Osteoporosis, Bullous Pemphigoid
Conditions
Keywords
osteoporosis, dermocortocoids, bullous pemphigoid, pharmacoepidemiology
Brief summary
Bullous pemphigoid is the most common type of bullous skin disease and is clinically characterized by clear-tense bullae, which result in post-bullous cutaneous erosions, altering the skin barrier. The treatment of this pathology consists of the application of high doses of topical corticosteroids (clobetasol propionate) for a prolonged period of at least 6 months. The main objective of this study is to demonstrate a change in bone mineral density at 6 months after initiation of treatment, in subjects with bullous pemphigoid and treated with topical corticosteroid.
Detailed description
Glucocorticoids have direct effects on bone remodeling by suppressing bone formation (inhibition of osteoblastic differentiation, inhibition of mature osteoblasts function and apoptosis of mature osteoblasts) and by increasing bone resorption (decrease in osteoclast apoptosis and stimulation of osteoclastogenesis). They also have indirect bone effects by decreasing the intestinal absorption of calcium and increasing its urinary excretion, and by inhibiting the somatotropic and gonadotropic axis. This pathophysiology results in excessive bone fragility. Bone loss and increased incidence of fractures occur within 6 months after the introduction of oral corticosteroid therapy, with a partially reversible phenomenon within months of discontinuation. The extent of bone loss depends on the dose and duration of glucocorticoid administration. The systemic transition of topical corticosteroids depends on several parameters such as excipients, anatomical location, cutaneous state, the dose used and the duration of exposure. Clobetasol propionate, used for long-term use in bullous pemphigoid, is a Class IV dermocorticoid (highly potent). Patients with bullous pemphigoid will benefit from bone densitometry at the initiation of treatment, at 3 months (theoretical end of the treatment of attack) and at 6 months (theoretical end of the treatment). Patients will also benefit a blood test of serum calcium, phosphoremia, albumin, 25 OH vitamin D and cortisol at 8 to highlight possible correlations between changes in bone mineral density and phosphocalcic parameters and 8 cortisolemia (braking of the hypothalamic-pituitary-adrenal axis). Patients will also benefit from standard radiographs of the thoracic and lumbar spine at the initiation of treatment and at 6 months. Follow-up is planned over 6 months, with 2 follow-up visits at 3 months and 6 months.
Interventions
PROCEDUREbone densitometry
Patients with bullous pemphigoid will benefit from bone densitometry at the initiation of treatment, at 3 months (theoretical end of the treatment of attack) and at 6 months (theoretical end of the treatment).
BIOLOGICALblood test
Blood test of serum calcium, phosphoremia, albumin, 25 OH vitamin D and cortisol at 8 hours to highlight possible correlations between changes in bone mineral density and phosphocalcic parameters and 8 hours cortisolemia.
PROCEDUREradiographs of the thoracic and lumbar spine
standard radiographs of the thoracic and lumbar spine will be done at the initiation of treatment and at 6 months.
PROCEDUREClobetasol propionate
Clobetasol propionate (Dermoval® 0,05% cream), administered for 6 months.
Sponsors
Centre Hospitalier Universitaire, Amiens
University Hospital, Rouen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Patients aged ≥ 18 years * Patients with newly diagnosed bullous pemphigoid (BP), treated according to the national diagnostic and care protocol issued by the French Reference Center for Autoimmune Bullous Diseases in April 2016. * In patients for whom lumbar spine bone densitometry cannot be interpreted at several vertebral levels from L1 to L4 (severe lumbar osteoarthritis, history of lumbar vertebroplasty, osteosynthesis hardware), the data will be interpreted using the remaining evaluable vertebrae. If the BMD of none of the vertebrae from L1 to L4 is evaluable, only hip BMD will be interpreted. * Patients, or their legal representative, who have received written and oral information and have signed an informed consent form. * Social Security affiliation.
