Reversal of adynamic bone disease by lowering of dialysate calcium.

Adynamic bone disease (ABD) is increasingly recognized, especially in dialysis patients treated with oral calcium carbonate, vitamin D supplements, or supraphysiological dialysate calcium. We undertook this study to assess the effect of lowering dialysate calcium on episodes of hypercalcemia, serum parathyroid hormone (PTH) levels as well as bone turnover. Fifty-one patients treated with peritoneal dialysis and biopsy-proven ABD were randomized to treatment with control calcium, 1.62 mM, or low calcium, 1.0 mM, dialysate calcium over a 16-month period. In the low dialysate calcium group, 14 patients completed the study. This group experienced a decrease in serum total and ionized calcium levels, and an 89% reduction in episodes of hypercalcemia, resulting in a 300% increase in serum PTH values, from 6.0+/-1.6 to 24.9+/-3.6 pM (P<0.0001). Bone formation rates, all initially suppressed, at 18.1+/-5.6 microm2/mm2/day rose to 159+/-59.4 microm2/mm2/day (P<0.05), into the normal range (>108 microm2/mm2/day). In the control group, nine patients completed the study. Their PTH levels did not increase significantly, from 7.3+/-1.6 to 9.4+/-1.5 pM and bone formation rates did not change significantly either, from 13.3+/-7.1 to 40.9+/-11.9 microm2/mm2/day. Lowering of peritoneal dialysate calcium reduced serum calcium levels and hypercalcemic episodes, which resulted in increased PTH levels and normalization of bone turnover in patients with ABD.

Vascular access survival and incidence of revisions: a comparison of prosthetic grafts, simple autogenous fistulas, and venous transposition fistulas from the United States Renal Data System Dialysis Morbidity and Mortality Study.

OBJECTIVE: The study's aim was to evaluate access patency and incidence of revisions in patients initiating hemodialysis and to determine differences in access performance by type of access among patient subgroups. METHODS: The study used data from the United States Renal Data System Dialysis Morbidity and Mortality Study Wave 2, which contained a random sample of dialysis patients initiating dialysis in 1996 and early 1997. Failures and revisions were evaluated among 2247 newly placed hemodialysis accesses by using Cox proportional hazards regression model and Poisson regression. Primary and secondary patency rates were estimated using the Kaplan-Meier method. RESULTS: Fifteen hundred seventy-four prosthetic grafts, 492 simple autogenous fistulas, and 181 venous transposition fistulas were available for evaluation. Prosthetic grafts had a 41% greater risk of primary failure compared with simple fistulas (relative risk, 1.41; 95% CI, 1.22-1.64; P < .001) and a 91% higher incidence of revision (relative risk, 1.91; 95% CI, 1.60-2.28; P <.001). At 2 years, autogenous fistulas demonstrated superior primary patency (39.8% versus 24.6%, P < .001) and equivalent secondary patency (64.3% versus 59.5%, P = .24) compared with prosthetic grafts. When compared with simple fistulas, vein transpositions demonstrated equivalent secondary patency at 2 years (61.5% versus 64.3%, P = .43) but inferior primary patency (27.7% versus 39.8%, P = .008) and had a 32% increased incidence of revision (P = .04). Autogenous fistulas had superior primary patency compared with prosthetic grafts in all patient subgroups except for patients with previously failed access. Vein transpositions showed the greatest benefit in terms of patency and incidence of revision in women and in patients with previously failed access. CONCLUSIONS: The preferential placement of autogenous fistulas may increase primary patency and decrease the incidence of revisions. Vein transpositions had similar secondary patency compared with simple fistulas, but required more revisions. The greatest benefit of a vein transposition fistula was seen in women and in patients with a history of access failure.

Assessment of a policy to reduce placement of prosthetic hemodialysis access.

