Osteoporotic Fractures: Diagnosis, Evaluation, and Significance From the International Working Group on DXA Best Practices.

Osteoporotic fractures, also known as fragility fractures, are reflective of compromised bone strength and are associated with significant morbidity and mortality. Such fractures may be clinically silent, and others may present clinically with pain and deformity at the time of the injury. Unfortunately, and even at the time of detection, most individuals sustaining fragility fractures are not identified as having underlying metabolic bone disease and are not evaluated or treated to reduce the incidence of future fractures. A multidisciplinary international working group with representation from international societies dedicated to advancing the care of patients with metabolic bone disease has developed best practice recommendations for the diagnosis and evaluation of individuals with fragility fractures. A comprehensive narrative review was conducted to identify key articles on fragility fractures and their impact on the incidence of further fractures, morbidity, and mortality. This document represents consensus among the supporting societies and harmonizes best practice recommendations consistent with advances in research. A fragility fracture in an adult is an important predictor of future fractures and requires further evaluation and treatment of the underlying osteoporosis. It is important to recognize that most fragility fractures occur in patients with bone mineral density T scores higher than -2.5, and these fractures confirm the presence of skeletal fragility even in the presence of a well-maintained bone mineral density. Fragility fractures require further evaluation with exclusion of contributing factors for osteoporosis and assessment of clinical risk factors for fracture followed by appropriate pharmacological intervention designed to reduce the risk of future fracture. Because most low-trauma vertebral fractures do not present with pain, dedicated vertebral imaging and review of past imaging is useful in identifying fractures in patients at high risk for vertebral fractures. Given the importance of fractures in confirming skeletal fragility and predicting future events, it is recommended that an established classification system be used for fracture identification and reporting.

Postmenopausal Osteoporosis: Latest Guidelines.

Significant development has occurred in the treatment of postmenopausal osteoporosis. We review the most recent guidelines from the American Association of Clinical Endocrinologists/American College of Endocrinology, Endocrine Society, and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis/International Osteoporosis Foundation Guidelines.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS-2020 UPDATE.

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Methods: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. Results: The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options. Conclusion: This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis. Abbreviations: 25(OH)D = 25-hydroxyvitamin D; AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; AFF = atypical femoral fracture; ASBMR = American Society for Bone and Mineral Research; BEL = best evidence level; BMD = bone mineral density; BTM = bone turnover marker; CI = confidence interval; CPG = clinical practice guideline; CTX = C-terminal telopeptide type-I collagen; DXA = dual-energy X-ray absorptiometry; EL = evidence level; FDA = U.S. Food and Drug Administration; FRAX® = Fracture Risk Assessment Tool; GI = gastrointestinal; HORIZON = Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly Pivotal Fracture Trial (zoledronic acid and zoledronate are equivalent terms); ISCD = International Society for Clinical Densitometry; IU = international units; IV = intravenous; LSC = least significant change; NOF = National Osteoporosis Foundation; ONJ = osteonecrosis of the jaw; PINP = serum amino-terminal propeptide of type-I collagen; PTH = parathyroid hormone; R = recommendation; ROI = region of interest; RR = relative risk; SD = standard deviation; TBS = trabecular bone score; VFA = vertebral fracture assessment; WHO = World Health Organization.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS- 2020 UPDATE EXECUTIVE SUMMARY.

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Methods: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. Results: The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options. Conclusion: This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis.

MANAGEMENT OF HYPERPARATHYROIDISM IN KIDNEY TRANSPLANTATION CANDIDATES: A NEED FOR CONSENSUS.

