RESUMO
UNLABELLED: The role of acid-base metabolism in bone health is controversial. In this meta-analysis, potassium bicarbonate and potassium citrate lowered urinary calcium and acid excretion and reduced the excretion of the bone resorption marker NTX. These salts may thus be beneficial to bone health by conserving bone mineral. INTRODUCTION: The role of acid-base homeostasis as a determinant of bone health and the contribution of supplemental alkali in promoting skeletal integrity remain a subject of debate. The objective of this study was, therefore, to conduct a meta-analysis to assess the effects of supplemental potassium bicarbonate (KHCO3) and potassium citrate (KCitr) on urinary calcium and acid excretion, markers of bone turnover and bone mineral density (BMD) and to compare their effects with that of potassium chloride (KCl). METHODS: A total of 14 studies of the effect of alkaline potassium salts on calcium metabolism and bone health, identified by a systematic literature search, were analysed with Review Manager (Version 5; The Cochrane Collaboration) using a random-effects model. Authors were contacted to provide missing data as required. Results are presented as the standardised (SMD) or unstandardized mean difference (MD) (95 % confidence intervals). RESULTS: Urinary calcium excretion was lowered by intervention with both KHCO3 (P = 0.04) and KCitr (P = 0.01), as was net acid excretion (NAE) (P = 0.002 for KHCO3 and P = 0.0008 for KCitr). Both salts significantly lowered the bone resorption marker NTX (P < 0.00001). There was no effect on bone formation markers or BMD. KHCO3 and KCitr lowered calcium excretion to a greater extent than did KCl. CONCLUSIONS: This meta-analysis confirms that supplementation with alkaline potassium salts leads to significant reduction in renal calcium excretion and acid excretion, compatible with the concept of increased buffering of hydrogen ions by raised circulating bicarbonate. The observed reduction in bone resorption indicates a potential benefit to bone health.
Assuntos
Bicarbonatos/farmacologia , Conservadores da Densidade Óssea/farmacologia , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Citrato de Potássio/farmacologia , Compostos de Potássio/farmacologia , Bicarbonatos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/prevenção & controle , Cálcio/urina , Humanos , Compostos de Potássio/uso terapêuticoRESUMO
Muscle strength plays an important role in determining risk for falls, which result in fractures and other injuries. While bone loss has long been recognized as an inevitable consequence of aging, sarcopenia-the gradual loss of skeletal muscle mass and strength that occurs with advancing age-has recently received increased attention. A review of the literature was undertaken to identify nutritional factors that contribute to loss of muscle mass. The role of protein, acid-base balance, vitamin D/calcium, and other minor nutrients like B vitamins was reviewed. Muscle wasting is a multifactorial process involving intrinsic and extrinsic alterations. A loss of fast twitch fibers, glycation of proteins, and insulin resistance may play an important role in the loss of muscle strength and development of sarcopenia. Protein intake plays an integral part in muscle health and an intake of 1.0-1.2 g/kg of body weight per day is probably optimal for older adults. There is a moderate [corrected] relationship between vitamin D status and muscle strength. Chronic ingestion of acid-producing diets appears to have a negative impact on muscle performance, and decreases in vitamin B12 and folic acid intake may also impair muscle function through their action on homocysteine. An adequate nutritional intake and an optimal dietary acid-base balance are important elements of any strategy to preserve muscle mass and strength during aging.
Assuntos
Fenômenos Fisiológicos da Nutrição do Idoso/fisiologia , Força Muscular/fisiologia , Sarcopenia/fisiopatologia , Idoso , Envelhecimento/fisiologia , Proteínas Alimentares/administração & dosagem , Humanos , Desnutrição/complicações , Estado Nutricional , Sarcopenia/etiologia , Sarcopenia/terapia , Vitamina D/administração & dosagemRESUMO
This position paper of the International Osteoporosis Foundation makes recommendations for vitamin D nutrition in elderly men and women from an evidence-based perspective.
