Changes In Bone Turnover Markers Research Articles

Changes in bone turnover markers and bone mineral density after radiofrequency ablation for mild primary hyperparathyroidism: a prospective cohort study

Changes in bone turnover markers and bone mineral density after radiofrequency ablation for mild primary hyperparathyroidism: a prospective cohort study

Comparison of the pleiotropic effect of atorvastatin and rosuvastatin on postmenopausal changes in bone turnover: A randomized comparative study.

Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin. This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment. There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations. These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.

Daily yogurt consumption does not affect bone turnover markers in men and postmenopausal women of Caribbean Latino descent: a randomized controlled trial

BackgroundCaribbean Latino adults are at high risk for osteoporosis yet remain underrepresented in bone research. This increased risk is attributed to genetics, diet, and lifestyle known to drive inflammation and microbial dysbiosis.ObjectiveThe primary objective of this study was to determine whether consuming 5 oz of yogurt daily for 8wks improves bone turnover markers (BTMs) among Caribbean Latino adults > 50 years; and secondarily to determine the impact on the gut microbiota and markers of intestinal integrity and inflammation.MethodsFollowing a 4wk baseline period, participants were randomized to an 8wk whole fat yogurt intervention (n = 10) daily, containing only Streptococcus thermophilus and Lactobacillus bulgaricus, or to an untreated control group that did not consume yogurt (n = 10). Blood and stool samples collected at week-0 and week-8 were used to assess BTMs, inflammation, intestinal integrity biomarkers, and gut microbiota composition, short chain fatty acids (SCFAs), respectively. Data were evaluated for normality and statistical analyses were performed.ResultsParticipants were 55% women, with a mean age of 70 ± 9 years, BMI 30 ± 6 kg/m2, and serum C-reactive protein 4.8 ± 3.6 mg/L, indicating chronic low-grade inflammation. Following 8wks of yogurt intake, absolute change in BTMs did not differ significantly between groups (P = 0.06–0.78). Secondarily, absolute change in markers of inflammation, intestinal integrity, and fecal SCFAs did not differ significantly between groups (P range 0.13–1.00). Yogurt intake for 8wks was significantly associated with microbial compositional changes of rare taxa (P = 0.048); however, no significant alpha diversity changes were observed.ConclusionsIn this study, daily yogurt did not improve BTMs, inflammation, intestinal integrity, nor SCFAs. However, yogurt did influence beta diversity, or the abundance of rare taxa within the gut microbiota of the yogurt group, compared to controls. Additional research to identify dietary approaches to reduce osteoporosis risk among Caribbean Latino adults is needed.Trial registrationThis study is registered to ClinicalTrials.gov, NCT05350579 (28/04/2022).

Changes in Serum Concentrations of Bone Turnover Markers in Healthy Pregnant Women.

Changes in bone metabolism during pregnancy have not received sufficient attention because of the lack of effective screening tools. Bone turnover markers (BTMs) could reflect the changes of bone metabolism. Currently, reference intervals for bone metabolism during normal pregnancy are inconclusive. This study aimed to determine reference intervals for BTMs in pregnant women taking prenatal care and to facilitate clinical research on diseases affecting bone metabolism during pregnancy. We surveyed 120 low-risk pregnant women attending routine antenatal care from January 2020 to March 2020. The serum levels of procollagen type I N-propeptide (PINP), N-terminal osteocalcin (N-MID), and C-terminal telopeptide of type I collagen (β-CTX) were measured in the first trimester (<13 weeks), second trimester (14-27 weeks), and third trimester (>28 weeks). Reference intervals for BTMs during pregnancy were analyzed. The Kruskal-Wallis test and paired t-test are used to analyze differences between groups. Spearman correlation coefficients expressed the measure of linear association. The bone resorption marker β-CTX in third trimester increases compared to the first trimester and the second trimester (P < 0.001, P < 0.001). The bone formation markers PINP and N-MID were decreased from the first trimester to the second trimester (P = 0.01, P < 0.001) and then raised from the second trimester to the third trimester (P < 0.001, P < 0.001). Two indices of bone turnover rate, β-CTX/PINP and β-CTX/N-MID, were increased from the first trimester to the second trimester (P < 0.001, P < 0.001) and then decreased from the second trimester to the third trimester (P = 0.02, P < 0.001). This study established reference intervals for BTMs in pregnant women and observed the changes in BTMs during the different trimesters of pregnancy. The present findings can help in clinical monitoring of the effects of pregnancy diseases on the bone metabolism of pregnant women.

