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1.
In a randomized double-masked placebo-controlled parallel-group trial 166 hysterectomized (± oophorectomy) perimenopausal
and postmenopausal women aged 45–55 years with a follicle stimulating hormone level above 20 IU/l were treated with one daily
dose of either 0.5 mg 17β-estradiol (E2), 1 mg E2, 2 mg E2 or placebo for 2 years. Bone mineral density (BMD) and biochemical bone markers were determined. All three doses of E2 were significantly better than placebo with respect to change in BMD at the lumbar spine (L1–L4) (p<0.0001 for all pairwise comparisons) and hip (femoral neck, trochanter, Ward’s triangle). The mean percentage change from
baseline at the lumbar spine was −0.2%, 0.8% and 1.8% in the 0.5, 1 and 2 mg E2 groups respectively compared with −3.5% in the placebo group. Both 1 and 2 mg E2 were significantly better than placebo in increasing the BMD at the femoral neck (p<0.001), trochanter (p<0.01) and Ward’s triangle (p<0.0001), while 0.5 mg E2 was significantly better than placebo at the femoral neck (p<0.001) and Ward’s triangle (p<0.0001). The overall difference in mean percentage change in BMD at the femoral neck versus placebo (−0.2%) was 3.8% for
0.5 mg, 4.0% for 1 mg and 3.9% for 2 mg E2; the corresponding numbers for trochanter were −0.3%, 1.3%, 3.3% and 3.2%, respectively, and −2.2%, 2.9%, 2.9% and 4.0%,
respectively, for Ward’s triangle. More than half the women who received placebo presented with a decrease in BMD at the hip.
The percentage of women in the 0.5 mg E2 group who maintained or increased BMD at the femoral neck, trochanter and Ward’s triangle was 69%, 56% and 44%, respectively.
For 1 mg E2 the numbers were 69%, 78% and 61% respectively, and for 2 mg E2 were 59%, 68% and 59% respectively. Osteocalcin, serum pyridinium crosslinks, urinary pyridinium crosslinks and urinary hydroxyproline/creatinine
decreased significantly (p<0.0001, p<0.05) in the 0.5, 1 and 2 mg E2 groups compared with the placebo group after 6 and 24 months of treatment.
Received: 28 May 2001 / Accepted: 11 October 2001 相似文献
2.
Adverse events (AEs) associated with bisphosphonates are usually gastrointestinal, but elevation of aminotransferases (alanine
and aspartate aminotransferase) has also been described in many cases. The frequency of such elevation is, however, poorly
investigated. The Probone study is a continuing phase II trial of 610 osteopenic women randomized for 3 years to receive placebo or clodronate at the
following clodronate doses: 65 mg, 400 mg and 800 mg daily, and 400 mg for 15 days out of 90 (intermittent group). During
the first study year, gastrointestinal AEs were reported by 20–26% of the patients in the five study groups, but no differences
appeared between groups. The high-dose clodronate groups (400 mg and 800 mg daily) had no more hepatic side-effects than the
low-dose groups, and no serious AE due to liver disease was reported. These higher doses of clodronate caused, however, a
mean alanine aminotransferase (ALT) elevation of 5.4–5.8 U (25–24%) which differed significantly from the change in the placebo
group (p = 0.002 and p<0.0001, respectively). In those volunteers with initially normal aminotransferase values the risk ratio for an aminotransferase
increase to an above-normal value (compared with the placebo group) during the study year was up to 1.8 in the clodronate
400 mg group and up to 2.5 in the clodronate 800 mg group. Among these groups an elevation above the normal limits occurred
in up to 11.7% of the volunteers for aspartate aminotransferase (AST) and up to 17.7% for ALT. The respective percentages
in the placebo group were 6.2% and 7.2%. All analyzed bilirubin values were normal. We conclude that oral clodronate use may
elevate serum aminotransferase levels, and that these enzymes most likely come from the liver. This elevation has also been
described for several other bisphosphonates. However, clinically significant liver injury is unlikely.
Received: 23 October 1997 / Accepted: 8 January 1999 相似文献
3.
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
4.
