July 12-15, 2017
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October 11-14, 2017
Caribe Royale Orlando, Florida

MEDS eNews

Vol. 3 No. 18

Boost in public awareness urged
by expert in skeletal-health issues

SOUTHBURY, CONN. – Public awareness of skeletal health’s urgency needs an upgrade.

That’s the assertion of an osteoporosis expert who says health-care professionals---notably physician assistants (PAs) and nurse practitioners (NPs)---and, hopefully, a celebrity or two, can help open a larger window into the importance of bone issues.

Rick Pope, (PA)-C, Department of Rheumatology, Western Connecticut Medical Group, Danbury, Conn., says NPs and PAs “can reach out to patients” to battle “under-recognition and under-treatment.”

Pope, a Southbury, Conn., resident, founder and past three-time president of the Society of Physician Assistants in Rheumatology (SPAR), and faculty member of the Metabolic & Endocrine Disease Summit (MEDS) says skeletal health is among “the last things primary-care providers discuss with patients. Weight, exercise, the need for older patients to stop smoking, not to drink excessively, come up instead. Practitioners don’t put osteoporosis high up on their list, even though it is now easier to manage with bone density and meds.”

He sees the need for “a pre-eminent leader in some area” to increase awareness, noting, for instance, actress Sally Field, who publicized her battle with osteoporosis.

“We need money to be made available to promote awareness, via Facebook, PBS, social media. We need more awareness that poor skeletal health can kill you. It leads to a downward spiral. It’s an older person’s nightmare.”

One such nightmare, the most common fracture among osteoporosis patients, is that of vertebral compression fractures (VCFs). Pope says systematic VCF management lends itself to “four tenants”:

  • provide bed rest for most severe pain for a short period of time
  • pharmacological solutions such as acetaminophen and opioids. Regarding the latter, Pope notes that medical practitioners are “more cautious” with these because of side effects and increased fall risk. He suggests milder ones, and, for those with codeine, such precautions as using them at certain times of day
  • posture support (such as braces)
  • physical therapy

Regarding VCFs, Pope agrees with an International Osteoporosis Foundation (IOF) review of balloon kyphoplasty and vertebroplasty (both involving placement of cement into a fractured vertebra) in managing VCFs.

The IOF noted that the “long-term risks of subsequent vertebral fractures have not been clearly demonstrated and further prospective randomized studies are needed with standards for reporting.” Pope sees a need for more randomized studies about both cementing procedures and says he has seen “the pendulum swing for these procedures, first a downward spiral then an upward swing. We need more studies to show what they mean for patients.”

The cases of two of Pope’s patients bear this out:

  • A 62-year-old retired nurse with aggressive rheumatoid arthritis who became heavy and less mobile from prednisone. She experienced bladder dysfunction and eventually underwent vertebroplasty, after which she voided 800-to-1,000 ccs. “She needed this procedure,” Pope concludes.
  • An 85-year-old woman with post-menopausal osteoporosis as well as scoliosis, who then developed severe acute back pain. She has co-morbidities of diabetes, hypertension and heart disease. Surgery was ruled out; however, there was another treatment possibility, an injection of salmon calcitonin, which was rejected due to its cost. Instead, she received physical therapy at home, plus acetaminophen. (Pope adds in hindsight that he should have considered calcitonin nasal spray, which would have likely been less expensive and approved by insurance)

Pope concurs with a conclusion of a study published this year in the Global Spine Journal that there is a lack of standard of care for osteoporotic VCF patients along with treatment recommendations, including a comment that most American Academy of Orthopedic Surgeons (AAOS) clinical-practice guidelines on the issue are weak or inconclusive.

“Further studies,” he says, “are needed to clarify when surgery is needed: 12-and-24-month-and-longer, high-level studies.”

Also needed is medical help like that offered in two drugs he mentions.

One, involving sclerostin-antibody treatment for osteoporosis and developed by Amgen, is not yet on the market, while another, from Radius Health Inc., is Tymlos, an injection for the treatment of post-menopausal women with osteoporosis who are at high-fracture risk, which received Food and Drug Administration (FDA) approval this year.

“There is a great variety of approaches to medical management, and now these two surgical procedures for VCFs are making a comeback,” Pope concludes. “It depends largely on the situation with the orthopedic surgeon or interventionalist in the local community.”

CITATION: Ivo K. Genev, Matthew K. Tobin, et. al. Spinal Compression Fracture Management. A Review of Current Treatment Strategies and Possible Future Avenues. Global Spine Journal. 2017 Feb; 7(1): 71–82. Published online 2017 Feb. 1. PMCID: PMC5400164. PMCID: PMC5400164. Borgström F1, Olafsson G, et. al. The impact of different health dimensions on overall quality of life related to kyphoplasty and non-surgical management. Osteoporosis International. 2013 Jul;24(7):1991-9. Epub 2013 Apr 27.  Boonen, S., Wahl, D.A., et. al. Balloon kyphoplasty and vertebroplasty in the management of vertebral compression fractures. Osteoporosis International. 2011. 22:2915.

