Procollagen Aminoterminal Propeptide Research Articles

POLYCYSTIC OVARY SYNDROME AND BONE TURNOVER IN POSTMENOPAUSAL WOMEN

Considering the metabolic and hormonal changes associated with polycystic ovary syndrome (PCOS), their potential affect bone health has been proposed. The aim of the current study was to evaluate the effect of several hormonal and metabolic alterations associated with polycystic ovary syndrome on bone in postmenopausal women. Materials and methods: The study included 56 patients with PCOS and 42 women without this disease aged 50–65 years. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) of the lumbar spine and femoral neck. Serum levels of amino-terminal propeptide of procollagen 1 (P1NP) and carboxy-terminal telopeptide of type I collagen (b-CTx), as well as levels of parathyroid hormone (PTH), vitamin D (25(OH)D3), anti-Mullerian hormone (AMH), insulin, testosterone (T), 17-hydroxyprogesterone (17-OHP), dehydroepiandrostenedione sulfate (DHEAS), follicle stimulating hormone, luteinizing hormone, and estradiol were determined. The HOMA-IR index and anthropometric indicators were calculated. Statistical data were analyzed by nonparametric testing using BioStat Pro 6.2.2.0 software (AnalystSoft Inc., Walnut, USA). Quantitative data are presented as median and quartiles 1 and 3 (Me [Q1; Q3]); The significance of intergroup differences was established using the Mann–Whitney U test (p<0.05). To identify relationships between indicators, a univariate analysis was carried out with the calculation of the Spearman rank correlation coefficient (r). Results. Women with PCOS had late-onset menopause (p=0.007) and a higher body mass index (BMI, p=0.009) than the control group. Additionally, women with PCOS had higher levels of DHEAS, total T, and 17-OHP than controls. P1NP and b-CTx were significantly different from controls (p=0.028 and p=0.032, respectively). A direct relationship was found between BMI and the activity of the resorption marker b-CTx (r=0.342, p=0.002) and an inverse collinear relationship between AMH values with b-CTx (r=–0.507, p=0.001). BMD in PCOS was higher compared to controls. An inverse relationship exists between BMD of L1–L4 and b-CTx level (r=–0.387, p=0.026) and positive with insulin (r=0.267, p=0.042), AMH (r=0.561, p=0.031) and testosterone (r=0.458, p=0.039). Higher DHEAS levels were associated with higher femoral neck BMD (r=0.473, p=0.035). P1NP was negatively correlated with femoral neck BMD (r=-0.429, p=0.038). Conclusions. Bone mineral density in women with polycystic ovary syndrome declines more slowly with age compared to their peers, possibly due to the effects of excess androgens and insulin. In postmenopausal women with polycystic ovary syndrome, metabolic processes in bone tissue accelerate, while bone resorption exceeds bone formation. Thus, women affected by polycystic ovary syndrome may be considered at risk of developing osteopenic syndrome.

The effects of alfacalcidol combined with calcitonin in the treatment of osteoporosis and its influence on levels of inflammation.

To investigate the effectiveness of Alfacalcidol combined with Calcitonin in the treatment of osteoporosis and its influence on the degree of pain, bone metabolism indexes, bone mineral density and inflammatory factor levels. In this retrospective study, 110 patients with osteoporosis treated in The Second Affiliated Hospital of Shandong First Medical University from January 2019 to June 2021 were selected as the study subjects. According to different treatment methods, these patients were divided into an observation group and a control group with 55 cases in each group. Patients from the control group were treated with the alfacalcidol capsules alone, while those from the observation group were treated with the alfacalcidol capsules combined with intramuscular calcitonin injection. Patients in both groups were treated for 6 months continuously. The treatment effect, visual analogue scale (VAS) score and Oswestry disability index (ODI), bone mineral density (BMD), serum markers levels such as calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase-5b (TRACP-5b), insulin-like growth factor (IGF-1), type I procollagen amino terminal propeptide (PINP) and β-collagen special sequence (β-Crosslaps), the levels of inflammatory factor including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), quality Life Questionnaire Core 30 (QLQ-C30) scores and incidences of adverse reactions were evaluated and compared between the two groups. The effective rate of patients in the observation group was 90.91%, which was significantly higher than 74.54% in the control group (P<0.05). There was no significant difference in the term of VAS score, ODI score, serum markers levels, bone mineral density, inflammatory levels, QLQ-C30 before treatment between the two groups. Compared with the control group, the post-treatment VAS score, ODI score, the levels of IL-6, TNF-α, TRACP-5b, PINP and β-Crosslaps in the observation group were obviously lower, while the post-treatment QLQ-C30, bone mineral density, Ca, P, ALP, IGF-1 levels were significantly higher (all P<0.05). No statistical differences were found in the incidences of adverse reactions between the two groups (P>0.05). The combination of Alfacalcidol combined with Calcitonin is effective in the treatment of osteoporosis patients, which can effectively improve the levels of bone metabolism indexes and bone mineral density, alleviate the symptoms, enhance the life quality and reduce the levels of inflammation. Therefore, it is worth promoting.

