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1.
This study analyzes the relationship between the function of femoral regions in the rat and the extent of collagen type I
posttranslational modifications, to assess whether the different functional roles, i.e., mechanical or metabolic, of the bone
tissues are related to the molecular structure of the matrix. For this purpose, 18 female, 100-day-old Sprague-Dawley rats
were sacrificed, under anesthesia, and their femurs were removed and dissected free of adhering tissue. The spongy bone of
the proximal metaphysis and the diaphysis were then selected as regions exerting prevalently a mechanical function, and the
spongy bone of the distal metaphysis was selected as mainly related to metabolic function. Bone prepared from these regions
was used to extract and purify the major component of the matrix, type I collagen. The content of hydroxyproline, hydroxylysine,
glycosylated hydroxylysine, and pyridinium crosslinks was evaluated and the amount of each compound was expressed as a molar
ratio to hydroxyproline. The amount of glycosylated hydroxylysine and pyridinium crosslinks in the distal metaphysis are significantly
different from the amounts measured both in the diaphysis and the proximal metaphysis. On the contrary, the amounts of the
same compounds in the diaphysis and the proximal metaphysis are statistically the same. The amount of free hydroxylysine,
however, appears to be different in the proximal metaphysis and in the diaphysis. The conclusion is that matrix composition
differs among different skeletal regions according to the main function they exert.
Received: 5 February 1999 / Accepted: 13 August 1999 相似文献
2.
Effects of Clodronate on Cortical and Trabecular Bone in Ovariectomized Rats on a Low Calcium Diet 总被引:5,自引:0,他引:5
T. S. Kaastad O. Reikerås J. E. Madsen S. Narum J. H. Strømme K. J. Obrant L. Nordsletten 《Calcified tissue international》1997,61(2):158-164
The aim of this study was to evaluate the contribution of a low calcium diet to the cortical and trabecular osteoporosis
seen in ovariectomized rats after 7 weeks on a low calcium diet and to investigate the effects of the bisphosphonate clodronate
on this development of osteoporosis. Thirty-six mature, female Wistar rats were randomized into four groups: Ovx−B (bisphosphonate)
and Ovx−C (control) were ovariectomized, and Sham−Ca (low calcium) and Sham+Ca (normal calcium) were sham operated. The first
three groups were fed a low calcium diet (0.01%) and Sham+Ca normal rat chow (Ca 1.1%). The Ovx−B received 10 mg/kg s.c. clodronate
daily for nine weeks, and Ovx−C, Sham−Ca, and Sham+Ca received the same volumes of saline. Bone mineral turnover measured
as 85Sr-uptake was increased in all low calcium groups compared to Sham+Ca. The Sham+Ca femora had higher dry weight and ash weight
than the other groups, and Ovx−C had higher dry weight compared with Ovx−B and Sham−Ca. Calcium content was lower in both
Ovx groups compared to both Sham groups. Magnesium was lower in all groups compared to Sham+Ca and higher in Ovx−B compared
with Ovx−C. In the femoral shaft, Sham+Ca had significantly higher ultimate bending moment, energy absorption, and deflection
compared to the other three groups. Ultimate bending moment was higher in Sham−Ca than in Ovx−C. Stiffness was increased in
both Sham+Ca and Ovx−B compared to Ovx−C. The maximum stress in the femoral midshaft was higher in Sham+Ca than in the other
groups, and higher in Ovx−B than in Ovx−C. Histomorphometry showed increased medullary area in all low calcium groups compared
to Sham+Ca and larger cortical area in Sham+Ca and Ovx−B compared to Ovx−C. Compared to Sham+Ca the trabecular bone volume
was decreased to 30% in Sham−Ca and to 9% in Ovx−C, but was unchanged in Ovx−B. The low calcium diet generally increased bone
mineral turnover and reduced the tibial bone volume. Femoral changes led to a reduction of cortical fracture strength and
maximal stress. Ovariectomy in addition to a low calcium diet reduced femoral strength even more. Daily injections of clodronate
to ovariectomized rats on a low calcium diet increased femoral shaft stiffness and maximum stress, and clodronate preserved
both trabecular and cortical tibial bone volume completely.
Received: 11 June 1996 / Accepted: 5 March 1997 相似文献
3.
H. Rico M. Gómez M. Revilla J. González-Riola C. Seco E. R. Hernández L. F. Villa J. J. Gervás 《Calcified tissue international》1999,65(4):272-275
The effect of promethazine on bone is debated. We studied the effect of promethazine on bone and the mechanism of action
involved by densitometric and histomorphometric measurements in female Wistar rats (100 days old, mean weight 25 ± 20 g).
