Telopeptide Of Type Research Articles

Biochemical Bone Markers During the Transition Period Are Not Influenced by Parenteral Treatment With a High Dose of Cholecalciferol but Can Predict Milk Fever in Dairy Cows

Despite being studied extensively, there are still many knowledge gaps in milk fever prevention and it is still a prevalent disease. Various interventions have been used in its prevention; however, none has proven to be entirely effective. The study aimed to assess the effectiveness of high dose vitamin D3 parenteral (intramuscularly) administration and the mechanism of its action by studying blood minerals and biochemical bone markers. Further, we assessed the potential of biochemical bone markers, measured in the close-up dry period, as predictors of clinical milk fever after calving. The study was conducted on 56 high yielding, clinically healthy dairy cows, before their 4th or higher lactation. They were divided into three groups based on season (summer and winter) and administration (vitamin D). The winter group was considered as the control group. Cows (n = 13) were parenterally administered a single dose of 10 million IU of vitamin D3 (DUPHAFRAL® D3) ranging between 10 and 2 days before calving (median = 3 days). Each cow was blood sampled once during four sampling period ranges: ~1 month before calving, 10 to 2 days before calving, 12–48 h after calving and 10–20 days after calving. The samples were analyzed for blood minerals, bone specific alkaline phosphatase (bALP) and C-terminal telopeptide of type I collagen (CTx), alkaline phosphatase, and estradiol. Values were compared between samplings and groups. A receiver operating characteristic (ROC) analysis and logistic regression were used to assess the diagnostic accuracy of biochemical bone markers in predicting milk fever. In this study high dose vitamin D3 supplementation did not statistically reduced the incidence of milk fever (milk fever incidences were 15.4, 39.1, and 25% in the vitamin D, winter and summer groups, respectively). A significant effect of vitamin D3 administration on blood minerals or biochemical bone markers was not found at any sampling. We found that the use of biochemical bone markers in the close-up dry period to predict clinical milk fever was applicable only in the winter (housed) group. The area under the curve (AUC) for bALP was 0.804 and 0.846 for CTx using ROC analysis. The bALP curve had the best ratio at the cut-off point 13.85 U/L with 90% sensitivity and 64.3% specificity. While CTx had the ratio of 90% sensitivity and 78.6% specificity at the cut-off point 0.149 ng/mL. Close-up dry dairy cows with CTx ≥0.121 ng/mL had a 3.8 times higher chance of succumbing to milk fever. We were unable to prove that high dose vitamin D3 parenteral administration is a viable technique for milk fever prevention. Biochemical bone markers are a promising tool for predicting milk fever; however, further studies are needed to confirm their clinical use.

Bone turnover markers in patients with isolated femoral shaft fracture undergoing systemic ozone therapy

Efferent physical therapy holds promise as an adjunct to the combination treatment of femoral fractures in young, working-age individuals. The aim of the study was to investigate the dynamics of bone turnover markers at different stages of femoral fracture consolidation in patients undergoing ozone therapy. The study enrolled 20 men (group 2, 47.8 ± 3.5 years) with a femoral shaft fracture (AO/ASIF 32А, 32В). The control group (group 1, 46.8 ± 3.7 years) comprised 10 healthy males. Subgroup 2a (n = 10) was assigned to receive standard therapy; subgroup 2b (n = 10) was assigned to receive standard therapy complemented by minor autohemotherapy (MAHT) at 20 mg/L ozone concentrations. On days 7, 30 and 90, fracture consolidation was assessed on the RUST scale and blood levels of С-terminal telopeptides of type I collagen (bCTx, pg/ml) and procollagen type I carboxy-terminal propeptide (PICP, ng/ml) were measured. On day 7, the total RUST score in subgroups 2a and 2b was 4 points; on day 30, it was 6.5 and 8.7 points, respectively, and on day 90, it reached 10 and 11.5 points, respectively. Bone mineral density was as high as 90% in the MAHT subgroup vs. 78% in subgroup 2а, indicating faster bone healing. On day 30, bCTx levels in subgroup 2b were higher than in subgroup 2a (2289.4 [2145.3; 2365.4] vs. 1894.6 [1745.3; 2098.2], respectively. On day 7, PICP was significantly elevated in subgroup 2b in comparison with subgroup 2a; its levels peaked on days 30 and 90 (day 30: 268.3 [231.2; 286.3] vs. 183.2 [174.6; 195.6]; day 90: 584.6 [512.3; 589.3] vs. 351.2 [312.3; 369.4]. Thus, MAHT produces a positive effect on the quality and intensity of bone healing in men with isolated closed femoral shaft fractures.

