A kinetic model of inorganic phosphorus mass balance in hemodialysis therapy

BACKGROUND: There is growing evidence that inorganic phosphorus (iP) accumulation in tissues (dTiP/dt) is a risk factor for cardiac death in hemodialysis therapy (HD). The factors controlling iP mass balance in HD are dietary intake (GiP), removal by binders (JbiP) and removal by dialysis (JdiP). If iP accumulation is to be minimized, it will be necessary to regularly monitor and optimize GiP, JbiP and JdiP in individual patients. We have developed a kinetic model (iPKM) designed to monitor these three parameters of iP mass balance in individual patients and report here preliminary evaluation of the model in 23 HD patients. METHODS: GiP was calculated from PCR measured with urea kinetics; JdiP was calculated from the product of dialyzer plasma water clearance (K(pwiP)) and time average plasma iP concentration (TACiP) and treatment time (t); a new iP concentration parameter (nTAC(iP), the TACiP normalized to predialysis CoiP) was devised and shown to be a highly predictable function of the form nTAC(iP) = 1 - alpha(1 - exp[-betaK(pwiP). t/ViP]), where the coefficients alpha and beta are calculated for each patient from 2 measure values for nTAC(iP), K(pwiP).t/ViP early and late in dialysis; we measured 8-10 serial values for nTAC(iP), K(pwiP). t/ViP over a single dialysis in 23 patients; the expression derived for iP mass balance is DeltaTiP = 12(PCR) - [K(pwiP)(t) (N/7)][CoiP(1 - alpha(1 - exp[-beta(Kt/ViP)]))] - k(b).Nb. RESULTS: Calculated nTAC(iP) = 1.01(measured nTAC(iP)), r = 0.98, n = 213; calculated JdiP = 0.66(measured total dialysate iP) + 358, n = 23, r = 0.88, p < 0.001. Evaluation of 10 daily HD patients (DD) and 13 3 times weekly patients with the model predicted the number of binders required very well and showed that the much higher binder requirement observed in these DD patients was due to much higher NPCR (1.3 vs. 0.96). CONCLUSION: These results are very encouraging that it may be possible to monitor the individual effects of diet, dialysis and binders in HD and thus optimize these parameters of iP mass balance and reduce phosphate accumulation in tissues.     

尿素氮动力学模型在血液透析中的应用

应用单室尿素氮动力学模型的方法,对30例慢性维持性血液透析患者进行质量平衡分析,着重研究了透析时效和两次透析间的间隔时数,即透析频率(次/周)这两个参数。透析时效根据Daugirdas法计算,透析间隔时效根据由动力学模型推导出来的计算式进行计算。将二者结果用于临床,根据临床康复状态进行判别,并经统计学检验分析,P>0.05,与临床情况无差异,此法的最大特点是根据个体差异定量预计欲达充分透析所需的时数和每周所需的透析次数,体现了个体化治疗方案,为确保透析质量提供了依提。     

A kinetic model of calcium mass balance during dialysis therapy

A kinetic model of Ca mass balance during dialysis has been developed. It is a single-compartment, variable-volume model to compute Ca mass balance during dialysis in its volume of distribution, the extracellular fluid. The model was used to analyze literature data which were suitable for the assessment of Ca mass balance over the course of dialysis. The modeled analyses predicted the serial plasma Ca concentrations very well. The mass balance analyses revealed a pool of rapidly diffusible Ca beyond the extracellular fluid distribution volume where Ca could be mobilized (M+(Ca)) or sequestered (M-(Ca)) very rapidly at rate equal but opposite in sign to dialyzer flux and thus effectively maintain near constant plasma Ca in the face of dialyzer Ca concentration gradients. This pool is likely the large pool of diffusible (miscible) Ca in connective tissue and on bone surfaces. Analysis of net Ca flux during dialysis with Cdi(Ca) = 2.50 mEq/l suggests that 80% of patients are in positive Ca balance during dialysis. Further studies are required to verify the model and to develop a model of interdialytic Ca mass balance.     

