Plasma Tartrate-resistant Acid Phosphatase Research Articles

Letrozole induced changes in bone mineral properties and mechanical functions of laying hens

Bone volumes and quality are related to their hormone levels in laying hens. In this study, we investigated letrozole (LZ) induced effects on the physicochemical properties of cortical bone in laying hens. After 9-wk LZ treatment, we observed that LZ could decrease estrogen level in laying hens. As a result, both the plasma tartrate-resistant acid phosphatase and bone Gla protein activities were suppressed significantly. In addition, carbonate substitution was inhibited significantly in humerus and femur confirmed by Raman spectroscopy. Meanwhile, the mineral density and yield load capacities of humerus and femur were improved. This study demonstrated that the high crystallinity and low carbonate substitution were tightly correlated with the relatively enhanced mechanical properties. Moreover, it elucidated biochemical mechanisms of estrogen in regulating mineralogical and mechanical properties of bones in laying hens.

The effect of colostrum intake on osteoprotegerin and bone metabolic markers in the blood of newborn calves during the first week of life.

The aim of this study was to elucidate the bone metabolic status after taking colostrum in newborn calves. Fourteen neonatal calves were randomly allocated to two groups fed either unheated or heated (60°C, 30 min) colostrum three times on the first day (2 l every 10 hr; 6 l in total). Heat treatment on colostrum was to reduce the bone metabolic markers assumed as heat-sensitive. The concentrations of four bone metabolic markers (the enzymes from bone cells or the bone collagen fragments) and a bone protective protein, osteoprotegerin (OPG), were measured in the blood of calves during a week after the birth and in the colostrum. The colostral concentrations of four bone metabolic markers were reduced by heating. Then those circulatory markers peaked after colostrum intake in the calves fed unheated colostrum; whereas those fed heated colostrum did not show such changes. However, the plasma tartrate resistant acid phosphatase 5b (TRAP5b) activity was transiently increased after taking colostrum in both groups. Meanwhile, heating did not decrease colostral OPG and there was no significant rise in the serum OPG concentrations after the first colostrum intake in both groups. The study revealed that the blood concentrations of studied bone metabolic markers depended on those colostral values except for TRAP5b. Based on the plasma TRAP5b changes, accelerated formation of premature osteoclast cells may be induced by colostrum intake. Meanwhile, colostral OPG absorption is less likely to impact on its circulating levels.

The decline of whole-body glucose metabolism in ovariectomized rats.

Age is a major risk factor for developing chronic diseases, including type 2 diabetes and osteoporosis. Emerging evidences suggest that the disorder of bone metabolism in osteoporosis is involved in the pathogenesis of glucose intolerance, insulin resistance and type 2 diabetes. However, their etiology and relative regulatory factors still remain elusive to clinicians and researchers. In this study, rats were divided into two groups: normal sham surgery control and ovariectomized (OVX) groups. We evaluated the global bone parameters, glucose metabolism, protein and gene expressions in both skeletal muscle and adipocytes. The present findings showed that the bone mineral density (BMD) and compression load of bone were markedly reduced in OVX rats as revealed by micro-CT, dual energy X-ray absorptiometry and bone biomechanics analysis. Besides, plasma estrogen, total alkaline phosphatase (TALP) and osteocalcin levels were significantly decreased in the OVX rats, but body weight, fat mass and plasma tartrate-resistant acid phosphatase (TRAP) and chemerin levels were significantly increased in the OVX rats. More interestingly, we found that p-AKT, p-P38MAPK, glucose transporter 4 (GLUT4) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) contents as well as GLUT4 and PGC-1α mRNA expression were significantly decreased in skeletal muscle and adipocytes of OVX rats. In conclusion, our results indicated that whole-body glucose metabolism and glucose intolerance in OVX rats was degressive, suggesting there was a novel link between osteoporosis and whole body glucose homeostasis, which are controlled by the P38MAPK/PGC-1α/GLUT4 signaling pathway.

Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets

Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD).Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD.Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography.Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice (P < 0.05), but it did not differ among mice fed the 3 diets. Plasma ALP and TRAP activities and bone formation and resorption in femur were similar among ovariectomized mice fed the HFD containing 0 or 1000 mg vitamin E/kg.Conclusions: The results suggest that excess vitamin E intake does not cause bone loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content.

Continual feeding of two types of microalgal biomass affected protein digestion and metabolism in laying hens.

A 14-wk study was conducted to determine the nutritional efficacy and ssmetabolic impact of 2 types of microalgal biomass as alternative protein sources in laying hen diets. Shaver hens (total = 150 and 26 wk old) were fed 1 of 5 diets: a control or a defatted green microalgal biomass (DG; Desmodesmus spp.) at 25% and a full-fatted diatom biomass (FD; Staurosira spp.) at 11.7% inclusion with or without protease. This experiment consisted of 5 replicates per treatment and each replicate contained 6 hens individually reared in cages (1 hen for biochemical data/replicate). Despite decreased ADFI (P = 0.03), hens fed DG or FD had final BW, overall hen-day egg production, and egg quality similar to the controls. Feeding DG or FD did not alter plasma concentrations of insulin, glutamine, and uric acid or alkaline phosphatase activity at wk 8 or 14 but decreased plasma 3-methyhistine concentrations (P = 0.03) and tartrate-resistant acid phosphatase (TRAP) activities (P < 0.001) at wk 14 and improved (P = 0.002) ileal total AA digestibility. Although DG or FD exhibited moderate effects on intestinal brush border protease activities and mRNA levels of duodenal transporters Pept1, Lat1, and Cat1, both substantially enhanced (P < 0.05) phosphorylation of hepatic protein synthesis key regulator S6 ribosomal protein (S6) and the ratio of phospho-S6 to S6 in the liver of hens. However, DG and FD manifested with different impacts on weights of egg and egg albumen, proteolytic activity of jejunal digesta, plasma TRAP activity, ileal total AA digestibility, and several intestinal genes and hepatic proteins. Supplemental protease in the DG and FD diets produced mixed effects on a number of measures. In conclusion, our findings revealed the feasibility of including greater levels of microalgal biomass as a source of feed protein for laying hens and a novel potential of the biomass in improving dietary protein digestion and body protein metabolism than previously perceived.

Prolonged overdose of all-trans retinoic acid enhances bone sensitivity in castrated mice

ObjectivesIntake of multivitamin preparations is very common in developed countries. However, excessive intake of vitamin A was associated with increased bone fragility. The aim of this study was to determine if chronic administration of the active metabolite of vitamin A all-trans-retinoic acid (ATRA) in slight excess is associated with changes of bone turnover and density in intact and castrated mice. MethodThree mo old male mice (C57B1/6) intact and castrated were injected intraperitonealy with 10 mg/kg/d of the ATRA or vehicle (control) once daily for 3 wk. The bone density, ash weights, calcium, and phosphorus content of the femur were measured. Plasma tartrate-resistant acid phosphatase (Tr-ACP) and serum bone alkaline phosphatase (B-ALP) were determined. ResultsATRA decreased bone density in both groups; however, this effect was more pronounced in castrated animals (1.487 ± 0.04 to 1,360 ± 0.05 g/cm3 ) than in intact mice (1.570 ± 0.03 to 1.510 ± 0.03 g/cm3 ). Bone density correlated with decreased B-ALP and increased Tr-ACP in ATRA-treated mice. ATRA treatment led to significantly lower thickness of cortical bone both in the intact and castrated animals. ConclusionOur results indicate that repeated administration of ATRA in slight excess leads to significant bone loss both in intact and castrated mice. This effect was more pronounced in testosterone-deficient animals. Testosterone deficiency as occurs following castration may sensitize the bone to resorption mediated by ATRA. Therefore, chronic vitamin A administration may be a risk factor for osteoporosis, especially in older and testosterone-depleted subjects.

