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1.
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
2.
3.
J. Y. Reginster C. Christiansen C. Roux J. Fechtenbaum A. Rouillon K. P. Tou 《Osteoporosis international》2001,12(3):169-177
The objective of the study was to determine the efficacy and safety of tiludronate in the treatment of postmenopausal osteoporosis.
Two placebo-controlled, randomized, double-masked, multicenter, cyclical, intermittent, dose-ranging studies including 1805
women with low vertebral bone mineral density and prevalent vertebral fractures and 488 women with low bone mineral density
and no prevalent fracture were conducted. Patients were randomized to either tiludronate 50 mg/day, tiludronate 200 mg/day
or placebo, given orally for the first 7 days of each month. A supplement of 500 mg elemental calcium was provided daily from
day 8 to the end of the month. Both studies demonstrated no statistically or clinically relevant trends in the incidence of
adverse effects accross the three treatment groups. However, tiludronate administered at these two doses in a cyclic intermittent
regimen was not effective in reducing the incidence of vertebral fractures or increasing spinal bone mineral density. Thus,
tiludronate, administered at these doses in a cyclic intermittent regimen, cannot be considered an appropriate treatment of
postmenopausal osteoporosis, notwithstanding a high safety profile.
Received: 6 July 2000 / Accepted: 25 September 2000 相似文献
4.
Bone Densitometry: A New, Highly Responsive Region of Interest in the Distal Forearm to Monitor the Effect of Osteoporosis Treatment 总被引:1,自引:0,他引:1
The bisphosphonates have been introduced as alternatives to hormone replacement therapy (HRT) for the treatment and prevention
of postmenopausal osteoporosis. The expected increasing application in at clinical practice demands cost-effective and easily
handled methods to monitor the effect on bone. The weak response at the distal forearm during antiresorptive treatment has
restricted the use of bone densitometry at this region. We describe a new model for bone densitometry at the distal forearm,
by which the response obtained is comparable to the response in other regions where bone densitometry is much more expensive
and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with
65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with
alendronate (n= 69), a 1-year trial with ibandronate (n= 141) and a 2-year trial with HRT (n= 121). Bone mineral density (BMD) at the distal forearm revealed a highly statistically significant dose-related response
and increased 3–5% per year with 2.5 mg ibandronate, 10 mg alendronate or HRT, whereas the decrease in the placebo groups
was 1–3% (p<0.001). The response at the distal forearm was similar to the response at the lumbar spine and hip. In conclusion, trabecular
bone at the distal forearm is as responsive to antiresorptive treatment as trabecular bone in other skeletal regions. Bone
densitometry at the new region of interest in the distal forearm has comparable performance characteristics to more expensive
and technically demanding methods. The method is more accessible clinically and has potential as an alternative for monitoring
bone mass changes during antiresorptive treatment.
Received: 9 February 1998 / Accepted: 30 July 1998 相似文献
5.
O. Sahota I. Fowler P. J. Blackwell N. Lawson S. A. Cawte P. San T. Masud D. J. Hosking 《Osteoporosis international》2000,11(11):959-966
A number of drugs are now available for the treatment of established osteoporosis and have been shown to significantly increase
bone mineral density (BMD). There are, however, few comparative treatment studies and, furthermore, adverse events remain
a problem with some of the newer agents, particularly in the elderly, in everyday clinical practice. We report a 12 month,
open labeled, randomized controlled, prospective treatment study in 140 postmenopausal women with established vertebral osteoporosis,
comparing the effect of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in terms of gain
in BMD, reduction in bone turnover markers and adverse event profile. The mean percentage increases in BMD at 12 months, at
the spine and hip respectively, were: continuous alendronate 5.7%, 2.6%; cyclical alendronate 4.1%, 1.6%; cyclical etidronate
4.9%, 2.0% (p<0.01) and calcitriol 2.0%, 0.4% (NS). In comparison with calcitriol, the mean changes in BMD at the spine and hip respectively
were greater in the other groups; continuous alendronate: 3.7% (95% CI 1.4 to 8.3), 2.2% (95% CI 0.7 to 4.0); cyclical alendronate:
2.1% (95% CI 1.2 to 6.4), 1.2% (95% CI −0.3 to 3.0); cyclical etidronate: 2.9% (95% CI 1.9 to 6.5), 1.6% (95% CI 0.9 to 3.1)).
