Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway / 中华医学杂志(英文版)

BACKGROUND@#Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23.@*METHODS@#We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined.@*RESULTS@#DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown.@*CONCLUSIONS@#Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.

Effects of 275 nm and 310 nm ultraviolet irradiation on bone metabolism in ovariectomized osteoporotic rats / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of 275 nm and 310 nm ultraviolet irradiation on ovariectomized rats' bone metabolism.@*METHODS@#Twenty four 3-month-old female Sprague-Dawley (SD) rat were randomly divided into control group, sham operated group, 275 nm ultraviolet (UV) irradiation group and 310 nm UV irradiation group. Each group contained 6 rats. The rats in the two irradiation groups were treated with bilateral ovariectomy. The rats in sham operated group received sham operation (They were given the same back incision and a bit of par-ovarian fat were removed). Control group received no disposition. About 24 weeks after operation, all the rats received detailed bone mineral density (BMD) detection again. Detection regions include cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur. Next, osteopenia rats in 275 nm irradiation group were UV irradiated 275 nm with fixed illumination intensity (15 μW/cm2) everyday for 16 weeks. The osteopenia rats in 310 nm irradiation group were UV irradiated 310 nm with fixed illumination intensity (15 μW/cm2) everyday for 16 weeks. The backs of the rats were shaved regularly as irradiation area (6 cm×8 cm). After 16-week irradiation, all the rats' BMD of cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur were measured. At the end of the trial, all the rats' blood specimens were obtained and serum 25(OH)D, procollagen type Ⅰ N-peptide (PINP) and osteocalcin (OC) were measured.@*RESULTS@#Compared with control group [(238.78±26.74) mg/cm3], the BMD of the whole body were significantly lower in 275 nm [(193.34±13.28) mg/cm3] and 310 nm [(191.19±18.48) mg/cm3] irradiation groups (P=0.002, P=0.001). There were no significant difference between sham operated group [(227.20±14.32) mg/cm3] and control group. After 16-week ultraviolet irradiation, the BMD of the whole body were significantly increased in 275 nm [(193.34±13.28) mg/cm3 vs. (221.68±25.52) mg/cm3, P=0.005] and 310 nm groups [(191.19±18.48) mg/cm3 vs. (267.48±20.54) mg/cm3, P < 0.001] after corresponding irradiation. The BMD of the four body regions (lumbar vertebra, proximal femur, mid femur and distal femur) had significantly increased after irradiation in 275 nm irradiation group. For 310 nm irradiation group, the BMD in cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur also had increased significantly after 310 nm ultraviolet irradiation. The concentration of serum 25(OH)D and OC was higher in 275 nm irradiation group than in control group [(46.78±5.59) μg/L vs. (21.32±6.65) μg/L, P=0.002;(2.05±0.53) U/L vs. (1.32±0.07) U/L, P=0.022]. Compared with the control, the concentration of serum 25(OH)D [(58.05±12.74) μg/L], OC [(2.04±0.53) U/L] and PINP [(176.16±24.18) U/L] was significantly higher (P < 0.001, P=0.015, P=0.005) in 310 nm irradiation group. However, there were no significantly difference between sham operated group and the control.@*CONCLUSION@#Both 275 nm and 310 nm ultraviolet could improve rats' vitamin D synthesis. Both 275 nm and 310 nm ultraviolet could improve osteopenia rats' bone condition. The irradiation of 310 nm might be more effective on bone condition improvement.

Behavioural and objective vestibular assessment in persons with osteoporosis and osteopenia: a preliminary investigation / Behavioural and objective vestibular assessment in persons with osteoporosis and osteopenia: a preliminary investigation

Abstract Introduction: Calcium is vital for the functioning of the inner ear hair cells as well as for the neurotransmitter release that triggers the generation of a nerve impulse. A reduction in calcium level could therefore impair the peripheric vestibular functioning. However, the outcome of balance assessment has rarely been explored in cases with osteopenia and osteoporosis, the medical conditions associated with reduction in calcium levels. Objective: The present study aimed to investigate the impact of osteopenia and osteoporosis on the outcomes of behavioural and objective vestibular assessment tests. Methods: The study included 12 individuals each in the healthy control group and osteopenia group, and 11 individuals were included in the osteoporosis group. The groups were divided based on the findings of bone mineral density. All the participants underwent behavioural tests (Fukuda stepping, tandem gait and subjective visual vertical) and objective assessment using cervical and ocular vestibular evoked myogenic potentials. Results: A significantly higher proportion of the individuals in the two clinical groups' demonstrated abnormal results on the behavioural balance assessment tests (p < 0.05) than the control group. However, there was no significant difference in latencies or amplitude of cervical vestibular evoked myogenic potential and oVEMP between the groups. The proportion of individuals with absence of ocular vestibular evoked myogenic potential was significantly higher in the osteoporosis group than the other two groups (p < 0.05). Conclusion: The findings of the present study confirm the presence of balance-related deficits in individuals with osteopenia and osteoporosis. Hence the clinical evaluations should include balance assessment as a mandatory aspect of the overall audiological assessment of individuals with osteopenia and osteoporosis.

