Bone Turnover Markers Research Articles

The underlying mechanisms of the association of bone health with depression – an experimental study

BackgroundDepression constitutes a risk factor for osteoporosis, but underlying molecular and cellular mechanisms are not fully understood. MiRNAs influence gene expression and are carried by extracellular vesicles (EV), affecting cell-cell communication. Aims: (1) Identify the difference in miRNA expression between depressed patients and healthy controls; (2) Analyze associations of these miRNAs with bone turnover markers; (3) Analyze target genes of differentially regulated miRNAs and predict associated pathways regarding depression and bone metabolism.Methods and resultsBlood samples from depressed patients (n = 11) were obtained from a previous study and healthy controls (n = 9) were recruited. Sociodemographic, depression diagnosis and depressive symptom (BDI-II) data were collected through questionnaires. Blood plasma was collected from each participant and real-time-quantitative PCR was performed on isolated plasma EVs; differences in miRNA expression between groups were analyzed using qbase+. Regression models assessed the associations of differentially regulated miRNAs with bone turnover markers procollagen-1 N-terminal-peptide, osteocalcin, and crosslaps; enriched pathways and miRNA target gene networks were analyzed. 19 miRNAs were differentially expressed between groups (p < 0.05). MiR-26b-5p and miR-106a-5p showed an association with procollagen-1 N-terminal-peptide; miR-330-5p and miR-377-3p were associated with osteocalcin, and miR-26b-5p, miR-34c-3p and miR-145 with crosslaps. Pathway analysis including the differentially expressed miRNAs predicted enriched pathways, including the FoxO signaling and p53 signaling pathway. Seven target genes were identified.ConclusionsMiRNAs (e.g. miR-26b-5p, miR-377-3p), genes (TNRC6B, HSPA8), and pathways (FoxO- and Hippo-signaling pathway) are identified which could be mediators between the influence of depression on bone health and could possibly serve as biomarkers in the treatment of bone diseases among people with mental disorders.

Efficacy and safety of teriparatide in kidney transplant recipients with osteoporosis and low bone turnover: a real-world experience.

Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD), enhancing survival and quality of life. However, kidney transplant recipients (KTRs) are at high risk for bone disorders, particularly low bone turnover disease, which increases fracture risk. Teriparatide, an anabolic agent, may provide a beneficial treatment option for these patients. This single-center, retrospective observational study involved 18 KTRs with osteoporosis, low bone turnover, and a history of vertebral or non-vertebral fractures. Patients received teriparatide (20μg/day) for up to 2 years. Areal bone mineral density (aBMD) at the lumbar spine (LS), total hip (TH), femoral neck (FN), and trabecular bone score (TBS) were measured at baseline, 1 year, and 2 years. In addition, bone turnover markers (BTMs), serum calcium, phosphorus, parathyroid hormone (PTH), and kidney function were monitored. Significant increases in LS aBMD were observed after 1 year (0.941 ± 0.152 vs 1.043 ± 0.165, p = 0.04) and maintained after 2 years compared to baseline (0.941 ± 0.152 vs 1.074 ± 0.154, p = 0.03). TH aBMD significantly increased after 2 years (0.753 ± 0.145 vs 0.864 ± 0.141, p = 0.04), while FN and TBS showed non-significant improvement. Teriparatide was well-tolerated, with mild and transient hypercalcemia and hypophosphatemia. Teriparatide significantly improved BMD at the LS and TH in KTRs with osteoporosis and low bone turnover, showing a favorable safety profile.