The reduction in bone turnover markers was between 26% and 32% in the alendronate and etidronate groups (p<0.01), with a trend toward greater reduction in the continuous alendronate group. Eight patients discontinued the study:
6 in the continuous alendronate group, 1 in the cyclical alendronate group and 1 in the calcitriol group. Two patients in
the cyclical etidronate group were unable to tolerate the Cacit component, but continued on substituting Cacit with Calcichew.
In summary, 12 months of treatment with continuous alendronate, cyclical alendronate and cyclical etidronate are effective
in terms of the gain in BMD at the anteroposterior spine and total hip in a comparable treatment population. These treatments
are more effective than calcitriol and were generally well tolerated. Continuous alendronate showed a trend toward a larger
gain in BMD and greater suppression of bone turnover markers than the other treatment groups, but had a higher incidence of
adverse events, particularly within the older subgroup. Cyclical alendronate offers a lower adverse event profile and appears
to be effective in comparison with continuous treatment, and may possibly be an alternative in the elderly. However, further
studies are necessary, but more importantly with fracture end-points.
Received: 6 April 1999 / Accepted: 8 June 2000 相似文献
6.
Effects of Alendronate on Bone Density in Men with Primary and Secondary Osteoporosis 总被引:5,自引:0,他引:5
Alendronate has been reported to increase bone mineral density (BMD) and reduce fracture risk in women with osteoporosis.
As there are no proven safe and effective treatments available for men with osteoporosis, we compared the effects of alendronate
(10 mg/day) on BMD, measured using dual-energy X-ray absorptiometry, in a 12-month prospective, controlled, open label study
involving (i) men with primary (n= 23) or secondary osteoporosis (n= 18), (ii) postmenopausal women with primary (n= 18) or secondary (n= 21) osteoporosis, and (iii) 29 male and 14 female untreated controls matched by age, height and weight. The patients had
one or more vertebral fractures and ranged in age from 34.6 to 85.1 years. BMD was detectably increased relative to baseline
by 6 months, and increased by comparable amounts in males and females with primary or secondary osteoporosis. At 12 months,
lumbar spine BMD was 5.4%± 1.1% to 7.0%± 2.2% higher in the treated groups compared with baseline and controls (p<0.05 to 0.0001). Trochanteric BMD increased by 2.6%± 1.5% and 3.7%± 1.7% in treated men with primary and secondary osteoporosis,
respectively (p = 0.06 to 0.08), and by 3.9%± 1.3% in treated women with primary osteoporosis (p<0.01) after 12 months. No significant changes were detected at the femoral neck or Ward’s triangle. BMD remained unchanged
in controls. We infer that alendronate has comparable incremental effects on BMD in men and women with primary and secondary
osteoporosis within 12 months of treatment. The changes are in the order of 0.5 SD – effects associated with a clinically
worthwhile reduction in fracture risk. The data provide room for optimism regarding the role of alendronate in the treatment
of osteoporosis in men. Randomized, double-masked and placebo-controlled trials are needed to confirm these preliminary findings
and demonstrate antifracture efficacy using vertebral and nonvertebral fracture rates as the primary endpoint.
Received: 23 February 1999 / Accepted: 2 June 1999 相似文献
7.