Effects of depressive symptoms on osteoporotic bone metabolism and prognosis of joint replacement surgery in elderly male patients with femoral neck fractures.

To investigate the effect of depressive symptoms on osteoporotic bone metabolism and prognosis of joint replacement surgery in elderly male patients with femoral neck fractures. 102 elderly male patients with femoral neck fractures hospitalized in the Beijing Hospital from January 2017 to January 2019 were included. The patients with femoral neck fractures were divided into the depression group and the control group. The observation indicators included: bone mineral density, serum alkaline phosphatase, serum calcium, serum phosphorus, 25-hydroxy-vitamin D, osteocalcin, Type I procollagen amino-terminal propeptide, serum β-isomer of C-terminal telopeptide of type I collagen, hip function scores, and pain visual analogue scale at pre- and post-operative examinations. The BMD was significantly lower in the depressed group than in the control group [either for lumbar spine or hip, P<0.05]. Serum 25-(OH)-D levels and serum OC levels were lower (both P<0.05) in the depression group, while serum -CTX levels were higher in the depression group than in the control group (P<0.05). Depression severity (GDS score) was negatively correlated with BMD (r=-0.456, P<0.05), 25(OH)D (r=-0.546, P<0.05), and OC (r=-0.215, P<0.05), while positively correlated with β-CTX (r=0.372, P<0.05). The Harris scores of the depression group were lower than the control group (P<0.001). In the control group, VAS scores decrease at 12 months postoperatively while in the depressed group, VAS scores increased (P<0.001). Depression is a risk factor for low bone mineral density and fracture, and adversely affects functional recovery and pain relief after artificial femoral head replacement. Special care should be taken for those patients with depressive symptoms in orthopedic practice.

The assessment value of pathological condition of serum adiponectin and amylin in primary osteoporosis and its correlation analysis with bone metabolism indexes.

This paper explores the assessment value of pathological condition of serum adiponectin (APN) and amylin in primary osteoporosis (POP) and their correlation with bone metabolism indexes. From January 2019 to June 2021, 79 cases of POP patients were selected as the research objects. A test of the patients' bone density was conducted, and clinical grading of POP was via T value (normal, mild, moderate, severe). The analysis of the assessment value of pathological condition of serum APN and amylin for POP and their association with bone metabolism indexes in patients was performed. APN and amylin in patients were declined with POP's aggravation. APN of 5.15 μg/mL or less and amylin of 15.38 pmol/L or less were risk factors influencing the aggravation of pathological condition of POP (P< 0 .0 5). The area under the curve (AUC) of combined detection of APN and amylin to assess the severity of POP was elevated vs. alone test of amylin (P< 0.05). 25-hydroxyvitamin D (25-(OH) D) and total type 1 procollagen amino-terminal propeptide (t-PINP) in patients were descended with the aggravation of pathological condition of osteoporosis (P < 0.05). At the same time, no distinct differences were presented in the three groups of type I collagen hydroxyl terminal peptide b degradation product (β-CTX) and N-terminal osteocalcin (N-MID) (P> 0.05). APN, amylin, 25-(OH)D, β-CTX, and t-PINP were negatively linked with POP clinical grade (P< 0.05). APN and amylin were associated with 25-(OH) D, β-CTX, t-PINP (P< 0.05), and APN and amylin were not linked with N-MID (P> 0.05). Serum APN and amylin are provided with evaluation values for the severity of POP and are associated with bone metabolism in patients.

Correlation of Serum Estradiol with Bone Mineral Density and Bone Metabolism in Patients of Postmenopausal Type 2 Diabetes Mellitus Complicated with Osteoporosis.

Type 2 diabetes mellitus (T2DM) complicated with osteoporosis, is a systemic metabolic disease that affects postmenopausal women. This disease is closely related to the lack of estrogen. This study aims to demonstrate the correlation between serum estradiol (E2) levels and osteoporosis, bone mineral density, and bone metabolism indicators in postmenopausal women with T2DM complicated with osteoporosis (T2DM-OP). 130 postmenopausal women with T2DM were divided into the T2DM group (n=62) and the T2DM-OP group (n=68) according to bone mineral density (BMD). In addition, 80 postmenopausal women with average blood glucose and bone density were selected as the healthy control group. We compare the serum levels of E2, bone metabolism indicators, and biochemistry indexes among the three groups of participants. Compared with the healthy control and T2DM groups, the BMD and serum level of E2 in T2DM-OP patients were significantly decreased, while the serum levels of bone alkaline phosphatase, type I procollagen amino-terminal propeptide, osteocalcin, and β-collagen C-terminal collagen cross-links were significantly increased. The serum levels of E2 in the postmenopausal T2DM-OP patients are positively correlated with BMD and negatively correlated with bone resorption indicators.

