Graves Ophthalmopathy
Conditions
Brief summary
Continuous use of systemic glucocorticoids decreases bone mineral density and increases fracture risk. Graves' orbitopathy is treated with weekly infusion of high-dose intravenous glucocorticoid. The investigators aim at investigating whether this treatment regimen also affects bone metabolism.
Detailed description
Systemic glucocorticoid increases bone resorption and decreases bone formation and thereby decreases bone mineral density and increases fracture risk. This effect is evident with a daily dose of 5 mg for three months or an accumulated dose of 450mg. There is, however, less evidence that intermittent use of glucocorticoids is harmful to bone. Graves orbitopathy is treated with a weekly infusion of the glucocorticoid methylprednisolone and the accumulated dose over a 12-week course sums up to 4,500mg. The investigators therefore want to investigate if that treatment regimen affects bone turnover, bone mineral density, or bone structure in 30 patients with Graves' orbitopathy.
Interventions
DRUGMethylprednisolone
Intravenous methylprednisolone
Sponsors
Odense University Hospital
Torben Harsløf
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Graves Ophthalmopathy that requires treatment with intra-venous methylprednisolone
Exclusion criteria
* Treatment with osteoporosis medication * Primary hyperparathyroidism * Hypoparathyroidism * Vitamin D \< 20mmol/L * Estimated glomerular filtration rate \< 30 mL/min * Liver disease * Peroral treatment with glucocorticoids within last three months prior to inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change Lumbar Spine Bone Mineral Density | 12 weeks | Percent change in lumbar spine bone mineral density from baseline to week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change Total Hip Bone Mineral Density | 12 weeks | Percent change in total hip bone mineral density from baseline to week 12 |
| Bone Resorption | 12 weeks | Change in bone resorption measured by the biochemical marker C-terminal telopeptide of type 1 collagen (CTx) where higher measures show increased bone resorption that decreases bone mineral density and strength. |
| Percent Change Femoral Neck Bone Mineral Density | 12 weeks | Percent change in femoral neck bone mineral density from baseline to week 12 |
| Percent Change in Bone Structure at the Radius | 12 weeks | Percent change in radial cortical volumteric BMD measured by high-resolution peripheral quantitative computed tomography |
| Percent Change in Bone Structure at the Tibia | 12 weeks | Percent change in tibial cortical volumetric BMD measured by high-resolution peripheral quantitative computed tomography |
| Bone Formation | 12 weeks | Change in Bone Formation Measured by the Biochemical Marker procollagen type I N-propeptide (P1NP) where higher measures in combination with increased CTx (see measure 4) show increased bone resorption that decrease bone mineral density and strength but where lower levels may suggest decreased bone formation that may alsodecrease bone mineral density and strength. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients 32 patients with Graves' ophthalmopathy in which treatment with intravenous methylprednisolone is indicated
Methylprednisolone: Intravenous methylprednisolone | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | Patients | — |
|---|---|---|
| Age, Continuous | 52.9 Years STANDARD_DEVIATION 10.2 | — |
| Femoral neck bone mineral density | 0.78 g/cm2 STANDARD_DEVIATION 0.11 | — |
| Lumbar spine bone mineral density | 1.0 g/cm2 STANDARD_DEVIATION 0.15 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Denmark | 32 Participants | — |
| Sex: Female, Male Female | 21 Participants | — |
| Sex: Female, Male Male | 11 Participants | — |
| Thyroxine | 90.4 nmol/L STANDARD_DEVIATION 35.4 | — |
| Total hip bone mineral density | 0.91 g/cm2 STANDARD_DEVIATION 0.13 | — |
| Tri-iodothyronine | 1.92 nmol/L STANDARD_DEVIATION 0.67 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
Percent Change Lumbar Spine Bone Mineral Density
Percent change in lumbar spine bone mineral density from baseline to week 12
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients | Percent Change Lumbar Spine Bone Mineral Density | 1.37 Percentage change | Standard Deviation 4.52 |
Secondary
Bone Formation
Change in Bone Formation Measured by the Biochemical Marker procollagen type I N-propeptide (P1NP) where higher measures in combination with increased CTx (see measure 4) show increased bone resorption that decrease bone mineral density and strength but where lower levels may suggest decreased bone formation that may alsodecrease bone mineral density and strength.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients | Bone Formation | -52.3 microgram/L | Standard Deviation 97.5 |
Secondary
Bone Resorption
Change in bone resorption measured by the biochemical marker C-terminal telopeptide of type 1 collagen (CTx) where higher measures show increased bone resorption that decreases bone mineral density and strength.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients | Bone Resorption | -0.27 microgram/L | Standard Deviation 0.32 |
Secondary
Percent Change Femoral Neck Bone Mineral Density
Percent change in femoral neck bone mineral density from baseline to week 12
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients | Percent Change Femoral Neck Bone Mineral Density | -0.32 Percentage change | Standard Deviation 4.75 |
Secondary
Percent Change in Bone Structure at the Radius
Percent change in radial cortical volumteric BMD measured by high-resolution peripheral quantitative computed tomography
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients | Percent Change in Bone Structure at the Radius | 0.98 Percentage change | Standard Deviation 0.38 |
Secondary
Percent Change in Bone Structure at the Tibia
Percent change in tibial cortical volumetric BMD measured by high-resolution peripheral quantitative computed tomography
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients | Percent Change in Bone Structure at the Tibia | 1.35 Percentage change | Standard Deviation 0.5 |
Secondary
Percent Change Total Hip Bone Mineral Density
Percent change in total hip bone mineral density from baseline to week 12
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients | Percent Change Total Hip Bone Mineral Density | -0.18 Percentage change | Standard Deviation 2.62 |