Associations of Changes in Bone Turnover Markers with Change in Bone Mineral Density in Kidney Transplant Patients.

Bone loss after kidney transplantation is highly variable. We investigated whether changes in bone turnover markers associate with bone loss during the first post-transplant year. Bone mineral density (BMD) was measured at 0 and 12 months, with biointact parathyroid hormone, bone-specific alkaline phosphatase (BALP), intact procollagen type I N -terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) measured at 0, 3, and 12 months post-transplant ( N =209). Paired transiliac bone biopsies were available in a subset ( n =49). Between-group differences were evaluated by Student's t test, Wilcoxon signed-rank test, or Pearson's chi-squared test. Changes in BMD varied from -22% to +17%/yr. Compared with patients with no change (±2.5%/yr), patients who gained BMD had higher levels of parathyroid hormone (236 versus 136 pg/ml), BALP (31.7 versus 18.8 μ g/L), and Intact PINP (121.9 versus 70.4 μ g/L) at time of transplantation; a greater decrease in BALP (-40% versus -21%) and Intact PINP (-43% versus -13%) by 3 months; and lower levels of Intact PINP (36.3 versus 60.0 μ g/L) at 12 months post-transplant. Patients who lost BMD had a less marked decrease, or even increase, in Intact PINP (+22% versus -13%) and TRAP5b (-27% versus -43%) at 3 months and higher Intact PINP (83.7 versus 60.0 μ g/L) and TRAP5b (3.89 versus 3.16 U/L) at 12 months compared with patients with no change. If none of the biomarkers decreased by the least significant change at 3 months, an almost two-fold (69% versus 36%) higher occurrence of bone loss was seen at 12 months post-transplant. Bone loss after kidney transplantation was highly variable. Resolution of high bone turnover, as reflected by decreasing bone turnover markers, associated with BMD gain, while increasing bone turnover markers associated with bone loss.

Changes in bone turnover markers and bone modulators during abatacept treatment

Rheumatoid arthritis (RA) causes bone loss, only partly related to inflammation. The impact of RA treatments on bone metabolism and their ability to mitigate bone loss remains uncertain. The primary goal of our study was to examine the influence of abatacept on serum levels of markers and regulators involved in bone turnover. Secondary objectives included evaluating changes in bone mineral density (BMD), bone health parameters, erosions, and exploring potential correlations among these parameters. We conducted a prospective observational study on patients with active seropositive RA failure to biological disease modifying anti-rheumatic drugs initiating treatment with abatacept. We measured at baseline and after 1, 2, 3, 6, 9 and 12 months: serum bone turnover markers (CTX, P1nP, B-ALP), bone modulators (Dkk-1, sclerostin, vitamin D, PTH, OPG and RANKL), BMD and radiographic parameters (modified Sharp van der Heijde score [mSvdH], bone health index [BHI] and metacarpal index [MCI]). Disease activity and glucocorticoid intake was monitored. 33 patients were enrolled in the study. We found a significant increase in markers of bone formation (B-ALP and P1nP) from baseline to M6 and M12. PTH increased significantly at M6 but not at M12. All other bone markers and modulators did not change. We found a significant decrease in BHI and MCI from baseline to M12 (median difference − 0.17 95% CI − 0.42 to − 0.10, p 0.001 and − 0.09 95% CI − 0.23 to − 0.07, respectively). BMD at femoral neck transitorily decreased at M6 (mean difference − 0.019 g/cm2 95% CI − 0.036 to − 0.001 p 0.04). BMD at total hip, lumbar spine and mSvdH score did not change significantly. P1nP delta at M12 correlated with delta mSvdH. Treatment with abatacept was associated with a significant increase in bone formation markers. The secondary and transient increase in PTH serum levels may be responsible of the transitory bone loss.

Understanding the characteristics of idiopathic osteoporosis by a systematic review and meta-analysis.

