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1.
Twenty-four late postmenopausal women with osteoporosis were studied. The patients were separated in three subgroups according
to the BsmI polymorphism of the vitamin D receptor (VDR) gene: BB (n= 8), Bb (n = 10) and bb (n = 6). They did not differ in age (mean ages were 66.0 years, 65.9 years and 63.9 years, respectively), years after menopause
(18.7 years, 18.1 years and 18.4 years) or body weight (64.9 kg, 65.3 kg and 63.8 kg), the variables known to be associated
with bone mineral density (BMD). The results show that the response to antiresorptive bisphosphonate therapy in combination
with calcium supplementation is modified by VDR genotype. The lumbar spine BMD increased significantly faster in the BB and
Bb groups (7.3% and 7.0%, respectively) compared with the bb group (2.5%) during 1 year of cyclic etidronate therapy (400
mg/day) and calcium supplementation (1000 mg/day). The biochemical marker of bone resorption (urinary hydroxyproline excretion)
as well as the bone formation marker (serum levels of osteocalcin) decreased during the treatment. With respect to VDR genotype,
a significantly higher decrease in osteocalcin level was observed in bb as compared with BB subjects. We conclude that the
VDR genotype is involved in an individual’s response to cyclic etidronate therapy with calcium supplementation.
Received: 12 December 1998 / Accepted: 18 March 1999 相似文献
2.
Vitamin D Receptor Gene Polymorphisms, Bone Mass, Bone Loss and Prevalence of Vertebral Fracture: Differences in Postmenopausal Women and Men 总被引:7,自引:0,他引:7
C. Gómez M. L. Naves Y. Barrios J. B. Díaz J. L. Fernández E. Salido A. Torres J. B. Cannata 《Osteoporosis international》1999,10(3):175-182
Bone mineral density (BMD), the major determinant of fracture risk, is under strong genetic control. Although polymorphisms
of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass, the influence
of VDR genotypes on osteoporosis remains controversial. Previous published studies have focused mainly on women, but the pattern
of response in men has not been determined. Using the BsmI restriction enzyme, we studied the influence of the different VDR genotypes on bone mass, bone loss and the prevalence of
vertebral fractures in a population-based sample of both sexes (n = 326). BMD was measured at the lumbar spine and femoral neck, with a 4-year interval, using dual-energy X-ray absorptiometry.
Vertebral fractures were assessed by two lateral radiographs at the beginning and end of the study. The prevalence of the
three possible VDR genotypes was similar to those in other Caucasian populations and no differences were found between men
and women. Women with the favorable bb genotype showed significantly higher BMD values at the lumbar spine and femoral neck,
and a positive rate of BMD change at the femoral neck compared with women with the BB and Bb genotypes. Moreover, women with
the bb genotype showed a trend toward a lower prevalence and incidence of vertebral fractures (p= 0.07). We have not found any differences between VDR genotypes in men. In conclusion, VDR gene polymorphisms are related
to bone mass and bone loss in women; also a trend in the prevalence of vertebral fractures was observed in postmenopausal
women but not in men.
Received: 8 June 1998 / Accepted: 7 December 1998 相似文献
3.
The Contribution of Vitamin D Receptor Gene Polymorphisms in Osteoporosis and Familial Osteoporosis 总被引:5,自引:0,他引:5
L. Fountas P. Moutsatsou I. Kastanias N. Tamouridis M. Tzanela M. Anapliotou C. E. Sekeris 《Osteoporosis international》1999,10(5):392-398
It is well established that genetic factors play a major role in the pathogenesis of osteoporosis. Previous reports have
suggested that vitamin D receptor (VDR) gene polymorphisms, particularly the BB, tt and AA genotypes, are associated with
low bone mineral density (BMD). If these VDR genotypes are indeed an important determinant of BMD, then a population of related
osteoporotic individuals (mother–daughter or sister–sister relationship) should have a high prevalence of the BB, tt or AA
VDR genotypes. To test this hypothesis we determined the VDR genotypes in 26 osteoporotic persons (age 44.3 ± 12.7 years,
mean ± SD) belonging to 12 families. Furthermore, for comparison with existing studies, we applied the VDR genotype analysis
in a population of 53 unrelated healthy subjects (age 45.2 ± 9.8 years, mean ± SD) and 59 unrelated osteoporotic subjects
(age 52.1 ± 9.0 years, mean ± SD). The menopausal status of the healthy and osteoporotic populations was pre-, peri- and mostly
early postmenopausal. The proportions of the three genotypes, BB, tt and AA, within the 12 osteoporotic families were 15%,
12% and 27%, respectively, whereas the proportions of the other three homozygous genotypes (bb, TT, aa) were 50%, 50% and
23%. The distribution of the BB, tt and AA genotypes in the normal population was 21%, 21% and 36%, respectively (vs bb, TT,
aa: 36%, 38%, 21%), whereas in the osteoporotic population it was 24%, 20% and 34% (vs bb, TT, aa: 27%, 34%, 14%). Our data
indicate that there is not a statistically significant (p>0.05) difference in the VDR genotype frequencies within osteoporotic families as compared with the same genotypes in the
population of unrelated normal or osteoporotic subjects. VDR genotype analysis showed no significant relation between VDR
polymorphisms and BMD or Z-score values at the lumbar spine. This study demonstrates the lack of a heritability pattern between the BB, tt and AA genotypes
and low BMD.
