Bone Turnover Markers Research Articles

Impaired Bone Tissue Quality Associated with Inflammation in HIV-Immunological Non-Responders: A Cross-Sectional Analysis

Abstract Introduction People with HIV (PWH) with poor immune response despite adequate antiretroviral treatment (ART) are susceptible to non-AIDS-related health issues. This study seeks to evaluate bone quality in Immunological Non-Responders (INRs) in comparison to those with proper immune response (IRs) using in vivo microindentation to quantify bone quality, in addition to conventional bone mineral density (BMD) evaluations. Methods A cross-sectional study was conducted at Hospital del Mar in Barcelona from January 2019 to June 2023. Participants were matched in a 1:2-ratio (INRs:IR) based on age, sex, body mass index (BMI), and ART. Participants underwent bone quality assessment using in vivo microindentation, BMD and analysis of bone turnover and inflammation markers. Statistical analyses involved multivariable regression to adjust for potential confounding variables. Results A total of 159 PWH were included, 53 INRs and 106 IRs. INRs had worse bone quality, with lower median Bone Material Strength index (BMSi) compared to IRs (79 (76-87) vs. 86 (82-89); p<0.001), and similar BMD. INRs shown increased high-sensitive C-Reactive Protein levels with lower 25-(OH)-Vitamin D3. A significant negative correlation between inflammation and bone quality was found, especially noticeable in INRs. Multivariable linear regression shown that INR status is a major predictor of decreased bone quality, regardless of conventional risk factors. Conclusion INRs condition is significantly associated with higher inflammatory levels, which may contribute to a deleterious effect on bone quality as measured by in vivo microindentation. Further studies are needed to confirm these results and to focus on non-AIDS comorbidities in this subgroup of PWH.

F2-Isoprostanes Are Associated With Increased Fracture Risk in Type 2 Diabetes

Abstract Context Fracture risk is higher in type 2 diabetes (T2D) for a given bone mineral density (BMD) level. Increased oxidative stress in T2D induces diabetic complications and may affect T2D bone fragility. Objective To investigate whether the levels of plasma F2-isoprostanes, a reliable oxidative stress marker, are associated with incident clinical fracture risk in older adults with diabetes. Design and Setting An observational cohort study was conducted in a well-characterized cohort from Health, Aging, and Body Composition study. Participants Older black and white ambulatory adults with baseline plasma F2-isoprostanes measurements (baseline age 70-79 years, T2D: N=132; non-diabetes: N=571) were selected from the study cohort of 3075 individuals. Main Outcome Measures Incident clinical fractures. Results In the Cox proportional hazard model with multivariate adjustments (including BMD, medications, and other risk factors), a 93% increase in incident clinical fracture risk was significantly associated with each SD increase in log plasma F2-isoprostanes in the T2D group (HR: 1.93, 95% CI 1.26-2.95, p=0.002), but there was no evidence of an association in the non-diabetes group (HR: 0.98, 95% CI 0.81-1.18, p=0.79, p for interaction < 0.001). Log plasma F2-isoprostanes were moderately correlated with a decline in baseline total hip BMD (r=-0.25, p=0.003), and with a 4-year decrease in total hip BMD (r=-0.28, p=0.008) in T2D. There was no evidence of correlation between log plasma F2-isoprostanes and circulating glycoxidation markers or bone turnover markers in either group. Conclusions Plasma F2-isoprostanes levels in individuals with diabetes are associated with increased incident clinical fracture risk independently of baseline BMD.

Changes in Angiogenesis and Bone Turnover Markers in Patients with Gaucher Disease Developing Osteonecrosis

Changes in Angiogenesis and Bone Turnover Markers in Patients with Gaucher Disease Developing Osteonecrosis

Fracture severity dependence of bone and muscle performance in patients following single or multiple vertebral fractures

