Calcitonin for osteoporosis and bone pain.

Calcitonin has been approved for the treatment of osteoporosis and other diseases involving accelerated bone turnover for approximately 25 years. The most commonly studied and prescribed form is salmon calcitonin, which has a greater efficacy in clinical use. A wealth of well-controlled clinical studies have demonstrated that calcitonin preserves or increases bone mineral density (BMD) and reduces the risk of vertebral fractures in osteoporosis. Recent studies have indicated that while a low BMD is correlated with an increase in fracture risk, increases in BMD alone do not explain the antifracture efficacy of antiresorptive therapies such as calcitonin. Therapies that moderately increase BMD may reduce fracture risk by reducing the rate of bone turnover and maintaining the integrity of the trabecular architecture, resulting in the preservation of bone strength and quality in osteoporotic patients. An advantage of calcitonin that is not shared by other antiresorptive therapies is its direct analgesic effect on bone pain. Calcitonin has been demonstrated to be clinically useful in improving pain, not only from the acute vertebral fractures of osteoporosis, but also in Paget's disease, bone malignancies, and other sources of musculoskeletal pain. Drugs containing calcitonin may be approved for additional indications in the near future, and as more convenient routes of administration such as the oral route become available, the demand for the calcitonin peptide is expected to increase.

Flow-dependent antiarrhythmic properties of ammonia during catecholamine-driven ventricular tachycardia.

Fifteen mongrel dogs weighing 22-34 kg were instrumented to investigate the antiarrhythmic effects of ammonia (0.1-0.2 mmol/min ammonium hydroxide), adenosine (1.87 mumol/min), and saline (0.9% NaCl) during norepinephrine-driven ventricular tachycardia, under conditions of controlled and natural coronary blood flow. Under natural flow conditions, the severe ectopy caused by norepinephrine (100-800 ng.kg-1.min-1) was reduced by 42 +/- 4% after 30 s of ammonia infusion. Adenosine infusion reduced percent ectopy by 97 +/- 2% at 30 s. Ammonia also significantly increased coronary blood flow by 26 +/- 4%, while adenosine increased blood flow by 72 +/- 14%. Saline infusion had no significant effect on either the severity of ventricular tachycardia or coronary blood flow. Norepinephrine consistently caused coronary functional hyperemia as previously reported. When coronary blood flow was controlled by a peristaltic pump to match natural coronary blood flow and to prevent norepinephrine-induced coronary functional hyperemia, the antiarrhythmic effects of ammonia were lost while those of adenosine were unaffected. Additionally, increasing coronary blood flow manually during norepinephrine-induced ventricular tachycardia, to a level seen with combined norepinephrine and ammonia under natural flow conditions, appeared to worsen the ventricular arrhythmias. We conclude that the antiarrhythmic properties of ammonia against norepinephrine-driven ventricular tachycardia might be dependent on coronary blood flow, while those of adenosine are independent of coronary blood flow.