N. B. Watts D. K. Jenkins J. M. Visor D. C. Casal P. Geusens 《Osteoporosis international》2001,12(4):279-288
Alendronate therapy in osteoporotic women decreases bone turnover and increases bone mineral density (BMD). Optimal patient
management should include verification that each patient is responding to therapy. Markers of bone turnover and BMD have both
been proposed for this purpose. We have investigated changes resulting from alendronate therapy with an enzyme immunoassay
for bone alkaline phosphatase (BAP) and compared it with total alkaline phosphatase (TAP) and BMD of the lumbar spine, hip,
and total body. Subjects were drawn from a multicenter randomized, placebo-controlled trial of alendronate in postmenopausal
women with osteoporosis. BAP and TAP levels were measured at baseline and following 3, 6 and 12 months of therapy with either
placebo (n= 180) or alendronate 10 mg/day (n= 134). All subjects also received 500 mg/day supplemental calcium. BMD was measured at baseline and following 3, 6, 12, 18,
24 and 36 months of therapy. To compare BAP, TAP and BMD at each site for identifying women that experienced a skeletal effect
of alendronate, we calculated least significant change (LSC) values from the long-term intraindividual variability in each
placebo-treated woman. Median levels of BAP decreased by 34%, 44% and 43% at 3, 6 and 12 months, respectively, in alendronate-treated
women (p<0.0001 compared with baseline and with placebo). These changes were significantly greater (p<0.0001) than changes observed for TAP. Following 6 months of alendronate therapy, 90% of the women had experienced a decrease
in BAP exceeding the LSC compared with only 71% for TAP. The greatest number of women similarly identified with BMD at any
site (i.e. a gain in BMD exceeding the LSC) was 81% for spinal BMD at 36 months. All other sites were less than 70% at 36
months. Short-term changes in BAP and TAP were modestly associated with subsequent changes in BMD at all sites (Spearman’s
rho −0.22 to −0.52, p<0.05). Compared with TAP and BMD, BAP testing rapidly and sensitively identified skeletal effects of alendronate thus enabling
appropriate drug monitoring of osteoporotic women. Though BAP and TAP changes were modestly predictive of BMD changes, the
value of the bone marker tests is their ability to detect rapidly a skeletal effect of therapy.
Received: 19 May 2000 / Accepted: 31 October 2000 相似文献
5.
Bisphosphonates such as etidronate and alendronate are widely accepted as effective agents for the treatment of osteoporosis.
However, some physicians find the choice of which one to use in different patients, and the comparative magnitude of response,
unclear. Fifty postmenopausal women with osteoporosis [group 1: 27 women who had received 3 years of previous cyclical etidronate
treatment, mean age 70.5 years, bone mineral density (BMD) mean T-score lumbar spine (LS) −3.58 and femoral neck (FN) −2.51; group 2: 23 women who had not previously received cyclical etidronate
treatment, mean age 73.7 years, BMD mean T-score LS −3.65 and FN −2.96] were treated with 10 mg alendronate daily, to determine whether pretreatment with etidronate
affected the response to alendronate, and whether patients who did not respond to etidronate, responded to alendronate. There
was a significant increase in LS BMD after 2 years of treatment with alendronate compared with baseline (group 1: 7.84%, p<0.001; group 2: 6.69%, p<0.001), but there was no statistical difference between the groups. In the group 1 patients there was a significant difference
between the initial response (at the LS BMD) to 2 years of cyclical etidronate (1.86%) and later response to 2 years of alendronate
(7.84%) (p<0.0001). The 10 patients who did not respond at the LS to etidronate alone, showed a significantly better response (mean
BMD change +6.3%) when subsequently treated with alendronate (a net difference of 9.3%, p = 0.002). In 15 patients who did not respond at the FN to etidronate alone, the mean response to alendronate was +0.96% (a
difference of 7%, p = 0.004). This study shows that pretreatment with 3 years of cyclical etidronate is not detrimental to the subsequent LS
BMD response to alendronate. There is evidence that alendronate produced a greater bone density response than etidronate,
and patients who did not respond to etidronate with an increase in LS bone density, subsequently did so following alendronate.
Received: 22 June 1999 / Accepted: 18 January 2000 相似文献
6.
J. Y. Reginster R. Deroisy M. Dougados I. Jupsin J. Colette C. Roux 《Osteoporosis international》2002,13(12):925-931
Early postmenopausal women (n = 160) were randomised to receive placebo or strontium ranelate (SR) 125 mg/day, 500 mg/day or 1 g/day for 2 years (40 participants
per group). All participants received calcium 500 mg/day. The primary efficacy parameter was the percent variation in lumbar
bone mineral density (BMD), measured using dual-energy X-ray absorptiometry. Secondary efficacy criteria included hip BMD
and biochemical markers of bone turnover. At month 24, SR 1 g/day significantly increased lumbar BMD compared with placebo
[mean (SD) +5.53% (5.12); p<0.001] for measured values and [mean (SD) +1.41% (5.33%); p<0.05] for values adjusted for bone strontium content. The annual increase for adjusted values was +0.66% compared with −0.5%
with placebo, with an overall beneficial effect after 2 years of about 2.4% with SR 1 g/day relative to placebo. There were
no other significant between-group differences in adjusted lumbar BMD. Femoral neck and total hip BMD were also significantly
increased at month 24 with SR 1 g/day compared with placebo [mean (SD): +2.46% (4.78) and +3.21% (4.68), respectively; both
p<0.001)]. SR 1 g/day significantly increased bone alkaline phosphatase at all time points (p<0.05) compared with baseline and between-group analysis showed a significant increase, compared with placebo, at month 18
(p = 0.048). No effect on markers of bone resorption was observed. SR was as well tolerated as placebo. The minimum does at
which SR is effective in preventing bone loss in early postmenopausal non-osteoporotic women is therefore 1 g/day.
