Fractional Intestinal Calcium Absorption Research Articles

Evidence in Favor of a Severely Impaired Net Intestinal Calcium Absorption in Patients with (Early-Stage) Chronic Kidney Disease

Introduction: Calcium and phosphorus are essential to many vital physiological processes. Little is known about the net and fractional intestinal absorption of calcium and phosphorus in patients with chronic kidney disease (CKD) and their clinical and hormonal determinants. Methods: Blood and 24-hour urine samples were collected in 20 healthy volunteers (HV) and 72 stable CKD stage 1–4 patients and analyzed for parameters of mineral metabolism including calcidiol, calcitriol, and parathyroid hormone (PTH). Dietary intake was assessed by dietary history. Results: The 24-hour urinary calcium excretion, as opposed to the phosphorus excretion, showed a stepwise decrease across CKD stages (median of 219, 84, 40, and 22 mg/day in HV and patients with CKD stages 1–2, 3 and 4, respectively). Younger age, high serum calcitriol, and high estimated GFR were associated with a high 24-hour urinary calcium excretion. High serum calcitriol levels and dietary phosphorus intake were associated with a high 24-hour urinary phosphorus excretion. The fractional intestinal calcium absorption, as estimated by the urinary-to-ingested calcium ratio, decreased across CKD stages. Conclusions: The 24-hour urinary excretion of calcium, as opposed to phosphorus, is markedly decreased in CKD, even in early-stage disease. This is partly explained by low calcitriol levels and older age. Assuming a neutral calcium balance at the time of urine collection, we infer that net intestinal calcium absorption may be severely impaired in CKD.

Take Another CYP: Confirming a Novel Mechanism for “Idiopathic” Hypercalcemia

Take Another CYP: Confirming a Novel Mechanism for “Idiopathic” Hypercalcemia

Evidence for metabolic origin of absorptive hypercalciuria Type II

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.

Randomized Controlled Trial of the Effects of Calcium With or Without Vitamin D on Bone Structure and Bone-Related Chemistry in Elderly Women With Vitamin D Insufficiency

There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status. The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone-related chemistry in elderly women with vitamin D insufficiency. Three hundred two elderly women (age, 77.2 +/- 4.6 yr) with serum 25(OH)D concentrations <60 nM participated in a 1-yr randomized, double-blind, placebo-controlled trial. All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol (vitamin D(2)) or identical placebo (control). The effects of time and time treatment interactions were evaluated by repeated-measures ANOVA. At baseline, calcium intake was 1100 mg/d, and 25(OH)D was 44.3 +/- 12.9 nM; this increased in the vitamin D group by 34% but not the control group after 1 year (59.8 +/- 13.8 versus 45.0 +/- 13.3 nM, p < 0.001). Total hip and total body BMD increased significantly, and procollagen type I intact N-terminal propeptide (PINP) decreased during the study with no difference between the treatment groups (hip BMD change: vitamin D, +0.5%; control, +0.2%; total body BMD change: vitamin D, +0.4%; control, +0.4%; PINP change: vitamin D, -3.9%; placebo, -2.8%). Although the fasting plasma and urine calcium increased in both groups equally, there was no detectable change in serum PTH. The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption, which fell equally in both groups (vitamin D, -17.4%; control, -14.8%). In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency, vitamin D(2) 1000 IU for 1 year has no extra beneficial effect on bone structure, bone formation markers, or intestinal calcium absorption over an additional 1000 mg of calcium. Vitamin D supplementation adds no extra short-term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency.

Un cas de pneumonie interstitielle lymphoïde liéeau VIH dans le cadre d'une restauration immunitaire

Nutritional rickets remains a global public health problem, despite effective and inexpensive means to prevent and treat the disease. It is most prevalent in the infant/toddler age groups and the adolescent, but vitamin D deficiency is also prevalent in women of child bearing age, resulting in babies being born with low vitamin D stores and the mothers having inadequate vitamin D in breast milk, thus exacerbating the risk for rickets in these infants. In a number of subtropical developing countries, rickets appears to be due to low-dietary calcium intakes (∼200 mg/day) rather than vitamin D deficiency. Biochemically these children are differentiated from those with vitamin D deficiency by having markedly elevated serum 1,25-dihydroxyvitamin D concentrations and high fractional intestinal calcium absorption. Nutritional rickets represents the outcome of a spectrum of causes ranging from vitamin D deficiency on one hand to dietary calcium deficiency on the other, while in between low dietary intakes and vitamin D insufficiency combine to cause the disease.

Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism

Background: Low-carbohydrate high-protein (LCHP) diets are used commonly for weight reduction. This study explores the relationship between such diets and acid-base balance, kidney-stone risk, and calcium and bone metabolism. Methods: Ten healthy subjects participated in a metabolic study. Subjects initially consumed their usual non-weight-reducing diet, then a severely carbohydrate-restricted induction diet for 2 weeks, followed by a moderately carbohydrate-restricted maintenance diet for 4 weeks. Results: Urine pH decreased from 6.09 (Usual) to 5.56 (Induction; P < 0.01) to 5.67 (Maintenance;P < 0.05). Net acid excretion increased by 56 mEq/d (Induction; P < 0.001) and 51 mEq/d (Maintenance; P < 0.001) from a baseline of 61 mEq/d. Urinary citrate levels decreased from 763 mg/d (3.98 mmol/d) to 449 mg/d (2.34 mmol/d; P < 0.01) to 581 mg/d (3.03 mmol/d; P < 0.05). Urinary saturation of undissociated uric acid increased more than twofold. Urinary calcium levels increased from 160 mg/d (3.99 mmol/d) to 258 mg/d (6.44 mmol/d; P < 0.001) to 248 mg/d (6.19 mmol/d; P < 0.01). This increase in urinary calcium levels was not compensated by a commensurate increase in fractional intestinal calcium absorption. Therefore, estimated calcium balance decreased by 130 mg/d (3.24 mmol/d; P < 0.001) and 90 mg/d (2.25 mmol/d; P < 0.05). Urinary deoxypyridinoline and N-telopeptide levels trended upward, whereas serum osteocalcin concentrations decreased significantly (P < 0.01). Conclusion: Consumption of an LCHP diet for 6 weeks delivers a marked acid load to the kidney, increases the risk for stone formation, decreases estimated calcium balance, and may increase the risk for bone loss. © 2002 by the National Kidney Foundation, Inc.

Abnormal arachidonic acid content of red blood cell membranes and main lithogenic factors in stone formers

Increased arachidonic acid content in red blood cell membranes of stone formers (SF) has recently been reported and is hypothesized as representing the underlying causal factor for both hyperoxaluria and hypercalciuria. We performed the present study to see whether we could confirm this finding and to test whether any relationship exists between the fatty acid composition of red blood cell membranes and the main metabolic factors involved in stone formation. In 21 SF and 40 healthy controls subjects the fatty acid composition of red blood cell membranes was assessed. In addition, the following parameters were evaluated in SF: daily and fasting urinary calcium excretion, fractional intestinal calcium absorption, 1,25-dihydroxy-vitamin D, intact parathyroid hormone, hydroxyproline in fasting urine, daily urinary excretion of oxalate, citrate, urate, electrolytes, urea, sulphate, relative supersaturation for calcium oxalate monohydrate. The red blood cell membrane of SF had a lower content of arachidonic acid, linoleic acid, and docosahexaenoic acid than that of control subjects. Arachidonic acid content was not correlated with any of the parameters studied. However, when patients were grouped according to the degree of oxalate excretion, hyperoxaluric SF had a higher arachidonic acid content and arachidonic/linoleic acid ratio than SF with normal oxalate excretion. Our results do not confirm the finding of an increased arachidonic acid content of red blood cell membrane in SF. On the contrary, reduced arachidonic acid levels were found in our patients. However, hyperoxaluric SF had a relatively higher arachidonic acid content than SF with normal urinary oxalate excretion.

High insulin and low IGF-I plasma levels following pancreas transplantation in rats. Implications for bone and mineral metabolism

