Increase In Bone Turnover Markers Research Articles

Bone structural changes after gastric bypass surgery evaluated by HR-pQCT: a two-year longitudinal study.

Objective, design and methodsRoux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X-ray absorptiometry, and volumetric BMD (vBMD) and bone microarchitecture at the distal radius and tibia by high-resolution peripheral quantitative CT in 25 morbidly obese subjects (15 females, 10 males) at 0, 12 and 24 months after RYGB. Bone turnover markers (BTMs), calciotropic and gut hormones and adipokines were measured at the same time points.ResultsAfter a 24.1% mean weight loss from baseline to month 12 (P < 0.001), body weight plateaued from month 12 to 24 (−0.9%, P = 0.50). However, cortical and trabecular vBMD and microarchitecture deteriorated through the 24 months, such that there was a 5 and 7% reduction in estimated bone strength at the radius and tibia respectively (both P < 0.001). The declines observed in the first 12 months were matched or exceeded by declines in the 12- to 24-month period. While a significant increase in BTMs and decrease in leptin and insulin were seen at 24 months, these changes were maximal at month 12 and stabilized from month 12 to 24.ConclusionsDespite weight stabilization and maintenance of metabolic parameters, bone loss and deterioration in bone strength continued and were substantial in the second year. The clinical importance of these changes in terms of increased risk of developing osteoporosis and fragility fractures remain an important concern.

Periodontitis and bone metabolism in patients with advanced heart failure and after heart transplantation.

AimsHeart failure (HF) is a multi­organ, pro‐inflammatory syndrome that impairs bone metabolism. Pro‐inflammatory cytokines and bone catabolism enhance periodontal disease, a local inflammatory, bacteria‐induced disease that causes bone loss and periodontal soft tissue destruction.Methods and resultsMedical and dental examinations were performed on patients with HF (n = 39), following heart transplantation (post‐HTx, n = 38) and controls (n = 32). Blood, saliva, and gingival crevicular fluid were analysed for bone metabolism and inflammation markers. HF average New York Heart Association classification was III. Average time since HTx was 1414 days. Pro‐inflammatory tumour necrosis factor‐alpha was higher in HF and HTx as compared with controls (P < 0.05). Both HF and HTx participants had higher levels of bone resorption marker C‐terminal telopeptide and parathyroid hormone with subjects in the HF group having the highest serum levels of all groups (P ≤ 0.05). In contrast, 25‐hydroxyvitamin D was lowest in HF. HF patients had greater clinical attachment loss, cumulative pockets depth (greater than 3 mm) and probing depth (P < 0.05) as compared with controls. Cumulative pockets depth correlated significantly with measures of the inflammatory burden, β‐glucuronidase in saliva (r = 0.4863, P < 0.01), interleukin‐1b in saliva (r = 0.5149, P < 0.01), and gingival crevicular fluid (r = 0.6056, P < 0.001) in HF. However, adjustment of periodontal results for measures of oral hygiene (plaque, bleeding on probing), systemic 25‐hydroxyvitamin D, and race attenuated significant differences between groups.ConclusionsPatients with HF exhibit more severe periodontal disease associated with increased bone turnover markers when compared with control patients. However, local and systemic factors may account for this association and should be evaluated in future studies.

Elevated Bone Turnover Markers are Associated with Distal Radius Fractures in Pre-menopausal Women: Level 3 Evidence