Received: 7 February 2002 / Accepted: 2 July 2002 相似文献
7.
P. D. Delmas E. Confavreux P. Garnero P. Fardellone M.-C. de Vernejoul C. Cormier J.-C. Arce 《Osteoporosis international》2000,11(2):177-187
The effects of 17β-estradiol (E2) 1 mg combined with low doses of norethisterone acetate (NETA) on postmenopausal bone loss and turnover were investigated
in a 2-year, randomized, double-masked, placebo-controlled trial. A total of 135 postmenopausal women with a lumbar spine
bone mineral density (BMD) T-score between −2 and +2 were randomized to daily treatment with an oral tablet of either placebo, E2 1 mg/NETA 0.25 mg, or E2 1 mg/NETA 0.5 mg. Significant (p<0.001) increases in BMD at the lumbar spine (L1–4) were observed with E2 1 mg/NETA 0.25 mg (5.2%) and E2 1 mg/NETA 0.5 mg (5.4%) compared with placebo (−0.9%). The total hip BMD increased significantly in the E2 1 mg/NETA 0.25 mg (3.1%) and E2 1 mg/NETA 0.5 mg groups (3.3%) compared with placebo. At the femoral trochanter, the increase in BMD in the E2 1 mg/NETA 0.5 mg group (6.3%) was significantly different from the placebo group (0.8%), while that in the E2 1 mg/NETA 0.25 mg group (3.3%) was not. No statistical differences were found between the active groups and placebo for the
change in BMD at the femoral neck. Significant increases in BMD at the distal radius and total body were found for both E2 1 mg/NETA 0.25 mg (0.9% and 2.5%, respectively) and E2 1 mg/NETA 0.5 mg (2.1% and 3.0%, respectively) compared with placebo (−0.7% and 0.4%, respectively).
At the end of the treatment, urinary pyridinoline type I collagen C-telopeptide had decreased by 65% and 60% in the E2 1 mg/NETA 0.25 mg and E2 1 mg/NETA 0.5 mg groups, respectively, while the mean serum concentrations of osteocalcin had decreased by 39% and 34%, bone-specific
alkaline phosphatase by 32% and 29%, and C-terminal propeptide of type I collagen by 21% and 19% had decreased by 34-39%,
29-32%, and 19-21% in the E2 1 mg/NETA 0.25 mg and E2 1 mg/NETA 0.25 mg groups, respectively.
In conclusion, combinations of E2 1 mg and NETA 0.25 or 0.5 mg prevent bone loss in postmenopausal women at the lumbar spine, hip, distal radius and total
body, and normalize bone turnover.
Received: 12 March 1998 / Accepted: 31 August 1999 相似文献
8.
Effects of 8 Years of Treatment with Tibolone 2.5 mg Daily on Postmenopausal Bone Loss 总被引:2,自引:0,他引:2
The objective of this study was to assess the long-term effects of tibolone 2.5 mg daily (Livial1; Organon) on bone mineral density in recently postmenopausal women. An 8-year, open, nonrandomized, prospective study was
designed to compare the effects of tibolone 2.5 mg daily (n= 59) with an untreated control group (n= 51). The subjects of this study were 110 recently postmenopausal women (6–36 months since last menstrual period). The main
outcome measures were bone mineral density of the spine and femur, measured by dual-energy X-ray absorptiometry, and assessment
of biochemical markers of bone metabolism. After 8 years of tibolone use, the mean (± SEM) increase in bone mineral density
compared with baseline was 4.1%± 0.8% (p<0.0001) in the spine and 4.6%± 1.8% (p= 0.015) in the femoral neck. Over the same period, bone mineral density in the control group decreased in the spine by –7.5%±
1.1%, (p<0.0001) and in the femur by –6.7%± 1.2% (p<0.0001). The bone resorption marker, calcium/creatinine ratio, decreased in the tibolone group but not in the control group.