N. H. Bjarnason S. Sarkar T. Duong B. Mitlak P. D. Delmas C. Christiansen 《Osteoporosis international》2001,12(11):922-930
We studied the relationship between change in bone turnover and vertebral fracture risk during raloxifene therapy using 3-year
data from the MORE trial, where 2622 of the 7705 randomized women had measurement of bone markers at baseline and after 6
and 12 months participation. Change in bone turnover was significantely related to future risk of vertebral fracture, also
after adjusting for baseline vertebral fracture status and BMD. Thus, for a decrease of 9.3 mg/l in serum osteocalcin after
1 year’s raloxifene therapy, the odds ratio (OR) for a new vertebral fracture during 3 years was 0.69 (0.54–0.88), p= 0.003. Similarly, for a decrease of 5.91 mg/l in serum bone alkaline phosphatase, OR was 0.75 (0.62–0.92), p= 0.005. The change in BMD over 12 and 24 months was not related to fracture risk in any of the analyses. The strongest predictor
for vertebral fracture was prevalent vertebral fracture – even during therapy. The predictive value of baseline BMD was in
the same order of magnitude as bone turnover change during raloxifene treatment. In conclusion, the change in bone turnover
is related to fracture risk during raloxifene therapy. In contrast the change in BMD is not related to fracture risk. The
strongest predictor for vertebral fracture is prevalent vertebral fracture.
Received: 2 January 2001 / Accepted: 30 May 2001 相似文献
8.
A. Cranney G. Guyatt N. Krolicki V. Welch L. Griffith J. D. Adachi B. Shea P. Tugwell G. Wells 《Osteoporosis international》2001,12(2):140-151
The aim of the study was to review the effect of etidronate on bone density and fractures in postmenopausal women. We searched
MEDLINE from 1966 to 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings.
We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources
for unpublished data. We included 13 trials that randomized women to etidronate or an alternative (placebo or calcium and/or
vitamin D) and measured bone density for at least 1 year. For each trial, three independent reviewers assessed the methodologic
quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.63 (95%
CI 0.44 to 0.92). There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69 to 1.42). Etidronate, relative
to control, increased bone density after 1–3 years of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the
femoral neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39 to 1.55). Effects were larger at 4
years, though the number of patients followed much smaller. Etidronate increases bone density in the lumbar spine and femoral
neck for up to 4 years. The pooled estimates of fracture reduction with etidronate suggest a reduction in vertebral fractures,
but no effect on nonvertebral fractures.
Received: 25 February 2000 / Accepted: 8 August 2000 相似文献
9.
Bone Turnover and the Response to Alendronate Treatment in Postmenopausal Osteoporosis 总被引:4,自引:0,他引:4
S. Gonnelli C. Cepollaro C. Pondrelli S. Martini A. Montagnani R. Monaco C. Gennari 《Calcified tissue international》1999,65(5):359-364
This study investigated whether bone turnover influences the response to alendronate in women with postmenopausal osteoporosis.
One hundred postmenopausal osteoporotic women were randomized to receive either alendronate (10 mg/day) plus calcium (1000
mg/day) (n = 50) or calcium alone (n = 50). Vertebral and radial bone density, measured by DXA, and markers of bone turnover
were assessed at baseline and after 1 and 2 years. At the end of treatment, alendronate users showed an increase of 5.0% and
2.3%, respectively, at the lumbar spine and ultradistal radius; in the group treated only with calcium, bone mineral density
(BMD) decreased by 1.6% at the lumbar spine and 1.3% at the ultradistal radius. The difference between the two groups was
significant (P < 0.001). The patients were divided into high (HT) or low (LT) bone turnover groups, as assessed by 24-hour whole body retention
(WBR%) of 99mTc-methylene-diphosphonate. The response to alendronate treatment was greater in HT patients compared with LT patients. In
fact, at the end of the study period, BMD at the lumbar spine had increased by 7.9% in HT patients and by 3.0% in LT patients;
the difference between the two groups was significant (P < 0.001). No significant difference between the two groups was found for BMD at the ultradistal radius. In conclusion, the
present study demonstrates that 2-year treatment with alendronate has highly positive effects on bone mass at both the lumbar
spine and ultradistal radius. The increase in bone mass, especially at the axial level, is influenced by bone turnover. Therefore,
the evaluation of bone turnover may be useful in predicting the response to alendronate treatment.