Assuntos
Vitamina D/administração & dosagem , Acidentes por Quedas/prevenção & controle , Administração Oral , Idoso , Esquema de Medicação , Medicina Baseada em Evidências , Feminino , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Humanos , Masculino , Necessidades Nutricionais , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
SUMMARY: This nested case-control analysis of a Swiss ambulatory cohort of elderly women assessed the discriminatory power of urinary markers of bone resorption and heel quantitative ultrasound for non-vertebral fractures. The tests all discriminated between cases and controls, but combining the two strategies yielded no additional relevant information. INTRODUCTION: Data are limited regarding the combination of bone resorption markers and heel quantitative bone ultrasound (QUS) in the detection of women at risk for fracture. METHODS: In a nested case-control analysis, we studied 368 women (mean age 76.2 +/- 3.2 years), 195 with low-trauma non-vertebral fractures and 173 without, matched for age, BMI, medical center, and follow-up duration, from a prospective study designed to predict fractures. Urinary total pyridinolines (PYD) and deoxypyridinolines (DPD) were measured by high performance liquid chromatography. All women underwent bone evaluations using Achilles+ and Sahara heel QUS. RESULTS: Areas under the receiver operating-characteristic curve (AUC) for discriminative models of the fracture group, with 95% confidence intervals, were 0.62 (0.56-0.68) and 0.59 (0.53-0.65) for PYD and DPD, and 0.64 (0.58-0.69) and 0.65 (0.59-0.71) for Achilles+ and Sahara QUS, respectively. The combination of resorption markers and QUS added no significant discriminatory information to either measurement alone with an AUC of 0.66 (0.60-0.71) for Achilles+ with PYD and 0.68 (0.62-0.73) for Sahara with PYD. CONCLUSIONS: Urinary bone resorption markers and QUS are equally discriminatory between non-vertebral fracture patients and controls. However, the combination of bone resorption markers and QUS is not better than either test used alone.
Assuntos
Reabsorção Óssea/diagnóstico , Calcâneo/diagnóstico por imagem , Fraturas por Osteoporose/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Aminoácidos/urina , Biomarcadores/urina , Reabsorção Óssea/diagnóstico por imagem , Cromatografia Líquida de Alta Pressão/métodos , Métodos Epidemiológicos , Feminino , Humanos , Fraturas por Osteoporose/diagnóstico por imagem , UltrassonografiaRESUMO
UNLABELLED: This review describes the vitamin D status in different regions of the world with the objective of understanding the scope of hypovitaminosis D and the factors related to its prevalence that may contribute to the pathogenesis of osteoporosis and fragility fractures. INTRODUCTION: Vitamin D status has been linked to the pathogenesis of hip fractures as well as other skeletal and non-skeletal disorders. The purpose of this review is to provide a global perspective of vitamin D status across different regions of the world and to identify the common and significant determinants of hypovitaminosis D. METHODS: Six regions of the world were reviewed-Asia, Europe, Middle East and Africa, Latin America, North America, and Oceania-through a survey of published literature. RESULTS: The definition of vitamin D insufficiency and deficiency, as well as assay methodology for 25-hydroxyvitamin D or 25(OH)D, vary between studies. However, serum 25(OH)D levels below 75 nmol/L are prevalent in every region studied whilst levels below 25 nmol/L are most common in regions such as South Asia and the Middle East. Older age, female sex, higher latitude, winter season, darker skin pigmentation, less sunlight exposure, dietary habits, and absence of vitamin D fortification are the main factors that are significantly associated with lower 25(OH)D levels. CONCLUSION: Reports from across the world indicate that hypovitaminosis D is widespread and is re-emerging as a major health problem globally.
Assuntos
Saúde Global , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Comparação Transcultural , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Deficiência de Vitamina D/etiologia , Adulto JovemRESUMO
With the menopause, the multiple positive effects of estrogens on bone come to an end, which leads to an increased bone turnover an accelerated bone loss and an increased fracture risk. Although the antifracture effect of calcium alone is questionable, several observations justify the recommendation to avoid calcium deficiency in this age: Very low Calcium intake is related to low BMD and higher hip fracture incidence in several studies; regular Calcium supplementation lowers fracture incidence, when observed over years. Calcium from dairy products, mineral waters and supplements is almost equally well absorbed. But the former contain also other nutrients with positive effects on bone, such as proteins, phosphorus, bicarbonates. The choice goes for the nutrient or supplement with the best acceptance by a given individual.