Objective: To assess the evolving standards of care for hyperparathyroidism in kidney transplant candidates. Methods: An 11-question, Institutional Review Board-approved survey was designed and reviewed by multiple institutions. The questionnaire was made available to the American Society of Transplantation's Kidney Pancreas Community of Practice membership via their online hub from April through July 2019. Results: Twenty percent (n = 41) of kidney transplant centers responded out of 202 programs in the United States. Forty-one percent (n = 17) of respondents believed medical literature supports the concept that a serum parathyroid hormone level greater than 800 pg/mL could endanger the survival of a transplanted kidney and therefore makes transplantation in an affected patient relatively or absolutely contraindicated. Sixty-six percent (n = 27) said they occasionally recommend parathyroidectomy for secondary hyperparathyroidism prior to transplantation, and 66% (n = 27) recommend parathyroidectomy after transplantation based on persistent, unsatisfactory posttransplantation parathyroid hormone levels. Forty-six percent (n = 19) prefer subtotal parathyroidectomy as their choice; 44% (n = 18) had no standard preference. Endocrine surgery and otolaryngology were the most common surgical specialties consulted to perform parathyroidectomy in kidney transplant candidates. The majority of respondents (71%, n = 29) do not involve endocrinologists in the management of kidney transplantation candidates. Conclusion: Our survey shows wide divergence of clinical practice in the area of surgical management of kidney transplantation candidates with hyperparathyroidism. We suggest that medical/surgical societies involved in the transplantation care spectrum convene a multidisciplinary group of experts to create a new section in the kidney transplantation guidelines addressing the collaborative management of parathyroid disease in transplantation candidates. Abbreviations: AACE = American Association of Clinical Endocrinologists; AAES = American Association of Endocrine Surgeons; AHNS = American Head and Neck Society; CKD = chronic kidney disease; CKD-MBD = chronic kidney disease-mineral and bone disorder; ESRD = end-stage renal disease; HPT = hyperparathyroidism; KDIGO = Kidney Disease Improving Global Outcomes; KT = kidney transplantation; KTC = kidney transplant candidate; PTH = parathyroid hormone; PTX = parathyroidectomy; US = ultrasonography.

Rare adverse effects of bisphosphonate therapy.

PURPOSE OF REVIEW: To give an update on the latest developments regarding rare adverse effects of bisphosphonate therapy. RECENT FINDINGS: Recent studies covering osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFFs) provided several updates to the literature. Identification of ONJ in large population databases is a challenge but based on one systematic review, the ICD-10 diagnosis code K10.2 (inflammatory conditions of the jaw) seems to be the most commonly used code for this condition. Duration of bisphosphonate therapy was determined to be an important predictor of AFFs. Appropriate duration of therapy followed by a timely drug holiday was shown to be the best strategy for improving bone mineral density and reducing fracture risk, while minimizing risk of rare adverse effects of therapy. The utility of bone turnover markers as a monitoring tool during drug holidays needs to be further investigated. SUMMARY: ONJ and AFFs are two of the rare adverse effects associated with bisphosphonate therapy. Population-level trends of bisphosphonate use suggest a decline in prescriptions, pointing to broad fears of these side effects. Careful patient evaluation, duration of bisphosphonate therapy, and use of drug holidays can help limit any risk associated with therapy.

Use of bone turnover markers in the management of osteoporosis.

PURPOSE OF REVIEW: Osteoporosis is a common public health problem that is often undertreated and underdiagnosed. The clinical management of osteoporosis is often reactionary to devastating fracture events. Bone turnover markers may improve the ease and rapidity at which osteoporosis is monitored and treated. Bone turnover markers are biochemical byproducts of bone formation or bone resorption. The clinical use of bone turnover markers is limited by significant preanalytical variability. Effective interpretation of bone turnover markers requires a detailed understanding of the variables that can affect their responses to osteoporosis treatment and monitoring. RECENT FINDINGS: Progress is continuously being made on the standardization of bone turnover markers. The literature on the response of bone turnover markers to unique clinical situations is expanding. Data for evidence-based reference intervals for bone turnover markers has increased. Variables that affect the appropriate timing of lab draws like diurnal variation, postprandial status, exercise and alcohol use have been described. Studies examining the expected response of bone turnover markers to treatments of osteoporosis and other medications that affect bone health continue to increase. SUMMARY: Bone turnover markers have clinical utility in the comprehensive evaluation of osteoporosis. When interpreted with caution and with a good understanding of their natural variability, bone turnover markers provide information that supplements osteoporosis management and provides useful clinical information about conditions that alter bone turnover.