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Efferent physical therapy holds promise as an adjunct to the combination treatment of femoral fractures in young, working-age individuals. The aim of the study was to investigate the dynamics of bone turnover markers at different stages of femoral fracture consolidation in patients undergoing ozone therapy. The study enrolled 20 men (group 2, 47.8 ± 3.5 years) with a femoral shaft fracture (AO/ASIF 32А, 32В). The control group (group 1, 46.8 ± 3.7 years) comprised 10 healthy males. Subgroup 2a (n = 10) was assigned to receive standard therapy; subgroup 2b (n = 10) was assigned to receive standard therapy complemented by minor autohemotherapy (MAHT) at 20 mg/L ozone concentrations. On days 7, 30 and 90, fracture consolidation was assessed on the RUST scale and blood levels of С-terminal telopeptides of type I collagen (bCTx, pg/ml) and procollagen type I carboxy-terminal propeptide (PICP, ng/ml) were measured. On day 7, the total RUST score in subgroups 2a and 2b was 4 points; on day 30, it was 6.5 and 8.7 points, respectively, and on day 90, it reached 10 and 11.5 points, respectively. Bone mineral density was as high as 90% in the MAHT subgroup vs. 78% in subgroup 2а, indicating faster bone healing. On day 30, bCTx levels in subgroup 2b were higher than in subgroup 2a (2289.4 [2145.3; 2365.4] vs. 1894.6 [1745.3; 2098.2], respectively. On day 7, PICP was significantly elevated in subgroup 2b in comparison with subgroup 2a; its levels peaked on days 30 and 90 (day 30: 268.3 [231.2; 286.3] vs. 183.2 [174.6; 195.6]; day 90: 584.6 [512.3; 589.3] vs. 351.2 [312.3; 369.4]. Thus, MAHT produces a positive effect on the quality and intensity of bone healing in men with isolated closed femoral shaft fractures.

PERK activator CCT020312 prevents inflammation-mediated osteoporosis in the ovariectomized rats

Objective To investigate the therapeutic effects of PERK activator CCT020312 (CCT) on inflammation-mediated osteoporosis (IMO) in ovariectomized rats. Methods Rats were divided into Sham, IMO, IMO + 1 mg/kg CCT and IMO + 2 mg/kg CCT groups. IMO models were constructed by bilateral ovariectomy (OVX) on 1st day followed by injection with magnesium silicate (Talc) on the 59th day. Sham rats did not undergo OVX surgery and were injected with saline instead of Talc. From 60th to 79th day, rats were treated with DMSO (vehicle control) in the Sham and IMO groups, and 1 or 2 mg/kg CCT020312 in treatment groups. Osteopontin (OPN), osteocalcin (OCN), tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type I collagen (CTX-I), and pro-inflammatory factors were measured on the 80th day. ProdigyDEXA was used to evaluate bone mineral density and content (BMD/BMC). Bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number (Tb.N), and trabecular separation (Tb.Sp) was assessed using 3D micro-CT scanner. Results CCT up-regulated Conn.D, BV/TV, and Tb.N, but down-regulated Tb.Sp in IMO rats. Besides, the declined femoral BMD and BMC in IMO rats were elevated after CCT treatment. Besides, IMO rats represented declined OPN and OCN, as well as increased TRAP, CTX-I, and pro-inflammatory factors, whereas those in the treatment groups were ameliorated regarding these indexes, with 2 mg/kg CCT showing better effect. Conclusion PERK activator CCT020312 can be served as a new therapeutic option for the protection against bone loss in the OVX rat model associated with inflammation probably by manipulating inflammatory factors.

Effect of alendronate on the femoral metaphyseal defect under carbamazepine in ovariectomized rats