Resumo: Introdução: O cálcio é vital para o funcionamento das células ciliadas, assim como para a liberação dos neurotransmissores que desencadeiam um impulso nervoso. Uma redução nos níveis de cálcio poderia, portanto, prejudicar o funcionamento vestibular periférico. No entanto, a avaliação do equilíbrio tem sido raramente explorada em casos de osteopenia e osteoporose, condições médicas associadas à redução dos níveis de cálcio. Objetivo: O presente estudo teve como objetivo investigar o impacto da osteopenia e da osteoporose nos resultados dos testes de avaliação comportamental e vestibular objetiva. Método: O estudo incluiu 12 indivíduos nos grupos controle e grupo de osteopenia e 11 indivíduos no grupo da osteoporose. Os grupos foram divididos com base nos achados da densidade mineral óssea. Todos os participantes foram submetidos a testes comportamentais (Prova dos Passos de Fukuda, Marcha em tandem e Vertical Visual Subjetiva) e à avaliação objetiva com o uso de potenciais evocados miogênicos vestibulares cervical e ocular (cVEMP e oVEMP). Resultados: Uma proporção significativamente maior de indivíduos nos dois grupos com condições clínicas mostrou resultados anormais nos testes de avaliação comportamental e do equilíbrio (p < 0,05) do que o grupo controle. Embora não tenha havido diferença significativa nas latências ou na amplitude de cVEMP e oVEMP entre os grupos, a proporção de indivíduos com ausência de oVEMP foi significativamente maior no grupo da osteoporose do que nos outros dois grupos (p < 0,05). Conclusão: Os resultados do presente estudo demonstram a presença de déficits de equilíbrio em indivíduos com osteopenia e osteoporose. Assim, as avaliações clínicas gerais e audiológicas de indivíduos com osteopenia e osteoporose deveriam incluir a avaliação do equilíbrio como um aspecto obrigatório.

Efecto del ranelato de estroncio sobre la densidad mineral ósea en hombres con osteoporosis / Effect of strontium ranelate on bone mineral density in men with osteoporosis

La osteoporosis afecta al 6-7% de la población masculina. Es alta la proporción de pacientes con fracturas sin diagnóstico previo de esta enfermedad. La mortalidad luego de una fractura es mayor en hombres que en población femenina; a pesar de esto, la mayoría de los pacientes no reciben tratamiento. Los fármacos aprobados, en nuestro medio, para tratar la osteoporosis masculina son: bifosfonatos, teriparatida y ranelato de estroncio. El objetivo de este estudio fue evaluar el efecto del ranelato de estroncio sobre la densidad mineral ósea en hombres después de 1 año de tratamiento. Se incluyeron los registros de 20 hombres de 67,8±3,0 años, tratados con ranelato de estroncio (2 g/día) durante 1 año. Todos los pacientes presentaban un T-score inferior a -2,5 en cadera o columna vertebral o un T-score inferior a -2,0 y factores de riesgo de fractura. No hubo modificación de parámetros de laboratorio luego del tratamiento (calcemia, calciuria, fósforo sérico, parathormona, 25(OH)vitamina D, fosfatasa alcalina y desoxipiridinolina) en relación a los basales. Luego del tratamiento con ranelato de estroncio se observó incremento de la densidad mineral ósea en columna lumbar: 0,953±0,029 versus 0,997±0,030 g/cm2 (p=0,0068), cuello femoral: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0,0084) y cadera total: 0,821±0,02 versus 0,834±0,02 g/cm2 (p=0,0419). Conclusión: el tratamiento con ranelato de estroncio produjo un incremento significativo de la densidad mineral ósea en columna lumbar y fémur proximal en hombres con osteoporosis. (AU)

