<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_431"
                     title="Down a Beer to Improve Bone Health? Not So Fast"
                     score="0.013"
                     href="http://www.medpagetoday.com/PrimaryCare/DietNutrition/tb/18347?impressionId=1265786337595"
                     
      &lt;p&gt;A flagon of ale may indeed be a good source of dietary silicon, a recent study showed, but experts say any attempt to link beer drinking to bone health is not based on scientific data.&lt;/p&gt;
&lt;p&gt;The study of 100 commercial beers in the February issue of the &lt;em&gt;Journal of the Science of Food and Agriculture&lt;/em&gt;, by Charles Bamforth, PhD, DSc, and Troy Casey, of the University of California Davis, examined the silicon content that results from different ingredients and brewing processes.&lt;/p&gt;
&lt;p&gt;Although a press release issued with the study prominently mentioned the link between silicon and bone health, the study itself did not look at bone mineral density or analyze any patient data at all, according to several researchers contacted by &lt;em&gt;MedPage Today&lt;/em&gt; and ABC News.&lt;/p&gt;
&lt;p&gt;The authors wrote that they explored the silicon content in beer because the popular beverage has been identified as one of the richest potential sources of dietary silicon in the Western diet. The average intake is 20 to 50 mg/day.&lt;/p&gt;
&lt;p&gt;The beers sampled contained an average of 29.4 mg/L of silicon, with a range of 6.4 to 56.4 mg/L. Beers made from a barley-based grist (as opposed to wheat-based beers ) and brews containing more hops had the highest silicon levels.&lt;/p&gt;
&lt;p&gt;The beer type with the overall highest silicon level was India Pale Ale, with an average of 41.2 mg/L. Other ales came in second with 32.8 mg/L.&lt;/p&gt;
&lt;p&gt;Nonalcoholic beers, light lagers, and wheat beers had the least silicon.&lt;/p&gt;
&lt;p&gt;In the end, the authors concluded that &quot;beer is a substantial source of silicon in the diet&quot; and that &quot;beers containing high levels of malted barley and hops are richest in silicon,&quot; but they did not attempt to establish a link between beer drinking and bone health.&lt;/p&gt;
&lt;p&gt;Experts contacted for comment on the study also cautioned the public against establishing any such connection.&lt;/p&gt;
&lt;p&gt;&quot;To conclude any bone health benefits from this study would require a great leap,&quot; Tim Byers, MD, MPH, deputy director of the University of Colorado Cancer Center in Aurora, wrote in an e-mail.&lt;/p&gt;
&lt;p&gt;Other researchers noted that previous studies have shown an association between alcohol consumption and an increased risk of fracture.&lt;/p&gt;
&lt;p&gt;That&apos;s probably because of a greater chance of falling after drinking, according to Walter Willett, MD, DrPH, of the Harvard School of Public Health.&lt;/p&gt;
&lt;p&gt;In fact, Stephen Richardson, MD, an endocrinologist at NYU Langone Medical Center, noted that &quot;alcohol consumption is a risk factor for osteoporosis.&quot;&lt;/p&gt;
&lt;p&gt;Still, there is some evidence supporting a positive link between overall dietary silicon and bone health.&lt;/p&gt;
&lt;p&gt;A 2004 cross-sectional study in the &lt;em&gt;Journal of Bone and Mineral Research&lt;/em&gt; that used data from the Framingham Offspring cohort found a significant association between greater dietary silicon intake, including that from beer, and higher bone mineral density in the hip in men and premenopausal women.&lt;/p&gt;
&lt;p&gt;The researchers concluded: &quot;These findings suggest that higher dietary silicon intake in men and younger women may have salutary effects on skeletal health, especially cortical bone health, that has not been previously recognized.&quot;&lt;/p&gt;
&lt;p&gt;Another study by the same group published last year in the &lt;em&gt;American Journal of Clinical Nutrition&lt;/em&gt; found that moderate consumption of alcohol, including beer, wine, and liquor, was associated with higher bone mineral density in men and postmenopausal women.&lt;/p&gt;
&lt;p&gt;However, it also showed that men who drank too much liquor were more likely to have lower spine and hip bone mineral density.&lt;/p&gt;
&lt;p&gt;The relationship between beer and bone mineral density appeared to be mediated by silicon, the researchers concluded.&lt;/p&gt;