Primary disturbances in mineral metabolism and deficiencies in insulin and insulin-like growth factor-I (IGF-I) have been implicated in the pathogenesis of diabetic osteopenia. This prompted us to investigate whether normal bone minerals and bone morphology are preserved after pancreas transplantation. To this end, 8 inbred rats (transplants) were compared with 9 sham-operated rats (controls) 20 months after orthotopic pancreas transplantation. While basal levels of insulin remained unaffected by transplantation, an oral glucose load elicited hyperinsulinemia (integrated incremental response: mean +/- SEM, 62+/-8 nmol l(-1) 60 min in transplants vs. 32+/-6 nmol l(-1) 60 min in controls; p<0.01) in the presence of normal glucose levels. Fecal and urinary excretion and fractional intestinal absorption of calcium, magnesium and phosphorus, net calcium absorption and the respective serum mineral levels were unchanged after transplantation, as were those of the calciotropic hormones. Serum osteocalcin and bone alkaline phosphatase remained unaffected, and urinary excretion of pyridinium and deoxypyridinium were unchanged. Fasting plasma IGF-I concentration was significantly decreased in transplants (930+/-42 ng ml(-1)) vs. control rats (1074+/-49 ng ml(-1); p < 0.05). Despite similar physical and chemical properties of bone in both groups, histomorphometry revealed slight osteopenia in transplant rats, as reflected by a 38% reduction in the cancellous bone area of the proximal tibial metaphysis. Plasma IGF-I levels were significantly correlated with bone mineral apposition rate (r=0.70, p<0.02), osteoblast perimeter (r=0.60, p<0.05) and osteoid perimeter (r=0.60, p<0.05). In conclusion, pancreas transplantation preserves physical and chemical properties of bone, but bone metabolism is not completely normal after transplantation, as evidenced by decreased cancellous bone. This might have resulted from the insulin resistance associated with the lowering of the plasma IGF-I level, which was correlated with the mineral apposition rate.

Age-related decline of bone mass and intestinal calcium absorption in normal males.

Although about 25% of all hip fractures occur in men, little is known about the pattern of their age-related bone loss and its main determinants. The aim of this cross-sectional study was to evaluate the age-related changes of intestinal calcium absorption, bone mass, and bone turnover in normal men. In 70 normal males (age 17-91 years), we measured spinal and forearm bone density (FBD) (by DXA), fractional intestinal calcium absorption (by oral test), serum immunoreactive parathyroid hormone (PTH), dietary calcium intake (diet records), biochemical markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin, urine calcium, creatinine, and hydroxyproline), and 1,25(OH)2D3 serum levels. Vertebral bone density (VBD) showed a modest decline before age 50 and a greater decline after age 50, whereas FBD presented a significant decrease with advancing age starting at age 40, suggesting a predominant age-related cortical bone loss. Intestinal calcium absorption (47CaFA) and serum 1,25(OH)2D3 also presented an age-related decline similar to FBD. Simple correlation analysis revealed that age was significantly related to 47CaFA (r = 0.60), calcium intake (r = 0.32), VBD and FBD (r = 0.79 and 0.63, respectively), serum 1,25(OH)2D3 (r = 0.69), and serum iPTH (r = 0.72). No significant correlation was found between age and biochemical markers of bone remodeling. Partial correlation and stepwise variable selection analyses, using 47CaFA and bone mass as dependent variables, showed that in normal males, serum 1,25(OH)2D3 and dietary calcium intake were the main contributors (64%) to 47CaFA variability, whereas only age accounted for 63% of VBD and age and dietary calcium accounted for 45% of FBD variability. These results indicate that bone loss in men accelerates after age 50 years and that among other factors, intestinal calcium malabsorption and 1,25(OH)2D3 serum levels play a role.

Limited Risk of Kidney Stone Formation During Long-Term Calcium Citrate Supplementation in Nonstone Forming Subjects

The physiological and physicochemical effects of long-term calcium citrate supplementation (25mmol, calcium per day) were assessed in 7 normal premenopausal women. Calcium citrate increased urinary calcium from 3.27 ± 0.42mmol, per day (standard deviation) before treatment to 5.16 ± 0.75mmol, per day after 1-month of treatment (p <0.0125). After 3 months of treatment urinary calcium decreased from the 1-month value to 4.54 ± 0.67mmol, per day (p <0.0125) but remained higher than the pretreatment value (p <0.0125). Fractional intestinal calcium absorption and serum 1,25-dihydroxyvitamin D levels decreased marginally at 1 month of calcium citrate therapy, from 0.457 ± 0.092 to 0.374 ± 0.035 (p <0.05) and from 103 ± 7 to 77 ± 14 pmol./l. (p <0.05), respectively. After 3 months of treatment fractional intestinal calcium absorption decreased further to 0.341 ± 0.061 (p <0.0125 compared to pretreatment), whereas serum 1,25-dihydroxyvitamin D remained unchanged at 82 ± 14pmol./l.Calcium citrate treatment decreased urinary phosphorus levels significantly from 18.9 ± 3.3 to 15.0 ± 2.5mmol, per day (p <0.0125) and 14.0 ± 2.5mmol, per day (p <0.05) at 1 and 3 months, respectively. Mean urinary oxalate decreased by 15 to 20% and urinary citrate increased marginally during treatment. Urinary saturation of calcium oxalate and brushite did not change during calcium citrate therapy, except at 1 month when the saturation of calcium oxalate increased marginally. The inhibitory activity of urine against spontaneous nucleation of calcium oxalate and brushite (formation product) did not change during treatment.In conclusion, long-term calcium citrate supplementation in normal subjects does not increase the propensity for crystallization of calcium salts in the urine. This protective effect is probably due to the attenuated increase in urinary calcium excretion (from a decrease in fractional intestinal calcium absorption), a decrease in urinary phosphorus and an increase in urinary citrate.