Magnesium and Osteoporosis: A Meta-Analysis of the Effects on Bone Turnover Markers, Fracture Incidence, and Quality of Life

Background: Osteoporosis, a prevalent bone disease characterized by reduced bone mineral density (BMD) and increased fracture risk, poses a significant public health challenge. Magnesium, an essential mineral involved in bone metabolism, has emerged as a potential therapeutic agent. This meta-analysis aimed to evaluate the effects of magnesium supplementation on bone turnover markers, fracture incidence, and quality of life in individuals with osteoporosis. Methods: A systematic search of PubMed, Embase, and Cochrane Library databases was conducted from January 2013 to December 2024 to identify randomized controlled trials (RCTs) investigating the impact of magnesium supplementation on adults diagnosed with osteoporosis. The primary outcomes were changes in bone turnover markers (serum calcium, phosphorus, alkaline phosphatase, and osteocalcin), fracture incidence, and quality of life scores. Standardized mean differences (SMD) and risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models. Results: Nine RCTs met the inclusion criteria, encompassing a total of 825 participants. Magnesium supplementation demonstrated a significant improvement in bone turnover markers, with a decrease in serum alkaline phosphatase (SMD = -0.35; 95% CI: -0.62, -0.08; p = 0.01) and osteocalcin (SMD = -0.29; 95% CI: -0.51, -0.07; p = 0.009). A trend towards reduced fracture incidence was observed in the magnesium group (RR = 0.72; 95% CI: 0.51, 1.02; p = 0.06). Furthermore, magnesium supplementation significantly improved quality of life scores, as measured by the Osteoporosis Quality of Life Questionnaire (OQLQ) (SMD = 0.41; 95% CI: 0.15, 0.67; p = 0.002). Conclusion: This meta-analysis provides evidence that magnesium supplementation may have beneficial effects on bone turnover markers and quality of life in individuals with osteoporosis. Although a trend towards reduced fracture incidence was observed, further large-scale RCTs are warranted to confirm this finding.

Case report: Persistent syndrome of inappropriate antidiuresis after traumatic brain injury: spontaneous resolution and impact on RAAS and bone metabolism over five years

The syndrome of Inappropriate Antidiuresis (SIAD) is a well-known cause of hyponatremia and can be associated with various etiologies, including traumatic brain injury (TBI). Most cases of SIAD following TBI exhibit a pattern in which hyponatremia develops several days to weeks after the trauma and resolves within a few weeks. Here, we present a rare case of persistent SIAD caused by TBI that resolved spontaneously after five years. The patient experienced prolonged hyponatremia for several years and was ultimately diagnosed with post-traumatic SIAD after excluding other potential causes. Notably, the patient exhibited an unusual sensitivity to tolvaptan, accompanied by decreased renin levels and increased bone turnover markers. The condition resolved spontaneously after five years, with renin, aldosterone, and bone turnover markers returning to normal upon re-evaluation.

Efficacy and safety of JMT103 in patients with bone metastases from solid tumors: A randomized Phase Ib clinical trial.

This study aimed to assess the efficacy and safety of three dosing regimens of JMT103 in patients with bone metastases from solid tumors. Eligible patients were randomly assigned to receive JMT103 subcutaneously, 120 mg every 4 weeks (Cohort 1), 120 mg every 8 weeks (Cohort 2), or 180 mg every 8 weeks (Cohort 3) for up to 49 weeks. The primary endpoint was change from baseline to Week 13 in creatinine-adjusted urinary N-telopeptide (uNTx/Cr). Two hundred and ninety-five patients were randomized, and 293 received at least one dose of JMT103, of whom 96 were assigned to Cohort 1, 97 were assigned to Cohort 2, and 100 were assigned to Cohort 3. The median (interquartile range) percentage reduction in uNTx/Cr at Week 13 was 80.0% (49.9%, 93.4%) in Cohort 1, 73.0% (34.5%, 94.0%) in Cohort 2, and 75.7% (40.4%, 92.0%) in Cohort 3, respectively. On-study skeletal-related events were reported by 3.1% of patients in Cohort 1, 6.2% in Cohort 2, and 7.0% in Cohort 3. Treatment-emergent adverse events occurred in 289 patients, 162 of whom were deemed treatment-related. The most common treatment-related adverse events were hypocalcemia (23.2%), hypophosphatemia (22.9%), and increased aspartate transaminase (11.9%). JMT103 demonstrated a good safety and a strong suppression of the bone turnover markers.

