was found in the BTMs of patients with and without chronic liver disease (CLD). However, there was a positive and significant correlation of BTMs, particularly CTX with age, bilirubin levels, and hepatomegaly.

The challenge of long-term adherence: The role of bone turnover markers in monitoring bisphosphonate treatment of osteoporosis.

Oral Bisphosphonates (BPs) are the mainstay of osteoporotic treatment, however long-term adherence remains a challenge, primarily owing to the chronic character of the disease and the regimen complexity. Poor compliance has been shown to have a clear link to fracture risk. The role of bone turnover markers (BTMs) as a tool to ascertain adherence and response to therapy is supported by their rapid response to treatment; a decrease in values is witnessed within days or weeks of commencing treatment. A greater reduction of serum CTX and NTX is evidenced with alendronate and ibandronate compared to risedronate. A change in bone formation BTMs appears to be related to vertebral fracture risk reduction, whereas no significant relationship is evident for hip and non-vertebral fractures. The utility of BTMs as an adjunct for monitoring withdrawal of treatment with oral BP has also been suggested. Finally, studies evaluating BTMs as an intervention, failed to demonstrate any effect on adherence. This review explores the challenge of long-term adherence with bisphosphonates and provides an analytic framework with respect to the role of BTMs in monitoring bisphosphonate treatment, adherence and the offset of treatment effect.

A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures.

Bone turnover markers (BTMs) derived from the secretory activities of osteoblasts and the matrix-degrading activities of osteoclasts are useful in monitoring the progression of osteoporosis and the efficacy of anti-osteoporotic treatment. However, the usefulness of BTMs in predicting osteoporosis remains elusive. Osteocytes play a central role in regulating bone formation and resorption. The proteins secreted by osteocytes, such as fibroblast growth factor-23 (FGF23), sclerostin (SOST), and dickkopf-1 (DKK1), could be candidates for osteoporosis screening and fracture prediction. This review summarizes the current evidence on the potential of osteocyte-related proteins as biomarkers for osteoporosis and fracture prediction. The literature reports that SOST may be a potential marker for osteoporosis screening but not for fracture prediction. FGF23 is a potential marker for increased fracture risk, but more studies are needed to confirm its usefulness. The role of DKK1 as a marker to predict osteoporosis and fracture risk cannot be confirmed due to a lack of consistent evidence. In conclusion, circulating osteocyte markers are potential osteoporosis biomarkers, but more studies are warranted to validate their clinical use.

Rare adverse effects of bisphosphonate therapy.

To give an update on the latest developments regarding rare adverse effects of bisphosphonate therapy. Recent studies covering osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFFs) provided several updates to the literature. Identification of ONJ in large population databases is a challenge but based on one systematic review, the ICD-10 diagnosis code K10.2 (inflammatory conditions of the jaw) seems to be the most commonly used code for this condition. Duration of bisphosphonate therapy was determined to be an important predictor of AFFs. Appropriate duration of therapy followed by a timely drug holiday was shown to be the best strategy for improving bone mineral density and reducing fracture risk, while minimizing risk of rare adverse effects of therapy. The utility of bone turnover markers as a monitoring tool during drug holidays needs to be further investigated. ONJ and AFFs are two of the rare adverse effects associated with bisphosphonate therapy. Population-level trends of bisphosphonate use suggest a decline in prescriptions, pointing to broad fears of these side effects. Careful patient evaluation, duration of bisphosphonate therapy, and use of drug holidays can help limit any risk associated with therapy.

Trabecular bone score and bone remodelling markers identify perimenopausal women at high risk of bone loss.