Received: 23 April 1998 / Accepted: 10 June 1999 相似文献
10.
N. Bravenboer S. E. Papapoulos P. Holzmann N. A. T. Hamdy J. C. Netelenbos P. Lips 《Osteoporosis international》1999,9(6):489-493
The effect of pamidronate therapy on bone histology was studied in patients with osteoporosis with at least one vertebral
fracture in a randomized, double-masked, placebo-controlled, multi-center trial. Patients received pamidronate 150 mg/day
or placebo in addition to calcium 500 mg/day and vitamin D3 400 IU/day. Transiliac bone biopsies were obtained before and after 1 or 2 years of treatment. Of these, 23 pairs of biopsies
obtained from 14 women and 9 men (mean age t SD, 61.5 t 10 years) were of sufficient quality for histomorphometry. Histomorphometry
was performed on sections stained with Goldner’s trichrome, using a drawing tube and a digitizer. Urinary hydroxyproline excretion
decreased significantly (p<0.005) following pamidronate treatment, indicating a decrease in bone resorption. Osteoid volume and osteoid surface also
decreased significantly in the pamidronate group (p<0.004 and p<0.003 respectively), consistent with a secondary decrease in bone formation. Osteoid variables did not change in the placebo-treated
patients. Cortical thickness, trabecular bone volume and trabecular thickness did not change after pamidronate or placebo
treatment. Wall thickness, however, showed a borderline increase following pamidronate treatment. After pamidronate, eroded
surface and mineral apposition rate did not change significantly in the placebo and pamidronate groups. Mineralizing surface
and activation frequency showed a borderline decrease in the placebo and pamidronate groups. The decrease in mineralization
lag time was of borderline significance in the pamidronate group, corroborating the absence of any negative effect on mineralization.
In conclusion, pamidronate treatment led to a decrease in bone turnover and did not interfere with bone mineralization.
Received: 2 February 1998 / Accepted: 19 October 1998 相似文献
11.
A retrospective chart review was carried out on all consecutive patients over 65 years of age admitted to a tertiary care
teaching hospital with a diagnosis of a new hip fracture. A further chart review occurred after discharge from post-surgery
rehabilitation. The primary objective was to evaluate the prevalence of osteoporosis diagnosis and treatment in both phases
of the study. Secondary objectives included evaluation of the mortality rates, length of stay, prevalence of osteoporosis
investigation, and prevalence of osteoporosis diagnosis based on the clinical subspecialty involved. There were 311 patients
evaluated in the initial phase, and 226 after rehabilitation. The mortality rate was 5.8% (10% for men, 4% for women; p<0.005) in the acute care hospital and 9.3% (8% men, 10% women) during rehabilitation. Previous hip fracture occurred in 17.4%,
and 1.5% were readmitted during the study period with fracture of the opposite hip. Osteoporosis was diagnosed in the acute
care hospital on admission in 11.9% and on discharge in 15.4%. In the rehabilitation hospital it was diagnosed in 9.7% on
admission and 11.2% on discharge (p = NS). Osteoporosis treatment (including calcium or vitamin D therapy) was instituted in 13% on admission to acute care and
in 9.7% at the time of discharge. For the rehabilitation hospital, treatment occurred in 12.8% on admission and 10.2% on discharge.
The diagnosis of osteoporosis significantly increased the prevalence of treatment (p<0.001). Use of specific agents (hormone replacement therapy, bisphosphonates or calcitonin) occurred in <6% of all patients.
Osteoporosis is under-diagnosed and under-treated in this group of elderly hip fracture patients. It is associated with significant
mortality and morbidity and every effort should be made to prevent future fractures. Physicians in the “front line” of hip
fracture treatment are missing this key aspect of management in their patients. Education of these physicians, as well as
the public, may be the key to addressing this care gap.
Received: 12 March 2001 / Accepted: 23 July 2001 相似文献
12.