BACKGROUND: The aim of this study was to evaluate the determinants of access patency and revision, including the effects of reducing the placement of prosthetic hemodialysis access. METHODS: A retrospective cohort study of all hemodialysis accesses placed at the Veteran's Administration Puget Sound Health Care System between 1992 and 1999 was conducted. A policy was instituted in 1996 that maximized the use of autogenous hemodialysis access. The impacts of the policy change, demographics, and comorbid factors on access type and patency, were examined. Primary and secondary patency rates were examined using the Kaplan--Meier method, and factors associated with failure and revision were examined using Cox proportional hazard models and Poisson regression. RESULTS: During the study, 104 accesses (61 prosthetic grafts and 43 autogenous fistulas) were placed prior to 1996, and 118 (31 prosthetic grafts and 87 autogenous fistulas) were placed after 1996. There was a significant increase in autogenous fistulas placed after 1996 (87 out of 118) compared with before 1996 (43 out of 104, P < 0.001). At one year, autogenous fistulas demonstrated superior primary patency (56 vs. 36%, P = 0.001) and secondary patency (72 vs. 58%, P = 0.003) compared with prosthetic grafts. After adjustment for age, race, side of access placement, and history of prior access placement, patients with a prosthetic graft were estimated to experience a 78% increase in the risk of primary access failure when compared with similar patients having an autogenous access [adjusted relative risk (aRR) = 1.78, 95% CI 1.21--2.62, P = 0.003)]. Similarly, the adjusted relative risk of secondary access failure for comparing prosthetic grafts with autogenous fistulas was estimated to be 2.21 (95% CI 1.38--3.54, P = 0.001). The adjusted risk of access revision was 2.89-fold higher for prosthetic grafts than for autogenous fistulas (95% CI 1.88--4.44, P < 0.001). CONCLUSIONS: Autogenous conduits demonstrated superior performance when compared with prosthetic grafts in terms of primary and secondary patency and number of revisions. A policy emphasizing the preferential placement of autogenous fistulas over prosthetic grafts may result in improved patency and a reduction in the number of procedures required to maintain dialysis access patency.

Bone density loss after allogeneic hematopoietic stem cell transplantation: a prospective study.

The incidence and course of bone density abnormalities following hematopoietic stem cell transplantation are poorly understood and complicated by the impact of multiple factors. Hip, spine, and wrist bone mineral densities (BMDs) were measured in 104 adults (54 women, 54 men; mean age, 40 years [range, 18-64 years]) at 3 and 12 months after allogeneic transplantation. Clinical and laboratory variables were evaluated using univariate and multivariate analyses to determine risk factors for osteoporosis, fracture, and avascular necrosis. At 3 months posttransplantation, combined (male and female) hip, spine, and wrist z scores were -0.35, -0.42, and +0.04 standard deviations, respectively. At 12 months both men and women experienced significant loss of hip BMD (4.2%, P < .0001); changes in the spine and wrist were minimal. The cumulative dose and number of days of glucocorticoid therapy and the number of days of cyclosporine or tacrolimus therapy showed significant associations with loss of BMD; age, total body irradiation, diagnosis, and donor type did not. Nontraumatic fractures occurred in 10.6% of patients and avascular necrosis in 9.6% within 3 years posttransplantation. The decrease in height between pretransplantation and 12 months posttransplantation was significant (P = .0001). Results indicate that loss of BMD after allogeneic stem cell transplantation is common and accelerated by the length of immunosuppressive therapy and cumulative dose of glucocorticoid. An increased incidence of fracture and avascular necrosis may adversely impact long-term quality of life. Prevention of bone demineralization appears warranted after stem cell transplantation.

Risk factors for hip fracture among patients with end-stage renal disease.

