Charles Y. C. Pak

University of Texas Southwestern Medical Center, Dallas, Texas, United States

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Publications (368)2087.08 Total impact

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    ABSTRACT: Background and objectives: We compared 3 animal protein sources for their effect on urinary stone risk. Design: 15 healthy subjects completed a 3 phase, randomized crossover metabolic study. During each 1-week phase, subjects consumed a standard, metabolic diet containing beef, chicken or fish. Serum chemistries and 24-hour urine samples collected at the end of each phase were compared using a mixed model repeated measures analysis. Results: Serum and urinary uric acid were elevated for each phase. Beef was associated with lower serum uric acid values than either chicken or fish (6.5 mg/dl vs 7.0 mg/dl and 7.3 mg/dl, respectively, p<0.05 for both) and fish (741 mg/day) was associated with higher levels of urinary uric acid than either beef (638 mg/day, p = 0.003) or chicken (641 mg/day, p = 0.04). No significant differences in urinary pH, sulfate, calcium, citrate, oxalate or sodium were noted among phases. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference reached significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). Conclusions: Consumption of animal protein is associated with elevated serum and urine uric acid levels in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid levels. However, stone-forming propensity, as reflected in saturation index, is marginally highest for beef compared to fish or chicken. Stone formers should be advised to limit their intake of all animal proteins, including fish.
    The Journal of urology 07/2014; 192(1). DOI:10.1016/j.juro.2014.01.093 · 3.75 Impact Factor
  • Khashayar Sakhaee · Charles Pak
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    ABSTRACT: BACKGROUND: Calcium supplementation is commonly recommended for patients after Roux-en-Y gastric bypass to avert bone loss. To test the hypothesis that effervescent (liquid) potassium-calcium-citrate (PCC) might be more bioavailable than a tablet formulation of calcium citrate (Citracal Petite), the present study compared a single dose response of the 2 compounds. The present study was conducted at the University of Texas Southwestern Medical School at Dallas. METHODS: A total of 15 patients who had undergone Roux-en-Y gastric bypass were included in a 2-phase, crossover, randomized study comparing the single-dose bioavailability of PCC versus Citracal Petite. After following a restricted diet for 1 week, the participants ingested either a single dose of 400 mg elemental calcium as PCC or Citracal Petite. Sequential serum and urine samples were collected for a 6-hour period after the dose and analyzed for calcium, parathyroid hormone, and acid-base parameters. RESULTS: Compared with citracal petite, PCC significantly increased the serum calcium concentrations at 2, 3, and 4 hours after the oral load. The peak to baseline variation and increment in serum calcium (area under the curve) were significantly greater after PCC (P = .015 and P = .002, respectively). Concurrently, the baseline to nadir variation and decrement in serum parathyroid hormone (area over the curve) were significantly greater after PCC (P = .004 and P = .005, respectively). Moreover, compared with Citracal Petite, PCC caused a significantly greater increment in urinary citrate (P < .0001) and potassium (P = .0004) and a significantly lower increase in urinary ammonium (P = .045). CONCLUSION: In patients who have undergone Roux-en-Y gastric bypass, PCC was superior to Citracal Petite in conferring bioavailable calcium and suppressing parathyroid hormone secretion. PCC also provided an alkali load.