BackgroundThe use of antiepileptic drugs and estrogen deficiency put forward higher requirements for bone defect regeneration. The present study investigated the effects of alendronate (ALN) on femoral bone defect in ovariectomized (OVX) rats under the influence of carbamazepine (CBZ).MethodsOne hundred female SD rats at 3 months of age were either sham-operated or OVX and divided into four groups: sham control (CON); OVX control (OVX); ovariectomized rats treated with CBZ via gavage (75 mg/kg/day; CBZ); ovariectomized rats treated with CBZ plus ALN (2 mg/kg/day; CBZ-ALN). A critical-sized femoral metaphyseal bone defect was established in all female SD rats. Animals from the CBZ and CBZ-ALN groups received drugs by gavage the day after bone defect surgery was performed. After the rats were sacrificed, the defected area located in the distal femur was harvested for evaluation by microcomputed tomography (micro-CT), hematoxylin and eosin (HE) staining, and Masson’s trichrome staining. The samples were also analyzed by biomechanics and immunohistochemical evaluation (IHC). Besides, biochemical analysis evaluates all serum samples.ResultsThe present study showed that ovariectomy changed the microstructural parameters of bone. The use of CBZ further decreased femur bone mass while treatment with ALN prevented bone loss. Compared to OVX and CBZ groups, CBZ-ALN group promoted bone neoformation and enhanced the ultimate load of the femur bone. However, the group of CBZ-ALN did not return to normal levels compared with the CON group. Besides, we noticed that CBZ-ALN group reduced tartrate-resistant acid phosphatase-5b (Tracp-5b) expression and had no significant effect on the expression of osteocalcin (OCN) and type I collagen (Col-I) in IHC compared with CBZ group. Biochemical analysis results presented that systemic delivery of CBZ showed pernicious effects on bone formation and resorption in ovariectomized rats, with the worse effects on C-terminal crosslinked telopeptide of type I collagen (CTX-1). Besides, a significant decrease in CTX-1 levels was observed in CBZ-ALN group as compared to the group of CBZ.ConclusionThese results demonstrated that ALN can effectively reverse the effects of CBZ on the microarchitectural properties of bone, and thus can have a positive effect on local bone neoformation in rats with osteoporosis.Clinical relevanceThe dose of 2 mg/kg ALN improves the negative effect of prescription of CBZ at 75 mg/kg and promotes bone neoformation of femoral bony deficits.

Serum levels of bone formation and resorption markers in relation to vitamin D status in professional gymnastics and physically active men during upper and lower body high-intensity exercise

Purpose/introductionTo compare serum levels of bone turnover markers in athletes and non-athletes, and to evaluate the relationship between serum levels of vitamin D metabolites and exercise-induced changes in biomarker levels.MethodsSixteen elite male artistic gymnasts (EG; 21.4 ± 0.8 years-old) and 16 physically active men (the control group, PAM; 20.9 ± 1.2 years-old) performed lower and upper body 30-s Wingate anaerobic tests (LBWT and UBWT, respectively). For biomarker analysis, blood samples were collected before, and 5 and 30 min after exercise. Samples for vitamin D levels were collected before exercise. N-terminal propeptide of type I collagen (PINP) was analysed as a marker of bone formation. C-terminal telopeptide of type I collagen (CTX) was analysed as a marker of bone resorption.ResultsUBWT fitness readings were better in the EG group than in the PAM group, with no difference in LBWT readings between the groups. UBWT mean power was 8.8% higher in subjects with 25(OH)D3 levels over 22.50 ng/ml and in those with 24,25(OH)2D3 levels over 1.27 ng/ml. Serum CTX levels increased after both tests in the PAM group, with no change in the EG group. PINP levels did not change in either group; however, in PAM subjects with 25(OH)D3 levels above the median, they were higher than those in EG subjects.ConclusionVitamin D metabolites affect the anaerobic performance and bone turnover markers at rest and after exercise. Further, adaptation to physical activity modulates the effect of anaerobic exercise on bone metabolism markers.

Evaluation of Gingival Crevicular Fluid and Serum Tartrate-resistant Acid Phosphatase Levels in Subjects with Clinically Healthy Periodontium and Chronic Periodontitis - A Clinico-biochemical Study.

Background:Periodontitis is a chronic inflammatory disease with conglomerate etiology making it difficult to diagnose at the early stages. Potential biomarkers in gingival crevicular fluid (GCF) would determine the presence of the current disease activity, predict sites vulnerable for future breakdown, and assess the response to periodontal interventions. Merely elevated levels of inflammatory soft-tissue markers do not indicate bone destruction. Since there is no single ideal biomarker established, bone-related biomarkers such as telopeptide of type I collagen, osteocalcin, calprotectin, osteopontin, and tartrate-resistant acid phosphatase (TRAP) seem to hold great promise as predictive markers to determine bone destruction and active phases in the disease progression. The present study is intended to explore the biologic plausibility of the levels of TRAP in health and chronic periodontitis.Materials and Methods:The present cross-sectional clinico-biochemical study comprised 30 systemically healthy subjects with 15 periodontally healthy and 15 chronic periodontitis subjects who were age and gender matched. GCF and blood samples were collected from all the patients. TRAP estimation was done in both the samples using an enzyme-linked immunosorbent assay kit. The data were analyzed using independent t-test and Pearson correlation test.Results:Serum and GCF TRAP levels in chronic periodontitis subjects were significantly higher when compared to the periodontally healthy group. There were no significant correlations found among serum and GCF TRAP levels with increasing age and gender in both the groups. An increase in disease severity, i.e., increase in probing pocket depth and clinical attachment level, did not show correlation with the GCF and serum TRAP levels in the chronic periodontitis group.Conclusion:Based on the findings of the present study, increased GCF TRAP levels in chronic periodontitis seem to be a potential marker for identifying ongoing periodontal destruction.

