RESUMEN

BACKGROUND/AIMS: This aim of this audit was to assess the extent of serum calcium testing and the frequency of hypercalcaemia in the primary care setting. We also assessed the appropriateness of subsequent investigations with repeat serum calcium and PTH testing if hypercalcaemia was identified. METHODS: All laboratory requests for adjusted calcium and PTH samples sent from primary care in Glasgow were analysed over a 12 month period. This covered approximately 125 GP practices and a patient population of over 590,000. RESULTS: There were 78,845 requests for adjusted calcium and 2053 PTH requests from 62,745 patients aged 16-105 years (median age 57, IQ range 30 years). Of these requests 1423 (2.3%) of patients had biochemical evidence of hypercalcaemia (adjusted calcium ≥ 2.61 mmol/L). Of the 1423 patients with hypercalcaemia, 368 patients (45.8%) had a single raised calcium level that was within the normal range on repeat testing. Of the 400 patients with persistent hypercalcaemia on 2 or more samples, 210 (52.5%) had a PTH measured. Eight patients had a PTH < 2.0 pmol/L, whilst 202 (96.1%) had a PTH ≥ 2.0 pmol/L (range 2.1-106.1 pmol/L). CONCLUSIONS: Serum calcium was checked in 10.6% of the population per year within primary care. In the 2.4% with a raised calcium on initial testing, approximately half (45.8%) will normalise on repeat testing. Of those who remained persistently hypercalcaemic, only half (52.5%) had a PTH measured and the majority (96.1%) were in keeping with primary hyperparathyroidism being the most common cause of hypercalcaemia.

Asunto(s)

Hipercalcemia , Hiperparatiroidismo , Humanos , Adulto , Calcio , Hipercalcemia/etiología , Hormona Paratiroidea , Atención Primaria de Salud

RESUMEN

Ideally those at highest risk of fracture should be identified prior to fracture occurrence to reduce mortality, morbidity and costs. Case-finding strategies for those at high risk of first fracture or systematic case-finding strategies following fracture are recommended in the UK, rather than population-based screening to identify individuals at high fracture risk. General practices in the UK hold relevant data on individuals beyond fracture history that could allow identification of a wider group of patients at highest risk of fracture. The aim of the paper is to evaluate the feasibility of applying the WHO-FRAX fracture risk calculator to general practice populations using existing recorded data. A cross-sectional study of 2467 women aged 50 years and older (mean 66.2 years, standard deviation = 11.3) registered with two Scottish General Practices with low deprivation (one semi-rural, one urban) was undertaken. Patient data were extracted from the two general practices' patient information databases and the WHO-FRAX calculator was applied to these data. WHO-FRAX calculation was possible on 1872 patients. Of these, 687 patients were found to have a high fracture risk (risk of major facture ≥15% and or risk of hip fracture ≥3% - 37% of the WHO-FRAX assessed cohort) and should be considered for follow-up. In conclusion, use of the WHO-FRAX calculator using general practice-held data is feasible and can help to identify a patient group at higher fracture risk. Further evaluation and treatments can then be targeted at this group.

Asunto(s)

Fracturas de Cadera/epidemiología , Osteoporosis/epidemiología , Atención Primaria de Salud , Medición de Riesgo/métodos , Absorciometría de Fotón , Anciano , Algoritmos , Conservadores de la Densidad Ósea/uso terapéutico , Análisis Costo-Beneficio , Estudios Transversales , Técnicas de Apoyo para la Decisión , Estudios de Factibilidad , Femenino , Fracturas de Cadera/economía , Fracturas de Cadera/prevención & control , Humanos , Osteoporosis/tratamiento farmacológico , Osteoporosis/economía , Reino Unido/epidemiología