A Double-Masked Multicenter Comparative Study Between Alendronate and Alfacalcidol in Japanese Patients with Osteoporosis 总被引:5,自引:0,他引:5
M. Shiraki K. Kushida M. Fukunaga H. Kishimoto M. Taga T. Nakamura K. Kaneda H. Minaguchi T. Inoue H. Morii A. Tomita K. Yamamoto Y. Nagata M. Nakashima H. Orimo 《Osteoporosis international》1999,10(3):183-192
To evaluate the efficacy and safety of alendronate, a double-masked, active (alfacalcidol) controlled comparative study for
48 weeks was carried out in a total of 210 Japanese patients with osteoporosis. The doses of alendronate and alfacalcidol
were 5 mg/day and 1 μg/day, respectively. The lumbar bone mineral density (LBMD) values observed at 12, 24, 36 and 48 weeks
after the initiation of alendronate treatment were 3.53 ± 0.53%, 5.37 ± 0.62%, 5.87 ± 0.74% and 6.21 ± 0.59% (mean ± SE),
respectively, higher than the baseline value. Corresponding values in the alfacalcidol group were 1.50 ± 0.43%, 0.69 ± 0.63%,
1.12 ± 0.60% and 1.36 ± 0.63%, respectively. There was a significant difference between the two groups at each time point
(p<0.05 or p<0.001). The bone turnover markers were depressed during treatment in the alendronate group: −32.2% for alkaline phosphatase,
−53.7% for N-terminal osteocalcin and −45.0% for urinary deoxypyridinoline compared with the corresponding baseline values.
On the contrary, no notable changes in these parameters were observed in the alfacalcidol group. Treatment with alendronate
caused a transient decrease in serum calcium concentrations associated with an increase in the serum level of intact parathyroid
hormone. In contrast, treatment with alfacalcidol resulted in a tendency of these parameters to change in the opposite direction.
No difference in fracture incidence between the two groups was observed. The overall safety of alendronate was comparable
to that of alfacalcidol. In conclusion, although it was a relatively short-term study of 48 weeks, the results of the present
study indicate that alendronate at the daily dose of 5 mg was effective in increasing LBMD and that no serious drug-related
adverse events were observed in the alendronate-treated patients. Alendronate is more efficacious than alfacalcidol in increasing
bone mineral density, although the mechanisms of the actions of the two drugs are apparently different.
Received: 2 July 1998 / Accepted: 4 February 1999 相似文献
13.
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
14.
A. Tenenhouse L. Joseph N. Kreiger S. Poliquin T. M. Murray L. Blondeau C. Berger D. A. Hanley J. C. Prior 《Osteoporosis international》2000,11(10):897-904
The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence
of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10 061 women and men aged ≥25
years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies
to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used
to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged ≥50 years. Participants were recruited
via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured
by dual-energy X-ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine
and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39
years giving a PBM of 1.042 ± 0.121 g/cm2 for women and 1.058 ± 0.127 g/cm2 for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken
as PBM and was found to be 0.857 ± 0.125 g/cm2 for women and 0.910 ± 0.125 g/cm2 for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged ≥50 years was 12.1% at the lumbar
spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at
the femoral neck with a combined prevalence of 6.6%.
Received: 23 April 1999 / Accepted: 14 April 2000 相似文献
15.