To understand the pathophysiology of idiopathic osteoporosis (IOP) better, we conducted a systematic review and meta-analysis of bone mineral density (BMD), hormones, and bone turnover markers (BTMs) between IOP patients and healthy controls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an appropriate search query was created, and three databases, including PubMed, ScienceDirect, and Google Scholar, were searched for screening relevant original articles. Feasible information, both qualitative and quantitative, was extracted and used to conduct meta-analyses. Publication bias and heterogeneity among studies were evaluated using appropriate statistical tools. A total of 21 studies were included in the meta-analysis. There was reduced BMD at the lumbar spine (LS) (pooled: SDM: -2.38, p-value: 0.0001), femoral neck (FN) (pooled: SDM: -1.75 p-value: 0.0001), total hip (TH) (pooled: SDM: -1.825, p-value: 0.0001) and distal radius (DR) (pooled: SDM of -0.476, p-value: 0.0001), of which LS was the most affected site. There was no significant change in BTMs compared with healthy controls. Total estradiol (SDM: -1.357, p-value: 0.003) was reduced, and parathyroid hormone (PTH) (SDM: 1.51, p-value: 0.03) and sex hormone-binding globulin (SHBG) (SDM: 1.454, p-value: 0.0001) were elevated in IOP patients compared with healthy controls. Our meta-analysis, the first of its kind on IOP, defines it as showing BMD decline maximally at LS compared with healthy controls without any alterations in the BTMs. Further studies are required to understand gender differences and the significance of altered hormonal profiles in this condition.

Changes of bone turnover markers and testosterone in Japanese male endurance runners: a pilot study.

The bone metabolism of male endurance runners during a competitive season has been little studied. Furthermore, Japanese runners have a special competitive season. This study aimed to investigate the change of bone turnover markers (BTMs) and other hormones in Japanese male endurance runners. We investigated biochemical markers, bone formation and resorption markers and sex hormones, body composition using dual-energy X-ray absorptiometry (DXA), and training volume during a competitive season. 11 (age: 24.0 ± 4.3years) Japanese male endurance runners were analyzed in this study. They participated in all measurements three times a year: the baseline (BL), the post-track period (PT), and the road race period (RR). Fat mass (FM) and percentage of body fat (% body fat) at RR (p = 0.009, p = 0.009) were lower than at BL. Specific bone alkaline phosphatase (BAP) decreased at PT (p = 0.004) and RR (p = 0.004) compared with BL. However, the bone resorption marker did not change. Free testosterone at PT (p = 0.032) was lower than BL. There was no correlation with blood variables and body composition or training volume. BAP and testosterone in Japanese male endurance runners decreased during the competitive season. However, there was no correlation between blood variables and training volume.

Efficacy of antiresorptive agents in fibrous dysplasia and McCune Albright syndrome, a systematic review and meta-analysis.

Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim of this systematic review and meta-analysis was to synthesize the available evidence on the use of antiresorptive drugs in FD in terms of changes in bone turnover markers (BTMs), bone mineral density (BMD), and reducing pain. Three databases were searched in October 2022, with an update in July 2023. Of the 1037 studies identified, 21 were retained after eligibility assessment. A random-effects model was used to calculate global effect size and the corresponding standard error. Pamidronate and Denosumab were the most reported drugs in a total of 374 patients assessed. The initiation of treatments was accompanied by an average reduction of 40.5% [CI95% -51.6, -29.3] in the bone resorption parameters, and 22.0% [CI95% -31.9, -12.1] in the parameters of bone formation after 6-12months. BMD was increased in both FD lesions and in the unaffected skeleton. Pain was reduced by 32.7% [CI95% -52.7, -12.6] after 6-12 months of treatment, and by 44.5% [CI95% -65.3, -23.6] after a mean 41.2 months of follow-up. The variation in pain was highly correlated to variation in bone resorption (R2 = 0.08, p < 0.0001) and formation parameters (R2 = 0.17, p < 0.0001). This study supports the overall efficacy of antiresorptive therapies in terms of reducing bone remodeling, improving bone density, and pain in FD.

Vitamin D level in patients with systemic lupus erythematosus: its relationship to disease course and bone mineral density

ObjectiveTo determine vitamin D levels in patients with SLE and evaluate their relationship to bone mineral density (BMD) and the disease course.MethodsThe study included 101 patients with SLE and 29...

Meta-analysis of the effects of denosumab and romosozumab on bone mineral density and turnover markers in patients with osteoporosis.