RESUMEN

The objective of this systematic review was to examine the influence of treatments for postmenopausal osteoporosis (parathyroid hormone [PTH], bisphosphonates, strontium ranelate, and denosumab) on bone quality and discuss the clinical implications. Most bone-quality data for PTH is from teriparatide. Teriparatide results in a rapid increase in bone-formation markers, followed by increases in bone-resorption markers, opening an "anabolic window," a period of time when PTH is maximally anabolic. Teriparatide reverses the structural damage seen in osteoporosis and restores the structure of trabecular bone. It has a positive effect on cortical bone, and any early increases in cortical porosity appear to be offset by increases in cortical thickness and diameter. Bisphosphonates are antiresorptive agents which reduce bone turnover, improve trabecular microarchitecture, and mineralization. Concerns have been raised that the prolonged antiresorptive action of bisphosphonates may lead to failure to repair microdamage, resulting in microcracks and atypical fragility. Strontium ranelate is thought to have a mixed mode of action, increasing bone formation and decreasing bone resorption. Strontium ranelate improves cortical thickness, trabecular number, and connectivity, with no change in cortical porosity. Denosumab exerts rapid, marked, and sustained effects on bone resorption, resulting in falls in the markers of bone turnover. Evidence from bone-quality studies suggests that treatment-naive women, aged 60-65 years, with very low BMD T scores may benefit from PTH as primary therapy to improve bone substrate and build bone. Post-PTH treatment with bisphosphonates will maintain improvements in bone quality and reduce the risk of fracture.

Asunto(s)

Anticuerpos Monoclonales/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Hormona Paratiroidea/uso terapéutico , Ligando RANK/uso terapéutico , Tiofenos/uso terapéutico , Anciano , Anticuerpos Monoclonales Humanizados , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Resorción Ósea/metabolismo , Denosumab , Femenino , Humanos , Persona de Mediana Edad , Teriparatido/uso terapéutico

RESUMEN

INTRODUCTION: Despite vertebral fracture being a significant risk factor for further fracture, vertebral fractures are often unrecognised. A study was therefore conducted to determine the proportion of patients presenting with a non-vertebral fracture who also have an unrecognised vertebral fracture. METHODS: Prospective study of patients presenting with a non-vertebral fracture in South Glasgow who underwent DXA evaluation with vertebral morphometry (MXA) from DV5/6 to LV4/5. Vertebral deformities (consistent with fracture) were identified by direct visualisation using the Genant semi-quantitative grading scale. RESULTS: Data were available for 337 patients presenting with low trauma non-vertebral fracture; 261 were female. Of all patients, 10.4% were aged 50-64 years, 53.2% were aged 65-74 years and 36.2% were aged 75 years or over. According to WHO definitions, 35.0% of patients had normal lumbar spine BMD (T-score -1 or above), 37.4% were osteopenic (T-score -1.1 to -2.4) and 27.6% osteoporotic (T-score -2.5 or lower). Humerus (n=103, 31%), radius-ulna (n=90, 27%) and hand/foot (n=53, 16%) were the most common fractures. For 72% of patients (n=241) the presenting fracture was the first low trauma fracture to come to clinical attention. The overall prevalence of vertebral deformity established by MXA was 25% (n=83); 45% (n=37) of patients with vertebral deformity had deformities of more than one vertebra. Of the patients with vertebral deformity and readable scans for grading, 72.5% (58/80) had deformities of grade 2 or 3. Patients presenting with hip fracture, or spine T-score

Asunto(s)

Fracturas de la Columna Vertebral/epidemiología , Absorciometría de Fotón/métodos , Factores de Edad , Anciano , Índice de Masa Corporal , Femenino , Fracturas Óseas/diagnóstico , Fracturas Óseas/epidemiología , Humanos , Vértebras Lumbares/anomalías , Vértebras Lumbares/lesiones , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Prevalencia , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Escocia/epidemiología , Fracturas de la Columna Vertebral/diagnóstico , Vértebras Torácicas/anomalías , Vértebras Torácicas/lesiones

RESUMEN

We compared peri-prosthetic bone mineral density between identical cemented and cementless LCS rotating platform total knee arthroplasties. Two matched cohorts had dual energy x-ray absorptiometry scans two years post-operatively using a modified validated densitometric analysis protocol, to assess peri-prosthetic bone mineral density. The knee that was not operated on was also scanned to enable the calculation of a relative bone mineral density difference. Oxford Knee and American Knee Society scores were comparable in the two cohorts. Statistical analysis revealed no significant difference in absolute, or relative peri-prosthetic bone mineral density with respect to the method of fixation. However, the femoral peri-prosthetic bone mineral density and relative bone mineral density difference were significantly decreased, irrespective of the method of fixation, particularly in the anterior distal portion of the femur, with a mean reduction in relative bone mineral density difference of 27%. There was no difference in clinical outcome between the cemented and cementless LCS total knee arthroplasty. However, both produce stress-shielding around the femoral implants. This leads us to question the use of more expensive cementless total knee components.