Assuntos
Cálcio/administração & dosagem , Climatério/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Disponibilidade Biológica , Densidade Óssea/efeitos dos fármacos , Cálcio da Dieta/administração & dosagem , Feminino , Fraturas Espontâneas/prevenção & controle , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Pamidronate is a second-generation bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. PURPOSE: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. METHODS: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. RESULTS: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (+/- SD) half-life of the distribution phase was 0.8 hour (+/- 0.3), the mean (+/- SD) of the area under the curve for drug concentration in plasma x time at 0-24 hours was 22.0 +/- 8.8 mumol/L x hours, and the mean (+/- SD) of the maximum plasma concentration was 9.7 mumol/L (+/- 3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. CONCLUSIONS: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases.
Assuntos
Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Difosfonatos/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/sangue , Neoplasias Ósseas/urina , Difosfonatos/administração & dosagem , Difosfonatos/sangue , Difosfonatos/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PamidronatoRESUMO
Overexpression of SV40 T-antigen (SV40 T-Ag) has been widely used to overcome replicative senescence of human primary cells and to promote cell immortalization. However, in the case of certain cell types, such as preadipocytes, the differentiation process of immortalized cells is blocked by SV40 T-Ag expression. In this study, human telomerase reverse transcriptase (hTERT) and papillomavirus E7 oncoprotein (HPV-E7) genes were coexpressed in human preadipocytes to test whether this combination could maintain cell differentiation capacity after immortalization. We demonstrated that the HPV-E7/hTERT expressing preadipocytes displayed an indefinite life span. Interestingly, immortalized cells were diploid and presented no chromosomic alterations. These immortalized cells were able to accumulate and hydrolyze intracellular triglycerides and to express adipocyte markers. These data demonstrate, for the first time, that coexpression of hTERT and HPV-E7 in human preadipocytes allows cells not only to display an indefinite life span but also to retain their capacity to differentiate.
Assuntos
Adipócitos/citologia , Transformação Celular Viral , Proteínas Oncogênicas Virais/metabolismo , Células-Tronco/citologia , Telomerase/metabolismo , Adipócitos/metabolismo , Adulto , Diferenciação Celular , Linhagem Celular Transformada , Células Cultivadas , Proteínas de Ligação a DNA , Feminino , Expressão Gênica , Humanos , Cariotipagem , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus , Células-Tronco/enzimologia , Células-Tronco/virologiaRESUMO
Fifty-two patients with malignant hypercalcemia were treated with a single dose of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose-response in humans, patients were divided into four groups receiving 30 mg, 45 mg, 60 mg, or 90 mg, respectively, as a 24-hour infusion. Initial plasma calcium was similar in all groups, except in the group receiving 90 mg, of which some patients had higher initial values. All patients responded to AHPrBP with a rapid decrease of plasma calcium concentration from 3.47 +/- 0.10 mmol/L at day 0 to 2.43 +/- 0.06 at day 6 (P less than .001). Plasma calcium became normal within four to six days in 43 patients. Eight of the nine patients whose calcium did not become normal were in the low-dose (30 and 45 mg of AHPrBP) groups. Slight and asymptomatic hypocalcemia occurred in only tow of the 26 patients in the low-dose groups, but in six of the 26 patients in the high-dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 1 month in five of ten patients in the group receiving 30 mg, in three of ten patients in the group receiving 45 mg, and in one of 20 patients in the groups receiving 60 and 90 mg, whereas mortality was almost identical in all four groups. In all groups, plasma phosphate, plasma creatinine, urinary calcium, and hydroxyproline excretion decreased significantly. In conclusion, when administered as a single-day infusion in the treatment of tumor hypercalcemia, AHPrBP leads to a dose-dependent decrease in plasma calcium. To prevent transient hypocalcemia and early relapse, the optimal dose should be adapted to the degree of severity of hypercalcemia.
