Roy Peterson

Ambulatory evaluation of nephrolithiasis. Classification, clinical presentation and diagnostic criteria.

Using the ambulatory protocol previously described, 241 patients with nephrolithiasis were evaluated. They could be categorized into 10 groups from the results obtained. Absorptive hypercalciuria type I (87 per cent male) comprised 24.5 per cent and was characterized by normocalcemia, normal fasting urinary calcium (less than 0.11 mg/100 ml glomerular filtration), an exaggerated urinary calcium following an oral calcium load (greater than 0.20 mg/mg creatinine), normal urinary cyclic adenosine monophosphate (AMP) (less than 5.4 nmol/100 ml glomerular filtration) and serum parathyroid hormone (PTH), and hypercalciuria (greater than 200 mg/day during a calcium- and sodium-restricted diet). Absorptive hypercalciuria type II (50 per cent male) accounted for 29.8 per cent; its biochemical features were the same as those for absorptive hypercalciuria type I, except for normocalciuria during a restricted diet and low urine volume (1.42 +/- 0.55 SD liter/day). Renal hypercalciuria (56 per cent male), disclosed in 8.3 per cent, was represented by normocalcemia and high values for fasting urinary calcium (0.160 +/- 0.054 mg/100 ml glomerular filtration), urinary cyclic AMP (6.80 +/- 2.10 nmol/100 ml glomerular filtration) and serum PTH. Primary hyperparathyroidism (57 per cent female), accounted for 5.8 per cent, typically included hypercalcemia, hypophosphatemia, hypercalciuria and high urinary cyclic AMP. Hyperuricosuric calcium urolithiasis (100 per cent male) comprised 8.7 per cent, and was characterized by hyperuricosuria (776 +/- 164 mg/day) and urinary pH exceeding pK for uric acid (5.91 +/- 0.33). In enteric hyperoxaluria (60 per cent female), encountered in 2.1 per cent of cases, urinary oxalate was increased (6.29 +/- 13.2 mg/day). Noncalcium-containing stones were found in 2.1 per cent of the patients with uric acid lithiasis (100 per cent male) and in another 2.1 per cent of the patients with infection lithiasis (60 per cent female). These conditions were typified by low urinary pH (5.29 +/- 0.12) and high urinary pH (6.69 +/- 1.16), respectively. Renal tubular acidosis was found in one patient (male, 0.4 per cent). In 10.8 per cent of the patients (81 per cent male), no metabolic abnormality could be found, although urine volume was low (1.41 +/- 0.51 liter/day). Hypercalciuria could not be differentiated between absorptive hypercalciuria and renal hypercalciuria in 5.4 per cent of the patients. Thus, this ambulatory protocol disclosed a physiologic disturbance in nearly 90 per cent of the cases and provided a definitive diagnosis in 95 per cent of the patients.

Treatment of Postmenopausal Osteoporosis with Slow-Release Sodium Fluoride: Final Report of a Randomized Controlled Trial