P0415 Bone turnover biomarkers alteration in patients with Inflammatory Bowel Disease

Abstract Background Because of glucocorticoids, chronic inflammation, malabsorption, and other factors, patients with inflammatory bowel disease (IBD) are at varying risk for osteoporosis (OP) and decreased bone mineral density. This puts individuals at risk for osteoporotic fractures, which have a negative impact on their quality of life. The purpose of this study is to measure bone turnover markers (BTMs) representing bone resorption and formation in an Egyptian cohort of IBD patients, compare them to healthy controls, and investigate their relationship to disease activity, extension, and treatment modalities. Methods The cross-sectional study included 92 participants: 45 IBD patients, 25 ulcerative colitis (UC), 20 Crohn’s disease (CD), and 47 controls. Overnight fasting blood samples were withdrawn for BTMs including bone formation markers (Procollagen I N-terminal propeptide {PINP} and bone specific alkaline phosphatase {BSAP}), bone resorptive marker (C-terminal telopeptide of type I collagen {CTX}). Results Serum CTX, PINP, and BALP levels increased significantly in IBD patients, indicating increased turnover and metabolic bone disease, but there were no significant differences between the UC and CD groups. In terms of disease activity and intestinal involvement, BTM levels in UC and CD patients were comparable. Anti-tumour necrosis-α (anti-TNF-α) users had considerably reduced CTX and PINP increases compared to non-users. Conclusion Biochemical testing with BTMs may be useful in the initial evaluation of bone health in IBD patients. Anti-TNF-α users were less likely to experience bone alterations compared to non-users.

The Use of Bone Biomarkers, Imaging Tools, and Genetic Tests in the Diagnosis of Rare Bone Disorders.

Rare bone diseases are clinically and genetically heterogenous. Despite those differences, the underlying pathophysiology is not infrequently different. Several of these diseases are characterized by abnormal bone metabolism and turnover with subsequent abnormalities in markers of bone turnover, rendering them useful adjuncts in the diagnostic process. As most rare bone diseases are inherited, genetic testing for implicated pathogenic variants, where known, is another relevant tool that can aid in diagnosis. While some skeletal disorders can be localized or monostotic, others can involve multiple skeletal sites and warrant imaging tools to localize them and determine the severity of disease and/or presence of complications as well as to assess bone quality and the potential risk of fractures. Rare bone disorders pose a great challenge in their diagnosis, ultimately resulting in delayed diagnosis, higher risk of complications and a poor quality of life in affected individuals. In this review we discuss the biochemical and radiological tools that can be utilized to diagnose selected orphan bone disorders, the clinical utility and limitations of these diagnostic tools, and areas where future research is warranted.

Assessment of Biochemical Markers of Bone Turnover and their Association in Iraqi Thalassemia Patients

Assessment of Biochemical Markers of Bone Turnover and their Association in Iraqi Thalassemia Patients

Factors influencing therapeutic efficacy of denosumab against osteoporosis in systemic lupus erythematosus

ObjectiveOsteoporosis is a common comorbidity in patients with SLE, and bone loss in patients with SLE has a multifactorial aetiology. This study aimed to evaluate the therapeutic efficacy of denosumab...

Bone turnover markers as predictors of hypocalcemia in patients with bone metastases receiving denosumab

Bone turnover markers as predictors of hypocalcemia in patients with bone metastases receiving denosumab

Modulation of Bone Turnover Markers with Dipeptidyl Deptidase-4: Interplay in Bone Health

Modulation of Bone Turnover Markers with Dipeptidyl Deptidase-4: Interplay in Bone Health

Osteopenia Metabolomic Biomarkers for Early Warning of Osteoporosis.