Received: 29 October 1998 / Accepted: 19 April 1999 相似文献
4.
J. M. Le Parc P. Plantin G. Jondeau M. Goldschild M. Albert C. Boileau 《Osteoporosis international》1999,10(6):475-479
Sixty adult patients (40 women, 20 men) with Marfan syndrome (MFS) according to the Berlin criteria had a full clinical examination
and bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry of the hip and nondominant forearm. BMD was
expressed as a Z-score and compared with the reference population of the Hologic database. In MFS men, BMD (g/cm2) was compared with the BMD of 45 normal tall Caucasian adults. Osteocalcin was measured by radioimmunoassay. In patients
with MFS, BMD was compared between patients with and without previous fractures and according to the phenotypic severity of
MFS. The mean age of the patients was 32.9 ± 9.3 years (women 32.5 ± 9.7, men 33.4 ± 8.6), mean height was 180.3 ± 10.3 cm
(women 176.3 ± 9.2, men 188.1 ± 7.5) and mean body mass index 20.9 ± 3.6 kg/m2 (women 20.8 ± 3.4, men 20.95 ± 3.97). Hyperlaxity score (Beighton criteria) was 6.9 ± 1.1. Six patients (10%) had a previous
fracture. Thirty per cent of patients had had at least one previous operation for scoliosis, aortic dilatation or eye problems.
BMD values in the 60 patients were as follows: Z-score of the hip, −1.26 ± 0.93, p<10−9 (neck, −0.93 ± 1.09, p<10−9; trochanter, −1.31 ± 0.85, p<10−9; intertrochanter, −1.39 ± 0.99, p<10−9; Ward’s triangle, −0.93 ± 1.88, p<10−9); Z-score of the radius: −1.6 ± 1.06, p<10−9 (1/3 proximal, −1.29 ± 1.03; mid-radius, −1.94 ± 1.04; ultradistal, −0.68 ± 1.1, p<10−9). The decrease in BMD was similar in men and women at both the hip and the radius. BMD in MFS patients was significantly
decreased at cortical compared with trabecular sites (radius 1/3 proximal vs ultradistal, p<0.0001; total femur vs Ward’s triangle, p<0.0005). No difference in BMD was found between MFS patients with or without previous fractures and those with severe or
less severe phenotypic expression of MFS. An influence of height and weight in MFS on BMD is suspected. Osteocalcin was not
increased in our group of MFS patients. Thus both men and women with MFS have a significant deficit of BMD at the hip and
radius. The decrease in BMD is present equally in both sexes and is more pronounced at predominantly cortical sites. In our
group of patients we found no increase in fractures and no relation between decreased BMD and phenotypic expression of the
syndrome.
Received: 30 October 1998 / Accepted: 26 May 1999 相似文献
5.
H.-Y. ChenChen W.-C. Chen W.-C. Chen F.-J. Tsai C.-H. Tsai C.-W. Li 《Osteoporosis international》2001,12(12):1036-1041
Osteoporosis is a common disorder with a strong genetic component. Our aim was to evaluate the correlation of the vitamin
D receptor gene intron 8 BsmI polymorphism with bone mineral density (BMD) and their relationship to osteoporosis. We determined the vitamin D receptor
gene intron 8 BsmI polymorphism using polymerase chain reaction-based restriction analysis in 171 postmenopausal Chinese women in Taiwan. The
polymorphism was detected using the restriction enzyme BsmI, where the B allele indicated absence of the cuttable site and the b allele its presence. BMD of the lumbar spine and proximal
femur were measured using dual-energy X-ray absorptiometry. The allelic frequencies for postmenopausal Chinese women in Taiwan
were 12.3% for B and 87.7% for b in BsmI restriction fragment length polymorphisms. The prevalence of each genotype in the study population was: 6.4% BB, 11.7% Bb
and 81.9% bb. The three genotypic groups differed significantly in BMD at the lumbar spine and the femoral neck. These differences
corresponded to significant gene-dose effects at the lumbar spine and femoral neck (p<0.001 for both sites). The relative risk for the development of osteoporosis was about 2–3 times as great as that predicted
by the differences between genotypes in BMD, and remained significant even after adjustment for age, height and weight. The
vitamin D receptor gene intron 8 BsmI polymorphism is associated with reduced BMD and predisposes women to osteoporosis.
