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J C Philcox

Publications and source records attributed to J C Philcox.

At least 37 records · Page 2Linked to original sources

Metallothionein induction in cultured rat hepatocytes by arthritic rat serum, activated macrophages, interleukin-6, interleukin-11 and leukaemia inhibitory factor.

Potential mediators of hepatic metallothionein (MT) synthesis in adjuvant-induced arthritis were investigated in cultured rat hepatocytes. Sera from arthritic rats (14 d post-adjuvant treatment) in the presence of Zn (50 mumol/L)+dexamethasone (Dex; 1 mumol/L) increased metallothionein (MT) accumulation by 34% above that obtained with control rat serum with Zn+Dex. Endogenous IL-6 activity in serum from arthritic rats was 93 +/- 49 U/mL and was undetectable in control rat serum. The activities of TNF, IL-1 and corticosterone concentrations were the same in control and arthritic rats. The accumulation of MT in hepatocytes in the presence of Zn (10 mumol/L)+Dex (1 mumol/L) was enhanced 29% and 49% by media from lipopolysaccharide (LPS)-stimulated peritoneal macrophage (PMM) and Kupffer cell cultures (KCM), respectively. The response with PMM and KCM was quantitatively the same as that with interleukin-6 (IL-6). Analysis of PMM and KCM showed activities of 1,000-10,000 U/mL for IL-6, 100-1000 U/mL for TNF and < 10,000 U/mL for IL-1, the latter detected only in PMM. LPS alone enhanced the accumulation of MT above Zn+Dex in a dose dependent manner. A significant LPS response was obtained at 5 mg/L with a maximal stimulation above Zn+Dex of 38% at 10 mg/L. This direct stimulation of MT by LPS was not part of the response observed with PMM and KCM where the final LPS concentration in culture was only 0.1 mg/L. Other cytokines capable of synergy with Zn+Dex on MT synthesis were investigated. Interleukin-11 (IL-11) increased the Zn+Dex induction in a dose dependent manner with maximal stimulation at 100 U/mL of 40%. A small stimulation of 12% above Zn+Dex was obtained with leukaemia inhibitory factor (LIF) at concentrations greater than 100 U/mL. No enhancement of the Zn+Dex response was obtained with interleukin-3 (1000 U/mL), interleukin-4 (10 micrograms/L), platelet activating factor (5 nmol/L) or granulocyte-colony stimulating factor (5 micrograms/L). Neither IL-11 nor LIF enhanced the response obtained with Zn+Dex+IL-6. The results demonstrate that mediators present in arthritic rat serum and in LPS-stimulated PMM and KCM cause a quantitatively similar response on MT accumulation as IL-6. IL-11 and to a lesser extent LIF, are also potential mediators of MT synthesis in inflammation.

Animals↗

Measurement of zinc in hepatocytes by using a fluorescent probe, zinquin: relationship to metallothionein and intracellular zinc.

Zinquin [ethyl (2-methyl-8-p-toluenesulphonamido-6-quinolyloxy)acetate], a new intracellular zinc fluorophore, was used to reveal and to measure Zn in cultured rat hepatocytes before and after metallothionein (MT) induction. Hepatocytes labelled with an intense extranuclear fluorescence. Culture with combinations of Zn, dexamethasone and interleukin-6, increased intracellular MT by 24-fold, Zn 3-fold, and Zinquin fluorescence by approx. 2-fold above control values. Zinquin fluorescence correlated in descending order with the total cellular Zn (r = 0.747), exchangeable Zn (r = 0.735), soluble cytosolic Zn (r = 0.669) and MT (r = 0.666). When Zinquin was incubated with a cytosolic fraction of liver proteins before Sephadex G-75 column chromatography, it fluoresced with free, MT-incorporated and protein-bound Zn. Although only a slight attenuation of fluorescence was seen with high-molecular-mass protein-bound Zn, MT was degraded by 60% in the presence of Zinquin. The undegraded Zn-MT fluoresced at about 20% of the expected intensity. Although Zinquin fluoresces with all cytosolic Zn, caution is required when comparisons are made between samples with different concentrations of MT. This limitation was demonstrated by staining liver slices from adjuvant-treated rats where MT was increased 24-fold, intracellular Zn by 77%, but Zinquin fluorescence by only 19% above controls. Nevertheless, Zinquin should prove to be a useful tool for studying the distribution of Zn in living cells.