Introduction: This study aimed to capture the early metabolic changes before osteoporosis occurs and identify metabolomic biomarkers at the osteopenia stage for the early prevention of osteoporosis. Materials and Methods: Metabolomic data were generated from normal, osteopenia, and osteoporosis groups with 320 participants recruited from the Nicheng community in Shanghai. We conducted individual edge network analysis (iENA) combined with a random forest to detect metabolomic biomarkers for the early warning of osteoporosis. Weighted Gene Co-Expression Network Analysis (WGCNA) and mediation analysis were used to explore the clinical impacts of metabolomic biomarkers. Results: Visual separations of the metabolic profiles were observed between three bone mineral density (BMD) groups in both genders. According to the iENA approach, several metabolites had significant abundance and association changes in osteopenia participants, confirming that osteopenia is a critical stage in the development of osteoporosis. Metabolites were further selected to identify osteopenia (nine metabolites in females; eight metabolites in males), and their ability to discriminate osteopenia was improved significantly compared to traditional bone turnover markers (BTMs) (female AUC = 0.717, 95% CI 0.547-0.882, versus BTMs: p = 0.036; male AUC = 0.801, 95% CI 0.636-0.966, versus BTMs: p = 0.007). The roles of the identified key metabolites were involved in the association between total fat-free mass (TFFM) and osteopenia in females. Conclusion: Osteopenia was identified as a tipping point during the development of osteoporosis with metabolomic characteristics. A few metabolites were identified as candidate early-warning biomarkers by machine learning analysis, which could indicate bone loss and provide new prevention guidance for osteoporosis.

Evaluation of Bone Mineral Metabolism in Pre-Dialysis Chronic Kidney Disease: Quantitative Computed Tomography vs. Dual-Energy Absorptiometry and Correlation with Bone Turnover Markers.

Background and Objectives: Bone and mineral disease (BMD) is a prevalent complication of advanced chronic kidney disease (CKD). The risk of fractures can be assessed via dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). This study aims to evaluate the effectiveness of two imaging modalities in identifying bone mineral status in individuals with pre-dialysis chronic renal disease and to assess their correlation with bone turnover markers. Materials and Methods: This controlled cross-sectional study, conducted at a single center from 2019 to 2022, assessed two groups of individuals aged 18 to 50. The patient cohort consisted of individuals with stage 4-5 chronic kidney disease, whereas the control cohort consisted of healthy participants. The participants' bone and mineral status was evaluated using both QCT and DXA methods. Diagnostic measurements of the lumbar spine and femoral neck, obtained using DXA and QCT, were compared. Z-scores were utilized to evaluate low bone mineral density, with low Z-scores identified in either lumbar spine or femoral neck measures being seen as indicative of low bone mineral density. Results: Data from 38 participants (patient group: 18; control group: 20) who underwent QCT and/or DXA were evaluated. Thirty-three subjects were assessed using both QCT and DXA (patient group: 14; control group: 19). The median age of the patient cohort was 44 (range: 22-50), whereas the median age of the control cohort was 42 (range: 27-48) (p = 0.72). Women constituted 33% of the patient cohort and 50% of the control cohort (p = 0.23). In the patient cohort, low bone mineral density was detected in four individuals (28%) through QCT, and in just two patients (14%) through DXA. Compared to DXA, QCT identified a higher number of cases of low bone mineral density in the CKD cohort; however, no statistically significant difference was observed (p = 0.06). In addition, our study found that TRACP5b had a strong negative correlation with the DXA L1-L4 Z-score. Conclusions: This study revealed that QCT may be more sensitive than DXA for detecting low bone density in pre-dialysis CKD patients. Additionally, DXA may overestimate lumbar spine BMD in this population, and the strong negative correlation between TRACP5b levels and the DXA L1-L4 Z-score highlights the potential role of biochemical markers in assessing bone status in CKD.

Real-world safety and effectiveness of romosozumab following daily or weekly administration of teriparatide in primary and secondary osteoporosis.

