Machine learning model for osteoporosis diagnosis based on bone turnover markers.

To assess the diagnostic utility of bone turnover markers (BTMs) and demographic variables for identifying individuals with osteoporosis. A cross-sectional study involving 280 participants was conducted. Serum BTM values were obtained from 88 patients with osteoporosis and 192 controls without osteoporosis. Six machine learning models, including extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), CatBoost, random forest, support vector machine, and k-nearest neighbors, were employed to evaluate osteoporosis diagnosis. The performance measures included the area under the receiver operating characteristic curve (AUROC), F1-score, and accuracy. After AUROC optimization, LGBM exhibited the highest AUROC of 0.706. Post F1-score optimization, LGBM's F1-score was improved from 0.50 to 0.65. Combining the top three optimized models (LGBM, XGBoost, and CatBoost) resulted in an AUROC of 0.706, an F1-score of 0.65, and an accuracy of 0.73. BTMs, along with age and sex, were found to contribute significantly to osteoporosis diagnosis. This study demonstrates the potential of machine learning models utilizing BTMs and demographic variables for diagnosing preexisting osteoporosis. The findings highlight the clinical relevance of accessible clinical data in osteoporosis assessment, providing a promising tool for early diagnosis and management.

Imaging bone turnover assessment through volumetric density-adjusted standardized uptake value using quantitative bone SPECT/CT in osteoporosis.

BACKGROUND: Serum bone turnover markers offer limited insight into metabolic activity at the individual vertebra level in osteoporosis. This study introduces a novel image-derived bone turnover marker for individual vertebrae to address this limitation, utilizing volumetric density-adjusted quantitative bone single-photon emission computed tomography/computed tomography (SPECT/CT) with [99mTc]Tc-DPD. This retrospective study included 177 lumbar vertebrae from 55 postmenopausal South Korean women. The mean standardized uptake value (SUVmean, g/cm3) and volumetric bone mineral density (vBMD, mg/cm3) were determined within a 2-cm³ volume of interest in the trabecular portion of each vertebra using quantitative SPECT and CT. The density-adjusted mean standardized uptake value (dSUVmean) was calculated by dividing the SUVmean by the vBMD and multiplying by 1,000. RESULTS: SUVmean correlated positively with vBMD (r = 0.60, p < 0.001). Conversely, dSUVmean correlated negatively with vBMD (ρ = -0.66, p < 0.001), highlighting the inverse relationship between bone mass and turnover after density adjustment of SUVmean. Patients with major osteoporotic fractures had lower vBMD (62.5 ± 29.4 vs. 92.3 ± 27.4 mg/cm³, p = 0.001) but higher dSUVmean (100.8 ± 60.7 vs. 62.6 ± 17.5, p = 0.001) compared to those without fractures, reinforcing the association between fracture prevalence, low bone mass, and high bone turnover. CONCLUSION: Volumetric density-adjusted quantitative bone SPECT/CT offers a novel image-derived bone turnover marker for assessing bone turnover in osteoporosis. This method provides a precise assessment of fragility at the individual vertebra level, which may enhance personalized osteoporosis management.

Comparison of bone turnover suppression in atypical femoral fractures and osteoporotic hip fractures.

We aimed to compare the extent of bone turnover suppression between patients with atypical femoral fractures (AFFs) and osteoporotic hip fractures (typical femur fractures, TFFs) using a one-to-one matching strategy. A single-center retrospective comparison of females aged ≥ 60 years who underwent operative treatment for AFFs and TFFs between January 2010 and March 2021 was conducted. Demographic characteristics and clinical data including fracture site, past medical history, bone mineral density (BMD), bisphosphonate (BP) medication history, and serum bone turnover marker (BTM) levels were examined. Moreover, we performed a logistic regression analysis to determine the risk factors for AFFs and a one-to-one matched-pair analysis to compare various BTMs. Overall, 336 consecutive females were included: 113 with AFFs and 213 with TFFs. The mean age, BMI, and lowest BMD T-score were 78.6 years, 22.8 kg/m2, and -3.3, respectively. Patients with AFF were younger, had lower BMD, higher BMI, higher prevalence of rheumatoid arthritis, a greater proportion with previous steroid or BP use, and a longer history of BP use than patients with TFF. The 48:48 matched-pair analysis revealed higher serum 25(OH) vitamin-D (30.5 vs 18.2 ng/mL, P < 0.001) and calcium levels (8.8 vs 8.3 ng/dL, P = 0.009) and lower serum CTX levels (0.33 vs 0.54 ng/mL, P = 0.010) in the AFF group than in the TFF group, suggesting a more suppressed bone remodeling. No differences in the other BTM levels were found. Despite identical histories and durations of BP use, the AFF group exhibited lower CTX levels, suggesting more suppressed bone remodeling. This observation leads us to infer that more suppressed bone remodeling, indicated by lower CTX levels, could be linked to the occurrence of AFFs.

