A Pharmacovigilance
Study on Steroid Induced Osteoporosis
Taqui Mohammed1, M. Swamivelmanickam2,
A Mohathasim Billah3
1PhD Scholar, Department of Pharmacy, Annamalai University,
Chidambaram, Tamil Nadu, India.
2Associate Professor, Department of Pharmacy, Annamalai
University, Chidambaram, Tamil Nadu, India.
3Department of Pharmacy, Sri Indu Institute of Pharmacy,
Hyderabad, Telangana, India.
*Corresponding Author E-mail:
taquipharma@gmail.com, swamivel@yahoo.com, billahs@yahoo.co.uk
ABSTRACT:
Background: In elderly people, osteoporosis and low bone density are
significant risk factors for morbidity and death. Low bone strength distinguishes
these illnesses, which are correlated to an increased risk of fractures from even
minor traumas. Objectives: To study pharmacovigilance on steroid induced
osteoporosis. Methods: A total of 950 individual who were diagnosed with
osteoporosis. These individuals were deemed to be at a high risk of osteoporosis.
Patients were given information regarding the risks of steroid-induced osteoporosis,
as well as a handout. The patient's steroid duration and any medicines used to control
the risks of steroid-induced osteoporosis were the focus of the initial evaluation.
Following that, evaluations of the pharmacological therapy being examined. Any problems
found were discussed with the patient and/or the prescribing practitioner. Data
was gathered at the start of the study and again after 6 months of observation.
Results: Glucocorticoids (prednisolone) was the main prescription drug of
the entire study sample. Family history of Osteoporosis was reported in 20% of
the cases. The history of fracture was reported in 30% of the cases. Low calcium
diet was reported in 35% of the cases. Osteoporosis was diagnosed in 17% of the
cases, Osteopenia in 22% of the cases. In 88% of the cases the drug prescribed was
>5mg daily. The duration of CS intake was high. This shows that the CS
drug is being abused mostly in history of allergies and asthma as its easily available
OTC leading to an increased risk of osteoporosis. Around 26% were prescribed antiosteoporosis
treatment with Bisphosphonate. Estrogen therapy was prescribed in 16% of the cases.
Calcium supplement consumption was increased by 17%. There was significant reduction
in BMD, Glucocorticoid’s usage and daily dosage and result was statistically significant.
Conclusion: Because all cells employ the same glucocorticoid receptor, corticosteroids'
antiinflammatory effects cannot be distinguished from their metabolic effects; thus,
precautions should be taken when corticosteroids are given. Clearly, the risk of
serious adverse effects rises as the amount and duration of therapy increases, thus
the smallest dose required to control the condition should be provided.
KEYWORDS: Osteoporosis, Glucocorticoids, Bisphosphonate, corticosteroids.
INTRODUCTION:
In elderly people, osteoporosis and low bone density are
significant risk factors for morbidity and death. Low bone strength distinguishes
these illnesses, which are associated to an increased fracture risk from even minor
traumas.1 It is a serious health concern by both the medical profession
and the general population in the last decade.2
Osteoporosis is commonly thought to be a female disease,
however its prevalence in men grows dramatically with age. Women's hip fracture
rates grow roughly ten years earlier than men's.3 By the age of 90, around
17% of males have suffered a hip fracture, compared to 32% of females.4
Hip fractures occur at a rate of 8/1000 in women and 4.3/1000 in men over the age
of 65 in the United States.5 Because males have a lower life expectancy
than women, they account for just 21% of all hip fractures.6 Men and
women have about the same rate of vertebral fractures. The European study found
a greater frequency of fractures in younger males, suggesting the possibility that
some of these fractures were caused by trauma suffered throughout their working
lives rather than osteoporosis.
Several medicines for treatment of osteoporosis have lately
been approved, but their modest advantages necessitate careful evaluation of their
cost. Because no therapy can entirely restore lost bone mass, prevention is preferable
than treatment The onset of osteoporosis is influenced by a variety of variables,
Among them include smoking, sedentary lifestyle, excessive alcohol use, lack of
calcium and Vitamin D, and low weight. A family history of the illness, early menopause,
some malignancies, and long-term use of certain drugs are all risk factors for osteoporosis.It
is also well acknowledged that the prevalence of osteoporosis differs from region
to region. Its variability is influenced by ethnicity, physical activity, dietary
status, lifestyles, and living environment.7
Because of their potent immunosuppressive effect, steroids
are used in the treatment of inflammatory and autoimmune diseases.8 The
discovery of cortisone and cortisol in the 1930s marked the beginning of the steroid
therapy era.9 Synthetic glucocorticoid derivatives are now widely employed
in a array of medical disciplines.10
Changes in steroid hormone levels are significant in the
onset of osteoporosis, is one of most common metabolic diseases among the world's
ageing populations.