Romosozumab is an anti-sclerostin antibody that increases bone formation and decreases bone resorption, and it became available for patients at high risk of osteoporotic fractures in Japan in 2019. The aim of this study was to clarify the clinical effects, safety, and predictors of the effectiveness of 12months of romosozumab therapy following daily or weekly administration of teriparatide. The study had an observational pre-post design and included 171 female patients. Romosozumab was administered at a dose of 210mg subcutaneously every 4weeks for 12months following daily or weekly administration of teriparatide. The incidence of new fractures, safety, and changes in bone mineral density (BMD) and bone turnover markers were recorded. New fractures occurred in 3 cases (2.2%). Four patients (2.3%) with secondary osteoporosis experienced cardiovascular events, which were fatal in 1 patient (0.6%). The percent changes in BMD at the spine and total hip at 12months from baseline were+7.9% and+2.4%, respectively. The percent change in spine BMD did not significantly differ according to whether daily or weekly teriparatide was given as previous treatment. Romosozumab following teriparatide showed greater effectiveness in patients with primary osteoporosis, high P1NP level at 1month, and low percent changes in TRACP-5b after 12months of treatment. Romosozumab after treatment with daily or weekly teriparatide was relatively safe and more effective in patients with primary osteoporosis than in those with secondary osteoporosis.

The serum level of sclerostin decreases in radiographic axial spondyloarthritis patients with fatty lesions

BackgroundCurrently, the pathophysiology of new bone formation in radiographic axial spondyloarthritis (r-axSpA) remains unclear. Cellular elements and their secreted bone turnover markers might be one of the underlying mechanisms that drive the new bone formation. Our study aimed to investigate the role of bone turnover markers in r-axSpA patients with fatty lesions.Methods73 r-axSpA patients were enrolled in this study. 48 and 25 patients were divided into r-axSpA group with and without fatty lesions. Clinical variables were collected and all patients received comprehensive rheumatologic assessment for disease activity, including Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Axial Spondyloarthritis Disease Activity Score (ASDAS). Fatty lesions in the sacroiliac joints (SIJs) were scored independently by two radiologists. Serum levels of bone turnover markers, including sclerostin, osteoprotegerin (OPG), procollagen I N-terminal propeptide (PINP), cross linked C-telopeptide of type I collagen (CTX-I), osteocalcin (OC), were measured using enzyme-linked immunosorbent assays.ResultsThere were no significant differences between two groups in terms of gender, age, body mass index (BMI), duration, smoking, HLA-B27 positivity rate, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), BASDAI, ASDAS-ESR, ASDAS-CRP, biological disease-modifying anti-rheumatic drugs (bDMARDs) rate. No significant differences were observed in terms of OPG, PINP, CTX-I or OC between two groups. The mSASSS were higher in fatty lesions group than in those without fatty lesions (p < 0.001). The serum sclerostin levels were significantly lower in r-axSpA patients with fatty lesions than in those without fatty lesions (p < 0.001). There were correlations between BMI, mSASSS and sclerostin with the comprehensive Berlin scoring method (CBM) scores in the univariate analysis (ρ = 0.311, ρ = 0.306, ρ = -0.920, respectively). However, only sclerostin had correlation with the CBM scores in multivariate analysis (ρ = -0.040, p < 0.001).ConclusionsIn the r-axSpA patients with fatty lesions, serum sclerostin levels are declined. Serum sclerostin might be useful as a biomarker to predict the progression of the chronic inflammation in SIJs in r-axSpA.

Impact of switching from bisphosphonates to denosumab, teriparatide, or romosozumab in patients with postmenopausal osteoporosis: a case-control study.