    Surgery for Obesity and Related Diseases 12/2011; 9(5). DOI:10.1016/j.soard.2011.11.011 · 4.94 Impact Factor
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    ABSTRACT: The classic definition of hypercalciuria, an upper normal limit of 200  mg/day, is based on a constant diet restricted in calcium, sodium, and animal protein; however, random diet data challenge this. Here our retrospective study determined the validity of the classic definition of hypercalciuria by comparing data from 39 publications analyzing urinary calcium excretion on a constant restricted diet and testing whether hypercalciuria could be defined when extraneous dietary influences were controlled. These papers encompassed 300 non-stone-forming patients, 208 patients with absorptive hypercalciuria type I (presumed due to high intestinal calcium absorption), and 234 stone formers without absorptive hypercalciuria; all evaluated on a constant restricted diet. In non-stone formers, the mean urinary calcium was well below 200  mg/day, and the mean for all patients was 127±46  mg/day with an upper limit of 219  mg/day. In absorptive hypercalciuria type I, the mean urinary calcium significantly exceeded 200  mg/day in all studies with a combined mean of 259±55  mg/day. Receiver operating characteristic curve analysis showed the optimal cutoff point for urinary calcium excretion was 172  mg/day on a restricted diet, a value that approximates the traditional limit of 200  mg/day. Thus, on a restricted diet, a clear demarcation was seen between urinary calcium excretion of kidney stone formers with absorptive hypercalciuria type I and normal individuals. When dietary variables are controlled, the classic definition of hypercalciuria of nephrolithiasis appears valid.
    Kidney International 07/2011; 80(7):777-82. DOI:10.1038/ki.2011.227 · 8.52 Impact Factor
  • Khashayar Sakhaee · Carolyn Griffith · Charles Y C Pak
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    ABSTRACT: Patients undergoing Roux-en-Y gastric bypass (RYGB) surgery are prone to developing bone loss and kidney stones. The goal of the present study was to test the hypothesis that an effervescent formulation of potassium calcium citrate (PCC) would avert metabolic complications by providing bioavailable calcium and alkali. A total of 24 patients with RYGB underwent a 2-phase crossover randomized trial comparing PCC and placebo. During the last 2 days of each 2-week phase, the serum and 24-hour urine samples were analyzed for calcium and bone turnover markers, acid base status, and urinary stone risk factors. Compared with placebo, PCC marginally reduced the serum parathyroid hormone level and significantly decreased urinary deoxypyridinoline by 12% (P <.001) and serum type 1 collagen C-telopeptide by 22% (P <.01). PCC significantly increased the net gastrointestinal alkali absorption, citrate, and pH and significantly lowered the urinary net acid excretion (P <.001). The urinary saturation of uric acid decreased significantly (P <.001). The supersaturation of calcium oxalate and brushite did not change despite an increase in calcium and pH. In untreated urine samples with citrate concentrations altered to mimic those of placebo and PCC, calcium oxalate agglomeration was significantly inhibited by PCC. In RYGB patients, PCC supplementation inhibited bone resorption by providing bioavailable calcium, reduced the urinary saturation of uric acid, and increased the inhibitor activity against calcium oxalate agglomeration by providing alkali that increased urinary pH and citrate.
    Surgery for Obesity and Related Diseases 05/2011; 8(1):67-72. DOI:10.1016/j.soard.2011.05.001 · 4.94 Impact Factor
  • The Journal of Urology 04/2011; 185(4). DOI:10.1016/j.juro.2011.02.2358 · 3.75 Impact Factor
  • Charles Y C Pak · Khashayar Sakhaee · Margaret S Pearle
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    ABSTRACT: We retrospectively analyzed the validity of a simple method of detecting absorptive hypercalciuria type I, a common stone forming condition with hypercalciuria that is believed to be due to high intestinal calcium absorption. The method is based on urinary calcium derived from 24-hour urine collections while on random and restricted diets rather than on a calciuric response to an oral calcium load. A group of 916 well characterized patients with idiopathic calcium oxalate urolithiasis comprised the study group. We also analyzed a subgroup of 695 patients, excluding 221 with dietary abuse, defined as urinary sodium greater than 150 mEq daily and/or sulfate greater than 35 mmol daily, to eliminate potential confounding dietary factors affecting the diagnosis. In each group absorptive hypercalciuria type I was detected by the old criteria, requiring an exaggerated calciuric response to an oral calcium load test, and by the new criteria, based on 24-hour urinary calcium 200 mg or greater daily while on random and restricted diets. Using the old criteria as the gold standard the positive and negative predictive values, sensitivity and specificity of the new criteria were 80.1%, 95.9%, 90.8% and 90.5%, respectively. When excluding patients with dietary abuse the values were 85.9%, 97.2%, 92.4% and 94.5%, respectively. Absorptive hypercalciuria type I may be reliably detected by a simple method based on high 24-hour urinary calcium while on random and restricted diets, especially when excluding patients with evidence of dietary abuse during the restricted diet.