BackgroundFew studies focus on the clinical, laboratory, radiological, and biological characteristics of bone and muscle of multiple vertebral fractures, which are associated with a more poor prognosis compared with single fracture.PurposeTo compare the BMD, bone turnover, muscularity, fatty infiltration of muscle, and prevalence of co-morbidities in patients with single and multiple vertebral fractures.MethodsWe recruited 100 patients with single fracture (age 66.96 ± 8.24 years) and 100 with multiple fractures (age 69.90 ± 7.80 years); performed dual-energy X-ray absorptiometry of the femoral neck, hip, and lumbar vertebrae; and measured biochemical markers of bone turnover, muscularity, and fatty infiltration.ResultsPatients with multiple vertebral fractures had lower hip BMD (p=0.010) than those with single fractures, but there was no difference in femoral neck and lumbar vertebral BMD nor in muscularity. However, fatty infiltration, an indicator of muscle quality, was significantly higher in participants with multiple fractures (p=0.006). Diabetes was significantly more common in patients with multiple fractures (p=0.042). There were no significant differences in markers of bone turnover, and Seperman analyses showed no correlations of CTX-1 or tPINP with the BMD of the hip, femoral neck, or lumbar spine. However, high CTX-1 was associated with high tPINP (r=0.4805; p<0.0001), and marked fatty infiltration was associated with low hip, lumbar vertebral, and femoral neck BMD. Cox regression analyses showed that age (OR 1.057; 95% CI 1.016–1.101; p=0.006) and low hip BMD (OR 0.016; 95% CI, 0.000–0.549; p=0.022) were associated with a higher risk of multiple fractures.ConclusionPatients with multiple fractures tend to have lower hip BMD, a history of type 2 diabetes, and more substantial fatty infiltration of muscle than in those with single fractures. Age and hip BMD rather than lumbar vertebrae BMD were found to be independent risk factors for multiple vertebral compression fractures, implying that hip BMD may be a more sensitive predictor for multiple vertebral fractures. More improvements in hip BMD and focus on older persons may be useful means of preventing multiple fractures.

Gastrointestinal health and serum proteins are associated with BMD in postmenopausal women: a cross-sectional study

BackgroundWith increasing age, the social and economic burdens of postmenopausal osteoporosis are steadily increasing. This study aimed to investigate the factors that influence the development of postmenopausal osteoporosis.MethodsPostmenopausal women at the Affiliated Hospital of Jiangnan University from January 2023 to December 2023 were recruited for BMD examination. The patients were divided into a normal group, an osteopenia group and an osteoporosis group according to their T value. Questionnaires, including the Gastrointestinal Symptom Rating Scale and Short Form 12, were administered through face-to-face interviews. Bone turnover markers and serum protein levels of Fasting venous blood were detected.ResultsA total of 222 postmenopausal women met the inclusion criteria were recruited. Univariate analysis revealed statistically significant differences in age, education, BMI, supplementation with soy products, supplementation with dairy products, supplementation with other nutritional supplements, exercise frequency, gastrointestinal symptom score, quality of life, 25(OH)D, total protein, albumin and prealbumin among the three groups (P < 0.05). Pearson correlation analysis revealed that gastrointestinal symptoms (r = -0.518, P < 0.01) was negatively correlated with BMD in postmenopausal women, while PCS (r = 0.194, P = 0.004), MCS (r = 0.305, P < 0.01), 25(OH)D (r = 0.531, P < 0.01), total protein (r = 0.324, P < 0.01), albumin (r = 0.341, P < 0.01) and prealbumin (r = 0.259, P < 0.01) were positively correlated with BMD. Logistic regression analysis revealed that both the gastrointestinal symptom score and serum 25(OH)D level were found to have a significant association with BMD (both P < 0.01). This association remained significant even after adjusting for age, BMI, education level, dietary habits, and exercise frequency.ConclusionGastrointestinal symptoms and serum 25(OH)D elevel are associated with increased risk of osteoporosis in postmenopausal women and may be useful in predicting osteoporosis in postmenopausal women.

The association between metabolite profiles and impaired bone microstructure in adult growth hormone deficient rats

