Cross-linked C-telopeptide Research Articles

Assessment of the state of mineral metabolism in patients with tooth loss during dental implantation against the background of vitamin D deficiency

Background. The widespread occurrence of mineral metabolism disorders in the modern world, including those due to vitamin D deficiency, affects the results of patient rehabilitation performed by dental surgeons using dental implants. The aim of the study was to assess the state of mineral metabolism during dental implantation in young and middle-aged patients with tooth loss due to vitamin D deficiency. Materials and methods. From 2011 to 2024, 450 patients aged 25–50 years with tooth loss due to identified vitamin D deficiency in the absence of other somatic pathology were examined and treated at Sechenov University and a private clinic. All patients underwent laboratory examination, including assessment of mineral metabolism indicators – the level of total calcium, vitamin D (25 (OH) D), parathyroid hormone, thyroid stimulating hormone. Also, 30 randomly selected patients underwent assessment of osteogenesis markers (bone matrix formation marker P1NP, serum cross-linked C-telopeptide of type I collagen CTX). Patients were referred to an endocrinologist due to detected vitamin D deficiency, therapy was prescribed. All patients underwent dental implantation and concomitant surgeries to increase bone volume, if necessary, considering the study group: in group 1 – until reference values of vitamin D were achieved, in group 2 – after. Comparison of parameters before and after drug therapy was performed using Student’s T-test or Mann-Whitney, the results were considered statistically significant at p < 0.05. Results. In the examined sample, 2.1 % of patients had a pronounced deficiency of (25(OH)D) (< 10 ng/ml), 60.4 % had a deficiency (< 20 ng/ml), and 37.5 % had insufficiency (20–30 ng/ml), with the initial level of vitamin D in both study groups not statistically different (< 20 ng/ml, p < 0.05). After the treatment, the level of (25(OH)D) in all patients reached the reference values (30–60 ng/ml, p < 0.05) also without statistically significant difference when compared by groups (median 1 = 42.75 and median 2 = 43.65, respectively, p > 0.05), but was significantly higher when assessed dynamically within eachgroup (p < 0.05). No deviations from reference values for osteogenesis markers were found over time, although a statistically significant slight decrease in both parameters within the normal range was noted after treatment compared to the initial level (p < 0.05). Conclusion. In young and middle-aged patients with tooth loss due to vitamin D deficiency, no significant changes in laboratory parameters (blood calcium levels, parathyroid hormone, and osteogenesis markers over time) were found during dental implantation and concomitant surgeries.

Effects of isoflavone interventions on bone turnover markers and factors regulating bone metabolism in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to assess the impact of isoflavone interventions on bone turnover markers and various biochemical markers of bone metabolism through systematic review and meta-analysis. Four electronic databases, including PubMed, Embase, Scopus, and Cochrane Library, were searched in September 2023 for investigating the effects of isoflavones on bone turnover markers as well as signaling molecules regulating osteoclast differentiation, bone minerals, and hormones regulating bone metabolism in postmenopausal women. The main effect estimates, obtained using a random-effects model, were summarized using the mean difference (MD) or standardized mean difference (SMD), as appropriate. A total of 73 randomized controlled trials were included, comparing an isoflavone intervention to a placebo. Our findings demonstrated that isoflavone interventions significantly reduced bone resorption markers, that is, β cross-linked C-telopeptide of type 1 collagen (β-CrossLaps) (MD = - 0.0943ng/mL; P = 0.0071) and pyridinoline (PYD) (SMD = - 0.9111; P = 0.0247). Moreover, isoflavone interventions positively affected bone mineral parameters by increasing serum calcium levels (MD = 0.3430mg/dL; P = 0.0267) and decreasing serum phosphorus levels (MD = - 0.0648mg/dL; P = 0.0435). Hormones involved in regulating bone metabolism, particularly insulin-like growth factor type 1 (IGF-1), exhibited significant increases following isoflavone interventions (MD = 9.8163ng/mL; P < 0.0001). Subgroup analysis suggested that the effects of isoflavones on bone turnover markers are influenced by factors such as the duration since menopause and the intervention duration. This systematic review and meta-analysis highlight the potential of isoflavone interventions to rectify imbalances in bone remodeling, enhance bone mineral homeostasis, and optimize hormones regulating bone metabolism in postmenopausal women.

