Levels Of Bone Metabolic Markers Research Articles

Coenzyme Q10 promotes osteoblast proliferation and differentiation and protects against ovariectomy-induced osteoporosis.

Coenzyme Q10 (CoQ10) is a fat‑soluble vitamin‑like substance used for the treatment of a variety of disorders, including osteoporosis. The exact mechanism underlying CoQ10‑mediated protection against osteoporosis remains to be elucidated. The present study aimed to evaluate the effect of CoQ10 on osteoblastic cell proliferation and differentiation, and therapeutic effects on a rat model of osteoporosis. Following treatment with different concentrations of CoQ10, cell proliferation and differentiation of rat bone marrow stromal cells (BMSCs), and expression of osteoblastogenic markers, were measured. Rats with osteoporosis subjected to ovariectomy (OVX) were treated with different concentrations of CoQ10. Serum levels of estrogen and bone metabolism markers were measured. Micro computed tomography scans were used to analyze morphological changes in bones. In addition, mRNA and protein levels of phosphatidylinositol 3,4,5‑trisphosphate 3‑phosphatase and dual‑specificity protein phosphatase PTEN (PTEN)/phosphatidylinositol 4,5‑bisphosphate 3‑kinase (PI3K)/RAC‑alpha serine/threonine‑protein kinase(AKT), were determined. CoQ10 significantly increased the proliferation and osteogenic differentiation of BMSCs in a dose‑dependent manner, with an increased expression of osteogenic markers. CoQ10 significantly decreased bone resorption but exhibited no effect on serum E2 levels invivo. CoQ10 markedly enhanced bone formation. Furthermore, the abundance of p‑PI3K and p‑AKT increased while PTEN levels decreased in a dose‑dependent manner following administration of CoQ10. CoQ10 stimulates the proliferation and differentiation of BMSCs and is effective for the treatment of OVX‑induced osteoporosis in rats. The above effects of CoQ10 may be mediated by activation of the PTEN/PI3K/AKT pathway.

Site-Specific Variations in Bone Mineral Density under Systemic Conditions Inducing Osteoporosis in Minipigs.

Osteoporosis is a systemic bone disease with an increasing prevalence in the elderly population. There is conflicting opinion about whether osteoporosis affects the alveolar bone of the jaws and whether it poses a risk to the osseointegration of dental implants. The aim of the present study was to evaluate the effects of systemic glucocorticoid administration on the jaw bone density of minipigs. Thirty-seven adult female minipigs were randomly divided into two groups. Quantitative computed tomography (QCT) was used to assess bone mineral density BMD of the lumbar spine as well as the mandible and maxilla, and blood was drawn. One group of minipigs initially received 1.0 mg prednisolone per kg body weight daily for 2 months. The dose was tapered to 0.5 mg per kg body weight per day thereafter. The animals in the other group served as controls and received placebo. QCT and blood analysis were repeated after 6 and 9 months. BMD was compared between the two groups by measuring Hounsfield units, and serum levels of several bone metabolic markers were also assessed. A decrease in BMD was observed in the jaws from baseline to 9 months. This was more pronounced in the prednisolone group. Statistically significant differences were reached for the mandible (p < 0.001) and the maxilla (p < 0.001). The administration of glucocorticoids reduced the BMD in the jaws of minipigs. The described model shows promise in the evaluation of osseointegration of dental implants in bone that is compromised by osteoporosis.

Negative impact of high cumulative glucocorticoid dose on bone metabolism of patients with myasthenia gravis.

This current study aimed to evaluate the frequency of low bone mass, osteopenia, and osteoporosis in patients with myasthenia gravis (MG) and to investigate the possible association between bone mineral density (BMD) and plasma levels of bone metabolism markers. Eighty patients with MG and 62 controls BMD were measured in the right femoral neck and lumbar spine by dual-energy X-ray absorptiometry. Plasma concentrations of osteocalcin, osteopontin, osteoprotegerin, tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, dickkopf (DKK-1), sclerostin, insulin, leptin, adrenocorticotropic hormone, parathyroid hormone, and fibroblast growth factor (FGF-23) were analyzed by Luminex®. The mean age of patients was 41.9years, with 13.5years of length of illness, and a mean cumulative dose of glucocorticoids 38,123mg. Patients had significant reduction in BMD of the lumbar, the femoral neck, and in the whole body when compared with controls. Fourteen percent MG patients had osteoporosis at the lumbar spine and 2.5% at the femoral neck. In comparison with controls, patients with MG presented lower levels of osteocalcin, adrenocorticotropic hormone, parathyroid hormone, sclerostin, TNF-α, and DKK-1 and higher levels of FGF-23, leptin, and IL-6. There was a significant negative correlation between cumulative glucocorticoid dose and serum calcium, lumbar spine T-score, femoral neck BMD, T-score, and Z-score. After multivariate analysis, higher TNF-α levels increased the likelihood of presenting low bone mass by 2.62. MG patients under corticotherapy presented low BMD and altered levels of bone markers.

