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.

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.
CONCLUSIONS: 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.

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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

BACKGROUND: 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 β-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 β-CTX levels for girls, not boys (P=0.022).
CONCLUSIONS: We provide age-, sex-, and puberty stage-specific P1NP and β-CTX reference curve. According to these, obesity appeared to be a negative factor for bone formation in boys and for bone resorption in girls.

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.

OBJECTIVE: 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.

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), β-collagen degradation product (β-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-1β), 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 β-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.
CONCLUSIONS: 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.