A control group of 15 rats was not manipulated. An experimental group of 15 rats were ovariectomized (OVX) at 100 days of
life and fed a diet supplemented with 4.8 mg/kg promethazine hydrochloride (OVX + Prom). The group that underwent OVX and
a group of 15 rats that underwent sham ovariectomy (Sham-OVX) were not treated with promethazine. After 30 days, all the rats
were killed. Their femur and 5th lumbar vertebra were dissected and cleaned of soft tissue. Femoral length and vertebral height
were measured with a caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone mineral
density (BMD) of the whole right femurs and 5th lumbar vertebras were measured by dual-energy X-ray absorptiometry (DXA).
Trabecular bone volume (Cn-BV-TV%), trabecular number (Tb-N mm−1), trabecular thickness (Tb-Th μm), and trabecular separation (Tb-Sp μm) were measured in the femurs by histomorphometric
study of nondecalcified bone. Our results showed that promethazine significantly inhibited postovariectomy loss of bone mass
(P < 0.0001) by significantly reducing bone resorption, as shown by the smaller trabecular spaces observed in the treated OVX
rats (P < 0.0001).
Received: 1 June 1998 / Accepted: 17 February 1999 相似文献
4.
P. Geusens S. Boonen J. Nijs Y. Jiang G. Lowet R. Van Auderkercke C. Huyghe F. Caulin J. M. Very J. Dequeker G. Van der Perre 《Calcified tissue international》1996,59(4):315-320
The aim of this study was to evaluate the effect of intermittent calcitonin on femoral bone quality in adult ewes from the
time of ovariectomy. Six months after the start of the experiment, bone density measurements and mechanical testing (torsion
and resonant frequency analysis of the diaphysis and compression of an excised trabecular bone cylinder from the femoral neck)
were performed in sham-control and ovariectomized (OVX) ewes treated with placebo or salmon calcitonin (50 or 100 units, 3
times/week). Crystallinity of bone was evaluated by measuring X-ray diffraction line broadening. After OVX, a nonsignificant
bone loss was found at all measured sites in the femur (−3 to −9%) together with a decreased biomechanical competence in the
trabecular bone (compressive strain −28%, P < 0.05). Treatment with salmon calcitonin, 50 or 100 IU subcutaneously three times a week from the time of ovariectomy, resulted
in a significant dose-dependent preservation of bone strength in the trabecular bone of the femoral neck compared with OVX.
No adverse effects of calcitonin were observed on bone crystal composition as assessed by diffractiometry. We conclude that
in adult ewes intermittent calcitonin treatment from the time of OVX was associated with a significant preservation of cancellous
bone strength and strain in trabecular bone of the femoral neck, without affecting crystalline properties of bone.
Received: 20 October 1995 / Accepted: 19 February 1996 相似文献
5.
A 12-Month Prospective Study of the Relationship Between Stress Fractures and Bone Turnover in Athletes 总被引:3,自引:0,他引:3
K. L. Bennell S. A. Malcolm P. D. Brukner R. M. Green J. L. Hopper J. D. Wark P. R. Ebeling 《Calcified tissue international》1998,63(1):80-85
Bone remodeling may be involved in the pathogenesis of stress fractures in athletes. We conducted a 12-month prospective
study to evaluate bone turnover in 46 female and 49 male track and field athletes aged 17–26 years (mean age 20.3; SD 2.0)
20 of whom developed a stress fracture. Baseline levels of bone turnover were evaluated in all athletes and monthly bone turnover
levels were evaluated in a subset consisting of the 20 athletes who sustained a stress fracture and a matched comparison group
who did not sustain a stress fracture. Bone formation was assessed using serum osteocalcin (OC) measured by human immunoradiometric
assay and bone resorption by urinary excretion of pyridinium cross-links (Pyr and D-Pyr); high performance liquid chromatography
and N-telopeptides of type 1 collagen (NTx) using ELISA assay. Athletes who developed stress fractures had similar baseline
levels of bone turnover compared with their nonstress fracture counterparts (P > 0.10). Results of serial measurements showed no differences in average levels of Pyr, D-Pyr, or OC in those who developed
stress fractures (P= 0.10) compared with the control group. In the athletes with stress fractures, there was also no difference in bone turnover
levels prior to or following the onset of bony pain. Our results show that single and multiple measurements of bone turnover
are not clinically useful in predicting the likelihood of stress fractures in athletes. Furthermore, there were no consistent
temporal changes in bone turnover associated with stress fracture development. However, our results do not negate the possible
pathogenetic role of local changes in bone remodeling at stress fracture sites, given the high biological variability of bone
turnover markers and the fact that levels of bone turnover reflect the integration of all bone remodeling throughout the skeleton.