To assess the alterations in bone mineral density and bone turnover marker concentrations following the administration of denosumab and romosozumab therapies in patients with osteoporosis. PubMed was searched for studies published until January 28, 2023, that investigated the clinical efficacy and bone turnover marker changes of denosumab and romosozumab in the treatment of osteoporosis, with a minimum follow-up of 3 months in each study. Studies were screened, and data on changes in bone mineral density (BMD), P1NP, and TRACP-5b levels after treatment were extracted and included in the analysis. Six studies were analyzed. At 3 months after treatment, the romosozumab group showed greater changes in lumbar BMD and bone turnover markers. BMD of total hip and femoral neck was relatively delayed. Beginning at 6 to 12 months, romosozumab showed greater changes in bone mineral density and markers of bone turnover. Both romosozumab and denosumab have antiosteoporotic effects, with greater effects on BMD and bone turnover markers observed within 12 months of romosozumab treatment. https://www.crd.york.ac.uk/prospero, identifier CRD42023395034.

The efficacy of alendronate for the treatment of thalassemia-associated osteoporosis: a randomized controlled trial.

With adequate blood transfusion and iron chelation, thalassemia patients have a longer life expectancy and experience long-term metabolic complications, including osteoporosis, fractures, and bone pain. Alendronate, an oral bisphosphonate, is currently used to treat various types of osteoporosis. However, the efficacy for the treatment of thalassemia-associated osteoporosis remains unclear. We conducted a randomized controlled trial to evaluate the efficacy of alendronate for the treatment of osteoporosis in thalassemia patients. Patients were included if they were males (18-50 years) or premenopausal females with low bone mineral density (BMD) (Z-score < -2.0 SD) or positive vertebral deformities from vertebral fracture analysis (VFA). Stratified randomization was performed according to sex and transfusion status. Patients were 1:1 allocated to receive once weekly alendronate 70 mg orally or placebo for a total duration of 12 months. BMD and VFA were re-evaluated at 12 months. Markers of bone resorption (C-terminal crosslinking telopeptide of type I collagen; CTX) and bone formation (Procollagen type I N-terminal propeptide; P1NP), and pain scores were measured at baseline, 6 months, and 12 months. The primary outcome was the change of BMD. The secondary endpoints were changes in bone turnover markers (BTM) and pain scores. A total of 51 patients received the study drug, 28 patients were assigned to receive alendronate and 23 patients to receive placebo. At 12 months, patients in the alendronate group had significant improvement of BMD at L1-L4 compared to their baseline (0.72 ± 0.11 vs 0.69 ± 0.11 g/cm2, p = 0.004), while there was no change in the placebo group (0.69 ± 0.09 vs 0.70 ± 0.06 g/cm2, p = 0.814). There was no significant change of BMD at femoral neck in both groups. Serum BTMs were significantly decreased among patients receiving alendronate at 6 and 12 months. The mean back pain score was significantly reduced compared to the baseline in both groups (p = 0.003). Side effects were rarely found and led to a discontinuation of the study drug in 1 patient (grade 3 fatigue). Alendronate 70 mg orally once weekly for 12 months effectively improves BMD at L-spine, reduces serum BTMs, and alleviates back pain in thalassemia patients with osteoporosis. The treatment was well tolerated and had a good safety profile.

Resveratrol-Induced Suppression of C-type Natriuretic Peptide Associates With Increased Vertebral Bone Density in Postmenopausal Women.

