Intermittent cyclical etidronate in the prevention of corticosteroid-induced bone loss. Prevention of bone loss in cardiac transplant recipients. A comparison of biphosphonates and vitamin D. Cyclical etidronate in the prevention of bone loss in corticosteroid-treated primary biliary cirrhosis. A prospective, controlled pilot study. Prevention of steroid-induced osteoporosis with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). Cyclical etidronate reverses bone loss of the spine and proximal femur in patients with established corticosteroid-induced osteoporosis. Therapy of steroid-induced bone loss in adult asthmatics with calcium, vitamin D, and a diphosphonate. Increased bone density in patients on steroids with etidronate.
We conducted a prospective study of etidronate's effects on corticosteroid-induced bone loss in postmenopausal women with temporal arteritis for whom high-dose prednisone therapy was indicated. Group A (n = 10) received etidronate (400 mg/day for 2 weeks, then 11 weeks off etidronate; four cycles total) and prednisone: Group B (n = 10) received only prednisone. Vertebral bone mineral density (BMD) was measured blinded by dual X-ray absorptiometry. At 3, 6 and 12 months, vertebral BMD was significantly (P < 0.01) increased in Group A and decreased in Group B, based on mean actual and percent changes in BMD and mean changes in BMD Z-score from baseline. Between-group comparisons were also significant (P < 0.002) at each time point. No adverse events related to etidronate treatment were reported. Our results suggest that corticosteroid-induced bone loss may be prevented by instituting intermittent cyclical etidronate therapy when high-dose prednisone therapy is begun. Further research into bisphosphonate use in corticosteroid-induced bone loss (with larger patient populations, longer follow-up and fracture assessment) is warranted. Bone mineral density is already abnormally reduced at the moment of cardiac transplantation and bone loss occurs at an impressive rate in the first postoperative year. The aim of the study was to compare two prophylactic medical regimens as to their efficacy in mitigating bone loss after transplantation. Forty-eight consecutive recipients were randomized to receive either alternating calcium carbonate and disodium etidronate (group A) or a daily supplement of calcium carbonate and alphacalcidol (group B). Bone mineral density measurements were performed immediately before hospital discharge and 6, 12, and 24 months after surgery using dual energy X-ray absorptiometry. Clinical events were recorded and roentgenograms of the spine were performed postoperatively and 1 and 2 years later. In both treatment groups bone loss remained significant at the level of the lumbar spine in the first postoperative year (P<0.005) and at the level of the femoral neck in the first (P<0.005) and the second (P<0.06) year after transplantation. Six months after transplantation, however, patients receiving alphacalcidol had a significant reduction in bone loss at the level of the lumbar spine (P=0.047) and at the level of the femoral neck (P=0.043). At the level of the femoral neck this decrease in bone loss was even more pronounced in the second postoperative year (P<0.001). In the group of patients treated with disodium etidronate, 4 recipients needed additional hospitalizations for treatment of symptomatic fractures at the level of the lumbar spine or the femoral neck. No such events happened in recipients receiving vitamin D supplements. Prophylactic administration of calcium carbonate and alphacalcidol after cardiac transplantation reduces bone loss and seems to decrease osteoporotic complications. Recently, promising disease modifying effects of low dose corticosteroid treatment in primary biliary cirrhosis have been reported. However, steroid-induced bone loss constitutes a potential drawback of this treatment option.
                To assess whether etidronate can reduce bone loss during corticosteroid treatment.
                Twelve primary biliary cirrhosis patients (all Child-Pugh Class A), treated with prednisone in the context of a 1-year placebo-controlled pilot study with prednisone (maintenance dose 10 mg daily), and azathioprine (50 mg daily), were randomized to receive either cyclical etidronate (400 mg daily, during 2 weeks) alternated with calcium 500 mg daily during 11 weeks or calcium alone. All patients had been receiving ursodeoxycholic acid during at least 1 year and this treatment was continued. Bone mass was measured in the lumbar spine and the femoral neck by dual energy X-ray absorptiometry before and after 3 and 12 months of treatment. Markers of bone formation (serum osteocalcin, procollagen-I-propeptide) and bone resorption (urinary deoxypyridinoline and calcium) were also monitored.
                The mean lumbar bone mineral density did not significantly change in the patients taking etidronate + calcium, in contrast to patients treated with calcium alone (+0.4 vs. -3.0%; p = 0.01). Changes in femoral bone mineral density and markers of bone turnover did not significantly differ between both groups. No adverse effects of etidronate were noted.