MATERIALS
AND METHODS:
Study Design:
This is a prospective cohort study which is used to evaluate
the overall risk of steroid induced osteoporosis in a tertiary care hospital. It
was conducted on patients who visited outpatient and inpatient departments of General
medicine, General surgery, Orthopaedics,
Nephrology, Neurology, Psychiatry and Dermatology department
Sample Size:
A total of 950 patients who were prescribed with Steroids.
Study Duration:
The study was conducted over a period of 9 months.
Inclusion criteria:
Patients of either gender who were prescribed with long
term (not less than 3 months) Glucocorticoids, for their respective clinical condition.
Patient age of 
30 years.
Sample for control group were selected from the respective
departments where cases were collected.
Exclusion criteria:
The patients who were not adherent to the prescribed medications
for a time period of 3 months.
Patient who are not willing to participate in the study.
The patients who did not show for at least 2 follow ups
during the study period.
Using the hospital's prescription dispensing records, individuals
18 and older who were <7.5mg of prednisone for minimum 6 months were selected.
These people were found to have a considerable risk of developing osteoporosis.
Patients were contacted and asked to participate in the research. Patients were
provided information and a handout on the risks of glucocorticoid-induced osteoporosis.
The initial assessment focused on the patient's glucocorticoid
regimen and any medications used to reduce the risk of developing glucocorticoid-induced
osteoporosis. Following that, evaluations of the medication history being examined,
Any problems found were discussed with the patient and/or the prescribing practitioner.
Data was gathered at onset of the study and again after 6 months of observation.
Statistical Analysis:
The SPSS 22 software was used and the outcomes were expressed
in the mean and percentages.
OBSERVATION
AND RESULTS:
A total of 950 patients were studied
Table 1: Distribution based on Age group
|
Age Group
|
Total (n=950)
|
Percentage
|
|
30-44
|
87
|
9.15%
|
|
45-60
|
374
|
39.36%
|
|
61-75
|
426
|
44.84%
|
|
>75
|
63
|
6.63%
|
|
Total
|
950
|
100%
|
Majority of the patients belonged to the age group of 60
to 75 years with 45%, followed by 45 to 60 years with 39%. Followed by 30 to 44
yrs age group with 9%. The least belonged to the age group of >75years with 6.63%.
The mean age was 60.17±10.92 years.
Table 2:
Distribution based on Gender
|
Gender
|
Frequency
|
Percentage
|
|
Male
|
498
|
52.42%
|
|
Female
|
452
|
47.57%
|
|
Total
|
950
|
100%
|
Male predominance was observed with 52.42% and females
were 47.57% in the sample.
From the Osteoporosis risk assessment instrument (ORAI),
17.78% of sample population were found to be having high risk for osteoporosis where
as 22.21% were found to have moderate and 60% of sample population were having low
risk for osteoporosis.
From the simple calculated osteoporosis risk assessment
(SCORE), 17.15% of sample population were found to be having high risk for osteoporosis
where as 22.31% were found to have moderate and 60.52% of sample population were
having low risk for osteoporosis.
Table 3:
Distribution based on daily dose of steroids
|
Daily dose of
steroids
|
Frequency
|
Percentage
|
|
1–4 mg
|
56
|
5.89%
|
|
5–9 mg
|
392
|
41.26%
|
|
10–14 mg
|
333
|
35.05%
|
|
15–19 mg
|
48
|
5.05%
|
|
20–29 mg
|
73
|
7.68%
|
|
More than 30 mg
|
48
|
5.05%
|
In 94% of the cases the drug prescribed was >5mg
daily, with highest dose being >30mg/day.