C-type natriuretic peptide (CNP) is a paracrine growth factor essential in driving endochondral bone growth in mammals including humans. Despite evidence from animal experiments and tissues that CNP signaling stimulates osteoblast proliferation and osteoclast activity, whether CNP participates in bone remodeling in the mature skeleton is unknown. Using stored plasma samples from a previous randomized controlled clinical trial (RESHAW) of resveratrol supplementation in postmenopausal women exhibiting mild osteopenia, we have studied changes in plasma aminoterminal proCNP (NTproCNP) and concurrent change in bone turnover markers of formation (osteocalcin [OC] and alkaline phosphatase [ALP]) and resorption (C-terminal telopeptide type 1 collagen [CTX]) with bone mineral density (BMD) over a 2-year period of study in 125 subjects. In year one, subjects received placebo or resveratrol, switching to resveratrol or placebo, respectively, in year two. Across all time points, there were no significant associations of NTproCNP with CTX, ALP, or OC. During year one, plasma NTproCNP declined significantly in both groups. In the crossover comparison, analysis of change within individuals showed that, compared with placebo, NTproCNP declined after resveratrol (p=0.011) and ALP increased (p=0.008), whereas CTX and OC were unchanged. Inverse association of NTproCNP (r=-0.31; p=0.025) and positive association of OC (r=0.32, p=0.022) with BMD at the lumbar spine were identified after resveratrol but not found after placebo. Decline in NTproCNP was independently associated with resveratrol treatment. This is the first evidence that CNP is modulated during a period of increasing BMD in postmenopausal women. Further study of NTproCNP and associations with drivers of bone formation or resorption can be expected to clarify CNP's role during other interventions directed to bone health in adults. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone turnover markers to monitor oral bisphosphonate therapy.

Bisphosphonates are widely used as first-line therapy to slow bone loss and decrease fracture risk in postmenopausal women with osteoporosis. Nonadherence to oral bisphosphonates diminishes the benefit of reduced bone loss and fracture risk of these medications. Strategies to enhance osteoporosis monitoring and adherence to therapy are crucial to improve outcomes. Dual-energy x-ray absorptiometry (DXA) is the gold standard for monitoring bone mineral density but is slow to detect change after initiation of oral bisphosphonate therapy. Bone turnover markers (BTMs) are by-products released during bone remodeling and are measurable in blood and urine. We review how the rapid change in BTMs can be a useful short-term tool to monitor the effectiveness of oral bisphosphonate therapy, which may ultimately improve adherence to therapy and outcomes.

Bone Turnover Markers Changes Induced by Plateletpheresis May Be Minimized with Oral Supplementation of Calcium, Minerals, and Vitamin D before the Procedures: A Non-Randomized, Controlled Study.

Apheresis allows the collection of specific blood components but changes serum calcium (Ca), magnesium (Mg), copper (Cu), zinc (Zn), and hormones involved in bone metabolism due to citrate infusion. We assessed the effect of oral supplementation of calcium, vitamin D, and minerals as pills or an enriched diet before plateletpheresis donation on levels of divalent cations, hormones, and bone turnover markers that may prevent metabolic changes. Methods: Non-randomized controlled study including 134 donors. Serum parathyroid hormone (PTH), Ca, Mg, Zn, Cu, osteocalcin (OC), vitamin D, and type-1 collagen C-terminal telopeptide (CTX-1) levels were measured at baseline and post-procedure. Donors were divided into four groups: supplemented with calcium carbonate and vitamin D (cal + vitd); those receiving calcium, minerals, and vitamin D (cal + vitd + min); those receiving a calcium-rich diet (diet) and a control group (control). Results: PTH levels increased >1-fold, whereas tCa, tMg, Zn, Cu, iCa, iMg, and vitamin D levels decreased immediately after apheresis amongst donors of any group; when these levels were measured two weeks later, donors in the calcium-vitd and cal + vitd + min groups returned to basal values; donors in the cal + vitd + min group were the only group that kept their levels of OC and CTX unchanged at the different study times. Conclusions: Bone turnover markers changes induced by plateletpheresis may be minimized with oral supplementation of calcium, minerals, and vitamin D two days before the procedures.

Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

Changes in Bone Turnover Markers after Osteoporotic Vertebral Compression Fractures in Males and Females.

To explore the normal changes in bone turnover markers (BTMs) and the correlations between the different BTMs after osteoporotic vertebral compression fracture (OVCF). Meanwhile, we explored the related differences that exist between sexes. A total of 130 OVCF patients were retrospectively reviewed. Using IBM SPSS 19.0 statistical software, the differences in the levels of BTMs and clinical parameters between sexes were assessed using Student's unpaired t test, and one-way ANOVA was used for the comparison of the three groups of samples. The correlations between P1NP, CTX, and clinical factors were assessed using Pearson's correlation coefficient. P1NP was 52.15 ng/ml within two weeks in male patients, and the level increased to 96.33 ng/ml after 12 weeks; in female patients, the increase was not as obvious as in male patients. CTX in male patients reached as much as approximately twice the initial value after 12 weeks. However, the situation in female patients was diverse. CTX was 0.58 ng/ml within two weeks and increased to 0.61 ng/ml within 2-12 weeks after the onset of OVCF. Subsequently, CTX decreased suddenly after 12 weeks. The increase in P1NP levels within 2 weeks after OVCF was significantly correlated with the levels of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Changes in CTX within 2 weeks after OVCF were considerably related to phosphorus, 25 hydroxyvitamin D (25-OHD), OC, and BAP. The levels of P1NP and CTX increased differently in males and females after OVCF. The levels of OC and BAP were correlated with the levels of P1NP and CTX within 2 weeks of OVCF.

