Marcadores de formación y resorción ósea y su utilidad para determinar el final del periodo de aposición ósea / Bone formation and resorption markers to evaluate the end of bone apposition

El pico de masa ósea (PMO) se alcanza entre los 20 y 35 años, pero la aposición ósea continúa hasta alcanzar el pico de fortaleza ósea (PFO). Se crea así una ventana entre ambos picos que podría ser evaluada mediante marcadores bioquímicos de recambio óseo, ya que durante dicho período la densidad mineral permanece constante. El objetivo fue determinar el final de la aposición ósea mediante marcadores bioquímicos óseos. Se evaluaron por décadas entre 20 y 49 años de edad 139 sujetos sanos de ambos sexos (69 hombres y 70 mujeres), determinando fosfatasa alcalina ósea (FAO), osteocalcina (OC), propéptido amino terminal del colágeno tipo 1 (P1NP) y telopéptido C-terminal del colágeno tipo 1 (CTX). Los marcadores correlacionan negativamente con la edad (OC: r= -0,3; p<0,01; P1NP: r= -0,4; p< 0,01 y CTX: r= -0,4; p<0,01), exceptuando FAO. En hombres de 20-29 años, P1NP y el CTX fueron significativamente mayores vs. 30-39 años (p<0,05 y p<0,001, respectivamente), y entre 30-39 años vs. de 40-49 años en P1NP y CTX (p<0,05; p<0,001, respectivamente). En mujeres de 20-29 años, P1NP y CTX fueron significativamente mayores vs. 30-39 años (p<0,0001 y p<0,01, respectivamente). Conclusión: los marcadores de remodelado óseo más sensibles y específicos permitirían determinar bioquímicamente el fin de la aposición ósea que se produce entre el PMO y el PFO. Si bien es necesario ampliar el número de sujetos evaluados, los datos que surgen de la presente investigación sentarían las bases para futuros estudios epidemiológicos referidos al fin de la aposición ósea. (AU)

Peak bone mass is achieved between 20-35 years; however bone apposition continues to reach an optimal skeleton strength. The window between peak bone mass and peak bone apposition may be evaluated by biochemical bone turnover markers. The objective of this study was to determine the end of bone apposition through biochemical bone markers in both sexes. A total of 139 subjects (69 men and 70 women) were divided by decades between 20 and 49 years of age. Bone alkaline phosphatase (BAL), osteocalcin (OC), type I collagen propeptide (P1NP) and type I collagen C-terminal telopeptide (CTX) were evaluated. Except BAL, the other bone markers negatively correlated with the age [OC (r= -0.3; p<0.01); P1NP (r= -0.4; p<0.01) and CTX (r= -0.4; p<0.01)]. Regarding men aged 20 to 29 years, P1NP and CTX were significantly higher vs. 30-39 years (p<0.05 y p<0.001, respectively) and. vs. 40-49 years (p<0.05; p<0.001, respectively). In women, the results were similar. Regarding 20-29 years, P1NP and CTX were higher vs. 30-39 years (p<0.001 y p<0.01, respectively). Bone remodeling rate decreases after the third decade, suggesting the end of the apposition period of peak bone mass. Conclusion: The most specific and sensitive bone markers would biochemically determine the end of bone apposition that extends between the peak of bone mass and the peak of bone strength. Although it is necessary to increase the number of subjects evaluated, the data that emerge from the present study would establish the bases for future epidemiological studies referring to the end of bone apposition. (AU)

Experimental osteonecrosis: development of a model in rodents administered alendronate

Abstract The main objective of this study was to cause bisphosphonate-related osteonecrosis of the jaws to develop in a rodent model. Adult male Holtzman rats were assigned to one of two experimental groups to receive alendronate (AL; 1 mg/kg/week; n = 6) or saline solution (CTL; n = 6). After 60 days of drug therapy, all animals were subjected to first lower molar extraction, and 28 days later, animals were euthanized. All rats treated with alendronate developed osteonecrosis, presenting as ulcers and necrotic bone, associated with a significant infection process, especially at the inter-alveolar septum area and crestal regions. The degree of vascularization, the levels of C-telopeptide cross-linked collagen type I and bone-specific alkaline phosphatase, as well as the bone volume were significantly reduced in these animals. Furthermore, on radiographic analysis, animals treated with alendronate presented evident sclerosis of the lamina dura of the lower first molar alveolar socket associated with decreased radiographic density in this area. These findings indicate that the protocol developed in the present study opens new perspectives and could be a good starting model for future property design.

