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1.
Association Study of Parathyroid Hormone Gene Polymorphism and Bone Mineral Density in Japanese Postmenopausal Women 总被引:15,自引:1,他引:15
Hosoi T Miyao M Inoue S Hoshino S Shiraki M Orimo H Ouchi Y 《Calcified tissue international》1999,64(3):205-208
Association of BST B1 restriction fragment length polymorphism (RFLP) of the parathyroid hormone (PTH) gene with bone mineral density (BMD)
was examined in 383 healthy postmenopausal women in Japan who were unrelated. The RFLP was represented as B or b, the capital
letter signifying the presence of and the small letter the absence of restriction site for BST B1. The frequency of each genotype—BB, Bb, and bb—was 82.5%, 16.7%, and 0.8%, respectively. When we statistically compared
age, years after menopause, body height, and body weight between the BB genotype and the Bb genotype groups, there was no
significant difference between the groups. However, the lumbar BMD and the score of BMD adjusted for age and body weight (Z
score) were significantly lower in the group of genotype Bb than in the BB: 0.859 ± 0.019 g/cm2 versus 0.925 ± 0.011 (mean ± SE, P= 0.01) and −0.412 ± 0.138 versus 0.067 ± 0.082 (mean ± SE, P= 0.01). In addition, the Z score of total body BMD in the Bb genotype group was lower than that in the BB group. Comparison
of serum and urinary biochemical bone metabolic markers suggested that the subjects with Bb genotype might be in a relatively
higher state of bone turnover than those with BB genotype. These results suggest that the polymorphism in the PTH gene would
be a useful genetic marker for lower BMD and the susceptibility for osteoporosis.
Received: 19 March 1998 / Accepted: 24 June 1998 相似文献
2.
Even though indirect evidence indicates that PTH exerts an anabolic effect on dentinogenesis, the existence of PTH receptors
and any second-messenger response in odontoblasts have not been demonstrated. The aim of this study was to investigate whether
rat incisor odontoblasts express PTH receptors, and to identify which second messenger pathway the hormone may activate. Odontoblasts
were dissected from rat incisors. Amino-terminal (1-34) fragment rat PTH [rPTH(1-34)] conjugated to fluorescein isothiocyanate
visualized receptor sites on the cell surface. Upon incubation of odontoblasts with rPTH(1-34), cAMP formation was increased.
However, no fluctuations in intracellular calcium activity were observed upon rPTH(1-34) stimulation when using Fura-2 as
a Ca2+ probe. In long-time incubations, stimulation with PTH(1-34) upregulated APase activity. The results demonstrate that rPTH(1-34)
evokes an anabolic response in dentinogenically active odontoblasts, and that this may be mediated through the protein kinase
A/cAMP pathway, whereas no indications for Ca2+ as a second messenger were evident.
Received: 12 March 1997 / Accepted: 26 June 1997 相似文献
3.
Parathyroid Hormone Modulates the Response of Osteoblast-Like Cells to Mechanical Stimulation 总被引:6,自引:0,他引:6
Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid
hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical
stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase,
was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like
cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid
forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced
a rapid increase in [Ca2+]i. Although PTH did not significantly change [Ca2+]i levels, flow and PTH did produce a significantly greater [Ca2+]i response and increased the number of responding cells than is found in fluid shear alone. The [Ca2+]i response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present.
These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response
may be mediated by alterations in [Ca2+]i by modulating the mechanosensitive channel.
Received: 5 October 1999 / Accepted: 15 February 2000 相似文献
4.
J. F. Whitfield P. Morley V. Ross E. Preston M. Soska J.-R. Barbier R. J. Isaacs S. Maclean L. Ohannessian-Barry G. E. Willick 《Calcified tissue international》1997,60(3):302-308
Parathyroid hormone (PTH), hPTH-(1-84), and its hPTH-(1-34), hPTH-(1-31)NH2, and hPTH-(1-30)NH2 fragments reduced the tail artery pressure in anesthetized female Sprague-Dawley rats by 42.4–67.1% within about 1 minute
after injection into a femoral vein, but reduced the pressure by only 8.5–36.2% 2–19 minutes after subcutaneous injection.
