J Clin Densitom. 2005 Spring;8(1):7-13. A systematic review of the effect of alendronate
on bone mineral density in men.
Sawka AM, Thabane L, Papaioannou A, Gafni A, Hanley DA, Adachi
JD.
McMaster University, Hamilton, Ontario, Canada L8N 1Y2; and St.
Joseph's Healthcare, Hamilton, Ontario, Canada L8N1Y2.
Alendronate is known to increase bone mineral density (BMD) at
the lumbar spine and hip in women, but less information is available
in men. We conducted a systematic review of randomized controlled
trials to determine whether oral alendronate improves BMD at the
lumbar spine and hip in men with low bone mass or prevalent fractures,
compared with men treated with placebo, calcium, or vitamin D.
In three trials in men, BMD (measured by dual-energy X-ray absorptiometry)
increased at 2-3 yr (compared to baseline) at the lumbar spine
and femoral neck in alendronate-treated patients compared to controls.
The pooled estimates of changes in BMD with 10 mg of alendronate
daily compared to controls were as follows: 7.8% over 2-3 yr (95%
confidence interval [CI] = 4.8- 10.8) at the lumbar spine and
3.8% (95% CI = 2.3-5.3) at the femoral neck (p < 0.001 for
treatment effect in each analysis). Statistically significant
heterogeneity of treatment effect was noted between trials. We
conclude that 10 mg of oral daily alendronate is significantly
associated with increase in BMD at the lumbar spine and hip in
men over 2-3 yr and that these changes are similar to those previously
observed in postmenopausal women.
J Periodontol. 2004 Dec;75(12):1579-85. Effect of alendronate on periodontal disease
in postmenopausal women: a randomized placebo-controlled trial.
Rocha ML, Malacara JM, Sanchez-Marin FJ, Vazquez de la Torre CJ,
Fajardo ME.
Institute of Medical Research, University of Guanajuato, Leon,
Mexico.
BACKGROUND: We investigated the effect of oral alendronate (ALN)
treatment on radiological and clinical measurements of periodontal
disease in postmenopausal women without hormone replacement therapy.
METHODS: We evaluated the effect of 6 months of ALN treatment
in 40 postmenopausal women, 55 to 65 years old with established
periodontal disease, in a controlled, double-masked, prospective
study. Volunteers were paired by age and randomized to receive
ALN (10 mg/day) or placebo for the study period. Periodontal mechanical
treatment was carried out in both groups. At baseline and after
treatment, clinical evaluation, hormone blood levels, distance
from the crestal alveolar bone (CAB) to the cemento-enamel junction
(CEJ), calcaneus bone mineral density (BMD), hormone levels, serum
N-telopeptide (NTx), and bone-specific alkaline phosphatase (BSAP)
were assessed. RESULTS: Periodontal disease conditions improved
in both groups, but greater improvement in probing depth (-0.8
+/- 0.3 mm versus -0.4 +/- 0.4 mm, P = 0.02) and gingival bleeding
(-0.3% +/- 0.13% versus -0.2% +/- 0.06%, P = 0.006) was found
in the ALN treated group. Calcaneus BMD increased in the ALN treated
group (68 +/- 47 mm3 versus -26 +/- 81 mm3, P = 0.0006). CAB-CEJ
distance diminished in the ALN group (-0.4 +/- 0.40 mm versus
0.60 +/- 0.53 mm, P = 0.00008). Marginal reduction in both NTx
and BSAP levels was found in the ALN group (-9.4 +/- 6.6 nmol
versus -4.3 +/- 4.7 nmol bone collagen equivalents, P = 0.08,
and -7.7 +/- 8.4 versus -1.5 +/- 5.0 U/l, P = 0.1, respectively).
Hormone levels were unchanged after treatment. Similar improvement
of calcaneus BMD and CAB-CEJ distance with ALN treatment was found
in obese and non-obese women. CONCLUSION: ALN treatment improved
periodontal disease and bone turnover in postmenopausal women.
