Effect of growth hormone therapy on bone metabolism of growth hormone deficient children

The effects of human growth hormone (hGH) therapy on biochemical markers of bone metabolism were studied in 17 children (10 boys and 7 girls, aged 3.7-13.1 years old) with idiopathic GH deficiency, before and 1 and 6 months after GH therapy (0.5 0.7 IU/kg weekly SC). Serum levels of calcium, phosphate, alkaline phosphatase osteocalcin, parathyroid hormone, 1,25 dihydroxyvitamin D, insulin-like growth factor I (IGF-I) and renal phosphate per 100 ml glomerular filtrate (TPO4/GFR) were assessed. During therapy with hGH a significant decrease of serum calcium levels and increases of phosphate, osteocalcin, parathyroid hormone 1,25 dihydroxyvitamin D and IGF-I were observed. TPO4/GFR was also significantly increased. Growth response (increment in HV) was positively related with changes in alkaline phosphatase and IGF-I levels after 6 months of hGH therapy. There was also a significant positive correlation between increment in HV and increment in TPO4/GFR after 1 month of GH therapy, whereas no correlation between HV and changes in osteocalcin levels was found. CONCLUSION: GH treatment significantly influences mineral metabolism and the measurement of TPO4/ GFR after 1 month of GH therapy may serve as a useful predictor of growth response to hGH therapy in GH-deficient children.     

In vivo regulation of chromogranin A messenger ribonucleic acid in the parathyroid by 1,25-dihydroxyvitamin D: studies in normal rats and in chronic renal insufficiency

Chromogranin-A (CgA) and PTH are the two major secretory products of the parathyroid gland. In vitro, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] increases CgA, but decreases PTH messenger RNA (mRNA) levels. We investigated the physiological significance of the induced changes in CgA expression by examining the effects of 1,25-(OH)2D3 on parathyroid CgA mRNA levels in vivo. Normal rats were injected with 1,25-(OH)2D3 at 48 and 24 h before blood sampling and isolation of both parathyroid glands. Parathyroid total RNA was extracted and CgA and PTH mRNA quantified by Northern blot analysis. CgA mRNA levels increased 1.6-, 3.2- and 5.6-fold, whereas PTH mRNA levels decreased by 37, 63 and 97%, respectively, with 1,25-(OH)2D3 doses of 10, 50, and 250 pmol/100 g BW. Parathyroid gland CgA expression also was examined in rats with mild chronic renal insufficiency, induced by a 5/6 nephrectomy 5 weeks earlier. Chronic renal insufficiency rats, fed normal chow, had elevated serum urea, creatinine, and PTH levels and reduced 1,25-(OH)2D3 but normal serum levels of calcium and phosphate. PTH mRNA levels were elevated 4-fold and CgA mRNA levels were 50% lower in the uremic animals. This indicates that the regulation of CgA expression in normocalcemic rats occurs at physiological 1,25-(OH)2D3 concentrations. In summary, increases and decreases in serum 1,25-(OH)2D3 levels are associated with corresponding increases and decreases in CgA mRNA levels in the parathyroid glands of rats. Therefore, this study is the first to demonstrate the physiological relevance of the earlier in vitro observations.     

Effect of RenaGel, a non-absorbed, calcium- and aluminium-free phosphate binder, on serum phosphorus, calcium, and intact parathyroid hormone in end-stage renal disease patients

