This will be a pilot study that aims to gain insight into the effect of Gaucher disease on bone metabolism. For this purpose we formulated the following research questions:What is the effect of inflammatory factors in the serum of patients with…
ID
Source
Brief title
Condition
- Blood and lymphatic system disorders congenital
- Bone disorders (excl congenital and fractures)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
osteoblast proliferation, osteoblast differentiation, osteoclastogenesis,
osteoclast function
Secondary outcome
na
Background summary
Gaucher disease is a rare inherited metabolic disorder resulting from deficient
activity of the enzyme glucocerebrosidase. Undegraded glucosylceramide
accumulates in macrophages. Clinically, the most prevalent type 1 form
manifests itselfs with hepatosplenomegaly and bone marrow involvement.
Skeletal disease can be a prominent feature of the disorder ranging from
slightly low bone mineral density (Fiore, 2002; Schiffmann, 2002) to severe
bone crises and avascular necrosis and fractures (Beutler and Grabowski).
Enzyme replacement therapy has altered the natural course of the disease, but
only partially improves pre-existing skeletal disease.
Gaucher disease has been regarded as a chronic inflammatory disorder, with
anti-inflammatory markers possibly reflecting a compensatory reaction to the
presence of large amounts of activated macrophages.
While it is likely that cytokines and chemokines are implicated in the
pathophysiology of bone disease, their exact role remains unclear. Gaucher
disease, as a complex disorder of pro-and anti-inflammatory factors, may serve
as a model to further study the effect of cytokines on osteoblasts. In
addition, the pathophysiology of bone disease deserves further study.
Study objective
This will be a pilot study that aims to gain insight into the effect of Gaucher
disease on bone metabolism. For this purpose we formulated the following
research questions:
What is the effect of inflammatory factors in the serum of patients with
Gaucher disease on the proliferation and differentiation of normal human
osteoblasts in vitro?
Which of the inflammatory factors is most responsible for this effect?
Study design
cross sectional
Study burden and risks
na
De Boelelaan 1117
1081 GH
NL
De Boelelaan 1117
1081 GH
NL
Listed location countries
Age
Inclusion criteria
Patients
1. Men and women between the age of 18 and 65 years
2. Informed consent
3. Patient with a proven diagnosis of Gaucher disease
4. Stable (< 5% change) body weight for at least 6 months and a BMI between 18-30;healthy controls
1. Men and women between the age of 18 and 65 years
2. Informed consent
3. Stable (< 5% change) body weight for at least 6 months and a BMI between 18-30
Exclusion criteria
Patients and healthy controls:
1. Documented inflammatory or malignant bowel disease
2. Previous bowel surgery, both small intestine and/or colon, with the exception of appendicular surgery.
3. Cholestatic disease defined by elevated values of AP or gammaGT > 2 x upper reference limit
4. Fever of unknown cause during the past 4 weeks prior to study
5. Co-morbidity influencing bone metabolism:
Renal insufficiency (creatinin clearance < 40 ml/min)
untreated hypo- / hyperthyroidism (stabily treated hypothyroidism may be included)
Paget*s disease or other metabolic bone diseases, Cushing*s disease or hyperprolactinemia
6. Patients who have received calcitonin, bisphosphonates and strontium within 1 year
7. Use of corticosteroids current use and in the last 3 months in case of longterm use or in the last 6 weeks in case of induction therapy
8. Patients who have been treated with anti-TNF in the last 6 months
9. Use of antitrombotic agents
10. Patients who are pregnant or breast-feeding
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL32394.029.10 |