    The Journal of urology 03/2011; 185(3):915-9. DOI:10.1016/j.juro.2010.10.067 · 3.75 Impact Factor
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    ABSTRACT: An abnormal urinary pH (UpH) represents an important risk factor for nephrolithiasis. In some stone formers, a fasting urine specimen is obtained instead of a 24-h urine collection for stone risk evaluation. We examined the relationship between 24-h and fasting UpH in non-stone forming individuals and stone formers with various etiologies and a wide range of urine pH to test the validity of fasting UpH. Data from 159 subjects was examined in this retrospective study. We included non-stone forming subjects and stone formers with hypercalciuria, distal renal tubular acidosis, idiopathic uric acid nephrolithiasis, or chronic diarrhea. Participants collected a 24-h urine followed by a 2-h fasting urine. For the entire cohort, a significant correlation was seen between fasting and 24-h UpH (r (2) = 0.49, p < 0.001). Fasting pH was significantly higher than 24-h UpH for the entire cohort (6.02 ± 0.63 vs. 5.89 ± 0.51; p < 0.001), and in the subgroups of non-stone formers and stone formers with hypercalciuria or distal renal tubular acidosis. Fasting UpH was >0.2 pH units different from 24-h UpH in 58% of participants. The difference between fasting and 24-h UpH did not correlate with net gastrointestinal alkali absorption or urine sulfate, suggesting that dietary factors alone cannot explain this difference in UpH. Fasting urine pH correlates moderately with 24-h urine pH in a large cohort of individuals. Significant variability between these two parameters is seen in individual patients, emphasizing the cardinal role of 24-h urine collection for evaluating UpH in nephrolithiasis.
    Urological Research 02/2011; 39(5):367-72. DOI:10.1007/s00240-011-0365-y · 1.31 Impact Factor
  • Charles Y C Pak · Margaret S Pearle · Khashayar Sakhaee
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    ABSTRACT: The objective of this retrospective data analysis was to test the hypothesis that absorptive hypercalciuria Type II (AH-II) is a less severe variant of absorptive hypercalciuria Type I (AH-I), a common cause of calcareous stones. 24-h urinary calcium obtained on constant metabolic diets was retrieved from several data sources, including those of the authors and another group. On a low calcium diet (10 mmol calcium), 35 patients with AH-II were compared with 70 non-stone formers (NSF) and 76 patients with AH-I. On a high calcium diet (25 mmol calcium/day), 10 patients with AH-II were compared with 35 NSF and 32 with AH-I. On a low calcium diet for all participants, 24-h urinary calcium in AH-II (4.13 ± 0.63 mmol/day) was significantly higher than in NSF (3.06 ± 1.17 mmol/day), but significantly lower than in AH-I (6.11 ± 1.14 mmol/day) (p < 0.001). In a smaller subset, fractional intestinal calcium absorption in AH-II (65.0 ± 11.1%) was intermediate between NSF (50.0 ± 6.4%) and AH-I (71.0 ± 6.7%) (p < 0.001 between AH-II and other groups). On a high calcium diet, the rise in urinary calcium in AH-II was significantly higher than in NSF, but not as marked as in AH-I. Estimated calcium balance in AH-II was similar to NSF, but significantly more positive than AH-I. In conclusion, AH-II shares with AH-I the same metabolic disturbance(s) stimulating intestinal absorption and renal excretion of calcium but to a lesser degree. Bone might be spared in AH-II.