The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following angiotensin-II type 1 receptor blockade

The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini-osmotic pumps during the losartan treatment period. Serum and urine bone metabolism biomarker levels were measured. Bone trabecular and cortical morphometry were quantified in distal femurs, whereas mineral contents were estimated in ashed bones, serum and urine. Finally, the expression of RAS components, the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) was determined. Losartan significantly improved the elevated bone metabolism marker levels and altered trabecular and cortical structures in OVX animals, and restored normal urinary and skeletal mineral levels. Mas receptor inhibition significantly abolished all osteo-protective effects of losartan and enhanced the deleterious effects of OVX. Losartan enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT1) receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG expression in OVX animals. However, A-779 significantly eradicated the effects of losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in the osteo-preservative effects of losartan via Mas receptor, which may add therapeutic value to this well-known antihypertensive agent.

Effect of Androgen Deprivation Therapy on Bone Mineral Density in a Prostate Cancer Cohort in New Zealand: A Pilot Study.

Introduction:Reduction in bone mineral density (BMD) is a common side effect of androgen deprivation therapy (ADT). We aimed to examine the cross-sectional and longitudinal variation in BMD and associated bone markers in patients with nonmetastatic prostate cancer (PCa) managed with and without ADT.Methods:Bone mineral density of the total body, lumbar spine, femoral neck, ultradistal forearm, and one-third distal radius was measured in 88 patients with PCa without bone metastases at baseline and at 6 months. Patients were categorized into 4 groups: (1) acute ADT (≤6 months), (2) chronic ADT (>6 months), (3) former ADT, and (4) no ADT (controls). Serum levels of bone metabolism markers, procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX), were also measured.Results:In the cross-sectional analysis, men receiving chronic ADT had significantly lower total body BMD as compared with former ADT users and men with no ADT. In longitudinal analysis, a significant reduction in ultradistal forearm BMD was observed in both acute and chronic ADT users after 6 months (4.08% and 2.7%, P = .012 and .026, respectively). A significant reduction in total body BMD was observed in acute ADT users (2.99%, P = .032). Former ADT users had a significant increase in both lumbar spine and femoral neck BMD (2.84% and 1.59%, P = .008 and .002, respectively). The changes in BMD were not significantly different between acute and chronic ADT users. In the cross-sectional analysis, higher levels of PINP and CTX were observed in acute and chronic ADT users than former ADT users or PCa controls. In longitudinal analysis, the level of serum PINP and CTX did not change significantly from baseline to 6 months in acute, chronic, and former ADT users, or PCa controls, and the percentage change did not differ among the 4 groups.Conclusions:Men on acute ADT had a similar rate of bone loss to men on chronic ADT. Reversibility in ADT-induced bone loss was observed in those who discontinued ADT. Serum levels of PINP and CTX were higher in acute and chronic ADT users and levels returned to the range of PCa controls when treatment was withdrawn.

Correlating oxidative stress-related factors with bone metabolic markers in older adult male patients exhibiting degenerative osteoporosis in the high-altitude hypoxic area of China: study protocol for a non-randomized controlled trial