R. W. Downs Jr. H. G. Bone H. McIlwain M. Z. Baker A. J. Yates A. Lombardi D. Krupa R. Harning 《Calcified tissue international》1999,64(6):463-469
We have recently reported the results of a 24-month, double-blind, placebo-controlled study in 359 elderly osteoporotic women
who were treated with daily oral alendronate (ALN) 1, 2.5, or 5 mg or placebo (PBO). We report the results of a 12-month,
open-label, extension study during which 246 patients from the original study were treated with ALN 10 mg/day. Significant
increases in lumbar spine bone mineral density (BMD) were observed in patients who had previously received PBO or ALN 1 and
2.5 mg/day for 24 months. Significant gains in trochanter BMD were seen in all treatment groups. Small changes were observed
in femoral neck, total body, and forearm BMD during the course of this extension study. In general, the greatest increases
in BMD during the open-label extension year occurred in patients who received either PBO or the lower doses of ALN during
the previous 2-year blinded study. The frequencies of all categories of upper gastrointestinal adverse experiences (AEs) were
less during months 25–36 (open-label extension) than during months 0–24 (original study). In conclusion, treatment with ALN
10 mg/day for 12 months in elderly women with osteoporosis who were previously treated for 24 months with PBO or ALN 1, 2.5,
or 5 mg/day increased or maintained BMD of the spine, trochanter, and forearm, and was generally safe and well tolerated,
especially in the upper gastrointestinal tract.
Received: 16 June 1998 / Accepted: 1 November 1998 相似文献
16.
P. D. Delmas G. Calvo M. Boers E. Abadie B. Avouac A. Kahan J. M. Kaufman A. Laslop J. F. Lekkerkerker P. Nilsson B. Van Zwieten-Boot G. Kreutz J. Y. Reginster 《Osteoporosis international》2002,13(1):1-5
Registration of new agents for the treatment of postmenopausal osteoporosis has been based over the past few years on placebo-controlled
phase III trials with the incidence of patients with new vertebral/nonvertebral fractures as the most usual primary endpoint.
The use of a placebo in diseases where an active treatment is available has been a matter of debate following the update of
the Declaration of Helsinki by the World Medical Association which questioned this trial design. Current regulatory recommendations
within the European Union suggest that placebo-controlled trials are still the best option when assessing the efficacy and
safety of new drugs intended for the treatment of postmenopausal osteoporosis. This suggestion seems to be in apparent contradiction
with the current content of the Declaration of Helsinki. This paper addresses the ethics and feasibility of placebo-controlled
trials in the treatment of postmenopausal osteoporosis, in the light of available therapeutic options, and discusses possible
alternative approaches in those patients where placebo treatment could be deemed to be unethical. It is concluded that placebo-controlled
trials remain the most efficient design to establish the efficacy and safety of a new agent for the treatment of postmenopausal
osteoporosis. Such trials are feasible and ethically acceptable in patients with osteoporosis but without prevalent vertebral
fractures. Conversely, in patients with prevalent vertebral fractures, placebo-controlled trials are ethically questionable
and non-inferiority trials are more appropriate. A relative margin of non-inferiority of 20–30% is suggested, to be discussed
on a case by case basis.
Received: 25 October 2001 / Accepted: 13 November 2001 相似文献
17.
Intravenous Pamidronate as Treatment for Osteoporosis after Heart Transplantation: A Prospective Study 总被引:4,自引:0,他引:4
M. A. Krieg C. Seydoux L. Sandini J. J. Goy D. Gillard Berguer D. Thie´baud P. Burckhardt 《Osteoporosis international》2001,12(2):112-116
Fractures due to osteoporosis are one of the major complications after heart transplantation, occurring mostly during the
first 6 months after the graft, with an incidence ranging from 18% to 50% for vertebral fractures. Bone mineral density (BMD)
decreases dramatically following the graft, at trabecular sites as well as cortical sites. This is explained by the relatively
high doses of glucocorticoids used during the months following the graft, and by a long-term increase of bone turnover which
is probably due to cyclosporine. There is some evidence for a beneficial effect on BMD of antiresorptive treatments after