Early effects of ovariectomy on bone microstructure, bone turnover markers and mechanical properties in rats

BackgroundFragility fracture is one of the most serious consequences of female aging, which can increase the risk of death. Therefore, paying attention to the pathogenesis of postmenopausal osteoporosis (PMOP) is very important for elderly women.Methods and materialsForty 12-week-old female rats were divided into two groups including the ovariectomy (OVX) group and the control group. Four rats in each group were selected at 1, 4, 8, 12 and 16 weeks after operation. Vertebral bones and femurs were dissected completely for micro-Computed Tomography (micro-CT) scanning, biological modulus detection and histomorphological observation.ResultsIn OVX group, bone volume/total volume (BV/TV), bone trabecular connection density (Conn.D) and trabecular bone number (Tb.N) decreased significantly with time (P < 0.05). The elastic modulus of femur in OVX group was lower than that in control group, but there was no significant difference between them (P > 0.05). Over time, the tartrate resistant acid phosphatase (TRAP), osteocalcin (BGP), type I procollagen amino terminal propeptide (PINP) and type I collagen carboxy terminal peptide (CTX-I) in OVX group increased significantly (P < 0.05). The micrographs of the OVX group showed sparse loss of the trabecular interconnectivity and widening intertrabecular spaces with time.ConclusionThe bone loss patterns of vertebral body and femur were different in the early stage of estrogen deficiency. The bone turnover rate of OVX rats increased, however the changes of biomechanical properties weren’t obvious.

Clinical Efficacy of Kangguzeng Capsule Combined with Basic Anti Osteoporosis Drugs in the Treatment of Postmenopausal Osteoporosis

Objective: To investigate the clinical efficacy of kangguzeng capsule combined with basic anti osteoporosis drugs in the treatment of postmenopausal osteoporosis. Methods: 96 patients who met the inclusion criteria in the First Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from June 2020 to June 2021 were included in the study. According to the random number table, the patients were divided into treatment group (48 cases) and control group (48 cases). The control group was treated with basic anti osteoporosis drugs, including alendronate sodium and calcitriol capsules; the treatment group was given kangguzeng Capsule on the basis of the control group. The patients were followed up regularly, and the TCM clinical syndrome score, pain visual analogue score (VAS), serum type I procollagen amino terminal propeptide (PINP) and type I collagen carboxyl terminal peptide were observed and recorded (β- CTX) and other indicators. Results: the clinical syndrome scores of the treatment group and the control group were improved. Compared with those before treatment, the clinical syndrome scores of the treatment group and the control group decreased significantly after treatment, and the difference was statistically significant (P < 0.05). The score of the treatment group was significantly better than that of the control group after treatment, and the difference was statistically significant (P < 0.05); In terms of VAS score, compared with that before treatment, the VAS score of the treatment group and the control group decreased significantly after treatment, and the difference was statistically significant (P < 0.05). The score of the treatment group after treatment was significantly better than that of the control group after treatment, and the difference was statistically significant (P < 0.05); In terms of PINP, the PINP of the treatment group and the control group were significantly higher than that before treatment (P < 0.05). The PINP of the treatment group was significantly higher than that of the control group after treatment (P < 0.05); stay β- In terms of CTX, the treatment group and the control group were compared after treatment and before treatment, β- CTX decreased significantly, and the difference was statistically significant (P < 0.05) β- CTX and control group after treatment β- There was significant difference in CTX (P < 0.05).Conclusion: kangguzeng capsule combined with basic anti osteoporosis drugs is effective in the treatment of postmenopausal osteoporosis. It can improve the clinical symptoms, biochemical indexes of bone metabolism and bone mineral density, and improve the quality of life of patients.

ANOVA-Based Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer with Bone Metastasis and Rehabilitation Treatment

This study was to analyze the magnetic resonance imaging (MRI) characteristics of prostate cancer patients with bone metastasis and the difference in the rehabilitation effect of patients with different bone metastases. The MRI, diffusion weighted imaging (DWI), magnetic resonance elastic imaging (MRE), and MRI + DWI + MRE imaging were performed on 200 prostate cancer patients in the First Affiliated Hospital of Kunming Medical University hospital. The prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate volume in patients with bone metastases were analyzed. The sensitivity, specificity, and accuracy of the four detection methods of bone metastases in prostate cancer were detected. In addition, the changes of the bone metabolism index β-special collagen sequence (β-CTX), type I procollagen amino terminal propeptide (PINP), and osteocalcin (BGP) of the patients were analyzed and compared before and after the treatment. The results showed that the levels of PSMA4 (17.35 ± 51.64 ng/mL) and PSA (15.86 ± 6.33 ng/mL) in nonbone metastatic prostate cancer patients were much lower than those of osteogenic bone metastases (668.95 ± 47.13 ng/mL and 202.15 ± 31.53 ng/mL), mixed bone metastases (637.63 ± 41.35 ng/mL and 186.45 ± 24.86 ng/mL) prostate patients. The sensitivity (96.25%), specificity (89.85%), and accuracy (98.53%) of MRI + DWI + MRE in the prostate cancer bone metastasis were obviously higher than those of MRI (86.46%, 78.31%, and 90.31%), DWI (88.11%, 82.53%, and 91.43%), and MRE (83.36%, 76.94%, and 89.76%). The levels of β-CTX (0.41 ± 0.07 ng/mL), PINP (39.04 ± 6.38 ng/mL), and BGP (17.56 ± 4.22 ng/mL) after treatment in patients with nonbone metastasis prostate cancer were greatly lower than those of osteogenic bone metastases (0.66 ± 0.08 ng/mL, 51.45 ± 7.45 ng/mL, and 33.65 ± 6.14 ng/mL) and patients with mixed bone metastases (0.75 ± 0.12 ng/mL, 53.66 ± 9.22 ng/mL, and 31.24 ± 5.73 ng/mL), showing statistically obvious differences ( P &lt; 0.05 ). In short, the sensitivity, specificity, and accuracy of MRI + DWI + MRE in detection of prostate cancer bone metastasis were better than those of a single examination method, showing significant impacts on the rehabilitation of patients with prostate cancer bone metastasis.

