Beta Blockers May Lessen Risperidone-Induced Bone Loss
A recent mouse study has shown that beta blockers could reduce bone loss caused by the atypical antipsychotic (AA) drug risperidone (RIS). The study was published recently in Endocrinology.
Researchers led by Katherine J. Motyl, PhD, of the Maine Medical Center Research Institute in Scarborough, and Karen L. Houseknecht, PhD, of the University of New England in Biddeford, pointed out that clinical data has shown that AA drugs “are associated with significant side effects, including obesity, hyperglycemia, and dyslipidemia,” as well as causing an increased risk in fracture risk and bone loss. Therefore, schizophrenic patients have a higher risk of fractures than the general population.
Motyl and her team wrote that “the pharmacology underlying the adverse effects on bone is unknown,” but they theorized that the central nervous system could be the culprit, since the sympathetic nervous system (SNS) “is known to uncouple bone remodeling” and RIS treatment in mice eroded bone and reduced bone formation. “Even a single dose of RIS transiently elevated expression of brown adipose tissue markers of SNS activity and thermogenesis, Pgc1a and Ucp1,” they wrote.
The researchers administered RIS or a vehicle to eightweek-old female mice that were also receiving the nonselective betablocker propranolol to test their theory. They found that RIS did not erode bone or hinder bone formation or cause any changes in bone volume. “Furthermore,” the authors wrote, “β2-adrenergic receptor null (Adrb2-/-) mice were also protected from RIS-induced bone loss.”
This is the first time RIS has been linked to SNSmediated bone loss, and the authors concluded that bone loss could be attenuated by betablockers. “Because AA medications are widely prescribed,” they wrote, “especially to young adults, clinical studies are needed to assess whether β-blockers will prevent bone loss in this vulnerable population.”
Testosterone Therapy Fails to Treat Ejaculatory Dysfunction
Men who have ejaculatory disorders and low testosterone levels did not experience improved sexual function after undergoing testosterone replacement therapy, according to a new study published in the Journal of Clinical Endocrinology & Metabolism. Researchers led by Darius A. Paduch, MD, PhD, of NewYork-Presbyterian Hospital and Weill Cornell Medical Center in New York, N.Y., conducted a multi-center, double-blind, randomized, placebo-controlled, 16-week trial, in which 76 men with ejaculatory dysfunction were assigned to receive either a 2% testosterone solution applied on the skin or a placebo. Sixty-six men completed the study. The men were all age 26 years or older with total testosterone levels of less than 300 ng/ dL found on two separate tests.
During the study, participants had their testosterone levels measured periodically to determine how well the hormone replacement therapy was working. To gauge ejaculatory function, researchers collected semen samples and had participants complete sexual health questionnaires and logs.
Although the men who received testosterone replacement therapy had higher scores on the Men’s Sexual Health Questionnaire on ejaculatory dysfunction than the men who took the placebo, the difference was too small to be statistically significant. The researchers also found little to no improvement in ejaculate volume or orgasmic function.
“This is the first clinical trial examining the treatment of a very common but poorly understood condition that affects men’s physical health as well as their interpersonal relationships,” Paduch says. “Although the participants in this study did not experience any significant improvement in ejaculatory function, we hope our work will spur the development of additional clinical trials to find treatments for this condition.”
“Our findings suggest physicians who are treating men with ejaculatory dysfunction should be cautious about prescribing testosterone therapy on an off-label basis,” said another of the study’s authors, Shehzad Basaria, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass. “More research is needed to determine whether a longer course of testosterone therapy or other treatment options can benefit men with ejaculatory dysfunction.”
Food Order Found to Have Significant
Impact on Glucose and Insulin Levels
Eating protein and vegetables before carbohydrates leads to lower postmeal glucose and insulin levels in obese patients with type 2 diabetes (T2D), according to a study published recently in Diabetes Care. This research could impact the way clinicians advise diabetic patients and other high-risk individuals to eat, focusing not only on how much but also on when carbohydrates are consumed.
Researchers led by Louis Aronne, MD, of Weill Cornell Medical College in New York, N.Y., looked to validate and advance previous research that showed eating vegetables or protein before carbohydrates leads to lower post-meal glucose levels. This time, though, investigators looked at a whole, typically Western meal, with a good mix of vegetables, protein, carbohydrates, and fat.