&lt;p&gt;Bottom line: considering the increased fracture risk and the various other problems associated with drinking too much alcohol, experts agree that guzzling beer is not strategy for improving bone health.&lt;/p&gt;
&lt;p&gt;&quot;In the absence of bone density values or preferably fracture incidence, it would be premature to tout beer as a preventative or treatment,&quot; Richardson said.&lt;/p&gt;
&lt;p&gt;David Katz, MD, MPH, of the Yale School of Public Health, agreed.&lt;/p&gt;
&lt;p&gt;&quot;This is NOT a reason to drink beer,&quot; he said in an e-mail. &quot;This is simply a bit of good news for those who do drink beer already  --  yours truly among them!&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The authors did not make any financial disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;&lt;p&gt;&lt;em&gt;This article was developed in collaboration with ABC News. &lt;/em&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; alt=&quot;&quot;&gt;&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_428"
                     title="Blocking Serotonin in Gut Reverses Osteoporosis in Mice (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Endocrinology/Osteoporosis/tb/18346?impressionId=1265786337595"
                     
      &lt;p&gt;Blocking serotonin production in the intestine might help restore lost bone mass, rather than just preventing further loss like most current osteoporosis treatments, an animal study suggested.&lt;/p&gt;
&lt;p&gt;Once daily treatment with a novel serotonin inhibitor prevented development of osteoporosis and also fully reversed existing low bone mass in mice, according Gerard Karsenty, MD, PhD, of Columbia University in New York City, and colleagues.&lt;/p&gt;
&lt;p&gt;These proof-of-principle findings came without any impact on serotonin levels in the brain, the researchers reported in the Feb. 7 issue of &lt;em&gt;Nature Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Just two years ago, Karsenty&apos;s group discovered that the vast majority of serotonin in the body acts to regulate bone formation.&lt;/p&gt;
&lt;p&gt;Only 5% plays the chemical&apos;s better-known role as a brain neurotransmitter. The rest comes from the gut for circulation below the blood-brain barrier which, in this regard, Karsenty called &quot;more hermetic than the Berlin Wall was.&quot;&lt;/p&gt;
&lt;p&gt;So the gut treatment is unlikely to affect mood and other critical functions serotonin plays in the brain, he emphasized in an interview. But he acknowledged that much more proof is needed on the way to the clinic.&lt;/p&gt;
&lt;p&gt;The tip-off to bone effects of serum serotonin came from a group of patients with a syndrome that produced high bone mass when they were into their 60s.&lt;/p&gt;
&lt;p&gt;Usually, bone destruction outpaces formation after menopause, eventually leading to osteoporosis. But something different was happening in these patients, who never developed the condition.&lt;/p&gt;
&lt;p&gt;&quot;The only cause we could find was that it was due to a decrease in the synthesis of serotonin in the gut,&quot; Karsenty told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;After their initial experiments showed serotonin did indeed boost the pace of bone formation, the researchers found that a biotech company had already developed a compound that would reduce gut synthesis of the hormone. It had been tested in women with irritable bowel syndrome.&lt;/p&gt;
&lt;p&gt;So Karsenty&apos;s group examined its effects on bone in mice and found a dose-dependent reduction in serum serotonin.&lt;/p&gt;
&lt;p&gt;Mice that got 250 mg/kg body weight per day of this compound  --  known as LP533401, a small molecule inhibitor of Tph1, the initial enzyme in gut serotonin synthesis  --  produced 30% less serotonin than controls, without a change in brain serotonin levels.&lt;/p&gt;
&lt;p&gt;Then the researchers tested the compound on mice whose ovaries had been excised to simulate the dramatic drop-off in hormones women experience after menopause. That condition, in turn, leads to an imbalance in bone resorption versus formation.&lt;/p&gt;
&lt;p&gt;Mice given the experimental drug at doses up to 10 mg/kg, starting the day after surgery, had elevated bone resorption but maintained higher bone mass than those that got placebo. The placebo group all developed osteopenia.&lt;/p&gt;