It seems logical to use fluoride in osteoporosis, because fluoride can stimulate osteoblastic proliferation and new bone formation [1, 2]. However, clinical trials with fluoride have yielded mixed results because excessive exposure to fluoride may cause abnormal bone formation, microfractures, and gastric bleeding [3, 4]. Thus, treatment with a high dosage of plain sodium fluoride did not decrease the spinal fracture rate despite markedly increasing vertebral bone density, and it increased the rate of appendicular fractures and microfractures [4]. To overcome the complications associated with sodium fluoride, we have advocated the cyclical, intermittent use of a lower dose of less bioavailable, slow-release sodium fluoride and continuous supplementation with calcium citrate [5, 6]. This treatment has been shown to maintain serum fluoride concentrations within the narrow therapeutic window [7, 8], thus avoiding toxic peaks in serum [9], and to stimulate the formation of normally mineralized bone [5, 10] with an improved intrinsic quality of cancellous bone [11-13]. We previously reported the results of an interim analysis [6] of a placebo-controlled randomized trial (median duration of treatment for fracture analysis, 2 years). Here, we present the final report of that trial (median duration of treatment for fracture analysis, 3 years). Methods Clinical Data Demographic and baseline presentations were described in the interim report [6]. We recruited 110 women with postmenopausal osteoporosis into the trial. All had radiologic evidence of osteopenia and osteoporosis; one or more vertebral fractures believed to be nontraumatic; and no secondary cause of bone loss. They were randomly assigned to one of two groups and stratified according to estrogen treatment. All study personnel were unaware of group assignment while data were being gathered. Ninety-nine patients completed at least 1 study cycle (1 year of actual treatment). The demographic or baseline presentations of these 99 patients did not differ according to treatment group [6] (Table 1). The two groups were similar in age, time since menopause, dietary calcium intake, height, weight, and number of spinal fractures. Both groups had moderate to severe osteoporosis: The average L2-L4 bone density was approximately 30% less than of a normal 30-year-old woman, and each group had a median of two spinal fractures at baseline. Table 1. Baseline Characteristics* Treatment Patients in the fluoride group received slow-release sodium fluoride (Slow Fluoride, Mission Pharmacal Co., San Antonio, Texas), 25 mg twice daily, orally before breakfast and at bedtime in repeated 14-month cycles (12 months receiving treatment followed by 2 months not receiving treatment). They also received calcium citrate (Citracal, Mission Pharmacal), 400 mg calcium twice daily, before breakfast and at bedtime continuously throughout the study. Those in the placebo group received placebo (identical in appearance to Slow Fluoride but containing excipient only [provided by Mission Pharmacal]) on the same time schedule. The Mission Pharmacal Company had no role in the design of the study or in data retrieval, analysis, or interpretation. Thirteen of 48 patients in the fluoride group and 16 of 51 patients in the placebo group received concurrent treatment with estrogen. Nine of the 29 patients treated with estrogen were recruited at the primary site at Dallas; the other 20 were enrolled and evaluated at the Scott and White Clinic, Temple, Texas. Fracture Quantitation Before treatment and at 12 months of each cycle, a lateral spine roentgenogram was obtained for the assessment of spinal fractures. In the interim analysis [6], prevalent fractures (fractures present at baseline) were identified with the aid of radiology reports. For this final report, prevalent fractures were also analyzed using a computer program that calculated the vertebral dimensions of clearly unaffected vertebrae from landmarks (anterior and posterior corners and midpoints). By comparing these dimensions with published normal values [14], we obtained a correction factor. Using this correction factor, we estimated idealized vertebral dimensions before a fracture had occurred for the remaining vertebrae in the given baseline radiograph. A reduction in any height of more than 20% (from idealized to actual) accompanied by a decrease of at least 10% in vertebral area represented a prevalent fracture. Incident spinal fractures (fractures occurring during the trial) were identified as described previously [6], using a computer-derived method. A reduction in any vertebral height of more than 20% accompanied by a decrease in vertebral area of more than 10% from one year to the next constituted a fracture [15]. A new incident fracture was a fracture that occurred during treatment in a previously unaffected vertebrae. A recurrent fracture was one that developed on a previously fractured vertebra. Bone Mass Measurements The use of different densitometers prompted us to calculate and use percentage changes per year rather than absolute values. The method for calculating changes in L2-L4 bone mineral content and bone density of the femoral neck and the radial shaft was described previously [6]. Safety Variables Serum fluoride concentrations were measured before the morning dose of the test drug at 0, 3, 6, 9, and 12 months of each cycle, and they were analyzed using an ion-specific electrode. At the same visits, a history was taken for gastrointestinal and musculoskeletal side effects. A microfracture was defined clinically as moderate to severe lower-extremity pain that persisted for more than 6 weeks despite a reduction in treatment dose and objectively as changes on bone scan or radiograph. The relation of each side effect to treatment was assessed. A symptom was considered to be related to treatment if it was moderate to severe in intensity, had no other cause, had newly appeared and persisted during the treatment phase, or had disappeared during the withdrawal period or with dose reduction. It was considered to be unrelated if it was present at baseline or during the late withdrawal phase, or if it had newly appeared but was not persistent. The severity and frequency of side effects were also quantitated as adverse symptom scores. We identified 10 gastrointestinal items (symptoms such as nausea, vomiting, and diarrhea), 4 rheumatic items (pain in the foot, knee, hip, and other joints), and 3 skeletal items (pain in the lower, mid-, or upper back). Each item was given a numerical value of 1 to 3 for frequency (infrequent, frequent, or very frequent) and a numerical value of 1 to 3 for severity (mild, moderate, or severe). Side-effect score was the product of the value for frequency and the value for severity for each item. Thus, a constant, severe back pain yielded a score of 9 (3 3). A gastrointestinal score was derived for each patient by adding the scores of the 10 gastrointestinal items for all relevant visits and dividing the sum by the number of visits. A similar computation was done to derive rheumatic and skeletal scores for each patient. Statistical Analysis The data for incident spinal fractures were compared between the two groups-using three methods. Individual Vertebral Fracture Rate For each patient, the individual vertebral fracture rate was obtained by dividing the total number of new fractures by the duration of treatment. Because the data were skewed, this rate was compared between the two groups using the Wilcoxon rank-sum test. Fracture-Free Rate This rate was the percentage of patients without new fractures, unadjusted for covariates. The two groups were compared using the log-rank test to account for differential follow-up. Survival The Cox proportional-hazards regression model [16] was constructed to estimate the relative risk for a new spinal fracture while adjusting for covariates (treatment group, age, prevalent spinal fractures, years since menopause, height, weight, estrogen treatment, and stratum of baseline L2-L4 bone density). Time (in years) to the first fracture was considered to be the survival time. Analyses of fracture rates and logistic regression were also done [6]; the data are not presented because findings were similar to those obtained using the above methods. The arithmetic difference in height from baseline to the end of treatment for each patient was compared between groups using a two-sample t-test and a two-way analysis of variance with the following factors: 1) treatment [fluoride vs placebo] and 2) fracture status (fracture-free vs one or more new or recurrent fractures). For each patient, we calculated the percentage change per year for L2-L4 bone mineral content and bone density of femoral neck and radial shaft. The individual mean change for each patient was calculated as the average of yearly changes. The group mean was obtained by averaging the individual means. One-sample t-tests were then used to compare the percentage change to zero for each year or for the mean. Comparisons between groups were made using two-sample t-tests. Missing data precluded implementing a repeated-measures analysis of variance. For related adverse events, the frequency of each event was compared between the two groups by using the Fisher exact test. Adverse symptom scores were compared between the groups by using the Wilcoxon rank-sum test and within the groups by using the Wilcoxon signed-rank test. For nonvertebral fractures, the exact tests based on the binomial distribution using person-year data were used to compare the two groups. Most analyses were done using BMDP Statistical Software (BMDP, Los Angeles, California). Programs for analyzing person-time data were developed by the authors. Data are presented as mean SD unless otherwise indicated. All reported P values are two-sided. Results Duration of Treatment The total duration of follow-up, including withdrawal periods, was 193 patient-years in th