Animals↗

Wasting in adjuvant-induced arthritis and its relationship to plasma zinc, copper and liver metallothionein.

The appearance of joint inflammation (JI) 14 days after the injection of adjuvant (AJ) in the tail of rats is associated with a cachectic syndrome which is characterised by marked weight loss (WL). The degree of weight loss was examined in relation to the extent of change in other markers of inflammation including increased plasma copper (pCu), decreased plasma zinc (pZn) and increased hepatic metallothionein (hMT). At 14 days post-AJ injection, arthritic rats showed the following changes, relative to the controls: body weight, 12% decrease, pZn, 50% decrease; pCu, 90% increase and hMT, 11-fold increase (all p < 0.001). Significant relationships were observed between JI, WL, pZn and hMT. The following coefficients of determination (r2) were observed; JI and WL, -0.530, JI and pZn, -0.485; JI and hMT, 0.286; WL and hMT, -0.510 (all p < 0.007). There was a strong relationship between the decreased pZn and increased hMT; r2 = 0.456 (p < 0.001). While increased pCu was clearly associated with AJ-arthritis in these rats, there was no quantitative relationship between the extent of change in pCu and the other parameters measured (r2 all < 0.01). The highest correlation observed was between pZn and WL (r2 = 0.637, p < 0.001). While the initial depression of pZn may be the result of increased hepatic hMT levels, longer term reductions in pZn levels are linked to systemic inflammation, the degree of arthritis and associated weight loss.

Animals↗

Metallothionein and zinc homeostasis during tumor progression. Effect of methotrexate treatment.

Zinc homeostasis was studied during the induction, growth, and methotrexate (MTX) treatment of Dark Agouti rat mammary adenocarcinomas (DAMA). A progressive fall in plasma Zn concentration (pZn), significant at a tumor burden of less than 1% body weight (bw), was sustained during tumor enlargement to give a 54% reduction in pZn at 16.3% bw (n = 6/group). The hypozincemia was attributed to the increasing Zn demand for tumor growth. Zn content of the 16.3% bw tumors equaled that of muscle (normally 60% of total body Zn). Tumor metallothionein (tMT) was sufficient to bind < 3% of total tumor Zn, and hepatic MT (hMT) remained at basal concentrations during early tumor growth, doubling only in the presence of significant necrosis in large tumors. Methotrexate (MTX, 0.5 mg/Kg im x 2 d) at respective tumor burdens of 5 and 10% bw (n = 9, 10/group) gave 2 therapeutic effects, dependent on tumor size: 1.5% bw tumors in 7 rats remained close to their original size until experiment end when pZn, hMT, and tMT were typical of 5% bw untreated tumors. 2. Tumors in 5 rats given MTX at 10% bw had marked subcapsular necrosis and regression to a size similar to those in group 1; pZn returned toward normal, whereas hMT was 6 times its 5% bw counterpart. Host weight loss was significantly reduced, as were tumor-associated changes in plasma glucose and calcium. In summary, neither tMT nor hMT appears to play a role in the hypozincemia that follows DAMA Zn sequestration and growth. Critically timed MTX can result in tumor regression and return of plasma Zn, Ca, and glucose toward normal. This is associated with an increase in hMT and reduction in host weight loss, suggesting a flow of Zn from the resorbing tumor to the host, enabling the synthesis of hMT and retention of host structural proteins.

Adenocarcinoma↗

Metabolic consequences of methotrexate therapy in tumour-bearing rats.

The metabolic response of the tumour-bearing host to methotrexate (MTX) therapy was investigated with particular attention to effects resulting from MTX-induced anorexia. Biochemical changes in female Dark Agouti rats bearing mammary adenocarcinomas and treated with MTX (0.5 mg/kg, 2 i.m. injections, 24 h apart) were compared with untreated (CON) tumour-bearing rats, and tumour-bearing rats pair-fed (PF) to the MTX group. MTX treatment halted progression of the tumour (tumour 6% of bodyweight) while the tumour burden doubled in the CON and PF groups. A number of biochemical and haematological changes were specific to MTX treatment and did not result from decreased food intake. MTX treatment was associated with significantly decreased plasma calcium, bilirubin, alkaline phosphatase, aspartate aminotransferase and the total white cell count. Decreases in plasma albumin and total protein concentrations were observed in both MTX and PF rats. Other parameters commonly used to assess renal and liver function were not significantly affected by MTX. MTX reversed the hypoglycaemia, hyperketonaemia and hypertriglyceridaemia induced by tumour-bearing. In contrast, PF rats had an even more pronounced hypoglycaemia and hyperketonaemia than the CON rats. Measurement of glucose uptake in vivo with 2-deoxy[U-14C]-glucose showed that MTX treatment halved the glucose requirement of the tumour (8.2% of bodyweight compared to 12.2% in the control). It is concluded that the potentially adverse effects of MTX treatment on host metabolism are outweighed by the beneficial effects of a reduced metabolic demand resulting from inhibition of tumour progression.

