Ursodeoxycholic Acid Enhances Fractional Calcium Absorption in Primary Biliary Cirrhosis

Abstract

Bone disease is a frequently reported complication in primary biliary cirrhosis (PBC), but its pathogenesis is poorly understood. Calcium malabsorption has been considered as an important contributing factor. Ursodeoxycholic acid (UDCA) is the treatment of choice in PBC, improving survival, but its effect on calcium absorption is unknown. In this study, we have measured fractional calcium absorption, using a single isotope method, in a group of female PBC patients (median age: 60 years, range: 46-78 years) and age-matched female controls (median age: 58 years, range: 36-74). Bone mineral density (BMD) in PBC patients was significantly lower than age-matched controls (g/cm(2) +/- SEM; lumbar spine: controls 1.139+/-0.028, PBC patients 1.004+/-0.026, p = 0.0028; femoral neck: controls 0.944+/-0.034, PBC patients 0.819+/-0.023, p = 0.0032). Twenty two PBC patients, who were not vitamin D-deficient, were off and on UDCA for approximately 1 month and approximately 8 weeks, respectively. Fractional calcium absorption in PBC patients prior to UDCA treatment (mean +/- SEM, 33.8+/-2.6%) was significantly lower than controls (52.0+/-2.4%, p<0.001). Following UDCA therapy, fractional calcium absorption increased significantly (Off UDCA: 33.1+/-2.6%, On UDCA: 36.6+/-2.5%, p<0.0058). Osteocalcin levels were significantly raised in the PBC group (mean +/- SEM, ng/ml, 41.4+/-2.02) compared to controls (31.1+/-2.64, p = 0.002). There were no differences in parathyroid hormone (PTH) or 25-hydroxyvitamin D levels between these two groups or following UDCA therapy. In conclusion, we found that PBC patients display low spinal and femoral neck BMD, reduced fractional calcium absorption, and elevated plasma osteocalcin. The calcium malabsorption is corrected partially by UDCA therapy. Long-term studies are required to determine whether this effect can be sustained, and whether a sustained increase in fractional calcium absorption can translate into a favorable change in bone strength in patients with PBC.

Ursodeoxycholic acid decreases bilirubin‐induced osteoblast apoptosis

“…The effects of UDCA, neutralising the apoptosis induced by bilirubin and a hydrophobic bile acid on osteoblastic cells, are relevant, as they might support the favourable consequences of UDCA, not only improving liver damage in patients with chronic cholestasis, but also in the course and from the consequences of decreased bone formation, thus preventing, or at least delaying the development of osteopenia and osteoporosis in these patients. Until now, few studies have assessed the potential favourable effects of UDCA therapy on metabolic bone disease in patients with PBC, considered as the result of improved cholestasis by enhancing fractional calcium absorption [44]. In a large series of patients with PBC, we observed that UDCA therapy before the assessment of bone mass and fracture rate had no major significant consequences on the results [45].…”

Glutathione depleting drugs, antioxidants and intestinal calcium absorption

“…In our laboratory, we have explored the possibility that UDCA could prevent the inhibition of intestinal Ca 2+ absorption caused by NaDOC, a hydrophobic bile acid that causes GSH depletion in the duodenum, as mentioned in the previous section. Verma et al[ 91 ] have demonstrated that UDCA therapy enhances fractional Ca 2+ absorption in PBC. In agreement with these data, we have observed that UDCA alone improves the intestinal Ca 2+ absorption by increasing the amount of Ca 2+ transporters involved in the transcellular Ca 2+ pathway via activation of the VDR gene and protein expression.…”

Transdermal hormone replacement therapy improves vertebral bone density in primary biliary cirrhosis: results of a 1‐year controlled trial

“…The patients were also routinely given ursodeoxycholic acid for their liver disease. Ursodeoxycholic acid has been reported to enhance fractional calcium absorption in primary biliary cirrhosis, 33 but, according to the results of one randomized controlled trial with a 3-year followup, 34 does not reduce the rate of bone loss in primary biliary cirrhosis. There are few treatment modalities which have been shown in adequately designed trials to reduce or reverse bone loss in primary biliary cirrhosis.…”