Effects of Aging on New Bone Regeneration in a Mandibular Bone Defect in a Rat Model.

The effects of aging on the healing capacity of maxillofacial bone defects have not been studied. The aim of this study was to evaluate the effects of aging on the regeneration of round bony defects in the mandible. We created a round-shaped bony defect in the mandibular angle area in rats of different ages (2-[2 M], 10-[10 M], and 20-month-old [20 M]) and evaluated new bone regeneration in these groups. Changes in bone turnover markers such as alkaline phosphatase, procollagen type I N-terminal propeptide (PINP), cross-linked C-telopeptide of type I collagen, and tartrate-resistant acid phosphatase 5B (TRAP5b) were investigated. The bone volume/total volume and bone mineral density of the 20 M group were significantly higher than those of the 2 M group (p = 0.029, 0.019). A low level of the bone formation marker PINP was observed in the 20 M group, and a high level of the bone resorption marker TRAP5b was observed in the 10 M and 20 M groups. Micro-computed tomography (µ-CT) results showed that older rats had significantly higher bone formation than younger rats, with lower serum levels of PINP and higher levels of TRAP5b. The local environment of the old rat bone defects, surrounded by thickened bone, may have affected the results of our study. In conclusion, old rats showed greater new bone regeneration and healing capacity for round mandibular bone defects. This result was related to the fact that the bone defects in the 20 M rat group provided more favorable conditions for new bone regeneration.

Adolescent girls with type 1 diabetes develop changes in bone prior to evidence of clinical neuropathy.

Neuropathy and fracture are prevalent complications of type 1 diabetes (T1D). Although correlated in the clinical literature, it remains unknown whether neuropathy contributes to the initiation of bone loss at the earliest stages of disease. We performed a single-center, cross-sectional study to quantify parameters of nerve and bone health in adolescent girls with T1D (n=21) and associated controls (n=12). Groups were well matched for age, height, strength, and physical activity. By HR-pQCT, participants with T1D had lower trabecular bone volume fraction at the distal radius (-14.6%, p-adj=0.095) and the tibia (-12.8%, p-adj=0.017) and decreased trabecular thickness (-8.3% radius, p-adj=0.007; -7.5% tibia, p-adj=0.034) after adjustment for body size. In the tibia only, cortical bone mineral density was increased by 8.6% (p-adj=0.024) and porosity was decreased by 52.9% with T1D (p-adj=0.012). There were no significant differences in bone density by DXA. Participants with T1D also had lower circulating levels of osteocalcin (-30%, p=0.057), and type I collagen cross-linked C-telopeptide (-36%, p=0.035), suggesting low bone formation and turnover in T1D. Based on the Michigan Neuropathy Screening Instrument, 9.5% of those with T1D had clinical evidence of diabetic peripheral neuropathy. However, consideration of neuropathy status failed to explain the widespread T1D-associated changes in bone. Our study defines early deficits in trabecular bone microarchitecture, decreased cortical porosity in the tibia, and suppression of biomarkers of bone turnover in adolescent girls with T1D, prior to the onset of symptomatic peripheral neuropathy. These findings inform our understanding of the rapid progression of skeletal disease in young girls with T1D and suggests that early detection and management strategies may help to prevent fracture and related co-morbidities later in life.

Calcitonin treatment for osteoarthritis and rheumatoid arthritis - a systematic review and meta-analysis of preclinical data.

The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new stabilized CT formulations are currently being introduced. A comprehensive and systemic literature search was conducted in PubMed/MEDLINE and Embase databases to identify articles with original data on CT treatment of preclinical OA and RA. Methodological quality was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool for animal intervention studies. To provide summary estimates of efficacy, a meta-analysis was conducted for outcomes reported in four or more studies, using a random-effects model. Subgroup analyses were employed to correct for study specifics. Twenty-six studies were ultimately evaluated and data from 16 studies could be analyzed in the meta-analysis, which included the following outcomes: bone mineral density, bone volume, levels of cross-linked C-telopeptide of type I collagen, histopathological arthritis score, and mechanical allodynia. For all considered outcome parameters, CT-treated groups were significantly superior to control groups (P = 0.002; P = 0.01; P < 0.00001; P < 0.00001; P = 0.04). For most outcomes, effect sizes were significantly greater in OA than in RA (P ≤ 0.025). High in-between study heterogeneity was detected. There is preclinical evidence for an antioxidant, anti-inflammatory, antinociceptive, cartilage- and bone-protective effect of CT in RA and OA. Given these effects, CT presents a promising agent for the treatment of both diseases, although the potential seems to be greater in OA.