Circadian Regulation of Bone Remodeling.

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.

Albumin-to-alkaline phosphatase ratio may be a better predictor of survival than sclerostin, dickkopf-1, osteopontin, osteoprotegerin and osteocalcin.

Objectives: The value of biochemical markers of bone turnover (BTMs) in predicting survival and disease remains unclear. In a prospective study we evaluated the novel biomarkers for bone turnover sclerostin, dickkopf-1 (DKK-1), osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC), as well as a traditional biomarker, alkaline phosphatase (ALP) in relation to risk of mortality, cardiovascular events and fractures. Participants: and Methods:Routine blood tests and serum BTMs, including ALP, were analyzed in patients with hip fracture n = 97, stroke n = 71 and healthy volunteers n = 83 (mean age 86, 83 and 77, respectively), followed for 7 years. Hazard Ratios (HR) were calculated for mortality, cardiovascular events and fractures in relation to these biomarkers. After adding the albumin-to-ALP ratio (AAPR) a post hoc analysis was performed. Results: 120 participants died during the study. In the entire group of patients and volunteers (n = 251) higher AAPR (HR 0.28, 95 % CI 0.14-0.59, p < 0.001) was associated with decreased mortality. OPN and OPG were associated with mortality risk only in the univariate statistical analysis. HR for high AAPR in relation to new cardiovascular events was borderline significant (HR 0.29, 95 % CI 0.08-1.06, p = 0.061). None of the examined biomarkers were associated with new fractures, nor with an increased risk of a new cardiovascular event. Conclusions: AAPR may be a better predictor of mortality than the more novel BTMs, and higher AAPR could be associated with longer life expectancy. Further studies should determine the clinical usefulness of AAPR as a biomarker of mortality and cardiovascular disease.

Prognostic value of serum tartrate­resistant acid phosphatase­5b for bone metastasis in patients with resectable breast cancer.

Bone metastasis significantly affects the quality of life of patients with metastatic breast cancer, and can shorten overall survival. Identifying patients with early-stage breast cancer at high risk for bone metastasis and preventing bone metastasis may lead to a better quality of life and prolonged survival. The present study investigated whether serum tartrate-resistant acid phosphatase-5b (TRACP-5b), a bone turnover marker, can be a prognostic factor for bone metastasis. Female patients who underwent resectable breast surgery between May 2002 and August 2006 were consecutively investigated. A total of 304 patients with a median follow-up of 3,722 days were retrospectively analyzed. TRACP-5b levels in sera prepared from patients' blood drawn preoperatively without any presurgical treatments were measured using an enzyme-linked immunosorbent assay. The cutoff of TRACP-5b levels, in order to separate patients into high and low TRACP-5b groups, was set at median (347 mU/dl). The associations of clinicopathological factors, including TRACP-5b, with bone metastasis-free interval (BMFI), which was defined as the duration between surgery and the diagnosis of bone metastasis at any time point, were examined. Multivariate analysis of various clinicopathological features revealed that lymph node metastasis and histological grade were independent factors associated with BMFI (P=0.017 and 0.030, respectively). In patients with node-positive breast cancer (n=114), a high TRACP-5b level and a high grade were significantly and independently associated with worse BMFI (log-rank P=0.041 and 0.011, respectively). In conclusion, these findings indicated that TRACP-5b may predict bone metastasis in patients with node-positive breast cancer.