    Urological Research 11/2010; 39(2):147-52. DOI:10.1007/s00240-010-0315-0 · 1.31 Impact Factor
  • Charles Y. C. Pak · Khashayar Sakhaee · Joseph E. Zerwekh
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    ABSTRACT: Long-term clinical effects of intermittent sodium fluoride (slow-release) therapy were assessed in 71 patients with primary osteoporosis. In Group I (receiving 1,25-(OH)2D3 2 micrograms/day for 2 weeks before 3 months of sodium fluoride treatment 25 mg twice a day, in each 5-month cycle), vertebral (L2-L4) bone mineral content did not change significantly. However, the L2-L4 bone mineral content significantly increased by 3.1% in Group II (those who did not receive 1,25-(OH)2D3 during 5-month cycle), 3.5% per patient year in Group III (combined NaF 25 mg twice a day with 1,25-(OH)2D3 0.5 micrograms/day for 12 months in each 13-month cycle), and by 7.8% per patient year in Group IV (combined NaF with calcium citrate for 12 months in each 13-month cycle). The rise in vertebral bone mineral content was sustained, with an annual increment of 4.2% during the third year compared with 4.4% during the first year. The vertebral fracture rate declined significantly from the pretreatment value in all groups, but comparison with a placebo control group was not available. There was no significant change in the bone density of the radial shaft or of the proximal femur. The rate of hip fracture (nontraumatic) during treatment was 1.8% per patient year, the same as before treatment. The drug was well tolerated with only minor infrequent gastrointestinal and rheumatic side effects. Thus, intermittent slow-release sodium fluoride treatment with adequate calcium supplementation augments spinal bone mass and apparently inhibits vertebral fractures, with a satisfactory safety of usage; however, it has no effect on appendicular bone mass or on hip fracture rate.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of Bone and Mineral Research 03/2010; 5 Suppl 1(S1):S149-55. DOI:10.1002/jbmr.5650051323 · 6.59 Impact Factor
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    ABSTRACT: We examined the effect of fluoride (F) on intracellular ionic calcium [Ca2+]i in normal human osteoblasts maintained in culture. Cells were grown on glass coverslips to near-confluency and loaded with the Ca-sensitive dye, fura-2AM. Fluorescence changes were monitored in single cells using an inverted microscope coupled by fiberoptic to a microspectrofluorometer. The addition of F (100 ng/mL) to the medium promoted a rapid and significant increase in free [Ca2+]i from a resting level of 245 +/- 36 SE nM to a peak concentration of 440 +/- 51 nM (p less than 0.04). This increase in [Ca2+]i began at 10-20 s after addition of F and was maximal by 30 s. Intracellular [Ca2+]i levels then returned to near resting values by 60-80 s after F addition. This response was evident with as little as 25 ng/ml of fluoride and was dose dependent up to 500 ng/ml. At concentrations greater than 500 ng/ml, there appeared to be an attenuation of the rise in [Ca2+]i. The observed rise in [Ca2+]i was dependent on extracellular calcium since lowering extracellular calcium concentration or incubation with calcium channel blockers abolished the response. This observation supports a role of increased [Ca2+]i as one of the initial events of fluoride on action osteoblasts.
    Journal of Bone and Mineral Research 03/2010; 5 Suppl 1(S1):S131-6. DOI:10.1002/jbmr.5650051320 · 6.59 Impact Factor
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    ABSTRACT: Controversy exists regarding the effect of fluoride on human osteoblast proliferation. To learn more of the cellular action of fluoride, we chose the clonal osteoblast cell line HOS TE85 as a model system. In these phenotypically osteoblast-like cells, sodium fluoride stimulated [3H]thymidine incorporation in a dose-dependent manner over the concentration range 1 x 10(-5)-2 x 10(-4) M. The fluoride-induced stimulation of [3H]thymidine uptake was dependent on cell density, being optimal at subconfluent cell numbers. Stimulation of [3H]thymidine uptake was inhibited by anti-transforming growth factor beta but not by antibody to insulin-like growth factor I or beta 2-microglobulin. Transforming growth factor beta was shown to be a biphasic stimulator of [3H]thymidine uptake in HOS TE85, with maximal stimulation occurring at 0.5 nM transforming growth factor beta. In the presence of fluoride the cells were more sensitive to stimulation by this growth factor, with maximum effect occurring at 0.1 nM. Fluoride did not increase mRNA for transforming growth factor beta following either 8 or 24 h of exposure. We conclude that fluoride activates osteoblast proliferation by modulating the cellular sensitivity to transforming growth factor beta, a known stimulator of bone growth.