Assuntos
Difosfonatos/uso terapêutico , Hipercalcemia/tratamento farmacológico , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/sangue , Creatinina/sangue , Difosfonatos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pamidronato , Fosfatos/sangueRESUMO
PURPOSE: The purpose of this article is to review the recent data on bisphosphonate use in oncology and to provide some guidelines on the indications for their use in cancer patients. DESIGN: The group consensus reached by experts on the rationale for the use of bisphosphonates in cancer patients and their current indications for the treatment of tumor-induced hypercalcemia and metastatic bone pain in advanced disease and for the prevention of the complications of multiple myeloma and of metastatic bone disease are reviewed. RESULTS: Bisphosphonates are potent inhibitors of tumor-induced osteoclast-mediated bone resorption. They now constitute the standard treatment for cancer hypercalcemia, for which we recommend a dose of 1,500 mg of clodronate or 90 mg of pamidronate; the latter compound is more potent and has a longer lasting effect. Intravenous bisphosphonates exert clinically relevant analgesic effects in patients with metastatic bone pain. Regular pamidronate infusions can also achieve a partial objective response by conventional International Union Against Cancer criteria and enhance the objective response rate to chemotherapy. In breast cancer, the prolonged administration of oral clodronate 1,600 mg daily reduces the frequency of morbid skeletal events by more than one fourth, whereas monthly pamidronate infusions of 90 mg for only 1 year in addition to chemotherapy reduce by more than one third the frequency of all skeletal-related events. The use of bisphosphonates to prevent bone metastases remains experimental. Last, bisphosphonates in addition to chemotherapy are superior to chemotherapy alone in patients with stages II and III multiple myeloma and can reduce the skeletal morbidity rate by approximately one half. CONCLUSION: Bisphosphonate use is a major therapeutic advance in the management of the skeletal morbidity caused by metastatic breast cancer or multiple myeloma, although many questions remain unanswered, notably regarding the optimal selection of patients and the duration of treatment.
Assuntos
Neoplasias Ósseas/secundário , Reabsorção Óssea/prevenção & controle , Osso e Ossos/efeitos dos fármacos , Difosfonatos/uso terapêutico , Hipercalcemia/prevenção & controle , Analgésicos não Narcóticos/uso terapêutico , Neoplasias Ósseas/complicações , Reabsorção Óssea/etiologia , Neoplasias da Mama/patologia , Ácido Clodrônico/uso terapêutico , Humanos , Hipercalcemia/etiologia , Ácido Ibandrônico , Mieloma Múltiplo/patologia , Dor/tratamento farmacológico , Dor/etiologia , PamidronatoRESUMO
Seventeen patients with malignant hypercalcemia were treated with a combination of a single dose of 3-amino 1-hydroxypropylidene-1-bisphosphonate (APD [also known as AHPrBP or palmidronate disodium]) and salmon calcitonin given as suppositories for 3 days. To assess whether such a combined short treatment has a significant benefit leading to earlier normalization of the plasma calcium level than does APD alone, 17 additional patients matched for the type of tumor, initial plasma calcium level, urinary hydroxyproline level, and the dose of APD served as controls. All patients receiving the combination of calcitonin and APD achieved normalization of the plasma calcium level within 9 days, with a decrease from 3.22 +/- 0.90 mmol/L (mean +/- SEM) to 2.29 +/- 0.03 mmol/L. In the group receiving APD alone, the plasma calcium level normalized in only 14 of 17 patients by day 9. In the group receiving calcitonin and APD, the drop in the plasma calcium level occurred more rapidly, and the plasma calcium values were lower from days 2 to 4. This advantage was explained by the calciuric effect of calcitonin, as reflected by a significant decrease in the notional setting of renal reabsorption of calcium, reaching 2.16 +/- 0.06 mmol/L compared with 2.34 +/- 0.06 mmol/L in the group receiving APD alone. There were no side effects of both treatments, in particular neither flushing nor nausea induced by the suppositories of calcitonin. Clinical Improvement occurred after 2 days in the group receiving the combined treatment. In conclusion, the combined treatment is rapidly effective and safe in the treatment of patients with hypercalcemia, particularly when the notional setting of renal tubular reabsorption of calcium is increased and a rapid correction of the plasma calcium level is needed.
Assuntos
Calcitonina/uso terapêutico , Difosfonatos/uso terapêutico , Hipercalcemia/tratamento farmacológico , Idoso , Calcitonina/administração & dosagem , Difosfonatos/administração & dosagem , Quimioterapia Combinada , Feminino , Hidratação , Humanos , Hipercalcemia/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Pamidronato , Supositórios , Fatores de TempoRESUMO
A 38-year-old woman with hypercalcemia, severe hypertension, and high renin levels was treated with the angiotensin-converting enzyme inhibitor captopril. This therapy, together with spironolactone, normalized blood pressure (BP), but even with three daily administrations of the converting enzyme inhibitor, intermittent rebound hypertension could not be avoided. The administration of only verapamil, an antagonist of calcium transport, did not induce BP control, but when verapamil therapy was combined with administration of captopril and spironolactone, BP could be normalized with only twice-daily administration of the converting enzyme inhibitor. Thus, high plasma calcium levels seem to sensitize the arterioles to the intermittent increase of angiotensin II levels that accompanies captopril therapy.
