16 OSTEOPOROSIS MARCH 2011 • CLINICAL ENDOCRINOLOGY NEWS Nitroglycerin Ointment Strengthened Bone

BY MARY ANN MOON cerin or a matching placebo ointment to included in the analysis: 126 in the ni- The primary end point was change in a piece of onion skin that was taped to the troglycerin group and 117 in the placebo lumbar spine areal BMD after 2 years. FROM JAMA upper outer arm overnight, every night. group. A total of 106 subjects dropped Those who received active nitroglycerin opical nitroglycerin ointment rais- The study subjects were women aged 50 out because of headache, nausea, or al- showed a significant increase of about es bone mineral density, cuts re- years or older (mean age, 62 years) who lergic reaction, and another 51 “lost in- 7%, compared with women in the place- Tsorption, and alters bone struc- were at least 1 year past menopause. terest” or became ineligible. bo group, in that measure. ture so that bone strength is increased, None had osteoporosis, but all had BMD After randomization, another 30 sub- They also showed comparable increas- according to results of a double-blind T scores of 0 to –2.0 at the lumbar spine jects in the treatment group and 15 in the es in areal BMD at the total hip (6%) and trial in 243 women. and higher than –2.0 at the total hip. placebo group discontinued or were lost femoral neck (7%). Compared with place- The magnitude of improvement equals Of 400 women enrolled, only 243 re- to follow-up, including 26 who cited ad- bo users, the nitroglycerin group also or exceeds that observed with other ther- mained in the study long enough to be verse reactions including headache. showed increases in volumetric trabecu- apies, including teriparatide. “Together, these findings suggest that nitroglycerin may significantly decrease the risk of frac- tures, including fractures in long bones such as the hip, legs, and upper arm, which are largely composed of cortical bone,” wrote Dr. Sophie A. Jamal of the University of Toronto and her associates. In a single-center double-blind clinical trial, they assessed the efficacy of daily application of 2% nitroglycerin ointment over the course of 2 years in increasing bone mineral density (BMD). The study was not large enough to directly deter- mine the drug’s effects on fracture risk. The study subjects were randomly as- signed to apply active 15 mg/d nitrogly- Proof Is In Fracture Risk Your advice helps patients in here.

hen added to previous Wresearch, the findings re- ported by Dr. Jamal and her as- sociates suggest that nitroglyc- erin both inhibits bone resorption and stimulates bone formation, which no single drug can do. These results “should set the stage for an adequately pow- ered, larger study using nitro-