Bone loss is accelerated in the late perimenopause and early menopause. The date of the final menstrual period cannot be stated until 1year after it has ended, and at that time, most of the rapid bone loss phase will have elapsed. Therefore, early detection of bone loss is crucial. To evaluate the utility of bone turnover markers (BTM) to identify the women who are more likely to lose more bone mass during the transition to menopause and quantify the loss of bone quality measured by trabecular bone score (TBS). Sixty-four healthy premenopausal women, mean age between 44 and 57years old, were enrolled and followed up for 5years. Clinical features, lifestyle, bone densitometry, TBS and BTM (CTX, P1NP and osteocalcin) were measured at baseline and follow-up. All women had densitometrically normal bone at the time of enrolment. After 5years, 48.4% had normal bone mineral density, 45.8% low bone mass and 6.3% osteoporosis. Women with osteopenia/osteoporosis at follow-up had higher CTX and P1NP at enrolment compared with women with densitometrically normal bone. The areas under the curve for the prediction of low bone mass or osteoporosis were 0.69 (P=0.011) for P1NP, 0.69 for CTX (P=0.013) and 0.77 (P 0.001) for OC. A significant correlation was found between P1NP increase after 5years and the decrease in lumbar bone density (r=-0.383, P=0.002). At baseline, 7 (10.9%) women had deteriorated microarchitecture (TBS<1.3). Three of these women developed osteoporosis and four osteopenia at follow-up. Women with higher P1NP and CTX and lower TBS at baseline had lower BMD in the transition to menopause suggesting these novel tools could have potential use in identifying women at high risk of rapidly decreasing bone mass.

Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis.

Measurement of bone turnover markers (BTMs) may be useful to monitor offset of treatment with bisphosphonates (BP) in osteoporosis. We assessed the effect of withdrawal of BP treatment by comparing the changes in BTMs and total hip (TH) bone density (BMD). We studied postmenopausal osteoporotic women who had completed a randomised study of three oral BPs. After 2years of treatment, participants with BMD T-score > - 2.5 and in whom it was considered clinically appropriate to discontinue treatment, were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs (CTX and PINP) with offset being defined by two criteria: (1) an increase greater than the least significant change (LSC) and (2) an increase above the reference mean value. Fifty women completed the study. At 48weeks after stopping BPs, CTX was greater than the LSC for 66% of women and PINP 72%; CTX was above the reference mean for 64% of women and PINP 42%. The decrease in THBMD was greater for women with the largest increase in BTM compared to those with continued suppression (mean difference for CTX was - 2.98%, 95%CI - 4.75 to - 1.22, P < 0.001, PINP - 2.25%, 95% CI - 4.46 to - 0.032, P = 0.046). The measurement of BTM after withdrawal of BPs is potentially useful to evaluate patients that are taking a pause from treatment. An increase in BTMs more than the LSC and/or reference mean reflects loss of treatment effect and identifies patients that are likely to have a decrease in BMD. Such changes could provide an indication for reintroduction of treatment.

Utility of bone turnover markers in metabolic bone disease detection in patients with phenylketonuria

Background and objectiveMineral bone disease is more common in phenylketonuric patients. The objectives of this study were to determine the usefulness of biochemical bone markers to identify phenylketonuric patients with mineral bone disease (MBD) and know the underlying bone remodelling alterations. Patients and methodCross-sectional study of 43 phenylketonuric patients >7 years (range 7.1–41 years). A nutritional survey was performed and bone alkaline phosphatase (BAP), procollagen type 1 N-terminal propeptide (PNP-1), beta-crosslaps and ratio calcium/creatinine in urine were determined. ResultsA percentage of 20.9 of patients had pathological biochemical bone markers, 90% of them being adults. BAP was decreased in 70% of them and beta-crosslaps in 42.8%. BAP values were more often pathological in phenylketonuric patients with a late diagnosis (41.7 vs. 10.7%; p<.05) and in patients with MBD (60 vs. 14.3%; P<.05). PNP-1 values and calcium/creatinine were similar among all phenylketonuric patients regardless of presenting MBD, late diagnosis or tetrahydrobipterin treatment (enzyme cofactor). Patients with decreased BAP and beta-crosslaps had lower natural protein intake: BAP (0.21±0.13 vs. 0.65±0.65g/kg; p<.05); beta-crosslaps (0.29±0.23 vs. 0.65±0.66g/kg; p<.05). None of the tetrahydrobiopterin treated patients showed altered values of BAP, PNP-1 or calcium/creatinine. ConclusionsAdult phenylketonuric patients with lower natural protein intake tend to have lower values of BAP, which is a marker that may be useful to identify patients at risk for MBD.