Bone health in cerebral palsy and introduction of a novel therapy / A saúde do osso na paralisia cerebral e a introdução de uma nova terapia

ABSTRACT Objective To assess the bone health status of children with cerebral palsy and the therapeutic effect of denosumab in a subgroup of children with cerebral palsy and decreased bone mass. Methods Children with cerebral palsy were evaluated according to their motor disability score (classification system gross motor functions III to V), bone density and bone turnover markers. Dual X-ray energy absorption was used to measure the lumbar spine, and total body, except the head. Thereafter a group of children with cerebral palsy and osteoporosis was treated with denosumab, a fully human monoclonal antibody. Bone turnover markers were measured before and three months after treatment. Results Reduction in bone mineral density was observed, particularly in children with greater impairment evaluated by the motor score. Decreased bone turnover markers were found in a selected group of children three months after exposure to denosumab. Conclusion Bone loss was present in children with significant impairment of motor function, as well as decreased serum levels of bone resorption markers with new forms.

RESUMO Objetivo Avaliar o estado de saúde dos ossos em crianças com paralisia cerebral e o efeito terapêutico do denosumabe em um subgrupo de crianças com paralisia cerebral e redução da massa óssea. Métodos Crianças com paralisia cerebral foram avaliadas de acordo com seu escore de incapacidade motora (sistema de classificação para funções motoras grossas, de III a V), e marcadores de turnover ósseo. Dual de absorção de energia de raios X foi utilizado para medir a coluna lombar e total do corpo menos cabeça. Posteriormente, um grupo de crianças com paralisia cerebral e osteoporose foi tratado com denosumabe, um anticorpo monoclonal totalmente humano. Marcadores de remodelação óssea foram medidos antes e três meses após o tratamento. Resultados Houve uma redução da densidade óssea, particularmente em crianças com maior comprometimento do escore motor; os marcadores de remodelação óssea diminuíram em um grupo selecionado de crianças três meses depois de terem sido expostas ao denosumabe. Conclusão A perda óssea esteve presente em crianças com importante comprometimento das funções motoras, além da redução nos níveis séricos de marcadores de reabsorção óssea com novos tratamentos.

Biomarcadores óseos y su relación con la densidad mineral ósea en adultas jóvenes y adolescentes en su primer año posparto / Bone biomarkers and its relation with bone mineral density in adults and adolescents during the first year postpartum

La información sobre biomarcadores óseos en adolescentes y adultas durante el periodo posparto es incierta, por lo que el objetivo de este artículo fue analizar el patrón de biomarcadores óseos en adolescentes y adultas a 15, 90, 180 y 365 días posparto (dpp) y su asociación con la densidad mineral ósea (DMO) y lactancia materna. Se realizó un estudio de cohorte en 32 madres adolescentes ≤17 años y 41 adultas de 18 a 29 años de edad en el primer año posparto. Se realizaron medidas antropométricas, DMO y biomarcadores óseos y así como datos del tipo y la duración de lactancia. Como resultados se encontró asociación entre la concentración basal de N-telopéptidos ≤24 μg/L y mayor aumento de DMO. Las adolescentes tuvieron mayor concentración de N-telopéptidos (p≤0.004) y menor concentración de osteocalcina (5±3 vs13±4, p <0.001) que las adultas. La lactancia no afectó el cambio de DMO (p>0.050), ni de biomarcadores óseos. La osteocalcina se asoció con el cambio en DMO (p<0.040). La prolactina fue mayor entre las que practicaron lactancia materna exclusiva (p<0.001). A menor edad menores concentraciones de osteocalcina (p<0.001) y mayores concentraciones de N-telopéptidos (p<0.001). Se concluyó que a menor concentración de N-telopéptidos y mayor de osteocalcina hubo un mayor aumento de DMO, lo cual implica menor aumento de ésta en el grupo de adolescentes. La lactancia no afectó la DMO.