BackgroundAdult growth hormone deficiency (AGHD) is associated with an increased risk of fractures and impaired bone microstructure. Understanding the metabolic changes accompanying bone deterioration in AGHD might provide insights into mechanisms behind molecular changes and develop new biomarkers or nutritional strategies for bone destruction. Our study aimed to investigate the association between altered metabolite patterns and impaired bone microstructure in adult rats with growth hormone deficiency.MethodsThirty seven-week-aged adult Lewis dwarf homozygous (dw/dw) rats (five females and five males), and adult Lewis dwarf heterozygous (dw/ +) rats (five females and five males) rats were compared. Micro-computed tomography (Micro-CT) was used to examine the bone's microstructure. Hematoxylin and eosin (H&E) staining were used to quantify the histological characteristics. Liquid chromatography-mass spectrometry untargeted serum metabolomic analysis was applied in the study. ELISA was used to measure serum bone turnover markers and IGF-1 levels.ResultsAdult dw/dw rats exhibited great reductions in trabecular volume bone density (Tb.vBMD), bone volume/total volume (BV/TV), and cortical thickness (Ct. Th) compared with adult dw/ + rats (all p values < 0.05), indicating significant impairment in bone microstructure. The serum metabolite profiles revealed substantial differences between the dw/dw rats and dw/ + rats. A total of 134 differential metabolites in positive ion mode and 49 differential metabolites in negative mode were identified. Five metabolites, including Lysophosphatidylcholine(LPC) 20:3, LPC22:6, LPC22:4, cortisol and histamine levels were upregulated in dw/dw rats. The steroid hormone biosynthesis and bile secretion pathways were the main perturbed metabolic pathways. There were significant associations between differential metabolites and the impaired bone microstructure parameters, indicating that the selected metabolites might serve as potential biomarkers for deteriorated bone microstructure in AGHD.ConclusionAdult dw/dw rats exhibit impaired bone microstructure and distinct serum metabolic profiles, and the altered metabolites were significantly associated with bone microstructure destruction. This provides a new insight into understanding the mechanism of bone deterioration in AGHD patients from a metabolic perspective.

Possible role of bone turnover markers in the diagnosis of adult hypophosphatasia.

Hypophosphatasia (HPP) is a rare disorder of the bone metabolism, characterized by genetically-determined low alkaline phosphatase (ALP) activity. Low ALP may also be observed in some common causes of bone fragility, such as in osteoporosis treated with antiresorptive drugs. This study aimed to verify whether differences in bone turnover markers (BTMs) could help differentiate adult patients with HPP from those with osteoporosis undergoing antiresorptive treatment. In this multicenter study, we enrolled 23 adult patients with a diagnosis of HPP and compared them with 46 osteoporotic subjects previously treated with zoledronic acid or denosumab. BTMs such as C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I procollagen (P1NP), total ALP, and bone ALP (bALP) were measured, and ratios between BTMs were also calculated. Considering that the control group included only females, in the primary analysis we compared their characteristics with that of the 16 female patients with HPP. Both individual BTMs (CTX and P1NP) and four BTM ratios (ALP/P1NP, bALP/P1NP, ALP/CTX, and bALP/CTX) showed satisfactory discriminatory power, outperforming ALP alone. P1NP, in particular, had an AUC of 0.962 with a cut-off of 32μg/L, while as for the BTMs ratios, the ALP/P1NP ratio had an AUC of 0.964 with a cut-off of 1.114. Similar results were confirmed when including male HPP patients, when adjusting for age and sex, and finally when performing a sensitivity analysis only in patients with ALP less than or equal to 32U/L (i.e., the median of the distribution of the entire population). In cases of low ALP and bone fragility, BTM and their ratios could help distinguish HPP patients from osteoporotic individuals treated with antiresorptive drugs, aiding in accurate diagnosis and reducing the risk of inappropriate treatment.

Sonification of Deproteinized Bovine Bone Functionalized with Genistein Enhances Bone Repair in Peri-Implant Bone Defects in Ovariectomized Rats

Estrogen deficiency is one of several contributing factors to catabolic changes in bone surrounding dental implants, impairing bone repair in defects requiring bone regeneration. Functionalizing bone substitutes is an alternative approach among various strategies to address this challenge. In this study, the aim was to evaluate the effect of functionalizing deproteinized bovine bone (Bio-Oss®, BO) with genistein via sonication on peri-implant bone defects in ovariectomized rats. The animals were randomly distributed according to the treatment into the following four groups (n = 10): BO sonicated with genistein (BOS + GEN), BO sonicated alone (BOS), untreated BO (BO), and blood clot only (CLOT). After twenty-eight days, implant removal torque was determined, and the peri-implant bone parameters were calculated based on computed microtomography. Additionally, the gene expression of bone turnover markers was evaluated. As a main result, the functionalization with genistein increased implant removal torque and the peri-implant bone volume in the BOS + GEN group compared to both BOS and BO groups (both p &lt; 0.05). These findings suggest that the sonification of deproteinized bovine bone functionalized with genistein improves bone repair in peri-implant bone defects in ovariectomized rats.