&lt;p&gt;Treated mice had a &quot;major&quot; increase in bone formation markers, including osteoblast numbers, bone formation rate, and osteocalcin serum levels. But again, brain serotonin remained unaffected.&lt;/p&gt;
&lt;p&gt;These benefits were achieved with a modest, roughly 30% reduction in serum serotonin  --  which appeared to be the threshold beyond which skeletal response increased only marginally.&lt;/p&gt;
&lt;p&gt;Some mice were left untreated for two weeks  --  &quot;a long time for a rodent,&quot; Karsenty noted  --  to develop osteopenia. Subsequently treated with a daily 250 mg/kg dose of LP533401, they had such an increase in bone formation over four weeks that it normalized their bone mass, the researchers noted.&lt;/p&gt;
&lt;p&gt;The same thing happened when researchers began treatment even longer after surgery, six or 12 weeks, when bone loss was already severe. Bone mass rose with serotonin inhibition in the vertebrae and long bones, but without a change in bone length or width.&lt;/p&gt;
&lt;p&gt;Nor were there effects on platelets, coagulation, or the GI tract with regard to the key measures of transit, colonic mobility, and gastric emptying.&lt;/p&gt;
&lt;p&gt;Serotonin inhibition in the gut as a potential anabolic treatment for osteopenia and osteoporosis appeared to work as well as the only currently available treatment that can increase bone formation sufficiently to compensate for the increased resorption caused by menopause  --  parathyroid hormone injections.&lt;/p&gt;
&lt;p&gt;Since serum serotonin inhibitors could be given in pill form, this pathway is much more attractive, Karsenty said.&lt;/p&gt;
&lt;p&gt;The specific agent used in this trial was designed for proof-of-principle and wouldn&apos;t necessarily be what is developed for clinical use, he cautioned.&lt;/p&gt;
&lt;p&gt;&quot;Although the data presented here are promising we remain fully aware that, since rodents do not remodel bones as much as humans do, our results will have to be confirmed in other species,&quot; the researchers also warned in the paper.&lt;/p&gt;
&lt;p&gt;Karsenty said the group plans to continue animal model studies for the time being, with no plans to move into clinical trials.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by grants from the National Institutes of Health and a Gideon and Sevgi Rodan fellowship from the International Bone and Mineral Society.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest or industry involvement in the study.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_352"
                     title="ICAO: Future Chronic Disease Risk Goes Beyond BMI (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Endocrinology/Diabetes/tb/18233?impressionId=1265786337595"
                     
      When it comes to predicting chronic disease, body mass index doesn&apos;t tell the whole story, according to a population-based study that found elevated risk with obesity and other metabolic risk factors independently.&lt;br&gt;
&lt;br&gt;Metabolically-healthy obese people tended toward being at least twice as likely to develop multiple metabolic risk factors and diabetes as healthy, normal weight individuals over the subsequent 3.5 years of a study led by Sarah Appleton, a postgraduate student at the University of Adelaide, Australia.&lt;br&gt;
&lt;br&gt;However, normal weight individuals with metabolic risk factors  --  a group the researchers called &quot;metabolically obese&quot;  --  were at greater risk, she told attendees at the International Congress on Abdominal Obesity in Hong Kong, a conference sponsored by the International Chair on Cardiometabolic Risk.&lt;br&gt;
&lt;br&gt;Overall, just 4.1% of the 3,743 adults in the population-based, North West Adelaide Health Study were in the normal body mass index range at baseline but had at least two of the following metabolic risk factors:&lt;ul&gt; &lt;li&gt;Triglyceride levels of 1.7 mmol/L or greater&lt;/li&gt; &lt;li&gt;HDL cholesterol under 1.0mmol/L for men or 1.3 mmol/L for women&lt;/li&gt; &lt;li&gt;Blood pressure of 130/85 mm Hg or higher&lt;/li&gt; &lt;li&gt;A fasting plasma glucose of at least 5.6mmol/L or self-reported diabetes&lt;/li&gt; &lt;li&gt;Treatment for any of these disorders &lt;/li&gt; &lt;/ul&gt;