Impact of Pheochromocytoma or Paraganglioma on Bone Metabolism: A Systemic Review and Meta-analysis

Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap. Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP). Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery. Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.

Dual-release hydrocortisone improves body composition and the glucometabolic profile in patients with secondary adrenal insufficiency

PurposeStudies have suggested improved metabolic profiles in patients with adrenal insufficiency treated with dual-release hydrocortisone (DR-HC) compared with conventional hydrocortisone (C-HC). This study investigates the effect of DR-HC compared with C-HC treatment on five health variables: diurnal salivary cortisol/cortisone, body composition, bone health, glucose metabolism, lipids, and blood pressure.MethodsProspective study of 27 participants (24 men) with secondary adrenal insufficiency with measurements during stable C-HC and 16 weeks after treatment switch to DR-HC.OutcomesDiurnal salivary-cortisol/cortisone, body composition assessed by Dual-Energy X-ray absorptiometry scan, bone status indices (serum type I N-terminal procollagen [PINP], collagen type I cross-linked C-telopeptide [CTX], osteocalcin, receptor activator kappa-B [RANK] ligand, osteoprotegerin, and sclerostin), lipids, haemoglobin A1c (HbA1c), and 24-hour blood pressure.ResultsAfter the switch to DR-HC, the diurnal salivary-cortisol area under the curve (AUC) decreased non-significantly (mean difference: −55.9 nmol/L/day, P = 0.06). The salivary-cortisone-AUC was unchanged. Late-evening salivary-cortisol and cortisone were lower (−1.6 and −1.7 nmol/L, P = 0.002 and 0.004). Total and abdominal fat mass (−1.5 and −0.5 kg, P = 0.003 and 0.02), HbA1c (−1.2 mmol/mol, P = 0.02), and osteocalcin decreased (−7.0 µg/L, P = 0.03) whereas sclerostin increased (+41.1 pg/mL, P = 0.0001). The remaining bone status indices, lipids, and blood pressure were unchanged.ConclusionThis study suggests that switching to DR-HC leads to lower late-evening cortisol/cortisone exposure and a more favourable metabolic profile and body composition. In contrast, decreased osteocalcin with increasing sclerostin might indicate a negative impact on bones.Clinical trial registrationEudraCT201400203932

The Role of Rosavin in the Pathophysiology of Bone Metabolism.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

Characteristics of bone metabolism in the male patients with diabetic neuropathy.

This study aimed to evaluate the characteristics of bone metabolism and fracture risk in the type 2 diabetes mellitus (T2DM) patients with distal symmetric polyneuropathy (DSPN). A total of 198 T2DM individuals were recruited from January 2017 to December 2020. Patients with DSPN were evaluated by strict clinical and sensory thresholds. Biochemical parameters and bone mineral density (BMD) were measured. The BMD, bone turnover markers, and probability of fracture were compared between two groups, and the factors related to BMD and probability of hip fracture in 10 years were further explored. Compared with type 2 diabetes mellitus without distal symmetric polyneuropathy (T2DN-) patients, type 2 diabetes mellitus with distal symmetric polyneuropathy (T2DN+) patients had lower level of cross-linked C-telopeptide (CTX) (0.32 ± 0.19 vs 0.38 ± 0.21 ng/mL, p = 0.038) and higher level of bone-specific alkaline phosphatase (BALP) (15.28 ± 5.56 vs 12.58 ± 4.41 μg/mL, p = 0.003). T2DN+ patients had higher BMD of lumbar L1-L4 (1.05 ± 0.19 vs 0.95 ± 0.37, p = 0.027) and higher probability of hip fracture (0.98 ± 0.88 vs 0.68 ± 0.63, p = 0.009) as compared to T2DN- individuals. Univariate correlation analysis showed that BALP level (coefficient (coef) = -0.054, p = 0.038), CTX level (coef = -2.28, p = 0.001), and hip fracture risk (coef = -1.02, p < 0.001) were negatively related to the BMD of L1-L4. As for the risk of hip fracture evaluated by WHO Fracture Risk Assessment Tool (FRAX), age (coef = 0.035, p < 0.001), use of insulin (coef = 0.31, p =0.015), and levels of BALP (coef = 0.031, p = 0.017) and CTX (coef = 0.7, p = 0.047) were positively related to the risk of hip fracture. Multivariate regression analysis showed that CTX level (coef = -1.41, p = 0.043) was still negatively related to BMD at the lumbar spine. This study indicates that T2DM patients with DSPN have special bone metabolism represented by higher BALP level and lower CTX level which may increase BMD at the lumbar spine.