Obstet Gynecol Surv. 2004 Jun;59(6):446-55; quiz
485. Hip fracture prevention in postmenopausal
women.
Kessel B.
Department of Obstetrics, Gynecology and Women's Health, University
of Hawaii, John A. Burns School of Medicine, and The Queen's Medical
Center, Honolulu, Hawaii 96813, USA.
Hip fracture is a devastating outcome associated with postmenopausal
osteoporosis. This fracture causes considerable pain, disability,
diminished quality of life, and mortality. Although bone loss
is an important factor associated with hip fracture, there are
other demographic and clinical factors such as those that increase
the risk of falling (e.g., unsteady gait, medications) that contribute
to the likelihood of experiencing a hip fracture. Nonpharmacological
interventions to reduce hip fracture risk include regular weight-bearing
exercise, fall intervention programs, and external hip protectors.
Patients should receive calcium and/or vitamin D supplementation
as necessary. Among available pharmacologic options, the bisphosphonates,
risedronate (Actonel) and alendronate (Fosamax), have reduced
the risk of hip fracture in postmenopausal women with osteoporosis.
Raloxifene (Evista), salmon calcitonin nasal spray (Miacalcin),
and teriparatide (Forteo) have not demonstrated hip fracture risk
reduction in controlled clinical trials. Hormone therapy (HT)
reduced hip fracture risk in a recent large placebo-controlled
trial; however, the risk/benefit profile of HT has resulted in
recommendations to consider alternatives for the management of
osteoporosis. Postmenopausal women with osteoporosis should receive
adequate calcium/vitamin D supplementation, be encouraged to exercise,
and institute risk factor interventions. Treatment with a bisphosphonate
should be considered for those who are also at increased risk
for hip fracture. TARGET AUDIENCE: Obstetricians & Gynecologyists,
Family Physicians LEARNING OBJECTIVES: After completion of this
article the reader should be able to list the demographic risk
factors for osteoporosis and related fractures, to outline the
cost and consequences of hip fractures, and to summarize the various
pharmacologic and non-pharmacologic interventions used to reduce
the risk of hip fracture.
Endocr Regul. 2003 Dec;37(4):225-38. Mechanisms of action of antiresorptive therapies
of postmenopausal osteoporosis.
Stepan JJ, Alenfeld F, Boivin G, Feyen JH, Lakatos P.
3rd Clinic of International Medicine, Charles University School
of Medicine, Prague, Czech Republic.
In the treatment of osteoporosis, the aim of the antiresorptive
therapy is to restore bone density by decreasing bone remodeling.
The process of bone remodeling plays a role in plasma calcium
homeostasis and serves to modify bone architecture in order to
meet changing mechanical needs, to maintain osteocyte viability,
and to repair microdamage in bone matrix. Estrogen deficiency
results in a number of detrimental effects on bone, including
suppression of osteocyte survival as well as impairment of osteoblast
response to mechanical stimuli and repair of ageing bone. In this
review, effects of available antiresorptive therapies on endocrine
regulations of bone metabolism in postmenopausal osteoporosis
are compared. The aim of antiresorptive treatment is to ensure
adequate bone remodeling, reparation of microdamage of bone, and
increased bone strength. Ideally, this effect should be maintained
long-term. Several agents are approved for the treatment of osteoporosis.
Calcitonin transiently inhibits osteoclast activity without decreasing
osteoblast collagen synthesis. Aminobisphosphonates decrease bone
remodeling by decreasing osteoclast activity and by inducing osteoclast
apoptosis. This allows more time for secondary mineralization
to proceed to completion in the existing bone tissue mass, so
increasing the mechanical resistance of bone to loading. Estrogens
and raloxifene (a selective estrogen receptor modulator that acts
as an estrogen agonist in bone) suppress bone remodeling to the
premenopausal range, maintaining the function of osteoblasts and
osteocytes. In the placebo-controlled osteoporosis treatment trials,
all the above treatments reduced the risk of fractures. Raloxifene
therapy was also associated with a favorable or neutral effect
in the cardiovascular system, and a reduced incidence of breast
cancer. Selection of appropriate drug for treatment of postmenopausal
osteoporosis should take into account the long-term effect of
the antiresorptive agent on bone. Moreover, the effects on other
tissues ++should also be considered, and this encompasses both
safety concerns, as well as the potentially beneficial effects
on other tissues. Further investigation is needed to evaluate
the different modes of action of these agents, and their long-term
effects on bone and other tissues.