Establishment of a regression model of bone metabolism markers for the diagnosis of bone metastases in lung cancer

BackgroundThe aim of this study was to establish a regression equation model of serum bone metabolism markers. We analyzed the diagnostic value of bone metastases in lung cancer and provided laboratory evidence for the early clinical treatment of bone metastases in lung cancer.MethodsA total of 339 patients with non-metastatic lung cancer, patients with lung cancer with bone metastasis, and patients with benign lung disease who were treated in our hospital from July 2012 to October 2015 were included. A total of 103 patients with lung cancer in the non-metastatic group, 128 patients with lung cancer combined with bone metastasis group, and 108 patients with benign lung diseases who had nontumor and nonbone metabolism-related diseases were selected as the control group. Detection and analysis of type I collagen carboxyl terminal peptide β-special sequence (β-CTX), total type I procollagen amino terminal propeptide (TPINP), N-terminal-mid fragment of osteocalcin (N-MID), parathyroid hormone (PTH), vitamin D (VitD3), alkaline phosphatase (ALP), calcium (CA), phosphorus (P), cytokeratin 19 fragment (F211), and other indicators were performed. Four multiple regression models were established to determine the best diagnostic model for lung cancer with bone metastasis.ResultsAnalysis of single indicators of bone metabolism markers in lung cancer was performed, among which F211, β-CTX, TPINP, and ALP were significantly different (P < 0.05). The ROC curve of each indicator was less than 0.712. Based on the multiple regression models, the fourth model was the best and was much better than a single indicator with an AUC of 0.856, a sensitivity of 70.0%, a specificity of 91.0%, a positive predictive value of 82.5%, and a negative predictive value of 72.0%.ConclusionMultiple regression models of bone metabolism markers were established. These models can be used to evaluate the progression of lung cancer and provide a basis for the early treatment of bone metastases.

The influence of a sustained 10-day hypoxic bed rest on cartilage biomarkers and subchondral bone in females: The FemHab study.

This study assessed the influence of a 10‐day hypoxic bed rest on cartilage biomarkers and subchondral bone density across the patellofemoral joint (PFJ). Within clinical settings hypoxic tissue may arise in several types of disorders. Furthermore, a hypoxic environment is being considered for space flight habitats in the near future. Female participants (N = 12) participated in this study comprising three 10‐day interventions: hypoxic ambulation (HAMB), normoxic bed rest (NBR), and hypoxic bed rest (HBR). Venous samples were collected prior to (day −2: Pre) and during the intervention (days 2 and 5), immediately before reambulation (D11) and 24 hr post intervention (R1). Blood samples were analyzed for: aggrecan, hyaluronan, Type IIA procollagen amino terminal propeptide (PIIANP), and cartilage oligomeric matrix protein (COMP). Total bone mineral density (BMD) in eight regions (2 mm × 10 mm) across the PFJ was determined. The three interventions (HAMB, HBR, and NBR) did not induce any significant changes in the cartilage biomarkers of hyaluronan or PIIANP. Aggrecan increased during the HAMB trial to 2.02 fold the Pre value. COMP decreased significantly in both NBR & HBR compared to HAMB on D5. There were significant differences in BMD measured across the PFJ from cortical patellar bone (735 to 800 mg/cm3) to femur trabecular (195 to 226 mg/cm3). However, there were no significant changes in BMD from Pre to Post bed rest. These results indicate that there were no significant detectable effects of inactivity/unloading on subchondral bone density. The biomarker of cartilage, COMP, decreased on D5, whereas the addition of hypoxia to bed rest had no effect, it appears that hypoxia in combination with ambulation counteracted this decrease.