BACKGROUND: Control of dietary phosphate absorption in end-stage renal disease patients is essential to prevent the deleterious sequelae of phosphorus retention. Efficacy of currently available calcium- and aluminium-containing phosphate binders is constrained by the side-effects associated with the absorption of calcium and aluminium. The current study examined the efficacy of RenaGel, a calcium- and aluminium-free, polymeric phosphate binder, in end-stage renal disease patients. METHODS: Administration of calcium- or aluminium-containing phosphate binders ceased during a 2-week washout period. RenaGel, at starting doses of one, two, or three 500-mg capsules three times per day with meals, was administered for 8 weeks. RenaGel dose was titrated up 1 capsule per meal at the end of each 2-week period if necessary to achieve phosphorus control. A second 2-week washout period followed the end of RenaGel treatment. RESULTS: Mean serum phosphorus rose from a pre-washout level of 6.9 mg/dl (2.23 mmol/l) to 8.1 mg/dl (2.62 mmol/l) at the end of the initial 2-week washout. With RenaGel treatment, serum phosphorus declined and returned to pre-washout levels after 4 weeks. Serum phosphorus reached a nadir of 6.5 mg/dl (2.10 mmol/l) after 7 weeks of RenaGel treatment. Serum phosphorus rose to 8.2 mg/dl (2.65 mmol/l) 2 weeks after cessation of RenaGel treatment. As anticipated, calcium declined during the initial washout period when calcium-based phosphate binders were stopped for the majority of patients. The rise in serum phosphorus and decline in serum calcium during washout resulted in an increase in median intact parathyroid hormone (iPTH) levels from 292 pg/ml to 395 pg/ml. iPTH fell to 283 pg/ml after 6 weeks of RenaGel treatment despite a persistently lower serum calcium. RenaGel treatment also reduced serum total and LDL cholesterol by 25 mg/dl (0.65 mmol/l) and 23 mg/dl (0.59 mmol/l) respectively. CONCLUSIONS: RenaGel appears to be an effective phosphate binder free of calcium and aluminium. Phosphorus control with two to four RenaGel capsules per meal appears to result in comparable phosphorus lowering seen with calcium- or aluminium-based phosphate binders. RenaGel may offer an alternative for the control of phosphorus retention in end-stage renal disease patients.     

Reduced expression of the renal calcium-sensing receptor in rats with experimental chronic renal insufficiency

Chronic renal insufficiency is associated with elevated serum parathyroid hormone (PTH) levels (2 degrees HPT), deficiency of 1,25-dihydroxyvitamin D (1,25(OH)2D), and hypocalciuria. In chronic renal insufficiency, the 2 degrees HPT may result from reduced expression of the parathyroid gland extracellular Ca(2+)-sensing receptor (CaSR). Since the CaSR was cloned from rat and human kidney, this study examined in rats whether expression of the renal CaSR is altered in experimental chronic renal insufficiency. Four weeks after chronic renal insufficiency was induced by 5/6 nephrectomy (Nx) in Sprague Dawley rats, the serum creatinine concentration was 0.96+/-0.06 mg/dl compared with 0.35+/-0.02 mg/dl in sham-operated animals (P < 0.05). The serum total Ca2+ and phosphorus concentrations were not different. In the Nx group, the serum concentration of amino-PTH was higher (65+/-8 pg/ml), and the concentration of 1,25(OH)2D was significantly lower (47+/-5 pg/ml) compared with 45+/-5 pg/ml and 61+/-4 pg/ml (P = 0.05) in the sham group, respectively. In a subset of rats studied, the Nx group was hypocalciuric (1.4+/-0.5 mg/kg per d) compared with the sham group (3.7+/-0.5 mg/kg per d) (P < 0.05). In the Nx rats, CaSR mRNA expression and CaSR protein levels were found to be reduced by 35 and 38%, respectively, than those observed in controls. These results suggest that reduced renal CaSR expression in chronic renal insufficiency may play a role in disordered mineral ion homeostasis, including hypocalciuria.     