Background and objectives: Hypoxia is an important factor that affects bone formation and regulates bone growth. Therefore, many older adult patients living in high-altitude hypoxic areas exhibit osteoporosis. Oxidative stress-related hypoxia-inducible factors can induce abnormal expression of various factors including vascular endothelial growth factor (VEGF), insulin-like growth factor, and endothelin. However, it remains unclear whether these factors influence changes in bone metabolic markers. This study protocol aimed to investigate the correlation between oxidative stress-related factors and bone metabolic markers in older adult male patients with degenerative osteoporosis who reside in the high-altitude hypoxic area of China. Design: A prospective, single-center, non-randomized, controlled trial. Methods: One hundred and twenty older adult male patients with degenerative osteoporosis residing in the high-altitude area of China who receive treatment at the Affiliated Hospital of Qinghai University of China between January 2015 and February 2018 are being included in the osteoporosis group. One hundred and twenty healthy older adult males who concurrently received physical examination are being included in the control group. One day after admission, serum levels of hypoxia-inducible factor 1-alpha (HIF-1α), HIF-2α, VEGF, osteocalcin, and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured using an enzyme-linked immunosorbent assay. Bone mineral density in L1–4 segments, right femoral neck, and the greater trochanter of the femur was detected using dual-energy X-ray absorptiometry. Outcome measures: The primary outcome measure of this study is serum HIF-1α levels at 1 day after admission. Secondary outcome measures include serum levels of HIF-1α, HIF-2α, VEGF, osteocalcin, and TRACP 5b at 1 day after admission, as well as the correlation between serum levels of oxidative stress indicators (HIF-1α, HIF-2α, and VEGF) and bone metabolic markers (osteocalcin and TRACP 5b) at 1 day after admission. Discussion: Findings from this study aim to validate the correlation between oxidative stress-related factors and bone metabolic markers in older adult male patients with degenerative osteoporosis who reside in the high-altitude area of China. Ethics and dissemination: This study was approved by the Ethics Committee of the Affiliated Hospital of Qinghai University of China (approval No. QHY1402G). The study was performed in accordance with the Declaration of Helsinki. Participants are informed of the study protocol and procedures, and sign an informed consent. Participant recruitment, blood sampling, and data collection began in January 2015 and will be ended in February 2018. Outcome measure analysis and trial completion will be in March 2018. Results will be disseminated through presentations at scientific meetings and/or by publication in peer-reviewed journals. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ROC-17012848).

Bone lesions in Chinese POEMS syndrome patients: imaging characteristics and clinical implications.

Objective. Bone lesion is crucial for diagnosing and management of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin change (POEMS) syndrome, a rare plasma cell disorder. This study is to compare the effectiveness of X-ray skeletal survey (SS) and computed tomography (CT) for detecting bone lesions in Chinese POEMS syndrome patients, and to investigate the relationship between bone lesion features and serum markers.Methods. SS and chest/abdomen/pelvic CT images of 38 Chinese patients (26 males, 12 females, aged 21–70 years) with POEMS syndrome recruited at our medical center between January 2013 and January 2015 were retrospectively analyzed. Bone lesions identified by CT were further categorized according to the size (<5 mm, 5–10 mm, >10 mm) and appearance (osteosclerotic, lytic, mixed). The percentage of plasma cells in bone marrow smears, type of immunoglobulin, platelet (Plt), and levels of serum bone metabolic markers and inflammatory factors including alkaline phosphatase (ALP), calcium, phosphate, parathyroid hormone (PTH), beta-isomerized C-telopeptide (β-CTx), vascular endothelial growth factor (VEGF), and interleukin (IL)-6 levels were also recorded.Results. Of the 38 POEMS syndrome patients, the immunoglobulin heavy chain isotypes were IgA in 25 patients (65.8%; 25/38) and IgG in 13 patients (34.2%; 13/38), and the light chain isotypes were λ in 35 patients (92.1%; 35/38) and κ in 3 patients (7.9%; 3/38). There were 23 patients with thrombocytosis. More patients with bone lesions were detected by CT than by SS (97.4% vs. 86.8%). The most commonly affected location was the pelvis (89.5%), followed by the spine, clavicle/scapula/sternum/ribs, skull, and long bones. Of the 38 POEMS syndrome patients, 35 (94.6%) had osteosclerotic and 32 (86.5%) had mixed lesions. Osteosclerotic lesions were typically scattered, variable in size, and plaque-like, whereas mixed lesions were pouch-shaped or soup bubble-like with a clear sclerotic margin and were generally larger. Although the majority of bone lesions were small in size, 23 (62.2%) had at least one lesion >10 mm. There was no correlation between serum marker levels and bone lesion patterns after Bonferroni correction (all P > 0.001).Conclusions. CT is more sensitive and accurate than SS in detecting bone lesions in POEMS syndrome.

Abnormal bone mineral density and bone turnover marker expression profiles in patients with primary spontaneous pneumothorax.