Asunto(s)

Artroplastia de Reemplazo de Rodilla , Densidad Ósea/fisiología , Absorciometría de Fotón/métodos , Anciano , Anciano de 80 o más Años , Cementos para Huesos , Enfermedades Óseas Metabólicas/fisiopatología , Cementación , Femenino , Fémur/fisiopatología , Cuello Femoral/fisiopatología , Humanos , Prótesis de la Rodilla , Vértebras Lumbares/fisiopatología , Masculino , Persona de Mediana Edad , Osteoporosis/fisiopatología , Factores Sexuales , Resultado del Tratamiento

RESUMEN

BACKGROUND: It is well established that vitamin D levels are sub-optimal in the elderly and that adults with fragility fracture are more likely to have serum vitamin D levels either lower than those of control patients of similar age, or below the normal range. OBJECTIVES: To investigate the prevalence of vitamin D inadequacy in an elderly population presenting to the South Glasgow Fracture Liaison Service with non-vertebral fragility fractures in order to assess the extent of the problem. RESEARCH DESIGN AND METHODS: The retrospective arm of this study used data from an established database to identify patients aged over 50 years admitted to South Glasgow University Hospitals over the previous 4 years with hip fracture. The prospective arm identified the first 50 patients aged over 50 presenting with a clinical non-vertebral fragility fracture with osteoporosis as measured by axial spine and/or hip DEXA (T-score < -2.5) after November 2004. RESULTS: In the retrospective arm, 626 patients were identified from the database: mean age 80.5 years; 94% were aged over 60 and 74% were aged over 75. Data analysis was limited to 548 patients aged over 60 years with vitamin D recordings and not receiving supplementation with calcium and vitamin D. The mean vitamin D level was 24.7 nmol/L (9.9 ng/ml) SD = 17, however, it is likely that the true mean is lower since in approximately 25% of cases vitamin D levels were reported as < 15 nmol/L (effectively unrecordable). These were transcribed as 15 nmol/L in order to permit a numerical value to be calculated. In the absence of an agreement on what should constitute a diagnostic serum level of vitamin D inadequacy, a number of thresholds were considered--97.8% had vitamin D levels below 70 nmol/L and 91.6% had vitamin D levels below 50 nmol/L. There were no significant differences by patient sex, age or season of presentation. The mean age of patients in the prospective arm was 65.8 years (range 50.6-83.8), 72% were aged over 60 and 16% were aged over 75. The mean vitamin D level was 44.1 nmol/L (18.4 ng/ml) SD = 25.3; 82% had vitamin D levels below 70 nmol/L and 72% had vitamin D levels below 50 nmol/L. Although numbers were too small to justify extensive subgroup analyses, the mean vitamin D level in the 13 patients with hip fracture (34.5 nmol/L) was lower than in the 37 with non-hip fractures (48.2 nmol/L). CONCLUSIONS: This study confirms almost universal vitamin D inadequacy among 548 elderly patients admitted to hospital with hip fracture, regardless of whether a threshold of 50 nmol/L or 70 nmol/L was used. However, among a prospective subset of 50 patients with clinical fragility fractures, especially those with non-hip fractures, the prevalence of inadequacy was substantially lower. It may be that vitamin D represents a correctable risk factor for fragility fracture in the elderly, possibly specifically for the hip.

