Osteogenesis and osteoclast inhibition in rheumatoid arthritis patients treated with bisphosphonates alone or in combination with pitavastatin over an 18-month follow-up after more than 4 years of treatment with bisphosphonates.
BACKGROUND
To investigate the effects of bisphosphonates (Bis) (etidronate, alendronate, and risedronate), alone and in combination with statin, on the BMD (bone mineral density) and bone metabolism of rheumatoid arthritis (RA) patients.


METHODS
Seventy-seven RA patients who had been receiving prednisolone (PSL) and Bis for over 4 years were divided into two groups: Bis and Bis + statin (n = 42 and 35; average age, 66.4 and 65.3 years; average disease duration, 24.9 and 20.8 years; average PSL dose, 2.4 and 2.7 mg, respectively). Serum levels of NTX (N-terminal telopeptide of type I collagen), TRACP-5b (tartrate-resistant acid phosphate-5b), PICP (C-terminal propeptide of type I procollagen), and RANKL (receptor activator of NF-κB ligand) were measured over an 18-month period of treatment and follow-up. The BMD levels of the two groups at the radius, lumbar spine, and femoral neck were compared using DXA (dual-energy x-ray absorptiometry).


RESULTS
A significant increase was only observed in the BMD of the lumbar spine at 18-months, but the BMDs of the radius and femoral neck decreased during the follow-up period in the Bis group. Meanwhile, a significant increase was observed in the BMD of the lumbar spine in the Bis + statin group during administration and the BMDs of the radius and femoral neck stayed at baseline. Among the markers of bone metabolism, serum NTX was up-regulated after 6 months in the Bis + statin group. Serum TRACP-5b was significantly increased during the follow-up period in the Bis + statin group, but only at 18 months in the Bis group. Serum PICP recovered to base line in the Bis + statin group, whereas that in the Bis group did not observably recover during the post-administration follow-up, but rather decreased.


CONCLUSIONS
Our findings suggest that both bone resorption and bone formation were inhibited by long-term administration of Bis alone, whereas combination therapy with Bis + statin may be associated with a less marked inhibition of bone metabolism. Cardiovascular disease is highly prevalent in RA patients and some patients are prescribed statins and bisphosphonate. Bis + statin may confer more benefit to the bone metabolism of these patients compared to Bis alone.
Masakazu
M
Nagashima
Hiroshi
H
Takahashi
Kenichi
K
Shimane
Yuichi
Y
Nagase
Koichi
K
Wauke
D015502:Absorptiometry, Photon; D000135:Acid Phosphatase / Q000378:metabolism; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015519:Bone Density / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007527:Isoenzymes / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use*; D053245:RANK Ligand / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D016896:Treatment Outcome
D024042:Collagen Type I; D004164:Diphosphonates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007527:Isoenzymes; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D011804:Quinolines; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; C108475:pitavastatin