Bone Turnover Biomarkers Research Articles

Characterization of Trivalently Crosslinked C-Terminal Telopeptide of Type I Collagen (CTX) Species in Human Plasma and Serum Using High-Resolution Mass Spectrometry.

With an aging population, the increased interest in the monitoring of skeletal diseases such as osteoporosis led to significant progress in the discovery and measurement of bone turnover biomarkers since the 2000s. Multiple markers derived from type I collagen, such as CTX, NTX, PINP, and ICTP, have been developed. Extensive efforts have been devoted to characterizing these molecules; however, their complex crosslinked structures have posed significant analytical challenges, and to date, these biomarkers remain poorly characterized. Previous attempts at characterization involved gel-based separation methods and MALDI-TOF analysis on collagen peptides directly extracted from bone. However, using bone powder, which is rich in collagen, does not represent the true structure of the peptides in the biofluids as it was cleaved. In this study, our goal was to characterize plasma and serum CTX for subsequent LC-MS/MS method development. We extracted and characterized type I collagen peptides directly from human plasma and serum using a proteomics workflow that integrates preparative LC, affinity chromatography, and HR-MS. Subsequently, we successfully identified numerous CTX species, providing valuable insights into the characterization of these crucial biomarkers.

Associations of AMH in mid-reproductive years with bone mineral density and turnover markers in mid-life.

Concentration of circulating anti-Müllerian hormone (AMH) predicts short-term (3-5 years) bone loss around menopause. Whether AMH during mid-reproductive years predicts bone health over a decade later is unknown. To study the association of AMH levels in mid-reproductive years with bone density and turnover biomarkers measured after ∼14 years of follow-up. We assessed plasma AMH in 2003-2006 (mean 37.0 years, SD 5.1) among 450 parous women (71% White) in a US longitudinal cohort, and bone mineral density (BMD; spine, hip, and femoral neck, measured by dual-energy X-ray absorptiometry) in 2017-2021 (mean 51.0 years, SD 5.1). Secondary outcomes were plasma levels of procollagen type I N-propeptide (PINP) and C-terminal telopeptide I (CTX-I). In linear regression models adjusted for demographics and lifestyle, compared to women with AMH >3.5 ng/mL, those with AMH <1.0 ng/mL had lower BMD (g/cm2) at follow-up (beta [95% CI]: spine: -0.06 [-0.10, -0.02]; hip: -0.05 [-0.08, -0.02]; femoral neck: -0.03 [-0.06, 0.00]) and higher bone turnover markers (beta [95% CI]: PINP: 0.36 SD [0.10, 0.63]; CTX-I: 0.34 SD [0.07, 0.60]). The association of AMH with spine BMD was more pronounced among post-menopausal women, in contrast to associations with bone turnover markers which were more pronounced among women who had not yet reached menopause. The associations between AMH and BMD were primarily mediated by menopausal status at follow-up. Lower AMH during mid-reproductive years is associated with lower BMD and higher bone turnover 14 years later. Ovarian reserve during mid-reproductive years may be a valuable predictor of long-term bone health.

Citrus tamurana Hort. ex Tanaka (Hyuganatsu orange)-derived arabinogalactan suppresses bone turnover in postmenopausal women: A randomized placebo-controlled study.

To evaluate Hyuganatsu oranges (Citrus tamurana Hort. Ex Tanaka) derived arabinogalactan for bone turnover, we performed a randomized placebo-controlled trial. Sixty-three postmenopausal women were age-stratified and randomly assigned to receive arabinogalactan-rich hyuganatsu juice (study group) or a placebo drink (control group) for 90 days. We measured blood tartrate-resistant acid phosphatase 5b (TRACP5b), type I procollagen N-terminal propeptide (P1NP), and other bone turnover biomarker levels at baseline, days 45 and 90 (T90) of the intervention, and day 30 of recovery. Cumulative effects were compared between groups using repeated-measures linear mixed model analysis. The primary endpoint was the difference between the pre- and post-intervention TRACP5b and P1NP levels. Using repeated measures linear mixed model analysis, the study group had significantly lower TRACP5b and P1NP levels at day 90 than the control group (mean [95% confidence interval]; TRACP5b: 310.0 [269.2-350.9] vs. 386.4 [341.2-431.6] mU/dL; P1NP: 53.7 [48.6-58.7] vs. 70.3 [64.1-76.4] ng/mL), whereas other biomarker levels showed no change. Arabinogalactan-rich Hyuganatsu juice suppressed bone mineral turnover and potentially improved ovarian hormone deficiency-induced osteoporosis in postmenopausal women.

