Mais la polymyxine n'est pas du tout absorbée dans le sang du système gastro-intestinal et n'a d'effet que dans l'intestin et est utile pour le traitement des infections intestinales metronidazole prix Internet en y faisant des achats permettant d’économiser jusqu'à soixante-dix pour cent, tout en étant sûr de la qualité des produits pharmaceutiques.
Effects of alendronate on bone density in thalassemic patients
Evaluation of alendronate efficacy on bone mineral density in thalassemic
Alendronate in the treatment of Thalassaemia induced osteoporosis
Thalassaemia is the most common genetic disorder in the world which is
afflicted about 200 million people in this disorder, the etiology of bone disease is
multifactorial. Seemingly, in the setting of increased bone turn-over which manifests by
increased bone resorption and remodeling; bone density decreases. In this research,
Thalassaemia patients with osteoporosis were placed on oral Alendronate therapy for one
year and their pre-and post-study bone mineral densitometry were compared.
Thalassaemia patients; comprising the major and intermedia types, in the range of
20 to 50 years old were included in the study. They were admitted at three different centers;
Tehran center of Thalassaemia, Iran blood transfusion organization and the rheumatology
clinic of hazard Rasool Akram(s) hospital. First of all, osteoporotic patients diagnosed on the
basis of densitometry were placed on oral regimen of 10mg of Alendronate daily. After a
year, their densitometries were repeated and compared for the changes in BMD(g/cm2) and T-
score. Also, patient’s serum calcium, phosphorus and alkaline phosphatase levels were
measured at the beginning and the end of the year and the results were compared.
Ninety-six patients of all 120 patients under the scope of the study did their both
first and second bone densitometries which showed increase in BMD and T-score at the
end of the study. Regarding to the BMD increase in patients who used their drugs regularly
and no increase in patients who used drugs irregularly or essentially did not use any
, we concluded that the role of bisphosphonates for example Alendronate in
increasing bone density of neck of femur and vertebral bones were remarkable without having
dangerous side effects. So early diagnosis; treatment and prophylaxis of osteoporosis in this
group of patients are highly recommendable.
Thalassaemia - Osteoporosis - BMD - Alendronate
Thalassemia is an inherited anemia in which production of polypeptide chains is disturbed,
lead to decline in hemoglobin (Hg) synthesis and makes anemia that in α and β thalassemia
Since Hg is responsible for carrying oxygen to the tissues, various symptoms of this disease
are created subsequent the anemia. First in 1925 this disease was introduced by a physician
called Thomas Koly which was seen in the migrators to the United States like Italians.
Thalssa means the sea and hemia is the synonym of anemia [1, 2].
Prevalence of genetic disorder of thalassemia is more in American and Asian regions and in
Northern Province of Iran. About 4% of the populations in Iran are carrying gen of
Thalassemia shows various symptoms in different organs; bone lesions, hormonal disorders
like hypogonadism, hypothyroidism, hypothyroidism, hepatomegaly, spelenomegaly and
changes in the personal appearance are some of these symptoms [3, 4].
One of the symptoms of this disease is osteoporosis which is preventable and curable with
proper diagnosis by bone mineral densitometry (BMD). Treatment of osteoporosis in these
patients includes exercise, consumption of calcium (Ca 1200 mg daily, vitamin D 400 U
daily, sexual hormone replacement, adequate treatment with desferal since childhood and
using bisphosphonates like alendronate [5, 6]. In one study about osteoporosis on 25 patients
with major thalassemia in Italy, alendronate 10 mg/d showed acceptable outcome after two
years . In another study on 26 thalassemic patients in Greece, pamidronate IV showed
considerable changes in BMD after one year and bone markers also changed .
Materials and methods
This study was performed on patients with major thalassemia and intermediate (age range of
20-50 years). Patients who were referred to the thalassemic outpatient clinic of Tehran center
of thalassemia, Iran blood transfusion organization and the rheumatology clinic of Rasool
At the beginning, bone densitometry of lumbar vertebras L2-L4 and neck of Femur were
measured using densitometry system (DXA), Norland type in all the participants and these
were repeated after one year treatment with alendronate,and T-Score of Ap spine and Neck of
fumre was evaluated. Serum levels of ferritin, calcium, phosphor, alkaline phosphatase were
also measured at the beginning and one year after use of alendronate 10 mg.
Patients received alendronate 10 mg/d (Modava company, Iran), calcium 100 mg/d
(Darupakhsh company, Iran) and vitamin D 400 U (two Ca-D tablets daily). All the patients
were visited in 1, 3, 6, 9 and 12 months. Accurate consumption of drugs and their side effects
were asked from the participants and were registered in the questionnaire.
Consumption of the drug was recorded in three ways:
1. Non-using of the drug that alendronate was discontinued in weeks 1-4 and was not
2. 2. Irregular use that less than 70 mg (7 tablets) was used in a week
3. 3. Regular use that at least 70 mg has been used in a week.