Abnormal Bone Turnover Observed in Obese Children Based on Puberty Stage -Specific Bone Turnover Marker Reference.

CONTEXT: Childhood and adolescence are critical periods for lifelong bone health. The impact of obesity on these phases is controversial, which may be due to the lack of standards for age-, sex-, and puberty-specific Bone turnover markers (BTMs) which could sensitively reflect bone metabolism. OBJECTIVE: To generate age-, sex, and puberty stage-specific BTMs reference curves in children and adolescents and to explore the effect of obesity on bone metabolism in the Chinese population. METHODS: Our study was part of the Evaluation and Monitoring on School-based Nutrition and Growth in Shenzhen study. 800 participants aged 6∼18 years with normal body mass index (BMI) were selected to establish BTM reference curves for boys and girls at different ages under different pubertal development stages. Additionally, 200 participants with obesity (BMI >P95th) were matched with healthy children from the original cohort at a 1:1 ratio. All participants underwent bone mineral density assessment, and serum levels of P1NP and ß-CTX were measured. RESULTS: The BTMs values presented significant age, sex, and puberty stage differences. Analysis of serum BTMs based on the established reference revealed a higher percentage of low-level P1NP in boys with obesity (P=0.005); no significant difference was observed in girls. However, the obese group showed a significantly higher proportion of high ß-CTX levels for girls, not boys (P=0.022). CONCLUSIONS: We provide age-, sex-, and puberty stage-specific P1NP and ß-CTX reference curve. According to these, obesity appeared to be a negative factor for bone formation in boys and for bone resorption in girls.

Amorphous Calcium Carbonate from Plants Can Promote Bone Growth in Growing Rats.

OBJECTIVES: This study aimed to investigate the effect of amorphous calcium carbonate (ACC) supplementation on bone growth in growing rats. METHODS: We used 3-week-old male Wistar rats to simulate childhood and adolescent growth stages. Rats were divided into four groups as follows: a control group (C), a low-dose group (L, 20.65 mg/kg body weight (BW) ACC), a medium-dose group (M, 206.5 mg/kg BW ACC), and a high-dose group (H, 413 mg/kg BW ACC) administered by gavage. Body length (BL) and BW were measured weekly. The bone mineral density (BMD) of two lumbar vertebrae (L3 and L4) and the left femur were analyzed by micro-computed tomography (µCT) at 0, 4, 8, and 12 weeks. At the end of 12 weeks, the rats were sacrificed. After that, blood samples were collected from the abdominal aorta. Femurs and tibias were collected and weighed, and their lengths were measured. Then, bone samples were used to perform histopathological and histomorphometric analyses. RESULTS: It showed that ACC supplementation in growing rats increased the trabecular bone thickness and serum bone formation biomarkers. Furthermore, high-dose ACC decreased serum bone resorption biomarkers and increased BMD. CONCLUSIONS: ACC supplementation can enhance osteoblast metabolism and inhibit osteoclast metabolism, resulting in a higher bone formation rate compared to bone resorption. This led to increased trabecular bone thickness, a higher BMD, and supported bone growth.

Time-Restricted Eating and Bone Health: A Systematic Review with Meta-Analysis.

Time-restricted eating (TRE) has emerged as a dietary strategy that restricts food consumption to a specific time window and is commonly applied to facilitate weight loss. The benefits of TRE on adipose tissue have been evidenced in human trials and animal models; however, its impact on bone tissue remains unclear. To systematically synthesize and examine the evidence on the impact of TRE on bone health (bone mineral content (BMC), bone mineral density (BMD), and bone turnover factors), PubMed, Scopus, Cochrane CENTRAL, and Web of Science databases were systematically explored from inception to 1 October 2023 searching for randomized controlled trials (RCTs) aimed at determining the effects of TRE on bone health in adults (≥18 years). The Cochrane Handbook and the PRISMA recommendations were followed. A total of seven RCTs involving 313 participants (19 to 68 years) were included, with an average length of 10.5 weeks (range: 4 to 24 weeks). Despite the significant weight loss reported in five out of seven studies when compared to the control, our meta-analysis showed no significant difference in BMD (g/cm2) between groups (MD = -0.009, 95% CI: -0.026 to 0.009, p = 0.328; I2 = 0%). BMC and bone turnover markers between TRE interventions and control conditions were not meta-analyzed because of scarcity of studies (less than five). Despite its short-term benefits on cardiometabolic health, TRE did not show detrimental effects on bone health outcomes compared to those in the control group. Nevertheless, caution should be taken when interpreting our results due to the scarcity of RCTs adequately powered to assess changes in bone outcomes.