Received: 12 August 1997 / Accepted: 8 January 1998 相似文献
6.
J. L. Cardenas M. Revilla E. R. Hernández F. Aguado L. F. Villa H. Rico 《Calcified tissue international》1997,61(5):358-361
Three techniques of bone mass measurement were evaluated in the diagnosis of postmenopausal osteoporosis; the overlap in
the measurements and the capacity for discriminating was determined among 51 postmenopausal normal (mean age 66.6 ± 8.4 years)
and 42 postmenopausal osteoporotic women (mean age 68.5 ± 7.5 years). All bone mass was evaluated by total body bone mineral
content (BMCTB), density (BMDTB), ultrasound bone velocity (UBV) in proximal phalanxes 2–5 of the nondominant hand (UBV = mean value of all ultrasound measurements),
and peripheral quantitative computed tomography of the nondominant forearm (pQCT). BMCTB was found to be significantly better (P < 0.0001) for diagnosing postmenopausal osteoporosis than the other methods; both cortical and trabecular pQCT measurements
were more discriminating than the corresponding UBV measurements (P < 0.001). T-score values in normals, subjects versus osteoporotic ones were BMCTB−1.15 ± 0.79 versus −3.17 ± 0.74; BMDTB−1.01 ± 0.97 versus −3.28 ± 0.81; UBV −1.51 ± 1.02 versus −2.34 ± 1.21; trabecular-pQCT −0.40 ± 0.72 versus −1.57 ± 0.37;
cortical-pQCT −1.00 ± 0.87 versus −2.67 ± 0.53; and total-pQCT −0.65 ± 1.01 versus −2.34 ± 0.27, respectively. The overlap
in values between the postmenopausal normal and postmenopausal osteoporotic groups was 50% with UBV, 6% with BMCTB, 9% with BMDTB, 25% with cortical pQCT, and 42% with trabecular pQCT. BMCTB, BMDTB, UBV, and pQCT correlated well with each other as measurements of bone mass, but BMCTB was more discriminating than the other measurements in the diagnosis of osteoporosis.
Received: 7 June 1995 / Accepted: 21 May 1997 相似文献
7.
The aim of this study was to evaluate whether fast trabecular bone loss in osteoporotic and osteopenic patients can effectively
be treated with active vitamin D metabolites. Thirty-one osteoporotic and osteopenic patients were monitored between 4 and
22 months before and between 8 and 18 months during the treatment. Fast bone losers were designated as osteoporotic or osteopenic
patients with a loss of trabecular bone density in the radius of 3% or more calculated for 1 year. For this differentiation,
the high precise peripheral quantitative computed tomography system (DENSISCAN 1000) was used (reproducability 0.3% in mixed
collectives). The pretreatment loss and the ``gain' under treatment with active vitamin D metabolites was calculated for
1 year. The treatment consisted of either 0.5 μg calcitriol daily or 1 μg of alfacalcidol daily. Before treatment, the trabecular
bone loss in the radius/year was −6.6 ± 0.5% (mean ± SEM). After treatment with vitamin D metabolites, the trabecular bone
gain in the radius/year was 0.01 ± 0.6% (mean ± SEM). The difference was highly significant (P < 0.001). In contrast to this, the loss of cortical bone density before treatment was −1.8 ± 0.3% (mean ± SEM) and the reduced
loss after treatment −0.2 ± 0.4% (mean ± SEM), both values calculated for 1 year. This difference was less significant (P < 0.05). This study shows that the treatment with active vitamin D metabolites is very effective in slowing fast trabecular
bone loss in osteoporotic and osteopenic patients. 相似文献
8.
Prostaglandin E2 (PGE2) is an anabolic agent of bone in vivo but the mechanism of its action still remains unclear. The aim of this study was to determine whether the effect of PGE2 on skeleton is mediated by pituitary hormones. Forty female, Sprague-Dawley rats were divided into four groups: baseline
control (basal), age-matched intact control (CON), hypophysectomy (HX), and HX + PGE2 (2 mg/kg/day) with 10 animals in each group. The basal group was sacrified at 2 months of age, and the remaining groups after
6 weeks of treatment. Cancellous and cortical bone histomorphometry was performed on double fluorescent-labeled 40 μm-thick
sections of the proximal tibia and tibial shaft. Our results show that HX resulted in a cessation of bone growth, a decrease
in cancellous bone volume, and cortical bone gain compared with the age-matched, intact CON rats. Compared with the HX group,
the HX + PGE2 group had a significantly greater tibial bone density (mean ± SE, HX + PGE2:1.595 ± 0.007 versus HX:1.545 ± 0.013), percent cancellous bone volume (21.4 ± 2.0 versus 8.41 ± 1.70), percent cortical
bone area (87.2 ± 0.85 versus 81.7 ± 0.7), and ratio of cortical area to marrow area (7.14 ± 0.56 versus 4.52 ± 0.21). Increased
bone masses by PGE2 in the HX animals were accompanied by an increase in the trabecular and endosteal-labeled surface and bone formation rate.