In cases of incorrect use of the drug or considerable gastrointestinal complications like gastric
ulcer or gastritis, patients were taken apart. BMD was performed at the beginning and after
one year treatment and changes more than 3% in spine and more than 6% in the neck of
Results were reported as mean ± standard deviation (SD) for quantitative variables and
percentages for categorical variables. Initial and final values of each variable were compared
using paired T test. Statistical significance was based on two-sided design-based tests
evaluated at the 0.05 level of significance. All the statistical analyses were performed using
SPSS version 16 (SPSS Inc, Chicago, IL, USA) for Windows.
A total number of 120 thalassemic patients with the mean age of 33 years (range, 20-50
years) were enrolled the study. Among them 59 patients (49.2%) were male and 61 others
(50.8%) were female. Twenty seven ones (64.2%) has major thalassemia while 43 patients
Among all the participants 96 patients complete both initial and final BMD, 14 cases were
excluded because of incorrect drug use or drug side effects and one patient died due to
The mean initial T-score of the Femur was -2.87±0.94 and its secondary average (after one
year) was -2.23±1.01 that based on the paired T test this difference was significant (P<0.001).
The mean T-score of the spine was -2.91±0.73 at the initial of the study and it changed
significantly in the second measurement to the average of -2.32±0.66 (P<0.01).
The mean value of BMD (gr/cm2) in the lumbar spine was 0.682±0.108 in the first session
and increased to the 0.773±0.11 that this increase was associated with the regular drug
consumption in a way that in 83 patients with regular drug use, 70 ones (95.2%) showed more
than 3% increase and in other 4 patients (4.85) decrease occurred. In the group with irregular
drug use, 3 patients (60%) had considerable increase while 2 others (40%) had decrease in the
Table 1. Association between use of alendronate and BMD changes in the spine.
Irregular use Non-use Regular use
A considerable increase was not seen in 13 (13.5%) patients; among them 7 ones consume
drug irregularly. In the group with noticeable increase in BMD, 95.2% (72) patients used drug
regularly and 3 ones consumed it irregularly which implies the significant association
between regular drug use and increase in BMD (P<0.01).
The mean values of BMD (gr/cm2) in Femur were 0.099±0.682 and 0.11±0.750 in the first
and second sessions that this increase associates with regular drug use in these patients. In 83
cases with regular drug use, 57 ones (68.7%) showed a considerable increase more than 6%
and in 26 (31.3%) decrease in this value was found. In 5 patients with irregular drug
consumption only one case (20%) showed a considerable increase while other 4 patients
(80%) had decrease in bone densitometry (Table 2).
Table 2. Association between use of alendronate and BMD changes in the Femur.
Irregular use Non-use Regular use
About calcium serum level, 95.8% (92) of the patients had normal level (8-10 mg/dl), 2-1%
(2) had less than 8 mg/dl and in 2 others it was more than 10 mg/dl which showed no
significant association between consumption of alendronate and calcium serum level
Sixty three (65.6%) of the patients had normal phosphor serum level (3.5-5 mg/dl) while 33
patients (34.4%) had increase in this value and there was not a significant relation between
increase in its serum level and drug consumption.
About ALP serum levels with the normal range of 150- 300, 89.6% (86) patients were
normal, 1% (1) less than normal and 9.4% (9) were upper than its normal range that its
association with drug use was not statistically significant (P=0.986).
Considering the fact that thalassemic patients are prone to osteoporosis and several factors
like bone marrow extension, iron concentration, genetic factors and decline in sexual
hormones are effective on it [3, 4]; so screening of these patients and finding their
osteoporosis with various diagnostic techniques is necessary that the best method is using
DXA system for evaluating bone density [1, 2]. In patients with age of lesser than 30 years
old shoud be used of Z-Score of spine and neck of femure.In this study , we measured T-
Score of spine and femure.However other methods like sonography are also user for bone
density measurement; in a study comparison of DXA system and ultrasound for measuring of
bone density showed that ultrasound is weaker than DXA system for bone densitometry .
Adequate treatment of the thalassemia since early childhood can decrease incidence of
osteoporosis, a study on 35 youngs with thalassemia (5-20 years0 with appropriate treatment
showed that they had normal Z-score compared to the control group . In one study in Iran
in 2007 by pediatric hematology group on 203 thalassemic patients (10-20 years old),
prevalence of osteoporosis was found 7.5% in spine, 10.8% in Femur and 7.9% in both.
Affecting factors on osteoporosis in the patients of this study were status of height, weight,
delay in puberty or hypogonadism, age at the beginning of desferal use and its duration and
serum level of zinc . In a study in 2008 after 2 years use of zoledronic acid annually, it
was found that patients who received treatment had significantly better bone density .