Vitamin D status and its associations with bone mineral density, bone turnover markers, and parathyroid hormone in Chinese postmenopausal women with osteopenia and osteoporosis.

Vitamin D is a key factor in bone metabolism, yet vitamin D insufficiency and deficiency are prevalent among postmenopausal women, with potential repercussions on bone mineral density (BMD), bone turnover markers (BTMs), and parathyroid hormone (PTH). Nonetheless, the findings from existing studies exhibit inconsistency, and a notable gap exists in the availability of large-scale investigations. In this real-world study, 8,532 postmenopausal women over 50 years old with a diagnosis of osteopenia (50.9%) and osteoporosis (49.1%) at the first visit were enrolled in this study. Serum 25(OH)D level, PTH, osteocalcin (OC) and Beta-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), were measured. BMD at all sites, including the lumbar spine, femoral neck, and total hip were obtained by dual-energy X-ray absorptiometry (DXA). The associations of serum 25(OH)D level with BMDs and BTMs were investigated using spearman correlation analysis and analysis of general linear model adjusted by age and body mass index. The serum 25(OH)D level was 22.17 ± 9.75 ng/mL among all patients included in this study. For the osteopenia group, the serum 25(OH)D level was 22.40 ± 9.41 ng/mL, while for the osteoporosis group, it measured 21.93 ± 10.08 ng/mL. In the osteopenia group, the prevalence of vitamin D deficiency, insufficiency and sufficiency was 45.8, 34.6, and 19.6%, respectively, which was close to that of the osteoporosis group (47.4, 34.3, and 18.3%) (p = 0.202). Spearman correlation analysis unveiled negative associations between serum 25(OH)D concentrations and both BTMs and PTH within both the osteopenia and osteoporosis group. In the osteoporosis group, there were positive correlations between 25(OH)D levels and femoral neck BMD (r = 0.040, p = 0.010) and total hip BMD (r = 0.053, p = 0.001). Furthermore, we found that for the osteopenia group, greater vitamin D levels were associated with greater femoral neck BMD (p = 0.020) and total hip BMD (p = 0.008) and lower β-CTX (p < 0.001), OC (p < 0.001), and PTH (p < 0.001). The same trends were seen in osteoporosis patients (p < 0.05), and with greater lumbar spine BMD with higher levels of 25(OH)D (p = 0.009). This study showed high prevalence of vitamin D deficiency and insufficiency in Chinese postmenopausal women with osteopenia and osteoporosis and the relationships between vitamin D and BMD, BTMs and PTH. The results contribute to a more comprehensive understanding of how vitamin D may impact bone health.

Effects of probiotic supplementation on bone health in postmenopausal women: a systematic review and meta-analysis.

The beneficial effects of probiotic supplementation on bone health in postmenopausal women require further validation. This study systematically reviewed and conducted a meta-analysis of randomized controlled trials (RCTs) to assess the relationship between probiotic supplementation and changes in bone mineral density (BMD) and bone turnover markers (BTMs) among postmenopausal women. A systematic search was conducted across four databases to retrieve data on lumbar spine BMD, hip BMD, collagen type 1 cross-linked C-telopeptide (CTX), receptor activator of nuclear factor-κB ligand (RANKL), osteocalcin (OC), osteoprotegerin (OPG), N-terminal propeptide of type 1 procollagen (P1NP), and bone-specific alkaline phosphatase (BALP) in postmenopausal women. Eligible RCTs were quantitatively analyzed using random-effects meta-analyses. Additional analyses, including subgroup, sensitivity, and meta-regression analyses, were performed. Twelve RCTs involving 1183 postmenopausal women were included. Compared with the control group, postmenopausal women who received probiotic supplementation showed significantly greater BMD in both the lumbar spine (standardized mean difference [SMD] = 0.60, 95% confidence interval [CI] 0.14 to 1.05) and the hip (SMD = 0.74, 95%CI 0.15 to 1.33). Additionally, probiotic supplementation was associated with reduced levels of CTX (SMD = -1.51, 95%CI -1.88 to -0.41) and BALP (SMD = -1.80, 95%CI -2.78 to -0.81). No significant differences were found between the probiotic and control groups in terms of other BTMs. Subgroup analyses revealed that the increase in BMD due to probiotic supplementation was more significant in postmenopausal women with osteopenia than in those with osteoporosis. The meta-analysis results for both lumbar spine and hip BMD remained robust after conducting sensitivity analyses and meta-regressions. Supplementation with probiotics may increase BMD among postmenopausal women, with stronger evidence in women with osteopenia than osteoporosis. Further RCTs are suggested to confirm and refine these findings. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024576764.