Research on lesions indicates
the possibility of misdiagnosis

NEW YORK – Lesions with follicular lesion of undetermined significance-like or oncocytic features are prone to misdiagnosis, according to a study published in June in Cancer Cytopathology.

The study---whose authors include Margaret Cho and Thaira Oweity, New York University Langone Medical Center, New York---identified distinct cytologic patterns in parathyroid lesions suggestive of parathyroid origin, which, together with parathyroid hormone (PTH) immunostains or assay, molecular studies, or sestamibi scans, aid in distinguishing parathyroid from thyroid lesions. 

The researchers noted that differentiating parathyroid and thyroid lesions can be challenging because of considerable morphologic overlap and anatomic proximity, and set out to identify characteristic morphologic patterns and useful adjunct tests to distinguish these two entities.

A data-base search was conducted for clinically-indeterminate thyroid nodules from 2000 through 2016, with an emphasis on confirmed parathyroid nodules.

Pathology reports, slides, ancillary studies, molecular analysis, and clinical-and-radiologic data were retrieved.

A total of 143 cases of clinically-indeterminate thyroid nodules were identified; 34 were confirmed parathyroid nodules.

Three cytologic patterns were identified:

  • oncocytic cell pattern (nine cases, 26%)
  • follicular lesion of undetermined significance-like/papillary-like pattern (14 cases, 41%)
  • non-specific endocrine cell clusters (11 cases, 32%)

Bare oval nuclei (100%), nuclear overlap (88%), crowded sheets (88%), and intracytoplasmic vacuoles (62%) were observed.

Ten cases (29%) demonstrated positive immunostaining for PTH; seven (21%) demonstrated a positive PTH assay; and nine (26%) had PTH detected by ThyroSeq v.2.

The remaining eight cases were morphologically either indeterminate or suggestive of parathyroid origin.

The cytologic diagnosis was confirmed clinically (20 cases) or surgically (14 cases). Based on cytology alone, eight cases were initially diagnosed as thyroid tissue and amended to parathyroid lesion after ancillary studies were performed, including five cases based on ThyroSeq v.2 results alone.


CITATION: Margaret Cho MD, Thaira Oweity MD, et. al. Distinguishing parathyroid and thyroid lesions on ultrasound-guided fine-needle aspiration: A correlation of clinical data, ancillary studies, and molecular analysis. Cancer Cytopathology. First published: 16 June 2017. Version of record online: 16 June 2017. Manuscript Accepted: 16 May 2017. Manuscript Revised: 12 May 2017. Manuscript Received: 28 April 2017.



Study shows increased CVD risk
is associated with hypoglycemia

WORCESTER, MASS. – A recent study provides evidence of increased cardiovascular-disease (CVD) risk associated with hypoglycemia---especially serious hypoglycemia events.

The study published in May in Diabetes, Obesity and Metabolism indicates that while associations were attenuated with non-serious hypoglycemia, the results suggested a potential increased risk.

Its authors, including Kristy Iglay, University of Massachusetts Medical School, Worcester, Mass., noted that certain treatments for type 2 diabetes mellitus cause hypoglycemia and weight gain, and thus might counteract the benefits of intensive glucose control.

The researchers quantified the association of CVD outcomes with hypoglycemia and weight gain among type 2 diabetes patients treated with sulfonylureas.

The cohort study included patients from January, 2009, through December, 2014, identified within a de-identified nationwide electronic-health records repository, including multiple-provider networks and electronic-medical records systems.

Hypoglycemia measures from structured data fields and free-text clinical notes were categorized as serious or non-serious.

Covariate adjusted Poisson regression analysis was used to assess the association between the frequency of hypoglycemia (by severity), or magnitude of weight change, and incidence of acute myocardial infarction (AMI), congestive heart failure (CHF), and stroke.

Among 143,635 eligible patients, the researchers observed:

  • 5,669 cases of AMI
  • 14,109 incident cases of CHF
  • 7,017 strokes

Overall incidence rates were 1.53, 4.26, and 1.92 per 100 person-years for AMI, CHF, and stroke, respectively.

The associations between overall hypoglycemia and each of the CVD outcomes were positive, with stronger associations observed for serious hypoglycemia and attenuated or null associations observed for non-serious hypoglycemia.

Weight change exhibited a U-shaped association with increased risks associated with both weight loss and weight gain relative to stable weight.

CITATION: Anthony P. Nunes Ph.D., Kristy Iglay Ph.D., et. al. Hypoglycaemia seriousness and weight gain as determinants of cardiovascular disease outcomes among sulfonylurea users. Diabetes, Obesity and Metabolism. Accepted manuscript online: 12 May 2017. Manuscript accepted: 30 April 2017. Manuscript revised: 28 April 2017. Manuscript received 9 January 2017.