Influence of metabolic acidosis on serum 1,25(OH)2D3 levels in chronic renal failure

Metabolic acidosis has been shown to alter vitamin D metabolism. There is also evidence that calcium may modulate 1,25(OH)2D3 by a parathyroid hormone (PTH)-independent mechanism. To investigate the effect of rapid correction of chronic metabolic acidosis on serum 1,25(OH)2D3 levels by free calcium clamp in chronic renal failure, 20 patients with mild to moderate metabolic acidosis (mean pH 7.31 +/- 0.04) and secondary hyperparathyroidism (mean intact PTH 156.47 +/- 84.20 ng/l) were enrolled in this study. None had yet received any dialysis therapy. Metabolic acidosis was corrected by continuous bicarbonate infusion for 3-4 h until plasma pH was around 7.4, while plasma ionized calcium was held at the preinfusion level by calcium solution infusion during the entire procedure. The plasma pH, bicarbonate, total CO2, sodium, and serum total calcium levels were significantly increased while serum concentrations of alkaline phosphatase and albumin were significantly decreased after bicarbonate infusion. The plasma ionized calcium, potassium, serum magnesium, inorganic phosphorus, and 25(OH)D levels showed no significant change before and after bicarbonate infusion. The serum 1,25(OH)2D3 levels were significantly increased (38.66 +/- 11.77 vs. 47.04 +/- 16.56 pmol/l, p < 0.05) after correction of metabolic acidosis. These results demonstrate that rapid correction of metabolic acidosis raises serum 1,25(OH)2D3 levels in vitamin D-deficient chronic renal failure patients, and may underline the importance of maintaining normal acid-base homeostasis in the presence of secondary hyperparathyroidism in chronic renal failure.     

The effect of 1-alpha-hydroxycholecalciferol on the renal handling of phosphate in parathyroidectomized man

In a previous investigation by our group it was suggested that the stimulating effect of 1-alpha-hydroxycholecalciferol (1-alpha-OH-D3) on the tubular reabsorption of phosphate is mediated via the parallel suppression of the parathyroid hormone (PTH). A direct effect of 1-alpha-OH-D3 on the renal tubule could however not be completely excluded. Therefore, the effect of 1-alpha-OH-D3 was studied in 5 totally parathyroidectomized patients, in whom concomitant suppression of PTH would not occur. TmP/GFR, i.e. the ratio between the maximal tubular reabsorption of phosphate (TmP) and the glomerular filtration rate (GFR), was used as an indicator of the renal handling of phosphate. Estimation of TmP/GFR was performed 1) when the patients were vitamin D depleted and hypocalcemic, and 2) after 14-27 days of treatment with 1-alpha-OH-D3 to obtain stable normocalcemia. In patients with absent parathyroid function, no effect of 1-alpha-OH-D3 on TmP/GFR could be demonstrated. It is therefore concluded that 1-alpha-OH-D3 exhbits no antiphosphaturic effect in the absence of PTH and that the previously demonstrated antiphosphaturic effect of 1-alpha-OH-D3 in man is mediated via a concomitant suppression of PTH.     

Normal linear growth in hypophosphataemic bone disease

A case of hypophosphataemic bone diseases is described. Despite prescribed phosphate (PO4) supplement and 1.25 dihydroxycholecalciferol therapy, serum PO4 levels have remained low with associated diminished theoretical renal threshold for phosphate (TmPO/GFR) over a seven and a half year follow up period. Linear growth, however, has been normal.     

Impaired vitamin D metabolism and response in spontaneously diabetic GK rats

Several studies of diabetes mellitus patients have demonstrated abnormalities in calcium, phosphate and vitamin D metabolism. In an earlier study, the authors reported impaired renal processing of phosphate in spontaneously diabetic GK rats, an animal model of type II diabetes mellitus. In the present study, which represents an extension of the earlier study, vitamin D metabolism and response are examined in 20-week-old GK rats. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] was found to be lower in GK rats than in Wistar rats. After intraperitoneal administration of 0.5 micrograms/kg 1,25-(OH)2D, serum calcium increased in GK rats, but not in Wistar rats, while serum phosphate remained unchanged in GK rats, but increased in Wistar rats. Although serum 1,25-(OH)2D rose abruptly in 3 h and decreased thereafter in both GK and Wistar rats, the decrease in serum 1,25-(OH)2D at 6 h was more marked in GK rats than in Wistar rats. Serum 24,25-dihydroxyvitamin D was consistently higher in GK rats than in Wistar rats. Northern blotting and dot blotting with use of a cDNA probe for the 24-hydroxylase gene showed an increased expression of the gene in the kidney of GK rats. These results demonstrate impaired vitamin D metabolism in GK rats. Increased activity of 24-hydroxylase, in addition to impaired phosphate metabolism, may play a role in impaired vitamin D metabolism in GK rats.     