Received: 21 February 2001 / Accepted: 31 May 2001 相似文献
6.
Osteocalcin Gene Polymorphism is Related to Bone Density in Healthy Adolescent Females 总被引:2,自引:0,他引:2
A. Gustavsson P. Nordström R. Lorentzon U. H. Lerner M. Lorentzon 《Osteoporosis international》2000,11(10):847-851
Recently a polymorphism was found in the human osteocalcin gene, and its association with bone mass was investigated in healthy
postmenopausal Japanese women. The osteocalcin gene allelic variant HH was found to be overrepresented in women with osteopenia.
The purpose of this study was to investigate whether the previously demonstrated polymorphism of the osteocalcin gene was
related to bone mineral density (BMD; g/cm2) or osteopenia in a group of 97 healthy Caucasian adolescent females (aged 16.9 ± 1.2 years, mean ± SD). BMD of the left
humerus, right femoral neck, lumbar spine and total body was measured using dual-energy X-ray absorptiometry. The relation
between the allelic variants and bone density was analyzed as presence or absence of the H allele. Presence of the H allele
was found to be related to a lower BMD of the humerus (0.97 vs 1.02, p = 0.03). There was also a strong tendency towards significance at the femoral neck (p = 0.06) and total body (p = 0.11). Using a multiple linear regression and including physical activity, weight, height and years since menarche, presence
of the H allele was found to be an independent predictor of humerus BMD (β=−0.21, p<0.05) and femoral neck BMD (β=−0.23, p<0.01). Using logistic regression, presence of the H allele was also independently associated with a 4.5 times increased risk
of osteopenia (p = 0.03) in the whole group. Osteopenia was defined as at least 1 SD lower bone density than the mean for the whole group
of at least one of the BMD sites measured. We have demonstrated that the osteocalcin HindIII genotype is independently related to bone density in healthy adolescent females. The present study also suggests that
presence of the H allele is predictive of osteopenia at an early age.
Received: 31 January 2000 / Accepted: 25 April 2000 相似文献
7.
Association Study of Parathyroid Hormone Gene Polymorphism and Bone Mineral Density in Japanese Postmenopausal Women 总被引:16,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
8.
Stiffness in Discrimination of Patients with Vertebral Fractures 总被引:4,自引:0,他引:4
We measured the ultrasound parameters of the heels of 49 women with vertebral fractures and 87 age-matched controls using
an Achilles ultrasound device. Average broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were significantly
lower in fracture patients (p<0.0001). We also estimated the ultrasound parameters of patients compared with age-matched non-fracture controls and found
the mean BUA to be −1.02 SD below control values. The mean SOS was −0.97 SD and the mean Stiffness was −1.12 SD below control
values.
Femoral bone mineral density (BMD) at the neck, Ward’s triangle and the trochanter, the total-body BMD and L2–4 BMD were
measured with dual-energy X-ray absorptiometry (DXA) and found to be significantly lower in fracture patients (p<0.0001). All correlation coefficients between ultrasound parameters and DXA measurements were >0.5 and statistically significant
(p<0.0001). A stepwise logistic regression with presence or absence of vertebral fracture as the response variable and all ultrasound
– DXA parameters as the explanatory variables indicated that the best predictor of fracture was Stiffness, with additional
predictive ability provided by spine BMD. Sensitivity and specificity of all measures were determined by the areas under the
receiver operating characteristic (ROC) curve, which were 0.76 ± 0.04 for BUA, 0.77 ± 0.04 for SOS, 0.78 ± 0.04 for Stiffness
and 0.78 ± 0.03 for spine BMD. The areas under the ROC curves of BUA, SOS, Stiffness and spine BMD were compared and it was
found that Stiffness and spine BMD were significantly better predictors of fracture than BUA and SOS. These results support
many recent studies showing that ultrasound measurements of the os-calcis have diagnostic sensitivity comparable to DXA, and
also demonstrated that Stiffness was a better predictor of fracture than spine BMD.
Received: 23 September 1997 / Accepted: 10 April 1998 相似文献
9.
T. L. N. Järvinen T. A. H. Järvinen H. Sievänen A. Heinonen M. Tanner X.-H. Huang A. Nenonen J. J. Isola M. Järvinen P. Kannus 《Calcified tissue international》1998,62(5):413-417
The objective of this prospective controlled study was to determine whether the osteogenic response of bone to mechanical
loading is dependent on the vitamin D receptor (VDR) polymorphism. Thirty-five healthy premenopausal women took part in a
progressive, high-impact exercise three times a week for a period of 18 months and 45 women served as nonexercising controls.