Romosozumab for the treatment of osteoporosis - a systematic review.

Romosozumab, a new treatment of osteoporosis, is a monoclonal antibody that targets sclerostin and thereby exhibits a dual mechanism of action by stimulating bone formation and inhibiting bone resorption. This systematic review aims to assess the clinical efficacy and safety of romosozumab for treatment of primary and secondary osteoporosis. A comprehensive literature search was conducted in October 2023 across multiple databases including Embase, PubMed and Cochrane Library. Randomized controlled trials (RCTs) and observational studies evaluating the impact of romosozumab on BMD, bone turnover markers (BTM), fracture outcomes, and its safety profile were included. Data extraction and quality assessment were performed independently by two reviewers in accordance with PRISMA guidelines. A total of 36 articles met the inclusion criteria. Romosozumab significantly increased BMD at the lumbar spine, total hip, and femoral neck compared to placebo and active comparators in patients with primary osteoporosis. Sequential therapy with romosozumab followed by antiresorptives maintained or further increased BMD and reduced fracture risk. Romosozumab was generally well tolerated, however, an imbalance in cardiovascular adverse event was observed in one large clinical trial. Observational studies supported these findings. Specific subgroups of patients with secondary osteoporosis were assessed, demonstrating overall positive outcomes with romosozumab treatment. Romosozumab effectively increases BMD and reduces fracture risk, particularly when used as initial therapy in high fracture-risk patients. Sequential therapy with subsequent antiresorptive treatment optimizes long-term benefits. While generally well-tolerated, its cardiovascular safety profile requires further long-term studies to ensure its safety in clinical practice. Additional studies are needed to confirm efficacy and safety in patients with secondary osteoporosis.

Bone Mineral Density, C-Terminal Telopeptide of Type I Collagen, and Osteocalcin as Monitoring Parameters of Bone Remodeling in CML Patients Undergoing Imatinib Therapy: A Basic Science and Clinical Review

Background: Chronic myeloid leukemia (CML) is one of the most commonly found types of myeloproliferative neoplasms, characterized by increased proliferation of granulocytic cells without losing their differentiation ability. Imatinib, a tyrosine kinase inhibitor (TKI), can be effectively used as therapy for CML. However, Imatinib can affect bone turnover thus having clinical implications on the bones of CML patients undergoing long-term Imatinib therapy. However, parameters that can accurately describe the bone condition in CML patients receiving Imatinib still need further study. A combination of imaging techniques such as bone mineral density (BMD) and bone turnover activity markers such as C-terminal telopeptide of type I collagen (CTX-1) and osteocalcin has the potential to be used as monitoring parameters for bone density abnormalities in CML patients receiving Imatinib. Objectives: This article explains the rationale for using BMD, CTX-1, and osteocalcin as monitoring parameters of bone remodeling in CML patients receiving Imatinib. Results: First, the physiological process of bone turnover will be explained. Then, we describe the role of tyrosine kinase in bone metabolism. Next, the impact of Imatinib on BMD, CTX-1, and osteocalcin will be explained. Conclusion: The assessment of bone health of CML patients on Imatinib should include both BMD tests and bone turnover marker assays such as CTX-1 and osteocalcin.

A prospective study of vitamin D, proinflammatory cytokines, and risk of fragility fractures in women on aromatase inhibitors for breast cancer.

Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs). In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up. Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1β and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1β: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98). Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer.

Bone turnover, areal BMD, and bone microarchitecture by second-generation high-resolution peripheral quantitative computed tomography in transfusion-dependent thalassemia.