Biochemical profile of stone-forming patients with diabetes mellitus

OBJECTIVES To test the hypothesis that stone-forming patients with type II diabetes (DM-II) have a high prevalence of uric acid (UA) stones and present with some of the biochemical features of gouty diathesis (GD). METHODS The demographic and initial biochemical data from 59 stone-forming patients with DM-II (serum glucose greater than 126 mg/dL, no insulin therapy, older than 35 years of age) from Dallas, Texas and Durham, North Carolina were retrieved and compared with data from 58 patients with GD and 116 with hyperuricosuric calcium oxalate urolithiasis (HUCU) without DM. RESULTS UA stones were detected in 33.9% of patients with DM-II compared with 6.2% of stone-forming patients without DM (P <0.001). Despite similar ingestion of alkali, the urinary pH in patients with DM-II and UA stones (n = 20) was low (pH = 5.5), as it is in patients with GD, and was significantly lower than in patients with HUCU. The urinary pH in patients with DM-II and calcium stones (n = 39) was intermediate between that in those with DM-II and UA stones and those with HUCU. However, both DM groups had fractional excretion of urate that was not depressed, as it is in those with GD, and was comparable to the value obtained in those with HUCU. The urinary content of undissociated UA was significantly higher, and the saturation of calcium phosphate (brushite) and sodium urate was significantly lower in those with DM-II and UA stones than in those with HUCU. CONCLUSIONS Stone-forming patients with DM-II have a high prevalence of UA stones. Diabetic patients with UA stones share a key feature of those with GD, namely the passage of unusually acid urine, but not the low fractional excretion of urate.