Serum bone formation markers decreased (alkaline phosphatase) or stayed approximately the same (osteocalcin) in the tibolone
group. Adherence was high, with 58% (34 of 59) of the tibolone group continuing treatment for 8 years. We conclude that tibolone
2.5 mg daily prevents bone loss in the lumbar spine and femoral neck over 8 years and adherence to treatment is high. The
greater bone density compared with untreated women would be expected to reduce the risk of bone fractures.
Received: September 2000 / Accepted: December 2000 相似文献
9.
The Prevention of Osteoporosis Using Sequential Low-Dose Hormone Replacement Therapy with Estradiol-17β and Dydrogesterone 总被引:6,自引:0,他引:6
Low-dose hormone replacement therapy (HRT) in postmenopausal women may produce fewer side-effects but its efficacy in the
prevention of bone loss and osteoporosis is not established. To address this we compared the effect of 1 mg estradiol-17β
with a 2 mg dose, in combination with cyclical dydrogesterone, in the prevention of postmenopausal bone loss. We conducted
a multicenter double-masked prospective randomized, placebo-controlled study in 595 apparently healthy postmenopausal women
randomized to either placebo, or continuous oral estradiol-17β 1 mg or 2 mg with sequential dydrogesterone for 2 years. The
primary endpoint was the percentage change from baseline in bone mineral density (BMD) in the lumbar spine (LS) and femoral
neck (FN) of actively treated groups compared with placebo. Women taking either 1 mg or 2 mg estradiol-17β showed a significant
increase in BMD of the LS (mean ± SD, 5.2 ± 3.8% and 6.7 ± 4.0% respectively, both p <0.001) whilst BMD in the placebo group decreased (–1.9 ± 4.0%). Increases were also observed in FN BMD in both treated groups
(2.7 ± 4.2% and 2.5 ± 5.2% respectively, both p <0.001) in contrast to the placebo group (–1.8 ± 4.8%). The oldest women showed the greatest treatment response. One milligram
estradiol-17β in combination with dydrogesterone is effective in conserving LS and proximal femur bone mass, both of which
are clinically important sites of osteoporotic fracture, and is as effective as 2 mg in preventing FN bone. The lower dose
of estradiol-17β is a particularly suitable treatment for osteoporosis management in older women since it should minimize
side-effects and improve the acceptability of HRT.
Received: 19 June 2000 / Accepted: 26 October 2000 相似文献
10.
Prevention of Bone Loss with Risedronate in Glucocorticoid-Treated Rheumatoid Arthritis Patients 总被引:2,自引:0,他引:2
R. Eastell J.-P. Devogelaer N. F. A. Peel A. A. Chines D. E. Bax N. Sacco-Gibson C. Nagant de Deuxchaisnes R. G. G. Russell 《Osteoporosis international》2000,11(4):331-337
The aim of the study was to assess risedronate’s effect on bone mineral density in postmenopausal women with rheumatoid arthritis
receiving glucocorticoids. We carried out a two center, 2 year, double-masked, placebo-controlled trial with a third year
of nontreatment follow-up. We studied 120 women requiring long-term glucocorticoid therapy at >2.5 mg/day prednisolone randomized
to treatment with daily placebo; daily 2.5 mg risedronate; or cyclical 15 mg risedronate (2 out of 12 weeks). At 97 weeks,
bone mineral density was maintained at the lumbar spine (+1.4%) and trochanter (+0.4%) in the daily 2.5 mg risedronate group,
while significant bone loss occurred in the placebo group (–1.6%, p= 0.03; and 4.0%, p<0.005, respectively). At the femoral neck, there was a nonsignificant bone loss in the daily 2.5 mg risedronate group (–1.0%)
while in the placebo group bone mass decreased significantly (–3.6%, p<0.001). The difference between placebo and daily 2.5 mg risedronate groups was significant at the lumbar spine (p= 0.009) and trochanter (p= 0.02) but did not reach statistical significance at the femoral neck. Although not significantly different from placebo
at the lumbar spine, the overall effect of the cyclical regimen was similar to that of the daily 2.5 mg risedronate regimen.
Treatment withdrawal led to bone loss in the risedronate groups that was significant at the lumbar spine. A similar number
of patients experienced adverse events (including upper gastrointestinal events) across treatment groups and risedronate was
generally well tolerated. Thus risedronate preserves bone mass in postmenopausal women with rheumatoid arthritis receiving
glucocorticoids while patients receiving a placebo have significant bone loss.