Effect of dietary calcium and vitamin D supplements on plasma bone turnover biomarkers, bone mineralization, bone strength, and lameness score in gilts.

This study investigated the impact of calcium (Ca) and vitamin D supplements on bone metabolism, bone measurement, lameness, and selection rate in gilts fed five dietary treatments. Two Ca levels (6.85/6.42 [adequate; ACa] or 8.99/8.56 [high; HCa] g/kg) were combined with either 856 IU/kg vitamin D3 (Danish feeding standards; adequate; AD3) or 50 μg/kg 25-hydroxyvitamin D3 (high; HHyD) to create ACaAD3, HCaAD3, ACaHHyD, and HCaHHyD diets. The values 6.85/6.42 and 8.99/8.56g/kg correspond to adequate and high Ca supply for gilts weighing 32 to 100 and 100 to 180kg body weight (BW), respectively. The fifth diet was a combination of HCa and 2,000 IU/kg vitamin D3 (high; HD3) to create HCaHD3. Two hundred gilts were phase fed the dietary treatments from 32 to 100 and 100 to 180kg BW until they were slaughtered, either at 100 or 180kg BW. The gilts were weighed fortnightly, and plasma and urine samples were collected at 100 and 180kg BW. At slaughter, the 2nd and 3rd metacarpal bones were collected for bone parameters measurements. Lameness and selection rate were assessed within the last 7 d at 100 and 180kg BW. Dietary treatments did not affect gilts' growth performance and plasma concentration of Ca, but urinary concentration of Ca was greater in HCa-supplemented gilts at both 100 (P = 0.003) and 180 (P = 0.05) kg BW. Plasma concentration of vitamin D3 (P < 0.001) and 25-hydroxyvitamin D3 (P < 0.001) showed dose-dependent responses at both 100 and 180kg BW. Bone-specific alkaline phosphatase was greater (P = 0.02) in the plasma sample collected at 180kg BW in gilts fed the HCaHD3 diet and tended to be greater in gilts fed the ACaAD3 diet (P = 0.06). The bone ash content (P = 0.02) was greater in gilts fed the HCaAD3 diet and slaughtered at 100kg BW compared with gilts fed the ACaAD3 and ACaHHyD diets. However, bone weight, length, thickness, dry matter, and mineral content did not differ among the dietary treatments at both 100 and 180kg BW (P > 0.05). Neither lameness nor selection rate was affected by the dietary treatments. The average daily gain of gilts weighing 32 to 100 and 100 to 180kg BW showed a positive correlation with bone strength (r = 0.37; P < 0.001) and bone ash content (r = 0.24; P = 0.02), respectively. In conclusion, higher Ca and vitamin D3 supplementation slightly increased bone ash content but had no effect on lameness or selection rate of the gilts compared to those fed according to the Danish nutrient standards.

Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats

We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption. We further demonstrate that the combination of LIV and RANKL antibody reduces SCI-related bone loss more than each intervention alone. Our findings that LIV is efficacious in maintaining sublesional bone mass suggests that such physical-based intervention approach would be a noninvasive, simple, inexpensive and practical intervention to treat bone loss after SCI. Because the combined administration of LIV and RANKL inhibition better preserved sublesional bone after SCI than either intervention alone, this work provides the impetus for the development of future clinical protocols based on the potential greater therapeutic efficacy of combining non-pharmacological (e.g., LIV) and pharmacological (e.g., RANKL inhibitor or other agents) approaches to treat osteoporosis after SCI or other conditions associated with severe immobilization.

Low T3 Syndrome is Associated with Imbalance of Bone Turnover Biomarker in Patients with Type 2 Diabetes.