Lower danger of mortality seen
for overweight diabetes patients

BEIJING – A meta-analysis of 20 studies involving more than 250,000 patients showed a significantly lower risk of all-cause mortality in overweight patients with diabetes compared to normal-weight patients.

The study published in June in the Journal of Diabetes Investigation also indicates that the survival benefits of obesity were only observed among elderly patients.

Its authors---including Fei Gao and Zhi Jian Wang, who are affiliated with An Zhen Hospital, Capital Medical University, Beijing---report that the more-pronounced beneficial prognostic impact of obesity was attenuated with longer follow-up durations.

The researchers also note that caution should be taken in interpreting the results, as the study’s design didn’t permit verification of the causal relationship between body weight and prognosis in patients with diabetes, and urged further studies.

Their assessment included searches of the OVID/MEDLINE, EMBASE and Cochrane data-bases for all reported studies investigating the relationship between body mass index (BMI) and mortality in diabetes patients.
Summary estimates of hazard ratios (HRs) were obtained with a random-effects model; univariate meta-regressions were carried out.

A total of 20 studies including 250,016 patients with diabetes were identified. The results of the present study showed a significantly reduced risk of all-cause mortality as compared to normal-weight patients.

The survival benefits of obesity were only observed in the elderly patients.

The beneficial prognostic impacts on overweight and obesity were attenuated with clinical follow-up duration.

Also: A study published in March in Drugs & Aging involving more than 8,000 subjects indicates that the dose-response for statins on new-onset of diabetes suggests that elderly women should not be exposed to higher doses of statins. The study can be accessed at

CITATION: Fei Gao, Zhi Jian Wang, et. al. Impact of obesity on mortality in patients with diabetes: Meta-analysis of 20 studies including 250,016 patients. Journal of Diabetes Investigation. Version of record online: 8 June 2017. Manuscript Accepted: 4 April 2017. Manuscript Revised: 28 March 2017. Manuscript Received: 3 February 2017.

Gluten avoidance may spur decrease
in beneficial whole-grain consumption

NEW YORK – Long-term dietary gluten intake was not associated with coronary heart-disease risk in a prospective-cohort study that also indicated that gluten avoidance may cause reduced beneficial-whole grain consumption.

The study published in May in BMJ also indicates that while people with-and-without celiac disease may avoid gluten because of a symptomatic response to this dietary protein, its findings don’t promote a gluten-restricted diet with a goal of reducing coronary-heart disease risk.

Its authors, including Benjamin Lebwohl, Columbia University College of Physicians and Surgeons, New York, and Yin Cao, Harvard Medical School, Boston, report that dietary- gluten avoidance may result in a low intake of whole grains, which are associated with cardiovascular benefits.

The researchers also state that the promotion of gluten-free diets for the purpose of coronary heart-disease prevention among asymptomatic people without celiac disease should not be recommended.

Their study involved 64,714 women in the Nurses’ Health Study and 45,303 men in the Health Professionals Follow-up Study without a history of coronary heart disease.

Among those 110,017 subjects eligible for analysis, the mean daily-estimated intake of gluten at baseline was 7.5 (standard deviation [SD] 1.4) g among women and 10.0 (2.0) g among men in the highest fifth, and 2.6 (0.6) g among women and 3.3 (0.8) g among men in the lowest fifth.

In 2010, the mean daily-estimated gluten intake was 7.9 (2.4) g among women and 9.2 (2.8) g among men in the highest fifth, and 3.1 (1.2) g among women and 3.7 (1.3) g among men in the lowest fifth.

Gluten intake correlated inversely with alcohol intake, smoking, total-fat intake, and unprocessed red-meat intake.

Gluten intake correlated positively with whole-grain intake and refined-grain intake; gluten did not correlate strongly with sodium intake.


CITATION: Benjamin Lebwohl, Yin Cao, et. al. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ. 2017;357: j1892. Published 02 May 2017.

Sweetened beverage-diabetes risk
assessed in Clinician Reviews article

An article published in July in the Clinical Edge section of Clinician Reviews takes on the topic of sweetened-beverage consumption and diabetes risk. Quoting a study published online in June in The American Journal of Clinical Nutrition, the article notes that artificially-sweetened beverages (ASBs) are associated with a 21% increased risk of developing diabetes mellitus (DM), about half the magnitude of sugar-sweetened beverages (SSBs, a 43% increased risk). The prospective Women’s Health Initiative observational study also indicates that replacing either ASBs or SSBs with water can potentially reduce this risk. The article can be accessed at


Vol. 3 No. 17

In testosterone-osteoporosis link,
a cautious approach is suggested

LAGUNA NIGUEL, CALIF. – A recent study on male hypogonadism and osteoporosis focuses on clinical consequences, effects, and treatment of testosterone deficiency in bone health…and, says one expert medical professional, raises issues that should be cautiously addressed.