heart transplantation. The aim of this study was to assess prospectively the effect on BMD of a 3-year treatment of quarterly
infusions of 60 mg of pamidronate, combined with 1 g calcium and 1000 U vitamin D per day, in osteoporotic heart transplant
recipients, and that of a treatment with calcium and vitamin D in heart transplant recipients with no osteoporosis. BMD of
the lumbar spine and the femoral neck was measured by dual-energy X-ray absorptiometry in all patients every 6 months for
2 years and after 3 years. Seventeen patients, (1 woman, 16 men) aged 46 ± 4 years (mean ± SEM) received only calcium and
vitamin D. A significant decrease in BMD was observed after 6 months following the graft, at the lumbar spine (−6.6%) as well
as at the femoral neck (−7.8%). After 2 years, BMD tended to recover at the lumbar spine, whereas the loss persisted after
3 years at the femoral neck. Eleven patients (1 woman and 10 men) aged 46 ± 4 years (mean ± SEM) started treatment with pamidronate
on average 6 months after the graft, because they had osteoporosis of the lumbar spine and/or femoral neck (BMD T-score below −2.5 SD). Over the whole treatment period, a continuous increase in BMD at the lumbar spine was noticed, reaching
18.3% after 3 years (14.3% compared with the BMD at the time of the graft). BMD at the femoral neck was lowered in the first
year by −3.4%, but recovered totally after 3 years of treatment. In conclusion, a 3-year study of treatment with pamidronate
given every 3 months to patients with existing osteoporosis led to a significant increase in lumbar spine BMD and prevented
loss at the femoral neck. However, since some of these patients were treated up to 14 months after the transplant, they may
already have passed through the phase of most rapid bone loss. In patients who were not osteoporotic at baseline, treatment
with calcium and vitamin D alone was not able to prevent the rapid bone loss that occurs immediately after transplantation.
Received: 31 June 2000 / Accepted: 23 August 2000 相似文献
18.
Bone Changes due to Glucocorticoid Application in an Ovariectomized Animal Model for Fracture Treatment in Osteoporosis 总被引:6,自引:0,他引:6
C. A. Lill C. A. Lill U. V. Gerlach C. Eckhardt J. Goldhahn E. Schneider 《Osteoporosis international》2002,13(5):407-414
In a pilot experiment comparing four different modalities for inducing osteoporosis in the sheep, a combination of ovariectomy,
calcium/vitamin D-restricted diet and steroid administration was found to generate the highest decrease in bone mineral density
(BMD). The aim of the present study was to quantify the outcome of this triple treatment in an animal model of osteoporosis
in terms of alteration in bone mass, bone structure and bone mechanics. A total of 32 sheep were divided into two equal groups.
Group 1 (age 3–5 years) was used as a normal control. Group 2 (age 7–9 years) was ovariectomized, fed a calcium/vitamin D-restricted
diet and injected with methylprednisolone (MP) over 7 months (22 weeks MP solution, 6 weeks MP suspension). The BMD at the
distal radius and tibia was determined preoperatively and at repeated intervals bilaterally using quantitative computed tomography.
Steroid blood levels were determined 4 and 24 h after selected injections. BMD was measured at L3 and L4 after 7 months. Biopsies
were taken from iliac crests, vertebral bodies and femoral heads, and bone structure parameters investigated by three-dimensional
micro-CT. Compressive mechanical properties of cancellous bone were determined from biopsies of vertebral bodies and femoral
heads. After 7 months of osteoporosis induction the BMD of cancellous bone decreased 36 ± 3% in the radius and 39 ± 4% in
the tibia. Steroid blood levels 24 h after injection of MP suspension were significantly higher than after injection of MP
solution. Changes in structural parameters of cancellous bone from the iliac crest, lumbar spine and femoral head in group
2 indicated osteoporosis-associated changes. In group 2 there was a significant reduction in BMD of the lumbar spine and a
significant reduction in stiffness and failure load in compression testing of biopsies of lumbar vertebrae. In sheep, changes
in the structural parameters of bone such as trabecular number and separation during osteoporosis induction are comparable
to the human situation. The sheep model presented seems to meet the criteria for an osteoporosis model for fracture treatment
with respect to mechanical and morphometric bone properties.
Received: 4 May 2001 / Accepted: 6 December 2001 相似文献
19.