应用尿素动力学模型评价血透患者透析充分性和营养状态的临床研究

应用尿素动力学参数时间平均尿素浓度（TACurea）、整体尿素清除率（KT／V）、蛋白质分解代谢率（PCR），对42例维持性血液透析患者透析充分性及营养状态进行评价，并与临床结果进行比较，发现TACurea和PCR是反映血液透析长期充分与否的重要指标．KT／V可直接反映单次透析效果，是调整透析方案的最佳指标．在透析不充分的情况下，KT／V对PCR有着重要影响．     

Correction of acidosis by hemodialysis: proposal of a correlation with urea kinetics

BACKGROUND/AIMS: We examined the effect of hemodialysis (HD) on acid-base status and its relation to urea kinetics in clinically stable renal HD patients. The purpose of this study was to design a practical approach to monitoring the correction of acidosis, as it can be assisted by routine parameters of adequacy. METHODS: Blood samples were drawn immediately before and after HD from 46 chronic renal patients to determine electrolytes, blood gases, serum albumin and blood urea nitrogen (BUN). Additional measurements of pH and serum bicarbonate were done in 35 patients in the periods before, immediately after and 4 h after HD. The normalized protein catabolic rate (nPCR) was calculated and correlated with the serum albumin and bicarbonate values before HD. Equilibrated KT/V (eKT/V) and urea reduction ratio (URR) were calculated and correlated with the degree of bicarbonate correction, defined as DeltaHCO(3)(-). RESULTS: There was no correlation between nPCR and pre-HD HCO(3)(-), while there was a significant correlation between URR and eKT/V and DeltaHCO(3)(-) (p < 0.003). CONCLUSIONS: The Deltabicarbonate was well correlated with URR and eKT/V, and the study suggests that in standard HD the correction of acidosis may be related to target URR and eKT/V levels.     

Ultrafiltration volume by once‐weekly hemodialysis is a predictor of technique survival of combination therapy with peritoneal dialysis and hemodialysis

Overhydration is a major cause of technique failure of peritoneal dialysis (PD). Hence, we investigated the impact of ultrafiltration (UF) volume by once‐weekly hemodialysis (HD), excess volume beyond their dry weight, on technique survival of PD and HD combination therapy (PD+HD). Forty‐six anuric PD+HD patients were divided into three groups according to baseline UF volume by HD: low‐UF (<mean ? 1SD), middle‐UF (≥mean ? 1SD and <mean + 1SD), and high‐UF (≥mean + 1SD). High‐UF group showed larger extracellular water normalized to height (P = .038) and longer HD sessions (P < .001) compared with low‐UF group, whereas low‐UF group was older than middle‐UF group (P = .001). Technique survival rate was significantly lower in high‐UF group than in low and middle‐UF groups (P < .001), and the rates at 44 months were 80%, 90%, 20% in low, middle, and high‐UF groups, respectively. Chronic overhydration was the leading cause of technique failure for all. This study suggests that fluid overload remains a major cause of technique failure of PD even after once‐weekly HD is added.     

A convenient method for producing the bleomycin-induced mouse model of scleroderma by weekly injections using a methylcellulose gel

Systemic sclerosis (SSc) is a connective tissue disease characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and internal organs. An animal model of SSc, the bleomycin-induced mouse model, has been established and used extensively to investigate the pathogenesis of SSc and to seek novel therapeutic agents. We recently developed thermo-reversible combination gels that can be injected subcutaneously and are made in aqueous solution by forming a complex coacervate with the substance of interest and cationic macromolecules, followed by co-formulation with methylcellulose (MC) as a negative thermosensitive polysaccharide. The objective of this study was to demonstrate whether weekly injections of bleomycin using combination gels loaded with bleomycin can induce the skin fibrosis model of SSc in susceptible mouse strains. A low molecular weight MC (4%) gel with 4.5% ammonium sulfate was made in aqueous solution, and mixed with bleomycin. This was injected subcutaneously into female C3H/He mice at weekly intervals. Control mice were injected with the gel made with phosphate-buffered saline. After 4 weeks, histological examination and gene expression assays of cytokines were performed. Examination in vitro showed that more than 80% of the bleomycin was released from the gel by the 4th day. Histological examination showed that dermal thickness increased in the MC-bleomycin-injected group compared with the control, and semi-quantitative analysis indicated that the extent of inflammation did not differ between the groups. In the MC-bleomycin-injected group, dermal fibrosis assessed with the Masson-Trichrome stain and numbers of alpha-smooth muscle actin-positive fibroblastic cells also increased. The procedure for inducing scleroderma in which bleomycin is injected weekly as an easily-made gel system using methylcellulose, can induce dermal fibrosis in susceptible mice without causing inflammation. We believe this system represents a time- saving and convenient procedure that should facilitate research on SSc.     

