Steven M. Petak

Bisphosphonate Associated Osteonecrosis of the Jaw

In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%–12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS - 2016.

ABBREVIATIONS AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial (FIT) Long-term Extension FRAX(®) = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B ligand RCT = randomized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization.

Skeletal health in long-duration astronauts: Nature, assessment, and management recommendations from the NASA Bone Summit

Concern about the risk of bone loss in astronauts as a result of prolonged exposure to microgravity prompted the National Aeronautics and Space Administration to convene a Bone Summit with a panel of experts at the Johnson Space Center to review the medical data and research evidence from astronauts who have had prolonged exposure to spaceflight. Data were reviewed from 35 astronauts who had served on spaceflight missions lasting between 120 and 180 days with attention focused on astronauts who (1) were repeat fliers on long‐duration missions, (2) were users of an advanced resistive exercise device (ARED), (3) were scanned by quantitative computed tomography (QCT) at the hip, (4) had hip bone strength estimated by finite element modeling, or (5) had lost >10% of areal bone mineral density (aBMD) at the hip or lumbar spine as measured by dual‐energy X‐ray absorptiometry (DXA). Because of the limitations of DXA in describing the effects of spaceflight on bone strength, the panel recommended that the U.S. space program use QCT and finite element modeling to further study the unique effects of spaceflight (and recovery) on bone health in order to better inform clinical decisions.

American association of clinical endocrinologists medical guidelines for the clinical use of dietary supplements and nutraceuticals

Reviewers Donald A. Bergman, MD, FACP, FACE Jeffrey R. Garber, MD, FACE Carlos R. Hamilton, Jr., MD, FACE Yehuda Handelsman, MD, FACP, FACE Kalman E. Holdy, MD John S. Kukora, MD, FACS, FACE Philip Levy, MD, FACE Pasquale J. Palumbo, MD, MACE Steven M. Petak, MD, JD, FACE Leonid Poretsky, MD Philip Rabito, MD, FACE Herbert I. Rettinger, MD, FACE, MBA Helena W. Rodbard, MD, FACE F. John Service, MD, PhD, FACE, FACP, FRCPC Talla P. Shankar, MD, FACE

Clinical Value of Monitoring BMD in Patients Treated With Bisphosphonates for Osteoporosis

Osteoporosis is a common disease with serious medical and economic consequences. Despite great efforts to educate healthcare professionals and the public, it remains underdiagnosed and undertreated. BMD testing by DXA is an extraordinarily useful clinical tool for assessment of fracture risk and to diagnose osteoporosis before the first fracture occurs. DXA is the only technology for measuring BMD that can be used with FRAX, the World Health Organization fracture risk assessment algorithm that is becoming widely used throughout the world. Several organizations recommend serial DXA testing for monitoring pharmacologic therapy of osteoporosis. The utility of BMD testing to monitor therapy was questioned almost a decade ago when the concept of ‘‘regression to the mean’’ was raised. Although this concept has relevance at a population level, it was subsequently refuted as misleading and irrelevant to the clinical management of individual patients. A study published recently in BMJ by Bell et al. raises the question anew. Despite the title, ‘‘Value of Routine Monitoring of Bone Mineral Density after Starting Bisphosphonate Treatment: Secondary Analysis of Trial Data,’’ the authors conclude that monitoring BMD ‘‘in postmenopausal women in the first three years after starting treatment with a potent bisphosphonate is unnecessary and may be misleading.’’ The authors go on to state that ‘‘routine monitoring should be avoided in this early period.’’ These conclusions are based on a secondary analysis of pooled data from the two arms of the Fracture Intervention Trial (FIT) in which postmenopausal women with low BMD were randomized to alendronate or placebo. They conclude that using BMD to monitor response to treatment with alendronate was of no value because (1) >97% of the patients on treatment ultimately showed an increase in BMD and (2) the withinsubject variability was considerable. Several of the same authors used a similar approach in a post hoc analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) to conclude that monitoring the initial blood pressure response after perindopril (an angiotensinconverting enzyme inhibitor) therapy was unnecessary. The purpose of this commentary is to address issues raised by Bell et al. and to place the need for BMD monitoring into an appropriate clinical context. Whereas we applaud all efforts to apply the best available medical evidence to clinical decision-making, the validity and applicability of evidence should be closely scrutinized before making recommendations. The conclusion of the recent BMJ article, that monitoring therapy with BMD testing is unnecessary, rests on four assumptions: (1) the goal of monitoring is to document effectiveness by showing an increase in BMD, (2) the increase in BMD in virtually all treated subjects in FIT can be expected to occur in patients in clinical practice, (3) the response to one bisphosphonate in a clinical trial is indicative of the response to all bisphosphonates in clinical practice, and (4) within-person

The Official Positions of the International Society for Clinical Densitometry: Body Composition Analysis Reporting