Asunto(s)

Fracturas Óseas/fisiopatología , Deficiencia de Vitamina D/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis , Prevalencia , Estudios Retrospectivos , Escocia/epidemiología , Medicina Estatal , Deficiencia de Vitamina D/sangre

RESUMEN

This study compares the investigation of and treatment for osteoporosis in two groups of fracture patients at two orthopaedic centres in the UK. One centre had a formal fracture liaison service (FLS) responsible for screening fracture patients for osteoporosis. The other centre relied upon individual clinicians to initiate investigation or treatment for osteoporosis in patients following fracture. Patients who had been treated in either centre for a proximal humeral or hip fracture during a 6-month period were followed up 6 months later to identify how many had received screening or treatment for osteoporosis. Information was retrieved from a prospectively compiled database or by postal questionnaire. The study revealed that in the centre with an FLS 85% of patients with a proximal humeral fracture and 20% with a hip fracture had been offered a dual-energy X-ray absorptiometry (DEXA) scan. Approximately 50% and 85%, respectively, were receiving treatment for osteoporosis 6 months following their fracture. This compared with DEXA being offered to only 6% and 9.7% of humeral and hip fracture patients, respectively, and 20% (hip) and 27% (proximal humerus) receiving osteoporosis treatment in the other centre. The presence of an FLS resulted in a considerably higher proportion of patients receiving investigation and treatment for osteoporosis following a hip or proximal humeral fracture.

Asunto(s)

Fracturas de Cadera/prevención & control , Fracturas del Húmero/prevención & control , Osteoporosis/diagnóstico por imagen , Absorciometría de Fotón/métodos , Estudios de Seguimiento , Fracturas de Cadera/etiología , Humanos , Fracturas del Húmero/etiología , Auditoría Médica , Persona de Mediana Edad , Osteoporosis/tratamiento farmacológico , Medición de Riesgo/métodos , Reino Unido

RESUMEN

Body composition studies using dual energy x-ray absorptiometry (DXA) are being increasingly reported in the literature. When DXA body composition measurements are combined with body water studies, stable bromide is often administered to measure extracellular water. Bromine attenuates x-rays significantly more than soft tissue and so could affect DXA body composition analysis. DXA scans were performed on 26 adults (12 F, 14 M) before and after the intravenous injection of 3 g sodium bromide (NaBr). No significant differences were noted pre- and post-NaBr infusion for whole-body fat mass, fat-free soft tissue mass and bone mineral content. These findings were supported by a simple mathematical analysis of the likely effect of the sodium bromide infusion. This showed that when 3 g NaBr was introduced into the body, the effect on fat mass estimates was expected to be marginally less than the precision of the DXA technique.

Asunto(s)

Composición Corporal , Absorciometría de Fotón/métodos , Tejido Adiposo/anatomía & histología , Adulto , Densidad Ósea , Bromuros , Intervalos de Confianza , Espacio Extracelular/química , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Caracteres Sexuales , Compuestos de Sodio

RESUMEN

Several studies have established that the circulating concentration of intact parathyroid hormone, PTH (1-84), over 24 h follows a circadian rhythm. The importance of this circadian rhythm is not known although some authors have detected alterations in the rhythm in metabolic bone disease and following dietary manipulation. We have studied the circadian rhythm of PTH (1-84) in 8 premenopausal women, 8 postmenopausal women with established osteoporosis and 8 postmenopausal women with no evidence of osteoporosis. Blood samples were obtained at 30-min intervals over a 24-h period and significant differences were found in the profiles of PTH (1-84) and serum phosphate in the three groups studied. Premenopausal women possessed a nocturnal/early morning increase in PTH (1-84) and phosphate (between 2200 and 0700 hours), as did postmenopausal women without osteoporosis. In postmenopausal women with osteoporosis the nocturnal increase in PTH (1-84) and serum phosphate was absent and PTH (1-84) decreased during the period 2200-0700 hours. A shift in acrophase is observed between premenopausal and postmenopausal women without osteoporosis. No acrophase was found in postmenopausal women with osteoporosis for either PTH (1-84) or serum phosphate. No circadian rhythm, acrophase or significant amplitude was observed in serum adjusted calcium or ionized calcium in any group studied. Alterations in the circadian rhythms for PTH (1-84) and serum phosphate occur in patients with postmenopausal osteoporosis that suggest that normal dynamics of PTH (1-84) secretion may play a role in both calcium and phosphate metabolism and the bone remodelling process. Whether these changes are causative or a response to the pathology will require further investigation.