To investigate the variation in bone turnover biomarkers among patients with type 2 diabetes (T2D) and low triiodothyronine levels (Low T3 syndrome). This retrospective analytic study included 418 inpatient records from Shanghai Pudong Hospital covering the years 2021 to 2023. Laboratory data related to metabolic and bone turnover biomarkers in patients were analyzed with T2D and the low T3 syndrome. The results indicated that patients with reduced serum T3 levels exhibited statistically significant variations in thyroid function, age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), and the proportion of medication history associated with diabetes in comparison to euthyroid patients. In addition to parathyroid hormones, bone turnover biomarkers including N-terminal middle molecular fragment of osteocalcin (NMID), plasma calcium (Ca2+), β C-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and 25-hydroxyvitamin D3 (25 OH VitD3) exhibited significant changes in patients with decreased T3 levels. Evident irregularities were observed in patients with a decreased T3 level, including elevated serum creatinine (SCr), decreased concentrations of albumin and total protein, and a decreased estimated glomerular filtration rate (eGFR), as assessed through hepatic and renal testing, respectively. Significant associations between bone turnover biomarkers and the subsequent variables (gender, adiposity, hepatic, renal, and thyroid function) were revealed through the correlational analysis. Further investigation utilized multivariate linear regression to determine that, in addition to thyroid function, several other factors such as age, gender, bodyweight, pancreatic, hepatic, and renal function, affected the variability in bone turnover biomarkers among patients demonstrating a low serum T3 level. This comparative study demonstrated that despite age, gender, bodyweight, hepatic, renal function, thyroid hormone and pancreatic function were significant factors associated with bone metabolism in patients with T2D and Low T3 syndrome, which may increase the risk of osteoporosis.

Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis.

Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions. The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

Changes In Bone Turnover Biomarkers In Men And Women During Marine Corps Officer Candidates School

Changes In Bone Turnover Biomarkers In Men And Women During Marine Corps Officer Candidates School

Moderate-to-vigorous physical activity modulates the association between serum 25-hydroxyvitamin D and bone stiffness in European children and adolescents

It remains unclear how serum 25-hydroxyvitamin D (25(OH)D) concentrations relate to childhood bone health. We hypothesized that 25(OH)D was inversely associated with bone turnover biomarkers and positively associated with bone stiffness. Cross-sectional analyses were performed using data from participants (2-15-year-old, 51% boys) from the IDEFICS/I.Family cohort, comprising 3,638 serum 25(OH)D measurements collected in 2007/2008 and 2012/2013 across eight European countries. A biomarker of bone formation (serum osteocalcin), a biomarker of bone resorption (serum C-terminal telopeptides of type I collagen [CTx]), and stiffness index measured using calcaneal quantitative ultrasound were considered outcomes. Linear mixed-effects models were used to adjust for confounders (i.e., age, sex, parental education, time spent in sports club, dairy products consumption, sedentary behavior, height and weight z-scores), the cluster effect of country and repeated measurements. Interactions of calcium intake, moderate-to-vigorous physical activity (MVPA) and weight status with 25(OH)D on outcomes were tested. Only 1 in 3 participants reached the sufficient 25(OH) D concentration of 20 ng/ml. Sufficient 25(OH)D was associated with higher stiffness index if participants had MVPA ≥ 60 min/day (β = 12.14, p < 0.05). Moreover, 25(OH)D was inversely associated with CTx (β = -7.09, p < 0.05); this association was positive but not statistically significant among primary school children living with overweight/obesity. No interaction was observed for calcium intake. In conclusion, serum 25(OH)D and CTx were inversely associated. MVPA interacted the positive association between 25(OH)D and bone stiffness, highlighting the importance of promoting MVPA guidelines in future vitamin D and bone health interventions.

The Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial design and methods

BackgroundAmong older adults living with obesity, intentional weight loss (WL) improves prognosis of many comorbidities. However, concomitant decline in bone mineral density (BMD) limits overall benefit of WL by increasing osteoporotic fracture risk. Identification of intervention strategies to maximize body fat loss, while minimizing harm to the musculoskeletal system, is an important area of clinical research. The main objective of the Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial (NCT05764733) is to compare the independent and combined effects of a 12-month intervention of resistance training (RT) plus bone-loading exercises and bisphosphonate use on dietary WL-associated bone loss among 308 older (≥60 years) adults living with an indication for WL and bisphosphonate use. MethodsAll participants will receive the same group-mediated dietary intervention targeting 8–10 % WL and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT++PL); no RT and oral bisphosphonate (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and oral bisphosphonate (RT++BIS). Total hip areal (a)BMD measured via dual-energy x-ray absorptiometry (DXA) is the primary, powered study outcome. Secondary skeletal outcome measures include femoral neck and lumbar spine aBMD, high resolution peripheral quantitative computed tomography (HRpQCT) bone assessments of the radius and tibia, and biomarkers of bone turnover. DiscussionBEACON will address an understudied, yet important, clinical research question by studying the independent and combined effects of two scalable intervention strategies aimed at optimizing skeletal integrity in older adults undergoing WL.Clinical Trials Registration: NCT05764733

Prevalence and Factors Associated with Sarcopenia in Post-Menopausal Women with Rheumatoid Arthritis.

To estimate the prevalence of sarcopenia in post-menopausal women with rheumatoid arthritis (RA) and to investigate possible correlation with disease parameters. Eighty post-menopausal women with RA and thirty post-menopausal controls were enrolled in this cross-sectional study. RA patients were further divided in two groups according to the existence of sarcopenia. Sarcopenia was defined according to EWGSOP-II recommendations and osteoporosis as a T-score≤-2.5 in femoral neck bone mineral density. Biomarkers of bone turnover were determined. RA disease activity was calculated using the DAS28-ESR score and inflammatory markers (ESR, CRP). Functionality was calculated with the HAQ-DI score and seropositivity was determined according to RF and anti-CCP antibodies. Thirty-two post-menopausal women with RA (39%) met the EWGSOP-II criteria for sarcopenia. None of the control subjects was detected with sarcopenia (p<0.0001). All parameters that define sarcopenia were significantly lower in the RA group. Sarcopenic RA patients had significantly lower mean BMI (27.1 kg/m2 vs. 30.5 kg/m2, p=0.008), daily physical activity (IPAQ score) (1213 vs 2867, p<0.0001), mean skeletal muscle mass (ASMI) (5.2 kg/m2 vs 6.6 kg/m2, p<0.0001) and handgrip strength (13.7 kg vs 20.1 kg, p<0.0001). No differences were observed in disease parameters or in biomarkers of bone turnover. IGF-1 was the only parameter that differed between the sarcopenic and non-sarcopenic RA patients (90.1 ng/ml vs 112.8 ng/ml, p=0.024). Sarcopenia is more common in RA patients. Sarcopenic RA patients had lower BMI, IPAQ, ASMI and handgrip strength. IGF-1 was the only parameter that was significantly lower in sarcopenic RA patients.

Establishment of Reference Intervals for Bone Turnover Biomarkers in Healthy Populations in Northern China.

This study was intended to establish the reference intervals of bone turnover markers (BTMs) for healthy populations. According to the Clinical Laboratory Standards Institute (CLSI) EP28-A3c, we recruited 774 healthy Chinese and investigated their clinical characteristics and relationships among gender, age, season and BTMs. The reference intervals of BTMs for healthy populations in Hebei of China were established through defining the central 95% range of all observations. We found that gender were associated with 25(OH)D, OC, β-CTX, and P1NP (P < 0.05), but not PTH1-84 (P=0.138). All serum BTMs showed differences among different age groups (P < 0.01). The level of 25 (OH) D in winter showed statistical differences with spring, summer, and autumn (P<0.05). The OC level showed statistical difference between summer and winter (P=0.000). The P1NP levels showed statistical difference between spring and winter (P=0.019), summer and winter (P=0.000), and summer and autumn (P=0.012), respectively. The PTH1-84 levels in winter showed statistical differences with spring, and summer (all P=0.000), while there was no statistically significant difference in β- CTX levels between seasons. We have established the reference intervals of several BTMs for healthy individuals in Hebei of China, which have statistical significance across different age groups and genders, and there are also significant differences between different seasons. Therefore, the Chinese medical laboratories in different locations should group individuals according to gender and age groups in different seasons, and establish corresponding biological reference intervals.