Assuntos
Captopril/uso terapêutico , Hipercalcemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Prolina/análogos & derivados , Verapamil/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Hipercalcemia/complicações , Hiperparatireoidismo/complicações , Hipertensão/complicações , Espironolactona/uso terapêuticoRESUMO
Malignant hypercalcemia is caused by both increased bone resorption and enhanced tubular reabsorption of calcium. First, the response to an infusion of APD was compared in two groups of patients: 23 with breast cancer versus 20 with squamous cell cancer. The decrease in plasma calcium was smaller in the latter group (p less than 0.05 at day 14), due to increased tubular reabsorption of calcium (TmCa/GFR 2.20 +/- 0.05 versus 2.58 +/- 0.06 mmol/liter; p less than 0.001), whereas the degree of bone resorption reflected by urinary hydroxyproline was identical. Therefore, at a given initial plasma calcium level, the type of tumor (on which TmCA/GFR depends) seems to be a determinant for the effectiveness of the treatment. Second, the response to the initial treatment was compared with that to a second treatment with the same dose in 12 patients whose malignant hypercalcemia relapsed. Within 9 days, plasma calcium decreased from 3.46 +/- 0.10 to 2.50 +/- 0.10 mmol/liter after the first course, but only from 3.37 +/- 0.08 to 2.79 +/- 0.09 mmol/liter after the second course (p less than 0.01). TmCa/GFR was similar before the first and the second treatment and did not vary during the days following the infusion of APD. Initial urinary hydroxyproline was slightly but not significantly higher before the second treatment. It dropped following both APD courses, but to a lesser extent after the second treatment, reflecting higher bone resorption or possible resistance to bisphosphonate.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Osso e Ossos/fisiopatologia , Neoplasias da Mama/complicações , Carcinoma de Células Escamosas/complicações , Difosfonatos/uso terapêutico , Hipercalcemia/tratamento farmacológico , Rim/fisiopatologia , Cálcio/metabolismo , Feminino , Humanos , Hidroxiprolina/urina , Hipercalcemia/etiologia , Masculino , PamidronatoRESUMO
Amino-hydroxypropylidene bisphosphonic acid (AHPrBP, previously APD) is a potent inhibitor of bone resorption. Since it remains in bone for a long time, and since it was not found to impair bone mineralization, it could be administered at high dose over a short period of time. Therefore, 11 patients with symptomatic Paget's disease received AHPrBP orally at 1200 mg/day over 5 consecutive days. Controls were performed after 1 month in all patients, 6 months in 8 patients, and one year in 4 patients. Clinical improvement and biochemical remission was observed in all patients, except one with severe disease. Side effects were negligible. Disease activity at bone scintigram decreased over 6 months. Plasma alkaline phosphatase activity fell progressively and significantly from 210 +/- 26 U/l (means +/- SEM) to 103 +/- 10 U/l after 6 months (nl less than 120 U/l). Urinary excretion of hydroxyproline decreased immediately and became normal (nl less than 2.3 mumol/lGF) as a mean at day 5 (from 4.6 +/- 0.4 mumol/lGF to 2.1 +/- 0.3 mumol/lGF). Thereafter it remained within the normal range (2.0 +/- 0.2 mumol/l at day 180). Plasma calcium and phosphate concentrations fell transiently between day 4 and 15, whereas plasma PTH levels increased over this period of time. In conclusion, a short course of AHPrBP given per os at high dose induces a rapid decline in activity and remission of moderate Paget's disease, without significant side effects.