Asunto(s)

Ritmo Circadiano , Osteoporosis Posmenopáusica/sangre , Hormona Paratiroidea/sangre , Fosfatos/sangre , Adulto , Anciano , Densidad Ósea , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/fisiopatología

RESUMEN

The effects of insulin-induced hypoglycaemia on the neutrophil respiratory burst were investigated in six patients with type 1 diabetes and six non-diabetic control subjects. Plasma glucose reached similar nadirs in control subjects (0.9 +/- 0.1 mmol 1(-1); mean +/- SEM) and diabetic patients (1.2 +/- 0.2 mmol 1(-1)) (NS). The resting neutrophil respiratory burst was similar in control subjects (1.26 +/- 0.15 mV) and diabetic patients (1.03 +/- 0.18 mV) (NS). The neutrophil respiratory burst fell following hypoglycaemia in control subjects and diabetic patients to 0.38 +/- 0.05 mV (P < 0.001) and 0.54 +/- 0.09 mV (P < 0.05), respectively. This fall was significantly greater in control subjects (ANOVA; P < 0.001). Resting neutrophil counts were not significantly different in control subjects (3.2 +/- 0.3 x 10(9) 1(-1)) and diabetic patients (6.1 +/- 1.5 x 10(9) 1(-1)). Following hypoglycaemia, neutrophil numbers increased in control subjects and diabetic patients to 11.5 +/- 1.4 x 10(9) 1(-1) (P < 0.01) and 9.7 +/- 1.7 x 10(9) 1(-1) (P < 0.05), respectively. This increase was significantly greater in control subjects (ANOVA; P < 0.001). These results suggest that the neutrophil respiratory burst is suppressed in response to hypoglycaemia and that this phenomenon is more pronounced in non-diabetic subjects.

Asunto(s)

Diabetes Mellitus Tipo 1/fisiopatología , Hipoglucemia/fisiopatología , Neutrófilos/fisiología , Estallido Respiratorio/fisiología , Enfermedad Aguda , Adulto , Glucemia/análisis , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Estudios de Cohortes , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/farmacología , Insulina/farmacología , Recuento de Leucocitos , Mediciones Luminiscentes , Masculino , Neutrófilos/efectos de los fármacos , Valores de Referencia , Estallido Respiratorio/efectos de los fármacos

RESUMEN

Hypercalcaemia associated with cancer is seen not infrequently in hospital practice and can be a source of considerable morbidity. Over the past decade, our understanding of the pathogenesis of this syndrome has advanced, allowing improved treatment protocols. Because one of the principal abnormalities relates to an increase in bone resorption, antiresorptive agents such as calcitonin and the bisphosphonates have been shown to be of value. In the medium to longer term, the bisphosphonates -particularly pamidronic acid[pamidronate;aminohydroxypropylidene bisphosphonate (APD)] and clodronic acid [clodronate; dichloromethyl bisphosphonate (Cl2MDP)]¿ appear to be more efficacious in terms of their calcium-lowering effect than calcitonin, and also appear to be associated with fewer adverse effects than most other agents. However, the importance of energetic re-expansion of the extracellular space with 0.9% sodium chloride before bisphosphonate therapy is extremely important. Cancer-associated hypercalcaemia, especially with squamous cancer, is often associated with the production of parathyroid hormone-related protein (PTHrP). Where this is the case, it usually reflects the presence of more advanced disease with shortened life expectancy, and poorer response to calcium-lowering therapy. Multiple treatments with larger doses of bisphosphonate may be required for these patients.

Asunto(s)

Formularios de Hospitales como Asunto , Hipercalcemia/tratamiento farmacológico , Neoplasias/complicaciones , Análisis Costo-Beneficio , Humanos , Hipercalcemia/economía , Hipercalcemia/etiología , Neoplasias/economía