The trainees were divided into three groups: bb (n = 12, 34%); Bb (n = 16, 46%); BB (n = 7, 20%) according to polymorphism
at the gene encoding the VDR (BB representing subjects without the restriction enzyme BsmI sites on the two VDR gene alleles). Bone mineral content (BMC) and areal bone mineral density (BMD) were measured at the
lumber spine, proximal femur, knee, calcaneus, and dominant distal radius before the beginning of the exercise regimen and
at 12 and 18 months of training using dual-energy x-ray absorptiometry (DXA). As an indicator of the total osteogenic effect
of the training, ΣBMC was derived by summing up the BMC values of the loaded sites (i.e., the lower limb sites and the lumbar
spine). The mean ΣBMC increased 2.0% in the bb group, 3.0% in the Bb group, and 2.8% in the BB group (P= 0.184 for the intergroup difference), but only 0.8% in the controls (exercisers versus controls, P < 0.001). Individuals with the BB genotype of the VDR gene, subjects with whom the BMC can be lower than normal and whose
bones can be less responsive to pharmacological therapies than bones of the other individuals, seem to have as good osteogenic
response to mechanical loading as subjects with other VDR genotypes. Thus, irrespective of the VDR genotype, physical activity
seems to be beneficial for bones of premenopausal women.
Received: 14 May 1997 / Accepted: 14 November 1997 相似文献
10.
The New Selective Estrogen Receptor Modulator MDL 103,323 Increases Bone Mineral Density and Bone Strength in Adult Ovariectomized Rats 总被引:1,自引:0,他引:1
P. Ammann S. Bourrin J.-P. Bonjour F. Brunner J.-M. Meyer R. Rizzoli 《Osteoporosis international》1999,10(5):369-376
Selective estrogen receptor modulators (SERMs) can prevent the bone loss induced by ovariectomy (OVX), but it is not established
whether they can increase bone mass and strength in a curative protocol in ovariectomized osteopenic animals. We investigated
the influence of a SERM of the new generation, MDL 103,323, on areal bone mineral density (BMD), as measured by dual-energy
X-ray absorptiometry, bone strength and remodeling in OVX osteopenic rats. Nine weeks after OVX, 8-month-old rats were divided
into six groups of 10 animals. MDL 103,323 was given by gavage at doses of 0.01, 0.1 or 0.6 mg/kg body weight, 5 days a week.
The effect of MDL 103,323 was compared with that of the bisphosphonate pamidronate (APD), which was injected subcutaneously
at a dose of 1.6 mmol/kg body weight for 5 days every 4 weeks. Lumbar spine (LS), femoral neck (FN), proximal tibia (PT) and
midshaft tibia (MT) BMD, bone strength, and proximal tibia histomorphometry, serum osteocalcin, urinary total deoxypyridinoline
and serum insulin-like growth factor I (IGF-I) were measured. After 16 weeks of treatment, BMD changes (means ± SEM) were
−11.4 ± 2.2, +4.0 ± 2.1 and +6.4 ± 1.0% respectively in OVX controls, in rats treated with 0.1 mg/kg MDL 103,323 (p<0.05) and in APD-treated rats (p<0.02) at the level of LS; −0.4 ± 1.1, +6.7 ± 1.4, +7.2 ± 1.8% (p<0.01 and NS) at the level of FN; and −2.6 ± 1.2%, +5.8 ± 1.2, +6.9 ± 1.4% (p<0.03 and 0.01) at the level of PT. MDL 103,323-treated animals had a higher trabecular bone volume, a higher number of trabeculae
and smaller intertrabecular spaces compared with OVX controls. Vertebral body ultimate strength was 186 ± 13, 292 ± 16, 249
± 23 N (p<0.05) in OVX controls, MDL 103,323-treated rats and APD-treated rats, respectively. The administration of 0.6 mg/kg of MDL
103,323 did not further increase BMD or bone strength, indicating a bell-shaped dose–response curve. MDL 103,323 lowered plasma
osteocalcin concentration and urinary deoxypyridinoline excretion. In rats treated with 0.1 mg/kg MDL 103,323, plasma IGF-I
was increased as compared with OVX controls (664 ± 36 ng/ml vs 527 ± 39 ng/ml, p<0.05). In conclusion, these results indicate that this new SERM positively influences BMD and lumbar spine bone strength
in estrogen-deficient rats.
Received: 30 October 1998 / Accepted: 12 April 1999 相似文献
11.