Grant received from: OREF Resident Research Project Grant There is no financial information to disclose. Vitamin D deficiency and increased bone turnover markers (BTM) are associated with an increased risk of fragility fractures. We hypothesized that young patients with distal radius fractures (DRF) would have lower levels of 25-hydroxyvitamin D (25(OH)D) and increased levels of serum BTMs compared to controls without fracture. Premenopausal women with DRF (n = 20) were prospectively enrolled and compared to age-matched individuals without a fracture (n = 20). Outcome measures included serum levels of 25(OH)D, parathyroid hormone (PTH), markers of bone formation (osteocalcin [OC], N-terminal extension propeptide of type I collagen [P1NP], and bone-specific alkaline phosphatase [BSAP], and markers of bone resorption (C-terminal telopeptide of type-I collagen [CTX-1]). Associations between BTM and DRF were assessed with conditional logistic regression and the utility of markers for fracture prediction was assessed with a receiver operator characteristic (ROC) analysis. The fracture group and control group were comparable in terms of age, body mass index, and age at menarche. Fracture patients had higher levels of OC (23.09 ± 6.86 versus 17.23 ± 8.19 ng/mL, mean difference = 6.01 ng/mL, 95%CI = 1.32 - 10.70) and P1NP (72.15 ± 25.80 versus 51.99 ± 24.18 ng/mL, mean difference = 20.44 ng/mL, 95% CI = 4.53 - 36.34) and trended toward higher levels of CTX (0.43 ± 0.21 versus 0.32 ± 0.21 ng/mL, mean difference = 0.10, 95% CI = -0.01 - 0.22). The levels of 25(OH)D, PTH, and BSAP were similar between groups. Conditional logistic regression revealed independent associations between DRF and CTX (OR = 7.4 per SD increase, 95% CI = 1.3 - 43.6, P = 0.026), and OC (OR = 2.4 per SD increase, 95% CI = 1.0 - 5.8, P = 0.043). Associations between DRF and P1NP (OR = 4.78 per SD increase, 95% CI = 0.97 - 23.66, P = 0.055) and BSAP (OR = 3.16 per SD increase, 95% CI = 0.96 - 10.37, P = 0.058) trended towards significance (Table 1). Serum 25(OH)D and PTH were not associated with DRF. ROC analyses demonstrated moderate performance for OC, P1NP, BSAP and CTX in predicting DRF (Figure 1). •25(OH)D levels were not associated with DRF in pre-menopausal women.•Patients with DRF had increased levels of BTMs of formation and resorption.•Women with increased levels of OC and CTX were at higher risk of fracture.•BTMs may be helpful in predicting fractures in pre-menopausal women.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Adverse bone health and abnormal bone turnover among perinatally HIV‐infected Asian adolescents with virological suppression

This study aimed to determine the prevalence of low bone mass and assess its relationship with abnormal bone turnover among HIV-infected Asian adolescents. A multicentre, cross-sectional study was conducted at four paediatric HIV centres in Thailand and Indonesia. Perinatally HIV-infected adolescents aged 10-18 years receiving antiretroviral therapy (ART) with virological suppression (HIV RNA < 400 copies/mL) were enrolled. Study assessments included lumbar spine (L2-L4) dual-energy X-ray absorptiometry and measurement of bone turnover markers. Bone mineral density (BMD) and bone mineral apparent density (BMAD) Z-scores were calculated based on Thai normative age- and sex-matched references. Low bone mass was defined as BMD or BMAD Z-scores ≤ -2. Of 396 participants, 57% were female. The median age was 15.0 [interquartile range (IQR) 13.3-16.9] years, and 73% were in Tanner stage 3-5. At enrolment, the median CD4 T-cell count was 734 (IQR 581-907) cells/μL, and 37% were on protease inhibitor (PI)-based regimens. The overall prevalence of lumbar spine BMD and BMAD Z-scores ≤ -2 were 16.4% and 8.3%, respectively. Z-scores were lower with older age, female sex, body mass index (BMI) <5th percentile, boosted PI exposure and CD4 T-cell percentage < 15% before ART initiation. Increased bone turnover markers were inversely associated with BMD and BMAD Z-scores. Low bone mass was linked to older age, female sex, low BMI, boosted PI exposure, and poor immunological status before ART commencement in our cohort of perinatally HIV-infected Asian adolescents. Dysregulation of bone turnover was associated with bone demineralization. Screening for low bone mass should be implemented to identify individuals who might benefit from interventions to preserve bone health.

Bone Metabolism Changes after Laparoscopic Greater Curvature Plication. A One-Year Study.

