Bone turnover, joint damage and bone mineral density in early rheumatoid arthritis treated with combination therapy including high-dose prednisolone.
OBJECTIVE
Exploration of bone metabolism changes at different levels of disease activity, both with and without oral corticosteroid therapy, and prediction of changes in joint damage and bone density from the observed changes 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 (diagnosis < 2 yr); one group treated with a combination of sulphasalazine (SSZ; 2000 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 SSZ alone. Prednisolone and MTX were tapered and stopped after weeks 28 and 40, respectively, while SSZ was continued. Urine and serum samples were collected at baseline and weeks 16, 28, 40 and 56. Measurements of urinary pyridinoline (PYD) and deoxypyridinoline (DPD) and serum alkaline phosphatase (tAP) and osteocalcin (OC) were performed, as well as standard clinimetry and bone densitometry.


RESULTS
Over time and in both treatment groups, bone formation and bone resorption 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 joint damage scores were significantly lower in the combined treatment group. Changes in bone density (of spine and hips) did not significantly differ between treatment groups. Mainly cumulative ESR explained progression of joint damage.


CONCLUSIONS
Prednisolone and disease-modifying anti-rheumatic drug therapy in patients with early and active RA are both independently associated with decreased levels of urinary excretion of bone collagen resorption markers PYD and DPD. Markers of bone formation and resorption closely followed changes in ESR in both treatment groups. Reduced bone resorption together with reduced bone formation-initially at a somewhat faster pace-resulted in less bone turnover and explain the observed (non-significant and partially reversible) extra bone loss in the lumbar spine associated with prednisolone (combined treatment).
Verhoeven
A C
AC
Internal Medicine/Rheumatology Department, Maastricht University Hospital, Maastricht, The Netherlands.
Boers
M
M
te Koppele
J M
JM
van der Laan
W H
WH
Markusse
H M
HM
Geusens
P
P
van der Linden
S
S
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000032:analysis; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D003094:Collagen / Q000032:analysis; D003432:Cross-Linking Reagents / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007596:Joints / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D017698:Postmenopause; D011239:Prednisolone / Q000008:administration & dosage*; D012044:Regression Analysis; D012460:Sulfasalazine / Q000008:administration & dosage
D000596:Amino Acids; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D003432:Cross-Linking Reagents; D012460:Sulfasalazine; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen; D011239:Prednisolone; D008727:Methotrexate