Ji Hyun Chun (CJ), PA-C, BC-ADM, OptumCare Medical Group, Laguna Niguel, Calif., has his own take on a statement in the study published in March in the International Journal of Endocrinology that hypogonadal males should be aware of the fact that those treated with testosterone have significant bone-density gains in short time periods.

Chun, president-elect of the American Society of Endocrine Physician Assistants (ASEPA) and a faculty member of Metabolic & Disease Summit (MEDS), says clinicians “often focus on patients’ sexual symptoms, overall well-being, and testosterone levels, and impact on bone mass density (BMD) is not often considered.”

Chun adds that “it is crucial for clinicians to recognize low testosterone as a possible secondary etiology of male osteoporosis if the patient presents with fracture and/or low BMD.”

The physician assistant (PA) says BMD tests “should be considered for patients with profound hypogonadism, especially if you suspect hypogonadism might have been going on for a while: You should also ask about fracture history, height loss, and back pain.”

The study’s mention that the risk of falls and fracture risk among elderly men is associated with lower testosterone levels also spurs circumspection on Chun’s part.

“Testosterone levels,” he asserts, “can drop or fluctuate for various reasons, and often are suppressed when the body is stressed for some reason.”

Chun says that while those causes may relate to the frail elderly (seniors with other comorbidities), there may be a “chicken-or-the-egg” relationship: Are they frail because of low testosterone, or do they have low testosterone because they are elderly and frail?

“Frail elderly,” he says, “are at higher risk for falls due to lack of balance and strength; again, is this due to low testosterone or just their overall frail status? Hard to distinguish.”

Chun points to two research efforts on the subject: a clinical trial of testosterone treatment in older men (its treatment phase was dropped in 2010 because of a higher rate of adverse cardiovascular events among older men receiving testosterone gel compared to those getting placebo), and another, reported this year, on testosterone treatment and coronary artery plaque volume among older men with low testosterone.

The latter study, Chun points out, indicates that neither physical function nor vitality improved significantly on testosterone as compared with placebo among 170 men aged 65-and-older (88 received testosterone).

While acknowledging that men with profoundly-low testosterone levels may experience bone loss, Chun says that age-related hypogonadism-testosterone levels rarely fall to that range. Yet, it may be helpful for health-care providers to make patients aware of hypogonadism-BMD considerations.

The BMD tie-in, he says, “might be something that is not thought of as often as that of sexual function.”

As to treatment, Chun says, “those with pathologic hypogonadism (pituitary or testicular surgery or radiation, or genetic disorders), with profound hypogonadism, patients who have low BMD, I think it is very reasonable to put them on testosterone replacement therapy (TRT) and monitor their BMD. Hopefully, we can catch it early enough, before they develop osteoporosis. And for those with high risk of fracture, or who already have fractures, I would definitely consider adding osteoporosis medications as well.

Finally, Chun says “there are cases where we intentionally lower testosterone levels (such as in prostate-cancer management) to almost zero. It is suggested that we use bisphosphonates to prevent bone loss while they are on that therapy. Obviously, TRT can’t be used during that time.”

CITATION: Gary Golds, Devon Houdek, et. al. Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health. International Journal of Endocrinology. March 2017. Volume 2017 (2017), Article ID 4602129, 15 pages. Review article. Adverse Cardiovascular Events Reported in Testosterone Trial in Older Men. National Institutes of Health. June 30, 2010.  Budoff MJ, Ellenberg SS, et. al. Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone. JAMA. 2017 Feb 21;317(7):708-716. PMID: 28241355

Researchers identify gene
tied to neural-tube defects

BALTIMORE – A gene has been identified that triggers a process leading to the formation of neural-tube defects (NTDs) commonly found in infants of pregnant women with diabetes, according to recent research.

This is the first time the gene has been shown to play this role, according to the study published in May in Nature Communications.

Its authors---including Fang Wang and Cheng Xu, who are affiliated with the University of Maryland School of Medicine, Baltimore---report that the identification of this gene opens up a new way to understand these defects and that their work may lead to new treatments that could prevent the problem or decrease its incidence.

The researchers note that even small, brief spikes in a pregnant woman’s blood-glucose level can spur diabetes-associated birth defects, and that even women who monitor and control blood sugar are at greater risk of having a baby with NTDs than those without the disease.

Since this developmental process takes place very early in pregnancy---often before the woman knows she is expecting---by the time pregnancy is confirmed, damage from elevated blood glucose to the developing central nervous system (CNS) may already have occurred.

The authors focused on a gene called Prkca, which plays a vital role in regulating autophagy…the process through which cells dispose of un-needed material, which is often broken or flawed.

In diabetes, the Prkca gene becomes over-active; as a result, autophagy is suppressed, and the flawed cellular material is used to create embryonic tissue that can lead to major birth defects.