Adenocarcinoma↗

Metallothionein induction in freshly isolated rat hepatocytes.

The control of metallothionein (MT) synthesis was investigated in freshly prepared rat hepatocytes in experiments of short-term duration. Viability and metabolic function were maintained in incubations of 6-h duration. MT synthesis was measurable in hepatocytes from fed rats at Zn concentrations down to 1 microM. Zn and dexamethasone induced concentration-dependent increases in the synthesis of MT with maximal increases above the 5-h control of 3.2- and 2.5-fold, respectively. Zn induction of MT was first measurable at 2 h and was inhibited by actinomycin C. Although initial (0 h) MT concentrations in hepatocytes from fasted rats were double those from fed rats, after 6-h incubation in the presence of 50 microM Zn, the fasted rat hepatocytes showed only half the MT concentrations of the fed rat hepatocytes. Glucagon and interleukin-6 (IL-6) were less effective inducers and increased MT synthesis by 28 and 17%, respectively. IL-6 (100 U/mL) was found to have an additive effect on MT synthesis above that of Zn alone (1-50 microM) or Zn plus dexamethasone (1 microM). A supernatant from LPS-stimulated macrophages increased MT synthesis by 40%. The basal MT synthesis was not increased by either tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1). All incubations were carried out in the presence of RPMI 1640 medium with Hepes (20 mM), bicarbonate (24 mM), and fatty acid-free albumin (FAFA; 0.5% w/v). MT synthesis was also seen using Krebs bicarbonate buffer with glucose (10 mM), Hepes (20 mM), and FAFA (0.5% w/v), and although the level of MT synthesis was less than in RPMI, the increases in concentrations of MT at 5 h were 225, 139, 36 and 20% for Zn, dexamethasone, glucagon, and control, respectively. It is concluded that MT synthesis occurs in freshly prepared hepatocytes and that these cells are responsive to some of the established inducers of MT. This system enables the study of MT synthesis in individual rats in various metabolic and pathological states.

Animals↗

Corticosterone enhances the zinc and interleukin-6-mediated induction of metallothionein in cultured rat hepatocytes.

The regulation of metallothionein induction in cultured rat hepatocytes was investigated with Zn, hormones, cytokines and either the synthetic glucocorticoid, dexamethasone, or the endogenous rat glucocorticoid, corticosterone. A concentration-dependent increase was seen with Zn (two- to fivefold increase in 24 h, Zn 10-50 mumol/L). Dexamethasone at 1 mumol/L increased metallothionein synthesis by fourfold that of the controls. Maximal metallothionein concentrations of 17-fold the control value were seen with 50 mumol/L Zn and 1 mumol/L dexamethasone. Interleukin-6 (1 x 10(5) U/L) alone did not induce metallothionein but increased it 35-65% with Zn+dexamethasone. Like dexamethasone, corticosterone had a dose dependent effect on metallothionein and synergy with Zn and Zn+interleukin-6. Dexamethasone was approximately 100 times more potent than corticosterone at 10-100 mumol/L. Physiological concentrations of corticosterone (1 mumol/L) when added alone, with Zn (10 mumol/L), and with Zn+interleukin-6 resulted in inductions of 2.2, 5.0 and 7.4-fold above the control cultures. Glucagon (1 mumol/L) had no independent effect but increased metallothionein by 31% and 33% with Zn(10 mumol/L)+dexamethasone (1 mumol/L) and Zn-dexamethasone+interleukin-6, respectively. There was no accumulation of metallothionein with interleukin-1 beta, tumor necrosis factor alpha or interferon gamma (1 x 10(5) U/L) alone, but interleukin-1 beta and tumor necrosis factor alpha enhanced the response obtained with Zn+dexamethasone with and without interleukin-6. Insulin (100 U/L) alone, caused metallothionein accumulation and further enhanced the response seen with Zn+dexamethasone+interleukin-6+glucagon. No additional enhancement was seen with interleukin 1 beta+tumor necrosis factor alpha+interferon. The results demonstrate that concentrations of corticosterone in rats with experimental inflammation facilitate metallothionein induction with Zn and interleukin-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in plasma zinc, copper, iron, and hepatic metallothionein in adjuvant-induced arthritis treated with cyclosporin.