Dual-energy x-ray absorptiometry (DXA) measurements of body composition increasingly are used in the evaluation of clinical disorders, but there has been little guidance on how to effectively report these measures. Uniformity in reporting of body composition measures will aid in the diagnosis of clinical disorders such as obesity, sarcopenia, and lipodystrophy. At the 2013 International Society for Clinical Densitometry Position Development Conference on body composition, the reporting section recommended that all DXA body composition reports should contain parameters of body mass index, bone mineral density, BMC, total mass, total lean mass, total fat mass, and percent fat mass. The inclusion of additional measures of adiposity and lean mass are optional, including visceral adipose tissue, appendicular lean mass index, android/gynoid percent fat ratio, trunk to leg fat mass ratio, lean mass index, and fat mass index. Within the United States, we recommend the use of the National Health and Nutrition Examination Survey 1999-2004 body composition dataset as an age-, gender-, and race-specific reference and to calibrate BMC in 4-compartment models. Z-scores and percentiles of body composition measures may be useful for clinical interpretation if methods are used to adjust for non-normality. In particular, DXA body composition measures may be useful for risk-stratification of obese and sarcopenic patients, but there needs to be validation of thresholds to define obesity and sarcopenia. To summarize, these guidelines provide evidence-based standards for the reporting and clinical application of DXA-based measures of body composition.

Clinical practice guidelines for healthy eating for the prevention and treatment of metabolic and endocrine diseases in adults: cosponsored by the American Association of Clinical Endocrinologists/the American College of Endocrinology and the Obesity Society: executive summary.

J. Michael Gonzalez-Campoy, MD, PhD, FACE1; Sachiko T. St. Jeor, PhD, RD2; Kristin Castorino, DO3; Ayesha Ebrahim, MD, FACE4; Dan Hurley, MD, FACE5; Lois Jovanovic, MD, MACE6; Jeffrey I. Mechanick, MD, FACP, FACN, FACE, ECNU7; Steven M. Petak, MD, JD, MACE, FCLM8; Yi-Hao Yu, MD, PhD, FACE9; Kristina A. Harris10; Penny Kris-Etherton, PhD, RD11; Robert Kushner, MD12; Maureen Molini-Blandford, MPH, RD13; Quang T. Nguyen, DO14; Raymond Plodkowski, MD15; David B. Sarwer, PhD16; Karmella T. Thomas, RD17

Official positions of the International Society for Clinical Densitometry

The International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences for the purpose of establishing standards and guidelines for indications, acquisition, and interpretation of bone density tests. Topics are selected for consideration by the ISCD Scientific Advisory Committee, reviewed by scientific working groups, and presented to an international panel of experts. Topic categories addressed to date include indications for bone density testing, selection of reference databases for T-scores and Z-scores, clinical applications for central and peripheral bone densitometry, serial bone density testing, instrument precision assessment, phantom scanning and calibration testing, requirements for a bone density report, nomenclature, and diagnosis of osteoporosis in postmenopausal women, premenopausal women, men, and children. After an open session for public comment and discussion, the panel convenes for consideration of each topic and makes recommendations for positions to the ISCD Board of Directors. Recommendations that are accepted become the Official Positions of the ISCD. This Special Report summarizes the methodology of the ISCD Position Development Conferences and presents selected Official Positions of general interest.

CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE QUALITY OF DXA SCANS AND REPORTS

OBJECTIVE High-quality dual-energy X-ray absorptiometry (DXA) scans are necessary for accurate diagnosis of osteoporosis and monitoring of therapy; however, DXA scan reports may contain errors that cause confusion about diagnosis and treatment. This American Association of Clinical Endocrinologists/American College of Endocrinology consensus statement was generated to draw attention to many common technical problems affecting DXA report conclusions and provide guidance on how to address them to ensure that patients receive appropriate osteoporosis care. METHODS The DXA Writing Committee developed a consensus based on discussion and evaluation of available literature related to osteoporosis and osteodensitometry. RESULTS Technical errors may include errors in scan acquisition and/or analysis, leading to incorrect diagnosis and reporting of change over time. Although the International Society for Clinical Densitometry advocates training for technologists and medical interpreters to help eliminate these problems, many lack skill in this technology. Suspicion that reports are wrong arises when clinical history is not compatible with scan interpretation (e.g., dramatic increase/decrease in a short period of time; declines in previously stable bone density after years of treatment), when different scanners are used, or when inconsistent anatomic sites are used for monitoring the response to therapy. Understanding the concept of least significant change will minimize erroneous conclusions about changes in bone density. CONCLUSION Clinicians must develop the skills to differentiate technical problems, which confound reports, from real biological changes. We recommend that clinicians review actual scan images and data, instead of relying solely on the impression of the report, to pinpoint errors and accurately interpret DXA scan images. ABBREVIATIONS AACE = American Association of Clinical Endocrinologists; BMC = bone mineral content; BMD = bone mineral density; DXA = dual-energy X-ray absorptiometry; ISCD = International Society for Clinical Densitometry; LSC = least significant change; TBS = trabecular bone score; WHO = World Health Organization.