CITATION: Fang Wang, Cheng Xu, et. al. Protein kinase C-alpha suppresses autophagy and induces neural tube defects via miR-129-2 in diabetic pregnancy. Nature Communications 8, Article number: 15182 (2017) Received: 07 July 2016. Accepted: 03 Marcg 2017. Published online: 05 May 2017.
University of Maryland School of Medicine researchers identify gene that controls birth defect common in diabetes.  University of Maryland School of Medicine.

Body-fat measures supported
for kidney-function estimates

MEXICO CITY – Anthropometric measures of body fat appear to provide equally-consistent estimates of kidney-function (KF) decline risk as computed tomography (CT) measures in elders, according to a study published in May in the Clinical Journal of the American Society of Nephrology.

Its authors---including Magdalena Madero, of the Instituto Nacional de Cardiología Ignacio Chávez, Mexico City---noted that while anthropometric body-fat measures are associated with chronic-kidney disease (CKD) development, they may be less accurate than CT measures.

The researchers compared the association of CT and anthropometric measures of obesity with kidney outcomes in the Health Aging and Body Composition Study.

Participants were recruited from March, 1997, through July, 1998. CT measures included:
visceral abdominal fat (VAT); subcutaneous adipose tissue (SAT); and inter-muscular fat area (IMAT).

 Anthropometric measures included: waist circumference (WC); and body mass index (BMI).

Kidney outcomes included KF decline or incident CKD.

Two-thousand four-hundred and eighty-nine subjects were included. Mean age was 74 (plus-or-minus three years); 49% were men, 39% were black, 59% were hypertensive, and 15% were diabetic.

KF decline occurred in 17% of the population, and incident CKD occurred in 17% of those at risk.

In continuous models, SAT, VAT, IMAT, BMI, and WC (per SD increase) were all significantly associated with KF decline.

There was a significant interaction between VAT and CKD with regard to KF decline.
Only VAT, BMI, and WC were associated with incident CKD, and only VAT remained a significant risk factor for incident CKD when other exposure variables were included in the same model.

There was no association between any measure of obesity and kidney outcomes when creatinine values at years three and 10 were used to estimate changes in estimated glomerular filtration rate (eGFR).

CITATION: Magdalena Madero, Ronit Katz, et. al.  Comparison between Different Measures of Body Fat with Kidney Function Decline and Incident CKD.  Clinical Journal of the American Society of Nephrology. May 2017. Received July 6, 2016. Accepted March 1, 2017 Published online before print, May 2017.

Study: Weight-loss intervention
won't preferentially target VAT

MILAN – A review published recently in the International Journal of Obesity concludes that there is no evidence of a weight-loss intervention (lifestyle modification, weight-loss promoting drugs, bariatric surgery) that preferentially targets visceral adipose tissue (VAT).

Authors of the research published in March---including Claudia Meriotti, who is affiliated with the Universita degli Studi di Milana, Milan---also indicate that basal VAT depots are smaller than basal subcutaneous adipose tissue (SAT) depots, and that VAT loss is linked to SAT loss.
Only percent VAT loss is greater than percent SAT loss; this applies to all strategies.

The researchers also note that there are no shortcuts to losing VAT through the available strategies.
This suggests that VAT, while more dangerous, is also more vulnerable than subcutaneous fat. This finding could spur deeper studies of the biology of VAT and hopefully lead to more specific targets for VAT reduction.

The authors analyzed 89 studies in their evaluations of visceral and subcutaneous fat changes, measured through ultrasound, computerized tomography, magnetic resonance imaging (MRS) and expressed as thickness, weight, area and volume.

They found that: subcutaneous fat was greater than visceral fat when measured as area, volume and weight, but not as thickness;  decrease of subcutaneous fat was greater than visceral fat when measured as area, volume and weight, though not as thickness; and that percent decrease of visceral fat was always greater than percent decrease of subcutaneous fat, with no differences between different strategies.

No intervention preferentially targets visceral fat, and basal visceral fat depots are smaller than basal subcutaneous fat depots.

Visceral fat loss is linked to subcutaneous fat loss, and, with all strategies, percent decrease of visceral fat prevails over subcutaneous fat loss.

CITATION: C Merlotti, V Ceriani, et. al. Subcutaneous fat loss is greater than visceral fat loss with diet and exercise, weight-loss promoting drugs and bariatric surgery: a critical review and meta-analysis. International Journal of Obesity (2017) 41, 672-682; published online 7 March 2017. Received 28 July 2016; Revised 30 December 2016. Accepted 20 January 2017. Accepted article preview online 2 February 2017; Advanced online publication 7 March 2017.

Vitamin D repletion is associated
with decreased disease activity

BOSTON – Vitamin D repletion is associated with decreased disease activity and increased quality of life (QOL) in Crohn’s disease (CD), according to a study published in May in Digestive Diseases and Sciences.