Analysis of bone mineral density and bone metabolism in elderly hip fracture patients of different genders

Objective To understand changes and characteristics of bone mineral density(BMD)and early-stage bone turnover biochemical markers in elderly hip fracture patients of different genders. Methods This was a retrospective cohort study.A total of 1 161 elderly patients with hip fractures hospitalized in Beijing Jishuitan Hospital from May 2015 to December 2017 were enrolled.Based on gender, patients were divided into the female group(n=831)and the male group(n=330). Clinical data, BMD, serum type I procollagen amino terminal propeptide(P1NP), and 25-hydroxyvitamin D3 [25-(OH)VD3], type I collagen cross-linked carboxy terminal peptide beta degradation products(β-CTX), osteocalcin(OC)and parathyroid hormone(PTH)were measured and compared between the two groups. Results Of the 1 161 elderly patients with hip fractures, 831 were female and 330 were male.The BMD of the lumbar vertebrae and the total hip in the female and male groups showed that 30.4%(353/1 161)and 6.8%(79/1 161)had T≥-1.0 SD respectively; 36.6%(425/1 161)and 44.7%(519/1 161)had -2.5 SD 0.05). The levels of tP1NP, β-CTX, OC and PTH in females were higher than those in males, and the level of 25-(OH)VD3 was lower than that in males(all P<0.05). As the T value decreased, β-CTX and OC increased and 25-(OH)VD3 decreased accordingly(all P<0.05). Conclusions With the increase of age, the BMD T value in elderly patients with hip fractures shows a downward trend, but its decline in women is faster and earlier.Overall, the BMD T value is not sensitive enough for osteoporosis diagnosis or hip fracture prediction in the elderly, especially in men.In the early stage of fractures, the bone turnover biochemical markers show varying degrees of change, and bone resorption and bone formation are both reduced.The significance of OC, β-CTX and VD levels in early bone metabolic abnormalities requires further study. Key words: Osteoporosis; Hip fractures; Bone density

Study protocol: design and rationale for an exploratory phase II randomized controlled trial to determine optimal vitamin D3 supplementation strategies for acute fracture healing

BackgroundObservational studies have found that 75% of healthy adult fracture patients (ages 18–50) have serum 25-hydroxyvitamin D (25(OH)D) levels < 30 ng/mL. Although lower serum 25(OH)D levels have yet to be correlated to fracture healing complications or poor fracture outcomes, many orthopedic surgeons are routinely prescribing vitamin D supplements to improve fracture healing in healthy non-osteoporotic patients. To address this gap in the literature, we propose a phase II exploratory randomized controlled trial comparing three vitamin D3 dosing regimens for early surrogate treatment response.MethodsWe will conduct a 4-arm blinded exploratory phase II trial in 96 adults aged 18–50 years with a closed or low-grade open (Gustilo type I or II) tibial or femoral shaft fracture. Eligible patients will be randomized in equal allocation ratio of 1:1:1:1 to one of the treatment groups: (1) 150,000 IU loading dose vitamin D3 plus daily dose placebo; (2) loading dose placebo plus 4000 IU vitamin D3 per day, (3) loading dose placebo plus 600 IU vitamin D3 per day, or (4) loading dose placebo plus daily dose placebo. The primary outcome is fracture healing, assessed as follows: (1) clinical fracture healing measured using the Function IndeX for Trauma, (2) radiographic fracture healing measured using the Radiographic Union Score for Tibial fractures, and (3) biological fracture healing measured using serum levels of cross-linked C-terminal telopeptides of type I collagen and amino-terminal procollagen propeptides of collagen type I. The main secondary outcome will be assessed by measuring serum 25(OH)D levels. All outcome analyses will be exploratory and adhere to the intention-to-treat principle. Per-protocol sensitivity analyses will also be conducted.DiscussionStudy results will be disseminated through a publication in an academic journal and presentations at orthopedic conferences. Study results will inform dose selection for a large definitive randomized controlled trial and provide preliminary clinical data on which dose may improve acute fracture healing outcomes in healthy adult patients (18–50 years) at 3 months.Trial registrationVita-Shock (A Blinded Exploratory Randomized Controlled Trial to Determine Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing) was registered at ClinicalTrials.gov (identifier NCT02786498) prior to enrollment of participants.

Effect of vitamin K2 on bone mineral density and serum cathepsin K in female osteoporosis patients

Purpose: To investigate the influence of vitamin K2 on bone mineral density, bone metabolism and serum tissue protease K (cathepsin K) in female patients with osteoporosis.Method: A total of 210 osteoporosis patients in Affiliated Hospital of Nanjing University of Chinese Medicine who met the inclusion criteria were selected from January 2017 to January 2018. The patients were randomly divided into vitamin K2 group, strontium renate group and blank control group (70 patients/group). Strontium ranelate group was orally given 2 g of strontium ranelate daily, while vitamin K2 group received 15 mg of Gulikang capsule 3 times a day. Bone mineral density (BMD) and serum osteocalcin (BGP), β-collagen degradation product (β-crosslaps), type I procollagen amino terminal propeptide (PINP), cathepsin K (cathe K) and TRAP were measured prior to drug treatment, and six months after surgery, using standard procedures.Results: Relative to the blank control, hip and lumbar spine density of vitamin K2 and strontium ranelate groups increased to varying degrees. Strontium ranelate group had significantly higher bone mineral density (BMD) than any other groups (p &lt; 0.05), and also had the lowest osteoclast activity (β-crosslaps and TRAP) and the highest osteogenic activity (BGP and PINP). On the other hand, osteoclast and osteogenic activities increased significantly (p &lt; 0.05) in the vitamin K2 group.Conclusion: Appropriate vitamin K2 treatment improves BMD in the hip and waist of women with osteoporosis by promoting osteogenic activity, and by reducing osteoclast activity and cathepsin K expression.Keywords: Osteoporosis, Bone mineral density, Strontium ranelate, Vitamin K2