In addition to the positive effect of weight loosing after bariatric surgery, the post-operative period is often associated with significant changes in bone metabolism. Aim. The aim of this study was to examine changes in bone turnover markers and indicators of dual-energy X-ray absorptiometry (DXA) within 12 months after laparoscopic greater curvature plication (LGCP). Materials and methods. We studied 54 patients from class III obesity who underwent LGCP. The average preoperative weight of the patients was 125,519.1 kg, and BMI of 43.04.9 kg/m2. The gender distribution of the cohort was 35.2% man and 64.8% women. At three time points after the operation (at 3, 6 and 12 months) control examination was conducted that included DXA and markers of bone metabolism. Results. After the surgical treatment we registered significant reduction of all the anthropometric indicators (0.05; EWL12 45.8±18.8%; EBL12 55.1±23.4%). According to the controlled studies on the 12th months, a significant increase in bone turnover markers was revealed (0.05; CTX, P1NP, OC, OPG, VTD) and reducing of PTH (0.05). The measure of DXA on the 12th month of observation showed no significant changes in bone metabolism. Strong positive correlation was uncovered between markers of bone metabolism: CTX / P1NP (r=0.790, p=0.000), CTX/OC, P1NP/OC (r=0.7, p=0.000), minor correlation between PTH/OC (r=0.249, p=0.027). We also report a minor and weak negative correlation between the markers of bone metabolism (CTX, P1NP, OC and VTD) and anthropometric data. Conclusions. Twelve months post LGCP markers of bone turnover (CTX, P1NP, OC, OPG, VTD) were significantly increased. The increased level of VTD is associated with the loss of FAT. Also the change in DXA was detected.

Minodronic acid ameliorates vertebral bone strength by increasing bone mineral density in 9-month treatment of ovariectomized cynomolgus monkeys

The effect of treatment for 9months with minodronic acid, a nitrogen-containing bisphosphonate, on vertebral mechanical strength was examined in ovariectomized (OVX) cynomolgus monkeys. Forty skeletally mature female monkeys were randomized into four OVX groups and one sham group (n=8) based on lumbar bone mineral density (BMD). OVX animals were treated orally with 15 and 150μg/kg QD of minodronic acid or 500μg/kg QD alendronate as a reference drug. Measurements of bone turnover markers and lumbar BMD were conducted at 0, 4 and 8months. Measurements of bone mechanical strength and minodronic acid concentration in vertebral bodies were also performed. OVX resulted in a decrease in lumbar BMD and an increase in bone turnover markers at 4 and 8months, compared to the sham group, and the ultimate load on the lumbar vertebra was decreased in OVX animals. Minodronic acid and alendronate prevented the OVX-induced increase in bone turnover markers and decrease in lumbar BMD. Minodronic acid at 150μg/kg increased the ultimate load on lumbar vertebra compared to untreated OVX animals. Regression analysis revealed that the ultimate load was correlated with lumbar BMD and bone mineral content (BMC), and most strongly with the increase in lumbar BMD and BMC over 8months. In a separate analysis within the sham-OVX controls and minodronic acid and alendronate treatment groups, the ultimate loads were also correlated with BMD and BMC. The load-BMD (BMC) correlation in the minodronic acid group showed a trend for a shift to a higher load from the basal relationship in the sham-OVX controls. These results indicate that treatment with minodronic acid for 9months increases vertebral mechanical strength in OVX monkeys, mainly by increasing BMD and BMC.

Changes in Inflammatory and Bone Turnover Markers After Periodontal Disease Treatment in Patients With Diabetes

BackgroundThe underlying mechanisms for increased osteopenia and fracture rates in patients with diabetes are not well understood, but may relate to chronic systemic inflammation. We assessed the effect of treating periodontal disease (POD), a cause of chronic inflammation, on inflammatory and bone turnover markers in patients with diabetes. Materials and MethodsUsing an investigator-administered questionnaire, we screened a cross-section of patients presenting for routine outpatient diabetes care. We recruited 22 subjects with POD. Inflammatory and bone turnover markers were measured at baseline and 3 months following POD treatment (scaling, root planing and subantimicrobial dose doxycycline). ResultsThere were nonsignificant reductions in high-sensitivity C-reactive protein (6.34–5.52mg/L, P = 0.626) and tumor necrosis factor-alpha (10.37–10.01pg/mL, P = 0.617). There were nonsignificant increases in urinary C-terminal telopeptide (85.50–90.23pg/mL, P = 0.684) and bone-specific alkaline phosphatase (7.45–8.79pg/mL, P = 0.074). Patients with >90% adherence with doxycycline were 6.4 times more likely to experience reduction in tumor necrosis factor-alpha (P = 0.021) and 2.8 times more likely to experience reductions in high-sensitivity C-reactive protein (P = 0.133). ConclusionsTreatment of POD in patients with diabetes resulted in nonsignificant lowering of inflammatory markers and nonsignificant increase in bone turnover markers. However, adherence to doxycycline therapy resulted in better treatment effects.