BACKGROUND: Although bone disease is well described among end-stage renal disease (ESRD) patients, little attention has been paid to the occurrence of fracture. We sought to identify factors that are associated with hip fracture among ESRD patients. METHODS: Data from patients who participated in the United States Renal Data System Dialysis Morbidity and Mortality Study Wave 1 were used for this study. Hip fractures occurring among these patients between 1993 and 1996 were identified from Medicare claims data available from the United States Renal Data System. Cox proportional hazards models were used to estimate the risk of hip fracture associated with demographic and medical variables. RESULTS: Of the 4952 patients included in this analysis, 103 sustained a hip fracture. In the multivariate analysis, age (per increasing decade, RR = 1.40, 95% CI 1.20, 1.64), female gender (RR = 2.26, 95% CI 1.48, 3.44), race (blacks compared with whites, RR = 0.58, 95% CI 0.37, 0.91), body mass index (per 1 unit increase, RR 0.89, 95% CI 0.86, 0.93), and the presence of peripheral vascular disease (RR 1.94, 95% CI 1.29, 2.92) were independently associated with hip fracture. Serum intact parathyroid hormone (iPTH), aluminum, diabetes, and bicarbonate levels did not appreciably influence the risk of hip fracture. CONCLUSIONS: Demographic and other characteristics that predict risk of hip fracture in the population at large also do so in ESRD patients. However, we could identify no characteristics of ESRD or its treatment that were independently related to hip fracture incidence.

Anthropometric measures and risk of death in children with end-stage renal disease.

We evaluated the association between anthropometric measurements and death among pediatric patients with end-stage renal disease (ESRD) using data from the Pediatric Growth and Development Special Study (PGDSS) from the US Renal Data System. Height, growth velocity, and body mass index (BMI) were used for the analysis of 1,949 patients in the PGDSS. To standardize these measurements, SD scores (SDSs) were calculated using population data from the Third National Health and Nutrition Examination Survey. Using Cox proportional hazards models, we assessed the association between anthropometric measures and death, controlling for demographic factors and stratifying by age. Multivariate analysis showed that each decrease by 1 SDS in height was associated with a 14% increase in risk for death (adjusted relative risk [aRR], 1.14; 95% confidence interval [CI], 1.02 to 1.27; P = 0.017). For each 1 SDS decrease in growth velocity among patients in our sample, the risk for death increased by 12% (aRR, 1.12; 95% CI, 1.00 to 1.25; P = 0.043). There was a statistically significant U-shaped association between BMI and death (P = 0.001), with relatively low and high BMIs associated with an increased risk for death. In children with ESRD, growth delay and extremes in BMI are associated with an increased risk for mortality.

Increased risk of hip fracture among patients with end-stage renal disease.

BACKGROUND: Although patients with end-stage renal disease (ESRD) are at increased risk for bone loss, the risk of hip fracture in this population is not known. We compared the risk of hip fracture among dialysis patients with the general population. METHODS: We used data from the United States Renal Data System (USRDS) to identify all new Caucasian dialysis patients who began dialysis between January 1, 1989, and December 31, 1996. All hip fractures occurring during this time period were ascertained. The observed number of hip fractures was compared with the expected number based on the experience of residents of Olmstead County (MN, USA). Standardized incidence ratios were calculated as the ratio between observed and expected. The risk attributable to ESRD was calculated as the difference between the observed and expected rate of hip fracture per 1000 person-years. RESULTS: The number of dialysis patients was 326,464 (55.9% male and 44.1% female). There were 6542 hip fractures observed during the follow-up period of 643, 831 patient years. The overall incidence of hip fracture was 7.45 per 1000 person years for males and 13.63 per 1000 person years for females. The overall relative risk for hip fracture was 4.44 (95% CI, 4.16 to 4.75) for male dialysis patients and 4.40 (95% CI, 4.17 to 4.64) for female dialysis patients compared with people of the same sex in the general population. While the age-specific relative risk of hip fracture was highest in the youngest age groups, the added risks of fracture associated with dialysis rose steadily with increasing age. The relative risk of hip fracture increased as time since first dialysis increased. CONCLUSIONS: The overall risk of hip fracture among Caucasian patients with ESRD is considerably higher than in the general population, independent of age and gender.