Characterization of Mineral and Bone Metabolism Biomarkers in a Chinese Consanguineous Twin Family with Primary Hypertrophic Osteoarthropathy.

Purpose Primary hypertrophic osteoarthropathy (PHO) is a rare, autosomal, recessive genetic disease characterized by digital clubbing, periostosis, and pachydermia. The underlying cause for the pathogenesis of this disease is a defect in prostaglandin E2 (PGE2) degradation, caused by mutations in HPGD or SLCO2A1. In this study, we describe the clinical characteristics, SLCO2A1 mutations, and bone metabolic markers of a PHO pedigree from a Chinese consanguineous twin family. Methods Whole blood and urine samples were collected from all the family members. All the exons and exon-intron boundaries of the HPGD and SLCO2A1 genes were amplified using polymerase chain reaction (PCR) and sequenced. The biomarkers of mineral and bone metabolism, including calcium, phosphorus, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), bone Gla-protein (BGP), C-terminal telopeptide of type I collagen (β-CTX), and urinary calcium/creatinine ratio (Uca/Ucr) were detected. Results A homozygous (nonsense) mutation in the SLCO2A1 gene (c.1807C >T/p.R603∗) was detected in the proband. Five heterozygous carriers were also identified among his relatives, including his twin brother. The serum BGP (225.5 ng/ml), β-CTX (4112 pg/ml), and Uca/Ucr (0.63) levels were significantly elevated, while the 25(OH)D (37.1 nmol/L) level was reduced in the proband. The proband's twin brother displayed increased levels of β-CTX (901 pg/ml) and insufficiency of 25(OH)D (67.29 nmol/L), while the other heterozygous carriers only displayed 25(OH)D insufficiency. Conclusion The patients with PHO displayed an active state of bone reconstruction. There may be a lack of vitamin D, accompanied by an increase in BGP and β-CTX levels. Heterozygous mutations of SLCO2A1 might lead to mild PHO.

Association between osteoporosis and hepatitis B cirrhosis: a case-control study.

Hepatitis B virus (HBV)-related cirrhosis is associated with decreased bone mineral density (BMD); however, the mechanism is yet unknown. To assess the incidence of osteoporosis in patients with HBV-associated cirrhosis and relevant mechanisms. A total of 80 hospitalized patients with HBV-associated cirrhosis and 80 healthy controls were enrolled. The levels of serum osteocalcin, total procollagen type 1 amino-terminal propeptide, β-C-terminal telopeptide of type I collagen (β-CTX), and 25-hydroxy vitamin D3 (25(OH)D3) was evaluated in the cirrhosis group. The BMDs of the lumbar spine (P<0.001) and hip joints (P=0.015) in the cirrhosis group were significantly lower than those in the controls. The incidence of osteoporosis in the cirrhosis group was significantly higher than that in the control group (P<0.001). Compared to the patients of the Child-Pugh grade A and B, the BMD of lumbar spine and 25(OH)D3 was significantly decreased in patients of grade C, while β-CTX was elevated. Patients in the cirrhosis group faced a higher risk of osteoporosis as compared to the controls(P<0.001). Enhanced bone resorption accounted for increased risk of osteoporosis in severe cirrhosis. Thus, HBV-associated cirrhosis was a risk factor for osteoporosis.

Bone Mineral Density and Bone Turnover 10 Years After a Single 5 mg Dose or Two 5-Yearly Lower Doses of Zoledronate in Osteopenic Older Women: An Open-Label Extension of a Randomized Controlled Trial.

Intravenous zoledronate reduces fracture risk (5 mg at 18-month intervals) and prevents bone loss (doses of 1 to 5 mg for 3 to >5 years), but the duration of action of a single 5 mg dose and the effects of lower doses beyond 5 years are unknown. We report the second open-label extension (years 5 to 10) of a 2-year randomized, multidose, placebo-controlled, double-blinded trial. A total of 116 older women who completed 5 years of participation either continued observation without further treatment (zoledronate 5 mg and placebo at baseline) or received repeat doses of 1 or 2.5 mg zoledronate (zoledronate 1 mg and zoledronate 2.5 mg at baseline, respectively). Outcomes were spine, hip, and total body bone mineral density (BMD) and serum markers of bone turnover. After a single 5 mg dose of zoledronate, mean BMD at the lumbar spine and total hip was maintained at or above baseline levels for 9 and 10 years, respectively. The mean level of the bone resorption marker β-C-terminal telopeptide of type I collagen (β-CTX) was at least 25% lower than that in the placebo group for 9 years. In women administered 5-yearly doses of 2.5 mg zoledronate, mean BMD at the total hip and lumbar spine was maintained at or above baseline levels for 9 and 10 years, respectively. Redosing with 1 or 2.5 mg zoledronate at 5 years reduced bone turnover markers for 3 to 4 years. BMD increased for 3 to 4 years after redosing with 1 mg zoledronate. In the group given 5-yearly 2.5 mg zoledronate, β-CTX was at least 20% lower than that in the placebo group for 10 years. Both a single baseline 5 mg dose of zoledronate and 5-yearly doses of 1 and 2.5 mg zoledronate prevented bone loss at hip and spine for 8 to 10 years in older postmenopausal women. Clinical trials to evaluate the effects on fracture risk of these very infrequent and lower doses of zoledronate are justified. © 2021 American Society for Bone and Mineral Research (ASBMR).