Changes in Plasma Bone Metabolic Markers in Periparturient Dairy Cows

We examined fluctuations in plasma tartrate-resistant acid phosphatase isoform 5b (TRAP5b) measured using fluorometry in conjunction with those in calcium (Ca) and other bone metabolic markers from 2 weeks prepartum to 2 weeks postpartum in 7 primiparous and 18 multiparous pregnant cows. The plasma Ca concentration decreased temporarily on the day of calving in multiparous cows only. Plasma TRAP5b peaked on the day of calving in primiparous and multiparous cows and was significantly lower in multiparous cows than in primiparous cows 2 weeks before and after parturition. Plasma hydroxyproline increased 1 week postpartum in multiparous cows. Bone-specific alkaline phosphatase and osteocalcin tended to decrease after parturition in primiparous and multiparous cows. These results suggest that bone resorption increases around parturition in healthy parturient cows from the viewpoint of the TRAP5b activity.

Diagnosis and treatment of osteoporotic fractures

Diagnosis and treatment of osteoporotic fractures

Fluorometric Method for Measuring Plasma Tartrate-Resistant Acid Phosphatase Isoform 5b and Its Application in Cattle

This study determined the appropriate biochemical assay for measuring plasma tartrate-resistant acid phosphatase isoform 5b (TRAP5b) activity; this information is important to clarify the relationship between plasma TRAP5b and known biochemical bone markers in cattle. When plasma TRAP5b was measured using fluorometric and spectrophotometric methods, hemolysis products in plasma did not affect the former method. In plasma from healthy cattle, there was a good correlation (r=0.66) between the 2 methods. In age-related profiles, plasma TRAP5b (r=-0.53), hydroxyproline (HYP, r=-0.56) and bone-specific alkaline phosphatase (BALP, r=-0.44) showed significant negative correlations with age; these three parameters decreased until 4 or 5 years of age and then remained constant. There were significant correlations between TRAP5b and HYP (r=0.83) or BALP (r=0.83). Our results show that the fluorometric assay can be performed with a high degree of precision and reproducibility without interference from hemolysis, and that the age-related changes in plasma TRAP5b, HYP, and BALP constitute additional background values for clinical guidance in bovine medicine.

Vitamin E does not Support Bone Quality in Orchidectomized Rats

Vitamin E is known to improve antioxidant status, but the effect of vitamin E on bone quality in orchidectomized rats is unknown. In the present study, thirty-two 1-y-old male rats were randomized to two groups: a sham-control group (n=8) and an orchidectomized group (n=24). The orchidectomized group was divided into three groups of eight and assigned to one of the following treatments: orchidectomy (ORX), low-dose vitamin E of 65.6 mg/Kg diet or high-dose vitamin E of 656 mg/Kg diet. Four months after the study began, all rats were killed, blood was collected, and plasma was harvested for antioxidant status, tartrate resistant acid phosphatase (TRAP), and IGF-I. Orchidectomy decreased (P < 0.05) plasma antioxidant and IGF-I, reduced bone (P < 0.05) quality and bone strength, increased (P < 0.05) plasma TRAP and urinary excretion of calcium and magnesium compared to the sham-control group. In contrast to ORX, vitamin E increased (P < 0.05) plasma antioxidant and had no beneficial effect on indices of bone quality, bone resorption and bone formation marker, or urinary calcium and magnesium excretion. In conclusion, vitamin E appears to decrease oxidative stress without improving bone quality in orchidectomized rats.