The trabecular number and width were increased whereas trabecular separation was decreased in the HX + PGE2 group compared with the HX group (P < 0.05). PGE2 treatment also caused a decrease in the tibial endosteal eroded surface and medullar cavity of the HX animals. In conclusion,
this study clearly demonstrates that PGE2 (2 mg/kg/day) in the HX rats increases both cortical and cancellous bones and improves trabecular architecture in the tibia
after 6 weeks of treatment. These skeletal alterations are due to a stimulation of bone formation and a suppression of bone
resorption activity. These findings suggest that the anabolic effect of PGE2 in bone is independent of pituitary hormones. 相似文献
9.
Does Leptin Have an Effect on Bone in Adult Women? 总被引:7,自引:0,他引:7
F. Rauch W. F. Blum K. Klein B. Allolio E. Schönau 《Calcified tissue international》1998,63(6):453-455
Recent studies have implicated leptin in the modulation of bone mass during skeletal development. Whether leptin also exerts
an influence on bone after growth has stopped is unknown at present. In this cross-sectional study on 94 women (60 premenopausal,
34 postmenopausal) aged 40–60 years, we analyzed the relationship between serum leptin and bone density and bone cortex geometry
and bone metabolism. Total and trabecular bone density as well as total and cortical bone area were determined by quantitative
computed tomography (QCT) at the distal radius. Bone metabolism was assessed by measuring bone-specific alkaline phosphatase,
osteocalcin, procollagen type I C-terminal propeptide (PICP) and collagen type I C-terminal telopeptide in serum, and deoxypyridinoline
in urine samples. None of the indices of bone density or geometry was significantly related to leptin serum concentrations
(P > 0.05) before or after adjustment for body mass index (BMI). PICP was associated with serum leptin in the postmenopausal
group only (r =−0.40 after adjustment for BMI; P= 0.009). Yet, as none of the other markers of bone metabolism exhibited a significant correlation with serum leptin in any
of the menopausal groups, this association is likely to be due to the influence of extraskeletal factors on PICP serum levels.
Thus, it appears that leptin has less influence on the mature than on the growing skeleton.
Received: 5 January 1998 / Accepted: 12 May 1998 相似文献
10.
Clodronate Prevents Bone Loss in Aged Ovariectomized Rats 总被引:1,自引:1,他引:0
K. Kippo R. Hannuniemi L. Laurén Z. Peng P. Isaksson T. Virtamo T. Österman I. Pasanen R. Sellman H. K. Väänänen 《Calcified tissue international》1997,61(2):151-157
The purpose of this study was to investigate the ability of clodronate to prevent ovariectomy (OVX)-induced osteopenia in
aged rats. Fourteen-month-old female Sprague-Dawley rats (n = 166) were randomized into six groups. One group was sacrificed
at the start of the study, four groups were ovariectomized, and one group was sham-operated (Sham). The OVX rats were given
subcutaneously either vehicle (veh) or clodronate at doses of 3, 7, or 25 mg/kg once a week for 3 months, and the Sham rats
were given the vehicle. At all dose levels clodronate inhibited trabecular bone loss in the distal femur and in the fourth
lumbar vertebral body (L4), and decreased bone resorption as evidenced by urinary deoxypyridinoline excretion. The lowest
dose of clodronate preserved serum osteocalcin and endosteal bone formation of secondary spongiosa in L4 at the level of the
Sham/veh group. The OVX-induced increase in periosteal bone formation of femoral diaphysis was unaffected by two smaller doses
of clodronate, but was decreased to the level of Sham rats after the highest dose. After 3 mg/kg clodronate, the percentage
of femoral cortical bone area and the mean relative cortical thickness were higher compared with the OVX/veh group. There
was a good positive correlation between the maximum load in three-point bending of the tibia and tibial ash weight. Normal
lamellar pattern of newly formed cancellous and cortical bone was found after clodronate treatment. No signs of adverse accumulation
of osteoid or any deleterious effect on mechanical strength of long bones and lumbar vertebrae were found.
Received: 28 August 1996 / Accepted: 5 March 1997 相似文献
11.