AHNS Series: Do you know your guidelines? Optimizing outcomes in reoperative parathyroid surgery: Definitive multidisciplinary joint consensus guidelines of the American Head and Neck Society and the British Association of Endocrine and Thyroid Surgeons.

BACKGROUND: Revision parathyroid is challenging due to possible diagnostic uncertainty as well as the technical challenges it can present. METHODS: A multidisciplinary panel of distinguished experts from the American Head and Neck Society (AHNS) Endocrine Section, the British Association of Endocrine and Thyroid Surgeons (BAETS), and other invited experts have reviewed this topic with the purpose of making recommendations based on current best evidence. The literature was also reviewed on May 12, 2017. PubMed (1946-2017), Cochrane SR (2005-2017), CT databases (1997-2017), and Web of Science (1945-2017) were searched with the following strategy: revision and reoperative parathyroidectomy to ensure completeness. RESULTS: Guideline recommendations were made in 3 domains: preoperative evaluation, surgical management, and alternatives to surgery. Eleven guideline recommendations are proposed. CONCLUSION: Reoperative parathyroid surgery is best avoided if possible. Our literature search and subsequent recommendations found that these cases are best managed by experienced surgeons using precision preoperative localization, intraoperative parathyroid hormone (PTH), and the team approach.

THE USE OF VITAMINS AND MINERALS IN SKELETAL HEALTH: AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND THE AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT.

ABBREVIATIONS: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; CV = cardiovascular; GI = gastrointestinal; IOM = Institute of Medicine; PTH = parathyroid hormone; RCT = randomized controlled trial; αTF = α-tocopherol; ucOC = undercarboxylated osteocalcin; VKA = vitamin K antagonist; WHI = Women's Health Initiative.

Surgical management of the recurrent laryngeal nerve in thyroidectomy: American Head and Neck Society Consensus Statement.

"I have noticed in operations of this kind, which I have seen performed by others upon the living, and in a number of excisions, which I have myself performed on the dead body, that most of the difficulty in the separation of the tumor has occurred in the region of these ligaments…. This difficulty, I believe, to be a very frequent source of that accident, which so commonly occurs in removal of goiter, I mean division of the recurrent laryngeal nerve." Sir James Berry (1887).

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.

OSTEOPOROTIC FRACTURES DURING BISPHOSPHONATE DRUG HOLIDAY.

OBJECTIVE: Bisphosphonate (BP) drug holidays are recommended to lower the risk of rare adverse events, such as atypical femoral fractures and osteonecrosis of the jaw. However, there are minimal data on the optimal duration of these holidays. Our aim was to determine the clinical and laboratory parameters associated with increased fracture risk in patients on BP drug holiday. METHODS: A retrospective chart review was conducted of 401 patients with osteopenia or osteoporosis who began a BP drug holiday from 2004 to 2013. Collected parameters included demographics, prior therapy, bone mineral density (BMD), bone turnover markers, parathyroid hormone, calcium & vitamin D status, and clinical reports of fractures. RESULTS: Sixty-two (15.4%) patients developed a fracture during follow-up. The yearly incidence of fractures ranged from 3.7 to 9.9%, peaking at 9.9% and 9.8% during years 4 and 5, respectively. The mean age of the fracture group was higher than the nonfracture group, though not significantly different (69.24 ± 12.26 years vs. 66.42 ± 10.18 years; P = .09). Compared to the nonfracture group, the fracture group had lower femoral neck BMD (0.75 ± 0.12 g/cm2 vs. 0.79 ± 0.10 g/cm2; P = .03) and T-scores (-2.13 ± 0.99 vs. -1.78 ± 0.79; P = .01) at baseline. CONCLUSION: Patients who begin BP drug holidays at high risk of fracture based on BMD, age, or other clinical risk factors warrant close follow-up, especially as its duration lengthens. Fracture risk analysis needs to be regularly assessed during the drug holiday and treatment resumed accordingly. ABBREVIATIONS: 25-OHD = 25-hydroxyvitamin D AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology BMD = bone mineral density BP = bisphosphonate BSAP = bone-specific alkaline phosphatase BTM = bone turnover marker FN = femoral neck LS = lumbar spine PTH = parathyroid hormone.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY PROTOCOL FOR STANDARDIZED PRODUCTION OF CLINICAL PRACTICE GUIDELINES, ALGORITHMS, AND CHECKLISTS - 2017 UPDATE.