To examine the bone mineral density (BMD) and the role of bone biomarkers, including bone formation marker procollagen type I aminoterminal propeptide (PINP) and N-terminal midmolecule fragment osteocalcin (N-MID), bone resorption marker b-C-telopeptides of type I collagen (b-CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) in the pathogenesis of PSP. Eighty-three consecutive primary spontaneous pneumothorax (PSP) patients (PSP group) and 87 healthy individuals (control group) were enrolled in this study. General data, including gender, age, height, weight, and body mass index (BMI), were recorded. Dual-energy X-ray absorptiometry, electrochemiluminescence immunoassay (ECLIA), and ELISA were used to evaluate bone mineral density and expression levels of bone metabolism markers, including PINP, b-CTX, TRACP5b, N-MID, and 25-hydroxyvitamin D (25-OH VD). Mean height was significantly greater in the PSP group compared with the control group, whereas weight and BMI were lower. Patients in the PSP group had significantly lower average bone mineral density, which mainly manifested as osteopenia (11/12, 91.7%); however, only one patient (8.3%) developed osteoporosis. Serum overexpression of PINP, b-CTX, TRACP5b, and N-MID were found in PSP patients. Expression of 25-OH VD was low in PSP patients. Bone resorption markers showed positive linear relationships with bone formation markers in all participants; whereas only TRACP5b expression negatively correlated with 25-OH VD. Expression levels of all bone turnover markers negatively correlated with BMI. Regression analysis identified risk factors of PSP as age, height, weight, and TRACP5b and 25-OH VD expression levels; whereas gender and PINP, b-CTX, and N-MID expression levels were not significantly associated with the onset of PSP. It had lower bone mineral density in PSP patients. Bone formation marker PINP, N-MID and bone resorption marker b-CTX, TRACP5b were upregulated in PSP patients. 25-OH VD expression was relatively low in this population of PSP patients. Age, height, weight, and expression levels of TRACP5b and 25-OH VD may be risk factors for PSP.

PREMATURE AGING MARKERS IN WOMEN OF REPRODUCTIVE AGE WITH HYPOPITUITARISM

Background: Premature aging reduces quality of human life, leads to development of “old age diseases” in younger age, and also shortens life expectancy. Aim: Investigation of premature aging markers in women of reproductive age with central untreated hypogonadism in association with other compensated pituitary deficiencies. Materials and methods: Hormonal and biochemical parameters, body mass index (BMI) and body mineral density (BMD) were investigated in 87 women of reproductive age (median – 24 y.o.) with the central untreated hypogonadism in association with other compensated pituitary deficiencies (hypopituitarism) and in 52 healthy age-matched controls. Results: Low levels of estrogens as well as androgens (total and free testosterone, DHEA-S) were found in women with hypopituitarism as compared to the controls. Such markers of premature aging as increased BMI (р=0,025), high levels of cholesterol (р <-2.5 SD in lumbar vertebra). Correlation analysis elucidated that hypoandrogenemia as well as hypoestrogenemia was pathogenetic basis of premature aging in women with hypopituitarism and untreated hypogonadism. Conclusion: Such markers of premature aging as BMI increase, dislipidemia, increased levels of bone metabolism markers, and low BMD were revealed in women of reproductive age with uncured hypogonadism and other compensated types of hypophysial insufficiency. Treatment of hypogonadism in this cohort of patients needs to be considered a prevention of the premature aging.

Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20% of calories from FA), and compared them to mice on a normal (R) caloric diet (10% of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p<0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p<0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p<0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

Prospective Evaluation of Zoledronic Acid in the Treatment of Bone Metastases from Differentiated Thyroid Carcinoma.

The objectives of this study were to prospectively delineate the efficacy and safety of zoledronic acid for treating bone metastases (BM) from differentiated thyroid carcinoma (DTC), and to evaluate the relationships between levels of bone metabolic markers and occurrence of skeletal-related events (SREs). This was a prospective, single-arm, single-center study. Nineteen patients with BM from DTC were assigned to receive zoledronic acid therapy every 4-5 weeks. Imaging studies for sites of BM were conducted every 6 months, and levels of bone metabolic markers, including serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide of type I collagen (NTx), were assessed every 3 months. To evaluate the efficacy of zoledronic acid use, data of SREs were compared with those of 16 historical controls. SREs developed in eight patients (42 %), but metastatic spinal cord compression (MSCC) appeared in only one patient. Pain scores were ameliorated in five patients, but aggravated in six patients. Ten patients had stable disease, six showed progressive disease, and none showed partial or complete response during the observation period. Decreases in levels of bone metabolic markers were observed in ten patients for BAP and 15 for NTx. However, no significant correlations were identified between changes in bone metabolic marker levels and development of SREs. Zoledronic acid may offer a mainstay of multidisciplinary treatment for patients with BM for the purpose of reducing SREs. Levels of serum BAP and urinary NTx do not appear reliable as indicators of amelioration of BM symptoms.

