Intestinal hyperabsorption of calcium and low bone turnover in hypercalciuric postmenopausal osteoporosis.

Hypercalciuria of intestinal origin has been linked with bone loss in calcium nephrolithiasis and idiopathic osteoporosis. This retrospective data analysis was performed to explore potential pathogenetic link between intestinal hyperabsorption of calcium and postmenopausal osteoporosis. Data were retrieved from postmenopausal women who were evaluated for osteoporosis or osteopenia at the Mineral Metabolism Clinic of UT Southwestern Medical Center. A total of 319 patients underwent the test of calciuric response to oral calcium load to obtain an indirect measure of intestinal calcium absorption. Serum and urinary biochemistry and L2-L4 bone mineral density (BMD) were compared between five quintiles of calciuric response. There was a statistically significant trend toward a rise in 24-h urinary calcium and a decrease in urinary deoxypyridinoline (DPD) and BMD, with increasing order of quintiles. The presentation of those in the 1st quintile was consistent with vitamin D insufficiency or deficiency, with impaired calcium absorption, secondary hyperparathyroidism, and stimulated bone turnover (high normal urinary DPD). In contrast, patients in the 5th quintile displayed a picture of absorptive hypercalciuria of stone disease, with intestinal hyperabsorption of calcium, high or high normal urinary calcium and suppressed bone turnover (low or low normal urinary DPD). Thus, the assessment of intestinal calcium absorption in a seemingly homogeneous group of postmenopausal women with osteoporosis or osteopenia revealed a spectrum of calciuric response whose extremes may represent two physiologically distinct subtypes that have important diagnostic and therapeutic implications.

Biochemical characterization of primary hyperparathyroidism with and without kidney stones.

The exact metabolic-physiological background for kidney stone formation in primary hyperparathyroidism (PHPT) is unclear. To obtain clarification, this retrospective data analysis was conducted in 131 patients with PHPT who had undergone a detailed ambulatory evaluation on a random diet since 1980. The baseline biochemical presentation of 78 patients with PHPT with stones was compared with that of 53 patients without stones. Compared to those without stones, the stone-forming patients had a more marked hypercalciuria (343 +/- 148 vs. 273 +/- 148 mg/day, P < 0.01). Urinary saturation of calcium oxalate and brushite was significantly higher in stone-formers. Serum PTH and fasting urinary calcium were similar between the two groups, but serum phosphorus was significantly lower in stone-formers. Serum calcitriol (available in some patients) showed a slightly higher mean value in stone-formers but the difference was not significant. The increment in urinary calcium after oral load of 1-g calcium was twofold higher among stone-formers. Radial shaft and L2-L4 bone mineral densities resided within the normal ranges. Stone-formers with PHPT display exaggerated urinary calcium excretion due to intestinal hyperabsorption of calcium, contributing to a greater enhancement of the saturation of stone-forming calcium salts.

Effect of dietary modification on urinary stone risk factors.

BACKGROUND: This study was undertaken to ascertain the effect of dietary modification on urinary stone risks, and to determine whether the response depends on the prevailing urinary calcium. METHODS: A retrospective data analysis was conducted from our stone registry involving 951 patients with calcareous stones undergoing ambulatory evaluation, whereby 24-hour urine samples were collected during random diet and after dietary modification composed of restriction of calcium, oxalate, sodium, and meat products. Samples were analyzed for stone risk factors. Urinary calcium was also obtained after overnight fast and following a 1 g-calcium load. Changes produced by dietary modification from the random diet were evaluated in 356 patients with moderate-severe hypercalciuria (>6.88 mmol/day, group I), 243 patients with mild hypercalciuria (5.00-6.88 mmol/day, group II), and 352 with normocalciuria (<5.00 mmol/day, group III). RESULTS: Urinary calcium postcalcium load and the percentage of patients with absorptive hypercalciuria type I were highest in group I, intermediate in group II, and lowest in group III. During dietary modification, urinary calcium declined by 29% in group I, 19% in group II, and 10% in group III. Urinary oxalate did not change. Urinary saturation of calcium oxalate declined by only 12% in group I, 6% in group II, and nonsignificantly in group III, owing to various physicochemical changes in urinary biochemistry, which attenuated the effect of the decline in urinary calcium. Urinary saturation of brushite declined in all 3 groups due to the fall in urinary calcium, phosphorus, and pH. This reduction was more marked in the hypercalciuric groups than in the normocalciuric group. Urinary saturation of monosodium urate also decreased from a decline in urinary sodium and uric acid. CONCLUSION: Secondary rise in urinary oxalate occurring from calcium restriction can be avoided by concurrent dietary oxalate restriction. Dietary modification (restriction of dietary calcium, oxalate, sodium, and meat products) is more useful in reducing urinary saturation of calcium oxalate among patients with hypercalciuria than among those with normocalciuria.