Its authors---including Samantha Zullow, Boston University School of Medicine, Boston---also indicate that in a tertiary-care inflammatory bowel disease (IBD) cohort, most patients have low vitamin D levels, and that non-Caucasian race and female gender are associated with low vitamin D.

The researchers also indicate that ulcerative colitis (UC) is associated with lower risk of vitamin D insufficiency.

Noting that many IBD patients are vitamin D deficient, the authors set out to identify risk factors for vitamin D deficiency in IBD and assess the impact of vitamin D repletion on disease activity and QOL.

The researchers evaluated patients with at least one 25-OH vitamin D level measured between 2004 and 2011; those with levels of less than 30 ng/ml at baseline were followed until time of repletion.
QOL and disease-activity scores were measured at baseline and repletion.

Two-hundred-and-fifty-five patients were identified; 33%, 29%, and 39% had vitamin D levels of at least 30, 20-to-29, and less than 20 ng/ml, respectively.

When adjusting for disease type and duration, gender, smoking, and race, non-Caucasians had 5.3 and UC patients 0.59 odds of having vitamin D of less than 30 ng/ml.
Women were 1.7 times more likely to have a 25-OH vitamin D level of less than 20 ng/ml than men; 55 patients underwent repletion.

CITATION: Zullow S, Jambaulikar G, et. al. Risk Factors for Vitamin D Deficiency and Impact of Repletion in a Tertiary Care Inflammatory Bowel Disease Population. Dig Dis Sci. 2017 May 25. [Epub ahead of print] PMID: 28547646.

Child-obesity treatments addressed
in study included in Clinician Reviews

An article in the Clinical Edge section of June's Clinician Reviews addresses the question of whether children need to be present during obesity treatments. Quoting from a study published in May in JAMA Pediatrics, the article notes that, in treatment for child-weight loss, parent-based (parent-only) treatment was as effective as family-based (parent-and-child) treatment. The study assessed 150 overweight-and-obese eight-to-12-year-old children and their parents. The article can be accessed at


Vol. 3 No. 16

Goal-directed treatment backed

as ’next level’ for osteoporosis

SOUTHBURY, CONN. – An expert on osteoporosis says the goal-directed treatment approach presented in a recent report may boost care "to the next level" following what he calls a "decline" in attention to the disease.

Rick Pope, physician assistant (PA)-C, Department of Rheumatology, Western Connecticut Medical Group, Danbury, Conn., has high hopes for the efforts of the working group formed by the American Society for Bone and Mineral Research (ASMBR) and the United States National Osteoporosis Foundation (NOF).

The group’s progress report published in December by the Journal of Bone and Mineral Research defines goal-directed treatment as a strategy in which:

  • treatment goals are established for patients
  • initial treatment choices are based on the probability of reaching goals
  • progress towards reaching goals is reassessed periodically
  • the overriding treatment goal is to achieve freedom from fracture or at least low-fracture risk

Treatment goals include:

  • t-scores of more than minus 2.5
  • achievement of an estimated risk level below the threshold for initiating treatment

Pope, a Southbury, Conn., resident, founder and past three-time president of the Society of Physician Assistants in Rheumatology (SPAR), and faculty member of the Metabolic & Endocrine Disease Summit (MEDS), points to expectations for two drugs that could hit the market this year as among his reasons for optimism.

One, from Radius Health, is abaloparatide-SC 80 mcg, an investigational, once-daily treatment for post-menopausal women with osteoporosis; if approved by the U.S. Federal Drug Administration (FDA), it would be the first new bone-anabolic treatment option in the U.S. since 2002 for post-menopausal women with osteoporosis; a New Drug Application (NDA) was submitted last year.

Also: Amgen and UCB last year announced that the FDA accepted for review the Biologics License Application (BLA) for romosozumab, an investigational monoclonal antibody for the treatment of osteoporosis in post-menopausal women at increased risk of fracture. Romosozumab---for which the FDA has set a Prescription Drug User Fee Act (PDUFA) target-action date of July 19---works by binding and inhibiting the activity of the protein sclerostin, a protein naturally occurring in the bone, thereby increasing bone formation and decreasing bone resorption.

"The recommendations in this [working-group] report," says Pope, "would make goals more targeted, with levels of osteoporosis treatment based on bone mineral density (BMD). The report can make significant headway in treatments and approaches that are user-friendly, especially for primary care."

The report notes that goal-directed treatment can’t be fully achieved without medications that provide greater BMD increases and greater fracture-risk reductions.

Pope says a goal-directed approach will benefit patients of PAs and nurse practitioners (NPs) once the new approach becomes a reality, possibly during the next three years.

"The direction," he says "is to give practitioners a more specific end-point for management. The patient is directed to a number on a bone-density machine. With that goal in mind treatment is started or a change in treatment is recommended. It will be easier to set and reach goals in many cases, which is not currently being done, as goals are fuzzy, and BMD maintenance and some measure of improvement is recommended."