                Cyclical etidronate appears to prevent bone loss associated with prednisone treatment in patients with primary biliary cirrhosis. These preliminary results encourage the further evaluation of long term prednisone treatment and concurrent bisphosphonate therapy in primary biliary cirrhosis. In a prospective, randomised, placebo-controlled trial comparing the effect of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) (150 mg/day) plus calcium (1 g/day) with that of calcium alone on the bone mass of patients receiving long-term glucocorticoid therapy, the mean metacarpal cortical area in patients receiving APD increased by 1.2% between 0 and 6 months (p less than 0.06) and then remained stable between 6 and 12 months. In contrast, this index progressively declined in the placebo group (p less than 0.05 at 12 months). The two groups differed significantly in the changes at both 6 and 12 months (p less than 0.01). Mean vertebral mineral density, as measured by quantitative computed tomography, increased by 19.6% over 12 months in the APD group (p less than 0.02) but showed a non-significant decline of 8.8% in controls. The differences between the changes were again significant (p less than 0.005). Biochemical indices and bone histomorphometry indicated a reduction in bone resorption and bone formation but there was no evidence of osteomalacia. APD may thus prevent bone loss in glucocorticoid-treated patients over a year. To compare the bone-mass effects of calcium supplementation and intermittent cyclic etidronate in patients with established corticosteroid-induced osteoporosis.
                Eighteen male and 21 female patients who had established corticosteroid-induced osteoporosis and were receiving chronic prednisone therapy (> or = 10 mg/d) were enrolled in a prospective 12-month, open-label study. In addition to continuing prednisone therapy, patients received continuous calcium supplementation 500 mg/d (n = 20) or four cycles of intermittent cyclic etidronate therapy consisting of etidronate 400 mg/d for 14 days followed by calcium 500 mg/d for 76 days (n = 19). Bone mineral density (BMD) of the spine (L1 through L4) and proximal femur (total hip, femoral neck, trochanter, Ward's triangle) was measured by dual-energy x-ray absorptiometry at baseline, 6 months, and 12 months by staff blinded to the treatment. Serum calcium, phosphorus, and alkaline phosphatase were also measured at these times.
                Treatment with intermittent cyclic etidronate for 12 months resulted in significant increases of 5.7% and 6.8% in BMD of the spine and proximal femur (total hip), respectively (P < 0.02 versus baseline; P < 0.001 versus calcium group). Calcium supplementation alone did not prevent significant losses of 3.4% and 4.1% in BMD at the respective sites (P < 0.02 versus baseline). At the end of the study Z scores reflected significant increases in BMD of the spine and proximal femur (all regions) in the etidronate group (P < 0.01), and significant decreases at the spine, proximal femur, and trochanter in the calcium group (P < 0.01). After 12 months, the difference between the groups was 9.1% (P < 0.01; 95% CI 6.3% to 11.9%) at the spine and 10.9% (P < 0.01; 95% CI 7.8% to 14.1%) at the proximal femur (total hip). Seventeen (89%) of the etidronate-treated patients had increases in BMD of both skeletal sites, whereas only 2 (10%) and 3 (15%) of the calcium-treated patients had positive changes in BMD of the spine and proximal femur (total hip), respectively (P < 0.01). Serum calcium, phosphorus, and alkaline phosphatase levels did not change significantly during the study in either treatment group. Both treatment regimens were well tolerated, with no interactions between prednisone therapy and the study medications. Analyses of response by subgroups (female/male, pulmonary/nonpulmonary indication for prednisone) showed no significant attribute-dependent changes during the 12-month study. At baseline, women had significantly lower BMD of the spine and proximal femur (total hip) (P < 0.01), and patients with pulmonary disease had significantly longer duration of prednisone therapy and cumulative prednisone dose (P < 0.03).
                Intermittent cyclic etidronate reversed the progressive loss of bone mineral density of the spine and proximal femur in female and male patients with established osteoporosis secondary to chronic corticosteroid (prednisone) therapy for pulmonary and nonpulmonary diseases. Calcium supplementation alone did not prevent or attenuate corticosteroid-induced losses. In a prospective, controlled, and randomized clinical trial, we examined the effects of treatment with vitamin D (1,000 IU/d), calcium (1 g/d), and ethane-1-hydroxy-1,1-diphosphonate (EHDP; 7.5 mg/kg body weight) on vertebral bone mass in fourteen asthmatics undergoing long-term treatment with systemically applied corticosteroids. The extent of steroid-induced bone loss was judged by vertebral bone density of the lumbar spine measured by dual-photon absorptiometry as well as by vertebral crush fracture incidence examined by conventional X-ray. Results of the measurements before treatment and after six mo were compared with those of an untreated control group of nineteen asthmatics. Bone density increased during the observation period by 5% in the treated group, compared with a decrease of 4.3% in the untreated control group (p < 0.01). Moreover, in the treated group no radiologically visible new fractures occurred; in the control group new fractures were observed in four patients. There were no serious side effects of the applied drugs during the 6-mo period. Therefore, the combination of EHDP, calcium, and vitamin D appears to be a useful regimen for the management of steroid-induced bone loss in adult asthmatics. nan
Bisphosphonates are effective at preventing and treating corticosteroid-induced bone loss at the lumbar spine and femoral neck. Efficacy regarding fracture prevention cannot be concluded from this analysis, although bone density changes are correlated with fracture risk.