72 MUSCULOSKELETAL DISORDERS NOVEMBER 15, 2010 • FAMILY PRACTICE NEWS BMD at Bisphosphonate’s End Predicts Fractures BY MITCHEL L. ZOLER density following the end of bisphos- therapy may not be useful for predicting with a T score of –2.1 to –1.5 when they phonate therapy had no significant link the patient’s fracture risk,” said Dr. Bauer, stopped bisphosphonate treatment had a FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY FOR BONE with subsequent fracture risk, Dr. Dou- professor of medicine, epidemiology, and 23% fracture rate during 5 years of follow- AND MINERAL RESEARCH glas C. Bauer said at the meeting. biostatistics at the University of Califor- up, and those who stopped with a T score The finding calls into doubt the com- nia, San Francisco. BMD at the time of al- lower than –2.1 had a 33% fracture rate TORONTO – The stronger a patient’s mon practice of running annual dual-en- endronate discontinuation “was highly over the next 5 years. The between-group bones are when bisphosphonate treat- ergy x-ray absorptiometry examinations predictive of who was going to fracture.” differences were statistically significant. ment is stopped, the less likely the bones on patients who have withdrawn from Patients who stopped alendronate ther- These data “are helpful as I try to de- are to fracture later, based on an analy- bisphosphonate treatment. apy with a total hip BMD T score of –1.4 cide which of my patients I should leave sis of 437 patients. Routine BMD measurement “1-2 years or greater had a 9% rate of clinical frac- on a bisphosphonate,” commented Dr. In contrast, changes in bone mineral after stopping prolonged alendronate ture during 5 years of follow-up. Patients Elizabeth Shane, a professor of medicine at Columbia University in New York. “Patients below –2.1 were at very high BYSTOLIC® (nebivolol) tablets Rx Only These adverse reactions have been chosen for inclusion due to a combination of seriousness, Brief Summary of full Prescribing Information frequency of reporting or potential causal connection to BYSTOLIC. Adverse reactions common risk of fracture, but even those in the Initial U.S. Approval: 2007 in the population have generally been omitted. Because these adverse reactions were reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency or INDICATIONS AND USAGE: Hypertension - BYSTOLIC is indicated for the treatment of hyperten- establish a causal relationship to BYSTOLIC exposure: abnormal hepatic function (including Measurement of sion [see Clinical Studies (14.1)]. BYSTOLIC may be used alone or in combination with other increased AST, ALT and bilirubin), acute pulmonary edema, acute renal failure, atrioventricular antihypertensive agents [see Drug Interactions (7)]. block (both second- and third-degree), bronchospasm, erectile dysfunction, hypersensitivity BMD ‘1-2 years CONTRAINDICATIONS: BYSTOLIC is contraindicated in the following conditions: Severe brady - (including urticaria, allergic vasculitis and rare reports of angioedema), myocardial infarction, cardia; Heart block greater than first degree; Patients with cardiogenic shock; Decompensated pruritus, psoriasis, Raynaud’s phenomenon, peripheral ischemia/claudication, somnolence, after stopping cardiac failure; Sick sinus syndrome (unless a permanent pacemaker is in place); Patients with syncope, thrombocytopenia, various rashes and skin disorders, vertigo, and vomiting. prolonged severe hepatic impairment (Child-Pugh >B); Patients who are hypersensitive to any component DRUG INTERACTIONS: CYP2D6 Inhibitors - Use caution when BYSTOLIC is co-administered of this product. with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc.) [see Clinical Phar- alendronate WARNINGS AND PRECAUTIONS: Abrupt Cessation of Therapy - Do not abruptly discontinue macology (12.5)]. Hypotensive Agents - Do not use BYSTOLIC with other β-blockers. Closely therapy may not BYSTOLIC therapy in patients with coronary artery disease. Severe exacerbation of angina, monitor patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, myocardial infarction and ventricular arrhythmias have been reported in patients with coronary because the added β-blocking action of BYSTOLIC may produce excessive reduction of sympa- be useful.’ artery disease following the abrupt discontinuation of therapy with β-blockers. Myocardial in- thetic activity. In patients who are receiving BYSTOLIC and clonidine, discontinue BYSTOLIC for farction and ventricular arrhythmias may occur with or without preceding exacerbation of the several days before the gradual tapering of clonidine. Digitalis Glycosides - Both digitalis angina pectoris. Caution patients without overt coronary artery disease against interruption or glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant DR. BAUER abrupt discontinuation of therapy. As with other β-blockers, when discontinuation of BYSTOLIC use can increase the risk of bradycardia. Calcium Channel Blockers - BYSTOLIC can exacerbate is planned, carefully observe and advise patients to minimize physical activity. Taper BYSTOLIC the effects of myocardial depressants or inhibitors of AV conduction, such as certain calcium over 1 to 2 weeks when possible. If the angina worsens or acute coronary insufficiency devel- antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] ops, restart BYSTOLIC promptly, at least temporarily. Angina and Acute Myocardial Infarction classes), or antiarrhythmic agents, such as disopyramide. middle tertile, with less than –1.5, were - BYSTOLIC was not studied in patients with angina pectoris or who had a recent MI. Bron- USE IN SPECIFIC POPULATIONS: Pregnancy: Teratogenic Effects, Category C - Decreased pup at a risk almost as high.” Dr. Bauer’s chospastic Diseases - In general, patients with bronchospastic diseases should not receive β body weights occurred at 1.25 and 2.5 mg/kg in rats, when exposed during the perinatal period -blockers. Anesthesia and Major Surgery - Because beta-blocker withdrawal has been associ- (late gestation, parturition and lactation). At 5 mg/kg and higher doses (1.2 times the MRHD), study “provides me with some comfort ated with an increased risk of MI and chest pain, patients already on beta-blockers should prolonged gestation, dystocia and reduced maternal care were produced with corresponding [on whom] I can stop safely.” generally continue treatment throughout the perioperative period. If BYSTOLIC is to be contin- increases in late fetal deaths and stillbirths and decreased birth weight, live litter size and pup ued perioperatively, monitor patients closely when anesthetic agents which depress myocardial The investigators used data collected in β survival. Insufficient numbers of pups survived at 5 mg/kg to evaluate the offspring for reproduc- function, such as ether, cyclopropane, and trichloroethylene, are used. If -blocking therapy is tive performance. In studies in which pregnant rats were given nebivolol during organogenesis, withdrawn prior to major surgery, the impaired ability of the heart to respond to reflex adrener- reduced fetal body weights were observed at maternally toxic doses of 20 and 40 mg/kg/day the FLEX (Fracture Intervention Trial gic stimuli may augment the risks of general anesthesia and surgical procedures. The β-block- β (5 and 10 times the MRHD), and small reversible delays in sternal and thoracic ossification Long-Term Extension) study, which ran- ing effects of BYSTOLIC can be reversed by -agonists, e.g., dobutamine or isoproterenol. associated with the reduced fetal body weights and a small increase in resorption occurred at However, such patients may be subject to protracted severe hypotension. Additionally, difficulty domized 1,099 postmenopausal women β 40 mg/kg/day (10 times the MRHD). No adverse effects on embryo-fetal viability, sex, weight or in restarting and maintaining the heartbeat has been reported with -blockers. Diabetes and morphology were observed in studies in which nebivolol was given to pregnant rabbits at doses Hypoglycemia - β-blockers may mask some of the manifestations of hypoglycemia, particularly who had completed 5 years of treatment β as high as 20 mg/kg/day (10 times the MRHD). Labor and Delivery - Nebivolol caused prolonged tachycardia. Nonselective -blockers may potentiate insulin-induced hypoglycemia and delay gestation and dystocia at doses ≥5 mg/kg in rats (1.2 times the MRHD). These effects were as- with alendronate to either continue on al- recovery of serum glucose levels. It is not known whether nebivolol has these effects. Advise sociated with increased fetal deaths and stillborn pups, and decreased birth weight, live litter size patients subject to spontaneous hypoglycemia and diabetic patients receiving insulin or oral and pup survival rate, events that occurred only when nebivolol was given during the perinatal endronate for another 5 years or switch hypoglycemic agents about these possibilities. Thyrotoxicosis - β-blockers may mask clinical β period (late gestation, parturition and lactation). No studies of nebivolol were conducted in preg- to placebo (JAMA 2006;296:2927-38). signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of -blockers may be followed nant women. Use BYSTOLIC during pregnancy only if the potential benefit justifies the potential by an exacerbation of the symptoms of hyperthyroidism or may precipitate a thyroid storm. β risk to the fetus. Nursing