Clinical practice guideline (CPG), clinical practice algorithm (CPA), and clinical checklist (CC, collectively CPGAC) development is a high priority of the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE). This 2017 update in CPG development consists of (1) a paradigm change wherein first, environmental scans identify important clinical issues and needs, second, CPA construction focuses on these clinical issues and needs, and third, CPG provide CPA node/edge-specific scientific substantiation and appended CC; (2) inclusion of new technical semantic and numerical descriptors for evidence types, subjective factors, and qualifiers; and (3) incorporation of patient-centered care components such as economics and transcultural adaptations, as well as implementation, validation, and evaluation strategies. This third point highlights the dominating factors of personal finances, governmental influences, and third-party payer dictates on CPGAC implementation, which ultimately impact CPGAC development. The AACE/ACE guidelines for the CPGAC program is a successful and ongoing iterative exercise to optimize endocrine care in a changing and challenging healthcare environment. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists ACC = American College of Cardiology ACE = American College of Endocrinology ASeRT = ACE Scientific Referencing Team BEL = best evidence level CC = clinical checklist CPA = clinical practice algorithm CPG = clinical practice guideline CPGAC = clinical practice guideline, algorithm, and checklist EBM = evidence-based medicine EHR = electronic health record EL = evidence level G4GAC = Guidelines for Guidelines, Algorithms, and Checklists GAC = guidelines, algorithms, and checklists HCP = healthcare professional(s) POEMS = patient-oriented evidence that matters PRCT = prospective randomized controlled trial.

AGING, DIABETES, AND FALLS.

KEY POINTS Falls are a major health issue for older adults, leading to adverse events and even death. Older persons with type 2 diabetes are at increased risk of falling compared to healthy adults of a similar age. Over 400 factors are associated with falls risk, making identification and targeting of key factors to prevent falls problematic. However, the major risk factors include hypertension, diabetes, pain, and polypharmacy. In addition to age and polypharmacy, diabetes-related loss of strength, sensory perception, and balance secondary to peripheral neuropathy along with decline in cognitive function lead to increased risk of falling. Designing specific interventions to target strength and balance training, reducing polypharmacy to improve cognitive function, relaxation of diabetes management to avoid hypoglycemia and hypotension, and relief of pain will produce the greatest benefit for reducing falls in older persons with diabetes. Abbreviation: DPN = diabetic polyneuropathy.

Proceedings of the 2016 Santa Fe Bone Symposium: New Concepts in the Management of Osteoporosis and Metabolic Bone Diseases.

The Santa Fe Bone Symposium is an annual meeting of healthcare professionals and clinical researchers that details the clinical relevance of advances in knowledge of skeletal diseases. The 17th Santa Fe Bone Symposium was held in Santa Fe, New Mexico, USA, on August 5-6, 2016. The program included plenary lectures, oral presentations by endocrinology fellows, meet-the-professor sessions, and panel discussions, all aimed to provide ample opportunity for interactive discussions among all participants. Symposium topics included recent developments in the translation of basic bone science to patient care, new clinical practice guidelines for postmenopausal osteoporosis, management of patients with disorders of phosphate metabolism, new and emerging treatments for rare bone diseases, strategies to enhance fracture healing, and an update on Bone Health Extension for Community Healthcare Outcomes, using a teleconferencing platform to elevate the level of knowledge of healthcare professionals in underserved communities to deliver best practice care for skeletal diseases. The highlights and important clinical messages of the 2016 Santa Fe Bone Symposium are provided herein by each of the faculty presenters.