Osteoporosis affects 6-7% of the male population. The proportion of patients with fragility fractures but without diagnosis of the disease is high. Mortality after hip fracture is higher in men than in women; in spite of this, most patients are left without treatment for osteoporosis. Drugs approved, for the treatment of osteoporosis in our country are bisphosphonates, teriparatide, and strontium ranelate (SrR). The objective of this study was to evaluate the effect of SrR on axial BMD in men after one year of treatment. We obtained pertinent data from medical registries of 20 men aged 67,8±3,0 years, treated with oral SrR (2 g/day) for 12 months. All patients had a T-score below -2,5 at the hip or the lumbar spine, or a T-score below -2,0 and one or more risk factors for fracture. The levels of serum calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, or PTH, or urinary calcium and desoxipyridinoline remained unchanged following SrR administration. After treatment with SrR there were significant increases in BMD at the lumbar spine: 0,953±0,029 versus 0,997±0,030 g/cm2 (p=0,0068), femoral neck: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0.0084), and total hip: 0,821±0,02 versus 0,834±0,02 g/cm2 (p=0,0419). Conclusion: in osteoporotic men, treatment with SrR significantly increases BMD in the lumbar spine and the proximal femur. (AU)

Hiperparatiroidismo primario asintomático en mujeres / Asymptomatic primary hyperparathyroidism in women

El hiperparatiroidismo primario puede tener diferentes características. Una de ellas es la forma asintomática. Esta es una variante leve del hiperparatiroidismo primario hipercalcémico, que se caracteriza por una calcemia no mayor a 1 mg/dl sobre el límite superior del método, hormona paratiroidea intacta (PTHi) elevada, ausencia de litiasis renal, deterioro de la función renal y de osteoporosis, edad menor de 50 años, y calciuria menor a 400 mg/día. No es una entidad quirúrgica, pero en su evolución puede llegar a serlo. Se estudiaron 24 mujeres postmenopáusicas, todas mayores de 50 años, con diagnóstico de hiperparatiroidismo asintomático, se describieron las manifestaciones clínicas, los cambios densitométricos, los parámetros bioquímicos y del remodelado óseo y se compararon los resultados con las variantes clásica y normocalcémica de la enfermedad. Se establecieron los criterios diagnósticos y se observó que solo 2 (8.3%) de las pacientes, durante un seguimiento de 44 ± 12 meses tuvo necesidad de paratiroidectomía. En definitiva, el hiperparatiroidismo primario asintomático es una alteración benigna, de seguimiento clínico periódico que, en pocas ocasiones, durante el seguimiento puede requerir cirugía.

Primary hyperparathyroidism may have different characteristics. One is the asymptomatic form. This is a mild variant of hypercalcemic hyperparathyroidism, characterized by a calcemia not greater than 1 mg/dl above the upper limit of the method, a high intact parathyroid hormone (iPTH), absence of renal stones, renal function impairement, and osteoporosis, less than 50 years of age, and less than 400 mg/day calciuria. It is not a surgical entity, but its evolution may require it. Twenty-four postmenopausal women, all older than 50 years, with a diagnosis of asymptomatic hyperparathyroidism, were studied. Clinical manifestations, densitometric changes, biochemical parameters and bone remodeling were analyzed and the results were compared with the classic and normocalcemic variants of the disease. Diagnostic criteria were established and observed that only 2 (8.3%) of patients, during a follow up of 44 ± 12 months, had need for a parathyroidectomy. In conclusion, the asymptomatic primary hyperparathyroidism is a benign disorder, of periodic clinical follow-up, which rarely may require surgery.

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

OBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

Factores de riesgo y marcadores bioquímicos de la enfermedad metabólica ósea del recién nacido prematuro / Risk factors and biochemical markers in metabolic bone disease of premature newborns