J. P. W. van den Bergh A. R. M. M. Hermus A. I. Spruyt C. G. J. Sweep F. H. M. Corstens A. G. H. Smals 《Osteoporosis international》2001,12(1):55-62
Klinefelter’s syndrome (KS) is a common sex chromosomal disorder associated with androgen deficiency and osteoporosis. Only
few bone mineral density (BMD) and no quantitative ultrasound (QUS) data are available in these patients after long-term testosterone
replacement therapy. We examined in a cross-sectional study 52 chromatin-positive KS patients aged 39.1 ± 12.4 years (mean
± SD). Patients had been treated with oral or parenteral androgens for 9.2 ± 8.2 years (range 1–32 years). Areal BMD and bone
mineral apparent density (BMAD, i.e., estimated volumetric BMD) at the lumbar spine, total hip and femoral neck were determined
by dual-energy X-ray absorptiometry. BMD T-scores in the patient group were calculated based on three different North American reference databases. The QUS parameters
broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus using an ultrasound imaging
device (UBIS 3000) and were compared with QUS results in a sex-, age- and height-matched control group. QUS T-scores were calculated based on the results of QUS measurements in 50 normal Dutch men between the ages of 20 and 30 years.
QUS and BMD results in the KS patient group were compared. Overall, based on the three reference databases, 46% and 63% of
the KS patients had a T-score between −1 and −2.5 and a further 10% and 14% had a T-score ≤−2.5 at the total hip and/or lumbar spine, as measured by areal BMD or BMAD, respectively. Thirty-nine percent of
the KS patients had a T-score between −2.5 and −1, while 2% had a T-score ≤−2.5 for BUA and/or SOS. BUA (77.7 ± 15.0 dB/MHz) and SOS (1518.8 ± 36.5 m/s) were significantly lower in the KS patients
than in age- and height-matched controls (87.1 ± 17.8 dB/MHz, p<0.005, and 1536.5 ± 42.5 m/s, p<0.05). Correlation coefficients between the QUS parameters and areal BMD (0.28 to 0.37) or BMAD (0.27 to 0.46) were modest.
ROC analysis showed that discrimination of a BMD or BMAD T-score ≤−2.5 with either BUA or SOS was not statistically significant.
Although a limitation of our study is that direct comparison of BMD and QUS T-scores is not possible because in the control group in which QUS parameters were determined no BMD measurements were performed,
we conclude that despite long-term testosterone replacement therapy, a considerable percentage of patients with KS had a BMD
T-score <−1 or even ≤−2.5, based on different North American reference databases. This percentage was even higher for BMAD.
QUS parameters were also low in the KS patient group when compared with Dutch control subjects. QUS parameters cannot be used
to predict BMD or BMAD in KS patients.
Received: 28 February 2000 / Accepted: 3 August 2000 相似文献
12.
This study aims to investigate the four vitamin D receptor (VDR) gene single nucleotide polymorphisms and their possible relationship
with bone mineral density (BMD) in Chinese 0–6-year-old Han children. Two hundred four 0–6-year-old Han children without metabolic
bone disease were randomly recruited in Shanghai, China. The BMD of the middle tibia was measured by an ultrasonic bone density
instrument. VDR genotypes were determined by polymerase chain reaction restriction fragment length polymorphism using endonuclease
ApaI, BsmI, TaqI and FokI. The alleles of a, T, b and F and the genotypes of aa, TT, bb and Ff were predominant. The frequency alleles of a, T, b
and F were, respectively, 70.6, 95.8, 95.3 and 57.6%. When the influences of confounders such as serum 25(OH)D, serum zinc
and outdoor activities on BMD were removed, the genotypes of BsmI and FokI were found apparently to be related to BMD. The BMD of the Bb carrier was much lower than that of the bb carrier (22.00 ± 27.84
and 43.14 ± 31.98, P < 0.05). The BMD of the ff carrier was lower than that of the Ff or FF carrier (26.97 ± 34.22 and 37.95 ± 29.70 and 53.52 ± 30.35,
P < 0.001), while the genotypes of ApaI and TaqI have no relation with BMD in 0–6-year-old Han children. These findings show that the Bb and ff genotypes of the VDR BsmI and FokI variants are significantly associated with a decreased BMD in Chinese Han children aged 0–6 years, while the VDR ApaI and TaqI polymorphisms are not significantly associated with it. 相似文献
13.
F. E. Alenfeld E. Diessel M. Brezger J. Sieper D. Felsenberg J. Braun 《Osteoporosis international》2000,11(5):400-407
Periarticular osteopenia is the earliest radiographic sign of rheumatoid arthritis (RA). Recent studies using dual-energy
X-ray absorptiometry (DXA) have indicated that the loss of periarticular BMD can be quantified by whole-hand bone mineral
density (BMD) measurements. The aim of this study was to analyze periarticular BMD in more detail by DXA and quantitative
ultrasound (QUS). In a cross-sectional study 23 women aged 30–76 years with early RA, mean disease duration 26 ± 19 months,
and 18 men aged 42–69 years, mean disease duration 24 ± 25 months, were examined. All patients received antirheumatic therapy.
