J. Somoza

Effect of melatonin on bone metabolism in ovariectomized rats

To assess the effect of pharmacological dose of melatonin on bone metabolism in ovariectomized rats, urinary deoxypyridinoline (a marker of bone resorption) and calcium excretion, circulating levels of calcium, phosphorus and bone alkaline phosphatase activity (a marker of bone formation), and bone mineral density (BMD), mineral content (BMC) and bone area (BA) of total body, were measured in adult rats for up to 60 days after surgery. Rats received melatonin in the drinking water (25 microg/ml water) or drinking water alone. Urinary deoxypyridinoline increased significantly after ovariectomy by 51% (30 days after surgery) and by 47% (60 days after surgery). The increase in urinary deoxypyridinoline found 30 days after ovariectomy was not observed in melatonin-treated rats. Urinary calcium concentration was similar in the 4 experimental groups studied, as was the circulating calcium concentration at every time interval examined. Fifteen days after surgery, a significant increase in serum phosphorus and bone alkaline phosphatase levels occurred in ovariectomized rats receiving melatonin as compared to their controls. Sixty days after surgery BMD, BMC and BA decreased significantly in ovariectomized rats, an effect not modified by melatonin. Serum estradiol decreased significantly by 30 days after ovariectomy to attain values close to the limit of detection of the assay by 60 days after ovariectomy. The results support the conclusion that a pharmacological amount of melatonin modifies bone remodeling after ovariectomy and that the effect may need adequate concentrations of estradiol.

Risk Factors for the Development of Vertebral and Total Skeleton Osteoporosis in Patients with Primary Biliary Cirrhosis

Abstract. The objectives of this work was to (1) study the bone mineral density (BMD) of the lumbar spine, total skeleton, and body composition in patients with primary biliary cirrhosis (PBC) and (2) evaluate the risk factors (premature menopause, stages of the disease, hyperbilirubinemia) and bone and liver biochemical parameters for the development of osteoporosis. We studied 23 women with a compatible diagnosis of PBC. The BMD and body composition were evaluated by X-ray absorptiometry (Lunar DPX-L). The average age of the population was 56.7 ± 10.2 years. The BMD of the lumbar spine and of the total skeleton was 1.3 SDs below the normal population matched for sex and age. In the total skeleton, the legs were the most severely affected area (Z score −1.5). The body composition showed no significant difference compared with the normal population. The BMD of 56% of the patients was less than −2.5 SDs from the average normal young values. Patients with a history of vertebral fractures had diminished mineral density of the lumbar spine, as did those who had had no fractures. Of the risk factors studied, patients with premature menopause had a lower bone mass compared with patients with normal menopausal age (Z score of the total skeleton was −2.1 ± 1.8 versus −1.1 ± 1.0) but the difference did not reach statistical significance. The bone mass was not affected in patients with regular menstrual cycles. There were no statistically significant differences in high levels of bilirubin, advanced stages of the disease, or the biochemical variables studied. It is concluded that patients with primary biliary cirrhosis present diminished cortical and trabecular bone mass, whereas body composition was unaffected. Premature hormone deficit, possibly triggered by the chronic hepatic pathology, is a contributing factor to the osteoporosis in this population.

Interrelationship between bone turnover markers and dietary calcium intake in pregnant women: a longitudinal study

This longitudinal study evaluated bone turnover and the interrelationship between changes in bone biomarkers and habitual dietary calcium intake during pregnancy in a group of women ranging widely with regard to dietary calcium intake. Thirty-nine healthy pregnant and 30 nonpregnant women were studied. Calcium, phosphorus, 1alpha,25-dihydroxyvitamin D (1,25diHOD), bone alkaline phosphatase (bALP), carboxyterminal propeptides of type I procollagen (PICP) and carboxyterminal telopeptides of type I collagen (betaCTX and ICTP) were measured in serum and calcium, and creatinine and aminoterminal telopeptide (NTX) were determined in urine. Serum calcium and phosphorus did not change but the urinary Ca/Creat ratio and 1,25diHOD increased throughout pregnancy (P < 0.001 and P < 0.0001, respectively). Serum b-ALP and PICP increased during the last two trimesters (P < 0.0001 and P < 0.001, respectively). All studied bone resorption markers increased compared to nonpregnant values throughout pregnancy. The highest increment was observed in the third trimester. The level of significance decreased as follows: betaCTX > NTX >ICTP. Serum 1,25 diHOD versus calcium intake showed a positive and significant correlation (r = 0.51, P < 0.02). A negative correlation between the absolute change in betaCTX, NTX, and b-ALP between the third and second trimester and calcium intake at the end of pregnancy was observed in pregnant women who did not cover adequately calcium intake requirements (r = -0.47, P < 0.03; r = -0.41, P < 0.05; and r = -0.43, P < 0.05, respectively). These results suggest that skeletal response to pregnancy may not be entirely independent of maternal calcium intake, especially in women with usually low calcium intake. In summary, not only hormonal changes in calcium metabolism that occur during pregnancy but also other considerations, such as low dietary calcium intake, may lead to an increment in the biological activity of the skeleton. Additional studies must be conducted to confirm our findings and to gain a better understanding of skeletal response to a low calcium intake during pregnancy.

Olpadronate prevents the bone loss induced by cyclosporine in the rat.

The aim of the present in vivo experimental study was to investigate changes in bone turnover and bone mineral density (BMD) induced by cyclosporine (CsA) administration. The effectiveness of olpadronate (OPD) in preventing bone loss associated with CsA treatment was also evaluated. Forty male Sprague-Dawley rats (approximately 5 months old) were treated as follows: Group I: CsA+OPD vehicles (control); Group II: CsA 15 mg/kg + OPD vehicle; Group III: CsA 15 mg/kg + 4 ug OPD/100g rat; Group IV: CsA 15 mg/kg + 8 ug OPD/100g rat; Group V: CsA 15 mg/kg + 16 ug OPD/100g rat. CsA was administered by daily oral gavage and OPD by intraperitoneal injection once a week. Serum bone-alkaline phosphatase (b-ALP) and urinary deoxypyridinoline (DPyr) were measured on days 0, 14 and 30. Total skeleton, femur, lumbar spine, proximal, and middle tibia BMDs were measured on days 0 and 30. No significant differences were found between the CsA and the control groups as regards serum bALP levels, on days 14 and 30. CsA+OPD treated rats presented a transient increment in serum b-ALP on day 14 and a significantly lower level on day 30 compared to the control and CsA groups (P < 0.05). On days 14 and 30, DPyr excretion increased in the CsA group compared to control animals (P < 0.05). The three studied doses of OPD induced a significant decrease in DPyr excretion in the CsA group on days 14 and 30 (P < 0.05). Group V (receiving the highest dose of OPD) presented a significantly lower level of DPyr compared to the other two OPD-treated groups (P < 0.05). On day 30, the CsA group presented a significant reduction in proximal tibia, spine and whole femur BMDs (P < 0.05) compared to controls. On day 30, OPD treatment increased BMD of all the studied areas in CsA rats. Proximal tibia BMD of group V reached significantly higher values than the other studied OPD groups (P < 0.05). In summary, this study suggests that CsA-induced high bone resorption and trabecular bone loss is prevented by cotreatment with OPD. Moreover, it encourages the possible use of OPD to treat patients receiving CsA as immunosuppressive therapy.