hPTH-(1-84) and hPTH-(1-34) stimulate both adenylyl cyclase and phospholipase-C in their target cells, but the hypotensive
action must have been stimulated specifically by adenylyl cyclase activation, because hPTH-(1-30)NH2 and hPTH-(1-31)NH2, which can only stimulate adenylyl cyclase, were potently hypotensive when injected intravenously whereas hPTH-(7-84), which
can only stimulate phospholipase-C, was not significantly hypotensive when injected intravenously. Since PTH's osteogenic
action is also mediated by adenylyl cyclase stimulation, it was expected that the hypotensive response might be used to screen
new PTH constructs for possible osteogenicity. Indeed, the osteogenic activities of subcutaneously injected hPTH-(1-31)NH2, hPTH-(1-34), and hPTH-(1-84) correlated closely to their hypotensive activities, with hPTH-(1-34) being much more hypotensive
and significantly more osteogenic than the other two molecules. hPTH-(1-31)NH2 and hPTH-(1-84) were equally osteogenic and hypotensive. However, this correlation broke down with hPTH-(1-30)NH2 which does not stimulate bone formation, but in the present study it stimulated adenylyl cyclase and reduced tail artery
pressure almost as much as hPTH-(1-31)NH2 and hPTH-(1-34). Nevertheless, the ability to significantly reduce arterial pressure is a common property of osteogenic PTH
and PTH fragments and is thus a rapidly determinable preliminary indicator of in vivo bioactivity of PTH fragments.
Received: 2 May 1996 / Accepted: 9 August 1996 相似文献
5.
R. Gagnemo-Persson A. Samuelsson R. Håkanson P. Persson 《Calcified tissue international》1997,61(3):210-215
Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens,
omeprazole induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also
of the parathyroid glands (hypertrophy + hyperplasia), while suppressing bone density and body weight gain without affecting
blood calcium. The first part of the present study was concerned with the effect of omeprazole, ergocalciferol (vitamin D2), and restricted food intake on the gene expression of parathyroid hormone (PTH) in the parathyroid glands of the chicken.
Chickens were treated with omeprazole (400 μmol/kg/day, I.M.), food restriction, omeprazole + food restriction, ergocalciferol
(250 000 IU/kg/day, S.C.), or ergocalciferol + omeprazole for 5 weeks. The weight gain of the chickens was monitored, and
the weights of the parathyroid glands and femurs were determined at sacrifice. PTH mRNA in the parathyroid glands was analyzed
by Northern blot. The second part of the study examined the effect of 3 weeks of continuous gastrin infusion (chicken gastrin
20–36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the parathyroid glands. Omeprazole reduced the body weight and
femur density (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression.
Food restriction alone and ergocalciferol alone (at a dose that raised blood Ca2+) were without effect, but food restriction greatly enhanced the omeprazole-evoked increase in parathyroid gland weight and
PTH gene expression. Gastrin increased the weight of the parathyroid glands and reproduced the effect of omeprazole on PTH
gene expression. Hence, it seems likely that the effect of omeprazole reflects the ensuing hypergastrinemia.
Received: 6 August 1996 / Accepted: 23 April 1997 相似文献
6.
The present study was an attempt to evaluate the relative importance of familial/genetic factors in interindividual variation
of plasma concentrations of parathyroid hormone (PTH) and bone mineral density (BMD). We also examined to what extent common
genetic and environmental factors may be involved in covariation between the hormone concentrations and BMD levels.
Ninety-five nuclear pedigrees (consisting of 187 males and 168 females, aged 18–91 and 18–86 years old, respectively), from
several small villages in the Chuvasha Autonomy, Russia, were assessed for PTH, sex hormones, and BMD. PTH plasma levels were
measured in duplicate by immunoradiometric assay using an N-tact PTH SP kit. Standard roentgenography was done from the second
and third phalanges of the middle finger on both hands for assessment of compact and cancellous bone BMD separately. The present
study clearly confirmed the results of the previous genetic analyses of BMD which indicated that between 47% and 60% of the
total variance of BMD, adjusted for sex and age effects, were attributable to genetic factors. Genetic factors also contributed
significantly to interindividual variation of PTH. Constraining these additive genetic effects to zero dramatically increased
the likelihood ratio (P < 0.001), indicating that at least 30% of the hormone plasma variation was attributable to genetic sources. The results of
bivariate decomposition analysis were not clear cut. Two types of bivariate analyses showed that PTH-BMD genetic correlations
according to sex and between the opposite sexes were consistently negative, but only marginally significant.