Assuntos
Difosfonatos/uso terapêutico , Osteíte Deformante/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Feminino , Humanos , Hidroxiprolina/urina , Masculino , Pessoa de Meia-Idade , PamidronatoRESUMO
Twenty patients with malignant hypercalcemia were treated with amino-hydroxypropylidene bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. To assess the efficacy of a single-day treatment and determine the optimal dose of this compound, all patients received AHPrBP intravenously over 24 h, but they were divided into two subsequent groups of 10 patients: Group A received a single dose of 60 mg AHPrBP and group B received a single dose of 30 mg. In both groups all patients responded to AHPrBP with a decrease in plasma calcium concentration after a mean time lag of 1 day. Within 6 days, plasma calcium (corrected for serum proteins) fell from 3.24 +/- 0.14 to 2.24 +/- 0.06 mmol/liter in group A (p less than .001), but only from 3.22 +/- 0.15 to 2.49 +/- 0.10 mmol/liter in group B (p less than .005). Whereas in all patients from group A plasma calcium was within the normal range at days 9 and 14, in 4 patients of group B it was still above the normal range at day 9, and in 5 patients at day 14. There was a significant difference in plasma calcium between group A and group B from days 5 to 14 (p less than .005). In both groups, urinary calcium excretion fell dramatically and similarly, and plasma phosphate concentration decreased significantly (p less than .01) to values slightly below the normal range from days 4 to 6.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Difosfonatos/farmacologia , Hipercalcemia/tratamento farmacológico , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/sangue , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/etiologia , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , PamidronatoRESUMO
Growth factors, such as transforming growth factor beta (TGF-beta) and insulin-like growth factors (IGF) I and II, have been shown to exert anabolic effects on bone cells in vitro. Hormones, such as PTH and probably insulin and growth hormone, were recently shown to stimulate bone formation in vivo as well. The aim of the present study was to assess by northern blots, which were quantitated by densitometry, the effects of these anabolic growth factors and hormones in two osteogenic cell populations: CRP 10/30 cells, a clonal cell population derived from primary rat calvarial cells, and IRC 10/30-myc cells, which were established from CRP 10/30 by immortalization. Transcripts for alpha 1(I) collagen, biglycan, osteonectin, osteopontin, and osteocalcin were detected in both cell populations, which is consistent with the phenotype expressed by mature osteoblasts. There were no difference in the basal expression of bone matrix mRNAs between the two cell populations. PTH increased alpha 1(I) collagen mRNA levels in both osteoblastic cells but had no effect on the biglycan transcripts. Neither insulin nor growth hormone affected mRNA levels of either matrix protein after 24 h exposure. All three growth factors, TGF-beta, IGF-I, and IGF-II, increased alpha 1(I) collagen transcripts in a time- and dose-dependent manner in both cell populations. Biglycan mRNA levels were enhanced in both osteoblastic lines only by IGF-I and IGF-II, but not TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Colágeno/biossíntese , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Proteoglicanas/biossíntese , Animais , Biglicano , Northern Blotting , Linhagem Celular , Colágeno/genética , Relação Dose-Resposta a Droga , Proteínas da Matriz Extracelular , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like II/farmacologia , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteocalcina/biossíntese , Osteocalcina/genética , Osteonectina/biossíntese , Osteonectina/genética , Osteopontina , Hormônio Paratireóideo/farmacologia , Fragmentos de Peptídeos/farmacologia , Fenótipo , Proteoglicanas/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Sialoglicoproteínas/biossíntese , Sialoglicoproteínas/genética , Teriparatida , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/genética , Fator de Crescimento Transformador beta/farmacologiaRESUMO
Parathyroid hormone-related protein (PTHrP) is the primary mediator of hypercalcemia in patients with malignancy-associated hypercalcemia. We conducted this study to examine the effects of treatment with a bisphosphonate on serum PTHrP. We analyzed 41 episodes of hypercalcemia occurring in 38 patients: 22 patients received alendronate, and 16 were treated with pamidronate. At baseline, 29 patients had an increased serum PTHrP (group I) and 9 had low or undetectable levels (group II). The two groups did not differ significantly in baseline hypercalcemia (3.26 versus 3.41 mM) or the response of serum calcium to therapy. Serum calcium was normalized in 88% of group I and 70% of group II patients. Lowering of the mean calcium level was not associated with a change in the level of PTHrP in group I patients (40.2 versus 36.7 pgEq/ml) or group II patients. We also analyzed data on serum PTH and 1,25-(OH)2D in 20 of the patients. Serum PTH rose with treatment in group I patients (9.7-40.2 pg/ml, p < 0.05), as did the serum 1,25-(OH)2D (19.1-32.4 pg/ml, p < 0.001). Similarly, treatment of group II patients was associated with an increase in serum PTH (9.8-37.2 pg/ml) and serum 1,25-(OH)2D (22.9-40.2 pg/ml). The individual increases in 1,25-(OH)2D levels associated with therapy could not be predicted from the level of PTHrP or the changes in levels of serum calcium or PTH. Our data show that effective treatment of malignancy-associated hypercalcemia is not associated with a consistent change in serum levels of PTHrP. Therapy is associated with a variable increase in the serum levels of PTH and 1,25-(OH)2D.