Influence of 131I therapy on thyroid function and bone metabolism in patients with Graves disease

Objective To analyze the influence of 131I therapy on thyroid function and bone metabolism in patients with Graves's disease. Methods From February 2014 to January 2017, 60 Graves patients in Shaoxing Central Hospital were studied.According to the random number table method, they were divided into observation group and control group, with 30cases in each group.The patients in the control group were treated with methimidazole, and the patients in the observation group were treated with 131I combined with methimidazole.After treatment for 1 month, the clinical efficacy, three triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH) concentration, parathyroid hormone (PTH), procollagen amino terminal propeptide (PINP) and osteocalcin (OCN), 1, 25 hydroxyvitamin D3(1, 25(OH)2D3), bone mineral density (BMD), the incidence of goiter, exophthalmos, incidence of hypothyroidism of the two groups were observed. Results After treatment, the total effective rate of the observation group was 93.33%, which of the control group was 73.33%.There was statistically significant difference between the two groups (χ2=4.320, P=0.037). Before treatment, the levels of FT3, FT4, TSH between the two groups had no statisticallysignificant differences (all P>0.05). After treatment, the FT3, FT4 levels of the observation group were (12.41±1.24)pmol/L, (18.33±4.25)pmol/L, respectively, which were significantly lower than those of the control group[ (15.98±1.30)pmol/L, (22.75±4.31)pmol/L](t=10.884, P 0.05). After treatment, the PINP and OCN of the observation group were (43.21±3.69)μg/L, (27.42±6.48)μg/Lrespectively, which were significantly lower than those of the control group [(55.87±3.71)μg/L, (31.84±6.55)μg/L](t=13.252, P<0.0001; t=2.628, P=0.011). The PTH, 1, 25 (OH)2D3 and BMD of the observation group were (55.87±3.18)ng/L, (25.16±2.84)nmol/L, (0.98±0.17)g/cm2, respectively, which were significantly higher than those in the control group [(49.89±3.21)ng/L, (23.2±2.76)nmol/L, (0.85±0.15)g/cm2] (t=7.249, P<0.001; t=2.697, P=0.009; t=3.141, P=0.003). After treatment, the incidence rate of exophthalmos in the observation group was 6.67%, which in the control group was 30.00%, there was statistically significant difference between the two groups (χ2=5.455, P=0.020). The incidence rate of goiter of observation group was 3.33%, which was significantly lower than 23.33% of the control group (χ2=5.192, P=0.023). The incidence rate of hypothyroidism of the observation group was 13.33%, which in the control group was 10.00%, the difference between the two groups was not statistically significant (χ2=0.162, P=0.688). Conclusion 131I therapy has good clinical effect on Graves disease.It can effectively improve the thyroid function and bone metabolism and has high safety.It is worthy of widely application and popularizing in clinic. Key words: Hyperthyroidism; Thyroid function tests; Iodine radioisotopes; Bone density; Osteocalcin; Thyroxine; Thyrotropin-releasing hormone

Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men.

Selective serotonin reuptake inhibitors (SSRIs) have been shown to have a clinically significant impact on bone metabolism. To explore this further, we aimed to determine whether these agents are associated with serum markers of bone turnover utilising a population-based sample of men (n = 1138; 20-96year) participating in the Geelong Osteoporosis Study. Blood samples were obtained and the bone resorption marker, C-telopeptide (CTx) and formation marker, type 1 procollagen amino-terminal-propeptide (PINP) were measured. Anthropometry and socio-economic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Lifetime mood disorders were assessed using semi-structured clinical interviews. Thirty-seven (3.3%) men reported using SSRIs. Age was an effect modifier in the association between SSRIs and markers of bone turnover. Among younger men (20-60year; n = 557), adjusted mean CTx and PINP values were 12.4% [16.7 (95% CI 14.6-18.8) vs 19.1 (95% CI 18.7-19.4)pg/ml, p = 0.03] and 13.6% [5.6 (95% CI 4.9-6.3) vs 6.4 (95% CI 6.3-6.6)pg/ml, p = 0.02] lower among SSRI users compared to non-users, respectively. No differences in SSRI use and markers of bone turnover were detected among older men (61-94year; all p > 0.05). These patterns persisted after further adjustment for activity, alcohol, smoking, SES, depression, bone active medications and other antidepressants. Our data suggest that SSRI use is associated with alterations in bone turnover markers among younger men. The observed decreases in both CTx and PINP are likely to contribute to a low bone turnover state and increased skeletal fragility with this potential imbalance between formation and resorption resulting in subsequent bone loss.

Serum N-propeptide of collagen IIA (PIIANP) as a marker of radiographic osteoarthritis burden.

