Rheumatoid arthritis and osteoporosis MedDRA version: 20.0 Level: LLT Classification code 10031289 Term: Osteoporosis, unspecified System Organ Class: 100000004859 MedDRA version: 20.0 Level: LLT Classification code 10039076 Term: Rheumatoid arthritis and other inflammatory polyarthropathies System Organ Class: 100000004859
Conditions
Interventions
Trade Name: Alendronat "Teva"
Pharmaceutical Form: Tablet
INN or Proposed INN: Alendronic Acid
Other descriptive name: ALENDRONIC ACID
Concentration unit: g gram(s)
Concentration type: equal
Concentra
Sponsors
Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients (> 18 years) with rheumatoid arthritis according to the ACR/EULAR (2010) classification criteria (10) - patients must have been treated with oral bisphosphonatesalendronate for 5 years or longer, the last three years with alendronate - current T-score on DXA better than or equal to -2,5 (femoral) and -3,0 (vertebral) - receiving treatment on an outpatient basis - negative pregnancy test (serum HCG) prior to trial start and the use of contraception throughout the study period and for 1 month after conclusion of the study period for women of childbearing potential. Plasma T1/2 of ALN is less than 2 hours. The forms of contraception include: intrauterine device (IUD) and hormonal anticontraceptives (contraceptive pill, implant, patch or injection or vaginal ring). Sterile and non-fertile participants do not have to use contraception. Sterile or non-fertile is defined as having undergone surgical sterilization (vasectomy / bitalteral tubectomy, hysterectomy and bilateral ooferectomy) or post-menopausal status, defined as absence of menstrual period for at least 12 months prior to enrollment. Postmenopause will be confirmed by measurement of s-FSH prior to enrollment. - ability and willingness to give written informed consent and to meet the requirements of the trial protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: - history of hip fracture due to osteoporosis - - history of vertebral fragility fractures within the last three years OR fragility fractures in more than two vertebrae - - history of non-vertebral fragility fractures (fingers and toes not included) within the last three years - osteonecrosis of the jaw. - history of or ongoing systemic GC treatment within the last 6 months (intraarticular injections are approved) - known allergy toward any components of the study medicine - prior or ongoing treatment with with BPs other than ALN or other antiosteoporosis drugs such as hormone replacement therapy (HRT) or teriparatide (low-dose HRT up to 1mg/day is accepted) - evidence of active malignant disease - metabolic bone disease other than osteoporosis - hypo- or hyperthyroidism - hypocalcaemia - impaired renal function (eGFR <35ml/min) - known disease of the esophagus that might impair the ability to swallow the tablets such as achalasia, dysphagia or strictures - history of upper gastrointestinal disease within 1 year prior to enrollment such as peptic ulcer, upper GI bleeding, gastritis, duodenitis or surgical procedures to the upper GI-tract - allergy towards any of the substances in the study medicine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of discontinuation of alendronate on bone metabolism in patients with non-glucocorticoid treated rheumatoid arthritis and alendronate-treated osteoporosis with a current T-score in the range of osteopenia. - to assess the effect of discontinuation of ALN on C-terminal telopeptide crosslinks (CTX) and Type 1 procollagen amino-terminal-propeptide (P1NP) after 6 months - to assess the effect of discontinuation of ALN on BMD at 2 years ;Secondary Objective: - to assess the effect of discontinuation of ALN on vBMD at 2 years - to assess the effect of discontinuation of ALN on other biochemical markers of bone metabolism after 6, 12 and 24 months - to evaluate and compare the changes in vBMD in cancellous and cortical bone respectively, after discontinuation of ALN - to evaluate the correlation between RA activity and bone metabolism ;Primary end point(s): a) changes in serum CTX and P1NP from baseline 6 months b) changes in BMD from baseline to 2 years follow-up on DXA on left hip and spine ( vertebrae L2-L3) ;Timepoint(s) of evaluation of this end point: a) months 6 b) months 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): c) changes in vBMD from baseline to 2 years follow-up on HR-pQCT after 1 and 2 years in metacarpals 2-4 and at the distal radius d) changes from baseline to 6, 12 and 24 months in the following serological markers of bone metabolism and inflammation : - CTX - P1NP - Bone-specific alkaline phosphatase, (bsAP) - Tumor necrosis factor-alfa (TNF), - RANK-Ligand (RANK-L) - Osteoprotegrin (OPG) - Osteocalcin - Sclerostin,(SCL) - Interleukins, 6 and 17, (IL-6, IL-17) - C-reactive protein (CRP) e) changes in vBMD in cancellous and trabecular bone respectively from baseline to 2 years f) mean DAS-28-CRP throughout the study period (24 months) g) new erosions on X-ray according to the Sharp-van-der-Heijde-score ;Timepoint(s) of evaluation of this end point: c)months 12 and 24 d)months 6, 12 and 24 e)month 24 f)month 24 g)month 24 | — |
Countries
Denmark
Contacts
Public ContactReumatologisk Forskning
Aarhus University Hospital
Outcome results
None listed