    Journal of Bone and Mineral Research 12/2009; 8(1):19-25. DOI:10.1002/jbmr.5650080104 · 6.59 Impact Factor
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    ABSTRACT: The bioavailability, biochemical effects, and safety of a slow-release preparation of sodium fluoride were examined. In 8 normal volunteers, a single administration of slow-release sodium fluoride (25 mg) caused a slow rise and gradual decline in serum fluoride concentration, thus avoiding sharp peaks produced by a rapid-release preparation. In 37 patients with postmenopausal osteoporosis, serum fluoride concentration was kept within the "therapeutic window" (95-100 ng/ml) during long-term intermittent sodium fluoride (slow-release) therapy (25 mg twice/day, given for 3 months in each 5-month cycle over five cycles). Serum fluoride was also kept within the therapeutic window in 64 patients who took sodium fluoride (slow release) continuously over 12 months. Serum osteocalcin concentration increased progressively during fluoride treatment (correlation coefficient of 0.88, p less than .001 for the relationship between serum osteocalcin and duration of therapy). Side effects to slow-release sodium fluoride therapy, assessed in 101 patients at two study sites, were minor and included diarrhea in 2 patients, nausea in 2 patients, abdominal pain and cramping in 2 patients, foot pain in 2 patients, and joint pain in 6 patients. Thus, slow-release sodium fluoride confers desired level of fluoride in serum, while providing safety of usage.
    Journal of Bone and Mineral Research 12/2009; 1(6):563-71. DOI:10.1002/jbmr.5650010611 · 6.59 Impact Factor
  • Flavia Pietschmann · Neil A. Breslau · Charles Y.C. Pak
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    ABSTRACT: Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.
    Journal of Bone and Mineral Research 12/2009; 7(12):1383-8. DOI:10.1002/jbmr.5650071205 · 6.59 Impact Factor
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    ABSTRACT: Estimating calcium oxalate saturation in human urine is critical for nephrolithiasis clinical research and practice. The Joint Expert Speciation System (Mayhem Unit Trust and Council for Scientific and Industrial Research, Pretoria, South Africa) computer program has questioned the validity of the widely used EQUIL 2 program in estimating calcium oxalate urinary saturation. To attempt resolution the computer model based supersaturation index (by the Joint Expert Speciation System) and the relative saturation ratio (by EQUIL 2) were compared with the experimentally derived activity product ratio, that is the ratio of activity products before and after incubating urine with synthetic calcium oxalate. To determine the experimental conditions required to attain calcium oxalate steady state solubility the filtrate concentration product of calcium and oxalate was determined after incubating 8 urine samples with 2 to 15 mg/ml calcium oxalate for various intervals. In 20 urine samples the activity product ratio of calcium oxalate was compared with the relative saturation ratio and the supersaturation index. Steady state solubility occurred after incubating 15 mg calcium oxalate per ml urine for 72 hours. The mean +/- SD supersaturation index of 4.92 +/- 2.57 in the original urine samples closely approximated the activity product ratio of 5.08 +/- 3.10 but the relative saturation ratio of 7.47 +/- 3.89 was significantly higher than the activity product ratio. The supersaturation index was recalculated after omitting soluble complexes recognized by the Joint Expert Speciation System but not by EQUIL 2, including Ca(2)H(2)(PO(4))(2) and (CaCitPO(4))(4-). The corrected supersaturation index was compared with the relative saturation ratio. After correction the supersaturation index increased to 7.28 +/- 3.81, which was not significantly different from the relative saturation ratio. The Joint Expert Speciation System is more accurate than EQUIL 2 to estimate calcium oxalate saturation, probably by accounting for Ca(2)H(2)(PO(4))(2), (CaCitPO(4))(4-), and other minor complexes of calcium and oxalate.