RESUMEN

Neutrophil bactericidal activity was assessed in patients with type 1 (n = 45) and Type 2 diabetes mellitus (n = 68) and non-diabetic control subjects (n = 40) by measurement of whole blood chemiluminescence. Though chemiluminescence values tended to be highest in the non-diabetic subjects these differences were not statistically significant (mean +/- SD) (2.73 +/- 1.65 mV (controls), 2.33 +/- 1.41 mV (Type 1 diabetes) and 2.38 +/- 1.12 mv (Type 2 diabetes), F = 1.12, p = 0.33). Significant negative correlations were evident, however, in patients with both Type 1 and Type 2 diabetes between chemiluminescence and glycated haemoglobin (rs = -0.35, p = 0.005 (Type 1), rs = -0.45, p = 0.002 (Type 2), fructosamine (rs = -0.36, p = 0.003 (Type 1), r = -0.42, p = 0.004 (Type 2)), and random blood glucose (rs 0 -0.25, p = 0.04 (Type 1), rs = -0.48, p = 0.001 (Type 2)). Changes in whole blood chemiluminescence in a further group of 10 patients with Type 2 diabetes mellitus commenced on insulin therapy were followed for 21 days. Serum fructosamine concentrations fell significantly over this time (524 +/- 58 mumol l-1 to 405 +/- 47 mumol l-1, p < 0.001), however, although chemiluminescence values tended to rise these changes were not statistically significant (1.01 +/- 0.38 mV to 1.60 +/- 0.91 mV, S = 4.24, df = 5, p = 0.52). These results suggested that impaired neutrophil bactericidal function is associated with poor blood glucose control. While it is likely that neutrophil bactericidal function will improve as blood glucose control improves, further studies are required both to confirm this and to demonstrate a reduction in the incidence of clinical bacterial infection.

Asunto(s)

Actividad Bactericida de la Sangre , Glucemia/fisiología , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Neutrófilos/fisiología , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Fructosamina , Hemoglobina Glucada/análisis , Hexosaminas/sangre , Humanos , Mediciones Luminiscentes , Persona de Mediana Edad , Valores de Referencia , Estadísticas no Paramétricas

RESUMEN

Plasma concentrations of parathyroid hormone-related protein (PTHrP), parathyroid hormone, alkaline phosphatase, osteocalcin and albumin-adjusted calcium were measured along with nephrogenous cyclic adenosine monophosphate (NcAMP) in 10 normal women longitudinally through pregnancy. In addition, an assessment of bone resorption was made in these same subjects by the measurement in true fasting urine specimens of the calcium/creatinine ratio (Ca/Cr), hydroxyproline/creatinine ratio (HP/Cr), pyridinoline/creatinine ratio (Pyr/Cr) and deoxypyridinoline/creatine ratio (Dpyr/Cr). The PTHrP level rose through pregnancy from (mean +/- SEM) 0.8 +/- 0.2 pmol/l in the first trimester to 2.7 +/- 0.2 pmol/l 6 weeks postpartum (p < 0.0001). Serum alkaline phosphatase rose from 94 +/- 8 U/l (first trimester) to 347 +/- 25 U/l at term (p < 0.0001). A significant positive correlation was evident between PTHrP and alkaline phosphatase up to term (r = 0.44, p < 0.005). Parathyroid hormone concentrations remained unchanged during pregnancy but rose significantly postpartum from 1.8 +/- 0.2 pmol/l (first trimester) to 3.1 +/- 0.5 pmol/l (p < 0.0001). Similarly, osteocalcin, a marker of bone formative activity, remained unchanged through pregnancy but rose significantly at 6 weeks after delivery to 0.38 +/- 0.05 nmol/l from 0.19 +/- 0.03 nmol/l (first trimester) (p = 0.019). No significant change was noted in serum-adjusted calcium or NcAMP, either through pregnancy or at the postpartum assessment. Fasting urinary Ca/Cr fell through pregnancy from 0.70 +/- 0.11 (first trimester) to a nadir of 0.19 +/- 0.04 6 weeks postpartum (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Fosfatasa Alcalina/sangre , Huesos/metabolismo , Calcio/sangre , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Embarazo/sangre , Embarazo/metabolismo , Proteínas/análisis , Adolescente , Adulto , Aminoácidos/sangre , Aminoácidos/orina , Resorción Ósea/orina , Calcio/orina , Colágeno/orina , Creatinina/orina , Femenino , Humanos , Proteína Relacionada con la Hormona Paratiroidea , Embarazo/orina