The reference population consisted of 103 age-matched controls (68 females, 35 males) and young healthy controls. BMD measurements
were performed using a DXA Expert XL densitometer (Lunar). BMD of the whole-hand and two subregions was determined: two subchondral
regions of interest (S.CH.) were set within the trabecular bone, distal to the proximal interphalangeal joints of digits II
and III excluding the dense subchondral bone of the metacarpophalangeal (MCP) joint and two metacarpal regions of interest
(MCP) were set including the entire MCP joint of these fingers. QUS measurements at the proximal phalanges of digits II–V
were performed using a DBM Sonic (Igea); amplitude-dependent speed of sound (Ad-SoS) was determined. In comparison with whole-hand
BMD measurements, bone loss was pronounced in patients with a disease duration of 18–72 months at the subchondral regions
of interest in both genders compared with age-matched controls (women: mean BMD loss S.CH. −23%, p<0.001, whole-hand −16%, p<0.001; men: mean BMD loss S.CH. −19%, p<0.05, whole-hand −12%, p<0.05). The bone changes were also shown by QUS (women: Ad-SOS values of 1950 ± 90 m/s in RA vs 2137 ± 35 m/s in young healthy
controls (p<0.005); men AD-SOS 1956 ± 87 m/s in RA vs 2146 ± 41 m/s in young healthy controls (p<0.05)). These results show that BMD and Ad-SOS values are significantly lowered in patients with early RA and indicate that
periarticular osteoporosis in early RA might possibly be better detected using detailed hand scan analyses.
Received: 2 February 1999 / Accepted: 25 October 1999 相似文献
14.
Holmberg-Marttila D Sievänen H Järvinen TL Järvinen TA 《Calcified tissue international》2000,66(3):184-189
BsmI restriction fragment length polymorphism (RFLP) of the vitamin D receptor (VDR) gene and PvuII RFLPs of the estrogen receptor (ER) gene and their relation to changes in areal bone mineral density (BMD) were examined
in 43 healthy postpartum Finnish women aged 31.3 (SD 4.7) years. BMD was measured by dual energy X-ray absorptiometry at lumbar
spine, right femoral neck, and dominant distal radius immediately after delivery, 1 month after resumption of menses, and
1 year thereafter. The RFLPs were represented as Bb (BsmI) and Pp (PvuII), the capital letters denoting the absence of and the small letters the presence of the restriction sites. The frequency
of VDR alleles was as follows: bb (20.9%), Bb (60.5%), and BB (18.6%), and that of ER alleles was pp (39.5%), Pp (51.2%),
and PP (9.3%). Altogether, BMD decreased significantly during postpartum amenorrhea at all sites [the mean bone loss ranging
from −1.2 (SD 3.6)% at the distal radius to −3.7 (2.9)% at the femoral neck], and increased after resumption of menses [the
1-year follow-up BMD values ranging from −1.0 (2.4)% at the femoral neck to +3.3 (4.0)% at the lumbar spine as compared with
baseline]. No obvious genotype-related differences were found between these changes. These results suggest that the BsmI and PvuII polymorphisms may not have substantial influence on BMD changes postpartum.
Received: 20 November 1998 / Accepted: 30 September 1999 相似文献
15.
Does the vitamin D receptor genotype predict bone mineral loss in haemodialysed patients? 总被引:2,自引:0,他引:2
Karkoszka H; Chudek J; Strzelczyk P; Wiecek A; Schmidt-Gayk H; Ritz E; Kokot F 《Nephrology, dialysis, transplantation》1998,13(8):2077-2080
Background. It has been suggested that the vitamin D
receptor (VDR) gene BsmI-polymorphism is a genetic determinant of bone
metabolism. Design. To test this hypothesis, the
relationship between VDR genotypes, bone mineral density (baseline and
after 18 months) and parameters of calcium metabolism and bone turnover
were investigated prospectively in 88 haemodialysed patients not receiving
active vitamin D metabolites. Methods. Whole body,
lumbar spine and femoral neck bone mineral density (BMD) were assessed by
dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus,
25(OH)D3, 1,25(OH)2D3, osteocalcin serum concentrations, alkaline
phosphatase activity and intact, 1,84 PTH levels were measured.
Results. VDR genotype BB, Bb and bb were found in 27,
49 and 24% of patients. Initial BMD (g/cm2) of whole
body, lumbar spine and femoral neck did not differ between genotypes (whole
body: BB 1.055 ± 0.120, Bb 1.082 ± 0.102, bb 1.128
± 0.120; lumbar spine: BB 1.075 ± 0.199, Bb 1.079
± 0.185, bb 1.099 ± 0.170; femoral neck: BB 0.808
± 0.160, Bb 0.862 ± 0.127, bb 0.842 ±
0.125; mean ± SD), but the decrease of whole body and femoral
neck BMD during 18 months was significantly (P
< 0.02) different between the genotype groups (whole body: BB -0.048
± 0.028, Bb -0.031 ± 0.029, bb -0.024 ±
0.023; femoral neck BB -0.044 ± 0.069, Bb -0.032 ±
0.081, bb -0.012 ± 0.029 g/cm2).