Received: 21 July 1998 / Accepted: 30 September 1999 相似文献
7.
S. L. Bonnick D. L. Nichols C. F. Sanborn K. Lloyd S. G. Payne L. Lewis C. A. Reed 《Calcified tissue international》1997,61(4):263-265
The purpose of this study was to determine if differences exist in premenopausal women between z-scores for lumbar spine
and proximal femoral bone mineral densities (BMD). Participants were 237 women ranging in age from 20 to 45 years. BMDs of
the lumbar spine and proximal femur (femoral neck, Ward's area, and trochanter) were assessed using dual-energy X-ray absorptiometry
(Lunar DPX). Mean (±SD) age, height, and weight of the participants were 29.4 ± 6.9 years, 164.4 ± 6.1 cm, and 64.9 ± 12.1
kg, respectively. Lumbar spine BMD and BMD at the femoral neck, Ward's area, and trochanter were significantly correlated
with large SEEs (r = 0.59–0.65; SEE = 0.09–0.11). No positive correlation with age and BMD at any site was seen in this population
but a significant negative correlation with age was seen in the proximal femur beginning at age 30. Twenty to 24% of the 20–29-year-olds
exhibited a difference in z-scores of greater than 1 between the spine and sites in the proximal femur. This percentage increased
to 32–46% in the 30–45-year-olds but the nature of the observed differences changed. The differences in spine and proximal
femoral z-scores that are seen in the older age group appear to be the result of the earlier onset of bone loss in the proximal
femur rather than an initial difference in peak bone mass which has been maintained.
Received: 28 August 1996 / Accepted: 25 April 1997 相似文献
8.
J. F. Aloia A. Vaswani C. Delerme-Pagan E. Flaster 《Calcified tissue international》1998,62(6):481-485
Black women have 40% of the incidence rate for hip fracture and have a higher bone mineral density (BMD) than white women.
The possibility was raised that bone quality may be disproportionately greater than the advantage in bone density in protection
against osteoporotic fractures in black versus white women. Ultrasound (US) of the calcaneus is believed to measure properties
of bone in addition to its density. We performed bone density measurements and US of the calcaneus in 108 black and 177 healthy
white women, aged 20–70 years. The highest correlation was seen between total body bone density and speed of sound (r = 0.75).
The interracial differences in BMD were all statistically significant and varied from 3.4 to 7.6%. The US measurements had
lesser interracial differences than the bone density measurements, with velocity barely different between races. These findings
suggest that US of the calcaneus measures properties of bone different from density. Fracture prediction data using US from
prospective data in white women should not be extrapolated to black women because of the discordance between bone density
and US measurements. Prospective studies are needed comparing US measurements in black women to the occurrence of osteoporotic
fractures.
Received: 30 May 1997 / Accepted: 8 January 1998 相似文献
9.
This study was designed to determine the fate of new parathyroid hormone (PTH)-induced cortical bone after withdrawal of
PTH treatment, and to evaluate whether subsequent treatment with a bisphosphonate would influence this. Six groups of 21-month-old
rats were used: a baseline group killed at the beginning of the experiment, three groups injected with human PTH (1-34) (62
μg/kg) daily for 8 weeks (day 1-56), then one group was killed and the other two groups were injected for another 8 weeks
(day 57-112) with either saline or bisphosphonate (risedronate 5 μg/kg twice a week). Two control groups were injected with
vehicle for the first 8 weeks, then one group was killed and the other group injected with saline the next 8 weeks. All animals
were labeled with tetracycline and calcein on day 35 and day 49 of the experiment, respectively. PTH increased periosteal
(35%) and in particular endosteal mineralizing surfaces (188%), mineral appositional rates, and bone formation rates at the
femur diaphysis, leading to an increase in cortical cross-sectional area of 31%. Withdrawal of PTH induced a fast and pronounced
endosteal bone resorption whereas risedronate prevented this resorption. No differences were seen in apparent density of dry
defatted bone and ash among the groups. PTH increased the mechanical strength of the femur diaphysis; ultimate load increased
by 64% and ultimate stress by 25%. A pronounced decrease in mechanical strength and competence was found after withdrawal
of PTH: ultimate load decreased by 31% and ultimate stress by 21%. Risedronate, however, prevented this decrease in mechanical
strength and competence in these 2-year-old rats.
Received: 13 March 1997 / Accepted: 22 August 1997 相似文献
10.