“We’re always looking for ways to help people with diabetes lower their blood sugar,” Aronne says. “We rely on medicine, but diet is an important part of this process, too. Unfortunately, we’ve found that it’s difficult to get people to change their eating habits.”
“Carbohydrates raise blood sugar, but if you tell someone not to eat them — or to drastically cut back — it’s hard for them to comply,” Aronne continues. “This study points to an easier way that patients might lower their blood sugar and insulin levels.”
The researchers worked with 11 patients, all of whom are obese and have T2D, and take metformin. To see how food order impacted post-meal glucose levels, they had the patients eat a meal, consisting of carbohydrates (ciabatta bread and orange juice), protein, vegetables, and fat (chicken breast, lettuce, and tomato salad with low-fat dressing and steamed broccoli with butter) twice, on separate days a week apart.
On the day of their first meal, researchers collected a fasting glucose level in the morning, 12 hours after the patients last ate. The participants were then instructed to eat their carbohydrates first, followed 15 minutes later by the protein, vegetables, and fat. The scientists then checked the patients’ post-meal glucose levels via blood tests at 30-, 60-, and 120-minute intervals. A week later, researchers again checked the patients’ fasting glucose levels and then had them eat the same meal, but with the food order reversed: protein, vegetables, and fat first, followed 15 minutes later by the carbohydrates. The same post-meal glucose levels were then collected.
The results showed that glucose levels were much lower at the 30-, 60-, and 120-minute checks — by about 29%, 37%, and 17%, respectively — when vegetables and protein were eaten before the carbohydrates. Insulin was also significantly lower when protein and vegetables were eaten first. This finding confirms that the order in which we eat food matters and points to a new way to effectively control post-meal glucose levels in diabetic patients.
“Based on this finding, instead of saying ‘don’t eat that’ to their patients, clinicians might instead say, ‘eat this before that,’” Aronne says. “While we need to do some follow-up work, based on this finding, patients with type 2 might be able to make a simple change to lower their blood sugar throughout the day, decrease how much insulin they need to take, and potentially have a long-lasting, positive impact on their health.”
Bariatric Surgery Linked to Bone Loss
Bariatric surgery may be associated with bone loss that could lead to fracture, according to a study recently published in Obesity.
Researchers led by Sangeeta R. Kashyap, MD, of the Cleveland Clinic in Ohio, studied two-year outcomes of patients with type 2 diabetes in the STAMPEDE trial who underwent Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or intensive medical therapy (IMT). They looked at the respective treatments’ effects on lean body mass, total bone mass, and bone mineral density (BMD) measures. Kashyap and her team previously studied the impact of bariatric surgery on diabetes remission.
The authors noted that some studies have an increased fracture risk in patients with type 2 diabetes (T2D), but the fracture risk in obese patients with T2D who undergo bariatric surgery are not well depicted. “Reduction in BMD attributed to surgically induced weight loss has been reported in severely obese postbariatric subjects;” they wrote, “many additional factors contribute to the impact on bone health, including adipokines, menopause status, medication usage such as proton pump inhibitors/tzds, and smoking.”
The researchers analyzed 54 participants with T2D who were randomized to IMT, RYGB, or SG and underwent dual-energy X-ray absorptiometry (DXA) at baseline. At two years, the RYGB and SG patients showed a greater reduction in BMI than the IMT patients. The surgical cohort also showed greater reductions in lean mass (~10%), total bone mineral content (~8%), and hip BMD (~9%) than the IMT group. “The change in hip BMD correlated to weight loss (r = 0.84, p < 0.0001), and changes in lean mass (r = 0.74, p < 0.0001), and leptin (r = 0.53, p > 0.0001). Peripheral fractures were self-reported in RYGB (4/18 patients), SG (2/19 patients) and the IMT (4/16 patients),” the authors wrote.
Kashyap and her team concluded that surgically induced weight loss is linked to modest reductions in lean mass, bone mineral content, and BMD, despite calcium and vitamin D supplements taken by obese T2D patients at two years following surgery. “In addition,” they wrote, “vigilance for on-going nutritional deficiencies and bone loss in patients before and after bariatric surgery, especially sleeve gastrectomy, is critical.”
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