Association of lymphocyte subsets and cytokines with bone metabolism: a retrospective, cross-sectional study.

BACKGROUND: Previous research has shown that lymphocytes and cytokines can mediate bone metabolism. This study explored the clinical association and predictive ability of lymphocytes and cytokines levels for bone metabolism. METHODS: A total of 162 patients were enrolled in this study. The levels of N-terminal propeptide of type I procollagen (P1NP), ß-collagen degradation product (ß-CTX), total T lymphocytes, immature T lymphocytes, suppressor/cytotoxic T lymphocytes, helper/inducer T lymphocytes, B lymphocytes, natural killer (NK) cells, Interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), IFN-α, interleukin-1 beta (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL12p70 were evaluated. The relationship between these lymphocyte subsets and cytokines with bone metabolic status was examined and their predictive ability for bone metabolic status was assessed. RESULTS: The principal component analysis (PCA) and correlation analysis results varied on differences in lymphocyte subsets and cytokines in various bone metabolism states. Differential analysis revealed significant differences in the absolute counts of B lymphocytes (P < 0.05), level of IL-12p70 (P < 0.05), and IL-8 (P < 0.001) at different P1NP levels. Significant differences were observed in the absolute counts of total T lymphocytes (P < 0.05), B lymphocytes (P < 0.05), the level of IL-6 (P < 0.05), the percentage of B lymphocytes (P < 0.01), and NK cells (P < 0.05) at different ß-CTX levels. Furthermore, the receiver operating characteristic (ROC) curve showed that the absolute count of B lymphocytes and levels of IL-12p70 and IL-8 could be used to evaluate bone formation states, while the absolute counts of T and B lymphocytes, level of IL-6, and percentages of NK cells and B lymphocytes could be used to evaluate bone resorption states. CONCLUSION: The bone metabolism status changed based on the lymphocyte subsets and cytokine levels. Differentially expressed lymphocytes and cytokines could be used to distinguish bone metabolism status.

Osteoclast differentiation induced by total immune complex in serum of patients with rheumatoid arthritis leads to osteoporosis and its factors analysis / 中国组织工程研究

