The short-term effects of Eudragit-L-coated prednisolone metasulphobenzoate (Predocol) on bone formation and bone mineral density in acute ulcerative colitis.
BACKGROUND
The aetiology of bone loss in ulcerative colitis is multifactorial, but corticosteroid treatment is an important risk factor. A novel formulation of Eudragit-L-coated prednisolone metasulphobenzoate (Predocol) has been developed, in order to deliver high mucosal levels of prednisolone within the colon but with little systemic absorption. The aim of this study was to investigate its efficacy, and short-term effects on bone formation and bone mineral density.


METHODS
In a 12-week longitudinal study 13 patients with active colitis were treated with a reducing dose of Predocol. Disease activity scores were recorded and the bone formation marker osteocalcin was measured before, during and after treatment, with hip and spine bone mineral density assessed at baseline and after treatment.


RESULTS
Eleven of the 13 patients completed the study. Compared with baseline, disease activity scores improved significantly after 4 weeks [difference in means, 6.9; 95% confidence interval (CI), 5.2, 8.7; P < 0.0001] and 12 weeks (difference in means, 5.7; 95% CI, 3.3, 8.2; P < 0.0001) of treatment. Osteocalcin did not fall compared with baseline [16.91 mg/l (95% CI, 12.70, 21.12)], after 4 weeks [13.67 mg/l (95% CI, 8.72, 18.60)] (difference in means, 3.25; 95% CI, 2.37, 8.87; P = 0.23) or 12 weeks [23.91 mg/l (95% CI, 16.10, 31.74)] (difference in means, 13.23; 95% CI, 2.45, 16.48; P = 0.13) of treatment. Similarly, bone mineral density at the hip [0.99 g/cm (95% CI, 0.90, 1.09)] did not change after 12 weeks of treatment [1.00 g/cm (95% CI, 0.89, 1.11)] (difference in means, 0.01; 95% CI, 0.25, 0.34; P = 0.74). Spine bone mineral density did not fall from pre-treatment levels [1.20 g/cm (95% CI, 1.11, 1.30)] after 12 weeks [1.19 g/cm (95% CI, 1.10, 1.29)] (difference in means, 0.01; 95% CI, 0.004, 0.01; P = 0.26).


CONCLUSIONS
These results confirm that Predocol is effective treatment for acute ulcerative colitis and short courses of the steroid have no adverse effects on bone formation and bone mineral density. The encouraging results from this study suggest that Predocol may be a significant advance in preventing corticosteroid induced bone loss in ulcerative colitis.
Darlow
Simon J
SJ
Glenfield Hospital, Leicester, UK and Leicester General Hospital, Leicester, UK.
Mandal
Aditya
A
Pick
Barbara
B
Thomas
Titus
T
Mayberry
John F
JF
Robinson
Richard J
RJ
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015519:Bone Density / Q000187:drug effects*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000503:physiopathology; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004339:Drug Compounding; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects*; D011109:Polymethacrylic Acids; D011239:Prednisolone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; D015675:Osteocalcin; C038300:methylmethacrylate-methacrylic acid copolymer; C013218:prednisolone 21-3-sulfobenzoate; D011239:Prednisolone