The objective of this study was to describe the trend of bone biomarkers in adults and adolescents women at 15, 90, 180 and 365 postpartum days (ppd) and its relation with bone mineral density (BMD). It was a prospective cohort of 32 teenager’s ≤17 and 41 women from 18 to 29 years old. We evaluated diet, anthropometry, BMD, bone biomarkers and hormonal profile. In all, the concentration of N-telopeptide was higher at 15 days postpartum decreasing during first year postpartum, but adolescents had the highest concentration. The lowest N-telopeptide concentration was associated with highest increasing of the BMD. Osteocalcin concentration was lower in adolescents than in adults women (5 ± 3 vs 13 ± 4 ng/mL, p<0.001) during first year postpartum. Exclusive breastfeeding did not affect the BMD (p>0.050) or bone biomarkers. Osteocalcin concentration was positively associated with bone BMD (p<0.040), breastfeeding did not affect osteocalcin concentrations. Prolactin was higher among women who breastfed exclusively (p<0.001). Age and breastfeeding inversely correlated with bone biomarkers (p<0.001) N-telopeptide and PTHi respectively. We concluded that a lower N-telopeptide concentration and a higher osteocalcin concentration were associated with a higher increasing of BMD, so then, adolescents showed the lowest recovery of the BMD. Breastfeeding does not affect the BMD.

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

BACKGROUND/AIMS: Our 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. METHODS: Thirty-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). RESULTS: Bone-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). CONCLUSIONS: RA 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.

Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice

OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM). Cell proliferation was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of α-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc ...

Effect of Combined Sex Hormone Replacement on Bone/Cartilage Turnover in a Murine Model of Osteoarthritis

BACKGROUND: Estrogens act on estrogen receptors distributed in articular cartilages, synovial membrane, and ligaments, which are thought to be related with degenerative changes. Meanwhile, progesterone is known to have a weak anabolic action on bone formation This study evaluates the effects of estrogen and progesterone hormone on bone/cartilage turnover in ovariectomized (OVX) rats. METHODS: Thirty-five 7-month-old female Sprague-Dawley rats were randomly divided into 5 groups and then ovariectomized bilaterally except the sham control group. The first and the second group acting as controls did not receive hormonal therapy, the third group received estrogen, the fourth group received progesterone, and the fifth group received combination of both hormones 10 weeks after surgery. Evaluations were done using the serum levels of cartilage oligomeric matrix protein (COMP) for cartilage turnover, collagen type I C-telopeptide (CTX-1) and osteocalcin (OC) for bone turnover at 11, 15, 19 weeks after OVX and histology using the Osteoarthritis Research Society International (OARSI) osteoarthritis (OA) cartilage histopathology assessment system. RESULTS: Significantly less cartilage degradation (decreased levels of COMP) was found in the combined hormone treated group in comparison with OVX group. Similarly, both hormonal treatment resulted in increased bone formation and decreased bone resorption i.e., a low overall bone turnover status (decrease in the serum OC and CTX-1 levels). CONCLUSIONS: Combined estrogen and progesterone therapy was found to be convincing in terms of reducing the severity of OA in this experimental model.

Current Recommendations for Laboratory Testing and Use of Bone Turnover Markers in Management of Osteoporosis

Osteoporosis is a major health problem worldwide, and is projected to increase exponentially due to the aging of the population. The absolute fracture risk in individual subjects is calculated by the use of algorithms which include bone mineral density (BMD), age, gender, history of prior fracture and other risk factors. This review describes the laboratory investigations into osteoporosis which include serum calcium, phosphate, creatinine, alkaline phosphatase and 25-hydroxyvitamin D and, additionally in men, testosterone. Parathyroid hormone (PTH) is measured in patients with abnormal serum calcium to determine its cause. Other laboratory investigations such as thyroid function testing, screening for multiple myeloma, and screening for Cushing's syndrome, are performed if indicated. Measurement of bone turnover markers (BTMs) is currently not included in algorithms for fracture risk calculations due to the lack of data. However, BTMs may be useful for monitoring osteoporosis treatment. Further studies of the reference BTMs serum carboxy terminal telopeptide of collagen type I (s-CTX) and serum procollagen type I N-terminal propeptide (s-PINP) in fracture risk prediction and in monitoring various treatments for osteoporosis may help expedite their inclusion in routine clinical practice.