Introducción: La enfermedad metabólica ósea (EMO) del recién nacido prematuro (RNPT) es una complicación de origen multifactorial, que ha ido en aumento, consecuencia de la disminución progresiva de la mortalidad. El objetivo del estudio fue analizar los factores de riesgo (FR) pre y postnatales relacionados con la EMO severa y sus marcadores analíticos. Pacientes y Métodos: Estudio retrospectivo observacional, descriptivo y analítico, que incluyó RNPT nacidos con menos de 32 semanas y/o peso menor de 1.500 g entre enero de 2012 y diciembre de 2014. Se analizó la muestra en función del desarrollo de EMO severa. Resultados: 139 pacientes, con 25(OH)D3 media de 70,68 ± 25,20 nmol/l, mayor en los nacidos en primavera-verano que en otoño-invierno (80,94 ± 25,33 vs 61,13±21,07; p = 0,000). Los pacientes con EMO severa presentaron valores de 25(OH)D3 similares al resto de pacientes (65,61 ± 26,49 vs 72,07 ± 24,89; p = 0,283), y superiores de fosfatasa alcalina (FA) (1314,19 ± 506,67 vs 476,56 ± 188,85; p = 0,000). Mediante curva ROC se calculó un punto de corte de FA de 796,5 IU/l (S 95,2%, E 92,4%). Los FR más asociados al desarrollo de EMO severa fueron el crecimiento intrauterino restringido, el peso al nacimiento y la duración de ventiloterapia y nutrición parenteral. Conclusiones: Las cifras de FA son las que mejor se relacionan con el desarrollo de EMO severa. El riesgo de ésta aumenta a mayor número de factores de riesgo y menores cifras de vitamina D3. Niveles de 25(OH)D3 por encima de 70 nmol/l parecen proteger del desarrollo de EMO, incluso en pacientes con múltiples factores de riesgo.

Background: Metabolic bone disease (MBD) of prematurity is a complication of multifactorial aetiology, which has been increasing, due to progressive decrease in mortality of preterm newborns. The aim of the study was to analyze risk factors of severe MBD and its analytical markers. Patients and Method: Retrospective study involving preterm infants less than 32 weeks gestational age and/or weight less tan 1,500 g born between january 2012 and december 2014. Comparison was made according to the presence of severe MBD. Results: 139 patients were recruited. Mean value of 25(OH)D3 was 70.68 ± 25.20 nmol/L, being higher in patients born in spring-summer than in autumn-winter (80.94 ± 25.33 vs 61.13 ± 21.07; p = 0.000). Levels of 25(OH)D3 were similar in patients with severe MBD compared with the rest of patients (65.61 ± 26.49 vs 72.07 ± 24.89, P = 0.283). Higher levels of alkaline phosphatase (AP, IU/L ) (1314.19 ± 506.67 vs 476.56 ± 188.85; p = 0.000) were found in these patients. Cutoff point of AP 796.5 IU/L (S 95.2%, specificity 92.4%) was calculated by ROC curve. The risk factors most associated to severe EMO were restricted fetal growth, birth weight, duration of ventilation therapy and parenteral nutrition. Conclusions: AP levels were the best marker of severe MBD development. EMO risk increases with the number of risk factors and lower levels of 25(OH)D3. Levels of 25(OH)D3 higher than 70nmol/L appear to protect from the development of severe MBD, even in patients with multiple risk factors.

Bone and heart abnormalities of subclinical hyperthyroidism in women below the age of 65 years / Anormalidades ósseas e cardíacas do hipertireoidismo subclínico em mulheres com menos de 65 anos

The objective of the present study was to evaluate bone and cardiac abnormalities and symptoms and signs of thyroid hormone excess in women with subclinical hyperthyroidism (SCH) aged < 65 years. Forty-eight women with SCH were evaluated. The control group consisted of 48 euthyroid volunteers. The mean symptom rating scale score was significantly higher in patients. Cardiac involvement, both morphological and affecting systolic and diastolic functions, was also observed in patients. Women with SCH showed a significant increase in serum markers of bone formation and resorption. In addition, bone mineral density (BMD) was lower in the femoral neck but not in the lumbar spine in patients before menopause, whereas a lower BMD was observed at both sites in postmenopausal patients. SCH is not completely asymptomatic in women aged < 65 years, and is associated with heart abnormalities and with increased bone turnover and reduced BMD even before menopause.

O objetivo deste estudo foi avaliar as anormalidades ósseas e cardíacas, sintomas e sinais de excesso de hormônio tireoidiano em mulheres com hipertireoidismo subclínico (HSC) e menos de 65 anos de idade. Quarenta e oito mulheres com HSC foram avaliadas. O grupo-controle consistiu de 48 voluntárias eutireoidianas. A média do escore de sintomas foi significativamente maior em pacientes que em controles. Comprometimento cardíaco, morfológico e afetando as funções sistólica e diastólica, também foi observado. Mulheres com HSC apresentaram significativo aumento dos marcadores séricos de formação e reabsorção óssea. A densidade mineral óssea (DMO) foi menor no colo de fêmur, mas não em coluna lombar em mulheres antes da menopausa; enquanto e em ambos os sítios nas mulheres pós-menopausadas. HSC não é inteiramente assintomático em mulheres com menos de 65 anos, está associado a anormalidades cardíacas morfológicas e funcionais, incremento da remodelação óssea, e menor DMO, mesmo antes da menopausa.