    The Journal of urology 12/2009; 182(6):2951-6. DOI:10.1016/j.juro.2009.08.015 · 3.75 Impact Factor
  • Joseph E. Zerwekh · Peter Antich · Charles Y. C. Pak
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 09/2009; 11(9):1370 - 1371. DOI:10.1002/jbmr.5650110924 · 6.59 Impact Factor
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    ABSTRACT: We have previously reported that bone formation is impaired on histomorphometric analysis of bone in patients with idiopathic osteoporosis. In the present study, 30 patients with idiopathic osteoporosis (18 men and 12 women mean age 44 +/- 12 years) and spinal and/or appendicular fractures were studied. Compared with control values, bone biopsy analysis demonstrated reduced bone volume (13.0 +/- 4.4 vs. 23.2 +/- 4.4, p < 0.0001), osteoid volume (0.13 +/- 0.13 vs. 0.32 +/- 0.19, p = 0.001), osteoid surface (5.9 +/- 4.3 vs. 12.1 +/- 4.6, p = 0.0004), and diminished double-labeled mineralizing surface (MS/BS 2.0 +/- 2.1 vs. 5.1 +/- 2.7%, p = 0.0001) in the patients. Since insulin-like growth factor 1 (IGF-1) is one of the major determinants of bone growth and remodeling, we measured the circulating level of this growth factor in these patients. The mean serum IGF-1 concentration was lower in patients as compared with 33 healthy age-matched controls (193 +/- 59 SD ng/ml vs. 232 +/- 79). A significant difference was noted between the two groups only in subjects younger than 36 years. In patients with idiopathic osteoporosis, regression analysis of serum IGF-1 against the various histological parameters measured from the bone biopsy disclosed significant correlation's between serum IGF-1 and osteoblastic surface (r = 0.429, p = 0.032), mineralizing bone surface with a double label (r = 0.480, p = 0.015), and the bone formation rate (r = 0.457, p = 0.021). These findings suggest that in young eugonadal individuals with idiopathic osteoporosis, reduced IGF-1 concentrations may have an etiological role in the development of this disease.
    Journal of Bone and Mineral Research 08/2009; 10(8):1218-24. DOI:10.1002/jbmr.5650100812 · 6.59 Impact Factor
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    ABSTRACT: Clinical pharmacology of slow-release sodium fluoride given with calcium citrate was examined in acute and long-term studies. Following a single oral administration of 50 mg slow-release sodium fluoride, a peak serum fluoride concentration (Cmax) of 184 ng/ml was reached in 2 h; thereafter, serum fluoride concentration declined with a T1/2 of 5.9 h. The concurrent administration of calcium citrate (400 mg calcium) gave an equivalent Tmax (time required to attain Cmax) and T1/2, but a lower Cmax of 135 ng/ml. The coadministration of a meal with fluoride also reduced Cmax but increased Tmax. The area under the serum concentration curve of slow-release sodium fluoride was reduced 17-27% by a meal or calcium citrate. Thus, calcium citrate reduced fluoride absorption and peak fluoride concentration in serum of slow-release sodium fluoride but did not affect the time required to reach peak concentration or the rate of subsequent decline. The effect of a meal was similar, except for a longer period required to reach peak serum concentration. During long-term administration of 25 mg slow-release sodium fluoride coadministered with 400 mg calcium as calcium citrate on a twice daily schedule, the trough level of serum fluoride could be kept between 95 and 190 ng/ml, believed to be the therapeutic window.