Slow-Release Sodium Fluoride in the Management of Postmenopausal Osteoporosis: A Randomized, Controlled Trial

Although fluoride can cause osteoblastic proliferation [1, 2] and stimulate new bone formation [3], its use in managing osteoporosis has been associated with frequent and sometimes serious complications, including gastric bleeding and microfractures [3]. Excessive exposure may lead to fluorosis [4], characterized by a formation of abnormal bone that may be poorly mineralized and mechanically defective. Further, in a placebo-controlled randomized trial [3], continuous treatment with plain (nonsustained release) sodium fluoride and calcium carbonate supplementation did not produce a statistically significant decrease in the spinal fracture rate despite a substantial increase in the lumbar vertebral bone mass. We previously reported [5, 6] a nonrandomized trial in which intermittent slow-release sodium fluoride with continuous calcium citrate supplementation stimulated the formation of normally mineralized bone and decreased the spinal fracture rate without serious complications. In 1986, we initiated a randomized trial using slow-release sodium fluoride plus calcium citrate compared with placebo plus calcium citrate in 99 patients with postmenopausal osteoporosis. The trial is ongoing, with an average duration of treatment in the two study groups of 2.44 and 2.14 cycles (14 mo/cycle) and with 15 patients completing the intended 4 cycles of treatment. Although the study is not expected to be completed until August 1996, this interim analysis was done in response to a request for an update at the Fourth International Symposium on Osteoporosis [7]. The trial will be completed in order to determine if the treatment effect is sustained. We believe that the interim analysis will not affect the conduct of the remainder of the trial. Methods Clinical Data Recruited into the trial were 110 fully ambulatory white women with postmenopausal osteoporosis, all of whom were referred for symptomatic osteoporosis by practicing physicians because of an inadequate response to conventional therapy or the unwillingness of physicians to care for them. No other ethnic groups were enrolled, probably because of the rarity of postmenopausal osteoporosis and the nature of the referred patients in the study areas. The entry criteria were as follows: postmenopausal state, radiographic evidence of osteoporosis, and one or more vertebral fractures believed to be nontraumatic. Exclusion criteria were as follows: the presence of conditions causing bone loss such as hyperparathyroidism, adrenocorticosteroid excess, thyrotoxicosis, chronic diarrheal state or malabsorption, renal tubular acidosis, renal impairment (endogenous creatinine clearance less than 0.7 mL/min per kg); previous treatment with diphosphonate, calcitonin, or fluoride; active peptic ulcer disease; and skeletal fractures that could not be quantified for anatomic or technical reasons. Those taking pharmacologic doses of vitamin D preparations were accepted if they had discontinued the drug for at least 6 months. At recruitment, 31 patients were taking estrogen (treatment initiated after osteoporosis was diagnosed). Thirteen patients had documented recurrent spinal fractures while receiving estrogen. The total duration of estrogen therapy represented about a third of their postmenopausal state (mean, 8 years). This treatment, usually consisting of conjugated estrogen, 0.625 mg/d given continuously or intermittently (25 d/mo), and intermittent progesterone (5 mg/d for 10 d/mo), was continued during the trial. Patients receiving estrogen had similar baseline demographic characteristics as patients not receiving estrogen and were considered at increased risk for further fractures. Randomization and Treatment Scheme Participants were randomly assigned to the two treatment groups, stratified according to estrogen treatment (untreated or estrogen-treated). Patients in the treatment group received slow-release sodium fluoride (Slow Fluoride; Mission Pharmacal Company, San Antonio, Texas), 25 mg twice daily given orally before breakfast and at bedtime intermittently in repeated cycles of 14 months (12 months receiving treatment, followed by 2 months off treatment) and calcium citrate (Citracal, Mission Pharmacal Company) as 400 mg of calcium twice daily before breakfast and at bedtime. In the placebo group, medication identical in appearance to Slow Fluoride that was devoid of sodium fluoride was given on the same time schedule along with calcium citrate at the same dose and schedule. Study Protocol Patients were evaluated in an outpatient setting before treatment and at 3, 6, 9, 12, and 14 months of each cycle. At each visit, a careful history was taken for gastrointestinal and musculoskeletal side effects defined as symptoms that newly appeared or increased from baseline without apparent cause and persisted more than a month during treatment or disappeared during withdrawal. Where severe lower-extremity pain lasted more than 2 