Symptomatic hypercalcemia of immobilization in a patient with end-stage renal disease.

The phenomenon of hypercalcemia in immobilization is well known, but there is limited awareness of the potential for this complication in patients with end-stage renal disease (ESRD) on maintenance hemodialysis with reduced capacity for disposition of calcium. We describe such a patient who showed a calcemic response to just 3 days of immobilization in the setting of an acute illness marked by coma. Despite intensive initial therapy for hypercalcemia, including withdrawal of all calcium products and daily hemodialysis treatments using low calcium baths, her serum calcium rose to 14.0 mg/dL during the hospitalization; this metabolic abnormality appeared to perpetuate her stuporous state. Mobilization as an outpatient was the most effective therapy. Extensive testing was performed to rule out other causes for this patient's hypercalcemia. Greater recognition of acute hypercalcemia in patients with ESRD immobilized by various illnesses would preclude unnecessarily expensive and invasive testing for other causes of hypercalcemia.

Determinants of type and timing of initial permanent hemodialysis vascular access.

BACKGROUND: We undertook a population-based study of hemodialysis (HD) patients to determine which factors are important in predicting the type of permanent access initially placed and if a functional permanent access is in place at the start of HD. METHODS: Selected characteristics were abstracted from the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (DMMS) Wave 2. Logistic regression was used to estimate the independent contribution of specific characteristics in predicting whether the initial permanent access placed was an arteriovenous (AV) fistula compared with a polytetrafluoroethylene (PTFE) graft, and in predicting whether permanent access (fistula or graft) was in place at the initiation of dialysis. RESULTS: Sixty-seven percent of the patients had an AV graft placed as their first permanent access. Characteristics important in predicting if a fistula was initially placed included age (per decade; aOR = 0.84, P < 0.001), female gender (aOR = 0.52, P < 0.001), body mass index (per standard deviation; aOR = 0.70, P = 0.09), avoiding blood draws (aOR = 1.96, P < 0.001), ability to ambulate (aOR = 2.24, P = 0.008), underlying renal disease (glomerular compared with diabetes, aOR = 2.19, P = 0.009), college education (aOR = 1.72, P = 0.002), and sharing in decision making (aOR = 1.50, P = 0.02). Thirty-four percent of patients (34.4%) had functional permanent access at the start of HD. Characteristics important in predicting which patients had functional permanent access included serum albumin (per 1 mg/dL increase, aOR =1.55, P = 0.003), erythropoietin prior to starting HD (aOR = 1.79, P = 0.002), fewer predialysis nephrologist visits (aOR = 0.21, P < 0.001), and when the patient was told they had renal disease (aOR = 0.33, P = 0.002). CONCLUSIONS: PTFE grafts were the most common initial permanent access. The majority of patients did not have permanent access at the start of dialysis. Factors that are thought to compromise identification of adequate veins were important predictors of PTFE graft placement. Permanent access at the start of HD was largely a function of early patient education and early referral to a nephrologist.

Screening plasma aluminum levels in relation to aluminum bone disease among asymptomatic dialysis patients.

Aluminum accumulation in plasma and tissues is a well-described complication among persons undergoing peritoneal dialysis or hemodialysis. Excess bone aluminum is associated with low bone formation rates and increased risk for fractures. Current recommendations for care of patients with end-stage renal disease include screening for aluminum toxicity with plasma aluminum levels; patients with levels below 40 microg/L are considered to be at low risk for aluminum bone disease (ABD). We examined data from the Toronto Renal Osteodystrophy Study to evaluate the performance of plasma aluminum levels in screening for ABD. Two hundred fifty-eight unselected patients undergoing peritoneal dialysis (n = 143) or hemodialysis (n = 115) underwent diagnostic bone biopsy and measurement of plasma aluminum level. Sixty-nine patients (26.7%) were identified as having ABD, defined as low or normal bone formation rates with 25% or more bone surface aluminum staining. Plasma aluminum level was strongly associated with the presence of ABD; the odds ratio was 1.4 for each increase of 10 microg/L (95%CI, 1.2, 1.6). However, only 50.1% of patients with a plasma aluminum level of 40 microg/L or greater had ABD, whereas 14.2% of patients with a level below this threshold also had ABD. Using this cutoff level of 40 microg/L, the sensitivity and specificity were 65.2% and 76.7%, respectively. We conclude that although there is a correlation between high aluminum levels and ABD, a patient's plasma aluminum level does not predict well the presence of ABD in spite of a relatively high prevalence of disease.