Bone Impairment in a Large Cohort of Chinese Patients With Tumor-Induced Osteomalacia Assessed by HR-pQCT and TBS.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density (aBMD) in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral (distal radius and tibia) and axial (lumbar spine) skeleton using high-resolution peripheral quantitative computed tomography (HR-pQCT) and trabecular bone score (TBS) and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry (DXA) or HR-pQCT scans were enrolled. Compared with age-, sex-, and body mass index (BMI)-matched healthy controls, TIO patients (n=113) had lower volumetric BMD, damaged microstructure, and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS (<1.35) was higher than that with low L1 to L4 aBMD Z-score (Z ≤ -2) (43.9% versus 89.6%, p < 0.001). Higher intact fibroblast growth factor 23 (iFGF23), intact parathyroid hormone (iPTH), alkaline phosphatase, and β-isomerized C-terminal telopeptide of type I collagen (β-CTx) levels, more severe mobility impairment, and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection. © 2021 American Society for Bone and Mineral Research (ASBMR).

Detection and evaluation of haemophilic arthropathy: Which tools may be considered more reliable.

Progressive arthropathy is the main cause of morbidity in patients with severe haemophilia. Diagnostic imaging can detect even subclinical arthropathy and impact prophylactic treatment. However, in most clinical settings the regular joint evaluation and follow-up are based on clinical evaluation and patient's personal reporting of problems, while diagnostic imaging is not regularly employed. The aim of our prospective study was to assess how ultrasound (US), clinical examination, patient's subjective assessment and certain laboratory biomarkers correlate with magnetic resonance imaging (MRI) for detection and evaluation of haemophilic arthropathy in order to determine which tool is the most reliable. The study included 30 patients with severe haemophilia (age range 16-49years). MRI (IPSG), US (HEAD-US), clinical examination (HJHS 2.1) and patient's subjective assessment of elbows, knees and ankles were performed; additionally, blood samples for laboratory analysis were taken (s-25-OH vitamin D, s-ferritin, s-C-terminal telopeptide of type I collagen, s-N-terminal propeptide of type I procollagen and s-cartilage oligomeric matrix protein). MRI results were used as a reference standard for joint status. Pearson's r was used to assess correlation of other methods with MRI. The correlation with MRI was the highest for US (r=.92), considerably higher than for clinical evaluation (r=.62) and patient's subjective assessment (r=.66). There was no correlation between the presence or degree of haemophilic arthropathy and any of the laboratory biomarkers. The results of our study warrant the inclusion of US into the regular follow-up of patients with severe haemophilia, where the equipment and staffing permit.

Bone turnover markers to assess jawbone quality prior to dental implant treatment: a case-control study

BackgroundBone quality is as important as bone mineral density in terms of bone strength. Bone turnover markers (BTMs) are clinical indicators of bone quality. In implant dentistry, bone quality is considered equivalent to bone density on radiographic assessments. The purpose of this study was to determine whether the BTM values are reflected in jawbone condition by evaluating the relationship at baseline and during follow-up in patients with prosthodontic implants.Computed tomography (CT) scans were obtained and BTM (osteocalcin, bone-specific alkaline phosphatase, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and crosslinked N-telopeptide of type I collagen) levels in blood samples were measured in partially edentulous eighteen patients before implant surgery. During the follow-up observation after implant surgery, marginal bone loss (MBL) was measured on dental radiography. We investigated the relationship between the presence of BTM abnormalities and radiographic bone density.ResultsMore women than men had abnormal BTM values. Bone turnover was accelerated in the group of women with abnormal BTM values. The density of cancellous bone at the implant placement site was significantly lower in the patients with abnormally high BTM values than in their counterparts with BTM values in the normal range.ConclusionsFemale patients who undergo implant treatments may have reduced bone quality; evaluations of bone strength will require assessments of both BTMs and the density of cancellous bone.