Thalassemic osteopathy includes low bone mass and impaired bone microarchitecture. We aimed to evaluate the prevalence and determinants of bone quantity (osteoporosis) and quality (microarchitecture) in a cohort of adult patients with transfusion-dependent thalassemia (TDT). Patients with TDT (n = 63) and age- and BMI-matched controls (n = 63) were recruited in the study. Areal bone mineral density (BMD) was measured using DXA Hologic scanner. P1NP and β-CTX were estimated by electrochemiluminescence assay. Bone geometry and volumetric BMD (vBMD) were estimated by second-generation high-resolution peripheral quantitative computed tomography. Bone turnover marker β-CTX was significantly lower in the TDT group, but there was no difference in P1NP levels. Low bone mass (Z ≤ -2) was present in greater proportion of patients both at lumbar spine (LS) (54 vs 0%; p = .001) and femoral neck (FN) (33 vs 8%; p = .001). Hypogonadism was associated with low BMD at FN (OR 10.0; 95% CI, 1.2-86; p = .01) and low hemoglobin with low BMD at LS (OR 1.58; 95% CI, 0.96-2.60; p = .07). The mean trabecular bone score was also significantly lower in patients compared with controls (1.261 ± 0.072 vs 1.389 ± 0.058). Total, cortical and trabecular vBMD were significantly lower in cases than controls. The trabecular number and cortical thickness were significantly lower and trabecular separation higher in cases than controls. Adults with TDT have significantly lower areal, cortical and trabecular vBMD. The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness and area at both radius and tibia.

Low-Magnitude Mechanical Signals to Preserve Skeletal Health in Female Adolescents With Anorexia Nervosa

Malnourished adolescents and young adults with anorexia nervosa (AN) are at high risk for skeletal deficits. To examine whether low-magnitude mechanical signals (LMMS) could preserve bone mineral density (BMD) throughout 6 months in adolescents and young adults with AN. This double-blind, sham-controlled randomized clinical trial, conducted in a hospital-based specialty clinic, assessed female adolescents and young women without medical comorbidity or medication use that would compromise bone health. A total of 837 female adolescents were screened from January 1, 2012, to December 31, 2019, of whom 317 met the study criteria. Data analysis was performed from 2020 to 2024. Platform delivering low-magnitude mechanical signals (LMMS) (0.3 g at 32-37 Hz) or sham (ie, placebo) signals for 10 minutes daily for 6 months. The primary outcome was trabecular volumetric BMD (vBMD) as measured by peripheral quantitative computed tomography of the tibia at baseline and 6 months. Secondary outcomes included cortical vBMD, cross-sectional area (CSA), areal BMD and body composition measured by dual-energy x-ray absorptiometry, and serum bone turnover markers. Forty female adolescents and young women (median [IQR] age, 16.3 [15.1-17.6] years; median [IQR] percentage median BMI for age, 87.2% [81.0%-91.6%]) completed the trial. Total bone vBMD changes were nonsignificant in both groups (95% CI for difference in median change between groups, -57.11 to 2.49): in the LMMS group, vBMD decreased from a median (IQR) of 313.4 (292.9-344.6) to 309.4 (290.4-334.0) mg/cm3, and in the placebo group, it increased from a median (IQR) of 308.5 (276.7-348.0) to 319.2 (309.9-338.4) mg/cm3. Total CSA at the 4% tibia site increased from a median (IQR) of 795.8 (695.0-844.8) mm2 to 827.5 (803.0-839.4) mm2 in the LMMS group, whereas in the placebo group, it decreased from 847.3 (770.5-915.3) mm2 to 843.3 (828.9-857.7) mm2 (95% CI for difference in median change between groups, 2.94-162.53). Median (IQR) trabecular CSA at the 4% tibia site increased from 616.3 (534.8-672.3) mm2 to 649.2 (638.0-661.4) mm2 in the LMMS group but decreased in the placebo group from 686.4 (589.0-740.0) mm2 to 647.9 (637.3-661.9) mm2 (95% CI for difference in median change between groups, 2.80-139.68 mm2). Changes in cortical vBMD, cortical section modulus, and muscle CSA were not significant between groups. The 6-month changes in trabecular and total bone CSA at the tibia 4% site (weight-bearing trabecular bone) were significantly different between groups (these measures increased in the LMMS group but decreased in the placebo group; total bone CSA: 95% CI, 2.94-162.53; P = .01; trabecular CSA: 95% CI, 2.80-139.68; P = .02). Greater increases in body mass index were seen in the placebo group (median [IQR] gain, 0.5 [-0.3 to +2.1]) than in the LMMS group (median [IQR] gain, +0.4 [-0.3 to +2.1]), perhaps due to differences in fat mass accrual. No adverse events occurred related to the LMMS intervention. In this randomized clinical trial of female adolescents and young women with AN, a 6-month LMMS intervention did not yield improvement in tibial trabecular vBMD. However, LMMS led to increases in total and trabecular CSA at the tibia. These results suggest an early positive response of increased bone turnover and trabecular bone quantity due to the LMMS intervention. Future studies should use a longer duration of intervention, consider strategies to optimize adherence, and potentially focus on a more profoundly malnourished patient population. ClinicalTrials.gov Identifier: NCT01100567.