The report, Pope says, "is driven by data from studies, using large meta-data analysis to come up with conclusions. Meta-data analysis can be tricky. Studies are done with different end-points and populations, and conclusions may not be as specific as we like."


Pope echoes the report’s cautionary note that treatment selection is often based on or constrained by payer-reimbursement policies.


"Costs," he says, "will be closely calculated by insurance companies, and numbers needed to prevent fractures will be carefully estimated. If patients undertake any form of therapy, overall benefits will need to be shown as compared to the cost of care for hip fractures, spinal fractures and other incident fractures. An arduous task."


He underscores this emphasis by noting that "the most-costly, and most deadly, fracture is the hip fracture."


A goal-directed approach, Pope concludes, "can take osteoporosis treatment to the next level, getting to goals that will be verified and validated with newer and more potent medications that will be achievable for most."


"This is a large undertaking," he says, "and I applaud it. It will and should go this next step however better pharmaceuticals and more aggressive regimens are needed to make an important and recognizable difference in the osteoporosis population."

CITATION: Steven R. Cummings, Felicia Cosman, et. al. Goal-Directed Treatment for Osteoporosis: A Progress Report From the ASBMR-NOF Working Group on Goal-Directed Treatment for Osteoporosis. Journal of Bone and Mineral Research. First published 27 December 2016. Volume 32, Issue 1. January 2017. Pages 3-10.

Diabetic retinopathy targeted

in recommendations from ADA

BALTIMORE – A recent American Diabetes Association (ADA) position statement cites studies showing the positive effects tight glycemic control can have on diabetic retinopathy risks and progressions in patients with diabetes, and how those benefits can last for years.

The statement published in March in Diabetes Care outlines the stages of diabetic retinopathy and highlights recommendations on optimal blood-glycemic control and lowering blood pressure.

Its authors---including Sharon D. Solomon, Johns Hopkins Medicine, Baltimore, and Emily Chew, National Institutes of Health, Bethesda, Md.---also include screening recommendations suggesting that adults with type 1 diabetes receive comprehensive eye exams within five years of the onset of diabetes, and that those with type 2 diabetes have exams at time of diagnosis.

If there is no evidence of retinopathy for one or more annual eye exams, the statement indicates, exams every two years may be considered.

They also recommend that women with pre-existing type 1 or type 2 diabetes who are pregnant or planning to become pregnant be counseled on the risks of development and/or progression of diabetic retinopathy.

If any level of diabetic retinopathy is present, subsequent dilated retinal examinations for patients with type 1 or type 2 diabetes should be repeated at least annually by an ophthalmologist or optometrist; if retinopathy is progressing or sight-threatening, examinations will be required more frequently.

Treatment recommendations include:

  • prompt referral of patients with any level of macular edema; severe non-proliferative diabetic retinopathy (a precursor of proliferative diabetic retinopathy); or any proliferative diabetic retinopathy to an ophthalmologist who is knowledgeable and experienced in management and treatment of diabetic retinopathy
  • laser photocoagulation therapy reduces vision-loss risk in patients with high-risk proliferative diabetic retinopathy and, in some cases, severe non-proliferative diabetic retinopathy
  • intravitreous injections of anti-vascular endothelial growth factor are indicated for central-involved diabetic macular edema (DME)
  • while optimization of blood glucose, blood pressure, and serum lipid levels in conjunction with dilated eye examinations can substantially decrease the vision-loss risk from complications of diabetic retinopathy, a significant proportion of those affected with diabetes develop DME or proliferative changes requiring intervention


CITATION: Sharon D. Solomon, Emily Chew, et. al. Diabetic Retinopathy: A Position Statement by the American Diabetes Association. Diabetes Care. March 2017.

Research: High-protein diet won’t

significantly affect FFM changes

AMSTERDAM – A high-protein diet, though lower than targeted, does not significantly affect changes in fat-free mass (FFM) during modest weight loss in older overweight and obese adults, according to a study published in February in the Nutrition Journal.

Its authors---including Amely M. Verreijen and Mariélle F. Engberink, Amsterdam University of Applied Sciences, Amsterdam---also indicate that there is no significant interaction between the high-protein diet and resistance exercise for change in FFM.

The researchers, who investigated whether a high-protein diet and/or resistance exercise preserves FFM during weight loss among overweight and obese adults, determined that only the studied group with a combined intervention of high-protein diet and resistance exercise significantly increased in FFM.

This suggests that combining protein with resistance exercise is beneficial for FFM preservation during weight loss for older adults; the researchers add that this point should be confirmed by future studies using a larger protein contrast.

The authors, noting that intentional weight loss in older obese adults is a risk factor for accelerated muscle-mass loss, assessed 100 overweight and obese adults, aged 55-to-80 years-of-age, in a randomized controlled trial (RCT) with a two-by-two factorial design and intention-to-treat analysis.