Markers of bone metabolism in children with rickets

The problem of rickets remains relevant due to the widespread prevalence of the disease and unsatisfactory results of diagnosis and treatment. Objective. To identify changes in the biochemical parameters of bone metabolism and to establish their relationship with the clinical condition of children with rickets. Materials and methods . The authors conducted a simultaneous controlled clinical comparative study of 108 children aged from 5 months to 2 years. C-terminal telopeptide of type I collagen (CrossLaps), calcitriol, calcitonin, osteocalcin, and blood osteoprote-gerin were analyzed by the enzyme-linked immunosorbent assay method. The level of calcium was determined by colorimetric method, phosphorus — by photometric test. Alkaline phosphatase activity was evaluated in blood serum by an optimized kinetic method. Results . We determined a decrease in the level of serum calcitriol, calcitonin, calcium and phosphorus, as well as an increase in the concentration of the C-terminal telopeptide of type I collagen, osteocalcin, parathyroid hormone, osteoprotegerin, acid and alkaline phosphatase activity. The greatest increase in the level of osteoprotegerin was recorded in children with the II degree of rickets, both in acute and subacute course. The concentration of osteocalcin was increased in all groups of patients with the highest values in patients with the II degree of rickets, regardless of the course of the disease. The activity of acid phosphatase in the blood of patients was also increased. A decrease in the concentration of calcitriol, calcitonin, calcium and phosphorus in the blood was observed in all groups of children with rickets. Conclusion. The authors recorded the correlations between the studied indicators of bone metabolism in patients with rickets. An increase in the level of osteoprotegerin is apparently a new link in the pathogenesis of rickets.

A 24-Week Physical Activity Intervention Increases Bone Mineral Content without Changes in Bone Markers in Youth with PWS.

Bone mineral density (BMD) is of concern in Prader-Willi syndrome (PWS). This study compared responses to a physical activity intervention in bone parameters and remodeling markers in youth with PWS (n = 45) and youth with non-syndromic obesity (NSO; n = 66). Measurements occurred at baseline (PRE) and after 24 weeks (POST) of a home-based active games intervention with strengthening and jumping exercises (intervention group = I) or after a no-intervention period (control group = C). Dual x-ray absorptiometry scans of the hip and lumbar spine (L1-L4) determined BMD and bone mineral content (BMC). Bone markers included fasting bone-specific alkaline phosphatase (BAP) and C-terminal telopeptide of type I collagen (CTx). Both I and C groups increased their hip BMD and BMC (p < 0.001). Youth with PWS-I increased their spine BMC from PRE to POST (p < 0.001) but not youth with PWS-C (p = 1.000). Youth with NSO (I and C) increased their spine BMC between PRE and POST (all p < 0.001). Youth with PWS showed lower BAP (108.28 ± 9.19 vs. 139.07 ± 6.41 U/L; p = 0.006) and similar CTx (2.07 ± 0.11 vs.1.84 ± 0.14 ng/dL; p = 0.193) than those with NSO regardless of time. Likely, the novelty of the intervention exercises for those with PWS contributed to gains in spine BMC beyond growth. Bone remodeling markers were unaltered by the intervention.

Abstract 2059: Exploiting machine learning in local treatment strategies in cancer patients with bone metastases: A real world clinical trial

Abstract With rising life expectancy in cancer patients with bone metastases, the need for local treatment (LT) is expanding. Machine learning (ML) could create reasonable generalizations, the purpose of this article was to evaluate the use of ML model in LT strategies. Patients were treated by an interdisciplinary team in Shanghai Sixth People's Hospital. Visual analog scale (VAS) and Quality of Life (QoL) Questionnaire Bone Metastases Module scores were analyzed before, 1 week, 1, 3, and 6 months after treatments. ML models were used to calculate LT probability, and confusion matrix was used to calculate the accuracy, precision, recall and F1 score of models. ML models were further used to calculate pathological fracture (PF) probability in lung cancer patients. Of 386 patients enrolled between 2016 and 2017, 101 patients underwent LT. Significant improved VAS and pain domains scores were observed in 27 surgery patients at 1, 3 and 6m, while functional domains scores at 3 and 6m. All five scores improved significantly in 46 percutaneous osteoplasty patients at 1w, 1 and 3m. Significant improved VAS and pain domains scores were observed in 28 radiation patients at 1 and 3m, while functional domains scores at 3m. Compared with team decision-making, decision tree was superior to support vector machine and Bayesian neural networks in model building. The VAS scale, primary cancer, Frankel classification, Mirels score, C-terminal telopeptide of type I collagen (CTx), age, mid-fragment of osteocalcin (MID), character of bone metastases, CA153, and visceral metastases were included in the DT model. In 386 patients, the values of decision tree for the accuracy, precision, recall and F1 score were 86.53%, 78.44%, and 64.90% and 0.69 respectively. 124 lung cancer patients were used to calculate PF probability by decision tree. We also put driving gene mutation and five differentially expressed proteins into the model. The VAS scale, character of bone metastases, age, driving gene mutation, C-terminal telopeptide of type I collagen (CTx), mid-fragment of osteocalcin (MID) and enolase 1 (ENO1) were included in the DT model. The sensitivity, specificity and accuracy of DT model was 90.52%, 87.19% and 77.72%. Appropriate LT provided significant pain relief and improvement in QoL. The ML model is effective in helping physicians determine which patient may be the candidate for LT. Citation Format: Hui Zhao, zhiyu wang, jing Sun, yifeng Gu, mengdi Yang, guangyu Yao. Exploiting machine learning in local treatment strategies in cancer patients with bone metastases: A real world clinical trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2059.