11.
A. S. Turner J. M. Maillet C. Mallinckrodt L. Cordain 《Calcified tissue international》1997,61(2):110-113
Dual-energy X-ray absorptiometry (DXA) of the head has received little attention. We used DXA to measure bone mineral density
(BMD) of the entire skull including the mandible (BMDHead) and BMD of the cranial vault (BMDVault) in 91 normal young women. We also measured BMD of the total body (BMDTotal body), proximal femur (``total femur'), and lumbar vertebrae (L1–L4). BMD (g/cm2; mean ± SE) was 1.032 ± 0.011 for L1–L4, 0.995 ± 0.011 for total femur, and 2.283 ± 0.028 for BMDVault (cranial vault) and the mean body weight of all subjects was 59.8 kg. Correlation between BMDVault and BMDHead was 0.991 and this was not different from 1.0 (P= 0.473). The average difference between BMDVault and BMDHead was −0.004 g/cm2 suggesting that these two measurements of bone mass of the skull were similar. To determine the correlation between the different
variables after accounting for external sources of variation, partial correlation derived from multiple regression was determined.
Correlations between BMD at the various locations and with BMDTotal body were moderate to strong. Although small in magnitude, the partial correlations of body weight with BMDTotal body, total femur, and L1–L4 were significantly different from zero (P < 0.02). The results show that BMDVault, total femur, and L1–L4 were of equal value in predicting BMDTotal body and further, BMDVault was not influenced by body weight. Including body weight in multiple regression in addition to total femur or L1–L4 removed
the extraneous variation due to body weight, and predictions of BMDTotal body were as reliable as when BMDVault was based on goodness of fit tests (P= 0.314). The technique used to measure BMD of the cranial vault is a relatively new variation of DXA technology. The precision
was as good as other measurements of bone mass of the entire skull (including the mandible). Because the cranial vault is
less sensitive to mechanical influences, it may be a region where response to therapy could be evaluated. The cranial vault
may be a useful area to study certain heritable diseases that affect the skeleton, skeletal artifact, or evaluation of oral
bone loss.
Received: 22 December 1995 / Accepted: 24 September 1996 相似文献
12.
Biochemical Responses of Bone Metabolism to 1,25-Dihydroxyvitamin D Administration in Black and White Women 总被引:2,自引:0,他引:2
F. Cosman V. Shen D. Morgan S. Gordon M. Parisien J. Nieves R. Lindsay 《Osteoporosis international》2000,11(3):271-277
The basis for the racial difference in bone mass between black and white women is not known. Lower bone turnover, better
renal calcium conservation, and decreased sensitivity to parathyroid hormone (PTH) have been proposed as explanations. A dynamic
comparison of osteoblast function, utilizing stimulation by 1,25-dihydroxyvitamin D [1,25(OH)2D], has not been tested between these two ethnic groups. We compared well-matched black (n= 15) and white (n= 15) premenopausal women, before and during 5 days of 1,25(OH)2D administration (1.0 μg/day) in order to assess dynamic indices of bone metabolism. As expected, at baseline, black women
had lower levels of serum 25-hydroxyvitamin D and biochemical markers of bone turnover with slightly higher levels of PTH.
Black women also had superior renal calcium conservation than white women at baseline. In response to 1,25(OH)2D administration, black women had a slightly greater increase in serum calcium and greater decrement in PTH. Moreover, black
women showed a lesser increment in urinary calcium than white women and a more robust increase in two markers of bone formation
– osteocalcin and carboxyterminal propeptide of type 1 procollagen – than white women. There were no changes in bone resorption
indices in either race upon 1,25(OH)2D administration. These data provide preliminary evidence that black women conserve calcium more efficiently under both static
and dynamic conditions, and also appear to have better osteoblastic functional reserve than white women.
Received: 22 June 1999 / Accepted: 6 September 1999 相似文献
13.