Impacto da maturação esquelética em biomarcadores do metabolismo ósseo e na densidade mineral óssea em adolescentes brasileiros saudáveis / Impact of skeletal maturation on bone metabolism biomarkers and bone mineral density in healthy Brazilian male adolescents

OBJETIVO: Avaliar o comportamento de biomarcadores de formação e reabsorção óssea em adolescentes brasileiros em função da sua maturação biológica. MÉTODOS: Oitenta e sete voluntários foram divididos em grupos segundo a idade óssea (IO): 10-12 anos (n = 25), 13-15 anos (n = 36) e 16-18 anos (n = 26). Foram analisados peso (kg), estatura (m), índice de massa corporal (kg/m2), ingestão de cálcio de 3 dias (mg/dia), avaliação dos eventos pubertários pelos critérios de Tanner, níveis dos biomarcadores [osteocalcina (OC) (ng/mL), fosfatase alcalina óssea (FAO) (U/L), telopeptídeo carboxiterminal sérico (S-CTx) (ng/mL)] e sua correlação com a densidade mineral óssea (DMO) (g/cm2) por atenuação de raios X de dupla energia da coluna lombar, do fêmur proximal e de corpo total. RESULTADOS: Os biomarcadores mostraram comportamento semelhante, apresentando medianas elevadas dos 13 aos 15 anos (FAO = 154,71 U/L, OC = 43,0 ng/mL, S-CTx = 2,09 ng/mL; p < 0,01) e no estágio puberal G4. As medianas decresceram com o avançar da IO e da maturação sexual. Os níveis dos biomarcadores mostraram paralelismo com pico de velocidade em estatura, e, curiosamente, os biomarcadores de formação indicaram correlação negativa com a DMO, isto é, valores de DMO elevados se correlacionaram com valores baixos dos biomarcadores. CONCLUSÕES: Este é o primeiro estudo em adolescentes brasileiros com critérios de inclusão e exclusão rígidos e cuidadosos a avaliar a correlação entre marcadores ósseos e DMO frente a indicadores da maturação biológica. Os resultados ajudam a compreender o turnover ósseo e o monitoramento do metabolismo ósseo.

OBJECTIVE: To evaluate the behavior of biomarkers of bone formation and resorption in healthy male Brazilian adolescents according to their biological maturation. METHODS: Eighty-seven volunteers were divided into age groups according to bone age (BA): 10-12 years (n = 25), 13-15 years (n = 36), and 16-18 years (n = 26). Weight (kg), height (m), body mass index (kg/m2), calcium intake from 3 days assessed by 24-h food recall (mg/day), pubertal event evaluation by Tanner criteria, and serum biomarker levels (osteocalcin [OC] [ng/mL], bone alkaline phosphatase [BAP] [U/L], and serum carboxyterminal telopeptide [S-CTx] [ng/mL]) were recorded and correlated to bone mineral density (BMD) (g/cm2) measured by dual energy X-ray absorptiometry of the lumbar spine, proximal femur, and whole body. RESULTS: Biomarkers showed similar behaviors, presenting higher median values in the 13-15 year group (BAP = 154.71 U/L, OC = 43.0 ng/mL, S-CTx = 2.09 ng/mL; p < 0.01) and when adolescents were in the pubertal stage G4. Median biomarker values decreased with advancing BA and sexual maturation. Biomarker values showed parallelism with peak height velocity, and, interestingly, bone formation biomarkers indicated significant negative correlation with BMD in the different evaluated locations, i.e., higher BMD values correlated with lower bone biomarker values. CONCLUSIONS: This is the first study of healthy Brazilian adolescents with rigid and careful inclusion and exclusion criteria to assess the correlation of bone markers and BMD with biological maturation indicators. Our results can help understand bone turnover and monitor bone metabolism.

The effects of discontinuing long term alendronate therapy in a clinical practice setting / Efeitos da retirada do uso prolongado de alendronato na prática clínica

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7 percent) in G1 and one (5.2 percent) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