Clinical application of biochemical markers of bone turnover / Marcadores bioquímicos da remodelação óssea

With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies have markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. This review provides an overview of the current evidence regarding the clinical use of biochemical markers of bone remodelling in bone disease, with an emphasis on osteoporosis.

Tendo em vista o crescimento da população idosa na maioria dos países, os distúrbios do metabolismo ósseo e mineral estão tornando-se cada vez mais relevantes na prática clínica diária. Conseqüentemente, o interesse e a necessidade de medidas efetivas para serem usadas no rastreamento, diagnóstico e seguimento de tais patologias vêm crescendo acentuadamente. Além da avaliação clínica e de técnicas de imagens, os marcadores bioquímicos desempenham um importante papel na avaliação e diagnóstico das doenças ósseas metabólicas. Recentemente, a melhor caracterização dos componentes intracelulares e extracelulares da matriz óssea resultou no desenvolvimento dos marcadores moleculares, os quais refletem tanto a formação como a reabsorção óssea. Estes marcadores bioquímicos não são invasivos e comparativamente são de mais baixo custo, e quando aplicados e interpretados corretamente são instrumentos úteis no diagnóstico e tratamento das doenças ósseas metabólicas. Esta revisão abordará evidências atuais, levando em consideração o uso clínico dos marcadores bioquímicos da remodelação óssea nas doenças metabólicas ósseas, com ênfase na osteoporose.

Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest.

Efecto del calcio dietético vs el citrato de calcio sobre marcadores bioquímicos convencionales en mujeres perimenopáusicas / Effect of dietary calcium vs. calcium citrate on conventional biochemical markers in perimenopausal women

OBJETIVO: Comparación del efecto del citrato de calcio y una dieta con calcio en los alimentos sobre marcadores bioquímicos convencionales. MATERIAL Y MÉTODOS: Se estudiaron 82 mujeres de 30 a 35 años de edad divididas al azar en tres grupos: grupo control: 23 mujeres sin modificación de sus hábitos alimenticios ni actividad física. Grupo con calcio dietético: 28 mujeres con un régimen de 1 000 mg de calcio más actividad física de 30 minutos tres veces por semana. Grupo con citrato de calcio: 31 mujeres suplementadas con citrato de calcio (600 mg), más 500 mg de calcio dietético, y actividad física de 30 minutos tres veces por semana durante siete meses. Se hizo densitometría ósea de calcáneo para clasificarlas en normal y osteopenia, se determinaron parámetros bioquímicos al inicio y final del estudio: fosfatasa alcalina, magnesio, calcio y fósforo séricos, y relación calcio/creatinina en orina. RESULTADOS: El 34 por ciento de las mujeres presentaron osteopenia; éstas tuvieron una reducción significativa en el calcio final en el grupo de citrato de calcio en comparación con el grupo de calcio dietético (p<0.05, 7.4 mg/dl vs 8.8 mg/dl). En la valoración final se observó hipermagnesemia significativa en el grupo de calcio dietético, en comparación con el grupo de citrato de calcio (p<0.05). El fósforo disminuyó en el grupo con calcio dietético (3.5 a 3.2 mg/dl) (p>0.05). La relación calcio/creatinina fue normal en todos los grupos. CONCLUSIONES: El grupo con calcio dietético presentó mayor formación ósea que el grupo con citrato de calcio; en ninguno de ellos se observó resorción ósea.