Conclusions. This preliminary study suggests faster
mineral loss in BB genotype of VDR in haemodialysed patients. 相似文献
16.
Treatment of Postmenopausal Women with Osteoporosis or Low Bone Density with Raloxifene 总被引:3,自引:0,他引:3
P. J. Meunier E. Vignot P. Garnero E. Confavreux E. Paris S. Liu-Leage S. Sarkar T. Liu M. Wong M. W. Draper 《Osteoporosis international》1999,10(4):330-336
Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum
lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD,
biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This
Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal
women (mean age ± SD: 60.2 ± 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: −2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or
150 mg/day raloxifene-HCl (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and
total hip (+1.6%) in the RLX 60 group compared with the placebo group (p<0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated
patients, compared with those receiving placebo, had increased BMD (p<0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio
were significantly decreased in the RLX-treated groups, compared with the placebo group (p<0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p<0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study,
raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events,
and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density.
Received: 26 December 1998 / Accepted: 31 March 1999 相似文献
17.
Allogeneic Bone Marrow Transplantation is Associated with a Preferential Femoral Neck Bone Loss 总被引:1,自引:0,他引:1
N. Buchs C. Helg C. Collao B. Chapuis D. Slosman J.-P. Bonjour R. Rizzoli 《Osteoporosis international》2001,12(10):880-886
Osteoporosis is a major complication of organ transplantation. Little is known about the risk of developing osteoporosis
in bone marrow transplant (BMT) recipients. We studied early and late changes in bone mineral density (BMD), as well as biochemical
markers of bone remodeling, in patients at the time of allogeneic BMT (alloBMT) and up to 13 years thereafter. In a cross-sectional
study, 102 patients (40 women, 62 men, mean age ± SEM, 38.9 ± 1.6 years) were segregated into a first group (A, n= 48) and evaluated before or during the first weeks (mean ± SD 0.3 ± 0.1 month, range –0.5 to 3 months) following alloBMT,
and a second group (B, n= 54) studied 60.1 ± 5.6 months (range 6–156 months) following alloBMT. Lumbar spine (LS) BMD was similar in groups A and
B and was within normal limits. In contrast, femoral neck (FN) Z- and T-scores were significantly decreased in group B compared with group A (–0.68 ± 0.14 vs –0.03 ± 0.14 SD and –0.84 ± 0.14 vs
–0.22 ± 0.14 SD, respectively; p≤0.002). Osteopenia (T-score between –1 and –2.5 SD) was present in 35% of group A and 43% of group B patients (NS). Osteoporosis (T-score <–2.5 SD) was detected in 7% of group B patients, but in none of those in group A (p= 0.05). In a longitudinal study, 56 subjects were evaluated at the time of alloBMT, and 33 and 23 were studied 6 or 12 months
later, respectively (13 women, 20 men, 37.5 ± 1.6 years). All were treated with supplements of calcium and vitamin D. Amenorrheic
women received hormone replacement therapy (HRT). Three-monthly pamidronate infusions were given to 15 men and 10 non-amenorrheic
women who were osteopenic/osteoporotic or had elevated baseline bone turnover markers. Mean baseline LS and FN Z- and T-scores were within normal range. Six months after BMT, FN BMD decreased by 4.2 ± 0.7% (p<0.001), and whole body BMD and bone mineral content by 1.5 ± 0.4% and 3.1 ± 0.6%, respectively (p≤0.0001). Twelve months after the graft, there was no further significant bone loss and only FN BMD decrease remained significantly
different compared with baseline (–5.6 ± 1.1%, p≤0.0001). These results indicate that the risk of decreased BMD is higher for the femoral neck than the lumbar spine and whole
body levels in patients with allogeneic bone marrow transplantation, and that bone loss occurs mainly during the first 6 months
after the graft.
Received: 9 February 2001 / Accepted: 23 May 2001 相似文献
18.
In women with postmenopausal osteoporosis (PMO), response to therapy with bisphosphonates is conventionally monitored using
central-site (hip and spine) bone mineral density (BMD), but more convenient alternatives are desirable. During a randomized
parallel-group study of the efficacy of once-weekly (80 mg vs 160 mg) oral alendronate in the treatment of PMO, 81 women (mean
age 70.2 years ± 4.6 SD) had BMD measurements of total hip (TH) and lumbar spine (LS) (L1–L4, Hologic); and of the middle
phalanx of the middle digit of the non-dominant hand (accuDXA) at baseline and after 6 and 12 months of therapy with alendronate.