Study protocol for the ROLEX-DUO randomised placebo-controlled trial: ROmosozumab Loaded with EXercise – DUal effects on bone and muscle in postmenopausal Osteoporosis and Osteopenia

IntroductionNovel strategies are needed to address the rising burden of osteoporosis and fragility fractures. High-intensity resistance and impact (HiRIT) exercise has shown benefit in improving bone density in postmenopausal women...

Meat consumption and the risk of hip fracture in women and men: two prospective Swedish cohort studies.

To study the association between meat intake (predominantly red and processed meats) and the risk of hip fracture, as well as the association between meat intake and biomarkers of inflammation, oxidative stress, bone turnover, body composition, and bone mineral density (BMD). Data from the Swedish Mammography Cohort and the Cohort of Swedish men (n = 83,603, 54% men) with repeated investigations and their respective clinical sub-cohorts was utilised. Incident hip fractures were ascertained through individual linkage to registers. Associations were investigated using multivariable Cox and linear regression analyses. During up to 23years of follow-up (mean 18.2years) and 1,538,627 person-years at risk, 7345 participants (2840 men) experienced a hip fracture. Each daily serving of meat intake conferred a hazard ratio (HR) of 1.03 (95% confidence interval [CI] 1.00; 1.06) for hip fracture. In quintile 5, compared to quintile 2, the HR was 1.11 (95% CI 1.01; 1.21) among all participants. In the sub-cohorts, meat intake was directly associated with circulating levels of interleukin-6, C-reactive protein, leptin, ferritin, parathyroid hormone, and calcium. A modest linear association was found between a higher meat intake and the risk of hip fractures. Our results from the sub-cohorts further suggest that possible mechanisms linking meat intake and hip fracture risk may be related to the regulation of bone turnover, subclinical inflammation, and oxidative stress. Although estimates are modest, limiting red and processed meat intake in a healthy diet is advisable to prevent hip fractures.

Electroacupuncture ameliorates senile osteoporosis by promoting bone remodeling and regulating autophagy.

Osteoporosis is widely regarded as a typical aged-related disease caused by impaired bone remodeling. This research was designed to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in a rat model and investigate the underlying mechanisms. Three-month-old rats were randomly selected as the youth group, and 24-month-old rats were randomly assigned to the elderly and EA groups. Rats in the EA group received 30 min of EA at bilateral SP10, ST36, K13 and GB34 daily, 5 days a week for 8 weeks. Bone mineral density (BMD), microstructure of the bone tissue, bone turnover biomarkers and expression level of autophagy-related proteins were detected. Compared with the elderly group, EA treatment significantly increased BMD of the femur and ameliorated the microstructure. EA treatment increased trabecular bone volume ratio (= bone volume / total volume [BV/TV]) and trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp) in senile osteoporosis rats. Compared with the elderly group, the serum N-terminal telopeptide of type I collagen (NTX1) level in the EA group was lower, and the serum procollagen type I N-terminal propeptide (PINP) concentration was higher. In addition, the expression of Beclin 1, microtubule-associated protein I light chain 3 (LC3B) and P62 was inhibited in the senile osteoporosis rats after EA treatment. EA can effectively alleviate aging-related bone loss and improve the microstructure of bone tissue in senile osteoporosis rats, and the regulation of autophagy might be one of the important mechanisms.

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.

S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation.

Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. This study aimed to explore the effect of S-equol on different degrees of menopausal OA in female Sprague-Dawley (SD) rats induced by estrogen deficiency caused by bilateral ovariectomy (OVX) combined with intra-articular injection of mono-iodoacetate (MIA). Knee joint histopathological change; serum biomarkers of bone turnover, including N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX-I) and N-terminal telopeptide of type I collagen (NTX-I); the cartilage degradation biomarkers hyaluronic acid (HA) and N-terminal propeptide of type II procollagen (PIINP); and the matrix-degrading enzymes matrix metalloproteinases (MMP)-1, MMP-3 and MMP-13, as well as the oxidative stress-inducing molecules nitric oxide (NO) and hydrogen peroxide (H2O2), were assessed for evaluation of OA progression after S-equol supplementation for 8 weeks. The results showed that OVX without or with MIA injection induced various severity levels of menopausal OA by increasing pathological damage, oxidative stress, and cartilage matrix degradation to various degrees. Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation.