Parathyroidectomy Improves Bone Density in Women With Primary Hyperparathyroidism and Preoperative Osteopenia.

Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. Referral center. A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. Parathyroidectomy. BMD change between before and 1 year after parathyroidectomy. Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03-0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00-0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01-0.02)], and the forearm [+0.01 (95% CI 0.00-0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain.

Urolithiasis Problems in Finishing Pigs.

This paper describes cases of urolithiasis in fattening pigs on two farms (A and B). Bladder rupture due to urethral obstruction with calculi was the principal finding during the necropsy of the pigs. An in-depth diagnostic examination was performed to elucidate possible pathophysiological mechanisms, namely Fourier-transform infrared spectrophotometry (FT-IR) analysis of the uroliths, blood analysis (farm A: 5 samples, farm B: 10 samples) for assessing concentrations of minerals, the bone resorption marker cross-linked C-telopeptide of type 1 collagen (CTX), parathyroid hormone (PTH), and vitamin D components, biochemical urinalysis (farm A: 5 samples, farm B: 7 samples), microscopic examination of urinary sediment (Farms A and B: 7 samples each), mineral composition of the feed, and analysis of the drinking water. Calcium carbonate was the main component found in stones from both farms, and calcium carbonate and struvite were the main components found in crystals from farms A and B, respectively. On farm A, urinary calcium excretion and urinary pH were high; on farm B, urinary phosphorus was high and urinary calcium was low with a normal urinary pH. The mineral compositions of the feed and drinking water were similar on both farms and could therefore not explain the difference between the two farms. Disturbances in calcium and phosphorus absorption and homeostasis might have been involved in these problems. Further research should focus on the calcium, phosphorus, and vitamin D levels in the feed and take into account other factors, such as the absorption and excretion of minerals due to gut and urinary microbiota.

Effect of intra-articular injection of a hyaluronic acid-alendronate conjugate on post-traumatic osteoarthritis induced by destabilization of the medial meniscus in rats

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and cartilage damage. Intra-articular (i.a) viscosupplementation with hyaluronic acid (HA) is frequently used for the management of OA. Preclinical studies have reported that bisphosphonates (BPs) may have a therapeutic potential to slow down or reverse the progression of OA. Among these, alendronate (ALN) has demonstrated chondroprotective effects in both in vitro and vivo experiments. This study evaluated the effects of a novel alendronate-hyaluronic acid (ALN-HA) conjugate on an OA in vivo model induced by medial meniscus destabilization (DMM). DMM surgery was performed on the knees of Sprague Dawley rats that received, after four weeks, one intra-articular (i.a.) injection of: (1) ALN-HA; (2) HA; (3) sodium chloride (NaCl). Sham-operated rats were used as control. Allodynia was assessed by Von Frey test. Joint degeneration was evaluated eight weeks after treatment by micro-computed tomography (micro-CT), histology, and immunohistochemistry. Collagen cross-linked C-telopeptides (CTX-I and CTX-II) serum levels were determined by ELISA. Paw withdrawal threshold increased in ALN-HA group when compared to rats treated with NaCl or HA. Micro-CT did not show differences between ALN-HA, HA and NaCl groups. ALN-HA injection produced significant improvements in articular cartilage degeneration showing an OARSI score lower than those of HA and NaCl, and reduced matrix metalloproteinase (MMP)-13, MMP-3, interleukin-6, vascular endothelial growth factor and Caspase-3 expression. CTX-I was reduced after ALN-HA treatment when compared to NaCl. Our results indicate that i.a. use of ALN after conjugation with HA limits OA development and progression in the rat DMM model, and may lead to the development of novel therapeutic strategies in OA management.