Bratisl Lek Listy. 2003;104(10):309-13. The effect of alendronate in the treatment
of postmenopausal osteoporosis.
Rozkydal Z, Janicek P.
Ist Orthopaedic Department, St. Anna's Hospital, Masarykiensis
University, Brno, Czech Republic.
OBJECTIVES: The aim of the study was the evaluation of the effect
of alendronate in the treatment of postmenopausal osteoporosis
on subjective criteria and on bone mineral density after two years.
MATERIAL AND METHODS: The authors collected data from 44 women
by questionaire and analysed the data from DEXA examination. The
patients were given Fosamax 10 mg and calcium 500 mg per day in
the years 2001-2002. RESULTS: The compliance of alendronate was
good in 42 women (95.5%). 15 patients were very satisfied with
the treatment, 22 were satisfied and 5 patients claimed no improvement
at the end of the study. A positive effect of the treatment was
seen in 37 patients (88.1%). 21 patients claimed to have no pain
and 15 patients suffered mild intermitent pain at the end of the
study. 24 patients used no analgetics and 9 patients used them
irregularly. 11 patients claimed to have normal activity and 22
patients had mildly diminished activity in daily life. The authors
encountered no symptomatic vertebral or nonvertebral fracture
during the study. The mean BMD in the lumbar spine improved in
T score by 0.38 SD after one year and 0.35 SD after the second
year. The mean BMD has improved in the neck region in T score
by 0.21 SD after the first year and 0.21 SD after the second year.
The mean BMD in lumbar spine has improved in Z score by 0.31 SD
after one year and 0.02 SD after the second year. The mean BMD
in the neck region has improved in Z score by 0.31 SD after the
first year and 0.16 SD after the second year. The mean change
of bone mineral density in lumbar spine was +4.17% after the first
years and +4.19% after the second year. The mean change of BMD
in the femoral neck region was +4.46% after the first years and
+ 3.71% after the second year. According to student t-test all
the data of increased BMD were statisticaly significant at the
5% level of the significance (p < 0.05). CONCLUSION: Alendronate
therapy significantly reduced the pain and the need for analgesics.
It improved the daily activity and mobility of the spine in the
patients with postmenopausal osteoporosis. It resulted in a positive
change of BMD in vertebral region of +8.36% and +8.17% in the
femoral neck region after two years. The fracture risk in vertebral
region was diminished by 31% and in the femoral neck region by
38% at the end of the study. (Tab. 11, Ref. 14.).
JAMA. 2003 May 21;289(19):2525-33. Combination therapy with hormone replacement
and alendronate for prevention of bone loss in elderly women:
a randomized controlled trial.
Greenspan SL, Resnick NM, Parker RA.
Division of Endocrinology and Metabolism and Division of Geriatric
Medicine, University of Pittsburgh Medical Center, Pittsburgh,
Pa, USA.
CONTEXT: Therapy with individual antiresorptive agents has been
shown to be effective for prevention and treatment of postmenopausal
osteoporosis, but whether combination antiresorptive therapy with
hormones and bisphosphonates is safe or efficacious or how these
agents compare in elderly women is unknown. OBJECTIVE: To determine
whether hormone replacement and the bisphosphonate alendronate
sodium in combination are efficacious and safe, and how they compare
with monotherapy in community-dwelling elderly women. DESIGN:
Randomized, double-blind, placebo-controlled, clinical trial.