At the same timepoints, subjects also had measurements of speed of sound (SOS) through bone at four sites (distal 1/3 radius,
proximal phalanx of the third finger, midshaft of the tibia and fifth metatarsal) using the Sunlight Omnisense Ultrasound
Bone Sonometer. Data from both patient groups were pooled for this analysis. Mean TH BMD at baseline was 0.705 g/cm2± 0.093 (SD) and increased by 1.7%± 2.3% and 2.5%± 2.3% at 6 and 12 months respectively (p= 0.09 and p<0.0001). Mean LS BMD at baseline was 0.718 ± 0.076 g/cm2 and increased by 3.9%± 3.6% and 6.1%± 3.5 % at 6 and 12 months respectively (both p<0.0001). There was no statistically significant change from baseline in mean BMD by accuDXA at either 6 or 12 months. The
only statistically significant changes in SOS were at the radius (decrease in SOS at 12 months, p = 0.04) and tibia (increase at 6 months, p<0.01, but no change between baseline and 12 months). Baseline correlation coefficients between accuDXA and LS and TH DXA
were 0.22 (p= 0.05) and 0.27 (p= 0.02) respectively. Correlation coefficients between SOS and LS DXA ranged from 0.05 to 0.22; and between SOS and TH DXA
ranged from –0.08 to 0.10 (all p= NS). These data suggest that the response to alendronate therapy over this time period cannot be measured by accuDXA or
Sunlight SOS at the sites studied.
Received: 26 June 2001 / Accepted: 27 September 2001 相似文献
19.
The aim of this study was to assess bone mass in male elite athletes participating in an impact loading sport (volleyball)
and, in particular, to determine whether the asymmetric nature of this sport leads to differences in the skeletal tissue composition
of the limbs. Fifteen male volleyball players (VP) (26 ± 4 years, 192 ± 6 cm, 87 ± 9 kg; mean ± SD) and 15 non-active control
subjects (25 ± 2 years, 177 ± 8 cm, 72 ± 11 kg; mean ± SD) were studied. VP training sessions (3–6 days/week) included a variety
of jumping and weightlifting exercises. The VP were taller and heavier than the control subjects (p<0.001). Whole-body bone mineral content (BMC) and lean mass were higher in VP after adjustment for body mass and height (p<0.001). Axial skeleton and limb BMC and bone mineral density (BMD) were higher in VP than in control subjects (p<0.05). Adjusted lumbar spine (L2–4) BMD was 14% higher in VP than in control subjects (p<0.05). Similarly, a much greater adjusted BMD was observed in the femoral neck of VP (24%, 20%, 27% and 20% for the femoral
neck, intertrochanteric, greater trochanter and Ward’s triangle subregions respectively; p<0.05). The dominant arm was slightly heavier (≈3%) and had 4% more muscle mass than the contralateral arm in both the VP
(p<0.05) and control subjects (p<0.05). Greater BMC values (9%), BMD (7%) values and the area occupied by osseous pixels (5%) were recorded in the dominant
arm as compared with the nondominant arm in VP (p<0.05). No differences between arms were observed in control subjects. Right and left leg BMC and BMD values were similar
in control subjects while 4% higher BMC values were recorded for the left leg in the VP group (p<0.05). A close relationship between left leg muscle mass and BMD was observed in the femoral neck subregions of all the subjects
(r= 0.81, 0.81, 0.78 and 0.79 for the femoral neck, intertrochanteric, greater trochanter and Ward’s triangle subregions respectively;
p<0.001; n= 30). These findings clearly demonstrate a considerably high BMC and BMD in professional volleyball players which seems to
be related to the loading type of exercise they perform.
Received: 26 October 1998 / Accepted: 26 May 1999 相似文献
20.
M. K. Karlsson P.-O. Josefsson A. Nordkvist K. Akesson E. Seeman K. J. Obrant 《Osteoporosis international》2000,11(3):261-264
The reduced bone mineral density (BMD) found in patients with fractures may, in part, follow rather than precede the fracture.
We studied the magnitude and reversibility of bone loss in the 15 months following osteotomy in 21 men and 5 women with localized
medial arthritis of the knee. BMD (mean ± SD), measured using dual-energy X-ray absorptiometry, decreased by a maximum of
35 ± 21% in the mid-diaphysis of the affected tibia at 9 months after surgery (p<0.001). At 15 months, reversal of bone loss in nonfractured bones was incomplete; the remaining deficit was 20 ± 27% relative
to baseline (p<0.001). Maximum bone loss occurred at 9 months at the total body (5 ± 2%), spine (15 ± 17%) and at Ward’s triangle of the
proximal femur of the unoperated limb (10 ± 17%) (all p<0.01). In summary, post-traumatic bone loss is region-specific with incomplete reversibility, at least after about 15 months.
Deficits in BMD in cross-sectional studies of patients with fractures, held to be responsible for the bone fragility, may,
in part, follow rather than precede the fracture.
Received: 17 May 1999 / Accepted: 24 September 1999 相似文献