To investigate the impact of switching from bisphosphonates (BP) to denosumab (DMAb), teriparatide (TPTD), or romosozumab (ROMO) in postmenopausal osteoporosis. This retrospective, case-controlled, multicenter study included 389 patients who switched from BP to DMAb, TPTD, or ROMO due to treatment inefficacy. Propensity score matching was used to align patient backgrounds, resulting in 45 patients per group. Baseline characteristics included a mean age of 73.8years, prior BP treatment duration of 37.1months, and bone mineral density (BMD) T-scores of -2.8 in the lumbar spine (LS), -2.5 in the total hip (TH), and -2.7 in femoral neck (FN). BMD and bone turnover markers were assessed over 12months. Following the switch from BP, the ROMO group demonstrated a dual effect of decreased bone resorption and increased bone formation markers. The TPTD group exhibited the highest increases in both markers, while the DMAb group suppressed both. After 12months, the ROMO group demonstrated significantly greater BMD increases in the LS (11.4%) compared to the DMAb (6.3%; p < 0.001) and TPTD (5.9%; p < 0.001) groups. Additionally, the ROMO group showed greater increases in the TH (3.3%) than TPTD group (0.8%; p < 0.01). Only the ROMO group showed a significant BMD increase in the FN (2.0%; p < 0.01 from baseline). Significant BMD increases were observed in the LS for all groups, in the TH for the ROMO and DMAb groups, and in the FN for the ROMO group. ROMO showed the most substantial BMD improvements following BP therapy.

Effect of Chrysin, a Flavonoid Present in Food, on the Skeletal System in Rats with Experimental Type 1 Diabetes.

It seems that some substances of plant origin may exert health-promoting activities in diabetes and its complications, including those concerning bones. Chrysin (5,7-dihydroxyflavone), present in honey, some plants, and food of plant origin, has been reported to exert, among others, antioxidative, anti-inflammatory and antidiabetic effects. The aim of this study was to investigate the effects of chrysin on the skeletal system of rats with experimental type 1 diabetes (T1D). The experiments were carried out on mature male Wistar rats. T1D was induced by a single streptozotocin injection. Administration of chrysin (50 or 100 mg/kg p.o., once daily) began two weeks later and lasted four weeks. Serum bone turnover markers, bone mass, density and mineralization, mechanical properties and histomorphometric parameters of cancellous and compact bone were examined. T1D profoundly affected bone metabolism, leading to worsening of bone strength in comparison with the healthy controls. After administration of chrysin, slight improvement of only some parameters was demonstrated in relation to the diabetic controls. Results of the present study indicate that chrysin may exert some very limited favorable effects on the skeletal system in diabetic conditions.

The comparison of serum bone-turnover markers in different stage of chronic kidney disease and the associated impact of intradialytic cycling in patients with end-stage renal disease.

Bone turnover markers reflected the bone remodeling process and bone health in clinical studies. Studies on variation of bone remodeling markers in different stage CKD were scant, and this study investigated the role of bedside intradialytic cycling in altering concentrations of bone-remodeling markers in patients with end-stage renal disease (ESRD). Participants were segmented into four groups: a group with eGFR >60 ml/min/1.73 m2, a chronic kidney disease group with eGFR 15-60 mL/min/1.73 m2), an ESRD group with an exercise intervention, and an ESRD group with standard care. Comparison of bone turnover markers was performed among groups. The intervention consisting of 12 weeks of intradialytic cycling was performed during dialysis. The variation of bone-remodeling markers was compared between the ESRD with exercise along with the ESRD with standard care after 12-week monitoring. Bone-formative marker levels (bone-specific alkaline phosphatase and procollagen type 1 amino-terminal propeptide, P1NP) were higher in ESRD patients than in non-ESRD patients and were correlated with indoxyl sulfate and intact parathyroid hormone concentrations (p < 0.05). Postexercise concentrations of tartrate-resistant acid phosphatase-5b (p = 0.003) and N-terminal telopeptide-1 (p = 0.001) had increased in the ESRD patients after 12 weeks of bedside cycling. Bone-formative marker concentration was not altered in the exercise group after cycling. Bone-formative marker concentrations increased with the severity of chronic kidney disease. Bone formative markers concentration increased along with CKD severity. We demonstrated the bone resorptive markers tartrate-resistant acid phosphatase-5b and N-terminal telopeptide-1 increased after intradialytic cycling in ESRD patients.