Physicochemical metabolic characteristics for calcium oxalate stone formation in patients with gouty diathesis.

PURPOSE: We determined why calcium oxalate stones instead of uric acid stones form in some patients with gouty diathesis. MATERIALS AND METHODS: Gouty diathesis was diagnosed from absence of secondary causes of uric acid stones or low urinary pH, and reduced fractional excretion of urate with discriminant score of the relationship between urinary pH and fractional excretion of urate less than 80. From the stone registry 163 patients with gouty diathesis were identified, including 62 with uric acid stones (GD + UA) and 101 patients with calcium oxalate stones (GD + Ca). Metabolic data and 24-hour urinary chemistry study were compared between the 2 groups. RESULTS: Compared with GD + UA, GD + Ca had significantly greater urinary calcium (196 +/- 96 mg per day vs 162 +/- 82 mg per day, p <0.05) and significantly lower urinary citrate (430 +/- 228 vs 519 +/- 288 mg per day, p <0.05), resulting in higher urinary saturation of calcium oxalate. Both groups had low urinary pH (less than 5.5) and high urinary undissociated uric acid (greater than 100 mg/dl). Urinary calcium post-oral calcium load was significantly higher in GD + Ca than in GD + UA (0.227 vs 0.168 mg/dl glomerular filtrate, p <0.001). CONCLUSIONS: Calcium oxalate stones may form in some patients with gouty diathesis due to increased urinary excretion of calcium and reduced excretion of citrate. Relative hypercalciuria in GD + Ca may be due to intestinal hyperabsorption of calcium.

Reduction in normalized bone elasticity following long-term bisphosphonate treatment as measured by ultrasound critical angle reflectometry.

Using an improved version of ultrasound critical angle reflectometry, the bone quality of cortical and trabecular bone was assessed in vivo by measuring elastic moduli (normalized for bone density) at both principal axes, referred to as the minimum and maximum normalized elasticities. The measurements were made in 30 normal premenopausal women, 30 normal postmenopausal women, 22 untreated postmenopausal women with osteoporosis, 74 postmenopausal women with osteoporosis or osteopenia on bisphosphonate treatment, and 32 patients with renal transplantation (16 women and 16 men) taking steroids. Cortical elasticity was higher than trabecular elasticity; both declined slightly and non-significantly with age in normal women. Among untreated postmenopausal women with osteoporosis, cortical maximum normalized elasticity (E(cmax)) remained within 95% prediction intervals of normal women. Among patients on bisphosphonate, E(cmax) was low in the majority of patients. E(cmax) was significantly more depressed among those taking the drug > or =3 years than <3 years (22.1% below normal premenopausal women versus 17.2%, P =0.001), and among those with incident non-spinal fractures than without (75.9 vs. 81.5%, P =0.008). E(cmax) was independent of bone mineral density at the calcaneus. Most patients with renal transplantation had low E(cmax), with a mean 20.8% below the normal premenopausal mean. Qualitatively similar findings were found with cortical minimum elasticity and with trabecular minimum and maximum elasticities. Thus, the material bone quality of cortical and trabecular bone may be impaired following bisphosphonate treatment, as in renal transplantation on steroids.

Rapid Communication: relative effect of urinary calcium and oxalate on saturation of calcium oxalate.