The early changes in hepatic metallothionein (MT) and plasma zinc (Zn), copper (Cu), and iron (Fe) were investigated during the induction of adjuvant (AJ) arthritis in rats in conjunction with cyclosporin (CsA) treatment. Plasma Zn decreased after AJ injection (60% of control values at 8 h), and this was associated with a 4.5-fold increase in hepatic MT at 8 h. Plasma Zn was lowest at 16 h (40% of control), whereas hepatic MT concentrations increased to a maximum of 20-fold at 16 h. Changes in plasma Fe paralleled those of Zn, whereas plasma Cu levels were increased. Plasma metal and hepatic MT concentrations returned toward normal from d 1-7. At d 14, when marked paw swelling was apparent, hepatic MT and plasma Cu were again increased and plasma Zn decreased. Administration of CsA decreased MT induction in rats injected with AJ and also caused a marked recovery in plasma Zn and Fe levels. These changes were small but significant even in the early stages (up to 24 h) after AJ injection and were followed by a sustained improvement in all parameters, corresponding to the nonappearance of clinical arthropathy in CsA-treated rats. TNF-alpha and IL-6 production by peritoneal macrophages isolated from AJ-injected rats was significantly decreased by CsA treatment at d 7 and 14. The inhibition of hepatic MT induction during acute and chronic inflammation by cyclosporin emphasizes the role of the immune system in altered metal homeostasis in inflammation.

Animals↗

Hemoglobin A1c by HPLC with the Pharmacia Mono S HR 5/N cation-exchange column: influence of sample protein load on optimal chromatographic conditions.

The Pharmacia Mono S HR 5/5 column has been optimized for hemoglobin A1c analysis by HPLC by using a much smaller column load, decreased buffer flow rate, and a steeper gradient than was used in previously described methods. Superior chromatographic separation, shorter analysis time, and a greatly extended column life have resulted.

Cations↗

Improved method for calculating calcium fractions in plasma: reference values and effect of menopause.

Multiple linear regression analysis showed that total calcium was significantly and positively related to albumin, globulin, anion gap, and bicarbonate in plasma from 556 normal postmenopausal women. The residual constant of 1.21 mmol/L approximated the normal mean for ionized calcium in plasma. The coefficients derived from the multiple regression analysis were used to calculate ionized calcium from total calcium and ligand concentrations in a series of 105 clinical cases in whom ionized calcium was measured with the calcium electrode. The regression equation was y = 1.00x -0.0039 mmol/L, where x is measured and y calculated Ca2+ (r = 0.78, P less than 0.001). The protein-bound, ultrafiltrable, and complexed fractions of the calcium were also calculated for plasma from 69 normal young men, 66 normal young women, and 305 normal postmenopausal women. The increased plasma calcium in the postmenopausal group was accounted for by an increase in the complexed fraction, due to increases in plasma bicarbonate and anion gap.

Adult↗

Computerized chromatographic peak detection using the trigg tracking signal. An application devised for use with an online analog to digital converter connected between an amino acid analyser and a personal computer.

Manual integration of the amino acid peaks from physiological samples produced by conventional anion exchange liquid chromatography is a time-consuming process. This paper describes a combined unit, consisting of an analog to digital converter and a personal computer, which was connected in parallel with the chart recorder and the analyser's 570 nm channel of the colorimeter. The computer was programmed to log the digitized data, detect the start, maximum and end of each chromatographic peak, calculate the area under the peak and its retention time and provide a printout of the results at the end of the elution program. The computer program successfully exploited the Trigg Tracking Signal as both a peak detection and as a moving baseline monitoring device. This approach proved to have an equivalent performance to the manual method for 17 out of the 19 amino acids normally quantitated in physiological samples. The automated detection and quantitation of arginine was unsatisfactory due to its characteristically low profile peak shape, and proline was not measured because the device was not connected to the 440 nm channel of the colorimeter. The automated system provided economic and analytically acceptable solutions to the problem of providing an online integrator versatile enough to be used with the 255 min long amino acid analysis of physiological fluids.