&lt;p&gt;Although free of cardiovascular disease when they entered the study through a random population sample of the northwest region of Adelaide, after a mean of 3.5 years of follow-up, this group was 2.48 times at risk of incident cardiovascular disease or stroke events (95% CI 1.1 to 5.4).&lt;/p&gt;
&lt;p&gt;Compared with metabolically-healthy, normal weight individuals, those with metabolic risk factors tended to be&lt;strong&gt; &lt;/strong&gt;3.27 times as likely to develop diabetes (&lt;em&gt;P&lt;/em&gt;=0.07).&lt;/p&gt;
&lt;p&gt;Identifying these individuals for prevention efforts may require less emphasis on BMI and increased surveillance of central obesity in primary care, the researchers told the congress.&lt;/p&gt;
&lt;p&gt;&quot;The problem with BMI is it doesn&apos;t tell you where the fat is,&quot; Appleton added in an interview. &quot;Visceral fat is really bad for you.&quot;&lt;/p&gt;
&lt;p&gt;Obese individuals without multiple metabolic risk factors at baseline comprised a larger group (12.1%).&lt;/p&gt;
&lt;p&gt;They were more likely to be middle age, live in a disadvantaged neighborhood, have smoked at some point, and get less exercise than their metabolically similar, but slimmer peers.&lt;/p&gt;
&lt;p&gt;Over the subsequent 3.5 years, they were 2.82 times more likely to develop more than one metabolic risk factor than metabolically-healthy, normal weight individuals (95% CI 2.0 to 4.0).&lt;/p&gt;
&lt;p&gt;The metabolically-normal obese also tended to be 2.36 times more likely to develop diabetes (95% CI 0.8 to 7.1). On the other hand, their risk of cardiovascular disease wasn&apos;t elevated, &quot;which likely related to the younger age of that group,&quot; Appleton told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Notably, abdominal obesity as determined by a waist circumference of 80 cm and over for men or 95 cm and greater for women was 6.1 times more likely among metabolically healthy individuals if their BMI was in the obese versus normal range.&lt;/p&gt;
&lt;p&gt;But those who were in the normal BMI range were 2.2-fold more likely to be overweight or obese according to waist circumference if they had metabolic risk factors, which was statistically significant as well and likely contributed to the health risks they faced over the short-term future, Appleton said.&lt;/p&gt;
&lt;p&gt;Maintenance of metabolic health in the obese population was more likely for younger individuals (OR 2.83 for age 40 or younger, 95% CI 1.1 to 7.6) and those who were at least moderately physically active (OR 2.04, 95% CI 1.01 to 4.1).&lt;/p&gt;
&lt;p&gt;Appleton noted that these findings generally fit with data from the U.S. National Health Assessment Survey and Examination.&lt;/p&gt;
&lt;p&gt;Regardless of whether patients have abdominal obesity, BMI obesity, or other metabolic risk factors, the solution is likely similar  --  improved diet and exercise, she said.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the University of Adelaide and the South Australian Department of Health.&lt;/p&gt;&lt;p&gt;Appleton reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_207"
                     title="ISET: Women Fare Better in Small Leg Vessel Procedures (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/Cardiology/PeripheralArteryDisease/tb/18051?impressionId=1265786337595"
                     
      &lt;p&gt;HOLLYWOOD, Fla.  --  Contrary to expectations, women who undergo last-ditch, minimally-invasive procedures to open small blood vessels in the leg  --  and forestall amputation  --  generally have better outcomes than men, researchers reported here.&lt;/p&gt;
&lt;p&gt;Overall, 87.5% of women who underwent the infragenicular endoscopic angioplasty avoided amputation for at least two years, compared with 82.9% of the men who were similarly treated (&lt;em&gt;P&lt;/em&gt;=0.041), according to Tejas Shah, MD, of Mount Sinai Medical Center in New York City.&lt;/p&gt;
&lt;p&gt;&quot;This study is the first to compare the outcomes of men and women being treated for blocked lower-leg arteries with endovascular therapy,&quot; Shah said at the International Symposium on Endovascular Therapy (ISET). &quot;The results suggest endovascular therapy should be strongly considered in women with blocked arteries below the knee.&quot;&lt;/p&gt;