Do men improve their bone mineral density 1 year after parathyroidectomy for primary hyperparathyroidism? Results of a prospective study

BackgroundThe impact of parathyroidectomy on bone mineral density in men with primary hyperparathyroidism is poorly known. This study aimed to evaluate the bone mineral density and bone remodeling biomarker changes in men with primary hyperparathyroidism 1 year after parathyroidectomy. MethodsMen operated for sporadic primary hyperparathyroidism between 2016 and 2022, enrolled in a monocentric prospective cohort, were analyzed. Patients with follow-up <1 year or missing data were excluded. Bone mineral density (dual X-ray absorptiometry) was measured before and 12 months after parathyroidectomy. Bone mineral density change ≥0.03g/cm2 was deemed significant. Bone remodeling biomarkers were serum cross-linked C-telopeptide, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatases. ResultsForty-five men were included (mean age 58.8 ± 13.1 years). Before surgery, 49% had osteopenia, and 11% had osteoporosis. Mean serum calcium and median serum parathyroid hormone levels decreased significantly after surgery (P < .0001). One year after parathyroidectomy, the mean bone mineral density increased significantly at the lumbar spine (+0.04g/cm2 [0.01;0.70], P = .0054), femoral neck (+0.04g/cm2 [0.03;0.05], P < .0001) and total hip (+0.02g/cm2 [0.01;0.03], P = .0002). Considering significant bone mineral density gain (+1 point) and loss (–1 point) at each site, 29/45 patients (64% [95% CI 49;78]) improved. Bone remodeling biomarker concentrations significantly decreased (P < .001). ConclusionParathyroidectomy positively affects bone mineral density in men with primary hyperparathyroidism, supporting osteopenia as a surgical indication in these patients.

Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort

Mineral and bone disorder (MBD) in chronic kidney disease (CKD) is tightly linked to cardiovascular disease (CVD). In this study, we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular (CV) outcomes and mortality. In 5 217 participants of the German CKD (GCKD) study enrolled with an estimated glomerular filtration rate (eGFR) between 30–60 mL·min−1 per 1.73 m2 or overt proteinuria, serum osteoprotegerin (OPG), C-terminal fibroblast growth factor-23 (FGF23), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), cross-linked C-telopeptide of type 1 collagen (CTX1), procollagen 1 intact N-terminal propeptide (P1NP), phosphate, calcium, and 25-OH vitamin D were measured at baseline. Participants with missing values among these parameters (n = 971) were excluded, leaving a total of 4 246 participants for analysis. During a median follow-up of 6.5 years, 387 non-CV deaths, 173 CV deaths, 645 nonfatal major adverse CV events (MACEs) and 368 hospitalizations for congestive heart failure (CHF) were observed. OPG and FGF23 were associated with all outcomes, with the highest hazard ratios (HRs) for OPG. In the final Cox regression model, adjusted for CV risk factors, including kidney function and all other investigated biomarkers, each standard deviation increase in OPG was associated with non-CV death (HR 1.76, 95% CI: 1.35–2.30), CV death (HR 2.18, 95% CI: 1.50–3.16), MACE (HR 1.38, 95% CI: 1.12–1.71) and hospitalization for CHF (HR 2.05, 95% CI: 1.56–2.69). Out of the nine biomarkers examined, stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.

Phytosterols Protect against Osteoporosis by Regulating Gut Microbiota.

Osteoporosis is increasingly prevalent worldwide, representing a major health burden. However, there is a lack of nutritional strategies for osteoporotic therapy. Phytosterols, as natural bioactive compounds, have the potential to alleviate osteoporosis. In this study, a glucocorticoid-induced osteoporosis mouse model and treatment with low and high concentrations of phytosterols for 4 weeks were established. The results demonstrated that compared to the control group, low-concentration phytosterols (LP) (0.3 mg/mL) increased bone mass, improved trabecular microstructure, reduced serum levels of cross-linked C-telopeptide of type I collagen (CTX-1), and elevated serum levels of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Conversely, high-concentration phytosterols (0.5 mg/mL) showed no effect. Additionally, we validated the effect of LP in ameliorating osteoporosis using an ovariectomized (OVX)-induced osteoporosis mouse model. Mechanistically, phytosterols altered the microbial composition to counteract glucocorticoid-induced gut microbiota disorder and improve the length and morphology of the small intestine. Particularly, based on selection strategy and correlation analysis, phytosterols increased the relative abundance of Ruminococcus and decreased the relative abundance of Bilophila, which were significantly associated with glucocorticoid-induced osteoporosis indications. Overall, these findings suggest that phytosterols regulate gut microbiota to increase bone mass, thereby exerting an antiosteoporotic effect.