A Prospective Evaluation of the Awareness, Knowledge, Risk Factors and Current Treatment of Osteoporosis in a Cohort of Elderly Subjects 总被引:3,自引:0,他引:3
This was a prospective cohort study of 145 seniors attending a senior’s clinic and social day program using a self-administered
questionnaire. Its objective was to evaluate the awareness, knowledge, risk factors and current treatment of osteoporosis
in our two patient groups. A secondary objective was to determine differences between the two cohorts, and between men and
women. Participants included 39 men and 106 women, with an average age of 76 years. Of these, 89% were aware of osteoporosis
and 61% gave the correct definition. Awareness and accurate definition were less in men compared with women (p<0.01, and p<0.05) and clinic compared to day program groups (p<0.01). Only 54% of men knew osteoporosis could affect them. Television, newspapers and friends were identified as the main
source of information. Physicians ranked as fifth as a source of information. In all, 84% knew diet was important. Prevalence
of risk factors other than age were < 20%, except for senescence (38%) and alcohol use (40%). Utilization of specific therapies
for osteoporosis was only 18% overall with a rate of 3% in men (p<0.01). In women, 50% and were taking calcium supplements compared with 15% men (p<0.001) and for multivitamins the figures were 57% and 33% respectively (p<0.05). These results show a high level of awareness and correct definition of osteoporosis in this cohort of patients. Specific
therapy for prevention or treatment of osteoporosis was inappropriately low in the face of high risk. This study highlights
the care gap in osteoporosis in seniors and the need for increased physician involvement in patient education and treatment.
Proactive treatment requests from patients need to be encouraged, especially with the future demographic shift.
Received: 3 August 2000 / Accepted: 20 December 2000 相似文献
20.
J. Y. Reginster D. Kuntz W. Verdickt M. Wouters L. Guillevin C.-J. Menke`s K. Nielsen 《Osteoporosis international》1999,9(1):75-81
One hundred and forty-five patients suffering from diseases requiring long-term treatment with high doses of corticosteroids
(30 mg/day or greater of prednisolone) were recruited to the study. Patients had to be steroid naive on entry to the study
(not more than 15 days of treatment with a corticosteroid within the previous 24 months). Patients were randomized to receive
either 1 mg/day alfacalcidol or placebo capsules for 12 months. Bone mineral density (BMD) of the lumbar spine was assessed
by dual-photon absorptiometry on entry and after 3, 6 and 12 months’ treatment. Safety was monitored by the recording of all
adverse events reported by patients and the regular screening of blood samples for hematology and serum biochemistry. Of the
145 patients, 74 were randomized to alfacalcidol and 71 to placebo. The treatment groups were well matched at baseline with
no significant differences in demographic, clinical or biochemical parameters. The mean equivalent dose of prednisolone at
baseline was 46.6 mg/day and 46.3 mg/day for the alfacalcidol and placebo group respectively. From the 145 patients randomized
to treatment, 71 (38 who received alfacalcidol and 33 who received placebo) provided BMD data both at baseline and at 3, 6
and 12 months. The percentage change in BMD after 6 months’ treatment was –2.11% in the alfacalcidol group and –4.00% in the
placebo group (p= 0.39). After 12 months the percentage change in BMD was +0.39% (CI: –4.28 to 4.81) in the alfacalcidol group and –5.67%
(CI: –8.13 to –3.21) in the placebo group, this difference (6.06%, CI: 0.88 to 11.24) being statistically significant (p= 0.02). An intention to treat analysis also showed a significant difference between the two treatment groups in alfacalcidol’s
favor (3.81%, p= 0.01; CI: 0.92 to 6.70). There was no significant difference between the two treatment groups in the corticosteroid dose
at any time point during the study. Serum calcium was measured throughout and there were no significant differences between
the two treatment groups at any visit. This study suggests that alfacalcidol can prevent corticosteroid-induced bone loss
from the lumbar spine. Long-term use of alfacalcidol was not associated with any significant adverse effects in this diverse
group of patients.
Received: 22 May 1997 / Accepted: 27 April 1998 相似文献