Amino Acids↗

Biochemical effects of a calcium supplement in osteoporotic postmenopausal women with normal absorption and malabsorption of calcium.

Although calcium supplements are widely used to reduce bone resorption in osteoporosis, their beneficial effect is not conclusively established. We have studied the acute (after 12 h) effects of an oral calcium load (1 g) in a group of 35 osteoporotic postmenopausal women, comprising 19 subjects with normal absorption and 16 subjects with malabsorption of calcium. In the subjects with normal calcium absorption the fasting urinary total hydroxyproline/creatinine ratio fell from 0.021 to 0.017 (p less than 0.001), but in those with malabsorption of calcium it did not change significantly. This difference between the two groups was significant (p less than 0.01). These results indicate that an oral calcium load rapidly suppresses bone resorption in osteoporotic subjects with normal absorption of calcium, but not in those with malabsorption of calcium.

Aged↗

Calcium metabolism and osteoporosis in corticosteroid-treated postmenopausal women.

Osteoporosis is a common complication of corticosteroid therapy and it is associated with both decreased bone formation and increased bone resorption. We have measured radiocalcium absorption and the fasting urinary calcium/creatinine and hydroxyproline/creatinine ratios in 30 postmenopausal women receiving prednisolone therapy and compared the patients with normal spine radiographs (N = 14) with those whose spine radiographs showed osteoporosis (N = 16). The osteoporotic cases had lower radiocalcium absorption (p less than 0.001), higher fasting urinary calcium (p less than 0.05), and higher fasting urinary hydroxyproline excretion (p less than 0.001). As calcium absorption has a positive effect on calcium balance and urinary calcium a negative effect, the difference between these two variables was calculated in each case. This derived variable (radiocalcium absorption--fasting urinary calcium/creatinine) disclosed a greater difference between the osteoporotic and normal groups (p less than 0.0001) than either variable alone.

Aged↗

Two methods for monitoring the photodecomposition of sodium nitroprusside in aqueous and glucose solutions.

The photodecomposition of sodium nitroprusside (SNP) in aqueous and 5% glucose solutions results in the accumulation of cyanide and ferricyanide ions. Methods for the determination of these ions in such solutions have been devised. The continuous-flow method for cyanide involved the generation of cyanogen chloride, ClCN, by oxidation with chloramine T and subsequent reaction of the ClCN with barbituric acid and pyridine to produce a chromophore measurable by spectrophotometry at 580 nm. This cyanide method had a detection limit and sensitivity of 10-12 mumol/L and 1.40 X 10(-3) absorbance units (AU)/mumol/L, respectively, with a working concentration range of 0-800 mumol/L. This method employed mild reaction conditions, pH = 4.1, which rendered it suitable for use in time-course studies of cyanide production from SNP solutions exposed to 366 nm UV light. A simple method for the determination of ferricyanide in SNP solutions was developed which involved the addition of a 1% FeSO4 X 7 H2O in 1% H2SO4 reagent to the SNP solutions under test followed by spectrophotometry at 750 nm. The detection limit and sensitivity of the method were 2-3 mumol/L and 4.05 X 10(-3) AU/mumol/L, respectively, with a working concentration range of 0-100 mumol/L. This method was considered suitable for use as a quality control test of SNP solutions close to the site of their clinical use.

Drug Stability↗

The effect of calcium supplements on plasma alkaline phosphatase and urinary hydroxyproline in postmenopausal women.

Although calcium supplements are widely used in the treatment of osteoporosis, their beneficial effect is not conclusively established. We now report some effects of a calcium supplement (1 g/day) given for 6 to 12 weeks to 15 postmenopausal osteoporotic women. The mean fasting urinary hydroxyproline/creatinine ratio decreased from 0.021 +/- 0.002 to 0.015 +/- 0.001 (P less than 0.0025), indicating a significant reduction in bone resorption. The mean plasma alkaline phosphatase fell from 123 +/- 5 U/l to 104 +/- 3.1 U/l (P less than 0.01), probably representing some secondary reduction in bone formation following the inhibition of bone resorption. These results support the concept that calcium supplementation is useful in the treatment of postmenopausal osteoporosis.

Aged↗

The relation between calcium absorption, serum dehydroepiandrosterone, and vertebral mineral density in postmenopausal women.