Circulating miRNAs Respond to Denosumab Treatment After 2 Years in Postmenopausal Women With Osteoporosis-the MiDeTe study.

MicroRNAs (miRNAs)-short, single-stranded, noncoding RNAs-regulate several biological processes, including bone metabolism. We investigated circulating miRNAs as promising biomarkers for treatment monitoring in women with postmenopausal osteoporosis on denosumab (DMAB) therapy. In this prospective, observational, single-center study, 21 postmenopausal women treated with DMAB were included for a longitudinal follow-up of 2 years. Next-generation sequencing (NGS) was performed to screen for serological miRNAs at baseline, month 6, and month 24. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to confirm NGS findings in the entire cohort. Bone turnover markers (BTM) P1NP and CTX, and bone mineral density (BMD) by dual x-ray absorptiometry were assessed and correlated to miRNAs. BMD at the hip (5.5%, P = 0.0006) and lumbar spine significantly increased (11.4%, P = 0.017), and CTX (64.1%, P < 0.0001) and P1NP (69.3%, P < 0.0001) significantly decreased during treatment. NGS analysis revealed significant changes in miRNAs after 2 years of DMAB treatment but not after 6 months. Seven miRNAs were confirmed by RT-qPCR to be significantly changed during a 2-year course of DMAB treatment compared to baseline. Four of these were mainly transcribed in blood cells, including monocytes. Correlation analysis identified significant correlation between change in miRNA and change in BTMs as well as BMD. Based on effect size and correlation strength, miR-454-3p, miR-26b-5p, and miR-584-5p were defined as top biomarker candidates, with the strongest association to the sustained effect of denosumab on bone in osteoporotic patients. Two years of DMAB treatment resulted in upregulation of 7 miRNAs, 4 of which are mainly transcribed in monocytes, indicating a potential impact of DMAB on circulating osteoclast precursor cells. These changes were associated to BMD gain and BTM suppression and could therefore be useful for monitoring DMAB treatment response.

Changes in bone turnover markers in patients without bone metastases receiving immune checkpoint inhibitors: An exploratory analysis

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N-terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome.A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits.A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk.Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger prospective studies, it would identify a new class of skeletal-related irAEs.

Analysis of serum bone turnover markers in female cynomolgus monkeys of different ages.

ObjectiveThe purpose of this study was to examine bone turnover markers, estradiol, parathyroid hormone, and 25 hydroxyvitamin D, in cynomolgus monkeys at different ages to improve our understanding of the changes in bone turnover markers throughout the life cycle of cynomolgus monkeys and to provide a basis for the establishment of a non-human primate model of osteoporosis.MethodsTotal Body Bone Mineral Density and Total Body Bone Mineral Content were measured using Dual-Energy X-Ray Absorptiometry in cynomolgus monkeys at different ages. Serum bone turnover marker' levels were measured using enzyme immunoassays at each age group, and the relationship between bone turnover markers and age was assessed by Spearman rank correlation analysis to investigate the relationship between bone turnover markers and age in female cynomolgus monkeys.ResultsTotal Body Bone Mineral Density in female cynomolgus monkeys peaked at 10 years of age and then formed a plateau that was maintained until old age. Procollagen I Aminoterminal Propeptide, Bone Alkaline Phosphatase, Osteocalcin, and C-Terminal Telopeptide Of Type I Collagen peaked at 1 to 3 years of age and gradually decreased with age, leveling off by 10 years of age. Estradiol, parathyroid hormone, and 25 hydroxyvitamin D, follicle-stimulating hormone, luteinizing hormone, were not significantly different among age groups.ConclusionThis paper provides data on trends in bone turnover markers throughout the life cycle of female cynomolgus monkeys, which are similar to human changes.