Female Distance Runners Display Altered Bone Remodeling In Fasted Blood And 24 Hour Urine Biomarkers

An increase in underlying bone remodeling is associated with increased fracture risk. The International Osteoporosis Foundation recommend overnight fasted plasma C-terminal cross linked telopeptide type 1 collagen (CTX) and N-terminal propeptide of type 1 procollagen (P1NP) as bone turnover markers (BTM) of homeostatic bone remodeling. Reflected by an increase in plasma CTX, endurance exercise increases bone resorption acutely for a number of hours post-exercise. Female distance runners (FDR) engage in frequent weight-bearing endurance exercise that may alter homeostatic bone remodeling and fracture risk. PURPOSE: To compare bone remodeling in FDR and non-athletic controls (CON). METHODS: Daily 24 h urine samples and fasted morning blood samples were collected for 7 consecutive days of habitual activity in 7 FDR (training volume ≥ 60 km/week; mean ± SD age: 24.1 ± 4.6 y, height: 1.70 ± 0.05 m, mass: 58.5 ± 5.5 kg, fat %: 18 ± 4%) and 11 CON (≤3 h/week intentional vigorous physical activity; mean ± SD age: 23.9 ± 4.1 y, height: 1.67 ± 0.05 m, mass: 64.5 ± 4.4 kg, fat %: 33 ± 6%) who provided prior informed consent for a study which had ethical approval. Plasma CTX and P1NP was measured by automated immunoassay (Roche Diagnostics) and urinary N-terminal cross linked telopeptide type 1 collagen (NTX) by ELISA (Osteomark). Data were pooled and analyzed independent of participant. Data violated the assumption of normality and are reported as the median (IQR). Groups were compared by Mann-Whitney U test. RESULTS: Median CTX was 31.4% lower (0.393(0.147) vs 0.573(0.333) ng/ml; p<0.001; d=0.7) and P1NP was 14.5% lower (55.12(32.39) vs 64.43(16.73) ng/ml; p=0.012; d=0.5) in FDR compared to CON. In contrast, median 24 h NTX was 36.7% higher in FDR (434.2 (572.7) vs 317.6 (302.6) nM bone collagen equivalents; p=0.033; d=0.4) compared to CON. CONCLUSION: Lower overnight fasted CTX and P1NP are deemed devoid of influence exerted by previous exercise or food intake and may indicate an adaptive, regulatory effect of chronic exercise training on systemic (homeostatic) bone remodeling in FDR. By contrast, 24 h urine NTX captures total bone resorptive activity, including response to exercise and diet accrued during the previous 24 h and appear to confirm significantly greater net daily bone resorption in FDR compared to CON.

Differential time responses in inflammatory and oxidative stress markers after a marathon: An observational study

ABSTRACT Acute and adaptive changes in systemic markers of oxidatively generated nucleic acid modifications (i.e., 8-oxo-7,8-dihydro-2ʹ-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo)) as well as inflammatory cytokines (i.e., C-reactive protein, interleukin-6, interleukin-10, and tumour necrosis factor alpha), a liver hormone (i.e., fibroblast growth factor 21 (FGF21)), and bone metabolism markers (sclerostin, osteocalcin, C-terminal telopeptide, and N-terminal propeptide of type 1 procollagen) were investigated following a marathon in 20 study participants. Immediate changes were observed in inflammatory cytokines, FGF21, and bone metabolism markers following the marathon. In contrast, no immediate changes in urinary excretion of 8-oxodG and 8-oxoGuo were evident. Four days after the marathon, decreased urinary excretion of 8-oxodG (-2.9 (95% CI -4.8;-1.1) nmol/24 h, P < 0.01) and 8-oxoGuo (-5.8 (95% CI -10.3;-1.3) nmol/24 h, P = 0.02) was observed. The excretion rate of 8-oxodG remained decreased 7 days after the marathon compared to baseline (-2.3 (95%CI -4.3;-0.4) nmol/24 h, P = 0.02), whereas the excretion rate of 8-oxoGuo was normalized. In conclusion marathon participation immediately induced a considerable inflammatory response, but did not increase excretion rates of oxidatively generated nucleic acid modifications. In fact, a delayed decrease in oxidatively generated nucleic acid modifications was observed suggesting adaptive antioxidative effects following exercise. Abbreviations 8-oxodG: 8-oxo-7,8-dihydro-2ʹ-deoxyguanosine; 8-oxoGuo: 8-oxo-7,8-dihydroguanosine; CI: confidence interval; CTX: C-terminal telopeptide of type 1 collagen; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunosorbent assay; FGF21: Fibroblast growth factor 21; h: hour; hsCRP: high sensitivity C-reactive protein; IL: interleukin; IQR: interquartile range; MS: mass spectrometry: P1NP: N-terminal propeptide of type 1 procollagen; TNFα: tumour necrosis factor alpha; UPLC: ultra-performance liquid chromatography