Vertebral mineral density, measured by computerized axial tomography, radiocalcium absorption, serum dehydroepiandrosterone (DHA), and serum cortisol (C) were measured in 98 postmenopausal women aged 56-70 yr. On the basis of spine radiographs and fracture history, the women were classified into 49 normal subjects (mean age, 60.5 yr) and 49 with osteoporosis (mean age, 63.1 yr). Vertebral mineral density (VMD), radiocalcium absorption (alpha), serum DHA, and the ratio of DHA to cortisol (DHA/C) were all significantly lower in the osteoporotic than in the normal subjects. DHA was significantly related to C in both groups but the regression was significantly flatter in the osteoporotic than in the normal subjects. Calcium absorption did not fall significantly with age in either group. In the normal group VMD, DHA, and DHA/C fell with age but VMD was not related to alpha, DHA, or DHA/C. In the osteoporotic group, VMD did not fall significantly with age but was significantly related to alpha and DHA/C. Stepwise regression analysis showed that in the normal subjects, age was the only variable significantly related to VMD (P less than 0.05). In the osteoporotic group, calcium absorption was the main determinant of VMD, with age and DHA/C contributing much less to the variance. Discriminant function analysis showed a theoretical misclassification of 45% of cases using DHA, 39% using DHA/C, 32% using alpha, and 18% when alpha and DHA or DHA/C were both taken into account. It is concluded that malabsorption of calcium is a significant risk factor for postmenopausal osteoporosis, probably because of a secondary increase in bone resorption to maintain serum calcium. The severity of the osteoporosis is directly related to the severity of the calcium malabsorption. Low serum DHA appears to represent a further risk factor, either because of its role as estrogen precursor or (possibly) because it promotes bone formation. However, the severity of the osteoporosis was not related to the serum DHA level and only weakly to the DHA/C ratio.

Aged↗

1,25-Dihydroxycalciferol and calcium therapy in osteoporosis with calcium malabsorption. Dose response relationship of calcium absorption and indices of bone turnover.

We have studied some effects of small doses of 1,25-dihydroxycalciferol (calcitriol) and calcium, either combined or separately, in 45 patients with osteoporosis and malabsorption of calcium. In 24 patients on 0.25 micrograms/d of calcitriol the hourly fractional rate of radiocalcium absorption rose from 0.37 +/- 0.02 to 0.55 +/- 0.04 (p less than 0.001) and in 21 patients on 0.50 micrograms/d it rose from 0.36 +/- 0.02 to 0.69 +/- 0.05 (p less than 0.001). These responses were seen within 5 days and were not increased further at 6 weeks to 3 months. The combined therapy significantly reduced the fasting urinary hydroxyproline/creatine ratio (OHPr/Cr) and plasma alkaline phosphatase activity (ALP) in 6-12 weeks, the smaller dose of calcitriol (0.25 micrograms/d) being as effective as the larger one (0.50 micrograms/d) in this respect. Calcium alone (1 g/d) had no effect and calcitriol alone (0.25 mcg/d) had a lesser effect on both OHPr/Cr and ALP than the combined therapy. The falls in OHPr/Cr and ALP tended to be greatest in the cases with the highest initial levels but constituted only partial suppression of these variables towards the theoretical non-bone components. These results suggest that treatment with calcitriol and calcium suppresses bone resorption in osteoporosis associated with malabsorption of calcium and is more effective than calcium or calcitriol given alone.

Alkaline Phosphatase↗

Effect of calcium supplementation on urinary hydroxyproline in osteoporotic postmenopausal women.

Although calcium supplements are widely used to reduce bone resorption in osteoporosis, their beneficial effect is not conclusively established. We studied the effect of a calcium supplement (1 g/day for 8 days) in 14 postmenopausal osteoporotic women. The fasting urinary hydroxyproline/creatinine ratio decreased from 0.022 +/- 0.001 to 0.017 +/- 0.001 (p less than 0.005) indicating a significant reduction in bone resorption. Both the tubular maximum for phosphate reabsorption (1.12 +/- 0.06 to 1.34 +/- 0.07, p less than 0.005) and plasma phosphate concentration (1.04 +/- 0.04 to 1.14 +/- 0.04, p less than 0.01) increased, consistent with suppression of parathyroid hormone activity. These results support the concept that calcium supplementation is useful in the treatment of postmenopausal osteoporosis.

Aged↗