The utility of bone turnover markers in Paget's disease of bone

The utility of bone turnover markers in Paget's disease of bone

Clinical usefulness of bone turnover markers with the treatment of osteoporosis

Bone turnover markers (BTMs) are known the bone formation marker, the bone resorption marker and the bone matrix related marker participating in bone quality, respectively. In the Guidelines for the Use of Bone Metabolic Markers in the Diagnosis and Treatment of Osteoporosis (2012 Edition) from publishing Japan Osteoporosis Society Committee, the newly and commonly BTMs were considered to give the normal reference value in Japanese people, the reevaluation of MSC, and the influence of renal function on BTMs, respectively. The flow chart of the measurement of bone resorption markers and bone formation markers when selecting drug treatment for osteoporosis, the measurement of ucOC and bone resorption markers when selecting drug treatment in osteoporosis, and the evaluation of therapeutic effects of bone antiresorption drugs using bone resorption markers were corrected newly in the guideline 2012 edition. It is thought that the BTMs have been continued more developing as essential biomarker with the treatment of osteoporosis in the future.

The Clinical Utility Of Bone Turnover Markers In The Evaluation Of Bone Disease In Patients With Haemophilia A and B

AimHemophilia A and B has been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) is unknown. The aim of this study was to evaluate bone metabolism in men with hemophilia and investigate associations between BTM and bone disease. MethodsSerum N- (NTX-I), C-terminal telopeptide of type I collagen (CTX-I) and tartrate-resistant acid phosphatase band-5b (TRAP-5b), as bone resorption markers, and osteocalcin (OC) and bone-specific alkaline phosphatase (b-ALP), as bone formation markers, were assessed. ResultsSeventy men (mean age 45.4±14.7 years) with hemophilia A (n=59) or B (n=11) were studied. Patients with low BMD had significantly higher b-ALP concentrations compared with those with normal BMD, without any differences in the other BTM. NTX-I and CTX-I concentrations were negatively associated with estradiol concentrations and hip BMD and positively with HIV infection, number of affected joints and arthropathy scores. B-ALP and OC concentrations were negatively associated with hip BMD, severity of hemophilia and fracture history, and positively with the number of affected joints and testosterone concentrations.In men with low BMD, NTX-I, TRAP-5b and b-ALP concentrations were positively correlated with the number of affected joints, whereas TRAP-5b concentrations were positively associated with arthropathy scores and negatively with the level of physical activity. ConclusionIncreased bone metabolism exists in men with hemophilia and low BMD. Arthropathy, low physical activity and low estradiol concentrations are associated with increased bone resorption and may contribute to the pathogenesis of low BMD in these patients. Disclosures:No relevant conflicts of interest to declare.

The clinical utility of bone turnover markers in the evaluation of bone disease in patients with haemophilia A and B

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) remains unknown. The aim of this study was to evaluate bone metabolism in men with haemophilia and to investigate associations between BTM and bone disease. Serum N- (NTX-I), C-terminal telopeptide of type I collagen (CTX-I) and tartrate-resistant acid phosphatase band-5b (TRAP-5b), as bone resorption markers, and osteocalcin (OC) and bone-specific alkaline phosphatase (b-ALP), as bone formation markers, were assessed. Seventy men with haemophilia A (n = 59) or B (n = 11) were studied. Patients with low BMD had significantly higher b-ALP concentrations compared with those with normal BMD (12.8 ± 1.60 vs. 9.72 ± 0.58 μg/L, P = 0.009), without any differences in the other BTM. NTX-I and CTX-I concentrations were negatively associated with oestradiol levels and hip BMD and positively with human immunodeficiency virus infection, number of affected joints and arthropathy scores. B-ALP and OC concentrations were negatively associated with hip BMD, severity of haemophilia and fracture history, and positively with the number of affected joints and testosterone concentrations. After multivariate analysis, NTX-I levels remained negatively associated with oestradiol levels, whereas b-ALP concentrations negatively correlated with the level of physical activity and positively with the number of affected joints. Increased bone metabolism exists in men with haemophilia and low BMD. Increased b-ALP levels may identify patients at high risk for fracture. Increased number of target joints, low physical activity and low oestradiol concentrations are independently associated with increased bone metabolism.

AB1018 Clinical utility of bone turnover markers in a metabolic bone disease clinic

BackgroundBiochemical bone turnover markers (BTM) provide dynamic information on skeletal status and can complement information regarding bone mineral density (BMD) assessed by DEXA [1]. In the past, BTM were limited...

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

Background:Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA).Methods:This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (β-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded.Results:Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with β-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression.Conclusion:In patients with PCa and bone metastases treated with ZA, β-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Usefulness of bone turnover markers in the evaluation of fracture risk in type 2 diabetes

Usefulness of bone turnover markers in the evaluation of fracture risk in type 2 diabetes

Clinical utility of bone turnover markers

Clinical utility of bone turnover markers