Abnormalities of calcium, phosphorous and vitamin D metabolism with proximal renal tubular dysfunction in subjects environmentally exposed to cadmium

Calcium, phosphorus and vitamin D metabolism were examined in 21 male and 13 female subjects with renal tubular dysfunction in the cadmium-polluted Jinzu River basin in Toyama prefecture, Japan. Multiple proximal renal tubular dysfunction was detected in all subjects showing increased FE beta 2-m and FFua, generalized aminoaciduria and renal glucosuria. Reduced ability of tubular reabsorption of phosphate resulted in hypophosphatemia in 31% of the women. Despite decreased tubular reabsorption of calcium, the level of serum calcium remained normal in all subjects. Serum 1,25-dihydroxyvitamin-D [1,25(OH)2D], which is produced in the proximal tubules through 1 alpha-hydroxylation from 25-hydroxyvitamin-D [25OHD], was normal or increased to more than 60pg/ml. The serum level of 1,25(OH)2D was inversely related to creatinine clearance in both the men (p < 0.05) and women (p < 0.01). Serum iPTH was slightly increased to more than 0.9 mg/ml, whereas the levels of other hormones, including 25OHD, calcitonin, thyroxine (T4) and triiodothyronine (T3) were normal. The serum alkaline phosphatase activity and serum osteocalcin concentration were significantly increased compared to those of controls in both sexes. Bone loss detected by the measurement of bone density was prominent in female subjects. These results support the hypothesis that the serum phosphate concentration is more important than the serum concentration of 1,25(OH)2D for abnormalities of bone metabolism in cadmium-induced renal tubular dysfunction.     

Pharmacotherapy in outpatient psychiatric practice

Calcium metabolism was studied in 47 patients with borderline or lepromatous leprosy. Total and ionized calcium, phosphorus, creatinine, total alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D], and 1,25-dihydroxy vitamin D [1,25(OH)2D] were measured in serum; calcium and total hydroxyproline were determined in urine. Total subperiosteal diameter and medullar cavity diameter were measured on an X-ray of the hand of all patients. Average values were within normal ranges for all of the biochemical determinations. Total serum calcium was moderately below the normal range in eight patients but ionized calcium levels were within the normal ranges in all of the patients. Four patients, all of them with lepromatous leprosy, had levels of 1,25(OH)2D higher than normal but none of them was hypercalcemic and PTH levels were within normal range. Although all values were within the normal ranges, lepromatous leprosy patients had lower total calcium, higher alkaline phosphatase, and higher urinary hydroxyproline than borderline leprosy patients (9.1 +/- 0.4 vs 9.4 +/- 0.3 mg%, p < 0.001; 10.3 +/- 2.9 vs 7.4 +/- 2.3 King-Armstrong units, p < 0.02 and 27.2 +/- 12 vs 19.4 +/- 5.6 mg/24 hr, p < 0.02, respectively). No differences were found between patients and controls in the average micrometric measurements of the second metacarpal bone but significant osteopenia was found in 19% of the patients. The main finding of the present study in a representative sample of leprosy patients is that the average total serum calcium was in the lowest limit of the normal range, but the ionized serum calcium was in the middle of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium and vitamin D status of pregnant teenagers in Maiduguri, Nigeria