&lt;p&gt;In many endovascular procedures, women tend to do worse then men, generally because they tend to have smaller blood vessels. But in this study, involving the smallest leg blood vessels, the opposite occurred. &quot;We really don&apos;t have any good reason why there should be this gender difference,&quot; Shah said.&lt;/p&gt;
&lt;p&gt;&quot;What made this difference significant,&quot; Shah told &lt;em&gt;MedPage Today&lt;/em&gt;, &quot;was that the women in the study, overall, were at significantly greater risk of amputation than the male patients.&quot; He said that about 22.3% of men underwent treatment for claudication, compared with 12.3% of the women, but 77.7% of men were being treated for limb-threatening conditions compared with 87.7% of women.&lt;/p&gt;
&lt;p&gt;The retrospective study involved review of angioplasties, stenting, and atherectomies performed on 152 men and 125 women at Mount Sinai between July 1999 and November 2009.&lt;/p&gt;
&lt;p&gt;When adjusted for comorbidities, women treated for tibial lesions with concurrent proximal disease had higher 24-month primary patency rates compared with men.&lt;/p&gt;
&lt;p&gt;Some 46% of treated leg arteries in women remained open, compared with 30% (&lt;em&gt;P&lt;/em&gt;=0.016) in men. Shah said that a subanalysis of isolated tibial lesions indicated that 50% of women achieved 24-month primary patency rates, compared with 28.8% of men (&lt;em&gt;P&lt;/em&gt; =0.002).&lt;/p&gt;
&lt;p&gt;On the downside, women experienced higher rates of blood clots forming at the access site of the treatment (9% versus 0.6%, &lt;em&gt;P&lt;/em&gt;&amp;lt;.0001). Clotting, typically treated with blood thinners, may require a longer stay in the hospital (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;&quot;In both men and women it is hard to keep these smaller leg blood vessels open,&quot; said Constantino Pe&amp;#241;a, MD, medical director of vascular imaging at Baptist Cardiac &amp;amp; Vascular Institute, Miami.&lt;/p&gt;
&lt;p&gt;&quot;It might be possible that women do better because of their hormone status. But we need to do prospective clinical trials to see if we can determine what factor is involved in making the procedure work better for women.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Shah listed no relevant disclosures.  Pe&amp;#241;a reported financial relationships with Bard and Medtronic.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_2943"
                     title="ASBMR: Novel Osteoporosis Drug Promising in Early Study (CME/CE)"
                     score="-0.006"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASBMR/tb/16027?impressionId=1265786337595"
                     
      &lt;p&gt;DENVER  --  Another calcium sensing receptor (CaSR) antagonist has shown promise as an osteoporosis treatment in an early clinical study, but skeptics wondered whether it will ultimately succeed where an earlier effort in this direction failed.&lt;/p&gt;
&lt;p&gt;JTT-305, under development by Japan Tobacco, significantly increased lumbar spine bone density in a 12-week trial while showing favorable effects on markers of bone formation and resorption, according to Seiji Fukumoto, MD, of the University of Tokyo.&lt;/p&gt;
&lt;p&gt;Fukumoto reported the findings here at the American Society for Bone and Mineral Research&apos;s annual meeting.&lt;/p&gt;
&lt;p&gt;But Lorraine Fitzpatrick, MD, a researcher at a competing firm who led clinical development of a CaSR antagonist that failed in phase II testing, said the results suggested JTT-305 might have its own problems.&lt;/p&gt;
&lt;p&gt;The CaSR mediates release of parathyroid hormone, a critical player in bone dynamics. One current drug, teriparatide (Forteo), mimics the effects of parathyroid hormone to increase bone formation and density directly, while most other osteoporosis drugs, such as bisphosphonates, work by inhibiting resorption.&lt;/p&gt;
&lt;p&gt;Some researchers believe that inhibiting the CaSR will increase natural parathyroid hormone output to achieve the same effect as teriparatide. Where teriparatide is a recombinant peptide that requires a daily injection, the CaSR can be antagonized with orally active small molecules  --  including JTT-305.&lt;/p&gt;
&lt;p&gt;Fukumoto&apos;s study tested two doses of the drug against placebo for 12 weeks in 154 postmenopausal women with osteoporosis, average age 66, in a randomized, single-blind fashion.&lt;/p&gt;