BACKGROUND:The incidence of osteoporosis significantly increases in the patients with rheumatoid arthritis,and it remains unclear whether the presence of a large number of immune complexes in serum promotes the onset and development of osteoporosis. OBJECTIVE:To investigate the correlation between serum immune complexes and osteoporosis in patients with rheumatoid arthritis. METHODS:(1)Clinical trial:Serum and clinical data of 50 healthy controls and 50 patients with untreated rheumatoid arthritis were collected and retrospectively analyzed.Total immune complex level in serum was compared between two groups.Correlation of serum total immune complexes with bone mineral density,bone turnover markers and other clinical indicators in patients with rheumatoid arthritis was analyzed.(2)Cell experiment:Peripheral blood mononuclear cells from healthy volunteers were isolated and cultured,and divided into four groups:rheumatoid arthritis group was added with total immune complex suspension from rheumatoid arthritis patients;normal control group was added with total immune complex suspension from healthy medical checkups;positive control group was added with α-MEM medium containing macrophage colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand,and negative control group was added with α-MEM medium.Tartrate-resistant acid phosphatase staining was performed to observe the formation of osteoclasts after 7 days of treatment, RESULTS AND CONCLUSION:(1)Clinical trial:The total immune complex and serum alkaline phosphatase levels in patients with rheumatoid arthritis were significantly higher than those in health controls(P＜0.01,P＜0.05).Pearson correlation analysis showed that serum total immune complex level was positively correlated with erythrocyte sedimentation rate(r=0.330,P=0.019),serum alkaline phosphatase(r=0.545,P=0.001),anti-cyclic citrullinate peptide(r=0.377,P=0.007)and c-terminal telopeptide of type Ⅰ collagen(r=0.738,P=0.001),and negatively correlated with lumbar bone mineral density(r=-0.595,P=0.001)in patients with rheumatoid arthritis.Binary Logistic regression analysis showed that age[odds ratio(OR)=1.086,95%confidence interval(CI)(1.022,1.154),P=0.008],anti-cyclic citrullinate peptide[OR=1.002,95%CI(0.999,1.005),P=0.035],c-terminal telopeptide of type Ⅰ collagen[OR=0.141,95%CI(0.015,8.900),P=0.008]and serum total immune complexes[OR=2.895,95%CI(1.228,6.827),P=0.001]were the influencing factors for abnormal bone mass(reduced bone mass or osteoporosis)in patients with rheumatoid arthritis.(2)Cell experiment:Tartrate-resistant acid phosphatase positive osteoclasts were observed in the positive control group,normal control group and rheumatoid arthritis group,and there were more osteoclasts in the rheumatoid arthritis group than in the normal control group(P＜0.01).To conclude,serum total immune complexes can be used as a potential serologic predictor of rheumatoid arthritis complicated with osteoporosis,and removing immune complexes in serum or interfering with the binding of immune complexes to their receptors may be an effective means for the prevention and treatment of rheumatoid arthritis complicated with osteoporosis.

Changes in bone and mineral homeostasis after short-term androgen deprivation therapy with or without androgen receptor signalling inhibitor - substudy of a single-centre, double blind, randomised, placebo-controlled phase 2 trial.

BACKGROUND: Prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) have an increased fracture risk. Exploring biomarkers for early bone loss detection is of great interest. METHODS: Pre-planned substudy of the ARNEO-trial (NCT03080116): a double blind, randomised, placebo-controlled phase 2 trial performed in high-risk PCa patients without bone metastases between March 2019 and April 2021. Patients were 1:1 randomised to treatment with gonadotropin-releasing hormone antagonist (degarelix) + androgen receptor signalling inhibitor (ARSI; apalutamide) versus degarelix + matching placebo for 12 weeks prior to prostatectomy. Before and following ADT, serum and 24-h urinary samples were collected. Primary endpoints were changes in calcium-phosphate homeostasis and bone biomarkers. FINDINGS: Of the 89 randomised patients, 43 in the degarelix + apalutamide and 44 patients in the degarelix + placebo group were included in this substudy. Serum corrected calcium levels increased similarly in both treatment arms (mean difference +0.04 mmol/L, 95% confidence interval, 0.02; 0.06), and parathyroid hormone and 1,25-dihydroxyvitamin D3 levels decreased. Bone resorption markers increased, and stable calcium isotope ratios reflecting net bone mineral balance decreased in serum and urine similarly in both groups. INTERPRETATION: This exploratory substudy suggests that 12 weeks of ADT in non-metastatic PCa patients results in early bone loss. Additional treatment with ARSI does not seem to more negatively influence bone loss in the early phase. Future studies should address if these early biomarkers are able to predict fracture risk, and can be implemented in clinical practice for follow-up of bone health in PCa patients under ADT. FUNDING: Research Foundation Flanders; KU Leuven; University-Hospitals-Leuven.

Effects of blood flow restriction training on bone turnover markers, microstructure, and biomechanics in rats.