Osteosarcopenia is more than sarcopenia and osteopenia alone.

Sarcopenia and osteopenia/osteoporosis show a high prevalence in old age and incur a high risk for falls, fractures, and further functional decline. Physical performance and bone metabolism in patients suffering from the so-called osteosarcopenia-the combination of sarcopenia and osteopenia-are currently still unknown. This study investigates physical performance and bone metabolism in osteosarcopenic, prefrail, community-dwelling older adults. 68 prefrail adults between 65 and 94years were assigned to four groups according to mean DXA results: osteosarcopenic [low T-score and low appendicular lean mass (aLM)], sarcopenic (low aLM), osteopenic (low T-score), and controls. Multiple linear regression analysis, adjusted for age, gender, physical activity, and 25-OH-vitamin D3 serum level, was used to identify the influence of being osteosarcopenic, sarcopenic, or osteopenic on physical performance (hand grip, chair rise test, sit-to-stand power, gait speed, SPPB) and serum markers for increased bone turnover [osteocalcin, β-crosslaps and procollagen type 1 amino-terminal propeptide (P1NP)]. Only osteosarcopenic participants showed significantly reduced hand grip strength, increased chair rising time, and STS power time as well as significantly increased bone turnover markers. Due to low physical performance and high bone turnover, older adults with osteosarcopenia have to be regarded as the most at-risk population for fractures and further functional decline. Up-to-date osteoporosis and post-fracture management of older persons should aim at both, bone and muscle.

Abstract 20065: Periodontitis and Bone Metabolism in Patients With Advanced Heart Failure and After Heart Transplantation

Background: Heart failure (HF) is a multi-organ, pro-inflammatory syndrome that impairs bone metabolism. Proinflammatory cytokines and bone catabolism enhance periodontal disease, a local inflammatory, bacteria-induced disease that causes bone loss and periodontal soft tissue destruction. Hypothesis: Patients with advanced HF before and after heart transplantation (HTx) have more severe periodontal disease as compared to age and smoking-matched controls. Further, local inflammatory markers in the saliva and gingival crevicular fluid (GCF) can be used as markers of the local inflammatory periodontal burden in patients with HF. Methods: Medical and dental examinations were performed on patients with HF (n=41), following heart transplantation (post-HTx, n=40) and controls (n=32). Blood, saliva and GCF samples were taken to investigate markers of bone metabolism and inflammation. Results: Average New York Heart Association classification for HF was class III. Average time since HTx was 33.14 months. Overall periodontal diagnosis was more severe in patients with advanced HF and post-HTx versus controls (p&lt;0.0001). Pro-inflammatory tumor necrosis factor-alpha (TNF-α) was higher in HF and HTx patients as compared to controls (p&lt;0.05). Both, HF and HTx participants had higher levels of bone resorption marker C-terminal telopeptide and parathyroid hormone with subjects in the HF group having the highest serum levels of all groups (p≤0.05). In contrast, 25-VitD was lowest in patients with HF. The bone formation markers osteocalcin and procollagen-1 N-terminal peptide did not display differences between groups. Further, we found a significant correlation between beta-glucoronidase in saliva (r=0.4863, p&lt;0.01) and interleukin-1b in saliva (r=0.4999, p&lt;0.01) and GCF (r=0.5943, p&lt;0.001) and the severity of periodontal disease. Conclusion: Patients with advanced HF exhibit more severe periodontal disease associated with increased bone turnover markers when compared to control patients. Further, periodontal disease severity was detectable in saliva and GCF making it a potential useful tool for identifying the need for periodontal treatment in patients with advanced HF.