    Journal of Bone and Mineral Research 08/2009; 5(8):857-62. DOI:10.1002/jbmr.5650050809 · 6.59 Impact Factor
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    ABSTRACT: The Westernized diet is acidogenic due to the high content of sulfur-containing amino acids and relative deficiency of potassium organic anions. Chronic acid loads result in hypercalciuria and negative calcium balance often associated with loss of bone mineral. Alkali therapy tends to reverse the hypercalciuria but little is known regarding its effect on bone as assessed by bone histomorphometry. The present study utilized dynamic bone histomorphometry to evaluate the effects of alkali therapy on acid-induced changes in bone turnover. Serum and urine analyses and bone histomorphometry were assessed in adult rats after 2 months of either a low casein (LC) or high casein (HC) diet supplemented with either potassium chloride (KCl) or potassium citrate (KCit). Compared to animals on LC-KCl diet, HC-KCl diet delivered a substantial acid load as shown by significant increases in urinary sulfate, ammonium, and net acid excretion, and a lower urinary pH and citrate excretion without detectable changes in serum parameters. The acid load also resulted in hypercalciuria. Dynamic and static bone histomorphometry disclosed a significant reduction in cancellous bone volume and trabecular number associated with a 2.5-fold increase in eroded and a 3.5-fold increase in osteoclastic surfaces. There was also a near 2-fold increase in bone formation rate in rats on the HC-KCl diet. When animals on the HC diet were given KCit instead of KCl, all of the aforementioned changes in urine biochemistry and bone turnover were significantly attenuated or entirely prevented. These findings underscore the deleterious effects of high animal protein intake in promoting hypercalciuria and increasing bone turnover. Co-administration of potassium alkali attenuates or prevents these changes. In this animal model of high dietary animal protein intake, the major skeletal effect of alkali therapy is to reduce bone resorption, with little or no effect on bone formation.
    Bone 08/2009; 45(5):1004-9. DOI:10.1016/j.bone.2009.07.077 · 4.46 Impact Factor
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    ABSTRACT: The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).
    Journal of Bone and Mineral Research 07/2009; 8(7):789-94. DOI:10.1002/jbmr.5650080703 · 6.59 Impact Factor
  • Michael J. Nicar · Kathy Hill · Charles Y.C. Pak
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    ABSTRACT: Effect of citrate on the spontaneous precipitation of calcium oxalate was examined in synthetic media. Citrate significantly increased the formation product of calcium oxalate. This "direct" measure of inhibitor activity, representing activity product at the point of nucleation, rose by 76% by the addition of citrate sufficient to provide trivalent citrate concentration of 1.49 mM. Moreover, citrate inhibited calcium oxalate crystallization by complexing calcium and lowering calcium oxalate saturation. This "indirect" measure of inhibitor activity was assessed from the concentration product of calcium oxalate at the point of nucleation, since this measure should provide a reflection of both ion pair formation and direct inhibitor activity of citrate. The concentration product exceeded the formation product at all ionic (trivalent) citrate concentrations, particularly at high ionic citrate levels. At the ionic citrate concentration of 1.49 mM, the rise in the concentration product was 373%, which was nearly fivefold that observed for the formation product. The presence of ferric or aluminum cations at a physiologic concentration of 2 mg/l did not modify the increase in formation product produced by citrate. Thus, citrate inhibits calcium oxalate crystallization, largely by complexing citrate, but also by directly affecting nucleation. Presence of ferric or aluminum cations at a physiological concentration does not modify the inhibitor action of citrate.
    Journal of Bone and Mineral Research 06/2009; 2(3):215-20. DOI:10.1002/jbmr.5650020308 · 6.59 Impact Factor

Publication Stats

12k Citations
2,087.08 Total Impact Points

Institutions

  • 1973–2014
    • University of Texas Southwestern Medical Center
      • • Pak Center for Mineral Metabolism and Clinical Research
      • • Department of Internal Medicine
      • • Department of Physical Medicine and Rehabilitation
      Dallas, Texas, United States
  • 1977–2011
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 2009
    • University of North Texas at Dallas
      Dallas, Texas, United States
  • 1967–2007
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2003
    • Duke University
      Durham, North Carolina, United States
  • 1974–1988
    • University of Texas Health Science Center at Tyler
      Tyler, Texas, United States
    • University of Texas Medical School
      Houston, Texas, United States
  • 1983
    • Baylor Health Care System
      Dallas, Texas, United States
  • 1979
    • University of Texas Health Science Center at San Antonio
      • Department of Neurology
      San Antonio, Texas, United States
  • 1967–1969
    • National Institutes of Health
      • Branch of Endocrine Oncology
      Maryland, United States