Metabolic effects of thiazide and 1,25-(OH)2 vitamin D in postmenopausal osteoporosis

It was previously shown that the stimulation of intestinal calcium absorption by exogenous 25-hydroxyvitamin D (25-OHD) in postmenopausal women with osteoporosis was attenuated when thiazide was added, probably due to the suppression of endogenous synthesis of 1,25-(OH)2 vitamin D (1,25-(OH)2D). To test whether the above attenuation could be averted if exogenous 1,25-(OH)2D replaced 25-OHD, 10 women with postmenopausal osteoporosis participated in a three-phase study comprising control (pretreatment), treatment with 1,25-(OH)2D 0.5 microgram/day for 4 weeks, and combined 1,25-(OH)2D and trichlormethiazide (TZ) 2 mg/day for 4 weeks. The 1,25-(OH)2D treatment significantly increased serum 1,25-(OH)2D from 60 +/- 7.2 (SD) to 154 +/- 48 pmol/l, fractional intestinal calcium absorption (alpha) from 0.386 +/- 0.055 to 0.613 +/- 0.081, and urinary calcium from 3.7 +/- 0.8 to 6.6 +/- 1.9 mmol/day. Addition of TZ significantly reduced urinary calcium from 6.6 +/- 1.9 to 4.8 +/- 1.3 mmol/day, without changing alpha (0.613 +/- 0.081 to 0.584 +/- 0.070), serum calcium or 1,25-(OH)2D (154 +/- 48 to 154 +/- 38 pmol/l). Thus, estimated calcium balance (absorbed minus urinary calcium, increased marginally to +5.6 mmol/day on 1,25-(OH)2D alone (p = 0.028) and significantly to +6.8 mmol/day on 1,25-(OH)2D+TZ, from the control value of +4.0 mmol/day. Seven patients who were treated long-term with combined 1,25-(OH)2D and TZ for 11-29 months maintained their alpha (0.593 +/- 0.099) and a marginally more positive estimated calcium balance (+6.4 mmol/day, p = 0.025 from the control phase). Moreover, there was a stability of bone density of radial shaft, femoral neck, and lumbar spine.(ABSTRACT TRUNCATED AT 250 WORDS)

Disturbances of mineral and bone metabolism following gastric antrectomy in the rat

In antrectomized (B-I) and control rats, bone mineralization, the fractional intestinal absorption of calcium, magnesium and phosphorus, the balances of these minerals, their serum concentration and renal excretion, together with serum gastrin, calciotropic hormones (parathyroid hormone, calcitonin, 1,25-dihydroxyvitamin D), and osteocalcin were assessed four months after surgery. B-I evoked hypogastrinemia, but no changes in the serum concentrations of minerals and calciotropic hormones, or urinary cyclic AMP. The major significant changes brought about by B-I were: (1) a decrease in bone dry weight, specific density, bone ash calcium and magnesium content; (2) a decrease in the fractional absorption and urinary excretion of calcium and magnesium; (3) an increase in urinary hydroxyproline and serum osteocalcin in the presence of normal serum bone isoenzyme of alkaline phosphatase. It is concluded that in the rat (1) B-I over the long term decreases both bone mineral content and calcium and magnesium absorption, in the absence of any counterregulation; (2) B-I rats may have attained a new equilibrium which is characterized by decreased absorption and urinary excretion of calcium and magnesium, but maintenance of normocalcemia at the expense of bone; (3) the concomitant changes of serum bone markers are contradictory, which makes their interpretation and use in the present context difficult.