SETTING AND PARTICIPANTS: Five hundred seventy-three community-dwelling
women age 65 years or older were screened: 485 completed screening
and 373 (aged 65 to 90 years) were randomized following a 3-month,
open-label, run-in phase with hormone replacement and alendronate
placebo. The trial was conducted at a single academic US medical
center from January 1996 to May 2001. INTERVENTIONS: Participants
were randomly assigned in a 2 x 2 factorial design to receive
hormone replacement (conjugated equine estrogen, 0.625 mg/d, with
or without medroxyprogesterone, 2.5 mg/d) and alendronate, 10
mg daily, both agents, or neither. All participants received calcium
and vitamin D supplements. MAIN OUTCOME MEASURES: Annualized change
in bone mineral density of the hip and spine and occurrence of
adverse events. RESULTS: Bone mineral density at 3 years was significantly
greater at all femoral and vertebral sites in women treated with
combination therapy than with monotherapy, with mean (SD) increases
of 5.9% (3.8) at the total hip, 10.4% (5.4) at the posteroanterior
lumbar spine, and 11.8% (6.8) at the lateral lumbar spine. Mean
(SD) increases in bone mass at the hip in women treated with alendronate
alone were significantly greater than in those treated with hormone
replacement therapy alone (4.2% [3.8] vs 3.0% [4.9]; P<.05,
respectively), and alendronate resulted in more responders to
therapy. All therapies were well tolerated and participant retention
was 90% at 3 years. CONCLUSIONS: Combination therapy with hormone
replacement and alendronate was efficacious and well tolerated
in this cohort. Alendronate was superior to hormone replacement,
and combination therapy was superior to either therapy alone.
Combination therapy may represent an option for women with more
severe disease or for those who have failed to achieve an adequate
response to monotherapy.
Arch Intern Med. 2003 Apr 14;163(7):789-94. Alendronate prevents loss of bone density
associated with discontinuation of hormone replacement therapy:
a randomized controlled trial.
Ascott-Evans BH, Guanabens N, Kivinen S, Stuckey BG, Magaril CH,
Vandormael K, Stych B, Melton ME.
Groote Schuur Hospital and University of Cape Town, Cape Town,
South Africa.
BACKGROUND: Many women using hormone replacement therapy (HRT)
will discontinue HRT and lose its bone-protective effect. Methods
to preserve bone density in these women need to be explored. This
multicenter, international, randomized, blinded, 12-month study
was conducted to assess the effect of alendronate sodium on bone
density in women who had recently discontinued HRT. METHODS: The
144 postmenopausal women included in the study were diagnosed
as having low bone mineral density (BMD) and had recently discontinued
HRT. They were randomized to receive either a daily dose of 10
mg of alendronate sodium or matching placebo. The main outcome
measures were spine, hip, and total body BMD; biochemical markers
of bone turnover; and tolerability. RESULTS: Alendronate treatment
was associated with a 2.3% mean increase (95% confidence interval
[CI], 1.7%-3.0%) in spine BMD compared with a mean loss of 3.2%
(95% CI, - 4.6% to - 1.7%) in patients receiving placebo, for
a difference of 5.5% (95% CI, 4.2%-6.8%) between alendronate and
placebo. Greater hip and total body BMD preservation was also
observed with alendronate use. Bone turnover decreased significantly
with alendronate (bone-specific alkaline phosphatase levels decreased
by 20% and urinary N-telopeptide/creatinine ratio by 47%), but
increased in the placebo group (by 18% and 36%, respectively).
Alendronate was well tolerated, with no increase in adverse events
compared with placebo. CONCLUSIONS: A high rate of bone loss was
observed in the first 12 to 15 months after discontinuation of
HRT in postmenopausal women with low BMD. Treatment with alendronate
increased or maintained both spine and hip BMD and prevented the
increase in bone resorption seen with withdrawal of HRT in this
population.
Fertil Steril. 2003 Sep;80(3):541-5. Effects of hormone therapy and alendronate
on C-reactive protein, E-selectin, and sex hormone-binding globulin
in osteoporotic women.
Ylikorkala O, Evio S, Valimaki M, Tiitinen A.
Department of Obstetrics and Gynecology, Helsinki, Finland.
