[2009] [SAT0234] EVALUATION OF BONE MINERAL DENSITY IN PATIENTS WITH SYSTEMIC SCLEROSIS, DURING TREATMENT WITH BOSENTAN (PRELIMINARY REPORT)

S. Bellissimo, S. Stisi Rheumatology Unit, Rummo Hospital, Benevento, Italy

Background: Endothelin-1 (ET1) is a potent vasoconstrictor peptide, whick plays a key role in pathogenesis of systemic sclerosis (SSc). Bosentan is an active dual ET1 receptor (ETA and ETB) antagonist. This drug is utilized for management of pulmonary arterial hypertension (PAH) and prevention of ischemic digital ulcers (IDU) in patients with SSc.
ET1 is also a regulator of osteoblasts, with a primary role in the development of osteoblastic bone metastases (1). So, the blockade with ERA (Endothelin Receptor Antagonists) of the receptor of ET1 on osteoblasts might allow a better prognosis in patients with osteoblastic metastases in prostate or breast cancer (2). Based on this observation, we hypothesize that bosentan might influence the bone metabolism in SSc patients, during this treatment.
Objectives: The aim of the study was to evaluate the possible effect of bosentan on bone mineral density (BMD) in SSc patients with PAH or digital ulcers, compared with a group of SSc patients without bosentan treatment.
Methods: 12 female patients with SSc (10 postmenopausal, 2 premenopausal) fulfilling the ACR criteria for SSc (aged 42-78 years, median 59,9; 7 with limited and 5 with diffuse form) were included in the study. Disease duration was with a range of 7-23 years, median 13 years. Standard doses of bosentan were used in these 12 patients (3/12 for treatment of IDU; 9/12 for treatment of PAH).
The examination of BMD was performed at the lumbar spine (L2-L4) and at the femoral neck by dual energy X-ray absorptiometry (DEXA- Hologic QDR Delphi W), at baseline and 12 months later of bosentan treatment. This examination was performed in other 12 SSc patients (9 postmenopausal, 3 premenopausal) without bosentan treatment (all females; aged 43-76 years, median 62,6; 9 with limited and 3 with diffuse form; disease duration: median 11,3 years). Patients receiving or having ever received bisphosphonates, strontium ranelate or hormone replacement therapy were excluded.
In all SSc patients, pulmonary function tests (PFT), high resolution computed tomography (HRCT) of the lungs and doppler echocardiography were evaluated during the study.
Results: In SSc patients with PAH and IDU, we found no significative difference of BMD of the lumbar spine and femoral neck, before and after 1 year of treatment with bosentan (p=0,618 BMD L2-L4, p=0,543 BMD femoral neck). In SSc patients with bosentan, lumbar and femoral BMD was not significantly different from the controls (SSc patients without bosentan), at baseline and after one year. No correlation was found between BMD and duration of disease. Serum concentration of calcium, phosphorus and alkaline phosphatase was not significantly different in each group.
In SSc patients in treatment with bosentan, PA systolic pressure (PASP) and PFT results remained stable during the study. Besides, in patients with IDU in treatment with bosentan, no new digital ulcers were observed.
Conclusion: Despite small number of patients, the results of our study seem to indicate that in SSc patients, the use of bosentan (for management of PAH and IDU) should not determine significant decrease of bone mineral density. On the contrary, in this study we have observed that bosentan stabilizes PASP and PFT in SSc patients.
References:

1. Guise TA, Yin JJ, Mohammad KS. Role of endothelin-1 in osteoblastic bone metastases. Cancer. 2003;97:779-84.
2. Banerjee S, Hussain M, Wang Z et al. In vitro and in vivo molecular evidence for better therapeutic efficacy of ABT-627 and taxotere combination in prostate cancer. Cancer Res. 2007;67(8):3818-26.