OBJETIVO: Avaliar a evolução dos marcadores de metabolismo ósseo (MMO) e da densidade mineral óssea (DMO) após cinco anos de uso de alendronato em mulheres osteoporóticas na pós-menopausa. SUJEITOS E MÉTODOS: 40 pacientes (pct) osteoporóticas, na pós-menopausa, em uso de alendronato (10 mg/dia) por pelo menos 5 anos (Grupo 1 − G1) tiveram o uso do bisfosfonato suspenso. O grupo 2 (G2): 25 mulheres na pós-menopausa, em uso de alendronato (10 mg/dia) há pelo menos 1 ano. Grupo 3 (G3): 23 pct osteoporóticas, controles ainda sem tratamento. G1 e G2 submeteram-se à avaliação da DMO por DXA (basal e após 12 meses de seguimento). Todas as pct colheram amostras basais de CTX e P1NP, e G1 e G2 submeteram-se a coletas trimestrais de CTX e P1NP durante 1 ano. Resultados foram analisados por ANOVA on ranks e Mann-Whitney. RESULTADOS: Níveis médios de DMO não variaram em G1 ou G2 durante o estudo; no entanto, 16 pct (45,7 por cento) no G1 e 1 pct (5,2 por cento) no G2 apresentaram redução clinicamente significativa de DMO (P < 0,001). Níveis basais de CTX e P1NP não diferiram entre G1 e G2, com ambos inferiores aos níveis de G3. Em G1, observou-se elevação significativa de CTX e P1NP após 3 meses. Os níveis de CTX e P1NP em G2 permaneceram estáveis durante todo o seguimento. CONCLUSÃO: Não parece haver supressão excessiva do metabolismo ósseo na prática clínica. A suspensão temporária do alendronato após seu uso prolongado pode não ser segura.

Normocalcemic primary hyperparathyroidism in clinical practice: an indolent condition or a silent threat? / Hiperparatireoidismo primário normocalcêmico na prática clínica: condição indolente ou ameaça silenciosa?

OBJECTIVE: To describe the characteristics of normocalcemic primary hyperparathyroidism (NPHPT) in patients seen for osteoporosis evaluation. PATIENTS AND METHODS: We examined the records of 156 women who came to the hospital to be screened for osteoporosis. Measurements of total calcium, PTH, 25-hydroxy vitamin D, and β-C-telopeptide were recorded. Bone mineral density and T-scores were evaluated by densitometry of the lumbar spine, femoral neck and distal one-third of the radius. The latter was only measured in patients with primary hyperparathyroidism. Nephrolithiasis and bone fractures were documented by a review of the medical records. RESULTS: We identified 14 patients with NPHPT, accounting for 8.9 percent of the population studied. In the medical records, the occurrence of kidney stones was reported in 28.6 percent of the patients with NPHPT, in contrast with only 0.7 percent of the noncarriers. Regarding the presence of general fractures, 21.4 percent of the patients with NPHPT were affected versus 16.2 percent of noncarriers. CONCLUSION: Data from our study suggest that NPHPT has a diverse phenotypic presentation, implying that this may not be an "indolent" disease.

OBJETIVO: Avaliar as características do hiperparatireoidismo primário normocalcêmico (HPTPN) em pacientes atendidos para avaliação de osteoporose. PACIENTES E MÉTODOS: Foi realizada análise de um banco de dados de 156 mulheres que procuraram atendimento para avaliação de osteoporose. Todas apresentavam dosagem de cálcio sérico, PTH, 25-hidroxi-vitamina D e C-telopeptídeo. A densidade mineral óssea e escore-T foram avaliados por meio de densitometria óssea de coluna lombar, colo do fêmur e rádio distal, este último apenas em pacientes com hiperparatireoidismo renal primário. Nefrolitíase e fraturas ósseas foram documentadas pela revisão dos prontuários. RESULTADOS: Foram identificadas 14 pacientes com HPTPN, correspondendo a 8,9 por cento da população estudada. Nos registros médicos, o relato da existência de litíase renal ocorreu em 28,6 por cento dos portadores de HPTN em contraste com apenas 0,7 por cento nas mulheres não portadoras, com um p < 0,001. CONCLUSÃO: Os dados do estudo sugerem que HPTPN tem uma apresentação fenotípica variada, podendo não ser uma patologia "indolente".

Acute Effects of Intravenous Administration of Pamidronate in Patients with Osteoporosis