The aim of this study was to investigate the extent of lysyl and prolyl hydroxylation of collagen I in osteoporosis and compare
it with collagen I from ``bone healthy' individuals. Collagen I was isolated from femoral heads of osteoporotic women, from
women suffering from osteoarthrosis of the hip, and from healthy women 60–85 years of age. The femoral heads were dissected
into compact and trabecular bone of the neck region and from trabecular bone of the head region, and collagen I was extracted
by limited pepsin digestion. The amino acid analysis of individual α-chains showed a remarkably higher degree of hydroxylation
of lysine residues both in the α1(I)- and in the α2(I)-chains in osteoporotic bone compared with osteoarthrotic and ``normal'
bone, whereas the prolyl hydroxylation was nearly unchanged. The lysyl overhydroxylation was observed in the compact as well
as in the trabecular bone of osteoporotic femoral heads. These biochemical alterations may play a crucial role in the pathogenesis
of osteoporosis.
Received: 2 May 1996 / Accepted: 31 December 1996 相似文献
12.
Honda A Kurabayashi T Yahata T Tomita M Matsushita H Takakuwa K Tanaka K 《Calcified tissue international》2000,67(5):367-372
Changes in the structure and metabolism of trabecular bone and marrow adipocytes in rats during pregnancy and the early stage
of postpartum were evaluated by investigating bone mineral density (BMD) and bone and fat histomorphometry. Forty-nine female
virgin Sprague-Dawley rats aged 200 days were mated and divided into seven groups: (1) beginning controls; (2) antepartum-on-day-7;
(3) antepartum-on-day-21; (4) nonlactating on the fourth postpartum day; (5) nonlactating on the sixth postpartum day; (6)
nonlactating on the eighth postpartum day; (7) lactating on the eight postpartum day. The significant decreases occurred in
the trabecular bone at the end of pregnancy and lactation, and the bone formation increases and the bone structure is almost
recovered in nonlactating rats within 6 days of postpartum. The percent adipocyte volume, adipocyte number, and unit adipocyte
volume significantly decreased during postpartum whether lactating or nonlactating, and they significantly showed negative
correlation with the osteoid volume values. The serum triglyceride value and body weight of the seven groups correlated significantly
with the unit adipocyte volume value (r = 0.49, P= 0.004; r = 0.58, P= 0.0005, respectively). We concluded that bone resorption and formation are regulated separately during late pregnancy and
lactation and that the recovery of BMD from lactation appears to rely on an acceleration of bone formation. Furthermore, the
metabolism of the marrow adipocyte may be correlated with bone formation rates, serum triglyceride value, and body weight
during pregnancy and early stage of puerperium.
Received: 5 October 1999 / Accepted: 27 April 2000 / Online publication: 27 July 2000 相似文献
13.
Development and Application of a Serum C-Telopeptide and Osteocalcin Assay to Measure Bone Turnover in an Ovariectomized Rat Model 总被引:2,自引:0,他引:2
Srivastava AK Bhattacharyya S Castillo G Wergedal J Mohan S Baylink DJ 《Calcified tissue international》2000,66(6):435-442
Biochemical markers applicable to the ovariectomized rat model can provide important tools for studying the bone remodeling
process in this animal model of postmenopausal osteoporosis. We describe the development and application of two biochemical
markers, a C-telopeptide (of type-I collagen) enzyme-linked immunosorbent assay (ELISA) for measuring bone resorption and
an osteocalcin radioimmunoassay (RIA) for measuring bone formation in rat serum. The C-telopeptide ELISA is based on an affinity
purified polyclonal antibody generated against human sequence DFSFLPQPPQEKAHDGGR. The antibody epitope involves amino acid
sequence, which is similar in rat and human carboxyl terminal peptide of type-I (alpha 1) collagen. Sensitivity of the ELISA
was 0.3 ng/ml. The averaged intra- and interassay variation was CV <7%. Averaged dilution and spiked recoveries were 91% and
105%, respectively. The second marker developed is a synthetic peptide-based osteocalcin RIA, which does not require isolation
and purification of intact osteocalcin from rat bone. Osteocalcin antiserum used in the RIA was generated in rabbits against
a synthetic peptide comprising amino acids 33–49 of the rat osteocalcin sequence. The sensitivity of the RIA was 0.15 ng/ml
of peptide. The averaged intra (n = 10) and interassay variations for two controls were CV <9% and 12%, respectively. The
averaged dilution and spiked recoveries were 99.6%. In vivo validation of the C-telopeptide ELISA and osteocalcin RIA was performed in an ovariectomized (OVX) rat model. In 12-week-old
OVX Sprague Dawley rats, the C-telopeptide and osteocalcin concentrations were approximately 65% and 40%, respectively, higher
than the sham group. Estradiol repletion significantly lowered the C-telopeptide and osteocalcin concentration to the levels
of the sham group. In addition, changes in serum C-telopeptide concentration correlated negatively with trabecular BMD measured
by pQCT (r =−0.51, P < 0.001). In conclusion, the C-telopeptide ELISA and osteocalcin RIA exhibited required sensitivity, accuracy, and adequate
discriminatory power to be used for measuring bone resorption and bone formation in the ovariectomized rat model.