J. F. Whitfield P. Morley G. Willick S. MacLean V. Ross R. J. Isaacs J.-R. Barbier 《Calcified tissue international》1998,63(5):423-428
hPTH-(1-31)NH2, so far the smallest of the potently anabolic N-terminal fragments of the human parathyroid hormone, stimulates trabecular
growth in the distal femurs of ovariectomized (OVX) rats as strongly as hPTH-(1-34) when injected at a high daily dose such
as 1 nmol/100 g of body weight, but it is only about 70% as effective as hPTH-(1-34) when injected at the suboptimal 0.6 nmol/100
g of body weight. A lactam derivative of hPTH-(1-31)-NH2, [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2, is a much more effective stimulator of adenylyl cyclase in ROS 17/2 rat osteoblast-like cells and a significantly more effective
stimulator of femoral trabecular growth in OVX rats than hPTH-(1-31)NH2. We have now shown that [Leu27]-cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 prevents the OVX-induced loss of femoral trabeculae significantly more effectively than hPTH-(1-34) and stimulates the thickening
of the trabeculae remaining in severely depleted femoral trabecular bone of OVX rats as effectively as hPTH-(1-34) when injected
at 0.6 nmol/100 g of body weight.
Received: 26 December 1997 / Accepted: 23 March 1998 相似文献
14.
Hormone replacement therapy (HRT) prevents bone loss in postmenopausal women. Up to 20% of women demonstrate no increase
in bone mineral density (BMD) on HRT. We examined whether early changes in serum bone alkaline phosphatase (B-ALP) predict
long-term BMD changes in postmenopausal women on HRT. Ninety women within 1 year of menopause were randomly assigned to continuous
or sequential estrogen/progestin (beta estradiol/norethisterone acetate) if naturally postmenopausal, or beta estradiol if
within 1 month of surgical menopause. Spine, femoral neck BMD (DXA), and B-ALP were determined over 2 years. The mean percent
BMD changes were 3.8%, 2.9%, 1.6% in the spine and 2.4%, 4.0%, 1.1% in the femoral neck in sequential, continuous, and estrogen
alone treatment groups, respectively, significantly different from zero except for femoral neck BMD change in the estrogen
alone group. HRT was associated with spine and femoral neck BMD loss in 17.4% and 25.3% of women, respectively. In estrogen/progestin-treated
women, baseline B-ALP correlated with spine BMD change (r = 0.42, P < 0.01). At 3 months, B-ALP dropped significantly in the estrogen/progestin-groups with a maximal decrease at 12 months,
but no change from baseline in the estrogen alone group. Using quartile analysis, women with the greatest drop in B-ALP (≥50%)
at 6 months demonstrated the greatest gain in spine BMD at 2 years. A 40% decrease at 6 months in B-ALP had a 56% sensitivity,
83% specificity, 95% positive predictive value for spine BMD gain at 2 years. The decrease in B-ALP can be used to monitor
BMD response to HRT.
Received: 6 January 1999 / Accepted: 13 August 1999 相似文献
15.
L. M. Salamone T. Whiteside D. Friberg R. S. Epstein L. H. Kuller J. A. Cauley 《Calcified tissue international》1998,63(6):466-470
Cytokines such as interleukin-1 (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) can influence both bone resorption
and bone formation. The objective of this cross-sectional study was to examine the relationship between cytokine production
by peripheral blood mononuclear cells (PBMC) and bone mineral density (BMD); the annual rate of change in BMD was examined.
Subjects participating in a randomized clinical trial entitled the Women's Healthy Lifestyle Project in Allegheny County,
Pennsylvania were used. They included 50 healthy premenopausal women, aged 45–52 years, who had regular menses within the
past 3 months and were not on replacement estrogens. Dual-energy X-ray absorptiometry measurements at the AP lumbar spine
and femoral neck were made at baseline and at the first annual exam using a Hologic QDR 2000 densitometer. Cytokine production
of IL-1β, IL-6, and TNF-α by PBMC was measured at the annual exam. The median values for stimulated cytokine production by
PBMC were 3.92 ng/ml, 31.3 ng/ml, and 1.05 ng/ml, for IL-1β, IL-6, and TNF-α, respectively. There were modest correlations
between cytokine production and cross-sectional BMD, ranging from r =−0.30 to r =−0.13. Trends of greater spinal bone loss
were observed in women with ``high' (≥75th percentile) cytokine production of stimulated IL-1β and IL-6 (IL-1β: ``high'
=−1.56% ± 0.70 versus ``low' (<75th percentile) =−0.56% ± 0.35, P= 0.21). In contrast, greater annual gains in femoral neck BMD were observed in those with high cytokine production of IL-1β
and IL-6 (IL-1β: high = 3.39% ± 1.16 versus low =−0.85 ± 0.58, P= 0.002). There was no association between stimulated TNF production and annual change in BMD. In this population of healthy
premenopausal women, the relationship between cytokine production by PBMC and the rate of change in BMD was significantly
different for the lumbar spine and femoral neck, possibly reflecting differences in the proportion of trabecular and cortical
bone at these sites.