We investigated acute effects of intermittent large dose bisphophonate therapy in osteoporotic patients. Peripheral blood mononuclear cells were incubated with alendronate (100 micrometer) for 18 hr, in vitro and cytokine expressions were measured by real-time RT-PCR. Pamidronate 30 mg was administered on 26 osteoporotic patients; and acute phase reactants, inflammatory cytokines and bone biomarkers were measured. The in vitro study showed significant increase in mRNA expression of IL-6, TNF-alpha and IFN-gamma. A notable rise in serum C-reactive protein (CRP) was observed over 3 days after pamidronate infusion (P=0.026). Serum levels of TNF-alpha, IL-6 and IFN-gamma were also significantly increased (P=0.009, 0.014, 0.035, respectively) and the increase in IL-6 levels were strongly correlated with CRP levels (P=0.04). Serum calcium and c-telopeptide levels rapidly decreased after the treatment (P=0.02, <0.001, respectively). This study showed that mRNA expression of inflammatory cytokines at peripheral blood mononuclear cells (PBMC) level were observed within 18 hr and marked elevation of inflammatory cytokines and acute phase reactants were demonstrated after pamidronate infusion at the dose for osteoporosis. Our studies confirmed that intermittent large dose aminobisphosphonate causes acute inflammation.

C telopeptides of type I collagen inpostmenopausal women: an experience in a Tunisian clinical laboratory

The purpose of study was to evaluate the interest of C-telopeptides of type I collagen [CTX] in the diagnosis of osteoporosis in postmenopausal women and to define its cut-off value. A transverse descriptive study enrolled postmenopausal women: 139 osteoporotic [G1] and 39 non osteoporotic [G2]. The 2 groups were defined by bone density measurement. The followmg markers were measured: serum alkaline phosphatase [ALP] bone alkaline phosphatase [bone ALP], serum C-terminal telopeptide of type I collagen [CTX]. Statistical analyses were performed using SPSS 10, 5. The corresponding estimation of sensitivity and specificity of CTX have been presented as receiver Operating Curve [ROC]. There was no difference in the measurement of ALP and bone ALP in the 2 groups but CTX was statistically higher in G1 compared to G2 [p<0.001]. The percentage of osteoporotic women [G1] with CTX values>0.500 ng/ml was higher than that of non osteoporotic women [G2]. We have established a ROC curve to find the cut-off value of CTX that enables the distinction between osteoporotic women with high level of bone remodelling, and non osteoporotic women. The cut-off value of CTX 0.55 pg/mi was the best; it associated best sensitivity and specificity. The total increase and significance for CTX was greater in the group of osteoporotic women and appeared therefore to be a good bone turnover marker in the diagnosis of osteoporosis in comparison with ALP and bone ALP. The cut-off value of CTX 0.55 pg/mi may improve the sensitivity and specificity of prediction of future fractures

Serum cross-linked n-telopeptides of type 1 collagen (NTx) in patients with solid tumors / Dosagem sérica do N-telopeptídeo do colágeno tipo I (NTx) em pacientes com tumores sólidos

CONTEXT AND OBJECTIVE: Cross-linked N-telopeptides of type I collagen (NTx) increase in concentration in situations in which bone resorption is increased, such as osteoporosis and bone metastasis (BM). We aimed to evaluate the serum concentrations of NTx in a sample of patients with several types of solid tumors. DESIGN AND SETTING: Cross-sectional analytical study with a control group in a tertiary public hospital. METHODS: We performed the quantitative enzyme-linked immunosorbent assay (ELISA) on serum NTx levels in 19 subjects without a history of cancer and 62 patients with various solid tumors who had been referred for a bone scan. Three experienced analysts read all bone scans. RESULTS: The serum NTx levels in patients with cancer and BM, with cancer but without BM and without cancer were 46.77 ± 2.58, 32.85 ± 2.05 and 22.32 ± 2.90 respectively (P < 0.0001). We did not find any significant correlations of serum NTx with age, gender, history of bone pain, tumor type and bone alkaline phosphatase levels. We found a significant correlation between serum NTx and alkaline phosphatase levels (R² = 0.08; P = 0.022). CONCLUSIONS: Serum NTx levels are significantly higher in patients with solid tumors and bone metastases than they are in patients without bone metastases and in normal controls.