Is vitamin D 3 essential for mineral metabolism in the Damara mole-rat ( Cryptomys damarensis)?

The Damara mole-rat ( Cryptomys damarensis) leads a strictly subterranean existence in an extensive maze of plugged burrows and eats a strictly herbivorous diet. An obvious source of vitamin D 3 (D 3), an important hormone in mineral homeostasis, therefore is lacking in this mammal. The effects of orally ingested D 3 on mineral balance were investigated. In the normal D′ status group of mole-rats, the apparent fractional intestinal absorption of calcium (91.1%), magnesium (91.2%), and inorganic phosphorous (91.2%) was high and increased slightly, (calcium, 94.5%; magnesium, 93.2%; inorganic phosphorous, 92.9%) after D 3 administration. The amount of element absorbed was positively correlated with the amount ingested ( P < 0.001), suggesting that absorption occurs via a nonsaturable process. This might be an adaptation to the sparseness of natural food. The observed positive retention of calcium (94%), magnesium (85%), and inorganic phosphorous (99.9%) is attributed to their evergrowing teeth. These teeth are constantly worn down during digging and it is speculated that they represent a mineral “sink”, assisting in the maintenance of mineral homeostasis. It is also hypothesized that mole-rats have adapted to an environment devoid of D 3 and can attain sufficient calcium for their needs via nonvitamin D 3-dependent processes. Although mole-rats have the “machinery” to use D 3 and D 3 can affect mineral balance, this effect may be disadvantageous if invoked.

Intestinal absorption of calcium from yogurt in lactase-deficient subjects

Fractional intestinal absorption of calcium (FACa) was measured using radioactive calcium and 200 mg of calcium carrier provided either by yogurt or by CaCl2 in 7 lactase-deficient (L(-] and 7 normal (L(+] subjects. During the control period prior to yogurt consumption, mean calcium intake was 819 mg per day in L(-) and 931 mg per day in L(+) subjects (NS). In both groups of subjects yogurt increased FACa from 20.8 +/- 3.9% to 26.9 +/- 7.2% (P = 0.065) in L(+) subjects and from 20.2 +/- 5.6% to 23.5 +/- 6.4% (P = 0.050) in L(-) subjects. The significant increase in FACa observed in L(-) subjects indicates that yogurt, which is an autodigesting source of lactose, does not impair calcium absorption. FACa increase could reflect the lower dietary calcium intake in L(-) subjects when compared with L(+) subjects, due to avoidance of milk and non-fermented dairy products which could cause intestinal discomfort. It is concluded that yogurt is a well-tolerated and efficient source of calcium in subjects with lactase deficiency.

Hypercalciuria and altered intestinal calcium absorption occurring independently of vitamin D in incomplete distal renal tubular acidosis

Negative calcium balance and calcium nephrolithiasis are two sequelae of chronic metabolic acidosis. To establish the effects of acidosis on calcium and vitamin D metabolism, we have examined a group of nine patients with incomplete distal renal tubular acidosis. Patients were studied during a control phase and after eight months of potassium citrate treatment, 60 to 80 meq daily. Potassium citrate caused a significant decrease in urinary calcium. The fractional intestinal calcium absorption increased significantly, yet no change was observed in serum vitamin D levels. The estimated calcium balance increased significantly from −70.2 ± 63.8 to +66.7 ± 48.7 mg/d ( P < 0.01). Thus, potassium citrate treatment improved the estimated calcium balance by lowering urinary calcium while increasing the fractional intestinal calcium absorption. The original hypercalciuric state, its correction to normocalciuria, and the augmentation of intestinal calcium absorption seen in these patients are probably independent of vitamin D control since there was no change noted in serum 1,25-dihydroxyvitamin D levels.

Evidence that factors other than 1,25 dihydroxyvitamin D may play a role in augmenting intestinal calcium absorption in patients with primary hyperparathyroidism.