RESUMEN

We investigated expression of several cytokines and growth factors in explants of Pagetic and non-Pagetic bone samples using the technique of reverse-transcription/polymerase chain reaction (RT/PCR). Transcripts for IL-1 alpha and IL-1 beta, TNF-alpha, TNF-beta, IL-6, basic fibroblast growth factor (bFGF), transforming growth factor beta (TGF-beta) and insulin-like growth factor-I (IGF-I) were found to a variable degree in both Pagetic and non-Pagetic bone samples, but there was no significant difference in the patterns of expression for these factors in Pagetic bone (n = 18) as compared with non-Pagetic bone (n = 51). There was furthermore, no significant difference in the patterns of expression for the various factors studied when patients were subdivided into mild and severe categories of disease activity using markers of bone formation (serum alkaline phosphatase) or bone resorption (osteoclast counts on adjacent biopsy specimens). Although IL-6 and IL-1 have previously been implicated as bone resorbing factors in Pagetic bone, 40% of our patients with severe disease had not detectable IL-6 transcripts, 70% had no detectable IL-1 alpha transcripts and 50% no IL-1 beta transcripts. We conclude that patterns of expression for cytokine and growth factor mRNAs are not disturbed in Paget's disease. Although we cannot exclude the possibility that post-transcriptional processing of the mRNAs may differ in Pagetic and normal bone cells, our data raise the possibility that the abnormalities of bone turnover which are characteristic of active Paget's disease may be due to local elaboration of other, possibly novel osteotropic factors, which stimulate bone formation and resorption.

Asunto(s)

Citocinas/genética , Regulación de la Expresión Génica , Sustancias de Crecimiento/genética , Osteítis Deformante/genética , Fosfatasa Alcalina/sangre , Secuencia de Bases , Huesos/química , Huesos/patología , Citocinas/análisis , Citocinas/fisiología , ADN/análisis , ADN/genética , Femenino , Factor 2 de Crecimiento de Fibroblastos/análisis , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/fisiología , Sustancias de Crecimiento/análisis , Sustancias de Crecimiento/fisiología , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/fisiología , Interleucina-1/análisis , Interleucina-1/genética , Interleucina-1/fisiología , Interleucina-6/análisis , Interleucina-6/genética , Interleucina-6/fisiología , Datos de Secuencia Molecular , Osteítis Deformante/enzimología , Osteítis Deformante/patología , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/análisis , ARN Mensajero/genética , Transcripción Genética , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/fisiología

Asunto(s)

Difosfonatos/efectos adversos , Osteítis Deformante/tratamiento farmacológico , Osteomalacia/inducido químicamente , Calcificación Fisiológica/efectos de los fármacos , Humanos , Hiperparatiroidismo Secundario/inducido químicamente , Pamidronato

Asunto(s)

Asma/inducido químicamente , Difosfonatos/efectos adversos , Humanos

RESUMEN

Following a femoral neck fracture and vertebral compression fractures in two patients with severe haemophilia A, bone density and turnover were measured in 19 males with severe haemophilia A (all HIV negative, 18/19 hepatitis C antibody positive) and in 19 age/sex matched controls. Bone density at the lumbar spine (L2-4), measured by dual energy X-ray absorptiometry, was significantly lower in the haemophiliac patients (HPs) at (mean +/- SEM) 1.109 +/- 0.042 g/cm2 vs. 1.234 +/- 0.027 in controls; p = 0.018. Femoral neck density was also lower at 0.877 +/- 0.034 g/cm2 (HPs) vs. 1.067 +/- 0.032; p < 0.0005. No significant differences were evident between the groups for serum calcium, parathyroid hormone, luteinizing hormone, follicle-stimulating hormone or 1,25 dihydroxyvitamin D3, nor for fasting urinary hydroxyproline, pyridinoline or deoxypyridinoline excretion. Serum total alkaline phosphatases was elevated in HPs at 200 +/- 10 U/l vs. 158 +/- 8; p = 0.004. Similarly, gamma-glutamyl transferase was elevated at 42 +/- 7 U/l (HPs) vs. 20 +/- 2; p = 0.007. Serum total testosterone and sex-hormone-binding globulin (SHBG) were higher in HPs at 26 +/- 2.5 nmol/l vs. 17.4 +/- 1.6 (p = 0.009) and 56 +/- 6 nmol/l vs. 27 +/- 3 (p = 0.0005), respectively. Free androgen index, however, was lower in HPs at 44 +/- 5 vs 69 +/- 7; p = 0.008. These results suggest significant osteopenia associated with haemophilia A. This may be partly due to liver dysfunction in HPs, but other factors, e.g. relative immobilization, may also be relevant.