BACKGROUND: The study compared the effect of urinary calcium with that of oxalate on urinary saturation [relative saturation ratio (RSR)] of calcium oxalate. METHODS: A retrospective data analysis was conducted on urinary stone risk analysis from 667 patients with predominantly calcium oxalate stones. Urinary RSR of calcium oxalate was individually calculated using Equil 2. A "theoretical" curve of the relationship between urinary RSR of calcium oxalate and concentration of calcium or oxalate was obtained at two stability constants for calcium oxalate complex, while varying calcium or oxalate and using group mean values for urinary constituents. RESULTS: At the stability constant of 7.07 x 10(3), the increase in RSR of calcium oxalate was less marked with calcium than with oxalate. However, at the stability constant of 2.746 x 10(3) from the Equil 2 that is considered the "gold standard," calcium and oxalate were equally effective in increasing RSR of calcium oxalate. The above theoretical curves (relating RSR with calcium or oxalate) were closely approximated by the actual curves constructed with data from individual urine samples. Urinary saturation of calcium oxalate was equally dependent on urinary concentrations of calcium and oxalate (r= 0.75 unadjusted and 0.57 adjusted for variables, and P < 0.0001 for calcium; r= 0.73 unadjusted and 0.60 adjusted, P <0.0001 for oxalate). CONCLUSION: Among calcium oxalate stone-formers, urinary calcium is equally effective as urinary oxalate in increasing RSR of calcium oxalate.

Biochemical and physicochemical presentations of patients with brushite stones.

PURPOSE: We determined whether the biochemical and physicochemical backgrounds of patients with brushite stones differ from those with hydroxyapatite and calcium oxalate stones. MATERIALS AND METHODS: From a computer data base of patients completing ambulatory evaluation 19 with brushite stones, 24 with hydroxyapatite stones and 762 with calcium oxalate stones were identified with the specified composition in greater than 70% of stones. RESULTS: Absorptive hypercalciuria type I was present in 63% of patients with brushite, 17% with hydroxyapatite and 30% with calcium oxalate stones. Distal renal tubular acidosis was noted in 32% of patients with brushite, 42% with hydroxyapatite and 3% with calcium oxalate stones. Mean urinary calcium in the brushite group was significantly higher than in the hydroxyapatite and calcium oxalate groups (265 +/- 125 vs 186 +/- 103 and 187 +/- 95 mg daily, respectively). Urinary pH in the brushite group was slightly but significantly higher than in the calcium oxalate group (6.15 +/- 0.30 vs 5.91 +/- 0.42). The brushite relative saturation ratio in the brushite group was marginally higher than in the hydroxyapatite group and significantly higher than in the calcium oxalate group (3.25 +/- 2.03 vs 2.34 +/- 1.51 and 1.83 +/- 1.66, respectively). CONCLUSION: Patients with predominantly brushite stones could be distinguished from those with predominantly hydroxyapatite and calcium oxalate stones by higher urinary saturation with respect to brushite due mainly to hypercalciuria from absorptive hypercalciuria.

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.

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.

Biochemical distinction between hyperuricosuric calcium urolithiasis and gouty diathesis.

OBJECTIVES: To determine whether the biochemical presentation and urinary physicochemical environment of patients with hyperuricosuria presenting with calcium stones (hyperuricosuric calcium urolithiasis [HUCU]) differs from those of patients with gouty diathesis (GD) or idiopathic uric acid urolithiasis. METHODS: A total of 122 patients with HUCU and 68 patients with GD were identified from our "stone registry" of patients who underwent a full ambulatory evaluation. All patients with HUCU had urinary uric acid greater than 800 mg/day in men and greater than 750 mg/day in women and presented with calcium stones. Those with GD had pure uric acid stones or mixed uric acid-calcium stones and did not have secondary causes of uric acid urolithiasis. Data derived from the fasting serum and 24-hour urine samples collected on a random diet and on a diet restricted in calcium, sodium, and oxalate were compared between the two groups. RESULTS: Compared with patients with HUCU, those with GD had significantly higher serum uric acid and lower urinary uric acid and pH levels (mean value 5.38 and 5.35 on random and restricted diets versus 6.09 and 6.14, respectively). The fractional excretion of urate and the discriminant score of the relationship between urinary pH and the fractional excretion of urate were significantly lower in those with GD than in those with HUCU. Patients with HUCU displayed a greater urinary saturation of sodium urate and calcium oxalate compared with those with GD, and those with GD had a higher urinary content of undissociated uric acid and lower urinary saturation of brushite (calcium phosphate). CONCLUSIONS: Patients with HUCU presented with normal urinary pH and hyperuricosuria, accompanied sometimes by hypercalciuria, which produced increased urinary saturation of sodium urate and calcium oxalate. In contrast, those with GD had a low fractional excretion of urate (that contributed to hyperuricemia) and low urinary pH (that led to increased amount of undissociated uric acid). The varying biochemical and physicochemical presentations of the two conditions can be ascribed to overindulgence with purine-rich foods in those with HUCU and underlying primary gout in those with GD.

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.