Multivariate analysis of urea clearance index in maintenance hemodialysis patients from a single center

目的 计算维持血液透析患者的单次尿素清除指数(Kt/V),记录透析过程中的血流量、超滤量、血红蛋白和体重指数( BMI)等指标,并分析这些指标对Kt/V的影响.方法 选取我院血液净化中心维持血液透析3个月以上的终末期肾病患者135例,计算每个患者该次血液透析的Kt/V,Kt/V≥1.2为Kt/V达标组,Kt/V＜ 1.2为Kt/V不达标组,统计分析Kt/V与血流量、超滤量、血红蛋白、体重指数等指标的相关性.结果 135例患者中,血流量(β=0.052)和超滤量(β=1.143)与单次血液透析的Kt/V呈正相关(P＜0.05),BMI(β=-0.404)和血红蛋白(β=-0.063)与单次血液透析的Kt/V呈负相关(P＜0.05).结论 血流量、BMI、超滤量和血红蛋白是单次血液透析Kt/V的重要影响因素.     

Analysis of urea nitrogen and creatinine kinetics in hemodialysis: comparison of a variable-volume two-compartment model with a regional blood flow model and investigation of an appropriate solute kinetics model for clinical application

To investigate an appropriate solute kinetics model for clinical application, we analyzed urea nitrogen (UN) and creatinine (Cr) kinetics by a variable-volume two-compartmental model (2CM) and a regional blood flow model (RBF) in 44 hemodialysis patients with varying proportions of first compartmental volume and regional volume (p(1)). Solute kinetics could not be solved in some of the patients with higher p(1) values, and there were more solution failures by the RBF than by the 2CM. The solute generation rate (g) and solute distribution volume in the dry state (V(D)) increased with increases in p(1) in both models, but there were some differences between the two models. When g was normalized by V(D), it became relatively constant, irrespective of the p(1) value or model used (0.133 +/- 0.029 mg/min/l by the 2CM and 0.132 +/- 0.029 mg/min/l by the RBF for UN; 0.0200 +/- 0.0049 mg/min/l by the 2CM and 0.0198 +/- 0.0048 mg/min/l by the RBF for Cr). The intercompartmental mass transfer coefficient (K(c); liters/min) calculated by the 2CM decreased as p(1) increased (K(c) = -1.77.p(1) + 1.16, p < 0.0001, R = 0.999 for UN; K(c) = -0.847.p(1) + 0.556, p < 0.0001, R = 1.000 for Cr). The systemic blood flow (Q(sys); liters/min) calculated by the RBF also decreased as p(1) increased (Q(sys) = -11.1.p(1) + 6.21, p < 0.0005, R = 1.000 for UN; Q(sys) = -5.22.p(1) + 2.90, p < 0.001, R = 0.999 for Cr). Since the RBF more frequently failed to solve the solute kinetics and since there was a difference in its Q(sys) values for UN and Cr, the 2CM was considered to be a superior model. When p(1) was extremely low, the 2CM could be transformed into a modified variable-volume one-compartment model (1CM) which presented a similar g/V(D) (0.133 +/- 0.029 for UN; 0.0200 +/- 0.0048 for Cr). This modified 1CM was considered to satisfy appropriate conditions for clinical application, since it is simpler than the 2CM and provides useful information on the dialysis dose.     

L-carnitine supplementation decreases the left ventricular mass in patients undergoing hemodialysis.

BACKGROUND: Patients on long-term hemodialysis become deficient in carnitine and are frequently treated with carnitine supplementation to offset their renal anemia, lipid abnormality and cardiac dysfunction. The therapeutic value of carnitine supplementation on left ventricular hypertrophy (LVH) in patients with normal cardiac systolic function remains uncertain. METHODS AND RESULTS: The cardiac morphology and function of 10 patients given 10 mg/kg of L-carnitine orally, immediately after hemodialysis sessions 3 times per week for a 12-month period were compared with 10 untreated control patients. Using echocardiography, left ventricular fractional shortening (LVFS) and left ventricular mass index (LVMI) were measured before and after the study period. As a result, amounts of serum-free carnitine increased from 28.4+/-4.7 to 58.5+/-12.1 micromol/L. The LVMI decreased significantly from 151.8+/-21.2 to 134.0+/-16.0 g/m(2) in treated patients (p<0.01), yet the LVMI in untreated control patients did not change significantly (ie, from 153.3+/-28.2 to 167.1+/-43.1 g/m(2)). However, LVFS values remained unchanged in both groups. Although L-carnitine promoted a 31% reduction in erythropoietin requirements, hematocrit and blood pressure did not change during the study period. CONCLUSIONS: Supplementation with L-carnitine induced regression of LVH in patients on hemodialysis, even for those with normal systolic function.     