C-reactive protein and soluble E-selectin hold promise as surrogate
markers for future cardiovascular events. We studied the effects
of oral hormone therapy (HT) and alendronate, given alone or together,
on these markers and on sex hormone-binding globulin levels in
osteoporotic elderly women.Prospective, randomized, double-dummy
trial.Outpatient department of a university hospital.Ninety osteoporotic
women (T score
Fertil Steril. 2003 Sep;80(3):536-40. Effect of daily hormone therapy and alendronate
use on bone mineral density in postmenopausal women.
Davas I, Altintas A, Yoldemir T, Varolan A, Yazgan A, Baksu B.
Second Obstetrics and Gynecology Clinic, Sisli Etfal Training
and Research Hospital, Istanbul, Turkey.
To evaluate the effect of daily oral and transdermal hormone therapy
alone or in combination with alendronate on bone mineral density
in postmenopausal women.Comparative prospective clinical study.Outpatient
clinic of a training and research hospital.One hundred seventy-three
consecutive postmenopausal women with no previous hormone therapy
and a bone mineral density T score <-1 SD were randomly enrolled.Oral
conjugated estrogen, alone or with alendronate, or transdermal
estrogen, alone or with alendronate, given for 1 year. All patients
also received medroxyprogesterone acetate and calcium.Bone density
measurement at L2 to 4 region by dual-energy X-ray absorptiometry.At
the end of 1 year, significant increase in bone density measurements
were seen in all groups. Oral conjugated estrogen and transdermal
estrogen have the same effect on bone mineral density loss. Hormone
therapy alone stabilized the bone mineral density loss. Hormone
therapy together with alendronate resulted in better values in
all groups.Hormone therapy is adequate in osteopenic women. However,
hormone therapy plus alendronate is advantageous in women with
considerable bone mineral density loss.
Am J Med. 2003 Aug 15;115(3):209-16. Early discontinuation of treatment for osteoporosis.
Tosteson AN, Grove MR, Hammond CS, Moncur MM, Ray GT, Hebert GM,
Pressman AR, Ettinger B.
Department of Medicine, Dartmouth Medical School, Hannover, New
Hampshire 03756, USA.
PURPOSE: To identify factors associated with early treatment discontinuation
of three agents commonly prescribed for women with low bone density.
METHODS: A telephone survey was conducted in 2000 to 2001 in a
random sample of women aged 45 years or older who had bone density
T-scores -1.0 or lower and who had initiated treatment with hormone
replacement therapy, raloxifene, oral endronate. Logistic regression
was used to estimate adjusted odds ratios for early treatment
discontinuation. RESULTS: Among 956 women who were interviewed
an average of 7 months after treatment initiation, 334 were taking
hormone therapy, and 88 (26%) had discontinued; 256 were taking
raloxifene, and 48 (19%) had discontinued (P = 0.03 vs. hormone
therapy); and 366 were taking alendronate, and 70(19%) had discontinued
(P = 0.02 vs. hormone therapy).Women with bothersome side effects
(somewhat bothered: odds ratio [OR] = 4.0; 95% confidence interval
[CI]: 2.5 to 6.5; very or extremely bothered: OR = 25; 95% CI:
16 to 39) or who thought that their bone density test results
did not show osteoporosis (OR = 1.6; 95% CI: 1.0 to 2.5) were
more likely to discontinue therapy, as compared with women reporting
regular exercise (OR = 0.7; 95% CI: 0.4 to 1.0) or a willingness
to take prescribed medications (OR = 0.6; 95% CI: 0.4 to 0.9).After
adjustment for side effects and patient characteristics, the odds
of early treatment discontinuation did not differ significantly
among treatments. CONCLUSION: Improved adherence to osteoporosis
treatment requires that treatment side effects be minimized and
women be educated regarding their bone density test results.
Bone. 2003 Jul;33(1):132-43. Effect of alendronate and exercise on bone
and physical performance of postmenopausal women: a randomized
controlled trial.
