Endocrine Abstracts

Objectives

High-Dose-Intravenous-Steroid-Treatment-(HDIST) represents the first choice of treatment for MS relapses. Although chronic oral GC-administration is associated with bone loss there are still conflicting data regarding HDIST.

Methods

25 newly-diagnosed MS-patients (10-women) were prospectively enrolled meeting the following eligibility criteria: age 18–45 yrs, fully ambulatory, women with normal menstruation. Exclusion criteria: history of any chronic disease, previous GC-treatment in any dosage regimen. Patients received 1000 mg-Methylprednisolone intravenously daily for 5 consecutive days. 7/25pts were excluded due to mobility impairment, 8/25 were lost to follow-up. In the remaining 10pts (6-men) serum levels of: Calcium, Phosphorus, Albumin, Magnesium, Creatinine, 25-OH-D, Parathyroid-Hormone-(PTH), Thyroid-Hormones-(TH), Bone-fraction-Alkaline-Phosphatase-(BALP), N-terminal-propeptide-procollagen-type-1-(P1NP), C-terminal-peptide-type-of-collagen-(CTx), Receptor-Activator-of-Nuclear-Factor-Kappa-β-Ligand-(RANK-L), Osteoprotegerin, Sclerostin, Dickkopf-1-(DKK-1), Periostin, Interleukins-(IL)-1β, 6.17 were determined prior to GC-administration and consecutively the days: 2–4–6-90 and months: 6–12–18–24. BMD of both hips and lumbar spine as well as whole-body measurement of adipose/lean tissue were assessed with Dual-X-ray-Absorptiometry-(DXA)-scan, prior to GC-administration and consecutively every six months.

Results

Bone formation markers, P1NP and BALP, showed an initial non-significant fall (P1NP day 6:–0.414 ± 0.128 ng/ml, BALP day 4:–0.864 ± 0.334 µg/l) followed by a significant increase in day 90 (P1NP: + 0.567 ± 0.13 ng/ml, P < 0.05, BALP: + 1.838 ± 0.464 µg/l, P < 0.05). No other significant changes were observed. A transient non-significant fall of BMD was observed at all sites 6-months after GC-administration, which subsequently appeared to be restored while in the lumbar spine this trend for reduction continued up to 24-months. The percentage changes of Periostin levels from baseline to 24-months correlated positively with the changes in total-left-hip-BMD and left-trochanter-BMD (r =+ 0.709, P = 0.022 and r =+ 0.77, P = 0.009, respectively) and negatively with CTx (r = 0.806, P = 0.005). The changes in CTx levels negatively correlated with the changes in left-trochanter-BMD (r =–0.782, P = 0.008). A positive correlation of the changes in left-femoral-neck-BMD with the changes in Body-Mass-Index-(BMI) was observed (r = +0.661, P = 0.038). The percentage changes of 25-OH-D levels form baseline to 24-months negatively correlated with the changes of IL-1β from baseline to 3 and 6 months (r = –0.806, P = 0.005 and r = –0.867, P = 0.002, respectively).

Conclusions

In spite of the small sample this is the first-to our knowledge-prospective study aiming to elucidate the impact of HDIST on BMD and simultaneously on biochemical parameters of bone metabolism in newly-diagnosed MS-patients; high dose short term GC administration seems to have no long term negative effect on BMD in this group of patients. The observed transient increase in bone formation markers -90 days after GC administration- probably indicates a high bone turnover phase as a ’response’ to the transient adverse effects of GC on bone-metabolism. More prospective studies with larger sample size on similarly selected patients should be performed.