Received: 5 February 1997 / Accepted: 11 May 1998 相似文献
16.
The effects of OST-766, an inhibitor of vacuolar H+-ATPase activity, on adenylyl cyclase and phospholipase C activity were explored in the osteoblast cell line ROS 17/2.8. In
fresh homogenates of ROS 17/2.8 cells, OST-766 inhibited adenylyl cyclase activity (ACA) in response to guanine nucleotide
and forskolin but had no effect on basal ACA. OST-766 enhanced the basal generation of IP2, but not that formed in response
to Ca2+ or guanine nucleotides. In marked contrast, incubation of intact ROS 17/2.8 cells with OST-766 for at least 48 hours resulted
in an increase in basal ACA as well as in response to PTH, guanine nucleotides and forskolin. Under similar conditions, the
compound also increased IP1, IP2 and IP3 generation in response to guanine nucleotides and Ca2+. Levels of the guanine nucleotide binding proteins Gs and Gi were also increased in OST-766-treated cells. The results suggest
that the actions of this H+-ATPase inhibitor include effects on osteoblasts through PTH-sensitive signal transduction pathways.
Received: 20 August 1997 / Accepted: 7 August 1998 相似文献
17.
Stimulation of Femoral Trabecular Bone Growth in Ovariectomized Rats by Human Parathyroid Hormone (hPTH)-(1-30)NH2 总被引:4,自引:0,他引:4
J. F. Whitfield P. Morley G. E. Willick S. MacLean V. Ross J.-R. Barbier R. J. Isaacs 《Calcified tissue international》1999,65(2):143-147
It has been proposed that intermittent bursts of adenylyl cyclase and the surges of cyclic AMP (cAMP) they produce can trigger
PTH's bone anabolic action without the activation of phospholipase-C (PLC). This was based on the osteogenic action in ovariectomized
(OVX) rats of hPTH-(1-31)NH2, which can stimulate adenylyl cyclase but not PLC in ROS 17/2 rat osteosarcoma cells, and the osteogenic impotence of fragments
such as 1-desamino-hPTH-(1-34) and hPTH-(8-84) which strongly stimulate PLC but not adenylyl cyclase. But this seems to have
been disproven by the inability of hPTH-(1-30)NH2 to stimulate bone growth despite its having hPTH-(1-31)NH2's ability to strongly stimulate adenylyl cyclase but not PLC in cells with rat type1 PTH/PTHrP receptors. Because of the
importance of hPTH-(1-30)NH2's apparent osteogenic impotence for knowing how PTH triggers bone growth, we have reinvestigated the fragment's ability to
stimulate trabecular bone growth in the femurs of young OVX rats and have found it to be strongly osteogenic at doses 2–10
times higher than the highest dose used previously. Thus, 6 weeks of once-daily subcutaneous injections of 10–50 nmol of hPTH-(1-30)NH2/100 g of body weight into young rats starting 2 weeks after OVX significantly increased the femoral trabecular volume and
mean thickness of individual trabeculae above those in sham-operated control rats. In OVX rats treated with 50 nmol of hPTH-(1-30)NH2/100 g of body weight, the trabecular volume was 2.6 times higher and the mean trabecular thickness nearly 4 times higher
than in the sham-operated control rats. This very large increase in the mean trabecular thickness was as much as the increase
induced by 2 nmol/100 g of body weight of hPTH-(1-31)NH2, [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)NH2, hPTH-(1-34)NH2 and [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-34)NH2. These results have removed a major objection to the proposal that PTH's osteogenic action in rats can be triggered solely
by intermittent surges of cAMP and the bursts of cAMP-dependent protein kinase activity they cause.
Received: 16 September 1998 / Accepted: 15 December 1998 相似文献
18.