Effects of raloxifene on bone metabolism in postmenopausal women on chronic hemodialysis.

Postmenopausal women with end-stage renal failure are at an increased risk of fracture because of the effects of secondary hyperparathyroidism and postmenopausal osteoporosis. In the present study, we investigated the feasibility of using raloxifene to prevent fractures in postmenopausal women with end-stage renal failure on hemodialysis. This study was conducted using a multicenter, single-arm, prospective design. Raloxifene was administered to postmenopausal women aged ≥50 years who were on maintenance hemodialysis and met any of the following criteria after a 24-week run-in period: an alkaline phosphatase level (bone formation marker) of ≥6.18 µkat/L (≥370 U/L), a bone-specific alkaline phosphatase (BAP; bone formation marker) level of ≥0.59 µkat/L (≥35.4 U/L), or a bone-derived tartrate-resistant acid phosphatase (TRACP-5b; bone resorption marker) level of ≥4.2 U/L. A total of 48 individuals were eligible for study inclusion. Of them, 30 individuals participated in this study. The BAP levels were significantly decreased at week 4, but returned to the baseline levels at week 24. Similarly, the TRACP-5b levels were significantly decreased at week 4, but returned to the baseline levels at week 24. The serum calcium value decreased consistently after the start of raloxifene therapy. The intact parathyroid hormone (iPTH) levels were likely increased at week 4. The ratio of BAP to iPTH levels and the ratio of TRACP-5b to iPTH levels both showed significant decreases over time. During the raloxifene therapy, no thrombosis or other drug-related adverse events developed. The study results indicated that raloxifene can transiently reduce the levels of bone metabolism markers and might be useful for preventing fractures in postmenopausal women with end-stage renal failure, although raloxifene use over the long term may not have adequate efficacy in the absence of appropriate concomitant active vitamin D therapy.

DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats.

Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups (n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management.

Association of the (TTTA)n repeat polymorphism of CYP19 gene with bone mineral density in Greek peri‐ and postmenopausal women

Aromatase is encoded by the CYP19 gene and catalyses the conversion of androgens to oestrogens, which in turn regulate skeletal homeostasis. CYP19 gene polymorphisms have been studied for their association with bone mineral density (BMD) in the general population with mixed results. To explore the influence of the CYP19 (TTTA)n repeat polymorphism on BMD and serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κΒ ligand (RANKL), and bone metabolic markers in a Greek female population. Cross-sectional study. Two hundred and seventeen peri- and postmenopausal women aged 42-63 years were enrolled. All participants underwent spinal BMD evaluation by dual-energy X-ray absorptiometry (DXA). Genotyping of the (TTTA)n repeat polymorphism was performed by polymerase chain reaction. Levels of OPG, soluble RANKL (sRANKL) and bone metabolic markers were measured. Genotype analysis revealed alleles having 7-12 TTTA repeats. Women carrying the (TTTA)11 and/or (TTTA)12 alleles had significantly higher spinal BMD than women not carrying these alleles in the total study population as well as in the subgroup of women with osteoporosis (P = 0·042 and P = 0·006, respectively). The aforementioned associations remained significant after adjustment for age, years since menopause, smoking and body mass index (P = 0·048 and P = 0·023, respectively, by multivariate analysis). Moreover, the urinary calcium to creatinine ratio was associated with the (TTTA)n polymorphism. No association of the (TTTA)n polymorphism with circulating levels of OPG, sRANKL was observed. The (TTTA)n polymorphism of the CYP19 gene is associated with spinal BMD in peri- and postmenopausal Greek women.

