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Biomedical subjects

R G Erben

Publications and source records attributed to R G Erben.

At least 19 recordsLinked to original sources
PubMed2005

Effect of orthotopic small bowel transplantation on mineral metabolism in an experimental model.

BACKGROUND: Numerous experimental models have been described for investigation of short bowel syndrome. The aim of this study was to examine the effect of orthotopic small bowel transplantation (OSBT) on universal metabolism in an inbred rat model, with particular emphasis on mineral metabolism. METHODS: Jejunoileal resection and syngeneic OSBT was performed in 12-week-old male Lewis rats. Metabolic studies were performed over the following 16 weeks. Bones were analysed by physicochemical methods, dual X-ray absorptiometry, biomechanical procedures and histomorphometry. Biochemical markers of bone turnover were also measured. RESULTS: Jejunoileal resection induced severe short bowel syndrome with profoundly reduced food efficiency, bone size, fracturing energy and bone mineral content, but no cancellous bone osteopenia. After OSBT rats showed normal growth; bones were of normal size, and bone mineral content and fracturing energy were similar to those in sham-operated controls. However, tibial, but not vertebral, cancellous bone osteopenia was found after transplantation. CONCLUSION: OSBT with portal venous drainage achieves almost optimal mineral and bone metabolism. In the absence of immunosuppressive therapy, OSBT does not appear to have major untoward side-effects on bone in rats.

Anastomosis, Surgical↗
PubMed2004

Influence of pores created by laser superfinishing on osseointegration of titanium alloy implants.

The aim of this study was to assess the osseointegration of copper vapor laser-superfinished titanium alloy (Ti6Al4V) implants with pore sizes of 25, 50, and 200 microm in a rabbit intramedullary model. Control implants were prepared by corundum blasting. Each animal received all four different implants in both femora and humeri. Using static and dynamic histomorphometry, the bone-implant interface and the peri-implant bone tissue were examined 3, 6, and 12 weeks postimplantation. Among the laser-superfinished implants, total bone-implant contact was smallest for the 25-microm pores, and was similar for 50- and 200-microm pore sizes at all time points. However, all laser-superfinished surfaces were inferior to corundum-blasted (CB) control implants in terms of bone-implant contact. Within the 12-week study period, remodeling of woven bone initially formed within pores occurred only in the implants with 200-microm pores. Implants with 25-microm pores showed the highest amount of peri-implant bone volume at all time points, indicating that the amount of peri-implant bone was not correlated with the quality of the bone-implant interface. At 3 and 6 weeks postsurgery, we did not find any differences in mineral apposition rates or bone formation rates between the various implant surfaces. However, the peri-implant bone formation rate at the end of the trial was 70 and 62% higher in implants with 50- and 200-microm pores compared with CB implants, respectively. We conclude that, although laser-superfinished implants were not superior to CB control implants in terms of osseointegration, our study has provided further insights into the mechanisms of bone remodeling within pores of various sizes, and may form a basis for future experiments to design optimal implant surfaces with the help of modern laser technology.

Alloys↗
PubMed2004

Effect of surface finish on the osseointegration of laser-treated titanium alloy implants.

It was the purpose of this study to examine the osseointegration of laser-textured titanium alloy (Ti6Al4V) implants with pore sizes of 100, 200, and 300 microm, specifically comparing 200-microm implants with polished and corundum-blasted surfaces in a rabbit transcortical model. Using a distal and proximal implantation site in the distal femoral cortex, each animal received all four different implants in both femora. The bone-implant interface and the newly formed bone tissue within the pores and in peri-implant bone tissue were examined 3, 6, and 12 weeks post-implantation by static and dynamic histomorphometry. Here we show that additional surface blasting of laser-textured Ti6Al4V implants with 200-microm pores resulted in a profound improvement in osseointegration, 12 weeks postimplantation. Although lamellar bone formation was found in pores of all sizes, the amount of lamellar bone within pores was linearly related to pore size. In 100-microm pores, bone remodeling occurred with a pronounced time lag relative to larger pores. Implants with 300-microm pores showed a delayed osseointegration compared with 200-microm pores. We conclude that 200 microm may be the optimal pore size for laser-textured Ti6Al4V implants, and that laser treating in combination with surface blasting may be a very interesting technology for the structuring of implant surfaces.