CONTEXTO E OBJETIVO: Os N-telopeptídeos do colágeno tipo-I (NTx) elevam-se quando a reabsorção óssea está aumentada, devido a condições como osteoporose e metástase óssea. Sendo assim, temos por objetivo avaliar os níveis séricos de NTx em uma população heterogênea de pacientes com tumores sólidos. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico com grupo controle, realizado em hospital público terciário. MÉTODOS: 19 pacientes sem história de câncer e 62 pacientes com tumores sólidos de vários tipos, encaminhados para estadiamento e investigação dos sintomas esqueléticos, foram avaliados pela técnica de ELISA (Enzyme Linked Immuno Sorbent Assay) quantitativa para a dosagem de NTx. Três especialistas leram todas as imagens ósseas. RESULTADOS: O nível de NTx encontrado em pacientes com câncer e metástase óssea, sem metástase óssea e sem diagnóstico de câncer foi 46,77 ± 2,58, 32,85 ± 2,05 e 22,32 ± 2,90, respectivamente (P < 0,0001). Não encontramos correlação entre o NTx, idade, sexo, história de dor óssea, tipo de tumor e níveis de fosfatase alcalina óssea. Encontramos correlação significativa entre os níveis de NTx e de Fosfatase Alcalina (r² = 0,08, P = 0,022). CONCLUSÃO: O NTx sérico é significativamente mais elevado em pacientes com tumores sólidos e metástases ósseas quando comparado com pacientes sem metástases ósseas e controles normais.

Follow-up study of bone mineral density and C-terminal telopeptide marker as predicators of fracture risk

Osteoporosis is a major health problem in many countries. Osteoporotic fractures are the main consequence of osteoporosis. Our aim was to identify the usefulness of bone mineral density and C-terminal telopeptide of type 1 collagen as predictors of fracture risk. We evaluated both BMD and serum carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen [ICTP] in 212 subjects recruited from the community. This included healthy postmenopausal women and males over 60 years. Subjects were followed up for the occurrence of fractures jar one year. X-ray radio graphs of thoracic and lumber regions were done to detect silent vertebral fractures at baseline, and at the end of 1 year. Male gender was associated with a higher level of serum ICTP. BMD was insignificantly higher in males compared with females. Age, weight, BMI were significantly correlated with BMD. Age was significantly correlated with ICTP levels. BMD proved to be a strong predictor of incident fracture specially vertebral and hip fractures. Serum levels of ICTP were also predictors of incident fracture and this observation was more evident in females compared to males. Advancing age and low weight were predictors of increased incidence of fractures. Coffee was found to increases bone resorption, accordingly has a detrimental effect on bone strength. Other caffeine containing beverages [tea, cola] were not fond to have a significant effect on bone resorption

Bone density and bone turnover markers in patients with epilepsy on chronic antiepileptic drug therapy

In this comparative, cross-sectional study, we evaluated 55 patients with epilepsy on chronic use of antiepileptic drugs (AED); [(38 females and 17 males, 35 ± 6 years (25 to 47)] and compared to 24 healthy subjects (17 females/7 males). Laboratorial evaluation of bone and mineral metabolism including measurements of bone specific alkaline phosphatase (BALP) and carboxyterminal telopeptide of type I collagen (CTX-I) were performed. Bone mineral density (BMD) was measured by DXA. BALP and CTX-I levels did not differ significantly between the groups. CTX-I levels were significantly higher in patients who were exposed to phenobarbital (P< 0.01) than those who were not. Patients presented BMD of both sites significantly lower than the controls (0.975 ± 0.13 vs. 1.058 ± 0.1 g/cm²; p= 0.03; 0.930 ± 0.1 vs. 0.988 ± 0.12 g/cm²; p= 0.02, respectively). Total hip BMD (0.890 ± 0.10 vs. 0.970 ± 0.08 g/cm²; p< 0.003) and femoral neck (0.830 ± 0.09 vs. 0.890 ± 0.09 g/cm²; p< 0.03) were significantly lower in patients who had been exposed to phenobarbital, in comparison to the non-phenobarbital users. In conclusion, patients on AED demonstrate reduced BMD. Among the AED, phenobarbital seems to be the main mediator of low BMD and increases in CTX-I.

Neste estudo comparativo, transversal, 55 pacientes com epilepsia [38 mulheres e 17 homens; 35 ± 6 anos (25 a 47anos)] foram comparados com 24 indivíduos normais (17 mulheres / 7 homens). Foi realizada uma avaliação laboratorial do metabolismo ósseo e mineral incluindo a dosagem de fosfatase alcalina específica óssea (BALP) e telopeptídeo carboxiterminal do colágeno tipo I (CTX-I). Densidade mineral óssea (DMO) da coluna lombar e do fêmur foi medida por DXA. BALP e CTX-I não foram diferentes entre os grupos. CTX-I foi significativamente mais elevado nos pacientes expostos ao fenobarbital do que os que não usaram essa medicação (p< 0,01). DMO de ambos os sítios foi menor no grupo de pacientes (0,975 ± 0,13 vs. 1,058 ± 0,1 g/cm²; p= 0,03; 0,930 ± 0,1 vs. 0,988 ± 0,12 g/cm²; p= 0,02, respectivamente). DMO do fêmur total (0,890 ± 0,10 vs. 0,970 ± 0,08 g/cm²; p< 0,003) e colo do fêmur (0,830 ± 0,09 vs. 0,890 ± 0,09 g/cm²; p< 0,03) foi significativamente menor nos pacientes que usaram fenobarbital. Em conclusão, pacientes portadores de epilepsia em uso crônico de drogas antiepilépticas (DAE) demonstraram uma redução da DMO. Entre as DAE, o fenobarbital parece ser o principal mediador da diminuição da DMO e do aumento do CTX-I.