Received: 20 August 1999 / Accepted: 5 January 2000 相似文献
14.
Gaumet-Meunier N Coxam V Robins S Pastoureau P Pointillart A Davicco MJ Lebecque P Barlet JP 《Calcified tissue international》2000,66(6):470-475
At 45 days of age, 40 male Wistar rats were castrated, then randomly divided into four groups, S.C. injected for 60 days
after surgery either with 17β-estradiol (E) 10 μg/kg BW/48 hours, progesterone (P) 140 μg/kg BW/48 hours, dihydrotestosterone
(D) 2 μg/kg BW/48 hours, E + P + D same doses, or solvent alone (CX). Ten other rats were sham-operated (SH) and used as controls.
Animals were put in balance to determine Ca and phosphorus (Pi) intestinal apparent absorption (IA Ca, IA Pi) and urinary
pyridinium crosslinks excretion. Plasma was collected for measurement of intact-parathyroid hormone (PTH), calcitonin (CT),
insulin-like growth factor I (IGF-I), 1,25 dihydroxyvitamin D (1,25(OH)2D), Ca, and Pi. Orchidectomy induced marked seminal vesicles atrophy and increased plasma CT, PTH, and Ca concentrations.
IA Ca was significantly higher in P rats, however, neither castration nor any other treatment had significant effects. Orchidectomy
decreased femoral length, dry weight, and Ca content, whereas E or D given alone or together with P improved endochondral
growth and enhanced femoral Ca content. Again, bone mineral density was lowered by orchidectomy and reestablished by both
E and EPD, even above SH values, this effect being more important at the metaphyseal levels. Urinary pyridinium cross-links
excretion and plasma osteocalcin concentrations were higher in the CX animals than in the controls. Although E and D given
alone did reduce both biochemical turnover markers, they showed additive effect when given together (EPD). In conclusion,
in the young castrated male rat, E was more efficient than D for preventing bone loss, the most important effect being induced
by a combination of E + P + D.
Received: 28 June 1999 / Accepted: 12 January 2000 相似文献
15.
The goal of this study was to evaluate the effects of chronically-elevated male levels of the potent androgen testosterone
on the quality and quantity of both cancellous and cortical bone in a young (mean age 8.0 years), nonhuman female primate
model (M. fascicularis). Thirteen intact female monkeys received continuous testosterone supplementation via subcutaneous implants over a 24-month
period. A group of 16 untreated, intact, age-matched female monkeys served as controls. At sacrifice, the lumbar vertebrae
and femora were recovered in order to analyze the bone mineral quality and quantity of cancellous and cortical bone, respectively,
and compared to the control group. Mineralization profiles of the vertebrae and femora were obtained using the density fractionation
technique. Chemical analysis of the three largest fractions retrieved by density fractionation was performed to evaluate differences
in %Ca, %P, Ca/P ratio, and mineral content (%Ca + %PO4) between the control and experimental groups. In addition, unfractionated bone powder was examined by X-ray diffraction to
identify any changes in crystal size. Coronal sections of vertebrae were analyzed for structural parameters using histomorphometry
and image analysis. Cross sections taken at the midshaft diaphyseal femora were analyzed for structural macroscopic and intracortical
parameters. A nonsignificant shift in the mineralization profile of the vertebrae was observed whereas there was a significant
shift in the mineralization profile towards more dense bone in the treated femora as compared with controls (P < 0.05). There was no difference in terms of size/strain of the cortical or cancellous bone crystal as detected by X-ray
diffraction. There was a trend towards an increase in cancellous bone area (B.Ar.) in the testosterone-treated vertebrae (P= 0.08) as compared with controls. The architecture of the cancellous bone remained nonsignificantly different between the
treatment and control groups as evaluated by image analysis. There was a decrease in osteoid perimeter (P= 0.05) in the experimental group as compared with controls. There was a significant decrease in eroded perimeter measurements
in the experimental group as compared with controls (P < 0.03). Although there was a trend towards an increase in cancellous bone area, mineralization was not significantly different
in the vertebrae of testosterone-treated female monkeys, indicating that the newly-formed bone tissue became relatively normally
mineralized over the two-year period. An increase in bone area, with indices of an overall decreased remodelling pattern as
compared with controls, suggests that cancellous bone in the young, nonhuman female primate had been receptive to supraphysiologic
levels of testosterone supplementation over the two-year period. There was a trend for an increase in cortical bone area and
width with an increased periosteal perimeter in the testosterone-treated group as compare with controls. There was an increase
in intracortical remodelling activity with a significant increase in percent porosity (P < 0.05), osteonal bone (P < 0.05), and mean wall width (P < 0.05) in the testosterone-treated group. In conclusion, the cancellous bone from female monkeys appeared to respond to
the antiresorptive stimulus of male levels of testosterone with significantly diminished turnover parameters in this compartment.