Effects of soccer vs swim training on bone formation in sedentary middle-aged women.

The present study examined the effects of 15 weeks of soccer training and two different swimming training protocols on bone turnover in sedentary middle-aged women. Eighty-three premenopausal mildly hypertensive women [age: 45 ± 6 (± SD) years, height: 165 ± 6 cm, weight: 80.0 ± 14.1 kg, body fat: 42.6 ± 5.7 %, systolic blood pressure/diastolic blood pressure: 138 ± 6/85 ± 3 mmHg] were randomized into soccer training (SOC, n = 21), high-intensity intermittent swimming (HS, n = 21), moderate-intensity swimming (MS, n = 21) intervention groups, and a control group (C, n = 20). The training groups completed three sessions per week for 15 weeks. DXA scans were performed and resting blood samples were drawn pre- and post-intervention. In SOC, plasma osteocalcin, procollagen type I N propeptide and C-terminal telopeptide increased (P < 0.05) by 37 ± 15, 52 ± 23 and 42 ± 18 %, respectively, with no changes in MS, HS and C. The intervention-induced increase in SOC was larger (P < 0.05) than in MS, HS and C. In SOC, leg BMC increased (P < 0.05) by 3.1 ± 4.5 %, with a larger increase in SOC than in C. Femoral shaft and trochanter bone mineral density (BMD) increased (P < 0.05) by 1.7 ± 1.9 and 2.4 ± 2.9 %, respectively, in SOC, with a greater (P < 0.05) change in SOC than in MS and C, whereas total body and total leg BMD did not change in any of the groups. In conclusion, 15 weeks of soccer training with sedentary middle-aged women caused marked increases in bone turnover markers, with concomitant increases in leg bone mass. No changes in bone formation and resorption markers were seen after prolonged submaximal or high-intensity intermittent swimming training. Thus, soccer training appears to provide a powerful osteogenic stimulus in middle-aged women.

Improvement in Renal Function and Bone Mineral Density after a Switch from Tenofovir/Emtricitabine plus Ritonavir-Boosted Protease Inhibitor to Raltegravir plus Nevirapine: A Pilot Study

The antiretroviral regimens including tenofovir and a ritonavir-boosted protease inhibitor (r/PI) have been associated with a reduced bone mineral density (BMD), increased bone turnover markers and renal tubular dysfunction. An observational, prospective study was performed including HIV-1-infected, virologically suppressed patients treated with tenofovir/emtricitabine plus an r/PI for at least 12 months who switched to raltegravir plus nevirapine. The primary end point was changes after 48 weeks in estimated glomerular filtration rate (eGFR), prevalence of tubular dysfunction, BMD and concentration of two serum markers of bone turnover: collagen type-1 cross-linked C-telopeptide (CTX) and bone-specific alkaline phosphatase (BAP). A total of 46 patients were enrolled: 78% were male, 96% were Caucasian, the mean age was 45 years and the mean CD4(+) T-lymphocyte count was 681 cells/mm(3). A renal impairment was present in 72% of patients and was the main reason for the switch. After 48 weeks, prevalence of proximal tubular dysfunction decreased significantly (-72%; P<0.001), whereas the mean value of eGFR did not change significantly. At the same time, after 48 weeks a significant increase in both lumbar spine and total hip BMD, T-score and Z-score was reported (+11.5% in lumbar spine T-score; P<0.001), and there was a significant reduction in both CTX and BAP mean serum concentrations (-15% and -13%, respectively; P<0.001). Two (4.3%) patients had virological failure due to suboptimal adherence and one (2.2%) subject discontinued treatment due to a skin rash. Switching virologically suppressed patients from tenofovir/emtricitabine plus one r/PI to raltegravir plus nevirapine after 48 weeks significantly improved proximal tubular function, increased BMD and reduced serum markers of bone turnover.