Comparing the effect of short term post meals and bedtime calcium supplementation on the C-terminal telopeptide crosslinks and PTH levels in postmenopausal osteopenic women.

BACKGROUND: Calcium supplement for postmenopausal osteopenic women can significantly reduce bone loss and the risk of fractures. However, the optimal time for calcium supplementation remains controversial. OBJECTIVE: The aim of the present study was to compare the effect of twice daily post meals and bedtime calcium supplementation for a two week periods, on C-terminal telopeptide crosslinks and PTH levels in postmenopausal osteopenic women. DESIGN: A randomized double blind placebo-control, crossover design, was carried out on 3 consecutive periods 3 of a 2-week treatment regimen. In the first period, all the subjects randomly received either two calcium carbonate tablets (Chalk Cap all subjects randomly received either two calcium 334 mg per tab) or placebo at bedtime with one tablet of calcium tablet or placebo after breakfast and dinner for two weeks. In the second period, subjects received only placebo tablets after the meals and at bedtime for 2 weeks. In the third period subjects received either calcium carbonate or placebo for another two weeks. The C-terminal telopeptide crosslinks were measured at 8.00 am and serum PTH were sampled at 8 time points (12.00 am, 2.00 am, 4.00 am, 6.00 am, 8.00 am, 9.00 am, 5.00 pm, and 7.00 pm respectively by the end of each study at the first and third period. RESULTS: The present study showed thirty-six postmenopausal subjects (mean age 63.9 + 3.66 years) participated in the present study. The mean T-score BMD of the spine and hip were -2.96 + 0.87 and -2.96 + 0.77 gm/cm2. C-terminal telopeptide crosslinks levels of the bedtime supplementation were significantly lower than the post meal supplementation (0.228 + 0.002 ng/ml vs 0.313 + 0.003 ng/ml, p < 0.001). The mean night time serum PTH level during the bedtime was significantly lower than the post meal period. (25.17 + 2.31 pg/ml vs 31.930 + 2.677 pg/ml, p < 0.001). No differences in the post meal PTH level between two periods were observed CONCLUSION: The bedtime calcium supplementation appeared to reduce the bone resorption marker and night time serum PTH levels greater than the post meal calcium supplementation in this short term period study. However, long term comparison may be needed.

Different mechanism of bone loss in ageing women and men in Khon Kaen Province.

The changes of vitamin D status and biochemical markers of bone turnover have been reported with aging. In this study we determined age-related levels of vitamin D and biochemical markers of bone turnover in the general adult population between the ages of 20 and 84 years who were living in Khon Kaen province in northeastern Thailand. Serum 25 hydroxyvitamin D was determined as an indicator of vitamin D status. Serum total alkaline phosphatase and N-terminal mid fragment osteocalcin were measured as biochemical markers of bone formation and serum C-terminal fragment of type I collagen was measured as a marker of bone resorption. The levels of serum 25 hydroxyvitamin D were high in the Khon Kaen population. Men had higher levels of 25 hydroxyvitamin D than did women. However, there were no changes with age in either sex. In women, all biochemical markers of bone turnover increased with age after the fourth decade. The sharp increase was observed in the sixth decade which was around the menopausal age. In contrast, in men all biochemical markers of bone turnover except serum total alkaline phosphatase had a tendency to decrease with age. CONCLUSION: There was no evidence of vitamin D deficiency in a Khon Kaen population. In addition, serum vitamin D levels did not decline with ageing. Women and men showed different changes of biochemical markers of bone turnover with ageing indicating gender difference in the pathogenesis of osteoporosis.