In contrast, the cortical bone compartment responded by displaying significant intracortical remodelling over a two-year period.
Received: 22 December 1995 / Accepted: 3 April 1996 相似文献
16.
R. Dresner-Pollak R. A. Parker M. Poku J. Thompson M. J. Seibel S. L. Greenspan 《Calcified tissue international》1996,59(5):328-333
Although over 90% of hip fractures occur in patients over age 70, few data are available on femoral bone loss in this age
group. To examine the relationship between biochemical markers of bone turnover and femoral bone loss in the elderly, 36 female
and 17 male, healthy, community-dwelling elderly over age 65 (mean ± SD age: women 71 ± 4 years, men 75 ± 5 years) were followed
for 3 years. Annual bone mineral density measurements of the hip and lumbar spine by dual-energy x-ray absorptiometry (DXA)
were obtained and biochemical markers of bone resorption (urinary N-telopeptide crosslinks, free pyridinoline, total pyridinoline,
total deoxypyridinoline, and hydroxyproline) and bone formation (serum osteocalcin, bone-specific alkaline phosphatase) were
obtained at the end of year 3. In elderly women, longitudinal bone loss at the total hip was negatively correlated with markers
of bone resorption (r =−0.39 to −0.52, P < 0.05), bone formation (r =−0.38, P < 0.05), and age (r =−0.39, P < 0.05). Markers of bone resorption were correlated with markers of bone formation (r = 0.63 to 0.74, P < 0.01). In multiple regression analysis, urinary N-telopeptide crosslinks (marker of resorption), serum osteocalcin (marker
of formation), and serum parathyroid hormone explained 43% of the variability of bone loss at the total hip in women. These
parameters were not related to bone loss in men. We conclude that femoral bone loss increases with age in women over 65. Measurements
of specific biochemical markers of bone turnover are correlated with longitudinal bone loss in elderly women. These markers
may help identify women at greatest risk for bone loss who would benefit most from therapeutic interventions.
Received: 28 January 1996 / Accepted: 3 May 1996 相似文献
17.
The effects of 10% dietary xylitol supplementation in ovariectomized rats were studied on the degradation of bone organic
and inorganic structures. The osseal concentrations of hydroxyproline, pyridinoline, and deoxypyridinoline were analyzed by
high-performance liquid chromatography. Bone resorption was measured in [3H]tetracycline-prelabeled rats by urinary excretion of 3H, and by the amount of 3H preserved in bone. Bone trabeculation was measured by a computer image analyzer from sections stained by the method of von
Kossa. The amount of collagen in bone organic fraction was lower in ovariectomized rats as compared with the sham-operated
controls. This most likely is partly a consequence of an increased resorption, and partly a consequence of a higher proportion
of immature periosteal bone in the ovariectomized animals, leading to a higher ratio of noncollagenous protein to collagen.
The number of pyridinium crosslinks was lower in proportion, indicating no selective changes in the structure of collagen.
Dietary xylitol significantly retarded the ovariectomy-associated decrease in the relative amount of collagen and the number
of its mature crosslinks. Ovariectomy doubled the excretion of 3H and caused a significant decrease in the amount of 3H preserved in bone; both these changes were significantly retarded by the 10% dietary xylitol supplementation. Ovariectomy
significantly decreased the volume of bone trabeculae, but this effect was also significantly inhibited by the xylitol supplementation
in the diet. In conclusion, these findings suggest a dietary xylitol-induced normalizing effect on the rate of bone turnover
in ovariectomized rats.
Received: 12 February 1996 / Accepted: 20 August 1996 相似文献
18.
Serum Levels of Pyridinium Crosslinks in Postmenopausal Women and in Paget's Disease of Bone 总被引:1,自引:0,他引:1
L. Sinigaglia M. Varenna L. Binelli P. Beltrametti F. Zucchi M. Arrigoni S. Frignani G. Abbiati 《Calcified tissue international》1997,61(4):279-284
The purpose of this study was to measure pyridinium crosslinks in serum by high performance liquid chromatography (HPLC)
and to correlate levels with urinary excretion in patients with different osteometabolic conditions. Blood and spot urine
samples were collected between 9 and 11 A.M. in 92 early postmenopausal, untreated women (age 52.3 ± 2.6 years, months since
menopause 20.4 ± 9.6), 17 patients with active Paget's disease (10 males, aged 65.1 ± 12.6) and 24 healthy premenopausal women
(aged 28.4 ± 4.2). Urinary excretion of the total fraction (free + peptide bound) of pyridinolines (Pyr, Dpyr) was measured
by HPLC. Before HPLC analysis, serum samples were submitted to a clean-up procedure by ultrafiltration. In 42 postmenopausal
women, bone loss was calculated from two bone mass measurements (L2–L4, DXA), performed at study entry and after 12 months.