Alloys↗
PubMed2002

Regional bone loss after orthotopic liver transplantation in inbred rats: the role of hepatic denervation.

Bone loss and long-term persistence of osteoporosis with increased fracture risk are common after liver transplantation. It is unknown whether transplantation-induced disruption of hepatic nerves, serving numerous regulatory metabolic and sensory functions, is herein involved. To test this possibility, we measured bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and studied dynamic histomorphometry, radiocalcium kinetics, and biochemical parameters in 7 liver-transplanted and 7 sham-operated inbred rats. Although liver function was normal in TX rats, trabecular BMD of the first lumbar vertebra and total BMD of the femoral diaphysis were decreased by 13% and 6%, respectively, 9 months postsurgery. The breaking force of the femur was significantly lower by 21%. However, bone mass in the femoral and tibial metaphysis was preserved as evidenced by pQCT measurements and histomorphometry. Trabecular width and wall thickness were significantly decreased in vertebral cancellous bone, whereas indices of bone formation and resorption were normal or slightly reduced. Serum minerals, mineral balance, fractional and net absorption of Ca and Mg, serum calciotropic hormones, IGF-I, leptin, specific activity of 45Ca in bone, 45Ca excretion, and biochemical indices of bone formation and bone resorption remained unchanged. We conclude that liver transplantation-related denervation causes cancellous and cortical bone loss in well-innervated bone sites such as the lumbar spine and the long bone diaphysis. Cancellous bone loss in TX rats is due to an impairment of osteoblast team performance and subsequent trabecular thinning. The mechanism uncovered by our study may contribute to long-term bone loss after liver transplantation.

Animals↗
PubMed2001

Gene structure and regulation of the murine epithelial calcium channels ECaC1 and 2.

The recently discovered epithelial calcium channels ECaC1 and ECaC2 are thought to play an important role in active calcium absorption in the intestine and kidney. Vitamin D-responsive elements (VDRE) were detected in the promoter sequence of human ECaC1 and regulation of ECaC by the steroid hormone 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) has been postulated. In this study we describe the structure of two murine ECaCs genes, each consisting of 15 exons localized on chromosome 6. Murine ECaC2 expression was found in many target tissues of 1,25-(OH)(2)D(3), including skin and osteoblastic cells, while ECaC1 expression is confined to the kidney. By screening the murine promoter sequences, we detected a putative VDRE in ECaC1 and an estrogen response element in ECaC2. However, experiments in mice with a mutant, nonfunctioning vitamin D receptor showed that expression of ECaC1 in the kidney and of ECaC2 in duodenum is regulated by calcium levels, but not by 1,25-(OH)(2)D(3). Also, estrogen-deficient ovariectomized (OVX) mice and OVX mice supplemented with estradiol showed unchanged duodenal ECaC2 expression compared with control mice. We conclude that ECaC expression in the kidney and the intestine is regulated by extracellular calcium but not by vitamin D or estrogen in vivo in mice.

Amino Acid Sequence↗
PubMed2001

Testosterone prevents orchidectomy-induced bone loss in estrogen receptor-alpha knockout mice.

To examine the role of the estrogen receptor-alpha (ERalpha) during male skeletal development, bone density and structure of aged ERalphaKO mice and wild-type (WT) littermates were analyzed and skeletal changes in response to sex steroid deficiency and replacement were also studied. In comparison to WT, ERalphaKO mice had smaller and thinner bones, arguing for a direct role of ERalpha to obtain full skeletal size in male mice. However, male ERalphaKO mice had significantly more trabecular bone as assessed both by pQCT and histomorphometry, indicating that ERalpha is not essential to maintain cancellous bone mass. Six weeks following orchidectomy (ORX), both WT and ERalphaKO mice showed high-turnover osteoporosis as revealed by increases in serum osteocalcin and decreases in trabecular (-38% and -58% in WT and ERalphaKO, respectively) and cortical bone density (-5% and -4% in WT and ERalphaKO, respectively). Administration of testosterone propionate (T, 5 mg/kg/day) completely prevented bone loss both in ERalphaKO and in WT mice. As expected, estradiol (E2, 60 microg/kg/day) replacement did not prevent cancellous bone loss in ORX ERalphaKO mice. However, E2 stimulated bone formation at the endocortical surface in ORX ERalphaKO, suggesting that osteoblasts may respond to nonERalpha-mediated estrogen action. In conclusion, although functional ERalpha may play a significant role during male skeletal development, this receptor does not seem essential for androgen-mediated skeletal maintenance in older male mice.