ObjectiveCartilage homeostasis relies on a balance of catabolism and anabolism of cartilage matrix. Our goal was to evaluate the burden of radiographic osteoarthritis and serum levels of type IIA procollagen amino terminal propeptide (sPIIANP), a biomarker representing type II collagen synthesis, in osteoarthritis.MethodsOA burden was quantified on the basis of radiographic features as total joint faces with an osteophyte, joint space narrowing, or in the spine, disc space narrowing. sPIIANP was measured in 1,235 participants from the Genetics of Generalized Osteoarthritis study using a competitive enzyme-linked immunosorbent assay. Separate multivariable linear regression models, adjusted for age, sex, and body mass index and additionally for ipsilateral osteophytes or joint/disc space narrowing, were used to assess the independent association of sPIIANP with osteophytes and with joint/disc space narrowing burden in knees, hips, hands and spine, individually and together.ResultsAfter full adjustment, sPIIANP was significantly associated with a lesser burden of hip joint space narrowing and knee osteophytes. sPIIANP was associated with a lesser burden of hand joint space narrowing but a greater burden of hand osteophytes; these results were only evident upon adjustment for osteoarthritic features in all other joints. There were no associations of sPIIANP and features of spine osteoarthritis.ConclusionsHigher cartilage collagen synthesis, as reflected in systemic PIIANP concentrations, was associated with lesser burden of osteoarthritic features in lower extremity joints (knees and hips), even accounting for osteoarthritis burden in hands and spine, age, sex and body mass index. These results suggest that pro-anabolic agents may be appropriate for early treatment to prevent severe lower extremity large joint osteoarthritis.

Clinical study of medicinal-cake-separated moxibustion for senile osteoporosis

To explore the clinical efficacy and partial mechanism of medicinal-cake-separated moxibustion for senile osteoporosis. Sixty cases of senile osteoporosis were randomly divided into an observation group and a control group according to the random digits table, 30 cases in each one. The two groups were both treated with basic treatment of western medicine. The acupoints included four groups:① Dazhui (GV 14), Dazhu (BL 11) and Ganshu (BL 18); ② Zhongwan (CV 12), Danzhong (CV 17) and Zusanli (ST 36); ③ Pishu (BL 20), Shenshu (BL 23) and Mingmen (GV 4); ④ Shenque (CV 8) and Guanyuan (CV 4). Each group of acupoints was selected for one treatment. The observation group was treated with medicinal-cake-separated moxibustion, and the medicinal cake was consisted of fructus psoraleae (30 g), prepared rehmannia root (30 g), atractylodes (30 g), codonopsis pilosula (30 g), epimedium herb (20 g), rhizoma curculiginis (20 g), syzygium aromaticum (5 g) and cinnamon (5 g). The control group was treated with wheat-flour-cake moxibustion. Each acupoint was treated with 5 moxa cones in the two groups. The treatment was given once every other day for six months. The symptom score, lumbar and hip bone mineral density (BMD), serum type Ⅰ procollagen amino-terminal propeptide (PINP) and serum β-type Ⅰ collagen carboxy-terminal peptide (β-CTX) were observed before and after treatment. After treatment, the symptom score and serum β-CTX were significantly lowered (all P<0.05), while the lumbar and hip BMD and serum PINP were significantly increased (all P<0.05) of the two groups. After treatment, the symptom score and serum β-CTX in the observation group were significantly lower than those in the control group (both P<0.05), while the lumbar and hip BMD and serum PINP in the observation group were significantly higher than those in the control group (all P<0.05). The medicinal-cake-separated moxibustion has significant efficacy for senile osteoporosis, which is superior to wheat-cake-se-parated moxibustion.

The Usefulness of Bone Biomarkers for Monitoring Treatment Disease: A Comparative Study in Osteolytic and Osteosclerotic Bone Metastasis Models