Renal osteodystrophy in pre-dialysis patients: ethnic difference?

The purpose of the present study is to investigate whether an ethnic difference exists in the incidence of renal osteodystrophy between Asian and Western countries in end-stage renal disease (ESRD) patients. We evaluated bone histology in 58 pre-dialysis patients (28 male, 30 female; mean age: 47.7 years). All patients had bone biopsies with quantitative histomorphometry and serological parameters such as intact PTH, osteocalcin, total alkaline phosphatase, and basal and deferoxamine-stimulated serum aluminum levels. We observed that 91.4% of all evaluated patients showed renal osteodystrophy before the start of dialytic therapy. Mild osteitis fibrosa were observed in 21 patients (36.2%), severe osteitis fibrosa in 5 patients (8.6%), mixed lesions in 7 patients (12.1%), osteomalacia in 6 patients (10.3%), aplastic bone disease in 14 patients (24.1%), and normal bone in 5 patients (8.6%). Among the bone histomorphometric parameters, fibrosis area rate (%) showed the best correlation with intact PTH, and osteocalcin and osteoid area rate (%) with total alkaline phosphatase. Aluminum-related bone disease was not observed. Among patients with aplastic bone disease, only 14.3% showed aluminum deposition of any significance (5% < stainable bone surface aluminum < 25%). In the diabetic patients, aplastic bone disease was most common, but no case was related to aluminum intoxication. In conclusion, the distribution of renal osteodystrophy in our study was different from that of Western countries in pre-dialysis patients. Our patients tended to have more mild-form osteitis fibrosa and normal findings, and less severe-form osteitis fibrosa and aplastic bone disease. Aluminum-related bone disease was not observed.

A calcimimetic agent acutely suppresses parathyroid hormone levels in patients with chronic renal failure. Rapid communication.

The control of hyperparathyroidism in patients with chronic renal failure continues to be a problem, particularly when parathyroid hormone (PTH) suppression becomes refractory to calcitriol activation of parathyroid cell 1,25-dihydroxyvitamin D receptors. To evaluate whether parathyroid cell calcium receptor activation may be useful in suppressing PTH levels, we tested the safety and effectiveness of a novel calcimimetic agent in dialysis patients with hyperparathyroidism. In a prospective, dose finding study, the calcimimetic agent, NPS R-568, was administered orally to seven patients at the start of a hemodialysis session and again 24 hours later. Plasma PTH, calcitonin and ionized calcium levels were measured over a 48 hour period and patients were observed for adverse events. Plasma PTH levels fell abruptly in all patients after a single dose of the compound, with the maximum suppression occurring within one to two hours after its administration. Following the administration of low doses (40 or 80 mg), the suppressed PTH levels rose to baseline values over 48 hours, whereas in patients who received high doses (120 or 200 mg) the mean PTH level remained 51% below baseline. Plasma calcitonin increased after the administration of both low and high doses (peak effect within 4 to 6 hr), with levels always returning to baseline by 48 hours. There were no episodes of hypocalcemia and no adverse effects were reported. We conclude that the activation of parathyroid cell calcium receptors by a novel calcimimetic compound is safe and effective in acutely suppressing PTH secretion in dialysis patients with hyperparathyroidism. Whether concomitant stimulation of calcitonin secretion will provide added beneficial effects on bone remodeling remains to be determined in long-term studies.