Animals↗
PubMed2001

B lymphopoiesis is upregulated after orchiectomy and is correlated with estradiol but not testosterone serum levels in aged male rats.

Previous studies have shown that B lymphopoiesis is augmented after androgen withdrawal in male mice. As an analogy to the skeletal system, some effects of androgens on the proliferation of B cells may be mediated via aromatization into estrogens in vivo. The aim of the present study was to assess the effects of androgen withdrawal on B lymphopoiesis in bone marrow of aged male rats sequentially over a period of 9 months, and to correlate the flow-cytometric findings with changes in systemic levels of sex steroids. We first showed that androgen withdrawal is associated with enhanced B lymphopoiesis in bone marrow of 4-month-old male orchiectomized (ORX) rats, and that the changes in the bone marrow B cell compartment in ORX animals can be reversed by testosterone supplementation. In a subsequent, sequential experiment, we found that orchiectomy induced a sustained rise in Thy 1.1+/CD45R+ bone marrow cells committed for the B cell lineage that lasted for several months in 13-month-old aged rats. In a stepwise model of multiple regression analysis using estradiol, free and total testosterone as independent variables, estradiol was the strongest predictor of the percentage of B precursor cells in bone marrow in aged SHAM and ORX rats. Free and total testosterone did not correlate with B lymphopoiesis in aged SHAM rats. The current experiment has clearly shown that androgen withdrawal upregulates the number of B lineage cells over several months in rat bone marrow. Furthermore, our results provide evidence that estradiol may play an important role as a physiological suppressor of B lymphopoiesis in aged male rats.

Aging↗
PubMed2001

Partial rescue of PTH/PTHrP receptor knockout mice by targeted expression of the Jansen transgene.

The homozygous ablation of the gene encoding the PTH/PTHrP receptor (PPR(-/-)) leads to early lethality and limited developmental defects, including an acceleration of chondrocyte differentiation. In contrast to the findings in homozygous PTHrP-ablated (PTHrP(-/-)) animals, these PPR(-/-) mice show an increase in cortical bone, a decrease in trabecular bone, and a defect in bone mineralization. Opposite observations are made in Jansen's metaphyseal chondrodysplasia, a disorder caused by constitutively active PPR mutants, and in transgenic animals expressing one of these receptor mutants (HKrk-H223R) under control of the type alpha1(I) collagen promoter. Expression of the Jansen transgene under the control of the type alpha1(II) collagen promoter was, furthermore, shown to delay chondrocyte differentiation and to prevent the dramatic acceleration of chondrocyte differentiation in PTHrP(-/-) mice, thus rescuing the early lethality of these animals. In the present study we demonstrated that the type alpha1(II) collagen promoter Jansen transgene restored most of the bone abnormalities in PPR(-/-) mice, but did not prevent their perinatal lethality. These findings suggested that factors other than impaired gas exchange due to an abnormal rib cage contribute to the early death of PPR(-/-) mice.

Animals↗
PubMed2001

1alpha-hydroxyvitamin D2 is less toxic but not bone selective relative to 1alpha-hydroxyvitamin D3 in ovariectomized rats.