Exclusion criteria
: * Patients receiving anti-osteoporotic maintenance treatment (zoledronic acid, risedronate, alendronate, pamidronate, ibandronate, teriparatide, denosumab, raloxifene). * Patients requiring immediate initiation of anti-osteoporotic maintenance treatment (T-score \< -3 SD at at least one site or FRAX® score above the therapeutic intervention threshold). * Patients presenting with one or more major risk factors for osteoporosis: In men and premenopausal women: newly diagnosed or radiologically confirmed vertebral fracture without an obvious traumatic or tumor-related context; personal history of a peripheral fracture occurring without major trauma; systemic corticosteroid therapy prescribed for at least three consecutive months at a dose ≥ 7.5 mg/day prednisone equivalent; prolonged hypogonadism; untreated active hyperthyroidism; hypercortisolism; primary hyperparathyroidism; and osteogenesis imperfecta. * In postmenopausal women: premature menopause \< 40 years of age; BMI \< 19 kg/m²; parental history of femoral neck fracture without major trauma in a first-degree relative; history of corticosteroid therapy for at least three consecutive months at a dose ≥ 7.5 mg/day prednisone equivalent. * Patients who have received topical corticosteroids for more than one week during the two weeks preceding inclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Variation of the bone mineral density (BMD) expressed in g/cm² at the lumbar spine between baseline and the theorical end of the treatment. | 6 months after beginning of the treatment | Patients with bullous pemphigoid and treated with Clobetasol propionate will benefit from bone densitometry at the initiation of the treatment and at 6 months (theoretical end of the treatment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Variation of the bone mineral density (BMD) expressed in g/cm² at the lumbar spine between baseline and the theorical end of the treatment of attack. | 3 months after beginning of the treatment | Patients with bullous pemphigoid and treated with Clobetasol propionate will benefit from bone densitometry at the initiation of the treatment and at 3 months (theoretical end of the treatment of attack). |
| Variation of the bone mineral density (BMD) expressed in g/cm² at the hip between baseline and the theorical end of the treatment of attack. | 3 months after beginning of the treatment | Patients with bullous pemphigoid and treated with Clobetasol propionate will benefit from bone densitometry at the hip at the initiation of the treatment and at 3 months (theoretical end of the treatment of attack). |
| Variation of the bone mineral density (BMD) expressed in g/cm² at the hip between baseline and the theorical end of the treatment. | 6 months after beginning of the treatment | Patients with bullous pemphigoid and treated with Clobetasol propionate will benefit from bone densitometry at the hip at the initiation of the treatment and at 6 months (theoretical end of the treatment). |
| Variation in plasma concentrations of corrected calcemia, phosphoremia, 25 OH vitamin D and cortisolemia between Baseline and the theorical end of the treatment of attack. | 3 months after beginning of the treatment | Patients with bullous pemphigoid and treated with Clobetasol propionate will benefit from a blood test of serum calcium, phosphoremia, albumin, 25 OH vitamin D and cortisol at 8h at the initiation of the treatment and at 3 months (theoretical end of the treatment attack). |
| Variation in plasma concentrations of corrected calcemia, phosphoremia, 25 OH vitamin D and cortisolemia between Baseline and the theorical end of the treatment. | 6 months after beginning of the treatment | Patients with bullous pemphigoid and treated with Clobetasol propionate will benefit from a blood test of serum calcium, phosphoremia, albumin, 25 OH vitamin D and cortisol at 8h at the initiation of the treatment and at 6 months (theoretical end of the treatment). |
| frequency of fractures (axial and , or peripheral) | 6 months after beginning of the treatment | Patients with bullous pemphigoid and treated with Clobetasol propionate will benefit from standard radiographs of the thoracic and lumbar spine at the initiation of the treatment and at 6 months (theoretical end of the treatment). |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORBenjamin Batteux, MD
CHU Amiens
PRINCIPAL_INVESTIGATORCatherine Lok, Pr
CHU Amiens
PRINCIPAL_INVESTIGATORPascal Joly, Pr
CHU Rouen
Outcome results
None listed