Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
Condition: Systemic Lupus Erythematosus
MeSH terms: Osteoporosis; Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary aim of the present study was to investigate the prevalence of low bone mineral
      density (BMD) and vertebral fractures, as determined by a standardized assessment, and to
      elucidate the role of bone qualities, including micro-architecture, bone remodeling, bone
      turnover, mineralization and inflammation on bone density and prevalent vertebral fractures
      in a large population of systemic lupus erythematosus (SLE) patients.

      The secondary aim of the study is to evaluate the following parameters in women with steroid
      induced OP (SIOP) before and after 1 year of treatment using:

        1. The changes in BMD using dual energy X-ray absorptiometry (DXA)

        2. Bone mineralization and architecture in-vivo using a newly available high-resolution
           human micro-computed tomography (ExtremCT), which can provide us with new insights into
           how the degree and distribution of mineralization are affected by long-term oral
           Ibandronate treatment.

        3. Changes in perfusion and marrow edema before and after treatment of Ibandronate using
           dynamic Magnetic Resonance Imaging (MRI) in these patients with SIOP.

        4. The investigators prospectively evaluate the correlation between the changes in brachial
           arterial endothelial function and lumbar spine BMD in female lupus patients over the
           period of 1 year.
    

Detailed description: 
      In the first part of the study, 150 consecutive patients with a diagnosis of SLE were
      included in the study. All patients fulfilled the American College of Rheumatology (ACR)
      revised criteria for the classification of SLE and provided written informed consent. Data
      collected at the time of study inclusion were age, disease duration, race, menstrual status,
      age at menopause, periods of amenorrhea, family history of osteoporosis, ultraviolet (UV)
      light intolerance, sunshine avoidance, use of sunscreens in the previous year, calculated
      mean daily dietary calcium intake in the last 3 months, history of (non)vertebral fractures
      after the age of 25 years, comorbidity, alcohol and tobacco intake, and exercise status.Body
      weight, height, and body mass index (BMI) were assessed. Disease activity was scored using
      the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 54. Accumulated organ damage
      was assessed with the SLICC/ ACR damage index (DI) 55. A modified DI score was derived as the
      DI score excluding osteoporotic fractures as a damage item.BMD measurements of the hip (total
      hip and femoral neck) and the lumbar spine (L1-4; anteroposterior view) as well as lateral
      radiographs of the thoracic and lumbar spine (T5-L4)were performed. The prevalence of low BMD
      and vertebral fractures will be assessed.

      In the second part of the study, 40 female SLE patients with steroid induced osteopenia will
      be enrolled in a 12-month, randomized, parallel-group, controlled study. Patients will
      receive either oral Ibandronate 150 mg once monthly plus daily alfacalcidol (0.001 mg) or
      placebo ibandronate once monthly plus daily alfacalcidol(0.001mg).In addition, the intake of
      dietary calcium will estimate by a questionnaire on the screening visit. All patients will
      receive a daily calcium supplement(500 mg).

      Primary outcome is the improvement of bone mineral density measured by DEXA.

      Secondary outcome includes:

        1. Evaluation of the changes in bone mineralization and architecture measured by Xtreme CT.

        2. Evaluation of the changes in perfusion and marrow edema using MRI.

        3. Anti-proliferative and anti-inflammatory action of alfacalcidol using serum level of
           interleukin-6 (IL-6), transforming growth factor-beta-1, angiotensin-II, as well as
           urinary levels of TGF and monocyte chemoattractant protein-1 (MCP-1).
    

Intervention name(s): Ibandronate+alfacalcidol+calcium; placebo ibandronate+alfacalcidol+calcium
Intervention type(s): Drug; Drug
Intervention description(s): Ibandronate 150 mg monthly plus daily alfacalcidol (1ug)500mg plus calcium; placebo ibandronate monthly plus daily alfacalcidol(1ug)500mg calcium
Other intervention name(s): Bonviva; placebo Bonviva
Intervention MeSH terms: Calcium, Dietary; Ibandronic Acid; Alfacalcidol; Hydroxycholecalciferols; Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Bone mineral density; ibandronate; alfacalcidol