Effects of cis‐9, trans‐11, CLA in rats at intake levels reported for breast‐fed infants

CLA intake in exclusively breast-fed infants is close to levels found to have physiological effects in animals. However, in the majority of studies mixtures of CLA isomers have been used and the independent effects of the major CLA isomer in human milk, cis-9,trans-11 CLA, at the intake level in exclusively breast-fed infants have hardly been studied. We therefore studied the effects of cis-9,trans-11 CLA on plasma lipids and glucose, immune function, and bone metabolism in growing rats. Thirty male Sprague-Dawley rats (n = 10/group) were fed either 20 mg/kg/d cis-9,trans-11 CLA and 20 mg/kg/d sunflower oil (CLA20), 40 mg/kg/d cis-9,trans-11 CLA (CLA40), or 40 mg/kg/d sunflower oil (placebo) for 8 wk. No significant differences between groups were found in plasma lipids, glucose, insulin, C-reactive protein, or lipid peroxidation. Liver fat content was lowest in the CLA20 group. In vitro interleukin 2 (IL-2) production increased, and tumor necrosis factor alpha, IL-1beta, prostaglandin E2, and leukotriene B4 production decreased in the CLA20 group. No differences between groups were detected in IL-4, IL-6, or interferon gamma production, plasma osteocalcin, insulin-like growth factor, or urinary deoxypyridinoline crosslinks. Plasma tartrate-resistant acid phosphatase 5b activity was significantly increased in the CLA40 group. The results indicate anti-inflammatory effects and enhanced T-cell function for the CLA20 group. No adverse effects were seen in the CLA20 group, whereas indications of increased bone resorption rate were observed in the CLA40 group.

The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice

The pathogenesis of bone metastases may require the activation of osteoclasts by tumor-secreted factors, which promote important interactions with the bone microenvironment. We utilized an intratibial model of bone metastasis with bioluminescent imaging (BLI) to measure the effect of osteoclast inhibition on the interaction of human lung cancer cells with bone, and on tumor growth. Mice were injected with luciferase-transduced tumor cells (HARA, human pulmonary squamous carcinoma) and divided into three groups: (1) untreated, (2) twice weekly treatment with the bisphosphonate zoledronic acid (ZOL), or (3) osteoprotegerin (OPG). Histomorphometry and imaging were used to evaluate tumor burden, and parameters of osteoclast activity. Mice in the treated groups had increased bone density and decreased osteoclast numbers in nontumor-bearing tibiae. There was greater than 60% reduction in mean tumor volume in both treatment groups when evaluated by histomorphometry (P = 0.06 [OPG], P = 0.07 [ZOL]). However, bioluminescent imaging failed to show a reduction in tumor burden due to wide variability in the data. Osteoclast numbers along tumor-associated bone were significantly increased compared to tumor-free bone, and were not reduced by either treatment. Plasma calcium concentration was increased in all groups. Plasma tartrate-resistant acid phosphatase 5b was reduced in both treatment groups. Plasma PTHrP was significantly increased in the untreated tumor-bearing group, but was not significantly different in the two treatment groups compared to normal mice. OPG or ZOL did not change tumor cell proliferation, but ZOL increased HARA cell apoptosis. OPG and ZOL reduced tumor growth in the tibiae of treated mice, however, PTHrP production by HARA cells may have resulted in a high concentration in the bone microenvironment, partially overriding the antiosteoclast effects of both OPG and ZOL.

Association between changes in plasma calcium concentration and plasma tartrate-resistant acid phosphatase activity in periparturient cows.

Eight periparturient Holstein Friesian cows were examined for plasma tartrate-resistant acid phosphatase (TRAP) activity to assess the degree of bone metabolic activity and to evaluate the association between the change in calcium (Ca) concentration and bone metabolism during the periparturient period. Milk fever occurred in 1 of 8 cows just after parturition. Plasma TRAP activities did not markedly change in 5 of 8 cows during the experimental period. The changing rate of Ca between preparturition and just after parturition was under -20% in 3 of 8 cows, and low TRAP activities were observed in 2 of these 3 cows. This study suggests that cows with a low TRAP activity are at risk of developing milk fever in comparison to cows with high TRAP activity. Temporary increases of parathyroid hormone were observed in 7 cows, but not in the cow with milk fever.