Effect of high dietary sodium on bone turnover markers and urinary calcium excretion in Korean postmenopausal women with low bone mass

High salt intake is a well-recognized risk factor of osteoporosis for its modulating effect on calcium metabolism. To understand the effect of dietary sodium on bone turnover, we evaluated the association between urinary sodium excretion and bone turnover markers in Korean postmenopausal women with low bone mass. A retrospective review of medical records at a single institution identified 537 postmenopausal women who were first diagnosed with osteopenia or osteoporosis between 2008 and 2013. Subjects were stratified by low (<2 g/day, n=77), moderate (2-4.4 g/day, n=354) and high (⩾4.4 g/day, n=106) sodium excretion. A 24-h urine was collected to estimate sodium, calcium and creatinine. Bone turnover markers and calciotropic hormones were measured in serum. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Sodium intake was positively associated with urinary sodium excretion (P=0.006, r=0.29). Bone turnover markers were significantly higher in the moderate-to-high urinary sodium excretion group (⩾2 g/day) than in the low urinary sodium excretion group (<2 g/day); CTX-I (C-telopeptides of type I collagen) was 21.3% higher (P=0.001) and osteocalcin (OC) was 15.7% higher (P=0.004). Calciotropic hormones and BMD were not significantly different across the sodium excretion groups. High urinary sodium excretion (⩾2 g/day) increased bone turnover markers in Korean postmenopausal women, suggesting that excessive sodium intake might accelerate bone turnover.

Spontaneous Remission of Primary Hyperparathyroidism Related to an Autoimmune Disease: A Case Report

ABSTRACT Objective: To report the unusual case of a woman with unequivocal primary hyperparathyroidism (PHPT) for 13 years who experienced spontaneous remission of her disease concomitant with the diagnosis of psoriatic arthritis. Methods: Clinical presentation, clinical course over 23 years of follow-up, and review of the pertinent literature are presented. Results: A 42-year-old woman was referred for evaluation of persistent hypercalcemia 2 months after unsuccessful parathyroid surgery for PHPT, in which a single, hyperplastic parathyroid gland was removed. Further evaluation confirmed persistent PHPT evidenced by hypercalcemia (12.1 mg/dL), elevated parathyroid hormone (PTH) level (118 pg/mL), normal calcium urinary excretion, and increased bone turnover markers. Persistent hypercalcemia and serum levels of PTH above normal were observed for 11 years after the parathyroid surgery. Thereafter, the patient experienced a downward trend and ultimate normalization of her serum calcium and PTH, which was as...

Advanced Oxidation Protein Products as a Novel Marker of Oxidative Stress in Postmenopausal Osteoporosis.

BackgroundAdvanced oxidation protein products (AOPPs) are acknowledged as a novel marker of oxidation-mediated protein damage. This study aimed to investigate the plasma levels of AOPPs in postmenopausal osteoporotic women, and to determine the relationship between AOPPs accumulation and lumbar bone mineral destiny (BMD) or bone turnover markers.Material/MethodsLumbar BMD was measured by dual-energy X-ray absorptiometry. Plasma AOPPs levels as a marker of protein oxidation damage and malondialdehyde (MDA) levels as a marker of lipid peroxidation were measured by spectrophotometry. The concentrations of 2 specific markers of bone turnover, bone-specific alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase5b, (TRACP 5b) were quantified using ELISA kits.ResultsWe recruited 60 postmenopausal women meeting osteoporosis (OP) diagnostic criteria of World Health Organization (WHO) and 60 postmenopausal women without OP. Plasma levels of AOPPs (P<0.001), BALP (P<0.001) and TRACP 5b (P<0.001) were statistically significantly increased in the postmenopausal osteoporotic women compared with controls, but there was no statistically significant difference in MDA (P=0.124) between the 2 groups. Plasma AOPPs levels were negatively correlated with lumbar BMD and positively correlated with bone turnover markers both in postmenopausal osteoporotic women and in all subjects. However, plasma MDA levels were not correlated with lumbar BMD or bone turnover markers.ConclusionsIn postmenopausal osteoporotic women elevated AOPPs is associated with reduced BMD and increased bone turnover markers. Because AOPPs is stable and easy to detect it may be used as a simple plasma marker to predict the severity of postmenopausal OP.