Identification of bone selective vitamin D analogues would provide an interesting substance class for the treatment of osteoporosis. The synthetic prodrug 1alpha-hydroxyvitamin D2 [1alpha(OH)D2] has been shown to combine equal bone-preserving activity with distinctly reduced calcemic effects relative to 1alpha-hydroxyvitamin D3 [1alpha(OH)D3] in 3-month-old ovariectomized (OVX) rats. Therefore, 1alpha(OH)D2 may be a bone-selective compound. The aim of this study was to compare the bone protective and the calcemic activities of chronically administered 1alpha(OH)D2 and 1alpha(OH)D3 in 6-month-old OVX rats over a broad dose range from ineffective to toxic doses. Ninety-six female 6-month-old Fischer-344 rats were used for this experiment. Eighty rats were bilaterally OVX, 8 rats were sham-operated (SHAM), and 8 rats were killed at the time of surgery as a baseline control. Groups of OVX rats received vehicle alone (n = 16) or daily doses in the diet of 0.025, 0.05, 0.1, and 0.2 microg of 1alpha(OH)D2 or 1alpha(OH)D3 per kg body weight (BW) per day (n = 8 each). After calcein double-labeling, all animals were killed 3 months post-OVX. Orally administered 1alpha(OH)D2 was significantly less toxic compared with 1alpha(OH)D3 in terms of BW gain and kidney calcium content. The effects of 1alpha(OH)D2 and 1alpha(OH)D3 on serum calcium and urinary calcium excretion were generally similar at all doses in this study. Both 1alpha(OH)D2 and 1alpha(OH)D3 prevented the estrogen deficiency-induced bone loss in OVX rats, and induced profound bone anabolic effects at high dosages. 1alpha(OH)D3 and 1alpha(OH)D2 also dose-dependently increased total bone mineral density (BMD), cortical area, and cortical thickness in the tibial diaphysis of OVX rats. Bone resorption as assessed by osteoclast numbers (Oc.Ns) in vertebral cancellous bone and urinary excretion of deoxypyridinoline (DPD) was dose-dependently suppressed by 1alpha(OH)D2 and 1alpha(OH)D3. These data show that although 1alpha(OH)D2 was slightly but significantly less toxic compared with 1alpha(OH)D3, it did not have increased skeletal effects at any dose. Taken together, our findings argue against selective metabolic activation of 1alpha(OH)D2 in bone.

Animals↗
PubMed2001

Vitamin D analogs and bone.

Vitamin D analogs increase intestinal calcium absorption, and have been shown to possess antiresorptive and also bone anabolic properties in vivo. Therefore, the pharmacological profile of vitamin D analogs would be well suited for the treatment of osteoporosis. However, the calcemic side effects of this compound class, especially at higher doses, have hampered their wide use in osteoporotic patients. Nevertheless, the clear potential for bone anabolic properties together with oral availability have stimulated the interest in this substance class, and there is an active search for bone selective vitamin D compounds. After an overview of the physiological functions of vitamin D in bone, this article focuses on the effects of acute and chronic administration of pharmacological doses of vitamin D analogs on bone in animal models and humans. Furthermore, the endocrinological, cellular, and microanatomical mechanisms involved in the skeletal actions of vitamin D analogs are discussed. The final section briefly reviews the available data on possible bone selective vitamin D analogs.

Journal Article↗
PubMed2001

Skeletal effects of androgen withdrawal.

Hypogonadism is considered to be one of the major risk factors for osteoporosis in men. Therefore, it is an important goal for skeletal research to improve our understanding of the skeletal effects of androgens. Androgen deficiency during growth is associated with a failure to acquire normal peak bone mass, and there is good evidence that the effects of androgens on skeletal growth and the development of a male skeletal phenotype are mediated through the androgen receptor. In adult men, acute withdrawal of androgens by surgical or chemical castration induces high turnover bone loss. Similarly, orchidectomy of aged, non-growing male rats is associated with a pronounced and sustained increase in bone turnover and with true loss of cancellous and cortical bone. Interestingly, the changes in bone turnover induced by orchidectomy are paralleled by a concomitant increase in B lymphopoiesis in bone marrow of rats and mice. Although there is firm evidence that male bone metabolism can be influenced by androgens and estrogen, a variety of clinical and animal experimental data have strongly suggested that, under physiological circumstances, the maintenance of cancellous bone mass in males involves the skeletal action of estrogen derived from aromatization of androgens. Aged male rats appear to closely mimic the conditions induced by androgen withdrawal in adult humans, and this animal model may be used 1) to elucidate further the role of muscle as a mediator of the actions of androgens on bone, 2) to explore the regulatory functions of androgens and estrogens in the male skeleton and the immune system, and 3) to find new treatment strategies for the prevention and treatment of osteoporosis in men.

Journal Article↗
PubMed2000

Nephrocalcinosis and hyperlipidemia in rats fed a cholesterol- and fat-rich diet: association with hyperoxaluria, altered kidney and bone minerals, and renal tissue phospholipid-calcium interaction.