Effects of imidapril on left ventricular mass in chronic hemodialysis patients.

Left ventricular hypertrophy is considered to be a major cardiovascular risk factor in hemodialysis patients. Not only high blood pressure but also humoral factors such as angiotensin II and aldosterone are thought to contribute to the increase in left ventricular mass. We examined the effects of an angiotensin converting enzyme (ACE) inhibitor, imidapril, on left ventricular mass in patients with end-stage renal diseases on maintenance hemodialysis. Thirty patients on chronic hemodialysis were randomly divided into 2 groups of 15 patients each and given placebo or 2.5 mg imidapril once daily for 6 months. Before and after the 6-month period, left ventricular mass was evaluated by echocardiography, and circulating factors of the renin-angiotensin-aldosterone system were measured. Background characteristics such as age, gender ratio, causes of renal failure, duration of hemodialysis, body mass index and pre-dialysis blood pressure were comparable between the placebo and the imidapril groups. Systolic and diastolic blood pressures were not significantly changed in either group during the study period. In the imidapril group, serum ACE was reduced (12 +/- 1 to 5 +/- 2 U/l, p < 0.01) and plasma renin activity was increased (3.3 +/- 0.8 to 8.1 +/- 3.2 ng/ml/h, p < 0.01), but plasma angiotensin II and aldosterone were not significantly changed after 6 months (13 +/- 3 to 17 +/- 3 pg/ml and 365 +/- 125 to 312 +/- 132 pg/ml, respectively). On the other hand, left ventricular mass index was significantly decreased in the imidapril group (132 +/- 10 to 109 +/- 6 g/m2, p < 0.05) but was unchanged in the placebo group (129 +/- 6 to 126 +/- 5 g/m2). These results suggest that an ACE inhibitor reduces left ventricular mass in hemodialysis patients by a mechanism that is independent of changes in blood pressure.     

Severe methanol poisoning. Application of a pharmacokinetic model for ethanol therapy and hemodialysis

Two patients with extremely high blood methanol concentrations (260 and 282 mg/dl) were successfully treated using pharmacokinetic dosing of ethanol, hemodialysis and supportive measures. Both patients recovered completely without residual ophthalmologic deficits. Early hemodialysis and inhibition of methanol metabolism with effective ethanol concentrations were attributed to the patients' full recovery. Methanol elimination was enhanced by hemodialysis as evidenced by a decrease in half-life from eight to two and a half hours. Methanol dialysance was 98 ml/min. A dosage regimen for ethanol was devised, utilizing dose-dependent pharmacokinetic parameters and the ethanol dialysance (100 to 120 ml/min) from these two patients. An ethanol loading dose of 0.6 g/kg should be administered to an adult with an acute methanol ingestion. This dose will produce a blood ethanol concentration of approximately 100 mg/dl which can be maintained by an ethanol infusion of 66 mg/kg/hour for nondrinkers to 154 mg/kg/hour for chronic ethanol drinkers. Hemodialysis should be initiated if the blood methanol concentration is greater than 50 mg/dl. If hemodialysis is initiated, the ethanol infusion should be increased by 7.2 g/hour.     