Avascular necrosis following bone marrow transplantation: a case-control study.

The role of specific immunosuppressive agents in the development of avascular necrosis (AVN) following hematopoietic stem cell and solid organ transplantation remains unclear. To further explore this question, we conducted a case-control study of patients who underwent bone marrow transplantation (BMT) at the Fred Hutchinson Cancer Research Center. 96 of 1939 long-term survivors transplanted between May 1976 and October 1993 were identified as having AVN. Eight patients were excluded because AVN developed before transplant and one was excluded due to restrictions on reviewing follow-up records. The remaining 87 patients developed AVN a mean of 26.3 +/- 2 months posttransplant and were matched for age, gender, and date of transplant to other BMT recipients. Records were reviewed for corticosteroid and cyclosporine use, pretransplant conditioning with total body irradiation (TBI), and other information including disease for which the transplant was indicated, type of transplant, the occurrence of acute and chronic graft-vs.-host disease, and steroid use prior to transplant. Adjusted odds ratios (ORs) were obtained from conditional logistic regression for 87 matched pairs. Posttransplant steroid use was a risk factor for the occurrence of AVN (adjusted OR, 14.4; 95% CI, 2.8-73.2), with the greatest risk associated with those receiving steroids at the time of diagnosis of AVN (adjusted OR, 31.9; 95% CI, 4.4-248.9). There was no further increasing risk associated with increasing duration of steroid use. Conditioning with TBI was also associated with the occurrence of AVN (adjusted OR, 3.2; 95% CI, 1.1-9.7); however, cyclosporine was not a risk factor for AVN (adjusted OR, 0.5; 95% CI, 0.1-1.9). Our results support the hypothesis that AVN following BMT has a strong association with the administration of corticosteroids. TBI may be an additional risk factor, and cyclosporine does not appear to contribute to an increased incidence of AVN.

Evidence that serum phosphate is independently associated with serum PTH in patients with chronic renal failure.

There has been controversy regarding the initial pathogenic events involved with the hyperparathyroidism of chronic renal failure (CRF). Low serum levels of 1,25-dihydroxyvitamin D in uremic patients are postulated by some as having a role in permitting higher parathyroid hormone (PTH) secretion. However, recent animal and in vitro studies strongly suggest that phosphate has a direct effect on parathyroid cells to enhance PTH secretion. To evaluate the relationships among serum phosphate, calcium, PTH, and 1,25-dihydroxyvitamin D in uremic humans, we performed a cross-sectional analysis of 84 patients with varying levels of CRF. Using stepwise regression analysis after adjusting for multiple comparisons, we found that serum phosphate correlated directly with serum PTH (r = 0.62, P < 0.01) in patients with mild to moderate CRF (creatinine < or = 3.0 mg/dL), independent of serum calcium and 1,25-dihydroxyvitamin D levels. In patients with more severe renal failure (creatinine > 3.0 mg/dL), only the serum calcium correlated with serum PTH (r = -0.47, P < 0.01). While serum 1 ,25-dihydroxyvitamin D showed no correlations with PTH, phosphate, or calcium at any stage of renal failure, the mean 1,25-dihydroxyvitamin D level in patients with mild CRF was lower than that in age-matched controls (24 +/- 3 pg/mL v 37 +/- 2 pg/mL; P < 0.01), suggesting that low 1,25-dihydroxyvitamin D was permissive for enhanced PTH secretion. These data demonstrate an independent association of serum phosphate with PTH in patients with CRF and suggest that phosphate may directly enhance PTH secretion in this setting. This study supports recent animal studies showing a direct parathyroid cell effect of phosphate on PTH secretion.

Dimensional accuracy of improved dental stone and epoxy resin die materials. Part II: Complete arch form.