This study was undertaken to compare the effect of supraphysiological doses of thyroxine (T4) on bone metabolism in SHAM
and OVX young adult rats. Female Sprague Dawley rats (220 ± 2 g, approx. 5 months of age) were divided into four groups of
eight animals each. The animals were intraperitoneally injected 6 days per week with vehicle (Vh): 0.001 N NaOH/0.9% NaCl
(SHAM+Vh and OVX+Vh) or 250 μg of thyroxine/kg/day (SHAM+T4 and OVX+T4) during a 5-week period. Serum T4 and osteocalcin (BGP),
urinary pyridinolines (Pyr), and creatinine (creat) were determined. At the beginning and at end of the experiment, skeletal
bone mineral content (BMC), bone mineral density (BMD), and area (A) of the total skeleton, femur, spine, and whole tibia,
as well as proximal, middle, and distal areas of the tibia were assessed by dual X-ray absorptiometry (DXA) in an ultra-high-resolution
mode. T4 treatment of the SHAM rats did not induce significant changes in BGP level or Pyr/creat excretion compared with the
SHAM+Vh control group. However, these two biochemical bone markers significantly increased due to T4 treatment in OVX rats
compared with both OVX+Vh and SHAM+T4 groups (P < 0.05 and P < 0.001, respectively). The OVX+T4 group had a significantly lower ΔBMD than SHAM+T4 rats in all studied regions (P < 0.05) except for the middle tibia region. OVX+T4 groups presented a significantly lower ΔBMC and ΔA compared with SHAM+T4
animals (P < 0.001). OVX+T4 rats significantly impaired the ΔBMD in the femur (P < 0.01), spine (P < 0.05), whole (P < 0.05) and middle (P < 0.05) tibia whereas T4 treatment of SHAM rats only affected, significantly, the whole (P < 0.05) and the proximal tibia region (P < 0.01). T4 treatment affects bone growth in young adult rats. The effect is significantly greater in the estrogen-depleted
than in the estrogen-repleted state. The bone site most adversely affected by T4 treatment depends on the estrogen status.
The proximal tibia (principally trabecular bone) was the most affected area in estrogen-repleted rats. Conversely, in OVX
rats, the middle tibia (principally cortical bone) presented the greatest decrease in bone density.
Received: 20 May 1999 / Accepted: 4 February 2000 相似文献
19.
J. F. Aloia A. Vaswani M. Mikhail M. Badshah E. Flaster 《Calcified tissue international》1999,65(1):29-33
The bone mineral density (BMD) of the spine was measured in the posteroanterior (PA) and lateral projections as well as the
total body BMD in 447 black and white women. The lateral projection is comprised predominantly of cancellous bone whereas
the total body BMD is predominantly cortical bone, and the PA spine is intermediate in composition. Black women had a higher
BMD than white women for each measurement, but the difference was greatest in the lateral spine. Similarly, black women showed
less decline in cancellous bone density with aging. The development of a high peak cancellous bone mass with reduced involutional
loss may provide a major contribution towards protection against osteoporotic fractures in black women. Metabolic and pharmacologic
studies in black and white women should consider the possibility of the influence of a larger cancellous bone mass.
Received: 14 November 1997 / Accepted: 11 December 1998 相似文献
20.
The Association between Parathyroid Hormone, Vitamin D and Bone Mineral Density in 70-Year-Old Icelandic Women 总被引:4,自引:0,他引:4
G. Sigurdsson L. Franzson L. Steingrimsdottir H. Sigvaldason 《Osteoporosis international》2000,11(12):1031-1035
Parathyroid hormone (PTH) may be an important determinant of cortical bone remodeling in the elderly. Vitamin D status is
one of the determining factors in this relationship. The aim of this study was to quantify the relationship between serum
PTH, vitamin D and bone mineral density (BMD) in elderly women in Reykjavik (64° N), where daily intake of cod liver oil is
common and mean calcium intake is high. ln PTH correlated inversely with 25(OH)D (r=−0.26, p<0.01). In multivariate analysis PTH correlated inversely with whole body BMD (mostly cortical bone) (R
2= 2.2%, p = 0.04) but not with the lumbar spine BMD, reflecting more cancellous bone. No association was found between 25(OH)D levels
and BMD at any site in univariate or multivariate analysis. Osteocalcin, a measure of bone turnover, was negatively associated
with BMD and this association remained significant when corrected for PTH levels. In summary, in this fairly vitamin D replete
population with high calcium intake, PTH was negatively associated with total body BMD. We infer that suppression of PTH may
reduce cortical bone loss, but other factors are likely to contribute to age-related bone remodeling and osteoporosis.
Received: 3 January 2000 / Accepted: 10 April 2000 相似文献