weeks, the protocol required a bone scan followed by radiographs for detection of microfracture; however, none was required. In addition, systematic multichannel analysis of venous blood, complete peripheral blood count, and 24-hour urinary calcium were determined at each visit; serum parathyroid hormone, reticulocyte count, and 24-hour urinary hydroxyproline were measured before and at 6 and 12 months of each cycle. Serum fluoride was measured before the morning dose of slow-release sodium fluoride at 0, 6, and 12 months of each cycle. Before treatment and at 12 months of each cycle, a lateral spinal radiograph was obtained to detect spinal fractures; moreover, bone mineral content of the L2 to L4 vertebrae, bone density of the distal third of the radius of the nondominant forearm, and bone density of the femoral neck were measured. Quantitation of Spinal Fractures Lateral spinal films taken before treatment and at 12 months of the first cycle were compared in order to determine new and recurrent fractures occurring during the first cycle of treatment. For each vertebra from T3 to L5, landmarks (anterior and posterior corners and midpoints) were recorded using an electrostatic digitizing board (Scriptel Corporation, Columbus, Ohio) with a coefficient of variation of 1.5%. A computer software program developed by one of the authors was used to compute changes in vertebral heights and area, and to calculate the magnification error between the two sets of radiographs. After correction for the magnification error, if any, a decrease in height of more than 20% of anterior, middle, or posterior height, accompanied by a decrease in area of more than 10% in a previously unaffected vertebra, was considered a new fracture [8], or if the decrease was in a previously fractured vertebra, it was considered to be a recurrent fracture. Identical criteria were used to identify new and recurrent fractures occurring during the second cycle (by comparing 26 months with 12 months), during the third cycle (by comparing 40 months with 26 months), and during the fourth cycle (by comparing 54 months with 40 months). Moreover, spinal films taken after the last cycle of follow-up were compared not only with the immediately preceding films but also with earlier radiographs. The same procedure was followed for the identification of new and recurrent fractures. Thus, it was possible to detect fractures occurring during two or more cycles (cumulative fractures) that escaped disclosure by previous cycle-to-cycle analysis. Bone Mass Measurement During the course of this study, two instruments were used to measure the L2 to L4 bone mineral content and the femoral neck bone density. A dual-photon x-ray absorptiometer (1.5 version, Lunar Radiation, Madison, Wisconsin) was used initially. It was replaced by quantitative digital radiography (Hologic, Waltham, Massachusetts) that yielded different absolute values for bone mass. The following procedures were adopted to accommodate problems imposed by the measurement of bone mass by two different densitometers. First, in estimating the extent of spinal bone loss at baseline, a given patients L2 to L4 bone density obtained by either method was compared with the mean value for a normal 30-year-old woman established for the corresponding instrument. Second, in quantifying changes in the L2 to L4 bone mineral content and the femoral neck bone density produced by treatment, results were expressed as a percentage change for each cycle rather than as absolute values. When the same densitometer was used at the beginning and the end of a given cycle, the experimentally derived values were used to calculate the percentage change in bone mineral content or bone density. For a given cycle with the initial bone mass obtained by the Lunar method and the final bone mass measured by the Hologic technique, a correction factor was applied to convert the Lunar-derived value to the latter value. In patients who initially had bone mass determined by the Lunar method, a concurrent analysis by the Hologic instrument was done before converting to the latter technique for subsequent follow-up measurements. Thus, a correction factor could be calculated. The radial shaft bone density was obtained throughout the study by a single-photon absorptiometer (Norland, Ft. Atkinson, Wisconsin) [9]. For follow-up measurements, actual experimentally derived bone densities were used to calculate the percentage change in bone density for each cycle. The coefficient of variation for the L2 to L4 bone mineral content using the Lunar or Hologic method was 1%, whereas that for the femoral neck bone density and the radial shaft bone density was 1% to 2%. Biochemical Analysis The blood screen was done as SMA-20 (Smith-Kline Laboratory, Dallas, Texas). The serum parathyroid hormone level was analyzed by the whole-molecule, immunoradiometric assay (using a kit from Nichols Institute, San Juan Capistrano, California). The serum fluoride level was measured using an ion-specific electrode. The urinary