Received: 2 June 1999 / Accepted: 29 September 1999 相似文献
11.
K. S. Tsai M. L. Yen H. A. Pan M. H. Wu W. C. Cheng S. H. J. Hsu B. L. Yen K. E. Huang 《Osteoporosis international》2001,12(12):1020-1025
We treated 116 healthy postmenopausal women (age 47–66 years, mean 57 years) in Taiwan with either raloxifene (RLX) 60 mg
(n= 92) or 0.625 mg conjugated equine estrogen plus 5 mg medroxyprogesterone acetate (CCEP, n= 24) daily for 12 months in a randomized, double-masked, active-controlled fashion. The results showed that both regimens
increased bone mineral density (BMD) at hip sites (means: RLX 2.5–4.9%, CCEP 4.6–7.9%, all p<0.005 compared with baseline), and the difference between the two regimens was not significant. The spinal BMD increased
significantly in both groups (1.4% with RLX and 6.0% with CCEP, both p<0.01), and more with CCEP (p<0.003). Osteocalcin levels and urinary type I collagen C-telopeptide/creatinine ratios decreased significantly in both regimens,
but the decreases were significantly larger with CCEP. Compared with baseline, both RLX and CCEP decreased the total cholesterol
(median 4.9% and 8.6% respectively, p<0.001) and LDL-cholesterol (median 11% and 19% respectively, p<0.001), and increased HDL-cholesterol (median 8.6% and 10.7% respectively, p<0.01). Both regimens increased triglyceride levels (median 3.2% and 18.9% respectively, both p<0.05), although to a lesser extent with RLX than with CCEP (p<0.05). Only 3 subjects (3.3%) reported vaginal bleeding in the RLX group, as compared with 31% (7/22) with CCEP (p<0.05). We conclude that in healthy, postmenopausal Taiwanese women, RLX 60 mg given daily has favorable results in BMD, bone
turnover and serum lipids, although the dosage we used showed a potency less than that of conventional CCEP.
Received: 22 November 2000 / Accepted: 25 June 2001 相似文献
12.
R. Patel D. Collins S. Bullock R. Swaminathan G. M. Blake I. Fogelman 《Osteoporosis international》2001,12(4):319-325
Vitamin D status is known to be an important determinant of bone mineral density (BMD). There is a significant seasonal variation
in serum vitamin D, and some studies have reported an associated seasonal variation in BMD. The present study was devised
to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects, along with associated variations
in serum parathyroid hormone (PTH), intestinal calcium absorption and biochemical markers of bone turnover. A second aim was
to investigate whether, if such variations were identified, they could be suppressed by vitamin D supplementation. The subjects
were 70 healthy female volunteers (mean age 47.2 years, range 24–70 years) recruited into a double-masked crossover study
and followed over 2 years. During the first year 35 subjects received a daily oral supplement containing 800 IU (20 mg) cholecalciferol
(group 1) and 35 subjects received a placebo preparation (group 2). During the second year the treatment each group received
was reversed. Lumbar spine (L1–L4), left proximal femur and total body BMD were measured by DXA at 3-month intervals. Serum
25-hydroxyvitamin D (25-OHD), serum PTH, bone markers (bone-specific ALP (BSAP) and urinary crosslinks (DYPD/creatinine))
and calcium absorption were also measured at each visit. Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l (p <0.001), while a reciprocal decrease in serum PTH of 6.6 ng/l (p = 0.011) was seen in subjects in the lowest quartile of baseline serum 25-OHD. The treatment had no significant effect on
spine, femur or total body BMD, calcium absorption or bone markers. When Fourier analysis was used to analyze the data for
seasonal effect (defined as twice the amplitude of the 1-year period variation) a highly significant effect for 25-OHD of
18 nmol/l (p <0.001) was found. However, no effect was found for BMD, PTH, calcium absorption or bone markers. The analysis set a 95%
confidence limit to the seasonal effect of less than 0.6% for spine, total hip and total body BMD. It was concluded that in
the population of healthy women studied there was no evidence of seasonal variation in spine, femur or total body BMD, serum
PTH, calcium absorption or bone markers. Vitamin D supplementation was found to have no effect on BMD.
Received: 7 July 2000 / Accepted: 14 November 2000 相似文献
13.
