Ac. Verhoeven et al., Bone turnover, joint damage and bone mineral density in early rheumatoid arthritis treated with combination therapy including high-dose prednisolone, RHEUMATOLOG, 40(11), 2001, pp. 1231-1237
Objectives. Exploration or bone metabolism changes at different levels of d
isease activity, both with and without oral corticosteroid therapy, and pre
diction of changes in joint damage and bone density from the observed chang
es in markers of bone turnover.
Methods. Data analysis from a randomized clinical trial with 155 rheumatoid
arthritis (RA) patients; median age 50 yr, early and active disease (diagn
osis <2 yr), one group treated with a combination of sulphasalazine (SSZ; 2
000 mg/day), methotrexate (MTX; 7.5 mg/week) and prednisolone (initially 60
mg/day, tapered in six weekly steps to 7.5 mg/day), the other group with S
SZ alone. Prednisolone and MTX were tapered and stopped after weeks 28 and
40, respectively, while SSZ was continued. Urine and serum samples were col
lected at baseline and weeks 16, 28, 40 and 56. Measurements of urinary pyr
idinoline (PYD) and deoxypyridinoline (DPD) and serum alkaline phosphatase
(tAP) and osteocalcin (OC) were performed, as well as standard clinimetry a
nd bone densitometry.
Results. Over time and in both treatment groups. bone formation and bone re
sorption markers showed a pattern similar to erythrocyte sedimentation rate
(ESR): a significant decrease compared with baseline and a larger decrease
with combined treatment at weeks 16 and 28. PYD excretion, tAP, OC. and jo
int damage scores were significantly lower in the combined treatment group.
Changes in bone density (of spine and hips) did not significantly differ b
etween treatment groups. Mainly cumulative ESR explained progression of joi
nt damage.
Conclusions. Prednisolone and disease-modifying anti-rheumatic drug therapy
in patients with early and active RA are both independently associated wit
h decreased levels of urinary excretion of bone collagen resorption markers
PYD and DPD. Markers of bone formation and resorption closely followed cha
nges in ESR in both treatment groups. Reduced bone resorption together with
reduced bone formation-initially at a somewhat faster pace-resulted in les
s bone turnover and explain the observed (non-significant and partially rev
ersible) extra bone loss in the lumbar spine associated with prednisolone (
combined treatment).