Objective: The present study aimed to investigate the effects of blood flow restriction training on muscle strength, bone tissue structure material, and biomechanical properties in rats applying various exercise interventions and to analyze the process by identifying the bone turnover markers, it provides a theoretical basis for the application of BFRT in clinical rehabilitation. Methods: A total of 24, 3-month-old male SD (Sprague Dawley) rats were randomly divided into pressurized control group (CON, n=6), low-intensity training group (LIRT, n=6), high-intensity training group (HIRT, n=6), and blood flow restriction training group (LIBFR, n=6) for 8-week ladder-climbing exercises. The pressured control group were given only ischemia treatments and did not undertake any burden. The low-intensity training group was allowed to climb the ladder with 30% of the maximum voluntary carrying capacity (MVCC). The rats in the high-intensity training group were allowed to climb the ladder with 70% MVCC. The blood flow restriction training group climbed the ladder with 30% MVCC while imposing blood flow restriction. Before sampling, the final MVCC was measured using a ladder-climbing protocol with progressively increasing weight loading. The serum, muscle, and bone were removed for sampling. The concentrations of the bone turnover markers PINP, BGP, and CTX in the serum were measured using ELISA. The bone mineral density and microstructure of femur bones were measured using micro-CT. Three-point bending and torsion tests were performed by a universal testing machine to measure the material mechanics and structural mechanics indexes of the femur bone. Results: The results of maximum strength test showed that the MVCC in LIRT, HIRT, and LIBFR groups was significantly greater than in the CON group, while the MVCC in the HIRT group was significantly higher than that in the LIRT group (P<0.05). According to the results of the bone turnover marker test, the concentrations of bone formation indexes PINP (amino-terminal extension peptide of type I procollagen) and BGP (bone gla protein) were significantly lower in the CON group than in the HIRT group (P<0.01), while those were significantly higher in the LIRT group compared to the HIRT group (P<0.01). In terms of bone resorption indexes, significant differences were identified only between the HIRT and other groups (P<0.05). The micro-CT examination revealed that the HIRT group had significantly greater bone density index values than the CON and LIRT groups (P<0.05). The results of three-point bending and torsion test by the universal material testing machine showed that the elastic modulus and maximum load indexes of the HIRT group were significantly smaller than those of the LIBFR group (P<0.05). The fracture load indexes in the HIRT group were significantly smaller than in the LIBFR group (P<0.05). Conclusion: 1. LIRT, HIRT, LIBFR, and CON all have significant differences, and this training helps to improve maximum strength, with HIRT being the most effective. 2. Blood flow restriction training can improve the expression of bone turnover markers, such as PINP and BGP, which promote bone tissue formation. 3. Blood flow restriction training can improve muscle strength and increase the positive development of bone turnover markers, thereby improving bone biomechanical properties such as bone elastic modulus and maximum load.

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

INTRODUCTION: 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. MATERIALS AND METHODS: 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 ± 4.3 years) 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). RESULTS: 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. CONCLUSION: BAP and testosterone in Japanese male endurance runners decreased during the competitive season. However, there was no correlation between blood variables and training volume.

The levels of bone turnover markers and parathyroid hormone and their relationship in chronic kidney disease.

BACKGROUND: Chronic kidney disease-mineral bone disease (CKD-MBD) is a major complication of CKD. Bone turnover markers (BTMs) are important for clinicians to evaluate and manage patients with CKD-MBD. This study aimed to assess BTMs in patients with CKD and their correlation with parathyroid hormone (PTH) and other clinical characteristics of CKD. METHODS: A total of 408 subjects were included in this study. The serum BTMs including N-terminal midfragment osteocalcin (N-MID OC), ß-isomerized C-terminal telopeptides (ß-CTX), and total procollagen type 1 amino-terminal propeptide (tPINP) were measured. Spearman correlation and multiple stepwise regression models were used to investigate the association of N-MID OC, ß-CTX, and tPINP with the clinical characteristics of CKD patients. RESULTS: BTMs was no significant difference between non-CKD and CKD stages 1, 2, and 3. However, N-MID OC, ß-CTX were significantly increased in patients with CKD stage 4 compared to non-CKD patients and patients with CKD stages 1, 2, and 3. Compared with non-dialysis dependent (NDD)-CKD stage 5, BTMs were significantly higher in dialysis patients. The estimated glomerular filtration rate was negatively associated with N-MID OC (r = -0.479, P < 0.001), ß-CTX (r = -0.474, P < 0.001), and tPINP (r = -0.375, P < 0.001). Multiple analysis showed that N-MID OC (ß = 0.67, P < 0.001), ß-CTX (ß = 0.64, P < 0.001), and tPINP (ß = 0.81, P < 0.001) were independently associated with PTH. CKD patients with secondary hyperparathyroidism (SHPT) have higher ß-CTX (P < 0.05), and N-MID OC (P < 0.05) than patients with non-SHPT. CONCLUSIONS: BTMs in advanced CKD stages were significantly higher than in the early disease stages. PTH level was independently and positively associated with the BTM levels in patients with CKD. In the advanced stage of CKD, ß-CTX and N-MID OC levels were significantly higher in those with SHPT than those with non-SHPT.