Table 4:
Duration of treatment with corticosteroid
|
Duration of
treatment with corticosteroid (Prednisolone)
|
Frequency
|
Percentage
|
|
Less than 1 years
|
159
|
16.73%
|
|
1–2 years
|
119
|
12.52%
|
|
3–5 years
|
278
|
29.26%
|
|
6–10 years
|
238
|
25.05%
|
|
More than 10
years
|
156
|
16.42%
|
The duration of CS intake was as high as >10yrs in 16.42%
of the cases, 6 to 10yrs in 25%, 3 to 5yrs in 29%, 1-2yrs in 12.52% and 16.73% in<1
yrs of duration. This shows that the CS drug is being abused mostly in history of
allergies and asthma as its easily available OTC leading to an increased risk of
osteoporosis.
Glucocorticoids (prednisolone) was the main prescription
drug of the entire study sample. Family history of Osteoporosis was reported in
19.89% of the cases. The history of fracture was reported in 30% of the cases. Low
calcium diet was reported in 35% of the cases. Osteoporosis was diagnosed in 17%
of the cases, Osteopenia in 22% of the cases. In 88% of the cases the drug prescribed
was >5mg daily.
Around 26% were prescribed anti-osteoporosis treatment
with Bisphosphonate. Estrogen therapy was prescribed in 16% of the cases. Calcium
supplement consumption was increased by 17%. There was significant reduction in
BMD, Glucocorticoid’s usage and daily dosage and result was statistically significant.
DISCUSSION:
Due to a substantially lower bone strength based on BMD
and a considerable increase in fracture risk associated with their use, patients
taking glucocorticoids must follow special guidelines. According to American College
of Rheumatology (ACR) guidelines, the dosage and duration of glucocorticoid therapy
should be lowered to the bare minimum that is clinically beneficial in specific
conditions such as rheumatoid arthritis, asthma, and others.11 Lowering
dosage and reducing medication course can lessen the risk of fractures. Physical
activity, smoking abstinence, avoiding alcohol, calcium deficiency compensation
to a daily intake of 1200 – 1500mg/day, and regulation of vitamin D3 level is vital,
as are the standard guidelines for osteoporosis management.12 Preventative
vitamin D3 dosages of 800–1000 IU per day are recommended.13
Patients on 5mg or higher of prednisolone for more than
a month should commence medication with bisphosphonates which have been proved to
be beneficial in glucocorticoid-induced osteoporosis, such as alendronate or risedronate,14
and zoledronic acid15 should be explored if the steroid dosage is 7.5mg.16
During three months of glucocorticoid medication, the patient should receive one
of four treatments: zoledronate, risedronate, alendronate or teriparatide, All of
these substances have metabolic effects on bone. Reproduction and fertility is also
key factor to be considered.17
The ACR recommends a radiographic or morphometric assessment
of the spine in individuals receiving >5 mg/day of prednisolone. A global
fracture risk assessment should be performed prior to initiating medication, depending
on any concurrent risk factors beyond corticosteroids, such as parental hip fracture,
low BMI, smoking habits, alcohol intake of greater than 3 units, and a significant
loss in BMD.18
Long-term osteoporosis treatment involves consuming drugs
that have not yet been researched in pregnant women and potential implications on
foetal development and fertility has not yet assessed. As a result, The use of medications
with a short half-life is recommended as a treatment option. In addition, the antiosteoporosis
treatment eligibility for pregnant women have been eased. According to the ACR,
Steroid medication must be restricted to three months in pregnant women, with dose
of 7.5mg prednisolone or similar, and risedronate, alendronate, or teriparatide
administered simultaneously.19
There are some limitations to fracture risk calculators.
FRAX, for example, only takes hip BMD into consideration. The use of glucocorticoids
causes a significant loss of trabeculae, notably in the vertebral spine, This could
result in underestimating of fracture risk.20
Bisphosphonates are well-known antifracture drugs, but
they've been related to side effects including When orally administered, it causes
gastrointestinal complications, and when administered intravenously, it causes flu-like
symptoms. The majority of serious implications are uncommon, such as jaw osteonecrosis
atrial fibrillation, and the causal relationship between the occurrence with bisphosphonate
usage is uncertain.
CONCLUSION:
Because all cells employ the same glucocorticoid receptor,
corticosteroids' anti-inflammatory effects cannot be distinguished from their metabolic
effects; thus, precautions needs to taken when corticosteroids are given. Clearly,
the risk of serious adverse effects increases as the amount and duration of therapy
increases, thus the smallest dose required to control the condition should be provided.
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