Statistical analysis was performed by Student's t test for independent samples and linear regression analysis. In pagetic patients' serum levels of Pyr and Dpyr were more
than threefold increased over the mean observed in healthy controls and were closely correlated with total alkaline phosphatase
levels (Pyr: r = 0.73; Dpyr: r = 0.72, P < 0.0005). Compared with controls, postmenopausal women had significantly increased levels of both urinary and serum Pyr
and Dpyr (P < 0.003). In pagetic patients and postmenopausal women, crosslinks serum levels were correlated with their urinary excretion
with r values ranging from 0.46 to 0.84. In postmenopausal women, only serum Dpyr correlated with the rate of bone loss (r
=−0.36, P= 0.02). The data suggest that serum levels of pyridinium cross-links are correlated with urinary excretion in patients with
different osteometabolic conditions. The determination of serum levels prevents limitations related to urinary specimen collection
and may be a more practical method for routine application, avoiding corrections for urinary creatinine which could be misleading.
Received: 13 August 1996 / Accepted: 25 April 1997 相似文献
19.
S. S. Kohles J. R. Bowers A. C. Vailas R. Vanderby 《Calcified tissue international》1996,59(3):214-217
There is considerable interest in determining whether hypergravity can be used as a countermeasure for microgravity-induced
bone loss. This study was conducted on 20 immature male rats in order to investigate possible elastic adaptations of cortical
bone in rapidly growing rats exposed to chronic hypergravity. Ten rats were continuously centrifuged for 14 days at twice
gravitational acceleration (2G) on a 12.75 foot radius centrifuge and 10 rats concurrently acted as stationary controls. The
effect of hypergravity on the elastic characteristics of cortical bone was quantified via ultrasonic wave propagation. Propagation
velocities of longitudinal and shear waves were measured through cubic cortical specimens from the posterior femoral diaphyses.
Density was measured with an Archimedes' technique. The orthotropic elastic properties were calculated and used to compare
the difference between groups. Results showed an average increase in both the Young's moduli (Eii, + 2.2%) and shear moduli (Gij, + 4.3%) with a statistically significant increase only in G12 (+15.7%, P= 0.046). The ratio of transverse to axial strain (Poisson's ratio, νij) demonstrated statistically significant changes in ν12, ν21, ν13, and ν31 (P < 0.05). These findings suggest that although slight elastic changes were incurred via a hypergravity environment, the treatment
level or duration in this study do not dramatically perturb the normal elastic behavior of cortical bone and that dramatic
biomechanical differences noted in previous studies were due more to structural changes than material elasticity changes.
Hypergravity applied post facto to a microgravity environment would offer further illucidation of this method as treatment for a degenerative spaceflight
experience.
Received: 12 August 1995 / Accepted: 23 February 1996 相似文献
20.
The effects of 5, 10, and 20% dietary xylitol supplementations on the biomechanical properties, histological architecture,
and the contents of collagen, pyridinoline, and deoxypyridinoline in long bones of rats were studied. Tibiae were used for
the three-point bending test, and femurs were used for the torsion and loading test of the femoral neck. The 10 and 20% oral
xylitol administrations caused a significant increase of tibial stress, femoral shear stress, and stress of the femoral neck
as compared with the controls. Parallel, but not significant, effects were also seen in the 5% xylitol supplementation group.
No significant differences in strain or Young's modulus of the tibiae were detected between the groups. An increased shear
modulus of elasticity in femurs was detected in the 20% supplementation group as compared with the controls. The histomorphometrical
data for the secondary spongiosa of the proximal tibia revealed that trabecular bone volume was significantly greater in all
dietary xylitol supplementation groups as compared with the controls. The bone volume increased along with increasing xylitol
content. No significant differences between the groups were detected concerning the amount of collagen per dry weight of organic
matrix, the concentrations of pyridinoline or deoxypyridinoline in collagen, or the ratio of these crosslinks. This suggests
no xylitol-dependent selective changes in these structures of bone collagen. In conclusion, dietary xylitol supplementation
in rats improves the biomechanical properties of bone and increases the trabecular bone volume dose dependently.
Received: 30 January 1997 / Accepted: 1 October 1998 相似文献