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Low-dose Prednisolone and Bone in Early Rheumatoid Arthritis
on the osteoblasts and their function as well.
17
Therefore, bone remodelling in contrast to the increased remodelling seen in patients
resorption is increased and bone formation is normal or reduced, with hyperparathyroidism.
33
leading to an imbalance between bone resorption and formation with
subsequent bone loss. GCs also have a negative influence on the hypothalamic–pituitary–
gonad axis. Plasma concentrations of several sex hormones are
Peri-articular Bone Loss decreased in both genders taking GCs.
34,35
The actions of GCs and
Bone loss in the trabecular bone adjacent to inflamed joints is oestrogen deficiency on bone loss are additive, which in part can
associated with active synovitis and increased bone turnover.
18
explain the high susceptibility for bone loss in post-menopausal
Possible contributors to this bone loss are production of pro- women during GC treatment.
inflammatory cytokines and joint immobilisation.
An additional effect of GC is decreased synthesis of local insulin-
Generalised Bone Loss like growth factors (IGF-I, IGF-II), which are important local
Studies based on assessment of biochemical markers of bone regulators of bone cell functions. IGF-I and IGF II are synthesised in
remodelling support the fact that increased bone resorption is also the osteoblasts and increase the synthesis of type I collagen and
important for the generalised osteopenia in RA.
19
Besides activated decrease collagen degradation.
36
pro-inflammatory cytokines, treatment with GCs may contribute
to bone loss as well as traditional risk factors for osteoporosis such Treatment with Low-dose Prednisolone in
as age, menopausal status, smoking, low body mass index and Early Rheumatoid Arthritis
physical inactivity.
20
In recent years, GC treatment at low doses (≤7.5mg) has been
re-evaluated due to its ability to reduce radiographic damage in early
It is well-known that both local bone erosions and peri-articular RA.
8–10,37
Added to these prospective, randomised controlled trials
osteopenia occur early in the disease; therefore, they have achieved (RCT) performed with low-dose prednisolone are two RCTs performed
important clinical implications as being part of the classification with 10mg of prednisolone
38,39
(see Table 1). All but one study
37
showed
criteria for RA, as well as being major variables for monitoring the beneficial effects on radiographic progression of erosions, and one of
efficacy of disease-modifying antirheumatic drugs (DMARDs). them also showed decelerated peri-articular osteopenia.
40
The
evidence that GCs, given in addition to DMARDs, can reduce
There are only a few studies of bone mineral density (BMD) in patients radiographic erosion progression in early RA is thus convincing.
41
with early RA. In patients with disease duration of less than one year,
mean BMD did not differ from controls or age- and gender-matched Three of the RCTs assessed BMD by dual X-ray absorptiometry
reference materials,
21–23
although there was a subgroup of patients (DXA) at the lumbar spine and femoral neck.
10,37,42
None of these
with reduced BMD.
22
In prospective studies of patients with early RA, studies showed significant differences in mean BMD between the
disease duration, disease activity and disability were negatively treatment groups. However, when separating a subgroup of the
associated with BMD.
21,23–26
patients in one of the studies
10
according to menopausal status, it
was found that post-menopausal women treated with prednisolone
Effects of Glucocorticoids on Bone lost significantly more bone in the lumbar spine compared
The effects of GCs on bone are dose-dependent, although there is no
dose that is considered entirely safe.
27
The most significant effect is
inhibition of bone formation caused by depletion of mature
In recent years, glucocorticoid
osteoblasts through decreased cell proliferation and differentiation,
as well as enhanced apoptosis.
28
GCs also inhibit the function of
treatment at low doses (≤7.5mg) has
differentiated osteoblasts with inhibition of the synthesis of type I
been re-evaluated due to its ability to
collagen, the major component of bone extracellular matrix, with a
consequent decrease in bone matrix available for mineralisation.
29 reduce radiographic damage in early
rheumatoid arthritis.
The effects of GCs on bone resorption are less clear. GCs seem to
have a stimulatory effect in the early phase of osteoclast
differentiation, an effect that is difficult to differentiate from the with those not treated with GCs.
43
At the time when these studies
target of GC treatment, i.e. the inflammation. Pro-inflammatory were conducted, prevention of osteoporosis with calcium
cytokines as well as GCs act by the RANKL pathway and stimulate supplementation was common, while supplementation with vitamin
expression of RANKL and decrease expression of osteoprotegerin, a D or prevention with bisphosphonates or hormone-replacement
decoy receptor that binds RANKL, preventing RANKL binding to the therapy (HRT) was less common (see Table 1).
osteoclast receptor.
30
The effect of low-dose GC on BMD has been further evaluated in
Furthermore, GCs decrease calcium absorption in the gastrointestinal observational studies in early RA. The total intake of low-dose
system and increase the urinary excretion of calcium.
31,32
This may prednisolone over two years, during which time medical prevention of
cause a degree of secondary hyperparathyroidism, but the changes in osteoporosis was allowed, did not contribute to bone loss either at
bone metabolism observed after exposure to GC cannot be explained the lumbar spine or at the femoral neck.
23
BMD loss at the lumbar
by this condition. The serum levels of parathyroid hormone are not in spine was predicted by high disease activity, whereas bone loss at the
the hyperparathyroid range. Furthermore, bone biopsies from femoral neck was predicted by disability.
23
In a longitudinal,
patients with GC-induced osteoporosis display decreased bone observational study over one year, during which time calcium or
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