Risk Factors of Nonfusion after Anterior Cervical Decompression and Fusion in the Early Postoperative Period: A Retrospective Study.

OBJECTIVE: Although high fusion rates have been reported for anterior cervical decompression and fusion (ACDF) in the medium and long term, the risk of nonfusion in the early period after ACDF remains substantial. This study investigates early risk factors for cage nonfusion in patients undergoing single- or multi-level ACDF. METHODS: This was a retrospective study. From August 2020 to December 2021, 107 patients with ACDF, including 197 segments, were enrolled, with a follow-up of 3 months. Among the 197 segments, 155 were diagnosed with nonfusion (Nonfusion group), and 42 were diagnosed with fusion (Fusion group) in the early period after ACDF. We assessed the significance of the patient-specific factors, radiographic indicators, serum factors, and clinical outcomes. The Wilcoxon rank sum test, t-tests, analysis of variance, and stepwise multivariate logistic regression were used for statistical analysis. RESULTS: Univariate analysis showed that smoking, insufficient improvement in the C2-7 Cobb angle (p = 0.024) and the functional spinal unit Cobb angle (p = 0.022) between preoperative and postoperative stages and lower serum calcium (fusion: 2.34 ± 0.12 mmol/L; nonfusion: 2.28 ± 0.17 mmol/L, p = 0.003) ß-carboxyterminal telopeptide end of type 1 collagen (ß-CTX) (fusion: 0.51 [0.38, 0.71]; nonfusion: 0.43 [0.31, 0.57], p = 0.008), and N-terminal fragment of osteocalcin (N-MID-BGP) (fusion: 18.30 [12.15, 22.60]; nonfusion: 14.45 [11.65, 18.60], p = 0.023) are risk factors for nonfusion in the early period after ACDF. Stepwise logistic regression analysis revealed that poor C2-7 Cobb angle improvement (odds ratio [OR], 1.107 [1.019-1.204], p = 0.017) and lower serum calcium (OR, 3.700 [1.138-12.032], p = 0.030) are risk factors. CONCLUSIONS: Patients with successful fusion after ACDF had higher preoperative serum calcium and improved C2-7 Cobb angle than nonfusion patients at 3 months. These findings suggest that serum calcium could be used to identify patients at risk of nonfusion following ACDF and that correcting the C2-7 Cobb angle during surgery could potentially increase fusion in the early period after ACDF.

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

Purpose: 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. Methods: 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. Results: 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. Conclusion: Both romosozumab and denosumab have antiosteoporotic effects, with greater effects on BMD and bone turnover markers observed within 12 months of romosozumab treatment. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023395034.

Abaloparatide dose-dependently increases bone mineral density in postmenopausal women with osteoporosis: a phase 2 study.