Uusi-Rasi K, Kannus P, Cheng S, Sievanen H, Pasanen M, Heinonen
A, Nenonen A, Halleen J, Fuerst T, Genant H, Vuori I.
UKK Institute for Health Promotion Research, 33501 Tampere, Finland.
In this randomized, double-blind, placebo-controlled 12-month
trial we evaluated effects of weight- bearing jumping exercise
and oral alendronate, alone or in combination, on the mass and
structure of bone, risk factors for falling (muscle strength and
power, postural sway, and dynamic balance), and cardiorespiratory
fitness in postmenopausal women. A total of 164 healthy, sedentary,
early postmenopausal women were randomly assigned to one of four
experimental groups: (1) 5 mg of alendronate daily plus progressive
jumping exercise, (2) 5 mg alendronate, (3) placebo plus progressive
jumping exercise, or (4) placebo. The primary endpoint was 12-month
change in bone mass and geometry (measured with dual-energy X-ray
absorptiometry and peripheral computed tomography at several axial
and limb sites) and physical performance; the secondary endpoint
was change in biochemical markers of bone turnover. The jumping
exercise was conducted an average 1.6 +/- 0.9 (mean +/- SD) times
a week. Alendronate daily was effective in increasing bone mass
at the lumbar spine (alendronate vs placebo 3.5%; 95% CI, 2.2-4.9%)
and femoral neck (1.3%; 95% CI, 0.2-2.4%) but did not affect other
bone sites. Exercise alone had no effect on bone mass at the lumbar
spine or femoral neck; it had neither an additive nor an interactive
effect with alendronate at these bone sites. However, at the distal
tibia the mean increase of 3.6% (0.3-7.1%) in the section modulus
(that is, bone strength) and 3.7% (0.1-7.3%) increase in the ratio
of cortical bone to total bone area were statistically significant
in the exercise group compared to the nonexercise group, indicating
exercise-induced thickening of the bone cortex. Bone turnover
was reduced in alendronate groups only. Alendronate had no effect
on physical performance while the jumping exercise improved leg
extensor power, dynamic balance, and cardiorespiratory fitness.
As conclusion Alendronate is effective in increasing bone mass
at the lumbar spine and femoral neck, while exercise is effective
in increasing the mechanical properties of bone at some of the
most loaded bone sites, as well as improving the participants'
muscular performance and dynamic balance. Together alendronate
and exercise may effectively decrease the risk of osteoporotic
fractures.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002 Jun;24(3):306-9.
The efficacy of alendronate in the prevention
and treatment of postmenopausal osteoporosis.
Cheng ZQ, Yin W, Fan JY, Ma TJ.
Department of Endocrinology, General Hospital, Tianjin Medical
University, Tianjin 300075, China.
OBJECTIVE: To investigate the effectiveness of alendronate Chinese
national product in the prevention and treatment of postmenopausal
osteoporosis. METHODS: The 56 postmenopausal women with osteopenia
or osteoporosis were randomly divided into two groups: treated
with alendronate 10 mg/d (28 cases) orally and placebo (28 cases),
for 6 months. All subjects received 600 mg/d of calcium carbonate
and vitamin D 1,000 U/d. Bone mineral density (BMD) of the lumbar
spine, femoral neck, trochanter and Ward's triangle were measured
by dual energy X-ray absorptiometry as well as the markers of
bone turnover were analysed at the beginning and the end of the
study. RESULTS: The results showed that lumbar spine BMD increased
by 5% in the alendronate group (P < 0.01), but decreased in
BMD of the lumbar spine and femur in the placebo group (P <
0.05) after 6 months of treatment. In the alendronate group the
marker of bone resorption and bone formation were significantly
decreased after alendronate therapy. There were no change in placebo
group. CONCLUSIONS: Alendronate (Chinese national product) is
effective in reducing bone turnover and promoting bone mass of
postmenopausal osteoporosis.
J Biomed Mater Res. 2001;58(6):645-50. The effect of alendronate (Fosamax) and
implant surface on bone integration and remodeling in a canine
model.