Osteoporosis in postmenopausal Saudi women using dual x-ray bone densitometry

A pilot study to estimate the prevalence of osteopenia and osteoporosis in postmenopausal Saudi women. Lumbar spine bone density was measured in 830 postmenopausal Saudi women 50-80 years of age [average 59 years], using dual x-ray absorptiometry [DXA] at the King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between 1989 and 1999. The results of the bone mineral density [BMD] in gm/cm2 were compared to the peak bone density [PBD] in healthy young women [T-score]. Based on the definition of World Health Organization [WHO], the T-score value was considered for analysis. Accordingly, 248 [29.9%] subjects showed normal result, mean BMD of 1.117 +/- 0.13 and T-score of -0.66 SD; while 254 [30.6%] subjects showed osteopenia, mean BMD of 0.983 +/- 0.11 and T-score of -2.4 SD and 328[39.5%] subject showed osteoporosis, mean BMD of 0.767 +/- 0.11 and T-score of -3.4 SD. When the 830 subjects were analyzed by decades, there were 42.3% normal, 33.4% osteopenia and 24.3% osteoporosis in age 50-59 years; 11% normal, 27% with osteopenia and 62% with osteoporosis in age 60-69 years while in older age 70-79 years only 4.6% had normal BMD, 21.5% had osteopenia and 73.8% had osteoporosis. Osteopenia and osteoporosis are common among postmenopausal Saudi women and should be considered as a matter of public health. Bone densitometry should be used to assess the severity of bone loss, identify those who need therapy and for follow up and early diagnosis of those with osteopenia in order to institute proper therapy and avoid future osteoporosis

Effect of metabolic control on parathyroid hormone secretion in diabetic patients

The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH) secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 + or - 0.2 percent; range = 3.5-5.0 percent), 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 + or - 0.4 percent; range = 6.0-8.5 percent), and 8 patients with poor metabolic control (group P: HbA1C = 12.5 + or - 1.0 percent; range: 10.0-18.8 percent). Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight) and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 + or - 0.01 mmol/l) than in group N (1.21 + or - 0.01 mmol/l) and group G-R (1.22 + or - 0.01 mmol/l). After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01) in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 + or - 2.1 vs G-R = 13.7 + or - 1.6 vs P = 7.5 + or - 0.7 pmol/l; P<0.05 for P vs N and G-R). The present results show that PTH secretion is impaired in patients with poorly controlled diabetes

O papel dos marcadores bioquímicos do metabolismo ósseo no diagnóstico e seguimento laboratorial das doenças ósteo-metabólicas / The role of bone biochemical markers in the diagnosis and follow-up bone metabolic diseases

Os novos marcadores bioquímicos do metabolismo ósseo säo um novo recurso laboratorial com aplicaçöes cada vez mais amplas. Podem ser divididos em dois grupos principais: os de formaçäo óssea, representados principalmente pela fosfatase alcalina óssea e pela osteocalcina, e os de reabsorçäo óssea, representados basicamente pelos métodos que avaliam a excreçäo de fragmentos específicos produzidos pela hidrólise do colágeno tipo 1 (piridinolina, deoxipiridinolina, NTX, CTX). Suas aplicaçöes práticas se estendem desde a avaliaçäo da resposta terapêutica obtida pela introduçäo de terapêutica específica.

Efectos experimentales de olpadronato y pamidronato sobre la masa ósea / Experimental effects of olpadronate and pamidronate on bone mass

La ovariectomía y la inmovilización en ratas, han demostrado ser modelos útiles de osteopenia y se considera que imitan algunos aspectos de la osteoporosis humana asociada a déficit de hormonas ováricas y ausencia de uso mecánico del hueso. La administración de Pamidronato (APD)* y Olpadronato (OLPA)*, un nuevo aminobisfosfonato dimetilado, resultó eficaz para prevenir, con esquemas orales contínuos (APD: 8 y OLPA: 0.8 mg/kg/dfa) o intravenosos intermitentes (APD: 1.25 y OLPA: 0.075 mg/kg cada 15 días), la pérdida ósea trabecular mediada por inmovilización (ciaticectomía unilateral), por defecto en la secreción de estrógenos (ovariectomía bilateral) o por ambas, sin manifestaciones de deterioro de la masa ósea cortical. En un modelo de osteopenia por deprivación estrogénica pre-establecida, OLPA evitó la progresión de la pTrdida ósea (0,15 mg/kg i.v. cada 15 días) y restauró (0,30 - 0,60 mg/kg i.v. cada 15 días) la densidad mineral ósea (trabecular y compacta) afectada. La diferente acción de OLPA y APD sobre hueso trabecular y compacto parece acompañar la diferente respuesta de éstos frente a los estímulos negativos: las mejores respuestas fueron mßs evidentes en las regiones trabeculares, más lábiles. OLPA presentó similar eficacia y una potencia 5 a 10 veces superior cuando se lo comparó con APD. Posee un elevado margen de seguridad. En consecuencia, puede considerárselo en posición ventajosa para su uso en aquellas patologías óseas que resulten beneficiadas con el empleo de bisfosfonatos.