To determine whether an "atherogenic" diet (excess of cholesterol and neutral fat) induces pathological calcification in various organs, including the kidney, and abnormal oxalate metabolism, 24 male Sprague-Dawley rats were fed either normal lab chow (controls, n = 12) or the cholesterol- and fat-rich experimental diet (CH-F, n = 12) for 111 +/- 3 days. CH-F rats developed dyslipidemia [high blood levels of triglycerides, total, low-density lipoprotein (LDL)-, very low-density lipoprotein (VLDL)-, high-density lipoprotein (HDL)-bound cholesterol, total phospholipids], elevated serum total alkaline phosphatase and lactate dehydrogenase (LDH) levels, in the absence of changes in overall renal function, extracellular mineral homeostasis [serum protein-corrected total calcium, magnesium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D)], plasma glycolate and oxalate levels. There was a redistribution of bone calcium and enhanced exchange of this within the extraosseous space, which was accompanied by significant bone calcium loss, but normal bone histomorphometry. Liver oxalate levels, if expressed per unit of defatted (DF) dry liver, were three times higher than in the controls. Urinary glycolate, oxalate, calcium and total protein excretion levels were elevated, the latter showing an excess of proteins > 100 kD and a deficit of proteins > 30-50 kD. Urinary calcium oxalate supersaturation was increased, and calcium phosphate supersaturation was unchanged. There were dramatically increased (by number, circumference, and area) renal calcium phosphate calcifications in the cortico-medullary region, but calcium oxalate deposits were not detectable. Electron microscopy (EM) and elemental analysis revealed intratubular calcium phosphate, apparently needle-like hydroxyapatite. Immunohistochemistry of renal tissue calcifications revealed co-localization of phospholipids and calcium phosphate. It is concluded that rats fed the CH-F diet exhibited: (1) a spectrum of metabolic abnormalities, the more prominent being dyslipidemia, hyperoxaluria, hypercalciuria, dysproteinuria, loss of bone calcium, and calcium phosphate nephrocalcinosis (NC); and (2) an interaction between calcium phosphate and phospholipids at the kidney level. The biological significance of these findings for the etiology of idiopathic calcium urolithiasis in humans is uncertain, but the presented animal model may be helpful when designing clinical studies.

Absorptiometry, Photon↗
PubMed2000

Vagus-sparing gastric fundectomy in the rat: development of osteopenia, relationship to urinary phosphate and net acid excretion, serum gastrin and vitamin D.

In man and experimental animals, partial and total gastrectomy and gastric vagotomies disturb extracellular mineral homeostasis, osteopenia being among the late outcomes. The sequence of events is complex and insufficiently understood. We report on the long-term effects of gastric fundectomy (FX; FX-1, n=11; sham-operated controls, n=14) sparing gastric vagal fibers at the lesser curvature in the rat, a procedure eliminating gastric acid production but preserving gastric reservoir function. After FX-1 there was a marked increase of gastrinemia [FX-1: 590 (SE 95); controls: 82 (5) pg-equiv/ml; P<0.001], serum 1,25-dihydroxyvitamin D [FX-1: 188 (17); controls: 86 (6) pg/ml; P<0.001], phosphaturia [FX-1: 32 (2); controls 23 (2) micromol/h; P<0.001] due to increased fractional phosphate clearance, elevated urinary net acid [FX-1: 21 (2); controls: 16 (1) micromol/h; P=0.03], and low urinary pH. The urinary excretion of hydroxyproline was increased [FX-1: 137 (15); controls: 99 (8) micromol/h; P=0.01], and crosslinks were also high. These changes were associated with a significant decrease of bone ash calcium, magnesium, and phosphorus. Bone histomorphometry revealed signs of high bone turnover. No signs of hyperparathyroidism were detectable. Acute stimulation of serum gastrin by gastric acid abolishing omeprazole failed to provoke extra-osseous changes, as seen in the long-term after fundectomy. It was concluded that the described type of fundectomy disturbs gastrinemia, acid-base and phosphorus metabolism, thereby initiating osteopenia. This animal model may be suitable for research into post-gastrectomy bone disease.

Acid-Base Equilibrium↗
PubMed2000

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.

Animals↗
PubMed2000

Androgen deficiency induces high turnover osteopenia in aged male rats: a sequential histomorphometric study.

