Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. Controlled trial of calcitriol in hemodialysis patients. Initial dosing of paricalcitol based on PTH levels in hemodialysis patients with secondary hyperparathyroidism. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. Perioperative use of 0.12% chlorhexidine gluconate for the prevention of alveolar osteitis: efficacy and risk factor analysis.
Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women. Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcemia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 +/- 29%, 40 +/- 36%, 54 +/- 28%, or 55 +/- 39%, respectively. Plasma PTH levels decreased in all patients given doses of > or =25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease. Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride.
                Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase.
                Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose.
                Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism.
                Copyright 2004 Massachusetts Medical Society We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation. Adjustment of the initial dose of paricalcitol in hemodialysis patients with secondary hyperparathyroidism (SHPT) on the basis of severity of SHPT generally is preferred in current practice. Whether the proposed dose, based on the formula baseline intact parathyroid hormone (iPTH [picograms per milliliter]) divided by 80, is the most appropriate has not been assessed adequately.
                A double-blind randomized trial comparing iPTH/80 dose with the immediately lower iPTH/120 dose was undertaken. Forty-three hemodialysis patients with iPTH levels between 300 and 900 pg/mL (300 and 900 ng/L) were followed up for 12 weeks. The primary outcome was control of iPTH levels within a target range between 150 and 300 pg/mL (150 and 300 ng/L).
                No difference between the 2 dose groups was noted in time to achieve target iPTH levels of 150 to 300 pg/mL (150 to 300 ng/L). More episodes of excessive decrease in iPTH levels occurred in the iPTH/80 group compared with the iPTH/120 group (P = 0.003). Nine patients in the iPTH/80 group (45%) versus 2 patients in the iPTH/120 group (10%) had iPTH levels less than 150 pg/mL (<150 ng/L) in at least half the measurements performed during the second half of the study (P = 0.034). Increases in calcium levels were greater in the iPTH/80 group at all times during the study (P < 0.05 at weeks 4 and 10). The number of required dose reductions was significantly greater in the iPTH/80 group compared with the iPTH/120 group (P = 0.008).
                In hemodialysis patients with SHPT, a lower initial dose of iPTH/120 shows efficacy similar to that of the already widely used iPTH/80 scheme in reaching target iPTH levels (150 to 300 pg/mL [150 to 300 ng/L]), with less required dose adjustments, lower increase in calcium levels, and lower cost. In addition, the initial dose of paricalcitol based on the iPTH/80 formula leads significantly more patients to excessive suppression of iPTH (<150 pg/mL [<150 ng/L]) than the iPTH/120 dose. Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dose-titration study with single daily oral doses of AMG 073/placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium x phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P = 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH < or = 250 pg/ml compared with placebo patients (20%; P = 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH > or =30% compared with placebo patients (23%; P = 0.009). Calcium x phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P = 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium x phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism. The purposes of this study were to evaluate the use of 0.12% chlorhexidine gluconate as a prophylactic therapy for the prevention of alveolar osteitis and to further examine subject-based risk factors associated with alveolar osteitis.
                The trial was a randomized, double-blind, placebo-controlled, parallel-group study conducted among 279 subjects, each of whom required oral surgery for the removal of a minimum of one impacted mandibular third molar. Subjects were instructed to rinse twice daily with 15 ml of chlorhexidine or placebo mouthrinse for 30 seconds for 1 week before and 1 week after the surgical extractions. This regimen included a supervised presurgical rinse. Alveolar osteitis diagnosis was based on the subjective finding of increasing postoperative pain at the surgical site that was not relieved with mild analgesics, supported by clinical evidence of one or more of the following: loss of blood clot, necrosis of blood clot, and exposed alveolar bone.
                In comparison with use of the placebo mouthrinse, prophylactic use of the chlorhexidine mouthrinse resulted in statistically significant (p < 0.05) reductions in the incidence of alveolar osteitis. With chlorhexidine therapy, the subject- and extraction-based incidences of alveolar osteitis in the evaluable subset (271 subjects) were reduced, relative to placebo, by 38% and 44%, respectively. The corresponding odds ratios that describe the increased odds of experiencing alveolar osteitis in the placebo group were 1.87 and 2.05 for subject- and extraction-based analyses, respectively. In comparison with nonuse of oral contraceptives, the use of oral contraceptives in female subjects was related to a statistically significant increase in the incidence of alveolar osteitis (odds ratio = 1.92, p = 0.035). Relative to male subjects, the observed incidence of alveolar osteitis for female subjects not using oral contraceptives was not statistically significant (odds ratio = 1.18, p = 0.64). Smoking did not increase the incidence of alveolar osteitis relative to not smoking (odds ratio = 1.20, p = 0.33).
                These data confirm that the prophylactic use of 0.12% chlorhexidine gluconate mouthrinse results in a significant reduction in the incidence of alveolar osteitis after the extraction of impacted mandibular third molars. In addition, oral contraceptive use in females was confirmed to be a risk factor for the development of alveolar osteitis.
Calcimimetic treatment of SHPT leads to significant improvements in biochemical parameters that observational studies have shown to be associated with increased mortality, cardiovascular risk and osteitis fibrosa, but patient-based benefits have not yet been demonstrated in trials. For patients with SHPT, the benefits of calcimimetics over standard therapy remain uncertain until further RCTs become available.