Assuntos
Hipercalcemia/tratamento farmacológico , Hipercalcemia/etiologia , Neoplasias/complicações , Proteínas/metabolismo , Alendronato , Calcitriol/sangue , Cálcio/sangue , Creatinina/sangue , Difosfonatos/uso terapêutico , Feminino , Humanos , Hipercalcemia/sangue , Masculino , Pamidronato , Hormônio Paratireóideo/sangue , Proteína Relacionada ao Hormônio Paratireóideo , Fósforo/sangueRESUMO
UNLABELLED: Bone ultrasound measures (QUSs) can assess fracture risk in the elderly. We compared three QUSs and their association with nonvertebral fracture history in 7562 Swiss women 70-80 years of age. The association between nonvertebral fracture was higher for heel than phalangeal QUS. INTRODUCTION: Because of the high morbidity and mortality associated with osteoporotic fractures, it is essential to detect subjects at risk for such fractures with screening methods. Because quantitative bone ultrasound (QUS) discriminated subjects with osteoporotic fractures from controls in several cross-sectional studies and predicted fractures in prospective studies, QUS could be more practical than DXA for screening. MATERIAL AND METHODS: This cross-sectional and retrospective multicenter (10 centers) study was performed to compare three QUSs (two heel ultrasounds: Achilles+ [GE-Lunar] and Sahara [Hologic]; the phalanges: ultrasound DBM sonic 1200 [IGEA]) for determining by logistic regression nonvertebral fracture odds ratio (OR) in a sample of 7562 Swiss women, 75.3 +/- 3.1 years of age. The two heel QUSs measured the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). In addition, Achilles+ calculated the stiffness index (SI) and the Sahara calculated the quantitative ultrasound index (QUI) from BUA and SOS. The DBM sonic 1200 measured the amplitude-dependent SOS (AD-SOS). RESULTS: Eighty-six women had a history of a traumatic hip fracture after the age of 50, 1594 had a history of forearm fracture, and 2016 had other nonvertebral fractures. No fracture history was reported by 3866 women. Discrimination for hip fracture was higher than for the other nonvertebral fractures. The two heel QUSs had a significantly higher discrimination power than the QUSs of the phalanges, with standardized ORs, adjusted for age and body mass index, ranging from 2.1 to 2.7 (95% CI = 1.6, 3.5) compared with 1.4 (95% CI = 1.1, 1.7) for the AD-SOS of DBM sonic 1200. CONCLUSION: This study showed a high association between heel QUS and hip fracture history in elderly Swiss women. This could justify integration of QUS among screening strategies for identifying elderly women at risk for osteoporotic fractures.
Assuntos
Osso e Ossos/diagnóstico por imagem , Fraturas Ósseas/complicações , Fraturas Ósseas/diagnóstico por imagem , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico por imagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Calibragem , Estudos Transversais , Feminino , Humanos , Programas de Rastreamento/métodos , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Suíça , UltrassonografiaRESUMO
Secondary hyperparathyroidism (HP) has been reported to be characteristic of idiopathic hypercalciuria (IHC) of the renal type. Out of the 155 patients with urinary stone disease and a normal plasma calcium level, only 1 had a distinctively increased plasma parathyroid hormone (PTH) level; however, he was found to be hypercalcemic in a second control study. In 33 patients with renal IHC, none had an elevated PTH level measured under normal, low, and high calcium intake. The mean basal PTH level of these patients was identical to that of 86 normal controls; it was significantly lower than that of the patients with primary or secondary HP who had normal PTH levels. During EDTA infusion, seven of eight patients with primary HP and a normal basal PTH level showed PTH responses greater than those observed in six patients with renal IHC, all of the latter responses being in the normal range. Chlorthalidone, given to seven patients with renal IHC during 4 weeks (100 mg/day), did not decrease the PTH levels. Measurement of nephrogenous cAMP performed in only a few patients revealed a slightly increased value in one of them who had an exceptionally severe hypercalciuria. Beside this latter result, no evidence for secondary HP could be found. Although secondary HP is tempting pathophysiological explanation for many characteristics of renal IHC, it seems to be quite rare.