Bisphosphonates have been used effectively to treat established osteoporosis and prevent postmenopausal bone loss. However,
the optimal manner of its administration—whether cyclic or continuous—has not been well established. This study investigated
the efficacy of cyclic and continuous oral administration of clodronate in 54 newly identified osteopenic postmenopausal women
in a randomized, double-blind, crossover fashion. The participants were randomly separated into two groups. The cyclic group
(n = 29) received 800 mg twice daily of oral clodronate for 2 weeks every 3 months for the first 12 months followed by placebo
for the second 12 months. The continuous group (n = 25) received placebo in the first 12 months and ingested 400 mg of clodronate
once daily for the second 12 months. The urinary amino-terminal (NTX™) and carboxy-terminal (CrossLaps™) cross-linked fragments
of type I collagen, both markers of bone resorption, showed a marked decrease (25–50%) with both regimens during the period
of active treatment. In the cyclic group, the levels of these two markers increased in the second 12 months with placebo,
but did not return to the baseline completely. However, bone mineral density (BMD), determined by dual-energy X-ray absorptiometry
(DXA), showed no significant change of BMD at various sites after 1 year of active treatment in both groups. Thoracic and
lumbar spine X-ray showed no new vertebral fracture in either group after 2 years of treatment. With the two treatment protocols
in this study, oral clodronate was effective in decreasing postmenopausal bone resorption, causing no significant changes
in BMD at various sites.
Received: 16 April 1997 / Accepted: 1 October 1998 相似文献
14.
Ethnic and Gender Differences in Bone Mineral Density and Bone Turnover in Young Adults: Effect of Bone Size 总被引:6,自引:3,他引:3
Generally, the incidence of osteoporotic fracture is lower in black populations and in men. These effects of ethnicity and
gender may result from differences in peak bone mineral density (PBMD) and bone turnover (BT), which in turn are affected
by bone size. Therefore, the aims of this study were to examine the effects of ethnicity and gender on bone mineral density
(BMD) and BT in young African-Caribbean and Caucasian adults, and to adjust for the effect of bone size on BMD and BT. BMD
was measured at the lumbar spine, L2–L4 (LS), total body (TB) and femoral neck (FN) by dual-energy X-ray absorptiometry in
44 blacks (16 men, 28 women) and 59 whites (28 men, 31 women) ages 20–37 years. We measured serum bone-specific alkaline phosphatase
(BAP) and serum osteocalcin (OC) as markers of bone formation and urinary immunoreactive free deoxypyridinoline (ifDpd) and
crosslinked N-telopeptide of type I collagen (NTx) as markers of bone resorption. To adjust the data for any differences in
bone size, we calculated: (a) bone mineral apparent density (BMAD), an estimated volumetric bone density which attempts to
normalize BMD measurements for bone size; and (b) bone resorption markers as a ratio to total body bone mineral content (TB
BMC). Two-way analysis of variance was used to compare the effects of race and gender, and to test for any interaction between
these two factors. Blacks had higher BMD compared with whites at the TB (p<0.001), LS (p= 0.0001) and FN (p= 0.0005). This increase remained significant at the LS only after calculating BMAD. Men had higher BMD at all sites (except
at the LS). This increase was no longer significant at the FN after calculating BMAD, and LS BMAD was actually greater in
women (p<0.0001). Blacks and whites had similar concentrations of turnover markers, but men had higher bone turnover markers than
women (BAP, p<0.0001; OC, p= 0.002; ifDpd, p= 0.03; NTx, p<0.0001). This increase in bone resorption markers was no longer significant after adjusting for TB BMC (except for NTx in
whites). We conclude that the skeletal advantage in blacks during young adulthood is not explained by bone size. However,
it seems probable that bone size effects partially explain gender differences in BMD and bone turnover.
Received: 2 February 1999 / Accepted: 2 December 1999 相似文献
15.