The influence of nitric oxide synthase inhibitor L-NAME on bones of male rats with streptozotocin-induced diabetes.

The pathophysiological processes underlying the development of diabetic osteopenia has not hitherto been elucidated. Induction of streptozotocin diabetes leads in our experiments to decrease of bone density, ash, mineral content and to thinner cortical width compared to control male rats. In order to investigate the pathogenetic role of bone resorption by osteoclasts in streptozotocin-induced diabetes, we determined the circulating levels of tartrate-resistant acid phosphatase (TRAP), a biochemical marker for bone resorption. Plasma TRAP values in diabetic rats did not differ from their corresponding controls. Streptozotocin diabetes by itself did not have any effect on the weight of seminal vesicles which are highly testosterone-dependent. Low doses of nitric oxide cause bone resorption, but higher doses of NO inhibit bone resorbing activity. We examined the effect of L-NAME (inhibitor of nitric oxide production) after six weeks of administration to diabetic rats. There was no further significant loss of bone mineral density, ash and mineral content or tibia weight in diabetic rats treated with L-NAME. L-NAME itself did not decrease bone metabolism. In our study no evidence of an increased bone resorption was found. Our results have indicated that a predominance of bone resorption over bone formation is not involved in the pathogenesis of diabetes-associated osteopenia. Inhibition of NO neither increased osteoclastic activity (TRAP) nor induced osteopenia in L-NAME-treated rats. This suggests a possibility that NO is not involved in the pathogenesis of diabetic osteopenia.

Correlation of Bone Marrow Response with Hematological, Biochemical, and Visceral Responses to Enzyme Replacement Therapy of Nonneuronopathic (Type 1) Gaucher Disease in 30 Adult Patients

ABSTRACTPurpose. This investigation correlates the marrow response with the degree of increase in hemoglobin (Hb) and platelet count (Plt); decrease in concentrations of plasma tartrate-resistant acid phosphatase, serum angiotensin-converting enzyme (ACE), serum ferritin, and plasma chitotriosidase; and decrease in liver and spleen size, measured by ultrasonography. Methods. Thirty adult patients with nonneuronopathic (type 1) Gaucher disease (23% splenectomized) were followed for mean periods of 12 and 36 months. Results. The series achieved highly significant mean responses in all hematological, biochemical, and visceral parameters over both observation periods; over a mean 36 months, 19 (63%) had a marrow response, 11 (37%) did not. Six of 7 splenectomized patients attained a marrow response. There were no significant differences between the marrow responders and nonresponders in age, sex, spleen status, Gaucher genotype distribution, mean baseline hematological or biochemical values or liver size, or mean follow-up. At a mean follow-up of 12 months, no significant differences yet were evident between marrow responders and nonresponders in seven of eight response parameters, but marrow responders had a significantly greater reduction in plasma chitotriosidase and a trend toward significantly greater reduction in serum ACE. At a mean follow-up of 36 months, marrow responders had a significantly greater mean increase in Plt and mean decrease in serum ferritin concentration and liver size than did marrow nonresponders; the trend toward greater ACE reduction in marrow responders deepened. However, chitotriosidase response now was equivalent in both subgroups. Marrow nonresponders had a significantly greater mean diminution in spleen size than did marrow responders, but the marrow nonresponders had significantly larger mean spleen size at baseline. Marrow nonresponders also had a greater mean increase in Hb than did marrow responders, but the difference was not significant. The two subgroups had equivalent mean reductions of plasma TRAP. Conclusions. The clinical relevance of qualitative MRI of the bone marrow in monitoring patients receiving ERT for nonneuronopathic Gaucher disease show that marrow nonresponders can derive considerable benefit from ERT across a variety of other response parameters and suggest an influence of spleen size on marrow response to ERT.