VIEW ON THE NEWS glycerin ointment, with frac- ture as an outcome,” said Dr. Sundeep Khosla. “If such a study demonstrates efficacy for reducing fractures, clinicians would have a novel and inexpensive therapy for os- Helping to support patients with type 2 diabetes Important Safety Information starting Humalog, one small step at a time. teoporosis.” Contraindications The results of the current The Humalog Small Steps Patient Support program is a Humalog is contraindicated during episodes of hypoglycemia free series of 7 educational mailings designed to be and in patients sensitive to Humalog or one of its excipients. study also should spur develop- delivered to your patients over the first 3 months after Warnings ment of other agents that act as initiating Humalog® (insulin lispro injection [rDNA origin]). nitric oxide donors, preferably The program was created to complement the training you Humalog differs from regular human insulin by its rapid onset of action as well as a shorter duration of action. drugs with better adverse effect provide, reinforcing and supporting your efforts to help patients fit Humalog into their lives. Therefore, when used as a mealtime insulin, Humalog profiles that don’t cause so should be given within 15 minutes before or immediately many headaches. For more details, ask your Lilly sales representative or after a meal. call 1-800-LillyRx (1-800-545-5979). Future research also should Due to the short duration of action of Humalog, patients report data on any blood pres- Indication with type 1 diabetes also require a longer-acting insulin sure changes associated with ni- to maintain glucose control (except when using an Humalog (insulin lispro injection [rDNA origin]) is for insulin pump). troglycerin therapy, which Dr. use in patients with diabetes mellitus for the control Jamal and her associates did not of hyperglycemia. Humalog should be used with Glucose monitoring is recommended for all patients report on, he added. longer-acting insulin, except when used in combination with diabetes. with sulfonylureas in patients with type 2 diabetes. The safety and effectiveness of Humalog in patients less DR. KHOSLA is in the endocrine than 3 years of age have not been established. There are research unit at the Mayo Clinic, no adequate and well-controlled clinical studies of the use of Humalog in pregnant or nursing women. Rochester, Minn. He reported serving on a scientific advisory HI68138 0211 PRINTED IN USA ©2011, LILLY USA, LLC. ALL RIGHTS RESERVED. board for Amgen. These remarks were taken from his editorial accompanying Dr. Jamal’s report (JAMA 2011:305:826-7). MARCH 2011 • WWW.CLINICALENDOCRINOLOGYNEWS.COM OSTEOPOROSIS 17 lar BMD of 12% at the radius and 8.5% bone bending and twisting strength. mation and resorption appear to widen “The possibility that different prepa- at the tibia; increases in cortical thickness Compared with placebo, nitroglycerin with time, suggesting that its efficacy rations, doses, or schedules of adminis- of 14% at the radius and 25% at the tib- treatment was associated with significant continues or even increases during 24 tration would reduce the frequency of ia; and increases in periosteal circumfer- increases in bone-specific alkaline phos- months of use. In contrast, the effects of headaches without diminishing the ef- ence of 7% at the radius and 3% at the tib- phatase, a marker of bone formation. other antiresorptives and teriparatide ei- fects on bone should be explored in fu- ia. The latter finding has not been This rose 14% at 3 months, 21% at 12 ther plateau or wane with time,” Dr. Ja- ture studies,” the researchers conclud- reported with any other agent, the inves- months, and 35% at 24 months. At the mal and her colleagues wrote. ed. tigators said (JAMA 2011;305:800-7). same time, urinary N-telopeptide level, The incidence of serious adverse effects This study was supported by the Cana- Nitroglycerin therapy also was linked a marker of bone resorption, decreased was 4% in both groups. However, dian Institutes of Health Research and with increases in measures of bone by 20% at 3 months, 33% at 12 months, headaches were much more common Physicians’ Services Inc. Dr. Jamal re- strength, with rises of 11% and 10% in and 54% at 24 months. with nitroglycerin, and often led to dis- ported receiving support from Novartis, polar section modulus and of 7% and This concomitant change indicates that continuation of therapy. The number of Amgen, Warner-Chilcott, Genzyme, and 14.5% in polar moment of inertia at the nitroglycerin uncouples bone formation headaches markedly declined with time, Shire, and her associates reported ties to radius and tibia, respectively. These find- from bone resorption. Moreover, “the dif- and no subjects dropped out of the sec- numerous drug, device, and technology ings indicate significant improvement in ferential effects of nitroglycerin on for- ond year of the study owing to headache. companies. ■

And our support can help patients out here.

Important Safety Information, continued Important Safety Information, continued

Warnings, continued For additional safety profile and other important Starting or changing insulin therapy should be done prescribing considerations, see the accompanying cautiously and only under medical supervision. Brief Summary of the full Prescribing Information.

Hypoglycemia Humalog® is a registered trademark of Eli Lilly and Company and is Hypoglycemia is the most common adverse effect available by prescription only. associated with insulins, including Humalog. Hypoglycemia can happen suddenly, and symptoms may be different for each person and may change from time to time. Severe hypoglycemia can cause seizures and may be life-threatening. Other Side Effects Other potential side effects associated with the use of insulins include: hypokalemia, weight gain, lipodystrophy, and hypersensitivity. Systemic allergy is less common, but may be life-threatening. Because of the difference in action of Humalog, care should be taken in patients in whom hypoglycemia or hypokalemia may be clinically relevant (eg, those who are fasting, have autonomic neuropathy or renal impairment, are using potassium-lowering drugs, or taking drugs sensitive to serum potassium level).