Free and bioavailable 25-hydroxyvitamin D thresholds for bone metabolism and their associations with metabolic syndrome in Chinese women of childbearing age.

The free hormone hypothesis suggests that free and bioavailable 25-hydroxyvitamin D [25(OH)D] may better reflect vitamin D bioactivity. This study aimed to determine the free and bioavailable 25(OH)D characteristics, estimate their thresholds based on parathyroid hormone (PTH) and bone turnover markers (BTMs), assess their associations with the risk of metabolic syndrome (MetS), and evaluate their potential advantages. A cross-sectional study was conducted using a nationally representative database (n = 1,505, female, 18-45 years). Serum total 25(OH)D, vitamin D-binding protein, albumin, PTH, and BTMs [osteocalcin, β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and procollagen type 1 N-terminal propeptide (P1NP)] were measured. Free 25(OH)D and bioavailable 25(OH)D were calculated. The threshold associations of 25(OH)D with PTH and BTMs were analyzed. The relationship between 25(OH)D and MetS risk was examined. An intervention study was then performed in 39 women (18-47 years) to assess the associations of increasing 25(OH)D with PTH and BTMs after vitamin D supplementation. In the cross-sectional study, the three forms of 25(OH)D were found to have similar distribution characteristics. Free and bioavailable 25(OH)D correlated well with total 25(OH)D. Significant total 25(OH)D cutoffs were observed for PTH (14.19 ng/mL and 18.03 ng/mL), osteocalcin (15.14 ng/mL), β-CTX (14.79 ng/mL), and P1NP (15.08 ng/mL). Free and bioavailable 25(OH)D cutoffs were only found for P1NP (3.47 pg/mL and 1.66 ng/mL, respectively). A total 25(OH)D of <15.14 ng/mL was marginally associated with a higher risk of reduced high-density lipoprotein cholesterol (HDL-C) [odd ratios (OR) = 1.371 (0.991-1.899)]. The ORs of higher versus lower free and bioavailable 25(OH)D levels for reduced HDL-C were 0.770 (0.621-0.956) and 0.772 (0.622-0.958), respectively. The results of the intervention study indicated that PTH and BTMs responded more sensitively to total 25(OH)D than to free or bioavailable 25(OH)D. Free and bioavailable 25(OH)D only had a threshold effect on P1NP. The active 25(OH)D thresholds could be used for risk assessment of reduced HDL-C. However, no superiority of free or bioavailable 25(OH)D was found based on the response of PTH and BTMs to changes in 25(OH)D in Chinese women of childbearing age following vitamin D supplementation. http://www.chictr.org.cn, ChiCTR2200058290.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

Bone Turnover Markers in Adults with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Previous studies suggested that the level of bone turnover markers (BTMs) could be altered in patients with nonalcoholic fatty liver disease (NAFLD). We aim to provide a comprehensive understanding on the associations between BTMs and NAFLD in adults with a meta-analysis. Articles published up to January 31, 2023, were systematically searched in PubMed, Web of Science, Cochrane database, Embase, and CNKI. The search formula is as follows: "nonalcoholic fatty liver disease" combined with the terms that bone turnover markers such as "osteocalcin," "collagen type I trimeric cross-linked peptide," and "procollagen type I N-terminal peptide." Stata 15.0 software was used to calculate the pooled OR (95% CI) and perform the heterogeneity test, sensitivity analysis, and publication bias. We identified 18 studies with a total of 12,310 participants. Statistical differences were found between patients with NAFLD compared to the control group for osteocalcin (n = 15 studies; SMD: -0.69; 95% CI: -0.73--0.64; P=0.002), procollagen type I N-terminal propeptide (n = 5 studies; SMD: -0.40; 95% CI: -0.80--0.00; P=0.049), and collagen type I cross-linked C-telopeptide (n = 7 studies; SMD: -0.16; 95% CI: -0.23--0.09); P < 0.001). Bone turnover markers were lower in patients with NAFLD compared to the control group.