The aim of this study was to establish a normative database, assess precision, and evaluate the ability to identify women
with low bone mass and to discriminate women with fracture from those without for a highly portable, scanning calcaneal ultrasonometer:
the QUS-2. Fourteen hundred and one Caucasian women were recruited for the study. Among them were 794 healthy women 25–84
years of age evenly distributed per 10-year period to establish a normative database. Of these, 171 aged 25–34 years were
defined as the young normal group for the purpose of T-score determination. Precision was assessed within 1 day (short-term) and over a 16-week period (long-term) in 79 women aged
25–84 years. Five hundred twenty-eight women ranging from 50 to 84 years of age with or without prevalent fractures of the
spine, hip or forearm were measured to compare the QUS-2 with bone mineral density (BMD) of the hip and spine. Mean calcaneal
broadband ultrasound attenuation (BUA) was constant in healthy women from 25 to 54 years of age and decreased with increasing
age thereafter. Short-term precision, with and without repositioning of the heel, and long-term precision yielded comparable
results (BUA SDs of 2.1–2.4 dB/MHz, coefficients of variations (CVs) of 2.5–2.9%). Calcaneal BUA was significantly correlated
with BMD of the total hip (TH), femoral neck (FN) and lumbar spine (LS) in 698 women (r= 0.6–0.7, all p<0.0001). A similar relationship was observed for LS BMD compared with either TH or FN BMD (r= 0.7, p<0.0001). Prevalence of osteoporosis in our population (WHO criteria) was 20%, 17%, 21%, and 24% for BUA, BMD of the TH, FN
and LS, respectively. Age-adjusted values for a 1 SD reduction in calcaneal BUA and TH and FN BMD predicted prevalent fractures
of the spine, forearm, and hip with significant (p<0.05) odds ratios of 2.3, 2.0 and 2.1, respectively. Areas under the receiver operating characteristic curves for age-adjusted
bone mass values predicting prevalent fracture were 0.62 for BUA, 0.59 for TH BMD, 0.60 for FN BMD, and 0.57 for LS BMD; all
statistically equivalent. We conclude that the QUS-2 calcaneal ultrasonometer exhibits reproducible clinical performance that
is similar to BMD of the spine and hip in identifying women with low bone mass and discriminating women with fracture from
those without.
Received: 19 July 2000 / Accepted: 6 December 2000 相似文献
16.
Y. V. Ho E. M. Briganti Y. Duan R. Buchanan S. Hall E. Seeman 《Osteoporosis international》1999,9(2):134-138
Corticosteroid therapy (CST) is associated with reduced intestinal calcium absorption, bone loss and increased fracture risk.
As polymorphisms of the vitamin D receptor (VDR) gene may be associated with bone mineral density (BMD) and intestinal calcium
absorption, we asked whether patients with a given VDR genotype receiving CST may be at increased or decreased risk for corticosteroid-related
bone loss and osteoporosis. We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry in 193 women (50 premenopausal, 143 postmenopausal) and 70 men with rheumatoid arthritis
(n= 44), obstructive airway diseases (n= 128) and other corticosteroid-treated diseases (n= 91). All patients received a cumulative dose greater than 1.8 g per year or a minimum of 5 mg daily of prednisolone or equivalent
for at least 1 year. VDR alleles were typed by polymerase chain reaction assay based on the polymorphic BsmI and TaqI restriction sites. BMD in patients was expressed as a Z-score (mean ± SEM) derived from age- and gender-matched controls. BMD was reduced in patients at the lumbar spine (bb, −0.52
± 0.12; Bb, −0.47 ± 0.11; BB, −0.65 ± 0.18 SD; p<0.01), femoral neck (bb, −0.46 ± 0.10; Bb, −0.34 ± 0.10; BB, −0.54 ± 0.14 SD; p<0.01), Ward’s triangle (bb, −0.44 ± 0.10; Bb, −0.31 ± 0.10; BB, −0.45 ± 0.13 SD; p<0.01), and trochanter (bb, −0.50 ± 0.10; Bb, −0.30 ± 0.10; BB, −0.44 ± 0.14 SD; p<0.01). However, there was no significant difference in the deficit in BMD in any of the genotypes, either before or after
adjusting for age, sex, body mass index, disease type, age at onset of disease, disease duration, cumulative steroid dosage,
smoking status and dietary calcium intake. Similarly, there were no detectable differences between the BsmI genotypes and the rate of bone loss in 79 patients with repeated BMD measurements at an interval of 4–48 months. The data
suggest that the VDR genotypes may not be a means of identifying patients at greater risk of corticosteroid-related bone loss.
Received: 23 December 1997 / Accepted: 26 May 1998 相似文献
17.
We have assessed urinary deoxypyridinoline (Dpd) levels by immunoassay in women who participated in a double-masked, placebo-controlled
trial of the bone loss prevention effects of estrogen replacement therapy (ERT). Ninety-one women who had undergone recent
surgical menopause were randomdized to receive either placebo or 0.025, 0.05 or 0.1 mg/day transdermal 17β-estradiol for 2
years. Mean Dpd levels in the postmenopausal women were significantly elevated (p<0.0001) above mean Dpd levels in a reference population of healthy, premenopausal women. Subjects in the placebo group lost
6.4% of lumbar spine bone mineral density (BMD) and 4.9% of mid-radius bone mineral content (BMC) over 2 years. Dpd levels
at baseline were inversely correlated with BMD and BMC changes in the placebo group. The placebo group and subjects receiving
0.025 mg/day 17β-estradiol who had Dpd levels increased above the reference interval cut-off (mean + 2 standard deviations,
7.5 nmol/mmol) lost 2 times more bone mass than did those with Dpd levels below it. Dpd levels decreased significantly (p<0.01) from baseline at 6 months following initiation of treatment with 0.05 or 0.1 mg/day 17β-estradiol, changes that correlated
with increased lumbar spine BMD and with changes in mid-radius BMC. At 12 months, Dpd levels were lower than baseline and
placebo in all three treatment groups. These data suggest utility of this Dpd immunoassay in assessing changes in bone resorption
induced by surgical menopause and ERT. 相似文献
18.