Use of Potassium Citrate as Potassium Supplement During Thiazide Therapy of Calcium Nephrolithiasis

The effectiveness of potassium citrate as a potassium supplement was compared to that of potassium chloride in 13 patients with calcium nephrolithiasis treated with thiazide. Thiazide treatment alone reduced serum potassium, urinary calcium and citrate without affecting urinary pH. Urinary saturation of calcium oxalate and brushite decreased but not as much as the decrement in urinary calcium because of reduced citrate-calcium complexation. Potassium chloride supplementation averted thiazide-induced hypokalemia and hypocitraturia without influencing hypocalciuric action of thiazide or urinary pH. The decline in urinary saturation of calcium salts paralleled the decrement in urinary calcium. Potassium citrate supplementation also kept urinary calcium low and corrected hypokalemia. Moreover, it increased urinary pH and citrate above levels in other phases. Thus, the ability of thiazide to lower the urinary saturation of calcium oxalate was accentuated by potassium citrate supplementation but not by potassium chloride supplementation, probably owing to increased citrate complexation of calcium. Moreover, the potassium citrate therapy was more effective than potassium chloride supplementation in reducing the propensity for the spontaneous precipitation of calcium oxalate in urine. In conclusion, potassium citrate supplementation may be superior to potassium chloride supplementation in patients receiving thiazide in whom stones form.

Correction of hypocitraturia and prevention of stone formation by combined thiazide and potassium citrate therapy in thiazide-unresponsive hypercalciuric nephrolithiasis

Thirteen patients with hypercalciuric calcium nephrolithiasis continued to form calcium stones when treated with thiazide (4.69 +/- 6.62 [mean +/- SD] stones per patient-year to 5.12 +/- 10.87 stones per patient-year), despite adequate hypocalciuric response (a reduction in urinary calcium levels from 303 +/- 119 mg per day to 193 +/- 88 mg per day, p less than 0.01). Because they had hypocitraturia (250 +/- 86 mg per day versus 643 +/- 236 mg per day in normal subjects, p less than 0.001), potassium citrate (10 to 20 meq three times per day) was added to the ongoing treatment program. During combined treatment with thiazide and potassium citrate, urinary pH significantly rose, and normal levels of urinary citrate were restored. Ten patients stopped forming new stones and all 13 had reduced stone formation rate. Thus, potassium citrate supplementation should be considered in patients requiring thiazide therapy for the control of hypercalciuric nephrolithiasis, especially if they have concurrent hypocitraturia or if it develops during thiazide therapy.

Prevention of Stone Formation and Bone Loss In Absorptive Hypercalciuria by Combined Dietary and Pharmacological Interventions

PURPOSE We determined whether dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate treatment, would prevent stone formation and avert bone loss in 18 men and 10 women with type I absorptive hypercalciuria. MATERIALS AND METHODS Patients were treated with thiazide (20) or indapamide (8) and potassium citrate (average dose 35 mEq. daily) for 1 to 11 years (mean 3.7) while maintained on low calcium oxalate diet. Serum and urinary chemistry studies and bone mineral density were measured at baseline and at the end of treatment. New stones formed were quantitated during 3 years before and during treatment. RESULTS During treatment urinary calcium significantly decreased (346 +/- 85 to 248 +/- 79 mg. daily, p <0.001) but urinary oxalate did not change. Urinary pH and citrate significantly increased, and urinary saturation of calcium oxalate significantly decreased by 46%. Stone formation rate decreased significantly from 2.94 to 0.05 per year (p <0.001). L2-L4 bone mineral density increased significantly by 5.7% compared to normal peak value, and by 7.1% compared with normal age and gender matched value. Femoral neck bone mineral density also increased significantly. CONCLUSIONS Dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate, satisfactorily controlled hypercalciuria, prevented the secondary increase in urinary oxalate, reduced urinary saturation of calcium oxalate, virtually eliminated recurrent stone formation, and increased bone density of the spine and femoral neck. Thus, this dietary pharmacological program controlled stone formation as well as bone loss that often accompany type 1 absorptive hypercalciuria.