Association of bone turnover markers and craving reduction in patients with alcohol use disorder during withdrawal: Exploring the role of bone-brain axis.

Alcohol use disorder (AUD) is associated with imbalanced bone turnover and psychological symptoms, but the relationship between bone and brain remains unclear. The study analyzed serum levels of a bone formation marker, procollagen type 1 N-terminal propeptide (P1NP), and bone resorption marker, C-terminal telopeptide of type I collagen (CTX-1), in AUD patients before and after 2 weeks of alcohol withdrawal and investigated their correlation with psychological symptoms. Ninety patients with AUD and 117 healthy controls were recruited. P1NP and CTX-1 levels were measured using Enzyme-Linked Immunosorbent Assay. The Penn Alcohol Craving Scale (PACS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were assessed in the AUD group at baseline, week 1, and week 2 of withdrawal. Baseline CTX-1 levels, along with the CTX-1/P1NP and P1NP/CTX-1 ratio, were higher in the AUD group than controls. Over the 2-week withdrawal, PACS, BDI, and BAI scores demonstrated significant reductions. P1NP (p < 0.001) and P1NP/CTX-1 ratio increased (p < 0.001), while CTX-1/P1NP ratio decreased (p < 0.001), indicating a propensity toward bone formation. Univariate analysis revealed that reductions in PACS, BDI, and BAI scores during withdrawal correlated with increased P1NP levels and decreased CTX-1/P1NP ratios. However, multivariate analysis indicated that only PACS score reductions correlated with these changes. Bone metabolism shifted toward increased bone formation and decreased bone resorption during 2-week alcohol withdrawal. The correlation between improvements in bone turnover markers and reduction in craving scores during withdrawal supports the concept of the bone-brain axis.

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.

Osteoporosis and Normocalcemic Primary Hyperparathyroidism (Conservatively or Surgically Managed)

Asymptomatic primary hyperparathyroidism (PHPT) involves 80–90% of the parathyroid tumor-associated cases of PHPT in the modern medical era, while normocalcemic PHPT (NPHPT) has a prevalence of 0.1–11%. We aimed to analyze the bone status and mineral metabolism in NPHPT amid conservative or surgical management. In this narrative review, we searched PubMed (between January 2020 and July 2024) via different keywords. Fourteen studies from the final analysis (388 patients with NPHPT; 1188 with PHPT; and 803 controls) showed that mean serum calcium levels varied between 2.57 and 2.26 mmol/L in NPHPT. Ten studies identified a similar 24 h urinary calcium in NPHPT versus hypercalcemic PHPT (HPHPT). Except for one study, a mandatory vitamin D analysis was performed, but the 25-hydroxyvitamin D cut-offs varied. Osteoporosis (n = 6 studies; N = 172 with NPHPT) was confirmed in 41.7–100% of NPHPT subjects. In surgery candidates, this rate might be overestimated. A DXA analysis was performed in eight studies (235 subjects with NPHPT, and 455 patients with HPHPT); two studies identified a lower BMD in HPHPT &lt; NPHPT, but the results were not homogenous. A single study analyzed the TBS and found similar results in NPHPT. The prevalence of fractures (n = 9) varied between 7.4% and 42.8% in NPHPT. Bone turnover markers (N = 262 patients, n = 8 studies) showed lower bone formation markers in NPHPT versus PHPT (n = 3). Two studies analyzed the BMD and bone turnover markers following parathyroidectomy (161 patients, including 30 patients with NPHPT; mean ages over 60 years). To conclude, given the wide spectrum of complications associated with PHPT, an early diagnosis and proper management is essential. A more extensive screening in patients with osteoporosis and kidney stones might lead to the discovery of NPHPT, a more recently described form of PHPT. While it is still unclear whether NPHPT is an early stage of HPHPT or a separate entity, recent findings show similar osteoporosis and fracture occurrence, and an improvement in bone metabolism, following parathyroidectomy. More extensive prospective studies are crucial to understand the natural course of the disease, to reach a consensus regarding parathyroidectomy indications and surgery candidates’ selection, and to ensure proper personalized management for these patients. With the evolving diagnosis methods, PHPT has become a condition with a changing clinical presentation, which now requires modern evaluation and treatment approaches.