&lt;p&gt;Baseline lumbar spine T scores ranged from -3.1 to -3.2 among the three treatment groups.&lt;/p&gt;
&lt;p&gt;The marquee result was that lumbar bone mineral density (BMD) increased 2.35% in the patients taking 10 mg/day of JTT-305, a major improvement in just three months of treatment.&lt;/p&gt;
&lt;p&gt;Patients in the placebo group saw an increase of 0.90% (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05). A 20-mg dose of the drug led to a mean lumbar BMD increase of 1.80% (not significant versus placebo).&lt;/p&gt;
&lt;p&gt;The study did not measure fracture rates or effects on BMD at other sites such as the hip or wrist.&lt;/p&gt;
&lt;p&gt;Biomarkers of bone turnover, including collagen-associated peptides (NTX in urine and CTX and PINP in serum) as well as osteocalcin, indicated significant favorable effects for JTT-305 relative to placebo and to baseline.&lt;/p&gt;
&lt;p&gt;Unlike the lumbar BMD results, though, the higher dose generally had the more powerful impact on these markers.&lt;/p&gt;
&lt;p&gt;The downside for JTT-305 was that it led to significant, dose-dependent increases in corrected serum calcium relative to placebo.&lt;/p&gt;
&lt;p&gt;At week 12, mean corrected calcium levels were about 10.5 mg/dL in the 20-mg group and 10.1 mg/dL with the 10-mg dose. Calcium levels in the placebo group remained steady at 9.4 mg/dL. The normal range for serum calcium is 8.4 to 10.2 mg/dL.&lt;/p&gt;
&lt;p&gt;An earlier study in healthy postmenopausal women had shown that marked increases in parathyroid hormone seen after dosing persisted for about six hours, creating a &quot;shoulder&quot; in the concentration-time curve.&lt;/p&gt;
&lt;p&gt;Such a profile, along with the heightened serum calcium, suggested mild hyperparathyroidism, said Fitzpatrick, a senior researcher at GlaxoSmithKline.&lt;/p&gt;
&lt;p&gt;Fitzpatrick led clinical studies of a CaSR antagonist called ronacaleret, co-developed by GlaxoSmithKline and NPS Pharmaceuticals, for which favorable early-stage results were reported at ASBMR&apos;s 2008 meeting. (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ASBMR/10931&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ASBMR/10931&quot; target=&quot;_blank&quot;&gt;ASBMR: Old Idea for Keeping Osteoporosis in Check Gets New Airing&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;But two weeks later after those presentations, the company said it was terminating an ongoing phase II study and cancelling further development of the drug, citing lack of efficacy.&lt;/p&gt;
&lt;p&gt;Fitzpatrick provided a postmortem on ronacaleret in two presentations here preceding Fukumoto&apos;s.&lt;/p&gt;
&lt;p&gt;The drug had shown modest but significant efficacy in increasing lumbar spine BMD, but total hip BMD decreased, she said. Serum calcium levels had also increased, and parathyroid hormone was persistently elevated, similar to what Fukumoto reported for JTT-305.&lt;/p&gt;
&lt;p&gt;The combination of mild hyperparathyroidism and limited efficacy killed the drug, she said.&lt;/p&gt;
&lt;p&gt;In an interview after the presentations, Fitzpatrick said a narrow therapeutic index was probably a class effect for CaSR antagonists.&lt;/p&gt;
&lt;p&gt;&quot;The question is, can they get the dose low enough to miss [the parathyroid hormone shoulder], to get the anabolic effect or not?&quot;&lt;/p&gt;
&lt;p&gt;Noting that osteoporosis is not directly life-threatening and that other drugs are available, she said it could be difficult for products with a narrow therapeutic index to gain approval.&lt;/p&gt;
&lt;p&gt;The challenge for Japan Tobacco, she added, is to &quot;tweak the drug to make it behave just the way they want it&lt;strong&gt; &lt;/strong&gt;to.&quot;&lt;/p&gt;
&lt;p&gt;Fukumoto characterized the results as &quot;promising,&quot; adding that &quot;further study is necessary to prove the long-term efficacy,&quot; both for BMD and for reducing fracture rates.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The JTT-305 study was funded by Japan Tobacco.&lt;/p&gt;&lt;p&gt;Fukumoto reported a consulting relationship with Japan Tobacco. Other researchers on the study were Japan Tobacco employees.&lt;/p&gt;&lt;p&gt;Fitzpatrick is an employee of GlaxoSmithKline.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>