Familial Absorptive Hypercalciuria in a Large Kindred

The occurrence of calcareous renal stones in 12 members of a family was consistent with an autosomal dominant mode of inheritance. All 6 members with stones who were evaluated were shown to have absorptive hypercalciuria. The mother of 2 members with stones did not suffer stones but had biochemical evidence of absorptive hypercalciuria (increased intestinal calcium absorption, hypercalciuria and normal parathyroid function). Nephrolithiasis was encountered only in the progeny of members who had stones of biochemical absorptive hypercalciuria. The results suggest that physiological feature(s) of absorptive hypercalciuria may be an expression of the genetic trait.

Prevention of Spinal Bone Loss by Potassium Citrate in Cases of Calcium Urolithiasis

PURPOSE We determine if potassium citrate treatment stabilizes spinal bone density among patients with recurrent calcium oxalate nephrolithiasis. MATERIALS AND METHODS We studied a group of 16 men and 5 women with stones taking potassium citrate from 11 to 120 months. They represented all patients from the Stone Clinic who took potassium citrate alone for at least 11 months. L2-L4 bone mineral density data before and after potassium citrate treatment were retrieved retrospectively and analyzed. RESULTS In the combined group L2-L4 bone mineral density increased significantly by 3.1% over mean duration of 44 months. Z score, corrected for age matched normal values, increased significantly by 3.8%. Urinary pH, citrate and potassium increased significantly during treatment but urinary calcium did not change. CONCLUSIONS Potassium citrate, a commonly used drug for the prevention of recurrent nephrolithiasis, may avert age dependent bone loss. Spinal bone density increased in most patients when it normally decreases.

Effect of slow-release sodium fluoride on cancellous bone histology and connectivity in osteoporosis

We have previously demonstrated that a treatment regimen of slow-release sodium fluoride (SRNaF) and continuous calcium citrate increases lumbar bone mass, improves cancellous bone material quality, and significantly reduces vertebral fracture rate in osteoporotic patients. In order to assess whether such treatment also improves trabecular structure, we quantitated cancellous bone connectivity before and following 2 years of therapy with SRNaF in 23 patients with osteoporosis and vertebral fractures. In addition, we performed bone histomorphometry on the same sections used for connectivity measurements. There was a significant increase in L2-L4 bone mineral density during therapy (0.827 +/- 0.176 g/cm2 SD to 0.872 +/- 0.166, p = 0.0004). Significant histomorphometric changes were represented by increases in mineral apposition rate (0.6 +/- 0.4 microns/d to 1.1 +/- 0.7, p = 0.0078) and adjusted apposition rate (0.4 +/- 0.3 microns/d to 0.6 +/- 0.4, p = 0.016). On the other hand, trabecular spacing significantly declined (from 1375 +/- 878 microns to 1052 +/- 541, p = 0.05). Two-dimensional quantitation of trabecular struts on iliac crest histological sections disclosed significant increases in mean node number per mm2 of cancellous tissue area (0.22 +/- 0.12 vs. 0.39 +/- 0.27, p = 0.0077), the mean node to free-end ratio (0.23 +/- 0.21 vs. 0.41 +/- 0.46, p < 0.05), and in the mean node to node strut length per mm2 of cancellous area (0.098 +/- 0.101 vs. 0.212 +/- 0.183, p < 0.01). There were no significant changes in any of the measurements associated with free-end number or free-end to free-end strut length.(ABSTRACT TRUNCATED AT 250 WORDS)