Efecto de la lesión medular motora completa reciente en el recambio óseo y en la evolución de la masa ósea: resultados preliminares

Summary Background and aim: Spinal cord injury (SCI) has been associated with a marked increase in bone loss and a higher incidence of skeletal fractures, however the pathogenesis and clinical management of this condition remains unclear. The aim of this study was to analyze the bone mineral density (BMD) evolution in patients with complete SCI and its relationship with parameters of bone metabolism and bone turnover markers. Methods: Patients with a recent complete motor SCI (ASIA A)(<6 months) were prospectively included. Bone metabolism parameters (calcium, phosphate, PTH and 25-OHD), bone turnover markers (bone formation: procollagen type 1 aminoterminal propeptide -P1NP-, bone alkaline phosphatase -bone AP-, osteocalcin -OC-; bone resorption: C-telopeptides of type I collagen -CTx-) and BMD were assessed in all patients at baseline and at 6 months. The results were compared with a control group. Results: 23 men with complete SCI (ASIA A) and a mean age of 38±15 years were included at 102±33 days of SCI onset. 52% had paraplegia. 12 patients were assessed at 6 months of follow-up. Patients with SCI showed a significant increase in bone turnover markers, especially P1NP and CTx, compared to controls (P1NP: 191±90 vs 51±19 ng/ml, p<0.001; CTx: 1.37±0.49 vs 0.51±0.23 ng/ml, p<0.001). At 6 months, bone turnover markers decreased (P1NP: -34%, p=0.005 and CTx: -26%, p=0.002) and BMD had a mean decrease of 12% at total femur (p=0.002) compared to baseline, with osteoporosis development in 50% of patients. Bone markers (bone AP, P1NP and OC) were negatively correlated with total femur BMD values. Conclusions: Patients with complete SCI show a marked increase in bone turnover and bone loss, especially at the proximal femur, with the development of osteoporosis being observed in 50% of these patients at 6 months of follow-up. These findings indicate the need to implement preventive measures within the therapeutic approach in these patients.

OP0276 Efficacy of Daily Teriparatide for Two Years on Osteoporosis in Patients with Rheumatoid Arthritis – is IT Appropreate to Combine Daily Teriparatide and Biological Agents?

BackgroundAlthough medication of rheumatoid arthritis (RA) has been improved by early intensive treatment using MTX and biological agents (BIO) for decades, treatment of concomitant disease in RA patients, such as...

Unfavorable effect of trigonelline, an alkaloid present in coffee and fenugreek, on bone mechanical properties in estrogen-deficient rats.

Trigonelline (1-methylpyridinium-3-carboxylate), an alkaloid present in coffee and fenugreek seed, has been reported to exhibit phytoestrogenic activity. The aim of the present study was to investigate the effects of trigonelline on bone mechanical properties of rats with normal estrogen level and estrogen deficiency (developing osteoporosis). The experiments were performed on 3-month-old nonovariectomized and ovariectomized (estrogen-deficient) Wistar rats, divided into control rats and rats receiving trigonelline (50 mg/kg p.o. daily) for 4 weeks. The ovariectomy was performed 7-8 days before the start of trigonelline administration. Serum bone turnover markers and bone mineralization, as well as mechanical properties of the tibial metaphysis, femoral diaphysis, and femoral neck were examined. Estrogen deficiency caused worsening of bone mineralization and mechanical properties of the tibial metaphysis, as well as increases in bone turnover markers. Administration of trigonelline did not affect the investigated parameters in nonovariectomized rats, but it worsened the mineralization and mechanical properties of cancellous bone in ovariectomized rats. Unfavorable effects of trigonelline on the skeletal system depended on the estrogen status. They were observed only in cancellous bone of estrogen-deficient rats.

Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys

This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral density (BMD), mechanical strength and microstructure in ovariectomized (OVX) cynomolgus monkeys. Vehicle, ONO-5334 (3, 10 or 30mg/kg) or alendronate (0.5mg/kg) was orally administered for eight months to sham- and OVX-operated monkeys. ONO-5334 dose-dependently suppressed OVX-induced increase in bone turnover markers (urinary C-terminal cross-linking telopeptide of type I collagen (CTX) and serum osteocalcin). At the dose of 30mg/kg, ONO-5334 maintained urinary CTX at nearly zero level and kept serum osteocalcin around the level of the sham animals. Marker levels in the alendronate-treated animals were similar to those in the sham animals throughout the study. ONO-5334 dose-dependently reversed the effect of OVX on vertebral BMD as measured by dual-energy X-ray absorptiometry (DXA) with improvement of bone mechanical strength. Both ONO-5334 and alendronate suppressed OVX-induced changes in vertebral microstructure and turnover state. In the femoral neck, peripheral quantitative computed tomography (pQCT) analysis showed that ONO-5334 increased total and cortical BMD. In particular, ONO-5334 significantly increased cortical BMD with improvement of bone mechanical strength. In microstructural analysis, alendronate suppressed OVX-induced increase in femoral mid-shaft osteonal bone formation rate (BFR) to a level below that recorded in the sham group, whereas ONO-5334 at 30mg/kg did not suppress periosteal, osteonal and endocortical BFR. This finding supports the significant effect of ONO-5334 on cortical BMD and mechanical strength in the femoral neck. The results of this study suggest that ONO-5334 has good therapeutic potential for the treatment of osteoporosis.

Serum 25-OH Vitamin D in relation to Bone Mineral Density and Bone Turnover.

It is unclear which vitamin D status is optimal for bone health. In this study, we aimed to assess cutoffs of 25-hydroxyvitamin D (25OHD) derived by the literature (20, 25, or 30 ng/mL) in relation to bone turnover and bone mineral density (BMD). Serum 25OHD, PTH, osteocalcin, bone alkaline phosphatase, and C-telopeptide were measured in 274 consecutive postmenopausal women. BMD of the lumbar spine (L1–L4) and of femoral neck were also evaluated. 50 patients had normal BMD, while 124 had osteopenia and 100 had osteoporosis. 37.6%, 56.2%, and 70.8% subjects had serum 25OHD lower than 20, 25, or 30 ng/mL, respectively. No differences in bone turnover markers were found when comparing patients with low 25OHD defined according to the different cutoffs. However, a cutoff of 25 ng/mL appeared to differentiate better than a cutoff of 30 ng/mL in those subjects with reduced femoral neck BMD. The PTH plateau occurred at 25OHD levels of 26–30 ng/mL. In conclusion, vitamin D deficiency is common in Sicilian postmenopausal women and it may be associated with low BMD and increased bone turnover markers. Further studies are needed to better define the right cutoff for normal vitamin D levels in postmenopausal women.

Methanol Extract of Euchelus asper Prevents Bone Resorption in Ovariectomised Mice Model.

Marine molluscs are widely distributed throughout the world and many bioactive compounds exhibiting antiviral, antitumor, antileukemic, and antibacterial activity have been reported worldwide. The present study was designed to investigate the beneficial effect of methanol extract of Euchelus asper (EAME) on estrogen deficiency induced osteoporosis in ovariectomised mice model. Forty-two female Swiss albino mice were randomly assigned into Sham operated (Sham) group and six ovariectomised (OVX) subgroups such as OVX with vehicle (OVX); OVX with estradiol (2 mg/kg/day); OVX with EAME of graded doses (25, 50, 100, and 200 mg/kg/day). Bone turnover markers like serum alkaline phosphatase (ALP), serum acid phosphatase (ACP), serum calcium, and histological investigations of tibia and uterus were analysed. Metaphyseal DNA content of the femur bone was also studied. Antiosteoclastogenic activity of EAME was examined. Administration of EAME was able to reduce the increased bone turnover markers in the ovariectomised mice. Histomorphometric analysis revealed an increase in bone trabeculation and restoration of trabecular separation by EAME treatment. Metaphyseal DNA content of the femur of the OVX mice was increased by EAME administration. EAME also showed a potent antiosteoclastogenic behaviour. Thus, the present study reveals that EAME was able to successfully reduce the estrogen deficiency induced bone loss.