We examined 17 patients with primary hyperparathyroidism for their serum 1,25 dihydroxyvitamin D levels and for their fractional intestinal calcium absorption rates using a whole body counter and calcium-47. As controls, 10 normal volunteers were examined both before and after administration of 1 alpha-hydroxyvitamin D to increase serum 1,25 dihydroxyvitamin D. Values of serum 1,25 dihydroxyvitamin D were 71.6 +/- 37.6 pg/ml (mean +/- SD) in patients with primary hyperparathyroidism and 75.3 +/- 27.7 pg/ml (mean +/- SD) in normal volunteers after administration of 1 alpha-hydroxyvitamin D, while values of intestinal calcium absorption rate were 61.5 +/- 16.5% (mean +/- SD) in patients with primary hyperparathyroidism and 34.1 +/- 5.1% (mean +/- SD) in normal controls, respectively. There was a positive correlation between values of serum 1,25 dihydroxyvitamin D and intestinal calcium absorption in both groups. However, in patients with primary hyperparathyroidism, intestinal calcium absorption was more increased than that in normal volunteers when compared to their serum values of 1,25 dihydroxyvitamin D. This suggests that another factor than 1,25 dihydroxyvitamin D plays an important role in the intestinal calcium absorption in patients with primary hyperparathyroidism.

Postmenopausal osteoporosis as a manifestation of renal hypercalciuria with secondary hyperparathyroidism.

An apparently unique presentation of osteoporosis was encountered in eight postmenopausal women (mean age, 56.8 yr). They had renal hypercalciuria, since they had fasting hypercalciuria [0.17 +/- 0.04 (+/- SD) mg/100 ml glomerular filtrate (GF)] in the setting of normocalcemia and parathyroid stimulation (high serum immunoreactive PTH and/or urinary cAMP). Serum 1,25-dihydroxyvitamin D was not significantly different (28 +/- 7 vs. 34 +/- 2 pg/ml) from that in a nonelderly control group, but fractional intestinal calcium (Ca) absorption was significantly lower (0.382 +/- 0.123 vs. 0.49 +/- 0.06; P less than 0.025). Thus, the patients did not have compensatory intestinal hyperabsorption of Ca despite PTH excess. Treatment with hydrochlorothiazide (50 mg/day) produced a decline in fasting urinary Ca (to 0.07 +/- 0.02 mg/100 ml GF; P less than 0.01), serum PTH (from 39 +/- 19 to 21 +/- 1 microliters eq/ml; P less than 0.05), and urinary cAMP excretion (from 5.30 +/- 0.57 to 3.57 +/- 0.59 nmol/100 ml GF; P less than 0.0025). The results suggested that hyperparathyroidism was secondary. Histomorphometric analysis of bone showed reduced trabecular bone volume without mineralization defect, compatible with osteoporosis. Four of eight patients had high or high normal fractional resorption surfaces, fractional formation surfaces, and fractional osteoid volumes. That these abnormalities may reflect PTH-dependent osteoclastic resorption and bone turnover was supported by the reduction of these indices after correction of secondary hyperparathyroidism with hydrochlorothiazide therapy. The remaining four patients, however, had normal histomorphometric results. In summary, postmenopausal osteoporosis may occur sometimes with renal hypercalciuria and secondary hyperparathyroidism. The lack of compensatory intestinal hyperabsorption of Ca predisposes to negative Ca balance, and the hyperparathyroid state may be manifested by stimulated osteoclastic and osteoblastic activities.

A Lack of Unique Pathophysiologic Background for Nephrolithiasis of Primary Hyperparathyroidism