In a study in Athens in 2006 and Lykone general Hospital, 66 thalassemic patients with
osteoporosis were divided in 3 groups; 23 patients in group A that received zoledronic acid 4
mg/IV each 6 months, 21 patients in group B that received zoledronic acid 4 mg/IV each 3
months and 22 patients in group G that received placebo each 3 months. This study was last
about one year in which bone density of lumbar spine, neck of Femur and waist of hand, pain
and markers of bone resorption (Telopeptide collagen type I), markers of bone formation
(alkaline phosphatase) TRAP isoform b and osteocalcin and osteoclast stimulators
(Osteopontin, osteoprotegrine) were evaluated before and after treatment protocol. All
markers of bone formation and resorption and osteoclast stimulators were considerably high
before the study. After treatment bone density of group A did not differ with before but bone
pain and bone formation markers and osteoclast stimulators were decreased. In group B there
was a considerable increase in bone density of lumbar vertebra with decrease in bone pain
and markers for bone formation, resorption and osteoclast stimulators. Patients in group G
had no difference in bone density or bon pain, meanwhile showed an increase in bone
In a study in university of Messina in 2002, 25 patients with major thalassemia were
randomly divided in groups which received placebo, clodrinate 100 mg/IM each 10 days or
alendronate 10 mg/d. all the patients received calcium 500 mg and colecalciferolo 400 U with
their night food. After 2 years follow up, bone resorption markers in group with placebo did
not differ with before treatment but in those groups which were under treatment with
clodronate and alendronate these markers were considerably decreased. Osteocalcin and bone
formation markers did not show any difference in placebo group before and after the
treatment, but in other two groups they decreased a little but not significantly. At the end of
the study BMD of lumbar spine in placebo group decreased, in clodronate group did not show
a noticeable change, but in alendronate group increased not-significantly. BMD of neck of
Femur decreased in placebo group, did not change in clodronate group but increased
significantly in alendronate group. During this study no drug side effect was reported and
finally it was concluded that in thalassemic patients alendronate can considerable increase
In a study in Greece in 2004, 26 thalassemic patients with osteoporosis received
pamidronate/IV 30-60 mg for 12 months. BMD, osteoclast function markers (Soluble
receptor activator of nuclear factors Kappa B legends (SRANKL), osteoprotegrine (OPG),
bone remodeling, N terminal telopeptide collagen type I (NTx), tartrate-resistant acid
phosphatase-sb (TRACP-sb), bone alkaline phosphatase (ALP-b) and osteocalcin (OC). A
control group of 30 healthy individuals was selected. NTX, TRACP-sb, ALP-b and OC were
considerably higher in thalassemic patients compared to the control group, but OPG was
lower and SRANKL was in the normal range. After study completion, NTX, TRACP-sb,
OPG and OC had been decreased in thalassemic patient and BMD of lumbar spine had been
In our study thalassemic patients with osteoporosis that was diagnosed by BMD underwent
oral alendronate 70 mg/week. At the beginning and after one year treatment with alendronate
BMD was performed (neck of Femur, L2-L4). At the end of the study BMD of Femur and
spine increased significantly in group with regular drug use that was significantly associated
with increase in T-score and BMD (gr/cm2) (P<0.001).
Patients who did not have increase in BMD were among those with the history of irregular
drug use, discontinuing of drug because of gastrointestinal complications and low
compliance. In comparison with other studies that in two studies they have been used
administrative bisphosphonates that are not accessible in our country and we used oral
bisphosphonates that are FDA- approved for treatment of osteoporosis, are produced in the
country and all the patients were able to prepare the drug. Evaluation of bone resorption and
formation markers (except ALP) are used as treatment monitoring in some studies which
were not easly accessible in our country and monitoring was performed using BMD in this
This study was started with 120 thalassemic patients but only 96 persons complete the second
BMD. Because this study was sequential, time restriction for presentation of the study
outcomes and at the time of data gathering and analysis time for second BMD in those 24
patients had not common, those patients were taken apart.
In this study the rate of fracutres was not evaluated.It's better more studies with attention for
risk of fracures in thalasaemia patients is done.
There is another limitation about diagnosis of osteoporosis because all densitometry systems
are not able to measure BMD in patients under 20 years, so diagnosis of osteoporosis in
thalassemic patients whose problem begin at childhood is hard, but in such patients its
diagnosis and prevention and treatment should always in mind.
Regarding to the BMD increase in patients who used their drugs regularly and no increase in
patients who used drugs irregularly or essentially did not use any, we concluded that the role
of bisphosphonates in increasing bone density and decreasing risk of fractures in neck of
femur, vertebral and non-vertebral bones were remarkable without having dangerous side
effects. So, early diagnosis, treatment and prophylaxis of osteoporosis in this group of
The authors would like to thank Farzan Institute for Research and Technology for technical assistance.
Disclosure of Interest
None of the authors has conflict of interest.
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Appendix 6. Subcutaneous drug administration Indications for use of subcutaneous route The use of the subcutaneous route is indicated in those circumstances where the patient cannot take the medication orally or when the symptoms are not suffi ciently controlled by this route. In practice, the situations where the subcutaneous route is considered as a fi rst choice option are: uncontrolled nau
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