INTRODUCTION: This study aimed to determine the efficacy of abaloparatide in increasing bone mineral density (BMD) and its safety in postmenopausal Japanese women with osteoporosis. MATERIALS AND METHODS: Randomized, double-blind, placebo-controlled, dose-finding study of abaloparatide in postmenopausal Japanese women at high fracture risk. The primary endpoint was the change in lumbar spine (LS) BMD from baseline at the last visit after daily subcutaneous injections of placebo or 40 or 80 µg abaloparatide. Other endpoints included time-course changes in LS BMD at 12, 24, and 48 weeks, in total hip (TH) and femoral neck (FN) BMDs, and in bone turnover markers. RESULTS: Increases in LS BMD with 40 and 80 µg abaloparatide were significantly higher than that with placebo (6.6% and 11.5%, respectively), with significant between-group differences for the abaloparatide groups (4.9%). TH BMD increased by 0.4%, 1.6%, and 2.9% and FN BMD increased by 0.6%, 1.5%, and 2.4% in the placebo and 40 and 80 µg abaloparatide groups, respectively. Serum PINP rapidly increased by 67.3% and 140.7% and serum CTX slowly increased by 16.4% and 34.5% in the 40 and 80 µg abaloparatide groups, respectively. Although more adverse events were observed in the abaloparatide groups, they were mild to moderate and not dose dependent. CONCLUSION: In postmenopausal Japanese women with osteoporosis at high fracture risk, abaloparatide for 48 weeks dose-dependently increased LS, TH, and FN BMDs, supporting further investigation with 80 µg abaloparatide for the treatment of osteoporosis in this population. TRIAL REGISTRATION NUMBER: JapicCTI-132381.

Paget's Disease of the Bone and Lynch Syndrome: An Exceptional Finding.

Our objective is to present an exceptional case of a patient diagnosed with Paget's disease of the bone (PDB) while being confirmed with Lynch syndrome (LS). A 44-year-old woman was admitted for progressive pain in the left forearm 2 years ago, and was partially relieved since admission by non-steroidal anti-inflammatory drugs. Suggestive imaging findings and increased blood bone turnover markers helped the diagnosis of PDB. She was offered zoledronate 5 mg. She had two more episodes of relapse, and a decision of new medication was taken within the following years (a second dose of zoledronate, as well as denosumab 60 mg). Her family history showed PDB (mother) and colorectal cancer (father). Whole exome sequencing was performed according to the manufacturer's standard procedure (Ion AmpliSeq™ Exome RDY S5 Kit). A heterozygous pathogenic variant in the SQSTM1 gene (c.1175C>T, p.Pro392Leu) was confirmed, consistent with the diagnosis of PDB. Additionally, a heterozygous pathogenic variant of MSH2 gene (c.2634+1G>T) was associated with LS. The patient's first-degree relatives (her brother, one of her two sisters, and her only daughter) underwent specific genetic screening and found negative results, except for her daughter, who tested positive for both pathogenic variants while being clinically asymptomatic. The phenotype influence of either mutation is still an open issue. To our current knowledge, no similar case has been published before. Both genetic defects that led to the two conditions appeared highly transmissible in the patient's family. The patient might have an increased risk of osteosarcoma and chondrosarcoma, both due to PDB and LS, and a review of the literature was introduced in this particular matter. The phenotypic expression of the daughter remains uncertain and is yet to be a lifelong follow-up as the second patient harbouring this unique combination of gene anomalies.

Biochemical Markers of Bone Fragility in Patients with Diabetes. A Narrative Review by the IOF and the ECTS.

CONTEXT: The risk of fragility fractures is increased in both type 1 and type 2 diabetes. Numerous biochemical markers reflecting bone and/or glucose metabolism have been evaluated in this context. This review summarizes current data on biochemical markers in relation to bone fragility and fracture risk in diabetes. METHODS: Literature review by a group of experts from the International Osteoporosis Foundation (IOF) and European Calcified Tissue Society (ECTS) focusing on biochemical markers, diabetes, diabetes treatments and bone in adults. RESULTS: Although bone resorption and bone formation markers are low and poorly predictive of fracture risk in diabetes, osteoporosis drugs seem to change bone turnover markers in diabetics similarly to non-diabetics, with similar reductions in fracture risk. Several other biochemical markers related to bone and glucose metabolism have been correlated with BMD and/or fracture risk in diabetes, including osteocyte-related markers such as sclerostin, HbA1c and advanced glycation end products (AGEs), inflammatory markers and adipokines, as well as IGF-1 and calciotropic hormones. CONCLUSION: Several biochemical markers and hormonal levels related to bone and/or glucose metabolism have been associated with skeletal parameters in diabetes. Currently, only HbA1c levels seem to provide a reliable estimate of fracture risk, while bone turnover markers could be used to monitor the effects of anti-osteoporosis therapy.