Hypogonadism is considered to be one of the major risk factors for osteoporosis in men. However, the mechanisms of bone loss caused by androgen deficiency are still unclear. In the present study, we sequentially investigated the skeletal and hormonal effects of androgen deficiency in aged orchiectomized (ORX) rats over a time period of 9 months. One hundred seventy 13-month-old male Fischer-344 rats were either ORX or sham-operated (SHAM). Eight rats served as baseline controls. After in vivo fluorochrome labeling, groups of 8-15 SHAM and ORX rats each were killed at 2 weeks and at 1, 2, 3, 4, 6, and 9 months postsurgery. As expected, ORX induced a fall in serum total and free testosterone levels, but also reduced serum estradiol concentrations. Cancellous bone area (BAr) in the proximal tibia but not in the first lumbar vertebral body showed an age-dependent decline in SHAM rats. Relative to SHAM controls, ORX rats had significantly reduced cancellous BAr after 2 weeks post-ORX in the tibia and after 2 months post-ORX in the vertebral body. Thereafter, vertebral and tibial cancellous BAr continued to decline in ORX animals throughout the study. Osteoclast number (NOc), osteoblast surface, bone formation rate (BFR), and activation frequency were increased in ORX animals from 1 month postsurgery until the end of the trial. Moreover, in close temporal association with the histomorphometric findings, serum osteocalcin and urinary excretion of collagen cross-links and calcium were elevated in ORX rats. In a stepwise model of multiple regression analysis using estradiol and free and total testosterone as independent variables, estradiol was the only significant predictor of histomorphometric indices of bone formation and bone resorption in SHAM and ORX rats. These data show that androgen deficiency induces substantial loss of cancellous bone in the axial and appendicular skeleton of aged male rats and that this osteopenia is associated with a sustained increase in bone turnover. Thus, the skeletal effects of androgen withdrawal in aged male rats appear to resemble those induced by estrogen withdrawal in female rats. Furthermore, our study suggests that estradiol may act as a physiological suppressor of bone remodeling in aged male rats.

Aging↗
PubMed2000

Effects of partial and total colectomy on mineral and acid-base homoeostasis in the rat: magnesium deficiency, hyperphosphaturia and osteopathy, in the presence of high serum 1,25-dihydroxyvitamin D but normal parathyroid hormone.

The effects of colectomy on acid-base status, extra-osseous and bone minerals, calciotropic hormones and bone morphology have not yet been studied. To rectify this, groups of normally fed male rats were subjected to distal (n=11), proximal (n=12) or total (n=12) colectomy. Sham-operated rats (n=12) served as controls. At 112 (+/-2) days after colectomy the following changes were noted: (1) weight gain was delayed; (2) faecal excretion of calcium and phosphorus was normal, whereas that of magnesium was increased; (3) intestinal calcium secretion and absorption of calcium and phosphorus were normal, but magnesium absorption was decreased; (4) urinary excretion of magnesium was also decreased, that of phosphorus was increased, and that of pyridinium and deoxypyridinium tended to be high; (5) the serum levels of ionized magnesium, total calcium, 25-hydroxyvitamin D and parathyroid hormone were normal, while that of 1,25-dihydroxyvitamin D was markedly elevated; and (6) bone magnesium and phosphorus content were decreased, but bone calcium was normal, and thus the bone calcium/phosphorus ratio was high. These abnormalities were associated with moderate metabolic acidosis, as reflected by high urinary ammonium, low citrate and low total CO(2), but normal blood gases. Significant structural abnormalities of bone were not detectable, but trabecular bone tended to show rarefication. Distal colectomy had the least effect, whereas proximal and total colectomies had a distinct effect, on these parameters. It is concluded that colectomy in the rat causes: (1) a syndrome of magnesium deficiency of intestinal origin, compensated metabolic acidosis, urinary phosphorus loss, and high circulating 1,25-dihydroxyvitamin D levels, with the degree depending on the extent of surgical resection; and (2) brittle bones, a feature characteristic of low bone magnesium and more generalized magnesium deficiency. The mechanisms leading to this syndrome are unknown, but altered tissue levels of magnesium and phosphorus may play a key role.

Acid-Base Equilibrium↗