Inmaculada Ros

Alendronate is more effective than etidronate for increasing bone mass in osteopenic patients with primary biliary cirrhosis.

OBJECTIVES:Osteopenia increases the morbidity of primary biliary cirrhosis (PBC). In this study, we have compared two bisphosphonates, alendronate and cyclical etidronate, that inhibit osteoclast-mediated bone resorption and have examined their effects on bone mass in patients with this disease.METHODS:A total of 32 women with PBC were randomly assigned to receive alendronate (10 mg/day) or etidronate (400 mg/day) for 14 days every 3 months. Bone mineral density of the lumbar spine and proximal femur were measured initially and every 6 months. Bone fractures and markers of bone mineral metabolism were also evaluated.RESULTS:Sixteen patients were allocated to each group, which were comparable with respect to the severity of PBC and osteopenia. Thirteen patients in each group completed the 2-yr trial. Both treatments increased bone mineral density after 2 yr, although the increase at the lumbar spine and at the proximal femur was significantly higher in patients receiving alendronate than in patients on etidronate. This higher effect of alendronate paralleled with changes in the biochemical markers of bone turnover. No patient developed new vertebral fractures, but new peripheral fractures were detected in two patients on alendronate and in one on etidronate. There were no serious adverse effects. Neither treatment impaired liver function or cholestasis.CONCLUSIONS:Alendronate effectively increases bone mass and has greater antiresorptive power than etidronate in patients with primary biliary cirrhosis, and is associated with minor or no side effects.

Usefulness of biochemical markers of bone turnover in assessing response to the treatment of paget’s disease

The aim of this study was to investigate the usefulness of biochemical markers of bone turnover for monitoring treatment efficacy of Pagets disease of bone, and also to evaluate the utility of biological variation data in choosing the best markers for assessment of biochemical response to therapy. Thirty-eight patients with Pagets disease were included in a prospective study. All received 400 mg/day of oral tiludronate for 3 months. In 31 patients that completed treatment, biochemical markers were measured at baseline and at 1 and 6 months after treatment ended. In serum we determined the levels of total alkaline phosphatase (tAP), bone alkaline phosphatase (bAP), procollagen type I N-terminal propeptide (PINP), and C-terminal telopeptide of type I collagen (sCTx). Urine samples were analyzed for hydroxyproline (Hyp) and for C- and N-terminal telopeptides of type I collagen (CTx and NTx, respectively). Quantitative bone scintigraphy was performed at baseline and at 6 months after discontinuation of therapy. A ratio for monitoring response to treatment was obtained for each marker. This ratio reflected the size of treatment response of the marker in relation to the value of its critical difference. Thus, ratio values of >1 indicated a significant decrease of the marker after therapy. In addition, response to therapy was evaluated according to disease activity. Mean values of all markers of bone turnover decreased significantly after therapy. Serum bAP and PINP and urinary NTx showed the highest percentage reduction (between 58% and 68%). Furthermore, serum bAP and PINP showed the highest ratios for monitoring changes induced by treatment, followed by serum tAP and urinary NTx. sCTx and urinary CTx as well as Hyp showed mean ratios for monitoring changes of <1, indicating a low sensitivity for monitoring treatment. Patients with polyostotic disease showed a continuous decrease in mean values for all markers at 6 months from the end of therapy, whereas, in monostotic patients, there was a trend toward increased levels at this timepoint. In conclusion, serum bAP and PINP were the most sensitive markers for monitoring treatment efficacy in Pagets disease, although serum tAP and urinary NTx were also sensitive markers for monitoring changes. Data on biological variation are useful for assessing actual changes induced by treatment.

Hypophosphatemic osteomalacia: a report of five cases and evaluation of bone markers

In this study, we analyzed the changes in biochemical markers of bone turnover in five patients with hypophosphatemic osteomalacia. The following bone markers were evaluated: among bone formation markers, total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), osteocalcin (bone Gla protein, BGP) and procollagen type I N propeptide (PINP); among bone resorption markers, serum β C-terminal cross-linked telopeptide of type I collagen (s-CTx), urinary hydroxyproline (HYP), and N-terminal and α and β C-terminal cross-linked telopeptides of collagen (NTx and α- and β-CTx). In addition, the α/β-CTx ratio was evaluated. TAP and BAP were the markers with the highest increase in both frequency and magnitude. Conversely, BGP values were low in all patients. Collagen-related markers were slightly increased in nearly half of the patients. Among them, PINP showed the highest proportion of increased values. The α/β-CTx ratio was within normal values in all patients. In conclusion, TAP and BAP seem to be the best bone markers in the diagnostic evaluation of hypophosphatemic osteomalacia. In addition, their high values associated with low levels of BGP provide an even more reliable biochemical profile of this disorder, when associated with the classic mineral and skeletal homeostasis abnormalities.

Effect of surgical menopause and Paget's disease of bone on the isomerization of type I collagen carboxyterminal telopeptide: evolution after antiresorptive therapy.

Abstract. The objective of this study was to analyze the effect of surgical menopause and Pagets disease of bone, as well as the influence of therapy, on the isomerization of the carboxyterminal telopeptide of type I collagen (CTX). Fourteen women who had undergone surgical menopause and had begun hormone replacement therapy (HRT) after surgery were recruited. Results for these women were compared with those of 29 patients with Pagets disease of bone treated with tiludronate (400 mg/day) for 3 months, and with those of a group of 21 healthy premenopausal women (control group I). In addition, 14 healthy individuals with an age range similar to that of the pagetic patients (control group II) were included in the study. Urine samples were analyzed for levels of nonisomerized and β-isomerized CTX (α-CTX and β-CTX). Biochemical determinations were performed 3 months after surgical menopause and after 3 and 9 months of HRT, and at baseline, and 1 and 6 months after tiludronate treatment in the pagetic patients. The average levels of α-CTX and β-CTX were higher in patients than in controls. In patients after surgical menopause, because of their greater increase of β-CTX, the α-CTX/β-CTX ratio was lower than that of control group I (0.881 ± 0.3 vs 1.515 ± 0.8; P < 0.05). In contrast, at baseline, pagetic patients showed marked increases in α-CTX levels, resulting in a higher α-CTX/β-CTX ratio than that of control group II (2.879 ± 1.3 vs 0.96 ± 0.25; P < 0.0001). The average percent decrease in both markers after therapy was similar in both conditions (−60% for α-CTX and −44% for β-CTX after 3 months of HRT in the surgical menopause group, vs −66% for α-CTX and −41% for β-CTX in the pagetic group, 1 month after finishing tiludronate therapy; P, NS), resulting in a significant decrease of the α-CTX/β-CTX ratio in pagetic patients (2.879 ± 1.3 vs 1.614 ± 0.8; P < 0.001). In conclusion, surgical menopause is associated with a decrease in the urinary α-CTX/β-CTX ratio because of the higher increase in the β-CTX level after menopause. Pagetic patients show an increase in this ratio, compared with the control value, and the ratio decreases after bisphosphonate treatment. The response to therapy was similar in both conditions, with a comparable decrease of both markers. These findings show how bone markers may contribute to the understanding of pathophysiologic mechanisms in bone diseases.