Asunto(s)

Densidad Ósea , Hemofilia A/complicaciones , Osteoporosis/etiología , Absorciometría de Fotón , Adolescente , Adulto , Anciano , Fosfatasa Alcalina/sangre , Cuello Femoral/metabolismo , Hemofilia A/metabolismo , Humanos , Vértebras Lumbares/metabolismo , Masculino , Persona de Mediana Edad , Osteoporosis/metabolismo , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre

RESUMEN

The acute effects of a single intravenous injection of 2 micrograms of 1 alpha-hydroxycholecalciferol (alfacalcidol) were studied for a 24-h period in six normal males (mean age 33 years), six women with primary hyperparathyroidism (mean age 72 years) and six women with established osteoporosis (mean age 63 years). In all three groups, serum calcitriol levels rose to a peak 2-3 h after administration of alfacalcidol. Basal levels were highest in the primary hyperparathyroidism group at (mean +/- SEM) 81 +/- 2 vs 62 +/- 12 (normal males) (p < 0.05) and 56 +/- 5 pmol/l (osteoporosis) (p < 0.01). Highest peak levels were found also in the primary hyperparathyroidism group at 150 +/- 15 vs 114 +/- 15 (normal males) (p < 0.05) and 127 +/- 15 pmol/l (osteoporosis) (p < 0.01). The rise in calcitriol was higher in the primary hyperparathyroidism group than either the normal males or osteoporotic patients (p < 0.05). No significant differences were evident in basal serum calcidiol concentrations among the three treatment groups. As might be expected, highest basal concentrations of parathyroid hormone (PTH), serum calcium and serum osteocalcin were noted in the primary hyperparathyroid group (PTH: 17.1 +/- 7.7 vs 1.9 +/- 0.5 (normal males) (p < 0.01) and 2.1 +/- 0.3 pmol/l (osteoporosis) (p < 0.01); calcium: 3.06 +/- 0.08 vs 2.50 +/- 0.02 (normal males) (p < 0.01) and 2.43 +/- 0.02 mmol/l (osteoporosis) (p < 0.01); osteocalcin: 1.10 +/- 0.08 vs 0.56 +/- 0.16 (normal males) (p < 0.05) and 0.53 +/- 0.21 nmol/l (osteoporosis) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Calcitriol/sangre , Hidroxicolecalciferoles/farmacología , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Adulto , Anciano , Fosfatasa Alcalina/sangre , Análisis de Varianza , Calcio/sangre , Femenino , Humanos , Hidroxicolecalciferoles/administración & dosificación , Hiperparatiroidismo/sangre , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangre

Asunto(s)

Publicaciones Periódicas como Asunto , Edición/normas , Investigación

RESUMEN

Bone biopsy samples were taken from 20 patients with Paget's disease before and after intravenous pamidronate therapy. In 10 patients given 180 or 360 mg during 6 or 9 weeks, bone turnover decreased as measured biochemically and histologically, but osteomalacia developed in 1 patient and mineralisation defects in 3. 10 other patients received 45 mg every 3 months for 1 year. Bone turnover decreased biochemically but not histologically, and osteoid thickness increased, suggesting impaired mineralisation. Despite overall efficacy, pamidronate has a narrow therapeutic range between resorption inhibition and mineralisation defects. Short courses given to achieve biochemical remission should be administered with caution.

Asunto(s)

Calcificación Fisiológica , Difosfonatos/uso terapéutico , Osteítis Deformante/tratamiento farmacológico , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Femenino , Humanos , Masculino , Osteítis Deformante/metabolismo , Osteomalacia/inducido químicamente , Pamidronato