Bone Composition Changes and Calcium Metabolism in Obese Adolescents and Young Adults Undergoing Sleeve Gastrectomy: A Systematic Review.

Background/Objectives: Sleeve gastrectomy (SG) is increasingly used to treat severe obesity in adolescents, but its effects on bone health during this critical period of bone accrual are not fully understood. This systematic review aims to evaluate the impact of SG on the bone mineral density (BMD), bone microarchitecture, marrow adipose tissue (MAT), and bone turnover markers in adolescents. Methods: A comprehensive literature search was conducted to identify studies assessing bone health outcomes in adolescents undergoing SG. Nine studies met the inclusion criteria, comprising prospective cohorts, observational cohorts, and one randomized controlled trial, with sample sizes ranging from 10 to 197 participants aged 13 to 25 years, and a total sample size of 597 individuals. Data were extracted and synthesized into tables summarizing changes in BMD, bone microarchitecture, MAT, and bone turnover markers. Results: SG in adolescents is associated with significant reductions in areal BMD at critical skeletal sites, particularly the femoral neck and total hip, with decreases ranging from -4.7% to -8.9%. Studies utilizing high-resolution peripheral quantitative computed tomography (HRpQCT) reported deteriorations in bone microarchitecture, including a decreased trabecular number, increased trabecular separation, and reduced cortical thickness. Two studies observed significant increases in MAT at the lumbar spine post-SG. Elevated bone turnover markers, particularly C-terminal cross-linking telopeptide (CTX), indicate increased bone resorption following SG. Conclusions: SG leads to negative effects on bone health in adolescents, including reductions in BMD, deterioration of the bone microarchitecture, increases in MAT, and elevated bone resorption markers. These findings highlight the need for careful monitoring of bone health and the development of strategies to mitigate bone loss in adolescents undergoing SG.

Bone Turnover Markers Predict Changes in Bone Mineral Density in Men Treated with Abaloparatide: Results from ATOM.

Early increases in bone turnover markers (BTMs) in response to anabolic therapy correlate with 18-month bone mineral density (BMD) increases in postmenopausal women with osteoporosis; however, this relationship has not been assessed in men. In this analysis, the correlation between changes from baseline in fasting intact serum procollagen type I N propeptide (PINP) and serum carboxy-terminal cross-linking telopeptide of type I collagen (CTX) at 1, 3, 6, and 12months and percent increase from baseline in BMD at 12months in men from the randomized phase 3 ATOM study (NCT03512262) were evaluated using Pearson's correlation coefficients. The uncoupling index (UI), a measure of the balance between markers of bone formation (PINP) and bone resorption (CTX), with positive UI favoring bone formation, was calculated. Results in men were compared to 12-month results for women from the ACTIVE study using the z score test after Fisher's Z transformation. In abaloparatide-treated men, PINP increases at 1month (r = 0.485), 3months (r = 0.614), 6months (r = 0.632), and 12months (r = 0.521) were highly correlated (P<.0001) with 12-month lumbar spine BMD increases. The mean UI for abaloparatide-treated men was greater than placebo as early as 1month (2.26 versus -0.25). At month 3, the mean UI for men was greater (1.32) than for women (0.88) (P<.001). There was a significant correlation between 3-month UI and lumbar spine BMD at 12months in both men (r = 0.453; P<.001) and women (r = 0.252; P<.01); UI at months 6 and 12 were also significantly correlated with 12-month lumbar spine BMD in men and women, but the correlation was stronger in men than women. These data support that early changes in BTMs in men treated with abaloparatide are associated with subsequent changes in BMD similar to what has been reported in women. Trial registration: clinicaltrials.gov Identifier NCT03512262.