血液透析对新诊断终末期肾衰竭患者营养状况及体内水分布影响

目的探讨血液透析(HD)对新诊断终末期肾脏疾病(ESRD)患者营养状况及体内水分布的影响。方法选择2006年10月至2007年10月上海交通大学医学院附属新华医院血液净化中心进行HD的ESRD患者30例。HD前及后3、6个月使用生物电阻抗分析方法(BIA)评估体内水分布状况,应用BIA、人体测量、血液生化指标评估营养状况。结果新诊断ESRD患者总体液量、细胞外液、细胞内液、标化总体液量、标化细胞外液、标化细胞内液在HD后3、6个月较HD前明显下降(P<0.05),HD后3、6个月比较差异无统计学意义;机体蛋白质、无机盐、体脂肪、瘦体重、骨骼肌在HD后3个月较HD前明显增加(P<0.05),HD后6个月较3个月进一步增加(P<0.05),去脂体重、肱三头肌皮褶厚度在HD后3、6个月较HD前明显增加(P<0.05),HD后3、6个月比较差异无统计学意义,体重指数在HD后6个月较HD前明显增加(P<0.05),HD后3个月和HD前比较差异无统计学意义;血白蛋白、转铁蛋白在HD后3、6个月较HD前明显增加(P<0.05),HD后3、6个月比较差异无统计学意义,前白蛋白在HD后6个月较HD前和HD后3个月明显增加(P<0.05),血红蛋白在HD后3个月较HD前明显增加(P<0.05),HD后6个月较3个月进一步增加(P<0.05),超敏C-反应蛋白在HD后6个月较HD前明显增加(P<0.05)。结论及时HD可纠正新诊断ESRD患者体内水负荷过多,改善营养状况,提示有严重营养不良,体内水负荷过多的ESRD患者应尽早行HD。     

Acid-base balance in a canine model of cardiac arrest

Our study was performed to determine the pattern of arterial, venous, and cerebral spinal fluid (CSF) acidosis in a canine model of cardiac arrest and resuscitation; and the effect of bicarbonate treatment on arterial, venous, and CSF acidosis. Animals were instrumented to sample arterial blood, mixed venous blood, and CSF through a cisternal catheter. Following six minutes of ventricular fibrillation, manual CPR efforts were begun and continued for 30 minutes of cardiac arrest. Arterial, mixed venous, and CS fluids were sampled at baseline, six, 12, 18, 24, 27, and 30 minutes. Ten experimental dogs received sodium bicarbonate (2 mEq/kg) at 20 minutes of cardiac arrest, while ten animals in the control group received no alkali treatment. The experimental group showed a significantly higher arterial (7.79 +/- 0.20 vs 7.46 +/- 0.16 at 30 minutes) and venous pH (7.34 +/- 0.12 vs 7.19 +/- 0.10 at 24 minutes) following bicarbonate administration. This higher pH occurred despite a concomitant increase in arterial (31 +/- 10 vs 19 +/- 9 mm Hg at 27 minutes; 31 +/- 9 vs 10 +/- 8 at 30 minutes) and venous (104 +/- 30 vs 63 +/- 10 mm Hg at 24 minutes) pCO2. CSF analysis showed a gradually worsening acidosis. However, CSF pH (7.12 +/- 0.14 vs 7.16 +/- 0.23 at 30 minutes) and pCO2 were not significantly changed by the administration of bicarbonate.     

An experimental model for angina pectoris using krypton-81m. The dynamic balance between myocardial perfusion and metabolism.

16 anesthetized and open chest dogs were studied. Regional myocardial perfusion was assessed using a constant infusion of krypton-81m (half-life 13 sec) into the aortic sinuses and a gamma camera linked to a digital computer. The epicardial electrocardiogram was recorded and the plasma activity of creatine kinase was measured in serial blood samples from the aorta and a local coronary vein draining the area of myocardium supplied by the left anterior descending coronary artery (LAD). These parameters were observed throughout the whole period of a 5-h experiment. Two reversible snares were positioned on the middle portion of this artery. A critical narrowing of this vessel was produced and a peripheral venous infusion of isoproterenol (causing a 5--10% increase in heart rate and a 10--15% fall in blood pressure) was used to increase myocardial oxygen demand. During infusion there was both a relative and absolute fall in regional myocardial perfusion together with evidence of myocardial ischemia in the epicardial electrocardiogram. Provided the infusion was discontinued within 30 min (8 dogs) myocardial perfusion and the epicardial electrocardiogram returned to normal during a 5-h recovery period. In addition there was no efflux of creatine kinase activity from the ischemic area. When infusion was continued for 1 h (4 dogs) permanent alterations in myocardial perfusion and the epicardial electrocardiogram occurred and there was increased creatine kinase activity released from the area of myocardium by the narrowed vessel. Infusion for 40 min in 4 dogs produced permanent alterations in the parameters measured in 2 and complete recovery in the remaining 2. A further 4 dogs were studied in the same way but without a snare on the coronary artery. Isoproterenol given for 1 h produced no effects on any of the parameters either during or after infusion.     