Bone turnover biomarkers reflect radiation-induced bone injuries in women with non-metastatic rectal cancer.

Preoperative radiotherapy (RT) for non-metastatic rectal cancer reduces local recurrence rates but can cause pelvic insufficiency fractures. Despite the high morbidity from RT-induced skeletal injuries, predictive and preventive measures are lacking. How these injuries are reflected by bone biomarkers are largely unknown. The aim was to assess longitudinal changes in bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. This longitudinal cohort study includes 47 women with non-metastatic rectal cancer treated with surgery ± preoperative RT with or without chemotherapy. Sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr postoperatively. Pelvic magnetic resonance imaging was used for detection of skeletal injury. Sixteen of 36 (44%) irradiated women had radiation-induced bone injuries and were compared to 11 women (RT-) and 20 women (RT+) without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-induced bone injuries. The difference in mean change of CTX (p=.037) and BALP (p=.042) was conferred by longitudinal regression analyses adjusted for serum estradiol. Serum sclerostin and bioactive sclerostin remained stable over time. Taken together, bone markers may be of interest for future research on fracture prediction or preventive measures in women susceptible to radiation-induced bone injury. Due to few measure points, the full pattern cannot be captured regarding the relation over time between bone biomarkers and skeletal injury from irradiation.

Serum level of sclerostin and vitamin D in children with epilepsy

BackgroundEpileptic children can pose an additional risk of poor bone health; this study aimed to evaluate the influence of anti-seizure medications (ASMs) on vitamin D level and sclerostin as a bone turnover biomarker in children with epilepsy.Subject and methodsThis case–control comparative study was conducted on 180 children aged from 5–18 years diagnosed with epilepsy according to the definition of the International League Against Epilepsy on ASMs for more than 3 months and were classified into 90 epileptic children on ASM monotherapy and 90 epileptic children on ASM polytherapy, in addition to 90 healthy children age- and sex-matched who served as controls. After obtaining basic data, laboratory investigations were performed, including serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, vitamin D, and serum sclerostin.ResultsWhen we compared epileptic patients to the control group, there was a statistically significant low level of vitamin D, calcium, and phosphorus and a high level of sclerostin among both epileptic groups with mono or polytherapy. Sclerostin has a statistically significant negative correlation with vitamin D, alkaline phosphatase and parathyroid hormone. Additionally, it has a negative correlation with serum phosphorus, but without a significant correlation. On the other hand, sclerostin has a statistically positive correlation with age and serum calcium, but without a significant correlation. Multiple linear regression analyses were conducted to predict the contributing factors of sclerostin. Only duration of treatment and BMI were significant predictors of high levels of sclerostin. In contrast, the other factors failed to show any significant contribution.ConclusionThe present study showed that ASMs modulate the serum levels of sclerostin and vitamin D hence, might be involved in their adverse effects on bone.

Ethanol consumption in non-human primates alters plasma markers of bone turnover but not tibia architecture

Ethanol consumption is associated with positive, negative, and neutral effects on the skeletal system. Our previous work using a nonhuman primate model of voluntary ethanol consumption showed that chronic ethanol use has an impact on skeletal attributes, most notably on biochemical markers of bone turnover. However, these studies were limited by small sample sizes and resulting lack of statistical power. Here, we applied a machine learning framework to integrate data from 155 monkeys (100 ethanol and 55 controls) to identify the bone features associated with chronic ethanol use. Specifically, we analyzed the influence of ethanol consumption on biomarkers of bone turnover and cancellous and cortical bone architecture in tibia. We hypothesized that chronic ethanol use for 6 months to 2.5 years would result in measurable changes to cancellous features and the biochemical markers compared to control animals. We observed a decrease in bone turnover in monkeys exposed to ethanol; however, we did not find that ethanol consumption resulted in measurable changes in bone architecture.