Long term glucocorticoid (GC) therapy may cause osteopenia or osteoporosis in patients suffering from SLE (Systemic Lupus Erytematosus). Osteopenia and osteoporosis are conditions, where there occurs rarification of bone due to less availability of calcium for bone health. In other wards the bone mass is decreased.
The frequency of osteoporosis in SLE ranges from 4.0 to
48.8% and that of osteopenia from 1.4 to 68.7%.
There are several ways in which this can happen:
1.
Inhibiting calcium absorption from the
gastrointestinal track.
2.
Decreasing the renal tubular reabsorption of
calcium and consequent secondary hyperparathyroidism.
3.
Glucocorticoids reduce growth hormone (GH)
secretion and may alter the GH/insulin‐like growth factor (IGF)‐I axis. But,
this may play a minor role.
4.
There is also an alteration in hypothalamic
gonadotrophin‐releasing hormone secretion with subsequent reduction in serum
testosterone and oestradiol levels.
5.
Inhibiting IGF‐I transcription in osteoblasts (Bone forming cells).
6.
Reducing the replication, differentiation and
function of osteoblasts and increase the apoptosis rates of mature cells,
thereby depleting the osteoblastic cell population and inhibiting the function
of mature cells.
7.
In the presence of GCs, bone marrow stromal
cells do not differentiate into osteoblasts; instead, these cells differentiate
toward an adipocyte cell lineage.
8.
GCs increase the expression of macrophage colony
stimulating factor (M‐CSF) and receptor activator of Nuclear factor kappa beta
( NF‐kB) ligand (RANK‐L).
9.
In addition, GCs decrease the expression of
osteoprotegerin in stromal and osteoblastic cells.
Through these mechanisms, GCs can induce the formation of
osteoclasts (Act opposite Osteoblasts) to and favour bone resorption. GCs also reduce the rate of apoptosis among mature osteoclasts.
Bone mineral density (BMD) can be
tested by DXA (Dual-energy X-rays Absorptiometry). Results are scored compared with
the BMD of young, healthy people and is expressed in a measure called a
T-score. The scoring is as follows:
 |
| Dual-energy X-ray absorptiometry (DEXA) assessment of bone mineral density of the femoral neck (A) and the lumbar spine (B): T scores of - 4.2 and - 4.3 were found at the hip (A) and lumbar spine (B), respectively in a 53 year-old male patient affected with Fabry disease. Courtesy: Dr Caroline LEBRETON, CHU Raymond Poincaré, Garches, France. (Photo credit: Wikipedia) |
DXA T-Score
|
Bone Mineral Density (BMD)
|
Not lower than –1.0
|
Normal
|
Between –1.0 and –2.5
|
Osteopenia (mild BMD loss)
|
–2.5 or lower
|
Osteoporosis
|
To prevent
osteopenia and osteoporosis in the first place, some preventive measures can be
taken.
- Be physically active and do weight-bearing exercises, like walking, most days of each week.
- Change lifestyle choices that raise your risk of OP, such as quitting smoking.
- Implement strategies to help decrease your risk of falling, which raises the risk of fractures.
- Get DXA testing of your BMD.
Treatment of established
osteoporosis:
Vitamin D increases intestinal calcium absorption and
increases its reabsorption in distal renal tubules. Serum levels of at least
30 ng/mL (82 nmol/L), and optimally of 40–60 ng/mL, of
25‐hydroxyvitamin D should be the target treatment regimen for GIO management.
To achieve these levels, 1,000 to 2,000 IU of oral vitamin D daily or 50,000 to
60,000 IU per week may be necessary.
Bisphosphonates are indicated for the prevention and
treatment of GIO (Glucocorticoid Induced Osteoporosis) and most guidelines
recommend the use of these drugs. The prevention and treatment goals of bisphosphonate
use are stabilizing or increasing bone mineral density, as well as reducing
frequency of fractures.
Currently, alendronate (70 mg/week or 10 mg/day)
and risedronate (35 mg/week or 5 mg/day) are the some of the oral
antiresorptive drugs that are recommended in GIO. Zoledronic acid, in injection
form had been approved for the prevention and treatment of GIO.
Caution needs to be exercised when considering the use of
bisphosphonates in women of childbearing age with GIO, given that
bisphosphonates have an extended half‐life and may cross the placenta with
potentially unfavourable effects on foetal skeletal development. The adverse
effect like osteonecrosis of jaw (ONJ) has to be kept in mind, while prescribing
it.
Teriparatide a synthetic parathormone had also been approved
by USFDA for treatment of GIO. It is taken as subcutaneous injection daily. It
may not be continued for more than 2 years at a time. The injection comes in
pre-filled syringes containing 30 doses.
In a randomized multicenter trial, it had been seen that subcutaneous
teriparatide (20 µg/day) is more effective in comparison to the use of oral
alendronate (10 mg/day) over 18 months in patients with established GIO.
The key to prevent and treat Glucocorticoid Induced
Osteoporosis are adequate weight bearing physical exercise, calcium and vitamin
D intake in adequate doses.