Therapy with transitions from one bone-forming agent to another: a retrospective cohort study on Teriparatide and Romosozumab

Abstract This study aimed to evaluate the effectiveness of sequential therapy with a bone formation-promoting agent (either teriparatide or romosozumab) for osteoporosis treatment following prior treatment with the other bone-forming agent (teriparatide or romosozumab). This is a multicenter retrospective cohort study observing two groups for comparison: one with 69 patients transitioning from teriparatide to romosozumab (the T2R group) and the other with 25 patients transitioning from romosozumab to teriparatide (the R2T group), monitored for 12 months on the second drug. Key outcomes included changes in bone mineral density (BMD), bone turnover marker changes, and adverse events. The mean ages of each group were 72.3 years in the T2R group and 67.6 years in the R2T group, with the proportions of women being 91.3% and 80.0% respectively. The percent changes of BMD in the lumbar spine after 12 months of sequential therapy were + 10.78% in the T2Rgroup (P&amp;lt;.001 versus baseline) and − 0.02% in the R2T group (P=.875). The percent changes in BMD in the total hip and femoral neck were + 4.41% and + 4.41% in the T2R group, and -1.33% and -0.83% in the R2T group, respectively. When comparing the two groups, BMD changes at all sites in the T2R group were significantly higher than those in the R2T group (P&amp;lt;.001). Furthermore, when examining the changes in the proportion of patients who achieved the osteoporosis treatment goal of a T-score exceeding -2.5, no significant increase was observed in the R2T group, whereas a significant increase was observed in the lumbar spine in the T2R group. Regarding therapy switching between bone-forming agents, this study suggests that transitioning from teriparatide to romosozumab increases BMD more effectively than transitioning in the opposite sequence.

Geranylgeranyl diphosphate synthase inhibition impairs osteoclast differentiation, morphology and resorptive activity

Abstract Nitrogen bisphosphonates (NBPs), such as zoledronic acid, target the enzyme farnesyl diphosphate synthase (FDPS) in the isoprenoid biosynthetic pathway (IBP), and are the frontline treatment for osteolytic bone diseases. The strong affinity of these agents for bone limits their distribution out of the skeleton. Geranylgeranyl diphosphate synthase (GGDPS) is directly downstream to FDPS in the IBP and novel GGDPS inhibitors such as RAM2061 have been shown to have key drug-like features including prolonged half-life, metabolic stability, and systemic distribution. Furthermore, RAM2061 exerts anti-neoplastic benefits in mouse models of multiple myeloma and Ewing sarcoma. Therefore, we are interested in determining the potential impact of RAM2061 on osteoclast biology and bone remodeling. Studies utilizing undifferentiated RAW264.7 cells demonstrated that treatment with RAM2061 depletes cells of GGPP, impairs protein geranylgeranylation and induces markers of the unfolded protein response pathway and apoptosis. Differentiation of RAW264.7 cells to mature osteoclasts is disrupted by RAM2061, resulting in decreased numbers of mature osteoclasts, altered morphology and decreased tartrate resistant acid phosphatase activity. Treatment of fully differentiated RAW264.7 cells with RAM2061 led to decreased resorptive activity. Confocal microscopy studies revealed that RAM2061 disrupts Cdc42 localization, inhibiting proper actin ring formation in osteoclasts. No significant impact on bone turnover markers or bone histomorphology was observed following a 3-week treatment of CD-1 mice with RAM2061, although decreased numbers of osteoclasts were observed. Liquid chromatography–tandem mass spectrometry studies confirmed accumulation of RAM2061 in bone from the in vivo studies as well as hydroxyapatite binding in vitro. In conclusion, these studies are the first to demonstrate the anti-osteoclastic activity of GGDPS inhibitor treatment and support future studies exploring the therapeutic benefit of this novel therapy in the setting of pathological bone remodeling.