All subjects followed a hypocaloric diet during a 10-week weight-loss program; subjects were randomly allocated to either a high- or normal-protein diet, with-or-without a resistance-exercise program three times a week. FFM was assessed by air-displacement plethysmography.

Both high-protein diet and exercise did not significantly affect change in body weight, FFM and fat mass (FM).

No significant protein-exercise interaction effect was observed for FFM, although within-group analysis showed that high protein in combination with exercise significantly increased FFM.

Also: A March research letter in the Journal of American Medicine reports on a study of adults who were overweight or obese and trying to lose weight during three periods from 1988 through 2014. The letter---which can be accessed at that a growing number of such adults are not trying to loss excess weight.

CITATION: Amely M. Verreijen, Mariélle F. Engberink, et. al. Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial. Nutrition Journal. Received: 19 October 2016. Accepted: 16 January 2017. Published: 6 February 2017.

Novel assay targets benign,

malignant thyroid nodules

REHOVOT, ISRAEL – A novel assay utilizing microRNA expression in cytology smears is the subject of benign-and-malignant thyroid-nodule research published in February in the Journal of Clinical Pathology.

Its authors---including Gila Lithwick-and Nir Dromi, of Rosetta Genomics Ltd., Rehovot, Israel---note that the assay distinguishes benign from malignant thyroid nodules using a single fine-needle aspirate (FNA)-stained smear, and does not require fresh tissue or special collection-and-shipment conditions.

The assay offers a tool for the pre-operative classification of thyroid samples with indeterminate cytology.

The researchers present a new diagnostic assay and evaluate its performance on a blinded set of 189 samples from several sources.

The test described in the paper is a multi-center, clinically-evaluated, commercially-available assay that can accurately differentiate between malignant-and-benign thyroid nodules using routinely-prepared FNA-stained smears.

A training set of 375 FNA smears was used to develop the microRNA-based assay, which was validated with a blinded, multi-center, retrospective cohort of 201 smears.

Validation samples were from adult patients at least 18 years of age with nodule sizes of more than 0.5 cm, and a final diagnosis confirmed by at least one of two blinded, independent pathologists.

Take-home messages include:

  • 10%-to-40% of thyroid FNAs are not conclusively diagnosed by cytology and are categorized as indeterminate
  • the RosettaGX Reveal assay, which was blindly validated, differentiates benign from malignant thyroid nodules in indeterminate smears
  • smear used for the assay can be a routinely-prepared smear used to make the indeterminate diagnosis, and does not require a repeat FNA
  • the assay does not require fresh tissue or special collection and shipment conditions
CITATION: Gila Lithwick-Yanai, Nir Dromi, et. al. Multicentre validation of a microRNA-based assay for diagnosing indeterminate thyroid nodules utilising fine needle aspirate smears. Journal of Clinical Pathology. 02/06/2017.;
Harmonized-reference ranges

are assessed for testosterone

BOSTON – A recent study indicates that a substantial proportion of inter-cohort variation in testosterone levels is due to assay differences.

Data in the study published in January in The Journal of Clinical Endocrinology & Metabolism demonstrates the feasibility of generating harmonized-reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator.

The study---whose authors include Thomas G. Travison, Harvard Medical School, Boston, and Hubert W. Vesper, Centers for Disease Control and Prevention, Atlanta---indicates that the harmonized-normal range in the non-obese population of European and American men aged 19-to-39 years is 264-to-916 ng/dL.

The researchers note that reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men and set out to establish harmonized-reference ranges for total testosterone that can be applied across laboratories by cross-calibrating cohort-specific assays to a reference method and standard.

The research included 9,054 community-dwelling men in cohort studies in the United States and Europe from: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; Male Sibling Study of Osteoporosis.

Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method from the Centers for Disease Control (CDC). Generalized-additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values.

And in a related matter: An editorial published in February by the Journal of the American Medical Association assesses testosterone and male aging. It can be accessed at

CITATION: Thomas G. Travison, Hubert W. Vesper, et. al. Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the USA and Europe. The Journal of Clinical Endocrinology & Metabolism. Published: 10 January 2017.
Clinician Reviews addresses

issue of vitamin D’s role in MS

A March article in Clinician Reviews assesses the role of vitamin D in multiple sclerosis (MS). Written by Lisa Marie Fox, MSPAS, PA-C, who is affiliated with Johns Hopkins Hospital in Baltimore, the piece notes that living farther from the equator, not being exposed to sunlight, and having a low vitamin D level are correlated with increased risk for MS and MS relapse. The article---which can be accessed at that, in light of the anti-inflammatory effects of vitamin D and its purported reduction of MS risk, it is possible that MS patients should start vitamin D supplementation early in order to obtain maximum anti-inflammatory effects.


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