Effects of tofacitinib on bone turnover markers and bone modulators in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by bone loss. It is unclear whether JAK inhibitors can attenuate bone loss in RA by modulating bone metabolism. The main objective of our study is to investigate the effects of tofacitinib on serum levels of bone turnover markers and modulators. Secondary objectives were to assess changes in bone mineral density (BMD), metacarpal index, bone erosions. METHODS: We conducted a prospective observational study on patients with active RA failure to bDMARDs or tsDMARDs initiating treatment with tofacitinib. We measured at baseline and after 1, 2, 3, 6, 9 and 12 months: serum bone turnover markers (CTX, P1nP, B-ALP), bone modulators (Dkk-1, sclerostin, vitamin D, PTH, OPG and RANKL), BMD and radiographic parameters (Sharp van der Heijde score [SvdH], bone health index [BHI] and metacarpal index [MCI]). RESULTS: 30 patients were enrolled in the study of whom 21 completed the study through month 12. Tofacitinib was clinically effective by suppressing DAS28-CRP. Glucocorticoids daily dose significantly decreased from baseline. We found a negative correlation between pre-study cumulative and daily dose of glucocorticoids and baseline B-ALP serum levels (r -0.592, p 0.012). Sclerostin serum levels increased significantly during the study period, while P1nP and B-ALP (markers of bone formation) decreased significantly. BMD levels, BHI, MCI and SvdH score did not change. CONCLUSION: Treatment with tofacitinib was associated with a significant increase in sclerostin serum levels and a parallel decrease in markers of bone formation. However, no significant bone loss was observed.

Changes in bone turnover markers and bone modulators during abatacept treatment.

Rheumatoid arthritis (RA) causes bone loss, only partly related to inflammation. The impact of RA treatments on bone metabolism and their ability to mitigate bone loss remains uncertain. The primary goal of our study was to examine the influence of abatacept on serum levels of markers and regulators involved in bone turnover. Secondary objectives included evaluating changes in bone mineral density (BMD), bone health parameters, erosions, and exploring potential correlations among these parameters. We conducted a prospective observational study on patients with active seropositive RA failure to biological disease modifying anti-rheumatic drugs initiating treatment with abatacept. We measured at baseline and after 1, 2, 3, 6, 9 and 12 months: serum bone turnover markers (CTX, P1nP, B-ALP), bone modulators (Dkk-1, sclerostin, vitamin D, PTH, OPG and RANKL), BMD and radiographic parameters (modified Sharp van der Heijde score [mSvdH], bone health index [BHI] and metacarpal index [MCI]). Disease activity and glucocorticoid intake was monitored. 33 patients were enrolled in the study. We found a significant increase in markers of bone formation (B-ALP and P1nP) from baseline to M6 and M12. PTH increased significantly at M6 but not at M12. All other bone markers and modulators did not change. We found a significant decrease in BHI and MCI from baseline to M12 (median difference - 0.17 95% CI - 0.42 to - 0.10, p 0.001 and - 0.09 95% CI - 0.23 to - 0.07, respectively). BMD at femoral neck transitorily decreased at M6 (mean difference - 0.019 g/cm2 95% CI - 0.036 to - 0.001 p 0.04). BMD at total hip, lumbar spine and mSvdH score did not change significantly. P1nP delta at M12 correlated with delta mSvdH. Treatment with abatacept was associated with a significant increase in bone formation markers. The secondary and transient increase in PTH serum levels may be responsible of the transitory bone loss.

Risk factors of peptic ulcer in 4943 inpatients.

BACKGROUND: Over the past few years, major changes have taken place in the treatment of gastroduodenal peptic ulcer. AIM: To evaluate risk factors associated with the incidence of peptic ulcer in inpatients. METHODS: From 2001 to 2004, the number of prescriptions of H2-antagonists and proton pump inhibitors (PPIs) in each department of Verona University Hospital was monitored. Over the same period we prospectively recorded the number of upper endoscopies per department for inpatients with a diagnosis of peptic ulcer. RESULTS: We analyzed 4943 inpatients. A significantly decreasing trend in H(2)-antagonist prescriptions (r=-0,88; P<0.001) and an increasing trend in PPI prescriptions (r=0.97; P<0.001) were observed. The endoscopic incidence of duodenal ulcers decreased linearly from 2001 to 2004 as follows: 6.5% (94/1439) in 2001, 5.6% (82/1473) in 2002, 4.5% (63/1411) in 2003, and 3.1% (22/702) (P<0.001) in 2004. Gastric ulcer incidence, sex, age, indication for endoscopy, use of nonsteroidal anti-inflammatory drugs (NSAIDs), presence of Helicobacter pylori (32%), and smoking and drinking habits showed no significant changes over the study period. Considering time-dependent variables, multivariate regression analysis identified only PPI use and NSAID use as factors predictive of duodenal ulcer but not of gastric ulcer. CONCLUSIONS: In inpatients, PPIs are associated with a reduced risk of duodenal ulcer, whereas NSAIDs are associated with an increased risk. Gastric ulcer was not associated with any increased or degreased risk with the 2 above-mentioned variables.