Changes in calcium homoeostasis in patients undergoing liver transplantation: effects of a single infusion of pamidronate administered pre-operatively

Bone turnover, bone loss and fracture risk increase after liver transplantation. It has been postulated that peri-operative administration of a bisphosphonate might prevent bone loss and reduce fracture rate. We studied the effects of a single pre-operative dose of pamidronate on biochemical parameters of skeletal metabolism in the first month after liver transplantation. In a randomized, single-blind study, six of 12 patients with chronic liver disease received 60 mg of pamidronate intravenously on a single occasion 1-30 days before transplantation. Six other patients undergoing transplantation received no pamidronate. We measured serum calcium, phosphate, albumin, bone-specific alkaline phosphatase, plasma parathyroid hormone and tartrate-resistant acid phosphatase before pamidronate infusion and at frequent intervals during the first 30 post-operative days. In treated patients, plasma parathyroid hormone increased 12-fold over baseline values and remained elevated in comparison with baseline at days 26-30; serum calcium and phosphate fell significantly, returning to normal at around day 14 post-operatively. There were no significant changes in any parameter in the untreated group. No changes in bone formation or resorption markers were observed in either group. The large increase in plasma parathyroid hormone concentrations in the treated group is probably secondary to the fall in serum calcium. The magnitude of the increase is much greater than that seen after pamidronate infusion in other patient groups. The lack of change in, or correlation of, serum calcium and plasma parathyroid hormone in the untreated group suggests that additional factors release calcium from bone after liver transplantation, presumably by increasing bone resorption.

T Cell Numbers Relate to Bone Involvement in Gaucher Disease

ABSTRACT: The major elements of bone pathology in Gaucher disease are a failure of osteoclast and osteoblast function, resulting in osteopenia and also osteonecrosis. T lymphocytes have recently been found to be involved in the regulation of osteoblast/osteoclast activity in vitro. In the present report the peripheral blood T major lymphocyte subsets were investigated in a group of genotyped type 1 Gaucher disease patients. A total of 31 patients were studied: 21 non-splenectomized (5 N370S homozygotes) and 10 splenectomized (of whom 1 was a N370S homozygote). The results show that non-splenectomized patients present a decrease in absolute numbers of peripheral blood T lymphocytes, specially the CD4+ T subset. However, when patients were analyzed with respect to the presence of bone disease, the number of CD8+ T lymphocytes was found to be statistically significantly lower in patients presenting bone involvement. Furthermore, lower numbers of CD8+ T lymphocytes were significantly correlated with higher levels of plasma tartrate resistant acid phosphatase (TRAP) activity, a putative marker of osteoclast cell activity. These in vivo findings are in agreement with the results reached in vitro by others. They provide an additional marker of disease severity in Gaucher disease. In the group of genotyped Gaucher disease patients, the majority of the N370S homozygous patients presented a clinically milder phenotype, including the absence of bone involvement, confirming earlier reports predicting that a number of these patients may remain undiagnosed. Collectively the homozygosity for the N370S mutation and normal T cell numbers may provide additional markers for the clinical heterogeneity of Gaucher disease.

Beta 2-microglobulin does not behave as a biological marker of bone remodelling in patients with primary hyperparathyroidism

Parathormone has been shown to increase the secretion and production of lysosomal enzymes including tartrate-resistant acid phosphatase. All our 68 patients with proven primary hyperparathyroidism had signs of hyperparathyroid bone disease. Tartrate-resistant acid phosphatase and bone alkaline phosphatase activities are raised as a result of enhanced bone remodelling. Serum beta 2-microglobulin concentration in patients with primary hyperparathyroidism was normal 1.6 (1.4–1.8) mg/l versus 1.8 (1.7–2.2) mg/l in 51 control subjects. In hyperparathyroid patients, serum beta 2-microglobulin concentration does not correlate with plasma tartrate-resistant acid phosphatase activity which is known to be a sensitive biological marker of bone remodelling (r=0.088). Our findings indicate that serum beta 2-microglobulin does not behave as a biological marker of remodelling in patients with enhanced remodelling in primary hyperparathyroidism.

