Purpose To evaluate the influence of intravenous methylprednisolone (IVMP) pulse administration on bone mineral density (BMD) of the lumbar spine and the femoral neck in patients with moderate-to-severe Graves' orbitopathy (GO). Methods Thirty-five patients with GO in euthyreosis were treated with 12 IVMP pulses (6 × 0.5 g, 6 × 0.25 g on a weekly schedule). Supplementation with 1.0 g of calcium and 800 IU of vitamin D was initiated in all patients before beginning therapy. BMD of the lumbar spine (L1-L4) and the femoral neck were assessed at baseline and after the last IVMP pulse using dual-energy X-ray absorptiometry. To determine differences in BMD between values at baseline and after treatment, we used the least significant change (LSC) methodology. LSC values were calculated to be 3 and 5% for the lumbar spine and the femoral neck, respectively. Change in BMD equal to or exceeding the LSC was assessed as either increase or decrease of BMD. We then compared pre-treatment and post-treatment mean BMD values at the lumbar spine and the femoral neck. Results We did not observe a decrease of BMD at any site equal to or exceeding the LSC. We found an increase of BMD in at least one measurement site equal to or exceeding the LSC value in 43% of patients, mostly in the lumbar spine (31%). Mean femoral neck BMD did not change while mean lumbar BMD increased. Conclusions IVMP given in weekly intravenous pulses does not lead to loss of BMD of the lumbar spine and the femoral neck. Keywords Bone mineral density • Gucocorticoid-induced Osteoporosis • Methylprednisolone • Graves' ophthalmopathy • Graves' orbitopathy • Trabecular bone score

BackgroundTherapy with intravenous glucocorticoids (GCs) is associated with various side effects, however, the impact on bone remains elusive. Trabecular bone score (TBS) is a diagnostic tool providing information on bone microarchitecture based on images obtained from dual-energy X-ray absorptiometry. We investigated the influence of the intravenous methylprednisolone (IVMP) pulse administration on TBS in patients with moderate-to-severe Graves’ orbitopathy (GO).MethodsFifteen patients with GO were treated with 12 IVMP pulses (6x0.5g, 6x0.25 g on a weekly schedule). They received supplementation with 2000 IU of vitamin D and 1.0 g of calcium throughout the study period. TBS was assessed at baseline and after last IVMP pulse. To determine the difference between values at baseline and after treatment the least significant change (LSC) methodology was used. We compared pre- and posttreatment mean TBS values.ResultsWe found a significant decrease of TBS in 5 out of 15 (33%) patients. Mean TBS value decreased becoming 2.4% lower than at baseline (p<0.05).ConclusionsIVMP pulse therapy exerts negative effect on bone microarchitecture in TBS assessment. The analysis of the clinical risk factors for osteoporosis and the evaluation of bone mineral density and TBS should be considered before initiating IVMP therapy.

Background: Dysthyroid optic neuropathy (DON) is a sight-threatening complication of Graves’ orbitopathy (GO). Treatment of DON consists of the urgent administration of intravenous methylprednisolone (ivMP) in very high doses followed by orbital decompression if the response is poor or absent. It is advised to continue the therapy with pulses of ivMP in a weekly schedule. The purpose of this study was to evaluate the impact of the additional treatment with ivMP in a 12-week protocol on visual acuity (VA), color vision, clinical activity score (CAS) and proptosis in patients with DON. Methods: This study was performed on 19 patients with DON (26 eyes) treated with ivMP in very high doses, with further orbital decompression in 11 individuals (15 eyes). VA, color vision, CAS and proptosis were evaluated prior to the DON treatment, before and after the 12-week ivMP (first and last pulse). Additionally follow up was performed (22 eyes). Results: VA and color vision improved between the first and last pulse of the additional ivMP treatment (p = 0.04 and p = 0.003, respectively). CAS and proptosis were reduced at the end of the 12-week ivMP therapy compared to observations at the beginning (p < 0.001 and p = 0.04, respectively). Follow up confirmed stabilization of this achievement. Conclusions: The results of this study suggest that additional treatment with 12 pulses of ivMP improves or stabilizes the outcome of basic therapy in patients with DON.

Introduction. Dysthyroid optic neuropathy (DON) is a severe complication of Graves’ orbitopathy (GO). Treatment of DON should involve immediate administration of intravenous methylprednisolone (ivMP) in very high doses. It is recommended to include additional 12 pulses of ivMP according to a weekly schedule as a further step of the treatment process. The purpose of this study was to evaluate the influence of a 12-week ivMP treatment on the quality of life (QoL) in DON patients. Material and Methods. A retrospective study was conducted on 6 patients (the tests involved 8 individual eyes) with DON and treated with ivMP in very high doses, followed by orbital decompression in one patient. All patients were qualified for additional treatment with ivMP in a 12-week protocol and completed the Polish version of the GOQoL questionnaire before and after the therapy. Visual acuity (VA) and diplopia were examined prior to the administration of ivMP pulses for DON, as well as before and after the additional ivMP treatment. Results. A minimal clinically important difference in QoL was observed in four patients at the end of the additional ivMP therapy. A significant increase in VA was observed following additional pulses of ivMP compared to the evaluation at the time of the DON diagnosis (p=0.04). Conclusions. Applying additional 12 pulses of ivMP following DON therapy may impact QoL. Performing QoL assessment throughout the entire therapy in patients with DON is particularly important in the clinical practice. Final evaluation of QoL should be performed after completing the entire therapeutic process, which involves surgical treatment to correct diplopia.

Background: Treatment with glucocorticoids (GCs) is associated with side effects. In contrast to the well-known negative impact on bone tissue exerted by oral GCs, few data are available regarding intravenous GCs. We investigated the influence of intravenous methylprednisolone (IVMP) on bone turnover markers (BTM): amino-terminal propeptide of type I procollagen (P1NP) and the C-terminal telopeptide of type I collagen (CTX), and on calcium metabolism parameters: 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), calcium (Ca), phosphate (P), and intact parathormone (iPTH). Methods: In a prospective study, 23 consecutive subjects with Graves’ orbitopathy were included and treated with IVMP according to the European Group on Graves’ Orbitopathy recommendations. We evaluated effects on BTM occurring during the first 7 days after 0.5 g IVMP, and after the therapy with 12 IVMP pulses with a cumulative dose of 4.5 g. Results: We observed prompt but transient decrease of P1NP (p < 0.001) and the reduction of CTX (p = 0.02) after the first IVMP pulse. Following the full course of IVMP therapy, both P1NP and CTX were found decreased (p < 0.05 and p < 0.01, respectively). Conclusions: A single pulse of 0.5 g IVMP already decreases bone formation and resorption; however, this change is transient. The full therapy is associated with suppression of bone turnover.