This study investigates parameters related to calcium and bone metabolism by determining the concentrations of total calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, and phosphorous in young pregnant women. The patient population was 30 pregnant Nigerian teenage women grouped by trimester (10 per group), 10 women immediately following delivery, and 21 healthy age-matched controls. On the basis of serum prealbumin levels, the general nutrition of the pregnant women was found to be significantly below that of the more privileged and better-educated nonpregnant controls. The mean total calcium concentration in sera of the third-trimester women was 8.83 mg/dL, which was significantly below that of the controls (9.77 mg/dL) and the first-trimester group (9.30 mg/dL). Despite the 10% to 15% decline in the serum level of total calcium during pregnancy, the parathyroid hormone level decreased markedly from 0.60 to 0.61 ng/mL in the first and second trimesters to 0.41 ng/mL in the third trimester. Serum vitamin D and 1,25-dihydroxyvitamin D levels in the second and third trimesters were within the normal range. These data indicate that toward the end of gestation, pregnant teenagers in northern Nigeria appear to become calcium deficient and do not exhibit the expected increase in serum parathyroid hormone levels normally seen in pregnant women.     

The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis

BACKGROUND: Calcipotriol is an effective treatment of chronic plaque psoriasis. We have previously demonstrated that it has a small effect on systemic calcium homeostasis even at recommended doses. OBJECTIVE: We attempted to determine the mechanism of the effect of calcipotriol on systemic calcium homeostasis so we could assess the possible consequences of long-term use. METHODS: Sixteen patients with extensive chronic plaque psoriasis were hospitalized and treated with high-dose topical calcipotriol. Up to 360 gm of calcipotriol (50 micrograms/gm) ointment was applied per week for 2 weeks under controlled conditions. RESULTS: There was a dose-dependent rise in intestinal absorption of calcium. No effect on bone turnover was demonstrated over this short period. Five patients became hypercalcemic, and there was a dose-dependent rise in serum total adjusted calcium, serum ionized calcium, serum phosphate, urine calcium, and urine phosphate. There was a dose-dependent fall in serum parathyroid hormone and serum 1,25 dihydroxyvitamin D3. CONCLUSION: Calcipotriol exerts its effects on systemic calcium homeostasis by increasing intestinal absorption of calcium and probably phosphate. This results in suppression of parathyroid hormone and 1,25 dihydroxyvitamin D3.     

In vivo parathyroid hormone stimulates in vitro bone resorption by bovine monocytes

Cells of the monocyte-macrophage lineage have been thought to play a role in bone resorption. We examined the effects of in vivo administration of parathyroid hormone and 1,25-dihydroxyvitamin D3 on the ability of monocytes to degrade bone in vitro. Administration of parathyroid hormone for 4 d resulted in sustained hypercalcemia and a transient 1-d increase in plasma 1,25-dihydroxyvitamin D3. Parathyroid hormone significantly stimulated bone degradation by monocytes 2.6 times more than that of pretreatment controls. Parathyroid hormone treatment significantly enhanced (threefold) release of superoxide anion by monocytes stimulated with phorbol 12-myristate 13-acetate and increased migration of monocytes to bone particles in vitro. Continuous 7-d infusion of 1,25-dihydroxyvitamin D3 (50 micrograms/d) elevated plasma 1,25-dihydroxyvitamin D3 until infusions were discontinued. Increased 1,25-dihydroxyvitamin D3 was associated with hypercalcemia, which continued for several days postinfusion. In vivo administration of 1,25-dihydroxyvitamin D3 did not affect in vitro ability of monocytes to degrade bone. We concluded that in vivo administration of parathyroid hormone enhanced in vitro responsiveness of isolated monocytes in a manner consistent with a role for monocytes in bone remodeling. Furthermore, these data suggested that circulating monocytes could be a useful experimental model for further studies on parathyroid hormone responsiveness and bone resorption for the cow with milk fever.     

Lack of effect of hypocalcemia on renal phosphate handling

A possible effect of decreased plasma ionized calcium concentration on renal phosphate handling was investigated in dogs with control of parathyroid hormone. Intrarenal artery infusion of either EDTA or sodium citrate decreased ionized calcium concentration 25 per cent in renal vein blood but had no significant effect on fractional phosphate excretion. Similarly, intravenous infusion of chelators had no significant effect on fractional phosphate excretion. It is concluded that acute decreases in ionized calcium have no significant effect on the renal handling of phosphate.     