STATEMENT OF PROBLEM: Little information has been reported with regard to the dimensional accuracy of improved dental stone materials for reproduction of an entire arch form. PURPOSE: The purpose of this study was to evaluate the ability of an epoxy resin die material and a type IV dental stone to dimensionally reproduce an entire arch form. MATERIAL AND METHODS: Models were fabricated and measurements were made of reference marks to calculate dimensions from first molar to the midline bilaterally and between first molars. Each measurement was repeated three times and the mean measurement and percent relative change was calculated for each dimension. RESULTS: The results revealed that the difference in the relative change in two dimensions was statistically significant for the epoxy resin group (p < 0.05). CONCLUSIONS: The materials provided a similar degree of dimensional accuracy in reproducing a complete arch when used with addition silicone impression material.

Dimensional accuracy of improved dental stone and epoxy resin die materials. Part I: Single die.

STATEMENT OF PROBLEM: Improved dental stone has been widely used for producing dies for the fabrication of restorations with the lost-wax technique. Improved dental stone is used for several reasons, but it is selected most often because of its reasonable cost, ease of use, and ability to produce consistent results. PURPOSE: This study evaluated the ability of an epoxy resin die material and a type IV dental stone to dimensionally reproduce a custom-fabricated metal die. MATERIAL AND METHODS: Dies were fabricated and measurements were made from three reference lines. Measurements were repeated three times for the master die and for the specimen dies. A mean measurement and percent relative change for each dimension was calculated. RESULTS: A significant difference in the relative change for die height was found between the groups studied (p < 0.003). CONCLUSIONS: This epoxy die system will provide a degree of dimensional accuracy comparable to gypsum when used with addition silicone impression material.

Vasectomy is associated with an increased risk for urolithiasis.

We evaluated vasectomy as a potential risk factor for urolithiasis. Vasectomy is a common method of contraception among otherwise healthy men. This is also the population at highest risk for urolithiasis. We conducted a case-control study of patients in a large prepaid health maintenance organization. Cases were men experiencing initial episodes of urolithiasis, ascertained by reviewing radiology logs and medical records. The age-matched controls were men with no history of urolithiasis. In logistic regression models, the relative risk of urolithiasis for men with vasectomies compared with men without vasectomies was 1.9 for men younger than 46 years of age (95% confidence interval = 1.2 to 3.1, P = 0.005), and the relative risk was 0.9 (95% confidence interval = 0.5 to 1.5, P > 0.8) for men who were at least 46 years old. The relative risk of urinary calculi was 2.0 (95% confidence interval 1.0 to 4.1, P < 0.05) for men with vasectomies 0 to 4 years before evaluation compared with men without vasectomies, and the excess risk persisted as long as 14 years postvasectomy. Vasectomy was associated with a twofold increased risk for urolithiasis in men younger than 46 years of age. This increased risk may persist for up to 14 years postvasectomy. Given the large number of men who undergo vasectomy worldwide each year, the increased risk for urolithiasis among vasectomized men may result in substantial excess morbidity.

Burn-associated bone disease in sheep: roles of immobilization and endogenous corticosteroids.

To determine the role of immobilization in the pathogenesis of burn-associated bone disease, we selected the sheep as a model to study the effects of burn injury compared with a sham-burned control group. Seven of the sheep were subjected to controlled 40% flame burn, and seven underwent anesthesia with arterial and venous cannulation but without burn. After labeling newly formed bone with tetracycline and calcein, the sheep were killed 2 weeks after burn or sham burn, and the iliac crest and lumbar vertebrae were analyzed for histomorphometry. Analysis failed to demonstrate a significant reduction of bone formation rate in the burned sheep. Osteoid area and surface and osteoblast surface, which correlated significantly with bone formation rate (r = 0.49, p < 0.025), were reduced in the burned sheep. Results suggest that immobilization may play a primary role in the pathogenesis of burn-associated bone disease, but the presence of differences in other histomorphometric features indicates the bone disease is multifactorial.