Frenkel SR, Jaffe WL, Valle CD, Jazrawi L, Maurer S, Baitner A,
Wright K, Sala D, Hawkins M, Di Cesare PE.
Musculoskeletal Research Center and Department of Orthopaedic
Surgery, New York University Hospital for Joint Diseases, New
York, New York 10003, USA.
Patients at high risk for osteoporosis and its associated morbidity,
including postmenopausal women, are being pharmacologically managed
to stabilize and improve bone mass. Alendronate sodium (Fosamax)
is a commonly used antiresorptive agent effective in osteopenic
women for reducing bone resorption, increasing bone density, and
decreasing fracture incidence. With the increased incidence of
alendronate-treated women who are undergoing hip replacement or
fracture repair by prosthesis placement, data are needed to predict
how alendronate affects host bone integration with uncemented
surfaces. The aim of this study was to determine the effect of
alendronate on new bone formation and attachment to implant surfaces
in a normal and simulated estrogen-deficient, calcium-deficient
canine model, using an implantable bone growth chamber. Alendronate
did not affect host bone integration to surfaces commonly used
in uncemented total joint arthroplasty, but there were significant
differences dependent solely on the type of surface.
Int J Clin Pract Suppl. 1999 Apr;101:40-5. The antifracture efficacy of alendronate.
Seeman E.
Department of Endocrinology, Austin & Repatriation Medical
Center, Heidelberg, Melbourne, Australia. Alendronate Phase III
Treatment Study Group.
Two multicentre, double-blind, randomised trials were performed
involving 994 postmenopausal women (mean age 64 yr, range 45-80
yr) with osteoporosis and using identical protocols at centres
in the USA and internationally. Patients were included if bone
density was +/- 2.5 standard deviations below the young-normal
mean. The presence of fracture was not an inclusion criterion.
Patients received placebo or alendronate (ALN) (5 or 10 mg/day
for 3 yr, or 20 mg/day for 2 yr, then 5 mg/day for 1 yr). All
received 500 mg elemental calcium. Analysis of vertebral fracture
rates was based on preplanned pooling of all treatment groups.
Analysis of nonvertebral fracture rates was based on preplanned
pooling of this protocol and 3 similar studies in postmenopausal
women with osteoporosis. Bone density decreased in the patients
receiving placebo and increased in the patients receiving ALN.
The optimum dose to increase bone density was 10 mg daily. After
3 years, bone density was 8.8 +/- 0.4% (lumbar spine), 5.9 +/-
0.5% (femoral neck) and 7.8 +/- 0.6 (trochanter) higher in the
patients treated with 10 mg/day ALN than in patients receiving
placebo. One or more new vertebral fractures occurred in 17 of
526 patients receiving ALN (3.2%) and 22 of 355 patients receiving
placebo (6.2%) (a 48% reduction, (P = 0.034). Of the patients
having new vertebral fractures, > or = 2 fractures occurred
in 3 of 17 (18%) ALN-treated patients and 15 of 22 (68%) receiving
placebo (P < 0.001). Fewer patients receiving ALN had vertebral
fractures whether stratified by age or by the presence or absence
of vertebral fractures at entry. Among patients sustaining vertebral
fractures, height loss was 23.3 mm in patients receiving placebo
and 5.9 mm in patients receiving ALN. Clinical adverse events,
mainly upper gastrointestinal irritation, resulted in discontinuations
in 6% (placebo), 5.4% (5 mg), 4.1% (10 mg), 8% (20 mg/5 mg). In
the pooled analysis across all 5 osteoporosis treatment clinical
trials, nonvertebral fractures occurred in 73 of 1012 ALN-treated
women (76 fractures in 2240 patient-years) and in 60 of 590 women
receiving placebo (70 fractures in 1347 patient-years). After
3 years, the cumulative incidences (ALN vs placebo) were 9% and
12.6%, a 29% reduction in absolute risk compared with placebo
(P = 0.048). Alendronate is a well-tolerated new treatment that
reduces the risk and severity of new vertebral fractures, reduces
height loss and may reduce the risk of nonvertebral fractures.