Factors of mineral homeostasis impairment and bone mineral density loss in women with central hypogonadism

Objective The aims of the study were to estimate markers of mineral turnover and bone mineral density (BMD) in young women with central hypogonadism (CH) in comparison with healthy young and postmenopausal women, and to reveal the possible impact of different factors on BMD. Method We examined 73 patients with CH (mean age 25 [21.2; 30.5] years, mean duration of amenorrhea 5 [2.3; 10.1] years), 47 young healthy women (mean age 24 [23.1; 28.0] years) and 50 healthy women in natural postmenopause (mean age 56 [53; 58] years, mean duration of 6 [2; 10] years since last menstrual period). Women with CH were examined before and after 12 months of treatment with 17β-estradiol 2 mg and dydrogesterone 10 mg in continuous sequential fashion. Results Levels of calcium, alkaline phosphatase, and C-terminal telopeptide of type I collagen were statistically higher in women with CH without treatment than in young healthy women but did not differ from those in postmenopausal women. Prevalence of T-score ≤−2.5 standard deviations was higher in CH than in postmenopause both in lumbar vertebrae and total femur. Factors that were responsible for lower BMD in young women with CH included the duration of hypoestrogenism, primary amenorrhea, and hypoandrogenism. Conclusion Central hypogonadism at a young age poses a higher risk of bone metabolism impairment than physiological menopause.

A Preliminary Study of the Effect of Hyperadrenocorticism on Calcium and Phosphate Concentrations, Parathyroid Hormone and Markers of Bone Turnover in Dogs.

Reports on the effects of hyperadrenocorticism (HAC) on bone turnover in dogs are largely confined to radiographic studies. The aim of this study was to more accurately assess bone turnover in dogs with HAC by measuring circulating total and ionized calcium and phosphate concentrations, both intact and whole parathyroid hormone (PTH) concentrations and markers of both osteoblastic (osteocalcin) and osteoclastic [carboxyterminal cross-linked telopeptide of type 1 collagen (ICTP) and urine aminoterminal telopeptide of type 1 collagen (NTX) activity]. Dogs with HAC and a control group were prospectively enrolled for comparison. Results from 49 dogs with HAC were compared with 39 dogs from a hospital control population. Plasma intact and whole PTH concentrations were determined using a human immunoradiometric assay. Serum osteocalcin and NTX concentrations were measured using human enzyme linked immunosorbent assays. Serum ICTP concentration was measured using a human radioimmunoassay. Total calcium concentrations in dogs with HAC (2.67 ± 0.25 mmol/L) were not significantly different than in the control group (2.67 ± 0.14 mmol/L). By contrast, phosphate concentrations were significantly (P = 0.0143) higher in dogs with HAC (1.46 ± 0.30 mmol/L) compared to the control group (1.28 ± 0.33 mmol/L). The median intact PTH concentration in HAC dogs was 9.25 (range, 1.34–95.45) pmol/L, which was significantly (P < 0.0001) higher than in the control group [median, 3.88 (range, 2.01–10.31) pmol/L]. Whole PTH concentrations were also significantly (P < 0.0001) higher in the HAC group [median, 4.61 (range, 0.56–125.16) pmol/L] compared to the control group [median, 1.83 (range, 0.88–6.81) pmol/L]. Serum osteocalcin and urine NTX concentrations were not significantly different between the two groups of dogs. The median ICTP concentration in dogs with HAC was 2.98 (range, 1.15–6.62) ng/mL which was significantly (P < 0.0001) lower than in the control dogs [median, 7.30 (range, 3.68–21.25) ng/mL]. Both whole and intact PTH concentrations are increased in dogs with HAC compared to a hospital control population. This does not however appear to be associated with a decrease in bone formation (as assessed by osteocalcin) or an increase in bone resorption (as assessed by ICTP and urine NTX).