ADDITIONAL BENEFITS OF ANTIHYPERTENSIVE MOXONIDINE THERAPY IN POSTMENOPAUSAL WOMEN WITH ARTERIAL HYPERTENSION

Aim. To assess the effects of moxonidine in terms of target blood pressure (BP) achievement; to identify potential additional benefits of moxonidine and its effects on bone metabolism and bone mineral density (BMD) in postmenopausal women with arterial hypertension (AH).Material and methods. The study included 48 postmenopausal women with Stage 1-2 AH, aged 57-71 years.Results. All participants were divided into two groups by the type of antihypertensive therapy: those receiving moxonidine and those receiving angiotensin-converting enzyme inhibitors / angiotensin receptor antagonists (ACEI/ARA). All women also received calcium and vitamin D. All participants had AH and osteopenia (both in the lumbar spine and proximal femur, according to the X-ray absorptiometry results). In the moxonidine group, BP levels remained within the target range 48 weeks later. There was a significant reduction in the levels of a bone resorption marker (p=0,041), while the dynamics of an osteopoetic marker was statistically non-significant (p=0,31). A tendency towards increasing BMD in lumbar spine and proximal femur was also observed (p=0,059 and p=0,068, respectively). In the ACEI/ARA group, BP levels also remained within the target range 48 weeks later. However, no significant changes in the levels of bone metabolism markers were registered. There was a tendency towards decreasing BMD in lumbar spine and proximal femur (p=0,052 and p=0,054, respectively).Conclusion. Moxonidine therapy was associated with a significant reduction in bone resorption activity, as demonstrated by the decrease in the concentration of a bone resorption marker, as well as with a tendency towards increasing BMD.

Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use.

Background/AimsOur aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients.MethodsThirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched).ResultsBone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 ± 2.12 pg/mL at baseline to 2.51 ± 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755).ConclusionsRA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.

The limited effects of anti-tumor necrosis factor blockade on bone health in patients with rheumatoid arthritis under the use of glucocorticoid

We investigated the effects of biologics for rheumatoid arthritis (RA) patients on bone mineral density (BMD) and bone metabolic markers (BMM), retrospectively, and also clarified the effects of bisphosphonates (alendronate or risedronate 35 mg/week) and glucocorticoids. Participants in this study comprised 219 patients with RA, including 117 patients treated with biologics (infliximab, n = 90; etanercept, n = 27) and 102 patients with conventional disease-modifying anti-rheumatic drugs (DMARDs) for 1 year. Changes in BMD at the lumbar spine and total hip and BMMs [urinary type I collagen cross-linked N-telopeptide (NTX) and bone-specific alkaline phosphatase] were measured. BMD of the lumbar spine in both groups and total hip BMD in the biologics group were unchanged during treatment with biologics. However, BMD of the total hip was significantly decreased in the DMARDs group (from 0.731 ± 0.135 to 0.706 ± 0.135 g/cm2). Patients receiving glucocorticoids without bisphosphonates showed significant decrease in BMD of the total hip compared with patients not receiving glucocorticoids or receiving glucocorticoids with bisphosphonates in both biologics and DMARDs groups. Furthermore, BMD of the lumbar spine increased (p < 0.05) for patients in the biologics group who received bisphosphonates. NTX was significantly decreased only in the biologics group. Multiple regression analysis showed that BMD and bone metabolic marker levels correlated positively with bisphosphonate and biologics use and negatively with glucocorticoid use. BMD of the total hip was maintained in the patients using biologics without glucocorticoids or with bisphosphonates, but it was not maintained in the DMARDs patients, even without glucocorticoids or with bisphosphonates. Even if biologics have protective effect against bone loss of RA patients, we should consider reducing the dose of glucocorticoids and adding bisphosphonates for the treatment of osteoporosis.

Clinical results of alendronate monotherapy and combined therapy with menatetrenone (VitK2) in postmenopausal RA patients