Elevation of serum phosphate affects parathyroid hormone levels in only 50% of hemodialysis patients, which is unrelated to changes in serum calcium

Hyperphosphatemia is said to cause hyperparathyroidism either by depressing the plasma levels of ionized calcium and/or by affecting serum 1,25(OH)2 vitamin D3 levels. Direct evidence that hyperphosphatemia contributes to hyperparathyroidism in hemodialysis patients is unclear because previous published data are with older parathyroid hormone (PTH) assays. Phosphate was added to the dialysate of 15 patients for 12 wk whose predialysis serum phosphates were between 1.5 and 1.9 mM (4.7 to 5.9 mg/dL) in order to further increase their serum phosphate by 0.75 mM (2.4 mg/dL) without adjustments in other medications. No patient was on vitamin D therapy. In half of the patients, PTH levels remained unchanged (nonresponders; 214 +/- 64 versus 219 +/- 60 ng/L), whereas in the other patients, PTH rose from 204 +/- 53 to 338 +/- 60 ng/L (P < 0.05; responders). The degree of induced hyperphosphatemia was virtually identical in both groups, 1.7 mM increasing to 2.4 mM. Ionized calcium was unchanged in both groups after phosphate. Plasma 1,25(OH)2 vitamin D3 levels were low to start with and remained low throughout. Nonresponders had been on dialysis twice as long as responders and had consumed over seven times more aluminum salts. Nonresponders had higher postdeferoxamine increments in plasma aluminum (3,588 +/- 1,466 versus 603 +/- 390; P < 0.05), although neither these amounts nor plasma levels were in the toxic range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictors of short-term changes in serum intact parathyroid hormone levels in hemodialysis patients: role of phosphorus, calcium, and gender

Several factors have been identified as important in the pathogenesis of secondary hyperparathyroidism in end-stage renal disease, including serum calcium, phosphorus, and calcitriol. To examine the independent effects of key factors, we prospectively studied 52 new hemodialysis patients with mild secondary hyperparathyroidism (PTH, 110-670 pg/mL) treated with a standardized regimen of calcium supplements, phosphorus binders, and no vitamin D derivatives. We used simple and multivariable linear regression analysis to examine the relationship between changes in PTH (deltaPTH) levels observed over a 4-week period and various biochemical and demographic variables. By simple linear regression we found that changes in serum phosphorus (r2 = 0.31; beta = 41.6; P = 0.0001), initial phosphorus concentration (r2 = 0.15; beta = 33.4; P = 0.005), initial PTH level (r2 = 0.29; beta = 0.58; P = 0.0001), changes in serum calcium (r2 = 0.12; beta = -74.0; P = 0.01), and gender (r2 = 0.07; beta = 76.1; P = 0.05) were significantly associated with deltaPTH. However, upon multivariable regression analysis, only the changes in phosphorus (partial r2 = 0.31; beta = 37.0; P = 0.0001), initial PTH level (partial r2 = 0.23; beta = 0.50; P = 0.0001), and gender (partial r2 = 0.05; beta = 63.1; P = 0.02) remained significantly associated with deltaPTH. Neither the serum concentration of 1,25-dihydroxyvitamin D3, bicarbonate, aluminum, or albumin nor changes in the serum bicarbonate concentration, the presence of diabetes, KT/V, or age were significantly associated with the deltaPTH. Our findings are consistent with independent effects of phosphorus and gender on parathyroid gland function in patients with dialysis-dependent renal failure through mechanisms that remain to be defined.     