BACKGROUND: The skeleton is the most common site of colonization by metastatic cancers. Zoledronic acid (ZA) has been shown to be effective for the treatment of bone metastases regardless of whether the bone lesions are osteolytic or osteoblastic. Biochemical markers of bone turnover may be useful tools to quantify the degree of bone remodeling in the presence of bone metastases. The aim of this work was to establish the correlation between tumor dispersion (bioluminescence) and biochemical markers of bone turnover in two osteolytic and osteoblastic metastasis models in mice. METHODS: The A549M1 cell line that produces osteolytic metastases and the LADOB cell line extracted from a patient with a lung carcinoma and osteoblastic metastases cells were retrovirally transduced with a luciferase reporter gene for in vivo image analysis. Forty-four-week–old mice were inoculated in the left cardiac ventricle with A549M1 or LADOB cells. Twenty mouse of each group were treated with a single dose of ZA (70 μg/kg) 5 days after i.c. Ten animals of each group were sacrificed at 21 and 28 days postinoculation in A549M1 and 60 and 75 days in the LADOB assay. Bioluminescence analysis was quantified 7, 14, 21 ,and 28 days postinoculation in A549M1 mice and 33, 45, 60, and 75 days after inoculation in LADOB mice. Osteocalcin (BGP), aminoterminal propeptide of procollagen I (PINP), carboxiterminal telopeptide of type I collagen (CTX), and 5b isoenzyme of tartrate-resistant acid phosphatase were measured by ELISA (IDS, UK). RESULTS: Bioluminescence imaging revealed a significant increase of tumor burden on time in both osteolytic and osteoblastic mice models. ZA administration resulted in a significant decrease in tumor burden at 21 and 28 days in the A549M1 animals and 60 and 70 days postinoculation in the LADOB line. Biomarkers levels were significantly increased in the untreated group at every point in the osteolytic model. In the osteoblastic model, 2 months after inoculation, all biomarkers were significantly increased. However, 2.5 months postinoculation, only PINP and CTX were significantly increased. Serum bone remodeling markers decreased in ZA-treated mice as compared with tumor groups in both models. With respect to the correlation between bone turnover markers and tumor burden, in the osteolytic model, PINP and BGP demonstrate a strong correlation with bioluminescence in both tumoral and ZA animals, and only CTX was significantly associated with bioluminescence in the group of animals that were not treated with ZA. CONCLUSIONS: We found that the best biomarkers for the diagnosis of both osteolytic and osteoblastic metastasis are formation markers, especially BGP. Moreover, these markers can be useful in the follow-up of the treatment with ZA in both types of metastasis.

The relationship between serum fibrosis markers and restrictive ventricular filling in patients with heart failure with reduced ejection fraction: A technetium-99m radionuclide ventriculography study.

Myocardial fibrosis leads to a restrictive diastolic filling pattern of the left ventricle which is associated with a poor prognosis in patients with heart failure. We investigated the relationship between cardiac fibrosis and restrictive filling pattern of the left ventricle measured by Tc99m left ventriculography in patients with chronic symptomatic heart failure. Serum cardiac extracellular matrix markers including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2,9 (MMP-2,9), and tissue inhibitor of MMP-1 (TIMP-1) were analyzed. Fifty-one (39 males) patients were enrolled. Their median age was 51.8 years, and median left ventricular ejection fraction was 31.9%. Time to peak filling rate of the left ventricle was significantly correlated with serum levels of the three cardiac extracellular matrix markers (TIMP-1, PIIINP, and MMP-2). The patients with a restrictive diastolic filling pattern of the left ventricle (time to peak filling rate = 154 ms) had significantly higher levels of these extracellular matrix markers. In receiver operating characteristic curve analysis, areas under the curve of PIIINP, TIMP-1, and MMP-2 were 0.758, 0.695, and 0.751 to predict the presence of a restrictive pattern. In C-statistics, all three cardiac extracellular matrix markers significantly increased the area under the curve after adding creatinine. In net reclassification improvement and integrated discrimination improvement models, PIIINP and MMP-2 significantly improved the predictive power of age, creatinine and brain natriuretic peptide. In conclusion, serum extracellular matrix markers are significantly correlated with restrictive diastolic filling pattern of the left ventricle in patients with heart failure.

Zoledronic Acid Treatment After Acute Spinal Cord Injury: Results of a Randomized, Placebo-Controlled Pilot Trial

ObjectiveTo determine the effect of intravenous zoledronic acid 5 mg on the extent and course of bone loss after spinal cord injury (SCI). DesignDouble-blind, randomized, placebo-controlled parallel-group trial. SettingAcute in-patient, tertiary-care rehabilitation hospital. ParticipantsConvenience sample of 17 in-patients with SCI <12 weeks before randomization; American Spinal Injury Association Impairment scale A, B, or C and medically stable. Twelve patients were evaluated at the primary endpoint at 6 months. MethodsPatients meeting study criteria were randomly assigned to zoledronic acid 5 mg or matching placebo. Dual x-ray absorptiometry scan and serum for bone markers (type 1 procollagen amino-terminal propeptide, bone-specific alkaline phosphatase, collagen type 1 cross-linked C-telopeptide) were obtained at baseline and after 3 months, 6 months, and the every 6 months for up to 2 years. Main Outcome MeasuresThe primary endpoint was change in bone mineral density (BMD) at the total hip after 6 months; secondary endpoints were changes in BMD at other skeletal sites and changes in levels of serum bone markers. ResultsThe group treated with zoledronic acid had a smaller decrease in BMD at 6 months at the total hip than the placebo group (right: −2.2 ± 3.4% versus −8.6 ± 3.5%, respectively, P = .03; left: −3.7 ± 1.0% versus −12.3 ± 6.9%, P = .03). Differences in BMD at the femoral neck were similar (right: −5.1 ± 6.5% versus −20.0 ± 6.4%, P = .01; left: −1.1 ± 3.5% versus −11.1 ± 7.4%, P = .02) with larger bone loss and smaller between group differences at the knee. Zoledronic acid resulted in a decrease in serum levels of both formation and resorption markers. ConclusionsZoledronic acid is effective at mitigating bone loss after SCI. Duration of efficacy and activity at different skeletal sites may differ from that observed in able-bodied individuals and needs further study.