Inappropriate Reference Range for Peak Bone Mineral Density in Dual-energy X-ray Absorptiometry: Implications for the Interpretation of T-scores 总被引:1,自引:0,他引:1
An inappropriate reference range for peak bone mineral density (BMD) may result in identification of an incorrect proportion
of subjects with osteopenia and osteoporosis at dual-energy X-ray absorptiometry (DXA). In this study, we assessed the prevalence
of low BMD in Turkish young adults with respect to local population reference range T-scores and the US reference range T-scores. The BMD values of lumbar spine (L1–L4) and proximal femur (femoral neck, intertrochanter, trochanter, Ward”s triangle
and total) were measured by DXA in 323 healthy young adults (171 women, 152 men) aged 19–25 years. The World Health Organization
criteria for the diagnosis of osteopenia (−2.5 <T-score <−1) and osteoporosis (T-score ≤−2.5) were applied. In women, the means of the US reference range T-scores were significantly lower than zero at the spine and proximal femoral sites (p<0.0001). In men, the means of the US reference range T-scores were significantly lower than zero at the spine, femoral neck, intertrochanter, total femur (p<0.0001) and trochanter (p<0.05), but not at Ward”s triangle (p=0.92). When the diagnoses were based on local population reference range T-scores instead of the US reference range T-scores, the prevalence of low BMD (T-score <−1) in women fell from 50.3% to 14.0% at the lumbar spine and from 60.8% to 14.6% at the femoral neck, and in men
from 42.8% to 15.8% at the lumbar spine and from 30.9% to 17.1% at the femoral neck. Our data suggest that individual populations
should use their own reference range T-scores to avoid misdiagnoses of osteopenia and osteoporosis by DXA.
Received: 4 November 1999 / Accepted: 29 March 2000 相似文献
19.
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
20.
Progressive Hemiosteoporosis on the Paretic Side and Increased Bone Mineral Density in the Nonparetic Arm the First Year after Severe Stroke 总被引:9,自引:0,他引:9
A. Ramnemark L. Nyberg R. Lorentzon U. Englund Y. Gustafson 《Osteoporosis international》1999,9(3):269-275
Fractures are a common and serious complication after stroke and the risk of hip fractures among stroke patients is 2 to
4 times greater than among other elderly people. The aim of this study was to investigate prospectively the change in bone
mineral density (BMD) after severe stroke and to study the association between motor impairment, disability and the development
of hemiosteoporosis. The study comprised 24 stroke patients, with no persistent paresis from previous strokes or previous
osteoporotic fractures, included 1 month after stroke onset. BMD, motor function, ambulation and activities of daily living
(ADL) were assessed at 1, 4, 7 and 12 months after stroke onset. At inclusion, the patients’ BMD was normal for their age.
During the study, there was a significant loss of BMD in the total body (−2.0%; p<0.05), but not in the head or spine. BMD differed significantly between the paretic and the non-paretic arm at inclusion
(−4.8%; p<0.001). Decrease in BMD was most pronounced in the affected humerus (−17.4%; p<0.001) and proximal femur (−12.2%; p<0.01). BMD decreased significantly in both lower extremities during follow-up, but the losses were more pronounced on the
paretic side (p<0.01). In the nonaffected ultradistal radius there was a significant increase in BMD from inclusion to the end of the study
(+5.8%; p<0.01). There was no pattern in the bone losses correlating with presumptive risk factors for hemiosteoporosis such as motor
function, ability to perform ADL or ambulation. Two patients had fractures at follow-up, both on the paretic side. Loss of
bone mineral density in the paretic extremities is thus pronounced and progressive during the first year after stroke, indicating
that loss of BMD is probably an important risk factor for post-stroke fractures. Surprisingly, BMD in the nonaffected arm
increased significantly during the first year after stroke, most likely due to increased physical activity, and perhaps a
redistribution of bone minerals from the paretic extremities.
Received: 13 January 1998 / Accepted: 24 July 1998 相似文献