Objectives: We aimed to evaluate the clinical efficacy of monotherapy with alendronate and combined therapy with alendronate and menatetrenone (vitamin K2 [VitK2]) in postmenopausal rheumatoid arthritis (RA) patients with osteoporosis or osteopenia.Methods: Sixty-two postmenopausal RA patients with untreated osteoporosis or osteopenia (lumbar spine bone density ≤80 % of young adult mean [YAM]) were enrolled: 39 had abnormal serum undercarboxylated osteocalcin (ucOC) levels (>4.5 ng/mL) and received combined therapy with alendronate (35 mg/week) and VitK2 (45 mg/day) (ALN + K group); 23 had normal ucOC levels (≤4.5 ng/mL) and received alendronate monotherapy (35 mg/week) (ALN group). The clinical results for the 57 patients in both groups were evaluated after 1-year treatment.Results: The mean baseline/follow-up (FU) lumbar spine bone density (%YAM) values were 73.0/76.8 % (P < 0.01) in the ALN + K group and 77.0/80.3 % (P < 0.01) in the ALN group; a significant increase was shown in both groups. Mean proximal femoral bone density values at baseline/FU were 71.4/73.8 (P < 0.01) in the ALN + K group and 71.4/71.6 % (not significant; NS) in the ALN group; a significant increase was shown in the ALN + K group only. Serum ucOC levels were normalized in the ALN + K group at FU. At FU, bone metabolism markers [bone-specific alkaline phosphatase (BAP) and N-terminal cross-linked telopeptides of type I collagen] were decreased in both groups. One patient in the ALN + K group and three in the ALN group suffered new fractures.Conclusions: Combined therapy with alendronate and VitK2 decreases bone metabolism marker levels and serum ucOC levels, and increases lumbar spine and femoral neck bone density in postmenopausal RA patients with abnormal ucOC levels and osteoporosis or osteopenia.

Response of bone mineral density, inflammatory cytokines, and biochemical bone markers to a 32-week combined loading exercise programme in older men and women

This study examines the effects of 32 weeks of exercise training on balance, lower-extremity muscle strength, bone mineral density (BMD) and serum levels of bone metabolism and inflammatory markers in older adults. Forty-seven healthy older adults (women=24, men=23; mean age 68.2 years) participated in a exercise intervention (60min/session) that included resistance exercise training (2 days/week) at 75–80% of maximum plus a multicomponent weight-bearing impact exercise training (1 day/week). Outcome measures included lumbar spine and proximal femoral BMD, dynamic balance, muscle strength, serum levels of bone metabolism markers [osteocalcin (OC), C-terminal telopeptide of Type I collagen (CTX), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL)] and serum levels of inflammatory markers [high sensitive (hs)-C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ]. Potential confounding variables included body composition, dietary intake (using 4-day diet records), and accelerometer-based physical activity. After 32 weeks, both men and women increased dynamic balance (6.4%), muscle strength (11.0%) and trochanter (0.7%), intertrochanter (0.7%), total hip (0.6%), and lumbar spine BMD (1.7%), while OC, CTX, OPG and RANKL levels remained unchanged. In addition, hs-CRP and IFN-γ levels were decreased, while TNF-α levels were unchanged, and a decrease in IL-6 levels was only observed in men. These findings suggest that our combined impact protocol reduces inflammation and increases BMD, balance, and lower-extremity muscle strength, despite having little effect on bone metabolism markers. This reinforces the role of exercise to counteract the age-related inflammation, and the muscle strength, balance and BMD reduction.

Selected risk factors of fractures in children — own observation

Abstract Bone fractures may depend on Vitamin D Receptor Gene (VDR), bone mineral density, bone turnover markers. Patients and methods. 161 patients were recruited and underwent: skeletal densitometry (DXA) method and bone turnover studies (Osteocalcin and Ntx).The study group was evaluated using restriction enzyme digestion at BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236), polymorphic sites of the VDR gene. Multivariate logistic regression was used to assess factor significance. The model included variables with sex- and age-standardized parameters, VDR genotypes, and bone metabolism marker levels. Results. Factors associated with fractures were: osteocalcin concentration and Z-score BMDt. Odds Ratio (OR) values equaled: 1.01 (95%Confidence Interval (95%CI) 1.00–1.02) for osteocalcin (p=0.006), and 0.66 (95%CI 0.42-1.03; p=0.07) for Z-score BMDt. In patients with reduced bone mass, factors related to fractures were: osteocalcin (0.04) and carriage of BsmI b (0.07) or ApaI a alleles (0.08). ORs were 1.01 (95%CI 1.00–1.02) for OC, 0.29 (95%CI 0.07–1.14) for BsmI, and 2.13 (95%CI 0.91–4.99) for ApaI polymorphic allele carriage. Conclusions. Carriage of BsmI b allele reduces, while carriage of ApaI a allele and heightened osteoclacin level increase the risk of fractures in study children with reduced bone mass. VDR polymorphism, bone mineral density and bone formation’s marker — osteocalcin maybe considered as risk factor for fracure in children from Lodz region.