Int J Clin Pract Suppl. 1999 Apr;101:62-6. Alendronate in the treatment of Paget's
disease of bone.
Reid IR, Siris E.
University of Auckland, Auckland, New Zealand.
This review reports the results of 2 recently completed long-term,
randomised, double-blind, multicentre, controlled studies in which
men and women with moderate to severe Paget's disease received
oral alendronate 40 mg daily for 6 months One study conducted
in the United States, compared the effects of alendronate 60 mg/day
(n=41) with those of oral etidronate 400 mg/day (n=47); the other,
conducted in the United Kingdom, Australia, and New Zealand, compared
the effects of alendronate (n=27) with those of placebo (n=28).
In both studies alendronate significantly reduced serum concentrations
of alkaline phosphatase by more than 70%, which was significant
in comparison with baseline (P < 0.001) and the comparator
regimens (P < 0.001). Response to treatment (i.e. a > 60%
decrease in or normalisation of serum alkaline phosphatase) was
seen in more than three-quarters of patients treated with alendronate
in both trials, compared with less than one-third of patients
treated with etidronate and no patients treated with placebo.
Radiologic scores, reflecting the status of osteolytic lesions,
improved in a greater proportion of patients receiving alendronate
than in those receiving etidronate or placebo. Histomorphometric
analysis performed at 6 months showed that bone formed during
alendronate treatment was of normal quality, without evidence
of impaired mineralisation or other abnormalities. Alendronate
was well tolerated, with an adverse event profile comparable with
those of etidronate and placebo. These studies therefore showed
that 6 months of treatment with oral alendronate suppresses disease
activity in patients with Paget's disease of bone, with beneficial
effects on biochemical, radiologic, and histomorphometric indices
superior to those of etidronate and placebo.
Int J Clin Pract Suppl. 1999 Apr;101:14-7. The effects of alendronate on bone turnover
and bone quality.
Meunier PJ, Arlot M, Chavassieux P, Yates AJ.
Hopital Edouard Herriot, Lyon, France.
During Phase III clinical trials with alendronate, biochemical
and histological studies assessed bone turnover and bone quality
in patients treated for 3 years. Patients were randomised in double-blind
fashion to receive placebo, alendronate 5 or 10 mg/day for 3 years
or 20 mg/day for 2 years followed by 5 mg/day for 1 year. All
patients also received 500 mg/day of calcium carbonate. Decreases
in bone resorption with alendronate preceded decreases in bone
formation. After approximately 6 months of continuous treatment,
a new steady state of bone turnover was attained, leading to the
increase in bone density. No subsequent decrease in the rate of
bone turnover or of frozen bone was noted. Alendronate treatment
did not impair bone mineralisation, induce the formation of woven
bone or have any other adverse effects on bone quality.
Rev Med Liege. 1998 Apr;53(4):220-2. Drug clinics. The drug of the month. Alendronate
(Fosamax).
Scheen AJ.
Service de Diabetologie, Universite de Liege.
Alendronate (Fosamax, Merck Sharp & Dohme) is an aminobisphosphonate
which inhibits bone turnover by suppressing the activity of osteoclasts
without increasing the risk of osteomalacia. Alendronate is highly
effective at preventing bone loss associated to absence of endogenous
estrogen and induces a sustained increase in bone mass. Fosamax
is indicated and reimbursed in the treatment of osteoporosis in
postmenopausal women, with either an history of bone fracture
confirmed by X-ray exam or obvious osteoporosis assessed by bone
mineral density measurement. The recommended dosage is 10 mg once
daily, continuously. The drug should be absorbed after an overnight
fast to improve its bioavailability and with a big glass of plain
water to reduce the risk of oesophageal ulcerations. Large randomized
controlled trials for up to 3 years have demonstrated that alendronate
is able to reduce the risk and rate of occurrence of vertebral
and nonvertebral fractures in postmenopausal women.