25-Hydroxyvitamin D and blood pressure: a plateau effect in adults with African ancestry living at different latitudes.

OBJECTIVE: This study examined the association of 25-hydroxyvitamin D [25(OH)D] levels and blood pressure above and below 25(OH)D levels of 20 ng/ml in young adults with African ancestry. METHODS: This cross-sectional analysis utilized data from a pooled sample of 2242 adults with African ancestry from five different latitudes (403 in the United States, 474 in South Africa, 479 in Ghana, 448 in Jamaica, and 438 in Seychelles). Piecewise linear regression models with a single knot were fitted to determine above and below a 25(OH)D level of 20 ng/ml the slope of SBP and DBP while adjusting for covariates including calcium intake and site. RESULTS: The mean age was 34.4 (6.1) years, and 46.3% were men. Mean SBP and DBP were 118.1 (15.6) and 73.2 (12.2) mmHg, respectively, and were significantly higher among the United States vs Ghana, Jamaica, and Seychelles groups (P < 0.001 for all comparisons). 25(OH)D levels were significantly lower in the United States vs all other sites (P < 0.001 for all comparisons). When 25(OH)D levels were less than 20 ng/ml, slopes of SBP [-0.33 (95% confidence interval (CI) -0.57, -0.07)] and DBP [-0.21 (95% CI -0.40, -0.02)] were negative and significantly different from zero after adjustment for covariates. In contrast, with 25(OH)D levels above 20 ng/ml, the slopes of SBP [-0.03 (95% CI -0.13, 0.06)] and DBP [-0.04 (-0.11, 0.03)] did not differ significantly from zero. CONCLUSION: The cross-sectional association of 25(OH)D with blood pressure is strongest when 25(OH)D levels are less than 20 ng/ml in young adults with African ancestry.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON TESTING FOR AUTONOMIC AND SOMATIC NERVE DYSFUNCTION.

This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

Dietary factors and fibroblast growth factor-23 levels in young adults with African ancestry.

Fibroblast growth factor-23 (FGF23), a phosphaturic hormone secreted mainly by osteocytes, maintains serum phosphate levels within a tight range by promoting phosphaturia. Previous studies have mainly focused on the link between FGF23 levels and dietary intake of phosphate, but other dietary factors may also influence FGF23 levels. This cross-sectional study pooled three populations of young adults with African ancestry (452 in Chicago, IL, USA; 477 in Victoria, Seychelles; and 482 in Kumasi, Ghana) with estimated glomerular filtration rate >80 ml/min/1.73 m2 to examine the association of dietary factors based on two 24-h recalls with FGF23 levels measured using a C-terminal assay. Linear regression was used to examine the association between log-transformed FGF23 levels and quartiles of calorie-adjusted dietary factors with adjustment for covariates. In the pooled sample of 1411 study participants, the mean age was 35.2 (6.2) years and 45.3% were male. Median plasma C-terminal FGF23 values in relative units (RU)/ml were 59.5 [interquartile range (IQR) 44.1, 85.3] in the USA, 43.2 (IQR 33.1, 57.9) in Seychelles, and 34.0 (IQR 25.2, 50.4) in Ghana. With adjustment for covariates, increasing quartiles of calcium and animal protein and decreasing quartiles of vegetable protein, fiber, and magnesium intake were associated with significantly higher FGF23 levels compared to the lowest quartile. After further adjustment for dietary factors, significant trends in FGF23 levels were noted only for quartiles of calcium, fiber, and magnesium intake (P < 0.001). Dietary factors other than phosphate are associated with FGF23 levels in young adults.