Divergent associations of inflammatory markers with bone turnover markers in elderly patients with osteoporotic fractures

The association between inflammatory markers (IMs) and bone turnover markers (BTMs) in osteoporotic fracture patients has not been comprehensively studied. Therefore, this study examined the correlation between the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), or Monocyte-to-lymphocyte ratio (MLR) and BTMs in osteoporosis (OP) fracture patients. This retrospective cross-sectional study analyzed 740 OP fracture patients admitted to the hospital from January 2017 to July 2022. MLR, NLR, and PLR were calculated based on each patient’s complete blood count. The relationship between IMs and BTMs was assessed using three models by adjusting variables. Furthermore, the potential curve relationship between IMs and BTMs was also determined via the threshold effect analysis and curve fittings. In addition, stratified analysis was performed on each adjusted variable to confirm the stability of the results. After adjusting the variables, the results showed that NLR was negatively correlated with procollagen type 1 N-terminal propeptide (P1NP) (β = -1.1788, 95% CI: -1.7230 to -0.6345, P-value < 0.0001) and β-C-terminal telopeptide of type I collagen (β-CTX) (β = -0.0104, 95% CI: -0.0145 to -0.0062, P-value < 0.0001), Furthermore, MLR was negatively correlated with P1NP (β = -17.4523, 95% CI: -27.7335 to -7.1710, P-value = 0.0009) and β-CTX (β = -0.1327, 95% CI: -0.2211 to -0.0443, P-value = 0.0034). However, PLR indicated a positive correlation with P1NP (β = 0.0326, 95% CI: 0.0007 to 0.0645, P-value = 0.0458) and β-CTX (β = 0.0003, 95% CI: 0.0001 to 0.0006, P-value = 0.0204). The threshold effect analysis and curve fittings revealed the presence of a turning point between NLR, MLR, and P1NP, β-CTX. In addition, the stratified analysis validated the result’s stability. In conclusion, this study indicates a negative correlation between NLR and MLR with P1NP, while PLR shows a positive correlation with P1NP. Additionally, NLR and MLR exhibit a negative correlation with β-CTX, whereas PLR demonstrates a positive correlation with β-CTX. Further research is required to assess the intricate mechanisms linking IM with bone metabolism.

Assessment of trabecular bone score using updated TBSTT in anorexia nervosa-The AN-BO study.

Anorexia Nervosa (AN) is characterized by a distortion of body image, very low body weight, malnutrition and hormonal dysregulations, resulting in reduced bone mineral density (BMD) and impaired bone microarchitecture. The updated Trabecular Bone Score (TBS) algorithm accounts for soft tissue thickness (TBSTT) instead of BMI (TBSBMI). The aim of the study was to assess both TBS algorithms in adult AN patients compared to normal-weight controls(CTRL). This retrospective cross-sectional study investigated 34 adult female anorexia nervosa (AN) patients and 26 healthy normal-weighted age- and sex-matched controls (CTRL). Bone texture analysis was assessed by TBSTT and TBSBMI (TBS iNsight® V4.0 and V3.1), bone mineral density (BMD; lumbar spine LS, femoral neck, total hip) and body composition by DXA (GE Lunar iDXATM). Laboratory analyses included bone turnover markers (CTX; P1NP; sclerostin). Data analysis was performed using parametric (t-test) or non-parametric test (Mann-Whitney-U-Test) depending on normality, one-way ANCOVA and correlation analysis (Perason's or Spearman's). AN patients (BMI 14.7(1.6)) and CTRL (BMI 22.4(4.0)) were of comparable age (22.8(7.1) vs.25.0(4.0)years, p = 0.145). TBSTT(1.319±0.09 vs.1.502±0.07, p<0.001) and TBSBMI(1.317±0.10 vs.1.548±0.09, p<0.001) were significantly lower in AN patients compared to CTRL. Soft tissue thickness was lower in AN (p<0.001). Within the CTRL group, but not in AN, TBSTT and TBSBMI were significantly different (p<0.001). BMD was lower at all sites in AN patients (p<0.001 for all), being lowest at LS. Bone Mineral Content, Lean Body mass and Fat Mass were lower in AN (p<0.001). AN patients had lower P1NP (p = 0.05), but higher CTX (p = 0.001) and sclerostin (p = 0.003) levels. Adult AN patients have lower TBSTT and TBSBMI, reduced BMD and an uncoupling of bone turnover. In AN both TBS algorithms show similar reduced trabecular bone microarchitecture. The observed difference of TBSTT and TBSBMI in CTRL with normal body composition highlight the importance of the new algorithm.