The effect of profiled hemodialysis on intradialytic hemodynamics when a proper sodium balance is applied

BACKGROUND: Profiled hemodialysis (HD) has been claimed to ameliorate intradialytic complications such as hypotension. Frequently, these profiles are based on providing the patient with an accumulating sodium load. This increases the risk of interdialytic complications, such as hypertension and increased weight gain. The present study investigated the effect of profiled HD, without an accompanying sodium loading, on intradialytic hemodynamics in stable HD patients. METHODS: In eight stable HD patients a standard hemodialysis (S-HD) was compared to a decreasing Na(+)-profiled hemodialysis (Na-HD), and an ultrafiltration profiled hemodialysis (UF-HD). Care was taken to have the sodium balances similar during these sessions. The patients were monitored non-invasively during dialysis with respect to their cardiac performance by means of electrical impedance cardiography, their variation in blood volume by means of an on-line optical measurement, and their hydration state by means of body impedance analysis. RESULTS: Sodium balance and mean arterial sodium concentrations were similar in the three treatments. Intradialytic hemodynamics during UF-HD were similar to those of S-HD. However, Na-HD improved blood pressure preservation, remarkably without significant blood volume preservation, due to a better stroke volume preservation in the first hour of dialysis. CONCLUSION: Sodium-balanced, Na-profiled HD improves blood pressure preservation in stable HD patients without providing the patients with a sodium load. This effect is due to a better stroke volume preservation early in dialysis, without a significant reduction in blood volume decrease. UF-HD, as mono-therapy, has no beneficial effect on intradialytic hemodynamics in stable patients.     

Prescribing habits in primary biliary cirrhosis: a national survey.

BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown aetiology. A number of drugs have been used in its treatment, but only ursodeoxycholic acid (UDCA) has been shown to improve survival. Our aims were to determine the current prescribing habits in PBC of all practising gastroenterologists in the UK. METHODS: A postal questionnaire was sent to 454 gastroenterologists in 1996, followed by a second questionnaire a month later to the non-responders. RESULTS: Of 454 doctors sent questionnaires, 379 (83%) replied. Of these, 58 were excluded from further analysis as they were not practising gastroenterologists. There are an estimated 4337 patients with PBC being seen by gastroenterologists in hospitals. Of these, only 1376 (32%) are being seen in liver units. Ninety-one per cent of gastroenterologists look after patients with PBC (median 10 patients, range 1-500). Ninety-five per cent of gastroenterologists prescribe UDCA but there is a large dose range (median 11.5 mg/kg/day, range 1.5-23.1). Of these, 93% also prescribe cholestyramine. Only 45 (14%) gastroenterologists prescribed other treatments for PBC (13 colchicine, 24 steroids, nine penicillamine, 13 immunosuppressants). Only 53 (17%) treat the symptoms/complications of PBC (37 fat-soluble vitamins, 15 calcium, six bisphosphonates, one hormone replacement therapy, 10 antihistamines, 10 rifampicin). CONCLUSIONS: UDCA is being prescribed for PBC by the majority of practising gastroenterologists but over a wide dose range. Very few gastroenterologists are using preventive treatment for osteoporosis in this high-risk group. Other treatments, as yet unproven in trials, are being prescribed by a minority of gastroenterologists.     

Osteoporosis. Efficacy and safety of a bisphosphonate dosed once weekly

Trabecular and cortical bone is continuously being remodeled at microscopic loci called basic multicellular units (BMU). Estrogen deficiency in menopause contributes to an increase in osteoclastic resorption and/or a decrease in osteoblastic formation, which leads to microscopic bone loss at the BMUs. Drug treatments for osteoporosis are intended to inhibit bone resorption, reduce the rate of bone turnover, and increase bone mass. The bisphosphonate alendronate was recently approved for once-a-week dosing for the prevention and treatment of postmenopausal osteoporosis. A 70-mg, once-a-week dose of alendronate has been shown to be therapeutically equivalent to the standard daily 10-mg dose. Tolerability and safety of weekly dosing appear to be similar to daily dosing.