Circulating Levels of Tartrate-Resistant Acid Phosphatase in Rat Models of Non-Insulin-Dependent Diabetes Mellitus

In order to investigate the pathogenic role of bone resorption by osteoclasts in altered bone metabolism in non–insulin-dependent diabetes mellitus (NIDDM), the circulating levels of tartrate resistant acid phosphatase (TRACP) were simultaneously determined with osteocalcin, in rat models of NIDDM, i.e., genetic Wistar fatty rats and neonatally streptozotocin-induced diabetic rats (NSZ rats). In Wistar fatty rats exhibiting hyperglycemia and hyperinsulinemia, plasma TRACP was 40.0 ± 0.4 U/l (mean ± SE), significantly higher than that of 32.8 ± 1.3 U/l in their lean littermates ( p < 0.01). Bone length, bone strength, and weight of powdered bone in Wistar fatty rats were significantly decreased compared to control rats ( p < 0.02–0.001). On the other hand, plasma TRACP in NSZ rats was 13.6 ± 1.0 U/l, significantly lower than that of 31.4 ± 1.2 U/l in their controls ( p < 0.01). In addition, there were positive correlations between circulating TRACP and insulin levels in both NIDDM rat models ( p < 0.05–0.01). Furthermore, plasma osteocalcin levels in these NIDDM models were significantly decreased than those of their corresponding controls ( p < 0.001). Consequently, in Wistar fatty rats with hyperinsulinemia, it is suggested that the bone formation by osteoblasts was decreased, while the bone resorption by osteoclasts was increased. In contrast, in NSZ rats with hypoinsulinemia, both of bone formation and resorption were speculated to be decreased, indicating the decreased bone turnover. These results suggest that, although the deterioration in the osteoblastic function can be commonly observed in NIDDM animal models, the osteoclastic function is heterogeneous under NIDDM conditions.

Analysis of relationships between sex hormone dynamics and bone metabolism and changes in bone mass in surgically induced menopause.

A 3-year follow-up study was performed of bone metabolism and bone changes induced by surgical menopause as a consequence of hysterectomy and oophorectomy (OVX) is 52 nonmenopausal women. We investigated 22 bone parameters and determined seven bone indices as indicators of bone mineral content by dual energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and microdensitometry (MD). The significant correlations between levels of sex hormones and/or bone parameters and bone indices demonstrated that marked sex-steroid deficiency after surgical menopause induced bone uncoupling during high bone turnover and subsequent rapid bone loss on the early period after OVX. Principal component analysis using correlation coefficients suggested a seven-loading-factor matrix composed of bone parameters and a two-loading-factor matrix composed of bone indices. Two groups of parameters--estradiol and estriol, and androstenedione together, and luteinizing hormone and follicle stimulating hormone together--indicated that the rate of bone loss was greater in the trabecular bone than in the cortical bone. Three other groups of parameters--urine calcium, urine hydroxyproline, and serum bone Gla-protein together; serum alkaline phosphatase, serum calcium, and 1,25-dihydroxycholecalciferol [1,25(OH)2D] together; and plasma tartrate-resistant acid phosphatase--indicated that bone uncoupling, with a prevalence of resorption over formation of bone, was greater in trabecular bone than is cortical bone and also that magnitude and rate of bone loss in the axial vertebrae surpassed those in the appendicular metacarpals after OVX. Two other groups of parameters, namely, trabecular bone mineral density (Dd) and bone mineral content (Dc), both measured by DXA, and bone mineral density (L2, L3), measured by QCT, together; and the cortical thickness index (MCI), cortical bone mineral density (sigmaGS/D), and the ratio of GSmin/max, measured by MD, indicated that the relative rates of bone reduction at the 3-year follow-up were greater in the axial vertebrae than in the appendicular metacarpals. Thus, bone change in the trabecular bone was associated with rapid loss during the early phase after OVX, whereas that in the cortical bone was slow during the late phase.