Hypophosphatemia and the development of rickets in osteopetrotic (op/op) mice

Our previous work has shown that op/op mice hyperabsorb dietary calcium in the vitamin D-deficient state and shunt that calcium into bone. Under these conditions, the op/op mice are hypocalcemic. The purpose of this study was to examine calcium metabolism and bone mineralization in vitamin D-deficient op/op mice. First, the op/op mice and their normal littermates were placed on a vitamin D-deficient, low phosphorus diet to limit bone mineralization. Under these circumstances, op/op mice survived, even when calcium was also removed from the diet. If the diet contained phosphate, op/op mice died from hypocalcemic tetany when calcium was also removed from the diet. Furthermore, serum calcium levels became similar to wild type in the op/op mice administered the vitamin D-deficient, low phosphorus diet, and op/op mice were able to increase serum calcium in response to 1,25-dihydroxyvitamin D3. The op/op mice developed rickets when their serum phosphorus level was too low to support bone mineralization. The op/op mice became hypophosphatemic on regimens in which normal mice were able to maintain normal serum phosphorus levels. It appears that the op/op mouse simply requires a higher dietary calcium and phosphorus level to prevent rickets and hypocalcemic tetany since the bone is not available as a source of these minerals. However, the ability of the op/op mouse to mineralize bone at low serum calcium and phosphorus levels remains unexplained.     

Bone metabolism and phosphorus metabolism in patients with prostate cancer: paracrine and endocrine effects produced by prostate neoplasm

We examined whether paracrine factors produced by prostate cancer cells can modulate bone metabolism in proportion to the volume of cancer cells in bone metastasis. Endocrine factors produced by prostate cancer cells affect both phosphate and 1,25-dihydroxyvitamin D metabolisms. Levels of urine pyridinoline (U-Pyr) excretion and serum carboxy-terminal propeptide of type 1 procollagen (P1CP) in patients with bone metastasis were significantly higher than those in patients without bone metastasis (P < 0.05). In patients with bone metastasis (n = 17), serum prostate-specific antigen (PSA) levels were significantly correlated with the levels of U-Pyr and urine deoxypyridinoline (U-dPyr) excretion, serum cross-linked carboxyterminal telopeptide of type 1 collagen (1CTP), and P1CP levels (p < 0.05). However, serum PSA levels were not correlated with U-Pyr, U-dPyr excretions, serum 1CTP and P1CP levels in patients without bone metastasis. Therefore, prostate cancer cells appear to have some paracrine effects on bone cells. In controls (n = 15), serum 1,25-dihydroxyvitamin D levels (1,25-(OH)2D) were inversely correlated with serum phosphorus levels (P < 0.01). In prostate cancer patients with bone metastasis, the ability to regulate the serum 1,25-(OH)2D levels in response to serum phosphorus levels is lost. These results suggest that endocrine factors produced by prostate cancer cells disturb the regulation of serum 1,25-(OH)2D in response to serum phosphorus levels.     

Sustained reduction in urinary calcium during long-term treatment with slow release neutral potassium phosphate in absorptive hypercalciuria

PURPOSE: We tested whether UroPhos-K, a new slow release neutral form of potassium phosphate (155 mg. phosphate, 8 mEq. potassium per tablet) in a dose of 4 tablets twice daily would produce a sustained hypocalciuric response and maintain bone mass in patients with absorptive hypercalciuria, a major cause of nephrolithiasis characterized by excessive intestinal calcium absorption accompanied in some patients by excessive bone loss. MATERIALS AND METHODS: A total of 25 patients with absorptive hypercalciuria were studied in a 4-year, prospective, open trial with UroPhos-K at yearly intervals during a 4-day inpatient physiological study with a constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate daily. RESULTS: Treatment with UroPhos-K caused a sustained, marked reduction in urinary calcium (264 to 181 mg. daily). Fractional 47calcium absorption decreased modestly (74.0 to 64.6%) commensurate with a reduction in serum 1,25-dihydroxyvitamin D (42 to 34 pg./ml.). Intact parathyroid hormone increased within the normal range (30 to 42 pg./ml.). Bone mineral density was stable at the lumbar spine, femoral neck and distal third of the radius. CONCLUSIONS: UroPhos-K may provide a long-term alternative for hypercalciuric patients in whom thiazide therapy fails.