The metabolic picture of 32 patients with surgically proven primary hyperparathyroidism presenting with renal stones was compared with that of 37 patients without stones. Between stone-forming and nonstone-forming groups, there was no significant difference in serum 1,25-dihydroxyvitamin D [6.82 ± 2.62 vs. 6.22 ± 2.33 ng/dl (mean ± SD); P > 0.05], fractional (intestinal) calcium absorption (0.726 ± 0.141 vs. 0.690 ± 0.120), urinary clacium (299 ± 139 vs. 284 ± 144 mg/day), serum calcium, phosphorus, and parathyroid hormone, or bone density. Similarly, no differences were found between 29 patients presenting with stones alone and 9 presenting with bone disease alone with respect to the above measures. Moreover, urinary environment was typically supersaturated with respect to stoneforming salts regardless of the presence of stones. The results indicate that there is no unique pathophysiological background for the nephrolithiasis of primary hyperparathyroidism. (J Clin Endocrinol Metab 53: 536,1981) C nephrolithiasis is a frequent complication of primary hyperparathyroidism (1, 2). It is generally recognized that the formation of renal stones is pathogenetically related to the hyperparathyroid state and is not a coincidental occurrence. The most convincing evidence for the existence of this etiological relationship is provided by the favorable response to parathyroid surgery. After successful parathyroidectomy, the new stone formation often ceases, unless there has been a complication by a chronic urinary tract infection. The exact cause of the formation of renal stones in primary hyperparathyroidism has not been elucidated. It has been suggested that the biochemical and clinical picture of patients with primary hyperparathyroidism presenting with nephrolithiasis may be unique from that of patients without stones. Patients with stones were believed to have a longer duration of the disease process, a less severe hypercalcemia, and a smaller size of abnormal parathyroid tissue than patients who present with reduced bone density (3, 4). Hypercalciuria is frequently encountered in stone-forming patients with primary hyperparathyroidism (4,5). This disturbance has often been implicated as one of the causes of renal stone formation, since it is a frequent metabolic derangement associated Received February 9, 1981. Address requests for reprints to: Dr. Charles Y. C. Pak, Department of Internal Medicine, University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235. * This work was supported by USPHS Grants P50-AM20543, R01AM16061, and M01-RR-00633. with calcium nephrolithiasis (6). The hypercalciuria could have resulted from an excessive parathyroid hormone (PTH)-dependent bone resorption and/or an enhanced intestinal absorption of calcium ensuing from the PTH-dependent synthesis of 1,25-dihydroxyvitamin D [1,25-(OH)2D] (7, 8). There is some evidence that the hypercalciuria of intestinal origin may be more critical in the formation of renal stones (9). Thus, an apparent predilection for nephrolithiasis has been reported in the group of patients with primary hyperparathyroidism who possess a high circulating concentration of 1,25-(OH^D (9) and an increased intestinal absorption of calcium (9, 10). The current study was undertaken to determine if the stone-forming patients with primary hyperparathyroidism could be distinguished from their nonstone-forming counterpart on the basis of metabolic and biochemical presentations. It will be shown that the two groups of patients cannot be readily separated from the above criteria. Materials and Methods Sixty-nine patients with primary hyperparathyroidism participated in the study after informed written consent was obtained. These patients represented all of the patients with surgically proven primary hyperparathyroidism who were evaluated by us during the past 7 yr. Before surgery, they underwent an in-patient diagnostic evaluation according to the protocol previously described (5,8). The evaluation permitted an assessment not only of parathyroid function and vitamin D status,

A lack of unique pathophysiologic background for nephrolithiasis of primary hyperparathyroidism.

The metabolic picture of 32 patients with surgically proven primary hyperparathyroidism presenting with renal stones was compared with that of 37 patients without stones. Between stone-forming and nonstone-forming groups, there was no significant difference in serum 1,25-dihydroxyvitamin D [6.82 +/- 2.62 vs. 6.22 +/- 2.33 ng/dl (mean +/- SD); P greater than 0.05], fractional (intestinal) calcium absorption (0.726 +/- 0.141 vs. 0.690 +/- 0.120), urinary calcium (299 +/- 139 vs. 284 +/- 144 mg/day), serum calcium, phosphorus, and parathyroid hormone, or bone density. Similarly, no differences were found between 29 patients presenting with stones alone and 9 presenting with bone disease alone with respect to the above measures. Moreover, urinary environment was typically supersaturated with respect to stone-forming salts regardless of the presence of stones. The results indicate that there is no unique pathophysiological background for the nephrolithiasis of primary hyperparathyroidism.

Effect of growth hormone administration: reciprocal changes in serum 1 alpha,25-dihydroxyvitamin D and intestinal calcium absorption.

The mechanism by which GH stimulates intestinal calcium absorption was explored. In this study, seven children with idiopathic GH deficiency were studied before and during GH therapy while they were maintained on the same metabolic diet. After 5-14 months of GH administration, fractional intestinal calcium absorption increased from 0.364 +/- 0.114 to 0.449 +/- 0.159 (P less than 0.01), and serum 1,25-dihydroxyvitamin D decreased from 63.7 +/ 19.3 to 46.7 +/ 17.8 pg/ml (P less than 0.025). Serum immunoreactive parathyroid hormone, urinary cAmp, serum 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D did not change significantly. The data suggest that GH does not directly influence parathyroid hormone or vitamin D metabolism. The possibility that relative intestinal resistance to 1,25-dihydroxyvitamin D exists in patients with GH deficiency is considered.